HK1121681B

HK1121681B - Novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors

Info

Publication number: HK1121681B
Application number: HK08113191.2A
Authority: HK
Inventors: D．佩里索德; J．马蒂内; A.莫林; J-A．费伦茨; D．伯格林; L．德芒热
Original assignee: 阿特纳赞塔里斯有限公司; 国家科研中心; 蒙彼利埃第一大学; 蒙彼利埃第二大学
Priority date: 2005-08-15
Filing date: 2006-08-11
Publication date: 2013-02-15

Description

Novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors

Description of the invention

Technical Field

The present invention relates to novel triazole derivatives which act as ghrelin analogue ligands for growth hormone secretagogue receptors. These compounds are useful for modulating growth hormone plasma levels in mammals and for treating and/or modulating a variety of physiological and pathophysiological conditions such as growth retardation, obesity, food intake, energy balance, tumor cell proliferation, trauma/burn healing, metabolic disorders and inflammation.

Background

Ghrelin is a 28 amino acid peptide with a unique octanoyl modification at Ser-3 (Kojima M et al, Nature 1999, 402: 656-660), and was identified as an endogenous ligand for growth hormone secretagogue receptor type 1a (GHS-R1 a), a G-protein coupled receptor (Howard AD et al, Science 1996, 273: 974-977). Ghrelin is produced in the upper intestinal/gastric tract in nature, but small amounts are also detected in the intestine, pancreas, kidney, immune system, placenta, testis, pituitary, lung and hypothalamus (van der LelyAJ et al, Endocrine rev.2004, 25: 426-.

In humans, ghrelin stimulates Growth Hormone (GH) via a pathway independent of the GHRH receptor and has a synergy with GHRH for GH secretion (Arvat E et al, j.clin.endocrinol.meta.2001, 86: 1169-. In addition, it also stimulates ACTH, prolactin, cortisol, aldosterone and epinephrine secretion (Arvat E et al, J.Clin. Endocrinol. Metab.2001, 86: 1169-.

Ghrelin is thought to be involved in metabolic regulation and energy expenditure, and therefore, expression and secretion of Ghrelin from the stomach to the systemic circulation are expected to be affected by metabolic hormones. In obese humans, plasma ghrelin levels decreased, suggesting that increased insulin or leptin levels in obese patients decreased ghrelin secretion (Tschop M et al, Diabetes 2001, 50: 707-.

The release of growth hormone in humans and animals is believed to treat physiological or pathophysiological conditions characterized by defective growth hormone secretion, as well as those conditions ameliorated by the anabolic effects of growth hormone.

Initially, the clinical use of GH was limited to the treatment of GH-deficient children, but commercialization of recombinant human growth hormone (rhGH) has led to numerous studies showing other potential clinical uses for GH (Strobl JS et al, Pharmacol. Rev.1994, 46: 1-34; Torosian MH, J.Peditar. Endocrinol.1993, 6: 93-97). rhGH holds promise for treating burn, trauma, fracture patients, and more recently, for reversing the catabolic effects of glucocorticoids, chemotherapy and AIDS and for altering body composition (Rudman D et al, N.Engl. J.Med.1990, 323: 1-6; Papadaius MA et al, Ann.Intern.Med.1996, 124: 708-.

GH, synthesized and stored in the pituitary gland, is released under the control of two known hypothalamic hormones: growth Hormone Releasing Hormone (GHRH) and the inhibitory hormone Somatostatin (SRIF). In most cases, GH deficiency involves hypothalamic deficiency of GH, not pituitary deficiency. Thus, as an alternative to rhGH treatment, GH-deficient patients can also be treated with any compound that releases endogenous GH from the pituitary gland. This can be achieved either with GHRH, which stimulates GH release, or with synthetic Growth Hormone Secretagogues (GHs).

Many synthetic peptidyl and non-peptidyl GHSs, such as GHRPs 1, 2 and 6, Hexarelin, MK-0677, EP-01572, have been shown to specifically bind to several of the orphan receptor "GHS receptor" long before ghrelin and ghrelin/GHS receptors were discovered (see "camani F et al, Front neuroendinol.1998, 19: 47-72"; "casanuova FF et al, Trends endocrinol.metab.1999, 10: 30-38"; "van der Lely AJ et al, Endocrine rev.2004, 25: 426-. GHS also shows a strong GH-releasing action and has the same biological activity as ghrelin described above.

GHS is also disclosed in the following patents or patent applications (non exhaustive list): US 6,071,926, US 6,329,342, US 6,194,578, US 2001/0041673, US 6,251,902, US 2001/0020012, US 2002/0013320, US 2002/0002137, WO 95/14666, WO 96/15148, WO 01/96300.

Although ghrelin/GHS-induced GH secretion is mediated by ghrelin/GHS receptor type 1a (GHS-R1 a) activation, to date there is evidence that at least some other effects of ghrelin and GHS are also mediated by different receptors of the GHS receptor family or even different binding sites on a given GHS receptor.

GHS receptors are concentrated in the hypothalamic-pituitary area, but appear to be distributed in other central and peripheral tissues as well (Hattori N et al, J.Clin. Endocrinol. Metab.2001, 86: 4284-4291; Gnanapavan S et al, J.Clin. Endocrinol. Metab.2002, 87: 2988-2991; Muccioli G et al, J.Endocrinol.2000, 157: 99-106; Muccioli G et al, Ann. Endocrinol.2000, 61: 27-31; Muccioli G et al, Eur.J.Pharmacol.2002, 440: 235-254; Papotti M et al, J.Clin. Endocrinol.2000, 85: 3803, 3807; Soni P. Clin P, Clin. J.1997-42; Qinacrinol. M.2001; Met.23-368; Met.J.31; Met.J.11: Met.8, J.11: Met.11: 26, J.11-368; Met. J.11, J.11-11, J.Pharmacol. 11).

Two GHS 1 type receptors, GHS-R1 a and GHS-R1 b, have been identified which in humans can be assumed to be expressed and alternatively spliced by a single gene (van der Lely AJ et al, Endocrine Rev.2004, 25: 426-. In mammalian populations, a high degree of sequence identity for GHS-1a has been reported (Petersen S, Minerva Endocrinol.2002; 27: 243-256: between 91.8% and 95.6%).

Motilin receptors have been found to be members of the GHS receptor family with 52% identity (Smith RG et al, Endocrine 2001, 14: 9-14; McKee KK et al, Genomics 1997, 46: 426-434). The motilin receptor 1a and GHS-R1 a show high similarity (Smith RG et al, Endocrine 2001, 14: 9-14; Feighner SD et al, Science 1999, 284: 2184-2188).

Other GHS receptor family members appear to be neurotensin receptor, TRH receptor, GPR38(FM1), GPR39(FM2) and FM3(Smith RG et al, Endocr. Rev.1997, 18: 621-once 645; Smith RG et al, Horm. Res.1999, 51 (suppl.3): 1-8; Tan CP et al, Genomics 1998, 52: 223-229; Howard AD et al, Science, 273: 974-977). Further GHS receptor subtypes appear to exist in a wide range of central and peripheral tissues (van der Lely AJ et al, endogrine Rev.2004, 25: 426-457). For example, the predicted sequence of cardiac GHS-R (Bodart V et al, Circ. Res.1999, 85: 796-84802) has been reported to be similar to CD36, a multifunctional receptor known as glycoprotein IV (Bodart V et al, Circ. Res.2002, 90: 844-849). Cassoni et al (J.Clin.Endocrinol.Metab.2001, 86: 1738-1745) report the presence of the GHS-R subtype in neoplastic mammary cells, activated by ligands that bind to specific binding sites different from the classical GHS-R1 type. Furthermore, the data collected by these authors support the hypothesis that even different subtypes of the GHS-R binding site do exist in peripheral organs, possibly due to their endocrine or non-endocrine properties, as well as their normal or neoplastic properties.

The prevalence of GHS binding sites explains that ghrelin, and synthetic GHS, have implications in several important physiological and pathophysiological conditions, independently of their powerful growth hormone secretagogue properties.

Thus, potential clinical applications include, inter alia

a) Short, medium and long term regulation of energy balance and/or food intake (Tschop M et al, Nature 2000, 407: 908-913; asakawa a et al, Gut 2003, 52: 947-; US 2001/0020012; kojima M et al, curr, opin, pharmacol, 2002, 2: 665-; horvath TL et al, curr. pharm. des.2003, 9: 1383-; wren AM et al, j.clin.endocrinol.meta.2001, 86: 5992-5995)

Expression of GHS-R1a has been shown on neurons of the paraventricular nucleus of the hypothalamus. These neurons send output signals to the critical hypothalamic circuit to control food intake, like the arcuate nucleus that produces the media NPY. It is believed that ghrelin and/or GHS stimulation of food intake is mediated by an increase in NPY in the arcuate nucleus (Willesen MG et al, Neuroendicerin.1999, 70: 306-316). A single administration of anti-ghrelin IgG (icv or ip) inhibited acute feeding in lean rats (Bagnasco M et al, Regul. Pept.2003, 111: 161-167). Chronic twice daily icv administration of anti-ghrelin IgG reduced body weight over five days (Murakami N et al, J.Endocrinol.2002, 174: 283-.

A recent study using peptide GHS-R1a antagonists [ D-Lys-3] -GHRP-6 showed a decrease in food intake and weight gain in diet-induced obese mice (Asakawa A et al, Gut, 2003, 52: 947-. The fact that peptidyl compounds originally identified as growth hormone secretagogues are capable of selectively stimulating food intake in rats without inducing growth hormone secretion suggests the presence of the GHS-R subtype, other than GHS-R1a, in the hypothalamus (TorselloA et al, neuroendocrin.2000, 72: 327-129; Torsello A et al, Eur.J.Pharmacol.1998, 360: 123-129).

b) Adipogenesis, treatment of obesity and/or obesity and reduction of body weight (tschopp Met al, Nature 2000, 407: 908-913; asakawa a et al, Gut 2003, 52: 947-952)

Chronic administration of ghrelin and/or GHS in free-feeding mice and rats results in weight gain and reduced fat utilization (tschopp M et al, Nature 2000, 407: 908-913). Furthermore, ghrelin and deformylated ghrelin have been reported to promote adipogenesis in vivo (Thompson NM et al, Endocrinol.2004, 145: 234-242) and inhibit isoprenaline-induced lipolysis in rat adipocytes via non-GHS-R1 a-type (Muccioli G et al, Eur.J.Pharmacol.2004, 498: 27-35). On the other hand, it has been reported that GHS-R1a expression in rat adipocytes increases with age and during adipogenesis (Choi K et al, Endocrinol.2003, 144, 754-759).

c) Treatment of tumor cell proliferation

As is the case with other members of the hypothalamic-pituitary axis that regulate Growth hormone secretion, there is evidence that ghrelin and GHS-receptors may play important autocrine/paracrine roles in certain cancers (Jeffery PL et al, Cytokine Growth Factor Rev.2003, 14: 113-122). The specific binding sites for ghrelin, peptidyl and non-peptidyl GHS are present in tumor tissues like prostate cancer cell line PC3(Jeffery PL et al, J.Endocrinology2002, 172: R7-R11), thyroid tissue (Cassoni P et al, J.Endocrinol.2000, 165: 139-146), lung cancer cell CALU-1 (Gh. C et al, Endocrinol.2002, 143: 484-491) and breast cancer (Cassoni P et al, J.Clin. Endocrinol.Metab.2001, 86: 1738-1745).

In the case of the breast, specific binding sites for GHS are found in tumor tissue, while normal breast parenchyma does not reveal such receptors. Synthetic GHS has been reported to inhibit proliferation of lung cancer cell CALU-1 (ghe C et al, Endocrinol.2002, 143: 484-491) and breast cancer cell lines (Cassoni P et al, J.Clin. Endocrinol.Metab.2001, 86: 1738-1745).

Both ghrelin and non-acylated ghrelin bind to tumor tissue. Since non-acylated ghrelin is unable to bind to GHS-R1a, the binding site of GHS to tumor tissue is likely to be different from GHS-R1 a. From these data, one can expect that the binding site in tumor tissue recognizes the ligand of GHS-R1a and an otherwise uncharacterized chemical structure. The synthetic ligand of GHS-R1a thus has the potential to inhibit proliferation of tumor cells expressing a GHS receptor subtype.

d) Therapeutic/anti-inflammatory effects of inflammation

The ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) has been demonstrated to have anti-inflammatory effects in chronic arthritis with hypermetabolism and clinical manifestations of cachexia (Granado Met al., am.j.physiol.endocrinol.meta.2005, 288: E486-492). These data suggest that the anti-inflammatory effects of GHRP-2 are mediated by activation of ghrelin receptors expressed by immune competent cells.

e) Treatment of cachexia

It is possible to demonstrate the anti-cachexia effect of the administered recombinant growth hormone in animal models of cachexia (Roubenoff R et al, Arthritis Rheum.1997, 40 (3): 534-. These findings also fit data from patients with rheumatoid arthritis (Roubenoff R et al, J Clin I nvest.1994, 93 (6): 2379-.

f) Treatment of gastrectomy (ghrelin replacement therapy)

The gastric hormone ghrelin (Dornonville de la Cour C et al, Gut 2005, 54 (7): 907-913) was administered to mice that had undergone gastrectomy or sham surgery. The results listed show that ghrelin replacement therapy at least partially reverses gastrectomy-induced weight and body fat loss.

g) Treatment of post-surgical ileus

The effect of ghrelin on the motor function of rat gastrointestinal tract was evaluated. Ghrelin may be shown to reverse delayed gastric emptying and is a strong prokinetic agent useful in the treatment/reversal of post-operative gastrointestinal obstruction (Trudel L et al, Am J Physiol Gastrointest Liverphysiol 2002, 282 (6): G948-G952).

h) Treatment of diabetes (type I and type II diabetes)

The effect of ghrelin removal in leptin-deficient mice was studied (Sun et al, Cell Metabolism 2006, 3: 379-wall 386). The results show that deletion of ghrelin enhances insulin secretion in response to glucose challenge, which suggests that inhibiting ghrelin or counteracting its activity is a possible way of treating diabetes, including its subtypes I and II (see also WO 03/051389).

Further areas of application include accelerating recovery of patients who have undergone major surgery (e.g., US6,194,578); accelerating recovery in burn patients (e.g., US6,194,578); impaired protein catabolic response following major surgery (e.g., US6,194,578); reducing cachexia and protein loss caused by acute or chronic disease (e.g., US6,194,578); treating a central nervous system disorder in a patient undergoing a medical procedure in combination with an antidepressant (e.g., US2002/0002137a 1); accelerating fracture repair and cartilage growth (e.g., US6,194,578); treating or preventing osteoporosis; stimulating the immune system; accelerated wound healing (e.g., US6,194,578); treating growth retardation associated with Prader-Willi syndrome, turner's syndrome, and obesity; treating intrauterine growth retardation, skeletal dysplasia, hypercortisolism, and cushing's syndrome; treatment of osteochondral dysplasia, Noonan syndrome, schizophrenia, depression, and Alzheimer's disease; treatment of lung dysfunction and ventilation equipment dependence; treating hyperinsulinemia, including islet blast proliferation; the ovulation induction is treated in an auxiliary way; preventing age-related decline in thymus function; increasing muscle strength and motility (e.g. US6,194,578); maintaining skin thickness (e.g., US6,194,578); improving sleep quality (e.g., US6,071,926); prevention of congestive heart failure, alone (e.g. US6,329,342, US6,194,578) and in combination with corticotropin releasing factor antagonists (e.g. US 2001/0041673); metabolic or renal homeostasis (e.g. in the frail elderly) (e.g. US6,194,578); improved control of blood glucose (e.g., US6,251,902); treatment of systemic lupus erythematosus and inflammatory bowel disease (e.g., US 2002/0013320); treating or preventing frailty associated with aging or obesity (e.g., US6,194,578); and stimulating osteoblasts.

Potential applications in animals have been forgotten, such as stimulation of food intake (Wren AM et al, Diabetes 2001, 50: 2540-.

Due to their various biological activities, compounds containing triazole moieties have been widely recognized in medicinal chemistry. The following patent families all relate to heterocyclic compounds, said to exhibit certain biological effects, which can be used in different medical indications. These compounds implicitly or explicitly contain a triazole moiety. However, none of these patent families mention ghrelin analogue ligands of the GHS receptor family and the regulatory role, GH secretagogue properties, etc. of these receptors.

WO 2004/111015 discloses modulators of the glucocorticoid receptor. WO 2004/052280 describes anti-angiogenic compounds as inhibitors of VEGF receptor tyrosine kinase activity and their use in cancer. WO 2004/096795 also discloses tyrosine kinase inhibitors, preferably C-FMS inhibitors. Both WO 03/011831 and WO 03/011210 describe heteroarylheteroalkylamine derivatives as nitric oxide synthase inhibitors. WO02/00651 relates to factor XA inhibitors for use in thromboembolic disorders. WO 01/94318 and WO 01/94317 both describe chemical libraries of substituted pyrrole derivatives and their synthesis for use in high throughput screening for drug discovery. However, they do not provide any biological activity or any medical use, nor do they name a specific compound. Both WO 00/76971 and WO00/76970 claim serine protease inhibitors useful as antithrombotic agents. WO01/36395 discloses triazole derivatives as farnesyl transferase inhibitors. WO 96/33176 and US 5,703,092 relate to hydroxamic acid compounds as inhibitors of metalloproteases and TNF. WO 93/09095 describes 2-heterocyclic ethylamine derivatives and their use in neurological and neurodegenerative disorders. WO 2004/103270 claims compounds for the treatment of thrombosis, in particular factor XI a inhibitors. WO 98/38177, US 6,506,782, US 6,849,650 and US 2003/0130188 all describe heterocyclic compounds or their synthesis as inhibitors of β -amyloid peptide release, useful in alzheimer's disease.

Heterocyclic compounds that can be used as GHS have also been described in the literature.

For example, WO 00/54729 discloses heterocyclic aromatic compounds as GH secretagogues, which are said to stimulate endogenous production and/or release of GH, and may also contain a triazole moiety. In addition, methods of increasing endogenous GH levels or increasing endogenous production or release of GH are described, comprising administering such GHs. Further, there is provided a method of preventing or treating osteoporosis (improving bone density and/or strength), or treating obesity, or increasing muscle mass and/or muscle strength and function in the elderly, or reversing or preventing frailty in the elderly, comprising administering such GHS.

However, WO 00/54729 does not really demonstrate such an effect, although GH release in vivo is claimed. Neither in vitro nor in vivo data demonstrating any stimulation or increase in endogenous production and/or release of GH is included.

Furthermore, WO 00/54729 does not describe or show the effect of those claimed compounds on any biological target, that is, the claimed compounds are not shown/described as ligands for one or more specific receptors, e.g. receptor families, that bind to and modulate their activity.

Furthermore, WO 00/54729 does not describe and demonstrate the inhibitory and/or antagonistic activity of the claimed compounds. Indeed, such compounds have not been shown to reduce endogenous GH levels and/or inhibit or reduce endogenous GH production and/or release. There is neither mention nor clear inhibition of any receptor.

US 6,525,203, US 6,518,292, US 6,660,760 are members of the same family of patents as WO 00/54729, however, no triazole moiety is included as claimed subject matter. Regarding the biological activity, the above-mentioned facts about WO 00/54729 also apply.

WO 2004/021984 describes heterocyclic aromatic GH secretagogues which are said to be useful in stimulating the endogenous production or release of GH. However, the claimed compounds consist of a di-to tetracyclic aromatic ring, and do not contain triazoles.

GH release is claimed in vivo similarly to WO 00/54729, but neither in vitro nor in vivo data demonstrating any stimulation or increase in endogenous production and/or release of GH is included. Regarding the biological activity, the above-mentioned facts about WO 00/54729 also apply.

WO 97/23508 claims compounds that are peptidomimetic properties of GHS, are said to act directly on pituitary cells in vitro to release GH therefrom, and exhibit improved properties such as increased resistance to proteolytic degradation and improved bioavailability. In addition, the claimed compounds may also be administered in vivo to increase GH release. These compounds are peptide derivatives and do not explicitly contain a triazole moiety.

However, still similar to the above-mentioned WO 00/54729 and WO 2004/021984, WO 97/23508 does not show any in vitro or in vivo data demonstrating the claimed effects, such as direct effect on pituitary cells, release of GH therefrom and improved properties. Furthermore, the above-mentioned facts about WO 00/54729 also apply with respect to biological targets and inhibitory/antagonistic activities.

US 6,127,391, US 5,977,178 and US 6,555,570 are members of the family of WO 97/23508. The above-mentioned facts about WO 97/23508 also apply.

Description of the invention

The object of the present invention is to provide novel compounds which can be used for the treatment of physiological and/or pathophysiological conditions mediated by GHS receptors in mammals, in particular in humans. It is another object of the present invention to provide compounds for use in the above treatment, wherein the treatment is effected by modulation of the GHS receptor. It is a further object of the invention to provide GHS receptor antagonists for use in these treatments. It is another object of the present invention to provide GHS receptor agonists for use in these treatments.

The object of the present invention is surprisingly solved in one aspect by providing compounds according to formula (I):

wherein:

R1 and R2 are independently selected from the group consisting of: "hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl", optionally substituted in the alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/or heterocyclylalkyl groups with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,; and is preferably selected from the group consisting of: "alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl", said groups being optionally substituted with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

one of the radicals R3 and R4 is a hydrogen atom and the other radical is selected from the group consisting of: "hydrogen atom, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -alkyl-O-aryl, -alkyl-O-arylalkyl, -alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, -alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, -alkyl-C (O) O-arylalkyl, alkyl-C (O), aryl, heteroaryl, heterocyclyl, heteroaryl-CO-heterocyclylalkyl, heteroaryl-C (O), -alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O-heterocyclyl, -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH ₂-alkyl-CO-OH, -alkyl-NH₂-alkyl-NH-C (NH) -NH₂Alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, alkyl-S-alkyl, alkyl-S-H ", optionally in the form of aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/or heterocycleThe arylalkyl group is substituted with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,; and is preferably selected from the group consisting of: "arylalkyl, heteroarylalkyl, heterocyclylalkyl, -alkyl-O-aryl, -alkyl-O-arylalkyl, -alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, -alkyl-C (O) O-arylalkyl, -alkyl-C (O) O-heteroaryl, and, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O-heterocyclyl, -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH₂-alkyl-CO-OH, -alkyl-NH₂-alkyl-NH-C (NH) -NH ₂", said group being optionally substituted in aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/or heterocyclylalkyl with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

r5 is selected from the group consisting of: "Hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -CO-alkyl, -CO-cycloalkyl, -CO-cycloalkylalkyl, -CO-aryl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl, -CO-C^*(R9R10)-NH₂、-CO-CH₂-C^*(R9R10)-NH₂、-CO-C^*(R9R10)-CH₂-NH₂Alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl ", optionally substituted with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,; and isPreferably selected from the group consisting of: "Hydrogen atom, -CO-alkyl, -CO-cycloalkyl, -CO-aryl, -CO-heteroaryl, -CO-arylalkyl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-C ^*(R9R10)-NH₂、-CO-CH₂-C^*(R9R10)-NH₂、-CO-C^*(R9R10)-CH₂-NH₂Said group being optionally substituted with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

r6 is selected from the group consisting of: "hydrogen atom, alkyl group, cycloalkyl group, cycloalkylalkyl group", and preferably is a hydrogen atom;

r7 and R8 are independently selected from the group consisting of: "hydrogen atom, alkyl group, cycloalkyl group, cycloalkylalkyl group", and preferably is a hydrogen atom;

r9 and R10 are independently selected from the group consisting of: "hydrogen atom, alkyl group, natural alpha-amino acid side chain, non-natural alpha-amino acid side chain", and is preferably selected from the group consisting of: "hydrogen atom, alkyl group";

m is 0, 1 or 2, and preferably 0;

^*represents a carbon atom of R or S configuration when chiral;

they can be used for the preparation of a medicament for the treatment or prevention of physiological and/or pathophysiological conditions mediated by the GHS receptor in mammals.

In a preferred embodiment, there are provided compounds according to formula (I) above, wherein

R3 is selected from the group consisting of: "-alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, -alkyl-C (O) O-arylalkyl, -alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O-heterocyclyl, -alkyl-C (O) O -heterocyclylalkyl, -alkyl-CO-NH₂-alkyl-CO-OH, -alkyl-NH-C (NH) -NH₂alkyl-S-alkyl, alkyl-S-H ", and preferably selected from the group consisting of: "-alkyl-CO-arylalkyl, -alkyl-C (O) O-arylalkyl, -alkyl-CO-NH₂-alkyl-CO-OH ";

In another preferred embodiment, there are provided compounds according to formula (I) above, wherein

R4 is a hydrogen atom;

r5 is selected from the group consisting of: "hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, -CO-cycloalkyl-alkyl, -CO-aryl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl";

with the proviso that if R5 is "-CO-heteroarylalkyl", "heteroaryl" is not imidazole; and is

With the proviso that if R5 is "-CO-heterocyclyl", and "heterocyclyl" contains only nitrogen atoms as heteroatoms, at least two nitrogen atoms are contained in "heterocyclyl"; and is

With the proviso that if R5 is "-CO-heterocyclylalkyl" and "heterocyclyl" contains only nitrogen atoms as heteroatoms, in the case of "heterocyclyl" containing one or two nitrogen atoms, no nitrogen atom is located at the 1-position atom of the "heterocyclyl" directly connecting it to carbonyl "-CO-";

wherein "alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, -CO-cycloalkylalkyl-CO-cycloalkylalkyl, -CO-aryl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl and/or-CO-heterocyclylalkyl "is optionally substituted with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

with the proviso that if R5 is "-CO-cycloalkyl" or "-CO-cycloalkylalkyl", R5 is not substituted at the C atom in position 1 of "cycloalkyl" by NR7R8, said C atom being directly connected to "cycloalkyl" with carbonyl "-CO-" in the case of R5 ═ CO-cycloalkyl "or" alkyl "in the case of R5 ═ CO-cycloalkylalkyl";

With the proviso that if R5 is "-CO-aryl" or "-CO-arylalkyl", and "aryl" is phenyl/benzene and is substituted with only one substituent which is not-NR 7R 8;

r6 is a hydrogen atom;

r7 and R8 are independently selected from the group consisting of: "hydrogen atom, alkyl group, cycloalkyl group, cycloalkylalkyl group", preferably a hydrogen atom; and is

m is 0, 1 or 2, more preferably 0;

In a further aspect, the object of the present invention is surprisingly achieved by providing compounds according to formula (I), wherein

R1 is selected from the group consisting of: "hydrogen, methyl, (2-methoxyphenyl) -methyl, (3-methoxyphenyl) -methyl, (4-methoxyphenyl) -methyl, (3-methoxyphenyl) -ethyl, (4-methoxyphenyl) -ethyl, phenyl-methyl, phenyl-ethyl, (4-ethylphenyl) -methyl, (4-methylphenyl) -methyl, (4-fluorophenyl) -methyl, (4-bromophenyl) -methyl, (2, 4-dimethoxyphenyl) -methyl, (3, 5-dimethoxyphenyl) -methyl, 2-diphenyl-ethyl, naphthalen-1-yl-methyl, 1H-indol-3-yl-methyl, ethyl, benzyl, 2- (1H-indol-3-yl) -ethyl, 3- (1H-indol-3-yl) -propyl, 4-methyl-phenyl, 4-ethyl-phenyl, n-hexyl, (3, 4-dichlorophenyl) -methyl, (4-nitro-phenyl) -methyl, (pyridin-2-yl) -methyl, (pyridin-3-yl) -methyl, (pyridin-4-yl) -methyl, (thiophen-2-yl) -methyl, (thiophen-3-yl) -methyl, (furan-2-yl) -methyl, (furan-3-yl) -methyl,;

R2 is selected from the group consisting of: "methyl, 1H-indol-3-yl-methyl, 2- (1H-indol-3-yl) -ethyl, 3- (1H-indol-3-yl) -propyl, 2-phenyl-ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 2-methoxy-phenylmethyl, 3-methoxy-phenylmethyl, 4-methoxy-phenylmethyl, 2-methoxy-phenylethyl, 3-methoxy-phenylethyl, 4-methoxy-phenylethyl";

r3 is selected from the group consisting of: "hydrogen atom, methyl group, propan-2-yl group, 2-methyl-propan-1-yl group, butan-2-yl group, butan-1-yl group, -CH₂-SH、-(CH₂)₂-S-CH₃1H-indol-3-yl-methyl, phenyl-methyl, 2-phenyl-ethyl, -CH₂-O-CH₂-phenyl, -CH₂-CO-CH₂-phenyl, - (CH)₂)₂-CO-CH₂-phenyl, -CH₂-C (O) O-phenyl, - (CH)₂)₂-C (O) O-phenyl, hydroxy-methyl, 1-hydroxy-ethan-1-yl, -CH₂-CO-NH₂、-(CH₂)₂-CO-NH₂(1-hydroxy-phen-4-yl) -methyl, -CH₂-CO-OH、-(CH₂)₂-CO-OH、-(CH₂)₄-NH₂(1H-imidazol-5-yl) -methyl, - (CH)₂)₃-NH-C(NH)-NH₂、-(CH₂)₃-NH₂、-(CH₂)₃-NH-CO-NH₂", and preferably selected from the group consisting of: "1H-indol-3-yl-methyl, -CH₂-CO-CH₂-phenyl, - (CH)₂)₂-CO-CH₂-phenyl, -CH₂-C (O) O-phenyl, - (CH)₂)₂-C (O) O-phenyl ";

r4 is a hydrogen atom;

r5 is selected from the group consisting of: "Hydrogen atom, -CO-CH₂-NH₂(Gly residue), -CO-CH₂-CH₂-NH₂(alpha-Ala residue), -CO-CHCH₃-NH₂(D-and/or L-alpha-Ala residue), -CO- (pyrrolidin-2-yl) (D-and/or L-Pro residue), 2-amino-2-carbonyl-propane (2-amino-isobutyric acid/Aib residue), 4-carbonyl-1H-piperidine, 3-carbonyl-1H-piperidine, R- (3-carbonyl-1H-piperidine), S- (3-carbonyl-1H-piperidine), 2-carbonyl-1H-piperidine, R- (2-carbonyl-1H-piperidine), S- (2-carbonyl-1H-piperidine), 1-amino-2-carbonyl-benzene, L-amino-2-carbonyl-propane, L-isobutyric acid/Aib residue, 4-carbonyl-1H-piperidine, 3-carbonyl-1H-piperidine, L-carbonyl-1, Carbonyl-cyclohexane, 2-acetyl-pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine, 4-propionyl-pyridine, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-1H-imidazole, 2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-pyrazine, 2-carbonyl-4-hydroxy-1H-pyrrolidine, 4-carbonyl-1H, 3H-diazacyclohexane, methylsulfonyl, phenylsulfonyl, 1-carbonyl-1-amino-2-phenylethane, phenylmethyl, 1-carbonyl-4-azide-benzene, 2-carbonyl-2, 5-dihydro-1H-pyrrole, 2-carbonyl-piperazine, 2-carbonyl-1H-pyrrolidine, 2-aminoethane, carbonyl-benzene, 2-carbonyl-pyrazine, 3-carbonyl-pyrazine, 4-carbonyl-oxacyclohexane, 4-methyl-phenylsulfonyl, phenylmethyl-sulfonyl ";

R6 is a hydrogen atom;

m is 0;

R3 is selected from the group consisting of: "-CH₂-CO-CH₂-phenyl, - (CH)₂)₂-CO-CH₂-phenyl, -CH₂-CO-NH₂、-(CH₂)₂-CO-NH₂、-CH₂-CO-OH、-(CH₂)₂-CO-OH、-(CH₂)₃-NH-C(NH)-NH₂、-CH₂-SH、-(CH₂)₂-S-CH₃”；

R5 is selected from the group consisting of: "hydrogen atom, methylsulfonyl group, phenylsulfonyl group, carbonyl-cyclohexane, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine, 2-acetyl-pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine, 4-propionyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-1H-imidazole, 2-carbonyl-pyrazine, 4-carbonyl-1H, 3H-diazacyclohexane ";

In a further aspect, the object of the present invention is surprisingly achieved by providing novel triazole compounds selected from the group consisting of:

the compound 1(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 2(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 3(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 4(R) -N- (1- (5-benzyl-4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 5(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 6(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

The compound 7(R) -N- (1- (4- (3-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 8(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 9(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 10(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 11(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 12(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 13(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 14(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-bromobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 15(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 16(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 17(R) -N- (1- (4, 5-bis (2- (1H-indol-3-yl) ethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 18(S) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 19(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 20(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

The compound 21(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3, 5-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 22(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 23(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 24(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 25(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2-methoxy) benzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 26(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 27(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 28(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3, 4-dichlorobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 29(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-fluorobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 30(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 31(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

the compound 32(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

compound 33(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 34(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 36(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,

compound 37(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 38(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,

compound 39(R) -N- (1- (5-benzyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 40(2S, 4) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-hydroxypyrrolidine-2-carboxamide,

the compound 41(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

the compound 42(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

the compound 43(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

The compound 44(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

the compound 45(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

compound 46(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

compound 47(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

compound 48(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,

compound 49(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,

the compound 50(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

the compound 51(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

Compound 52(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide,

the compound 53(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) cyclohexanecarboxamide,

compound 54(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

the compound 55(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

compound 56(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3-aminopropionamide,

the compound 57(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopropionamide,

compound 58(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,

the compound 59(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3- (pyridin-3-yl) propionamide,

Compound 60(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

compound 61(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

compound 62(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

compound 63(R) -N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,

compound 64(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

the compound 65(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,

compound 66(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,

the compound 67(R) -N-1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,

Compound 68(S) -N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

compound 69(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

the compound 70(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

the compound 71(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,

compound 72(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,

compound 73(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

compound 74(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethylamine,

Compound 75(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

the compound 76(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,

the compound 77(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,

the compound 78(R) -N-1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,

compound 79(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

the compound 80(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

the compound 81(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,

compound 82(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

The compound 83(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

compound 84(R) -N-1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide,

the compound 85(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide,

compound 86(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-cis-aminocyclohexanecarboxamide,

the compound 87(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

compound 88(R) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,

compound 89(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

the compound 90(R) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

The compound 91(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

the compound 92(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 93(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide,

compound 94(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-carboxamide,

the compound 95(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 96(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 97(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 98(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

The compound 99(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 100(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 101(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 102(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 103(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 104(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 105(R) -N- (1- (5-benzyl-4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 106(R) -N- (1- (5-benzyl-4- (2, 2-diphenylethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 107(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 2-diphenylethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 108(R) -N- (1- (4- (3, 5-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 109(R) -N- (1- (4, 5-dibenzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 110(R) -N- (1- (5-benzyl-4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 111(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 112(S) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 113(R) -N- (1- (4- (3, 5-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 114(R) -N- (1- (4- (4-bromobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 115(R) -N- (1- (4- (2-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 116(S) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 117(R) -N- (1- (4, 5-diphenylethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 118(R) -N- (1- (4- (3, 4-dichlorobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 119(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethylamine,

the compound 120(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide,

compound 121(R) -N- (1- (4- (4-fluorobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 122(R) -N- (1- (4- (3, 4-dichlorobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 124(R) -N- (1- (4- (4-methylbenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 125(S) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 126(S) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 128N- ((R) -1- (4- (4-nitrobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 129(S) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 130(R) -N- (1- (4- (4-methoxyphenethyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 131(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 132(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 133(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-3-carboxamide,

compound 134(S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

compound 135N ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

compound 136N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide,

compound 137(2R) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide,

compound 138N ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

compound 139N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopyridine-3-carboxamide,

Compound 140(2S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopropionamide,

compound 141N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide,

the compound 142N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-carboxamide,

compound 143(2S) -N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) pyrrolidine-2-carboxamide,

compound 144N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-aminoacetamide,

compound 145N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

compound 146N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide,

compound 147N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

compound 148N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

The compound 149N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

the compound 150(2S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide,

compound 152N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

compound 153N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-trans-aminocyclohexanecarboxamide,

compound 154N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide,

compound 155(3S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

compound 156N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide,

compound 157N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

Compound 158N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

compound 159N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide,

the compound 160N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide,

the compound 161N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) pyrazine-2-carboxamide,

compound 162N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-aminoacetamide,

compound 163N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-carboxamide,

the compound 164N- ((R) -1- (5-benzyl-4- ((pyridin-2-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

compound 165N- ((R) -1- (5-benzyl-4- ((pyridin-2-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-acetamide,

Compound 166N- ((R) -1- (5-benzyl-4- ((pyridin-2-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

the compound 167N- ((R) -1- (5-benzyl-4- ((pyridin-4-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 168N- ((R) -1- (5- (4-methoxybenzyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 169N- ((R) -1- (5-benzyl-4- ((pyridin-4-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

compound 170N- ((R) -1- (5-benzyl-4- ((pyridin-4-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) 2-amino-acetamide,

compound 171(R) -benzyl-3- (2-aminoisobutyrylamino) -3- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -propionate,

compound 172N- ((R) -1- (5-benzyl-4- ((pyridin-3-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 173N- ((R) -1- (4-benzyl-5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 174N- ((R) -2- (1H-indol-3-yl) -1- (4-methyl-5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide,

compound 175N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 176N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) benzamide,

the compound 177(R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-phenylmethanesulfonamide,

compound 178(R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-toluenesulfonylethylamine,

compound 179N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

the compound 180N-1- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) ethane-1, 2-diamine,

compound 181N- ((R) -1- (4- ((furan-2-yl) methyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

The compound 182N- ((R) -1- (4- ((furan-2-yl) methyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

the compound 183N- ((R) -1- (4- ((furan-2-yl) methyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,

compound 184N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -tetrahydro-2H-pyran-4-carboxamide,

compound 185N- ((R) -1- (5- ((1H-indol-3-yl) methyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 186(2S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-3-phenylpropanamide,

the compound 187(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-toluenesulfonylethylamine,

compound 188N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-azidobenzamide,

compound 189N-benzyl- (R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethylamine,

The compound 190(2S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2, 5-dihydro-1H-pyrrole-2-carboxamide,

for the avoidance of doubt, if the chemical name and chemical structure of a compound described above are inconsistent by mistake, the chemical structure is considered to be a well-defined compound.

In a preferred embodiment, these compounds can be used for the preparation of a medicament for the treatment or prevention of physiological and/or pathophysiological conditions mediated by GHS receptors in mammals.

In a further preferred embodiment, all triazole compounds described herein, i.e. in general (formula (I) above and different R radicals) and specifically hereinafter referred to as compounds of the invention, can be used for the preparation of a medicament for the treatment or prevention of physiological and/or pathophysiological conditions mediated by GHS receptors in mammals, wherein the treatment is effected by means of GHS receptor modulation.

In another preferred embodiment, all compounds of the invention are GHS receptor antagonists.

More preferably, the GHS receptor antagonist is a compound selected from the group consisting of:

compound 1, 3, 12, 13, 14, 18, 20, 22, 23, 33, 36, 37, 38, 41, 46, 47, 48, 49, 50, 51, 52, 53, 57, 58, 59, 60, 61, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 79, 80, 82, 85, 86, 87, 88, 89, 90, 91, 93, 101, 102, 109, 114, 116, 119, 134, 135, 136, 137, 138, 139, 140, 145, 146, 147, 148, 150, 152, 153, 154, 156, 157, 159, 160, 161, 164, 171, 174, 176, 178, 179, 182, 184, 186, 188 and/or compound 190.

In a further preferred embodiment, all compounds of the invention are GHS receptor agonists.

More preferably, the GHS receptor agonist is a compound selected from the group consisting of:

compound 2, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 17, 19, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 39, 40, 42, 43, 44, 45, 54, 55, 56, 62, 67, 78, 81, 83, 84, 87, 92, 94, 99, 103, 104, 105, 106, 107, 108, 110, 111, 115, 117, 118, 121, 122, 124, 130, 131, 142, 155, 158, 163, 173, 175, 180, 181, 183, 185 and/or compound 187.

The terms used to explain the compounds of formula (I) above always have the following meanings, unless otherwise indicated in the specification or claims:

the term "substituted" means that the corresponding radical or group has one or more substituents. If the radical has a large number of substituents, and the choice of the various substituents is specified, these substituents are chosen independently of one another and need not be identical. The term "unsubstituted" means that the corresponding group has no substituents. The term "optionally substituted" means that the corresponding group is unsubstituted or substituted with one or more substituents. The term "substituted with up to 3 substituents" means that the corresponding radical or group is substituted with one or two or three substituents.

The term "alkyl" for the purposes of the present invention includes acyclic saturated hydrocarbons having C1-C12 carbon atoms, which may be straight-chain or branched. The term "alkyl" preferably denotes an alkyl chain of 1 to 8, particularly preferably 1 to 6, carbon atoms. Examples of suitable alkyl radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, tert-pentyl, 2-or 3-methyl-pentyl, n-hexyl, isohexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl.

The term "cycloalkyl" represents a saturated or partially unsaturated non-aromatic cyclic hydrocarbon group/radical containing 1 to 3 rings, including monocycloalkyl, bicycloalkyl and tricycloalkyl groups, and containing a total of 3 to 20, preferably 3 to 10 ring-forming carbon atoms, most preferably (C3-C8) -cycloalkyl. Examples of suitable cycloalkyl radicals are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclohexenyl, cyclopentenyl, cyclooctadienyl.

The term "cycloalkylalkyl" denotes a radical wherein the cycloalkyl group is attached via an alkyl group, wherein alkyl and cycloalkyl have the meaning as defined herein, preferably a (C3-C8) -cycloalkyl- (C1-C4) -alkyl radical. Examples thereof are cyclopropylmethyl, cyclohexylmethyl, cyclopentylethyl, cyclohexenylethyl.

The term "alkenyl" for the purposes of the present invention includes acyclic unsaturated or partially unsaturated hydrocarbons having C2-C12 carbon atoms, which may be straight-chain or branched, and contain one or more double bonds. The term "alkenyl" preferably represents an alkenyl chain of 2 to 8, particularly preferably 2 to 6, carbon atoms. Examples are ethenyl, propenyl, butenyl, pentenyl, hexenyl, octadienyl and the like.

The term "alkynyl" denotes an acyclic unsaturated or partially unsaturated hydrocarbon having C2-C12 carbon atoms, which may be straight-chain or branched, and which contains one or more triple bonds. The term "alkynyl" preferably represents an alkynyl chain of 2 to 8, particularly preferably 2 to 6, carbon atoms. Examples are propynyl, butynyl, pentynyl, hexynyl.

The term "aryl" denotes an aromatic hydrocarbon system having 3 to 14, preferably 5 to 14, carbon atoms, which may also be fused to another saturated, (partially) unsaturated or aromatic cyclic system. Examples of "aryl" are especially phenyl, biphenyl, naphthyl and anthracenyl, and also indanyl, indenyl or 1, 2, 3, 4-tetrahydronaphthyl.

The term "heteroaryl" denotes a 5-, 6-or 7-membered cyclic aromatic radical comprising at least 1, if appropriate also 2, 3, 4 or 5 heteroatoms, preferably nitrogen, oxygen and/or sulfur, where these heteroatoms are identical or different. The number of nitrogen atoms is preferably between 0 and 3 and the number of oxygen and sulphur atoms is between 0 and 1. The term "heteroaryl" also includes systems in which the aromatic ring is part of a bicyclic or polycyclic ring system, for example, in which the aromatic ring is fused to an aryl, cycloalkyl, heteroaryl, or heterocyclyl group as defined herein via any desired and possible heteroaryl radical ring members. Examples of "heteroaryl" include pyrrolyl, thienyl, furyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl, and isoquinolinyl.

The terms "arylalkyl" and "heteroarylalkyl" refer to radicals wherein an aryl or heteroaryl radical is attached via an alkyl group, wherein alkyl, aryl and heteroaryl have the meanings as defined herein. A preferred "arylalkyl" group is phenyl- (C)₁-C₄) -an alkyl radical, preferably a benzyl or phenylethyl radical. A preferred "heteroarylalkyl" is indolyl- (C)₁-C₄) -an alkyl radical, preferably 1H-indol-3-yl-methyl or 2 (1H-indol-3-yl) -ethyl.

The term "heterocyclyl" denotes a mono-or polycyclic ring system of 3 to 14, preferably 5 or 6 to 14 ring atoms, which may be carbon atoms only. However, the ring system may also comprise 1, 2, 3, 4 or 5 heteroatoms, in particular nitrogen, oxygen and/or sulfur. The cyclic system may be saturated, mono-or polyunsaturated, but may not be aromatic. In the case of a cyclic system consisting of at least two rings, these rings may be fused or spiro or otherwise connected. The "heterocyclyl" radical may be attached to any carbon or heteroatom that results in the creation of a stable structure. Examples include pyrrolidinyl, thiapyrrolidinyl, piperidinyl, piperazinyl, oxapiperazinyl, oxapiperidinyl, and oxadiazolyl.

The term "heterocyclylalkyl" denotes an atomic group wherein the heterocyclyl is attached through an alkyl, wherein alkyl and heterocyclyl have the meanings as defined herein.

The terms "alkylsulfonyl", "arylsulfonyl" and "arylalkylsulfonyl" denote wherein alkyl, aryl or arylalkyl is via-SO₂-a radical of atoms to which the groups are attached, wherein alkyl, aryl and arylalkyl have the meaning as defined herein. Examples are methylsulfonyl and phenylsulfonyl.

The term "halogen", "halogen atom" or "halogen substituent" (Hal-) denotes one, if appropriate a large number of fluorine (F), bromine (Br), chlorine (Cl) or iodine (I) atoms. The designations "dihalo", "trichloro" and "perhalo" refer to two, three and four substituents, respectively, wherein each substituent may be independently selected from the group consisting of fluorine, chlorine, bromine and iodine. "halogen" preferably denotes a fluorine, chlorine or bromine atom.

The term "natural alpha-amino acid side chain" means for the purposes of the present invention all side chains of the known 20 proteinogenic alpha-amino acids as well as side chains of naturally occurring (i.e. in any biological system) alpha-amino acids, such as selenocysteine, pyrrolysine, citrulline, ornithine, homocysteine, N-methylarginine, N-acetyl lysine, gamma-carboxyglutamic acid, 5-hydroxylysine, 3-methylhistidine and/or N, N-trimethyllysine. In this connection, "side chain" denotes a residue attached to an a-carbon atom, for example methyl in the case of the Ala side chain or benzyl in the case of the Phe side chain.

The term "non-natural alpha-amino acid side chain" for the purposes of the present invention means all side chains of known alpha-amino acids which are neither proteinogenic nor known to occur naturally (i.e. in any biological system). Examples are norleucine, cyclohexylglycine, 2-naphthylalanine, substituted alpha-amino acids (e.g. halogen substituted Tyr or Phe) and protected alpha-amino acid side chains, wherein protecting groups such as Fmoc, Boc, Z, CBZ, Aloc, trityl, acetyl and/or benzyl are directly attached/reacted to a functional group (e.g. an amino, hydroxyl and/or carboxyl residue). In this regard, "side chain" means a "natural α -amino acid side chain".

Examples of the above-mentioned embodiments of radicals R1 to R10 having functional groups (e.g. amino, hydroxyl and/or carboxyl residues), e.g. alkyl-CO-NH₂-alkyl-CO-OH, -alkyl-NH₂-alkyl-NH-C (NH) -NH₂、-CO-C^*(R9R10)-NH₂、-CO-CH₂-C^*(R9R10)-NH₂、-CO-C^*(R9R10)-CH₂-NH₂And/or 2-amino-2-carbonyl-propane (2-amino-isobutyric acid/Aib residue) may be protected with the above-mentioned protecting group. Such embodiments bearing protecting groups are considered to be within/fall within the scope and spirit of the present invention.

All stereoisomers of the compounds of the invention are contemplated, either as mixtures or in pure or substantially pure form. The compounds of the present invention may have asymmetric centers at any carbon atom, including any group of R atoms. The compounds according to the invention may therefore be present in their racemic form, in pure enantiomeric and/or diastereomeric form or in the form of mixtures of such enantiomers and/or diastereomers. The mixture may have any desired stereoisomer mixing ratio. All such stereochemical forms and mixtures are within the scope of the present invention.

Thus, for example, the compounds of the invention which have one or more chiral centers and are present as racemates or diastereomeric mixtures can be fractionated into their optically pure isomers, i.e. enantiomers or diastereomers, by methods known per se. The compounds of the invention can be isolated by chiral or achiral phase column chromatography, or by recrystallization from an optionally optically active solvent, or by derivatization with optically active acids or bases, or with optically active reagents, for example optically active alcohols, with subsequent elimination of radicals.

The compounds of the invention may, if possible, be in tautomeric form.

It is likewise possible for the compounds of the invention to be in the form of any desired prodrug, for example esters, carbonates or phosphates, in which case the actual biologically active form is released only by metabolic action. Any compound capable of being converted in vivo to provide a biologically active ingredient (i.e., a compound of the invention) is a prodrug within the scope and spirit of the invention.

Prodrugs in various forms are well known in the art and are described, for example, in the following references:

(i)The Practice of Medicinal Chemistry(Wermuth CG et al.，Chapter 31，Academic Press 1996)；

(ii)Design of Prodrugs(editor：Bundgaard H，Elsevier1985)；

(iii)A Textbook of Drug Design and Development(Krogsgaard-Larson P and Bundgaard H，eds.，Chapter 5：113-191，Harwood Academic Publishers 1991)。

said references are incorporated herein by reference.

It is further known that chemical substances are converted in the body into metabolic products which, where appropriate, likewise elicit the desired biological effect — in some circumstances even in a more prominent form.

Any biologically active compound metabolically converted in vivo from any of the compounds of the invention is a metabolite within the scope and spirit of the invention.

Compounds of the invention, if they have sufficiently basic groups, such as primary, secondary or tertiary amines, can be converted into salts with inorganic and organic acids. The pharmaceutically acceptable salts of the compounds of the present invention are preferably formed with the following acids: hydrochloric acid, hydrobromic acid, iodic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, p-toluenesulfonic acid, carbonic acid, formic acid, acetic acid, sulfoacetic acid, trifluoroacetic acid, oxalic acid, malonic acid, maleic acid, succinic acid, tartaric acid, racemic acid, malic acid, pamoic acid, mandelic acid, fumaric acid, lactic acid, citric acid, taurocholic acid, glutaric acid, stearic acid, glutamic acid, or aspartic acid. The salts formed are, in particular, the hydrochloride, chloride, hydrobromide, bromide, iodide, sulfate, phosphate, methanesulfonate, toluenesulfonate, carbonate, bicarbonate, formate, acetate, sulfoacetate, trifluoromethanesulfonate, oxalate, malonate, maleate, succinate, tartrate, malate, pamoate, mandelate, fumarate, lactate, citrate, glutarate, stearate, aspartate and glutamate salts. And the stoichiometry of the salt formed from the compounds of the invention can be an integer or non-integer multiple of one.

The compounds of the invention, if they contain sufficiently acidic groups, for example carboxyl, sulfonic acid, phosphoric acid or phenolic groups, can be converted with inorganic and organic bases into their physiologically tolerated salts. Examples of suitable inorganic bases are ammonium, sodium hydroxide, potassium hydroxide, calcium hydroxide, and examples of organic bases are ethanolamine, diethanolamine, triethanolamine, ethylenediamine, t-butylamine, t-octylamine, dehydroabietylamine, cyclohexylamine, dibenzylethylenediamine, and lysine. And the stoichiometry of the salt formed from the compounds of the invention can be an integer or non-integer multiple of one.

The compounds of the invention are likewise possible in the form of their solvates, in particular hydrates, which can be obtained, for example, by crystallization from solvents or from aqueous solutions. It is furthermore possible that one, two, three or any number of solvate or water molecules may be combined with the compounds of the invention to give solvates and hydrates.

Chemical species are known to form solids that exist in different sequential states, which are referred to as polymorphic forms or variants. The various variants of polymorphic substances may differ widely in their physical properties. The compounds of the invention may exist in various polymorphic forms, and certain changes may be metastable. All such polymorphic forms of the compounds of the invention are considered to be within the scope of the invention.

The triazole derivatives described herein (compounds of the invention) are ghrelin analog ligands of the GHS receptor. Thus, the above-described compounds of the invention are suitable for the treatment or prevention of physiological and/or pathophysiological conditions mediated by GHS receptors and/or physiological and/or pathophysiological conditions which can be influenced by the modulation of these receptors and thus prevented, treated and/or alleviated.

For the purposes of the present invention, the term "treatment" is also intended to include prophylactic treatment or alleviation.

The term "ghrelin analog ligand" or "ligand" is intended for the purposes of the present invention to mean every compound that binds to a receptor (the receptor in the present invention is the GHS receptor) in any way and induces activation, inhibition and/or another imaginable effect of such a receptor. The term "ghrelin analog ligand" or "ligand" thus includes agonists, antagonists, partial agonists/antagonists, inverse agonists and other ligands that cause a similar effect to that of an agonist, antagonist, partial agonist/antagonist or inverse agonist at a receptor.

For the purposes of the present invention, the term "GHS receptor antagonist" or "antagonist of GHS receptor" means a compound of the present invention that binds to the GHS receptor but does not elicit proper activation of the receptor as assessed by recording intracellular calcium increases that are characteristic of the activation of G-protein coupled receptors (GPCRs).

Test compounds (at 10) will be evaluated for the ability of any of the compounds of the invention to properly activate the receptor as follows^-6M concentration) degree of GHS-R1 a activation (intracellular calcium increase) and 10^-6The extent of activation of GHS-R1 a (increase in intracellular calcium) by Mghrelin (100%) was compared to basal levels (0%). Such assessment is easily performed by the person skilled in the art due to his expert knowledge. Results are percentage values for each test compound.

Any compound of the invention that does not exhibit at least a 20% degree of GHS-R1 a activation (increase in intracellular calcium) is considered to not elicit proper activation and is therefore a GHS receptor antagonist, as assessed by the above description. Preferably, such compounds do not show an antagonistic effect (counter/decreasing) on ghrelin and/or other GHS stimulated intracellular calcium increase, preventing such stimulation or even acting as inverse agonists (an inverse agonist is a ligand that binds to the same receptor binding site as an agonist or antagonist but results in inhibition of the basal/constitutive activity of the receptor, in principle an agonist with negative intrinsic activity). Such compounds may in turn exhibit inhibitory activity on GH secretion and/or other physiological or pathophysiological conditions or effects, such as food intake or adipogenesis. Their effects may be irrelevant. Thus, they may have no effect on GH secretion at all, while inhibiting other physiological effects. They may even stimulate other physiological effects.

For the purposes of the present invention, the term "GHS receptor agonist" or "agonist of GHS receptor" denotes a compound of the present invention that binds to the GHS receptor and initiates the proper activation of the receptor as assessed by recording the intracellular calcium increase that is characteristic of the activation of G-protein coupled receptors.

Any compound of the invention that exhibits a degree of GHS-R1 a activation (increase in intracellular calcium) of at least 20% is considered to elicit proper activation and is therefore a GHS receptor agonist, as assessed by the above description. Such compounds may mimic the effects of ghrelin and/or GHS on GH secretion, such as food intake or adipogenesis. Like antagonists, the effects of agonist compounds may be unrelated to GH secretion effects. Such compounds may even antagonize (counteract/reduce) ghrelin and/or other GHS-stimulated increases in intracellular calcium.

The term "GHS receptor" or "GHS-R" is intended to encompass, for the purposes of the present invention, receptors that bind at least one known peptidyl and/or non-peptidyl GHS and/or ghrelin. The term "GHS receptor" or "GHS-R" is also intended to encompass different GHS binding sites in the various tissues and/or organs described herein that bind at least one known peptidyl and/or non-peptidyl GHS and/or ghrelin, and may be a GHS-R subtype that has not yet been identified.

The skilled person can easily verify the binding of a given known peptidyl and/or non peptidyl GHS and/or ghrelin on the basis of his expert knowledge, e.g. a suitable binding assay representing only routine experimental methods.

Such GHS receptors may or may not be stimulated/activated by ghrelin (ghrelin responsive) with respect to acylated and non-acylated ghrelin, respectively. Stimulation/activation of such receptors may result in, but need not necessarily, trigger GH production and/or GH secretion and/or increase GH plasma levels.

Preferably, such GHS receptors are selected from the group consisting of "GHS type 1 receptors, GHS-R1 a, GHS-R1 b, motilin receptor 1a, neurotensin receptor, TRH receptor, GPR 38(FMI), GPR39(FM2), FM3, GHS binding site, GHS-R subtype, cardiac GHS-R, mammary GHS-R".

More preferably, such GHS receptors are selected from the group consisting of "GHS type 1 receptors, GHS-R1 a, GHS-R1 b", most preferably GHS-R1 a.

As discussed herein, GHS receptors (including GHS binding sites and GHS-R subtypes) are known to be concentrated in the hypothalamic-pituitary region, but also appear to be distributed in other central and peripheral tissues. Furthermore, they are also expressed in various tumor tissues, even from tumor tissues of organs that do not express these receptors under physiological conditions.

For the purposes of the present invention, all such GHS receptor (including GHS binding sites and GHS-R subtypes) expressing sex organs and/or tissues are intended to be encompassed by the scope of the present invention. The skilled person can easily verify, on the basis of his expert knowledge, the expression of the GHS receptor (including the GHS binding site and the GHS-R subtype) in a given organ and/or tissue, for example suitable molecular bioassays, such as immunofluorescence or immunoprecipitation assays, which represent only routine experimental methods.

Preferably, such GHS receptors are located in a tissue and/or organ selected from the group consisting of: "endocrine tissue, exocrine tissue, peripheral tissue, adipose/adipose tissue, brain, hypothalamus, thalamus, hippocampus, striatum, cortex, pituitary, central nervous system, spinal cord, gland, adrenal gland, thyroid gland, salivary gland, mammary gland, neuron, intestine (bowel), intestine (intestine), stomach, heart, liver, pancreas, kidney, bile (bile), bile (gall), bladder, prostate, spleen, muscle, skeletal muscle, aorta, artery, vein, immune cell, leukocyte, lymphocyte, T cell, B cell, granulocyte, monocyte, macrophage, dendritic cell, mast cell, NK cell, neutrophil, eosinophil, basophil, lymph node, bone marrow, tonsil, thymus, placenta, testis, ovary, uterus, lung, adipose cell, tumor/cancer cell, cancer cell, Prostate cancer cells, thyroid cancer cells, lung cancer cells, breast cancer cells.

As noted above, the compounds of the present invention are ghrelin analog ligands of the GHS receptor. They may be administered to a variety of mammalian species, including humans, for the treatment or prevention of physiological and/or pathophysiological conditions in such mammals.

For the purposes of the present invention, all mammalian populations are considered to be included. Preferably, such mammal is selected from the group consisting of "human, domestic animal, cow, domestic animal, pet, cow, sheep, pig, goat, horse, pony, donkey, hinny, mule, hare, rabbit, cat, dog, guinea pig, hamster, rat, mouse". More preferably, such mammal is a human.

The compounds of the invention are non-peptide ghrelin analog ligands of the GHS receptor, surprisingly characterized by strong binding affinity to such receptors. Such compounds may, for example, preferably exhibit a GHS-R1 a binding IC of less than 1000nM₅₀The value is obtained. More preferably, such compounds may exhibit a GHS-R1 a binding IC of less than 500nM, even more preferably less than 300nM, most preferably less than 100nM₅₀The value is obtained.

Due to their surprisingly strong receptor binding properties, the compounds of the invention can advantageously be administered at lower doses than other less effective binding agents, while still achieving an equivalent or even higher desired biological effect. In addition, such a reduction in dosage may advantageously result in less or even no medical adverse effects. Further, the high binding specificity of the compounds of the invention may be explained by an active reduction of unwanted side effects regardless of the applied dose.

Furthermore, the compounds of the present invention are resistant to degradation by gastrointestinal enzymes due to their non-peptidic nature. They therefore offer the advantage of being administered by the oral route. They surprisingly show improved metabolic stability and/or improved bioavailability. Thus, a favorable dose reduction may still be achieved, which may result in fewer or even no side effects.

The compounds of the present invention may be antagonists or agonists of the GHS receptor, as illustrated and defined herein.

The GHS receptor antagonists of the invention may be used, for example, to inhibit ghrelin and/or other GHS-stimulated GHS receptors, thereby reducing and/or blocking GH production and/or secretion and/or GH plasma levels. In addition, such GHS receptor antagonists may also be useful for inhibiting or preventing the physiological or pathophysiological effects of ghrelin not involved in GH production and/or GH secretion.

Thus, the GHS receptor antagonists of the present invention are suitable for the treatment and/or prevention of various physiological and pathophysiological conditions as disclosed herein, in particular for the short, medium and/or long term regulation of energy balance, short, medium and/or long term regulation (stimulation and/or inhibition) of food intake, the treatment of adipogenesis, obesity and/or obesity, weight gain and/or reduction, and the treatment of tumor cell proliferation.

In contrast, the GHS receptor agonists of the present invention may e.g. be used for activation of the GHS receptor and stimulation/increase of GH production and/or GH secretion, and thus will have similar effects or uses as growth hormone itself, ghrelin and/or known GHS.

Thus, the GHS receptor agonists of the present invention are suitable for the treatment and/or prevention of various physiological and pathophysiological conditions as disclosed herein, in particular growth retardation, cachexia, inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy).

For the purposes of the present invention, all physiological and/or pathophysiological conditions known to be mediated by the GHS receptor are intended to be included.

Preferably, these physiological and/or pathophysiological conditions are selected from the group consisting of: "acute fatigue syndrome after elective surgery (electon surgery) and muscle loss, adipogenesis, obesity, age-related hypofunction of the thymus, age-related hypofunction of the elderly (ARFD), aging in companion animals, alzheimer's disease, anorexia (e.g., associated with cachexia or aging), anxiety, blood pressure (reduction), weight gain/loss, fracture repair (acceleration), stimulation of bone remodeling, cachexia and protein loss caused by chronic diseases (e.g., cancer or AIDS), cardiac dysfunction (e.g., associated with valvular disease, myocardial infarction, cardiac hypertrophy or congestive heart failure), cardiomyopathy, stimulation of cartilage growth, disorders of catabolism associated with pulmonary dysfunction and ventilator dependence, catabolic side effects of glucocorticoids, catabolic states of aging, central nervous system disorders (combined with antidepressants), Chronic dialysis, Chronic Fatigue Syndrome (CFS), increased cognitive function (e.g. in dementia, alzheimer's disease), complex bone fractures (e.g. endo-dislocation osteogenesis), complications associated with transplantation, congestive heart failure (alone/in combination with corticotropin releasing factor antagonists), crohn's disease and ulcerative colitis, cushing's syndrome, dementia, depression, short-, medium-and/or long-term regulation of energy balance, short-, medium-and/or long-term regulation (stimulation and/or inhibition) of food intake, frailty (e.g. in the elderly), gastrectomy (ghrelin replacement therapy), post-gastric ileus, improved glycemic control, stimulation of growth hormone release in elderly, growth hormone replacement in stressed patients, growth promotion in livestock, growth retardation associated with Prader-Willi syndrome and tanner's syndrome, Growth retardation associated with crohn's disease, growth retardation, maintenance of hair/nail growth, hip fracture, hunger, hypercortisolism, hyperinsulinemia (including islet blast proliferation), hypothermia, immunodeficiency in subjects with reduced T4/T8 cell ratio, improved immune response from vaccination, stimulation of the immune system in companion animals, stimulation of the immune system, immunosuppression in immunosuppressed patients, inflammation or inflammatory effects, inflammatory bowel disease, insulin resistance of the heart, insulin resistance in type 2 diabetics, insulin resistance (including NIDDM), diabetes, type I diabetes, type II diabetes, intrauterine growth retardation, irritable bowel syndrome, lipodystrophy (e.g., HIV-induced), maintenance of metabolic homeostasis, increased milk production in livestock, increased muscle mass/strength, increased muscle motility, Increased muscle strength, maintenance of muscle strength/function in the elderly, muscle atrophy, musculoskeletal impairment (e.g., in the elderly), Noonan syndrome, obesity and obesity-related growth retardation, osteoblast stimulation, osteochondral dysplasia, osteoporosis, ovulation induction (adjuvant therapy), physiological short stature (including growth hormone deficient children), post-operative ileus, impaired protein catabolic response following major surgery/trauma, enhanced protein kinase B activity, psychosocial loss, pulmonary dysfunction and ventilator dependence, increased pulmonary function, induction of pulsatile growth hormone release, recovery of burn patients and reduction of hospitalization (acceleration) of burn patients, renal failure or insufficiency due to growth retardation, maintenance of renal homeostasis in weak elderly, sarcopenia, schizophrenia, maintenance of sensory function (e.g., auditory dysesthesia, hyperesthesia, etc.), Vision, smell and taste), short bowel syndrome, short stature associated with chronic disease, skeletal dysplasia, maintenance of skin thickness, sleep disorders, improvement in sleep quality, thrombocytopenia, stimulation of thymus development, tooth repair or growth, tumor cell proliferation, ventricular dysfunction or reperfusion events, wasting associated with AIDS, wasting associated with chronic liver disease, wasting associated with Chronic Obstructive Pulmonary Disease (COPD), wasting associated with multiple sclerosis or other neurodegenerative disorders, wasting secondary to bone fracture, stimulation of sheep wool growth, trauma healing (acceleration), delayed trauma healing ". More preferably, these physiological and/or pathophysiological conditions are selected from the group consisting of: "short, medium and/or long term regulation of growth retardation, cachexia, energy balance; short, medium and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, obesity and/or obesity; weight gain and/or loss; diabetes, type I diabetes, type II diabetes, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, and/or gastrectomy (ghrelin replacement therapy) ".

In a further aspect of the invention, the compounds of the invention may be used in combination with at least one additional pharmacologically active substance.

Such additional pharmacologically active substances may be other compounds of the present invention and/or other "suitable therapeutic agents" which may be used for the treatment and/or prevention of the above-mentioned physiological and/or pathophysiological conditions. The additional pharmacologically active substance may be an antagonist of the GHS receptor and/or an agonist of the GHS receptor, depending on the purpose of the combination. The skilled person can readily carry out the selection and combination of additional pharmacologically active substances on the basis of his expert knowledge and depends on the purpose of the combined use and on the physiological and/or pathophysiological condition to be addressed.

In a preferred embodiment, the compounds according to the invention are used for the treatment and/or prophylaxis of the abovementioned physiological and/or pathophysiological conditions in the form of medicaments, wherein such medicaments comprise at least one additional pharmacologically active substance.

In another preferred embodiment, the compounds according to the invention are used for the treatment and/or prophylaxis of the abovementioned physiological and/or pathophysiological conditions in the form of a medicament, wherein the medicament is applied before and/or during and/or after the treatment with at least one additional pharmacologically active substance.

Such "suitable therapeutic agents" include: "GHS, antidiabetic agent; anti-osteoporosis agents; anti-obesity agents; an anti-inflammatory agent; anxiolytic agents; an antidepressant; an antihypertensive agent; anti-platelet agents; antithrombotic and thrombolytic agents; a cardiac glycoside; cholesterol/lipid lowering agents; mineralocorticoid receptor antagonists; a phosphodiesterase inhibitor; protein tyrosine kinase inhibitors; thyroid mimetics (including thyroid receptor antagonists); an assimilating agent; HIV or AIDS therapy; therapies useful for the treatment of alzheimer's disease and other cognitive disorders; therapies useful for treating sleep disorders; an antiproliferative agent; an anti-neoplastic agent; antiulcer and gastroesophageal reflux disease agents; a Progestagen Receptor Agonist (PRA); an estrogen; testosterone; a selective estrogen receptor modulator; a selective androgen receptor modulator; parathyroid hormone; and/or bisphosphonates ", preferably a" suitable therapeutic agent "is selected from the group consisting of these drugs.

Examples of GHS suitable for use in combination with the compounds of the present invention include GHRP-6, GHRP-1, as described in U.S. Pat. No.4,411,890 and publications WO 89/07110 and WO 89/07111 and B-HT920, or growth hormone releasing factor and analogs thereof or growth hormone and analogs thereof, or growth promoting factors, including IGF-1 and IGF-2, and GHS, as described in WO 01/96300.

Examples of antidiabetic agents suitable for use in combination with the compounds of the present invention include biguanides (e.g., metformin), glycosidase inhibitors (e.g., acarbose), insulin (including insulin secretagogues or insulin sensitizers), meglitinides (e.g., repaglinide), sulfonylureas (e.g., glimepiride, glyburide, and glipizide), biguanide/glyburide combinations (e.g., glucovanine), thiazolidinediones (e.g., troglitazone, rosiglitazone, and pioglitazone), PPAR-alpha agonists, PPAR-gamma agonists, PPAR-alpha/gamma dual agonists, SGLT2 inhibitors, fatty acid binding protein (aP2) inhibitors (such as those disclosed in U.S. Pat. No.6,548,529), glucagon-like peptide-1 (GLP-1), and dipeptidyl peptidase IV (DP4) inhibitors.

Examples of anti-osteoporosis agents suitable for use in combination with the compounds of the present invention include alendronate, risedronate, raloxifene, calcitonin, non-steroidal progestogen receptor agonists, RANK ligand agonists, calcium sensing receptor antagonists, TRAP inhibitors, Selective Estrogen Receptor Modulators (SERMs), estrogens and AP-1 inhibitors.

Examples of anti-obesity agents suitable for use in combination with the compounds of the present invention include endocannabinoid receptor antagonists, such as CB1 receptor antagonists, for example rimonabant (5- (4-chlorophenyl) -1- (2, 4-dichlorophenyl) -4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide, monohydrochloride; CAS registry No. 158681-13-1; SR-141716A; U.S. patent No.5,624,941), aP2 inhibitors, such as those disclosed in U.S. patent No.6,548,529, PPAR γ antagonists, PPAR δ agonists, and orlistat.

Examples of anti-inflammatory agents suitable for use in combination with the compounds of the present invention include prednisone, dexamethasone, Enbrel, cyclooxygenase inhibitors (i.e., COX-1 and/OR COX-2 inhibitors such as NSAIDs, aspirin, indomethacin, ibuprofen, piroxicam, naproxen, celecoxib, pancreatin), CTLA4-Ig agonists/antagonists, CD40 ligand antagonists, integrin antagonists, α 4 α 7 integrin antagonists, cell adhesion inhibitors, interferon γ antagonists, ICAM-1, Tumor Necrosis Factor (TNF) antagonists (e.g., infliximab, OR1384), prostaglandin synthesis inhibitors, budesonide, clofazimine, CNI-1493, CD4 antagonists (e.g., priiximab), p38 mitogen-activated protein kinase inhibitors, Protein Tyrosine Kinase (PTK) inhibitors, pro-kinase inhibitors, c-b inhibitors, c-2, IKK inhibitors and therapies for treating irritable bowel syndrome (e.g., zelmac and Maxi-K openers such as those disclosed in U.S. patent No.6,184,231).

Examples of anxiolytics suitable for use in combination with the compounds of the present invention include diazepam, lorazepam, buspirone, oxazepam and pamoate hydroxyzine.

Examples of antidepressants suitable for use in combination with the compounds of the present invention include citalopram, fluoxetine, nefazodone, sertraline and paroxetine.

Examples of antihypertensive agents suitable for use in combination with the compounds of the invention include beta adrenergic blockers, calcium channel blockers (L-and T-forms; e.g., diltiazem, verapamil, nifedipine, amlodipine and mybefradii), diuretics (e.g., chlorothiazide, hydrochlorothiazide, flumethiazide, hydroflumethiazide, bendroflumethiazide, meclorthiazide, trichlorthiazide, polythiazide, bendrothiazide, ethacrynic acid tricrynafen, chlorthalidone, furosemide, musolimine, bumetanide, triamterene, amiloride, spironolactone), renin inhibitors, ACE inhibitors (e.g., captopril, zofenopril, fosinopril, enalapril, selapril, cilazapril, tandapril, pentopril, quinapril, ramipril, lisinopril), AT-1 receptor antagonists (e.g., losartan, ET receptor antagonists (e.g., valsartan), ET receptor antagonists (e.g., valsartan), and ET receptor antagonists (e.g., valsartan) atresentan and the compounds disclosed in U.S. patent nos. 5,612,359 and 6,043,265), dual ET/AII antagonists (e.g., the compounds disclosed in WO 00/01389), Neutral Endopeptidase (NEP) inhibitors, vasopeptidase inhibitors (dual NEP-ACE inhibitors) (e.g., omatrala and gemopatrilat), and nitrates.

Examples of antiplatelet agents suitable for use in combination with the compounds of the present invention include GPIIb/IIIa blockers (e.g., abciximab, eptifibatide, tirofiban), P2Y12 antagonists (e.g., clopidogrel, ticlopidine, CS-747), thromboxane receptor antagonists (e.g., itracin), aspirin, and PDE-III inhibitors (e.g., dipyridamole) with or without aspirin.

Examples of cardiac glycosides suitable for use in combination with the compounds of the present invention include digitalis and umbilicin.

Examples of cholesterol/lipid lowering agents suitable for use in combination with the compounds of the present invention include HMG-CoA reductase inhibitors (e.g. pravastatin, lovastatin, atorvastatin, simvastatin, NK-104(a.k.a. itavastatin or Nivastatin or nisstatin) and ZD-4522(a.k.a. rosuvastatin or atavastatin or vistatin)), squalene synthetase inhibitors, fibrates, bile acid sequestrants, ACAT inhibitors, MTP inhibitors, lipoxygenase inhibitors, cholesterol absorption inhibitors and cholesterol ester transfer protein inhibitors (e.g. CP-529414).

Examples of mineralocorticoid receptor antagonists suitable for use in combination with the compounds of the present invention include spironolactone and eplerenone.

Examples of phosphodiesterase inhibitors suitable for use in combination with the compounds of the invention include PDE III inhibitors, such as cilostazol, and PDE V inhibitors, such as sildenafil.

Examples of thyroid mimetics suitable for use in combination with the compounds of the present invention include thyroid stimulating hormone, polythroid, KB-130015 and dronedarone.

Examples of suitable alkylating agents for use in combination with the compounds of the present invention include testosterone and SARM.

Examples of HIV or AIDS therapies suitable for use in combination with the compounds of the present invention include indinavir sulfate, saquinavir mesylate, amprenavir, ritonavir, lopinavir, ritonavir/lopinavir combinations, lamivudine, zidovudine, lamivudine/zidovudine combinations, zalcitabine, didanosine, stavudine, and megestrol acetate.

Examples of therapies suitable for use in combination with the compounds of the present invention for the treatment of Alzheimer's disease and cognitive disorders include polylepezil, tacrine, revastigmine, 5HT6, gamma secretase inhibitors, beta secretase inhibitors, SK channel blockers, Maxi-K blockers and KCNQ blockers.

Examples of therapies suitable for use in combination with the compounds of the present invention for the treatment of sleep disorders include melatonin analogs, melatonin receptor antagonists, ML1B agonists, and GABA/NMDA receptor antagonists.

Examples of antiproliferative agents suitable for use in combination with the compounds of the present invention include cyclosporin A, paclitaxel, FK 506, and doxorubicin.

Examples of antineoplastic agents suitable for use in combination with the compounds of the present invention include paclitaxel, doxorubicin, epothilones, cisplatin, and carboplatin.

Examples of selective estrogen receptor modulators suitable for use in combination with the compounds of the present invention include tamoxifen and raloxifene.

Examples of selective androgen receptor modulators suitable for use in combination with the compounds of the present invention include those disclosed in Edwa rds, j.p.et al, bio.med.chem.let., 9, 1003-.

Examples of bisphosphonates suitable for use in combination with the compounds of the invention include MK-217 (alendronic acid).

The amounts of such other therapeutic agents used in combination with the compounds of the present invention may be determined, for example, by Reference to the Physicians' Desk Reference (PDR) or by one of ordinary skill in the art.

In a preferred embodiment, the compounds of the invention are used for the treatment and/or prophylaxis of the above-mentioned physiological and/or pathophysiological conditions in the form of medicaments, wherein such medicaments comprise as additional pharmacologically active substance an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant (5- (4-chlorophenyl) -1- (2, 4-dichlorophenyl) -4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide, monohydrochloride; CAS number 158681-13-1; SR-141716A; U.S. Pat. No.5,624,941) and a GHS-R antagonist as a compound of the invention.

In another preferred embodiment, the compounds according to the invention are used in the form of medicaments for the treatment and/or prophylaxis of the abovementioned physiological and/or pathophysiological conditions, wherein the medicament is applied before and/or during and/or after the treatment with the at least one additional pharmacologically active substance, wherein such additional pharmacologically active substance is an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant (5- (4-chlorophenyl) -1- (2, 4-dichlorophenyl) -4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide, monohydrochloride; CAS registry number 158681-13-1; SR-141716A; U.S. Pat. No.5,624,941) the compounds of the present invention are GHS-R antagonists.

The compounds of the invention may be administered in known manner. The route of administration may thus be any route which is effective in transporting the active compound to the appropriate or desired site of action, for example oral or non-oral, in particular topical, transdermal, pulmonary, rectal, intravaginal, nasal or parenteral, or by implantation. Oral administration is preferred.

The compounds of the invention are converted into a form capable of administration, if appropriate in admixture with a pharmaceutically acceptable carrier or diluent. Suitable excipients and carriers are described, for example, in Ullman's encyclopedia of Technical Chemistry, Vol.4, (1953), 1-39; journal of Pharmaceutical Sciences, Vol.52(1963), 918et seq; Czetsch-Lindenwald, "Hilfsstuff fur Pharmazie and dangrenzende Gebiete"; pharm. ind.2, 1961, 72et seq.; Dr.H.P.Fiedler, Lexikon der Hilfsstuffe fur Pharmazie, Kosmetik and angrenzende Gebiete ", Cantor KG, Aulendorf in Huntteberg, 1971.

Oral administration may take the form of, for example, solid forms such as tablets, capsules, gel capsules, coated tablets, granules or powders, but also drinkable solutions. For oral administration, the compounds of the invention are combined with known and customary, physiologically tolerated excipients and carriers, for example gum arabic, talc, starch, sugars (e.g. mannitol), methylcellulose, lactose, gelatin, surfactants, magnesium stearate, cyclodextrins, aqueous or nonaqueous carriers, diluents, dispersants, emulsifiers, lubricants, preservatives and flavoring agents (e.g. essential oils). The compounds of the invention may also be dispersed in a microparticle, e.g., nanoparticle composition.

Non-oral administration may take the form of, for example, sterile aqueous or oily solutions, suspensions or emulsified intravenous, subcutaneous, intramuscular injections, by means of implants or by means of ointments, creams or suppositories. Administration as a sustained release form is also possible as appropriate. The implant may comprise an inert material, such as a biodegradable polymer or a synthetic silicone, such as silicone rubber. Intravaginal administration is possible, for example by means of a vaginal ring. Intrauterine administration is possible, for example by means of a septum or other suitable intrauterine device. Transdermal administration is additionally provided, in particular by means of a formulation suitable for this purpose and/or suitable means, for example a patch.

The dosage may vary within a wide range depending on the type and/or severity of the physiological and/or pathophysiological condition, the mode of administration, the age, sex, body weight and sensitivity of the subject. Within the scope of the skilled person will be able to determine a "pharmacologically effective amount" of a compound of the invention and/or of an additional pharmacologically active substance. Administration may be in a single dose or in multiple divided doses.

Suitable unit doses are, for example, from 0.001mg to 100mg of active ingredient, i.e. at least one compound according to the invention and, where appropriate, at least one additional pharmacologically active substance per kg of body weight of the patient.

In another aspect, the present invention relates to a pharmaceutical composition comprising a pharmacologically active amount of at least one triazole compound selected from the group consisting of: compounds 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 111, 112, 113, 118, 122, 118, 124, 121, 124, 122, 114, 129, 122, 23, 70, 71, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, and/or compound 190.

In a further aspect, such a pharmaceutical composition may additionally comprise at least one pharmaceutically acceptable carrier and/or excipient, and/or may comprise at least one further pharmacologically active substance.

In a preferred embodiment, such further pharmacologically active substance is an endocannabinoid receptor antagonist, preferably a CB1 receptor antagonist, most preferably rimonabant [5- (4-chlorophenyl) -1- (2, 4-dichlorophenyl) -4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide, monohydrochloride ].

With regard to the pharmaceutical composition of the present invention, a pharmacologically effective amount of at least one triazole compound as exemplified above is contained, preferably in a unit dose, for example, the above-mentioned unit dose, specifically and preferably in an administration form in which oral administration is possible. Furthermore, reference may be made to the possible uses and administrations already described in connection with the compounds of the invention.

General synthetic schemes

The compounds of the present invention may be prepared according to the following general synthetic schemes and related published procedures known to those skilled in the art (e.g., WO 00/54729 and references cited therein).

Exemplary reagents and processes for these reactions appear below and in the working examples. Unless otherwise specified, various substituents (radicals) of the compounds have the meaning as defined herein for formula (I).

Amide bond formation (peptide coupling) is performed under standard peptide coupling procedures known in the art. The reaction is preferably carried out in a solvent such as Dichloromethane (DCM) at room temperature using benzotriazol-1-yloxytris (dimethylamino) phosphoniumHexafluorophosphate (BOP) (Castro Bet al, Tetrahedron Lett.1975, 14: 1219-1222) and a base, for example N-methylmorpholine or diisopropylethylamine.

Sulfurization of the amide formed was carried out using Lawesson's reagent (Pons JF et al, Tetrahedron Lett.2000, 41: 4965-.

Cyclization: the resulting thioamide was then subjected to the conditions reported by Hitosuyanagi et al (Hitossuyanagi Y.et al, J.or. chem.2002, 67: 3266-3271), with minor modifications (5eq. hydrazide and 1.1eq. mercury (II) acetate in acetonitrile). Cyclization to the triazole is generally complete in three hours. If the hydrazide is not commercially available, it is prepared from its acid or methyl ester precursor by known methods.

Deprotection of the tert-butyloxycarbonyl (Boc) group is carried out in acidic medium at room temperature as generally described.

With respect to R5 ═ -CO-alkyl, -CO-cycloalkyl, -CO-cycloalkylalkyl, -CO-aryl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl, -CO-C ^*(R9R10)-NH₂、-CO-CH₂-C^*(R9R10)-NH₂、-CO-C^*(R9R10)-CH₂-NH₂(R)：

With respect to R5 ═ alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl (R):

with respect to R5 ═ alkyl-SO₂-, aryl-SO₂-, arylalkyl-SO₂- (R ═ alkyl, aryl, arylalkyl):

the compounds of the invention, particularly compounds 1 to 190, were named from the drawn structural formula using Chem Draw Ultra 8 software (Cambridge soft Corporation, Cambridge, USA).

Brief description of the drawings

Shown in FIGS. 1-13 for¹²⁵I-His⁹Ghrelin and selected examples section compounds 9, 31, 39, 45, 50, 62, 64, 71, 73, 74, 79, 81 and 90, in the GHS-R1 a receptor-ligand binding assay competition maps.

FIGS. 14-40 show in vitro intracellular calcium release assay dose-response plots for selected compounds 1, 9, 12, 20, 22, 31, 39, 41, 42, 45, 46, 47, 48, 49, 50, 51, 55, 62, 64, 67, 71, 73, 74, 79, 81, 90 and ghrelin calculated using human GHS-R1 a transfected CHO cells, as described in example section III), and the EC of GHS receptor agonists₅₀And KI value and IC of GHS receptor antagonist₅₀And Kb value.

Figures 41-46 show the effect of selected compounds 9, 38, 50, 64, 74, 81 on the lipolysis inhibition curve of isoproterenol-induced unacylated ghrelin (uag) in primary adipocytes of diet-induced obese mice, as described in example section VIII).

The contents of all cited references and patents are incorporated herein by reference. The invention is explained in more detail by means of the following examples, without however being restricted thereto.

Examples

I) Synthesis of Compounds of the invention

Example 1:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 1)

Compound 1 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), (2, 4-dimethoxyphenyl) -methylamine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 35% after HPLC purification.

¹H NMR(400MHz，300°K，DMSO-d⁶)：

δ1.32(3H，s，CH₃ Aib)，1.36(3H，s，CH₃ Aib)，2.93(2H，m， CH ₂-CH₂Indole), 2.97(2H, m, CH)₂-CH ₂-indole), 3.31(1H, dd, J ═ 14.5, J ═ 6.1, 1 hch)₂βTrp)，3.38(1H，dd，J＝14.5，J＝9.1，1H CH₂βTrp)，3.66(3H，s，o-OCH₃)，3.72(3H，s，p-OCH₃)，4.93(1H，d，J＝16.9，1H CH₂o, p-dimethoxybenzyl), 5.10(1H, d, J ═ 16.9, 1 hch)₂o, p-dimethoxybenzyl), 5.23(1H, m, ca H Trp), 6.31(1H, dd, J ═ 8.5, J ═ 1.7, H₅o, p-dimethoxybenzyl), 6.45(1H, d, J ═ 8.5, H₆o, p-dimethoxybenzyl), 6.59(1H, d, J ═ 1.7, H₃o, p-dimethoxybenzyl), 6.88(1H, t, J ═ 7.5, H₅ Trp)，6.94(1H，t，J＝7.5，H₅Indole), 7.04(1H, t, H)₆ Trp)，7.06(1H，t，H₆Indole), 7.08(1H, s, H) ₂Indole), 7.11(1H, s, H)₂ Trp)，7.18(1H，d，J＝7.9，H₄ Trp)，7.33(3H，H₄，H₇Indole, H₇ Trp)，8.05(2H，s，NH₂Aib), 8.95(1H, d, J ═ 7.9, NH Trp), 10.80(1H, s, NH indole), 10.82(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ22.4(CH₂-CH₂Indole), 23.2 (CH)₃ Aib)，23.3(CH₃ Aib)，25.4(CH₂-CH₂Indole), 28.7 (C.beta.Trp), 41.3 (C.beta.Trp) ((R)CH₂-o, p-dimethoxybenzyl), 45.3 (C.alpha.Trp)，55.2(p-OCH₃)，55.4(o-OCH₃)，56.3(CqAib)，98.6(C₃o, p-dimethoxybenzyl), 104.7 (C)₅o, p-dimethoxybenzyl), 109.5 (C)₃ Trp)，111.3(C₇ Trp，C₇Indole), 112.9 (C)₃Indole), 115.2 (C)₁o, p-dimethoxybenzyl), 117.8 (C)₄Indole), 117.9 (C)₄ Trp)，118.2(C₅ Trp，C₅Indole), 120.9 (C)₆ Trp，C₆Indole), 122.4 (C)₂Indole), 124.3 (C)₂ Trp)，126.8(C₉Indole), 126.9 (C)₉ Trp)，127.5(C₆o, p-dimethoxybenzyl), 136.0 (C)₈ Trp)，136.2(C₈Indole), 154.6(2Cq triazole), 157.3 (C)₂o, p-dimethoxybenzyl), 160.4 (C)₄o, p-dimethoxybenzyl), 171.3 (COAib).

ESI-MS: actually measuring: m/z 606.3[ M + H ]]⁺Calculating: 604.3g/mol

Example 2:

(R) -N- (1- (5-benzyl-4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 4)

Compound 4 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), naphthalen-1-yl-methylamine, 2-phenylacethydrazide and Boc-2-amino-2-methylpropionic acid in 42% overall yield after HPLC purification.

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.18(3H，s，CH₃ Aib)，1.24(3H，s，CH₃Aib), 3.17(1H, dd, J ═ 14Hz and 5Hz, CH) ₂β Trp), 3.36(1H, dd, J ═ 14 and 9Hz, CH)₂ βTrp)，4.05(2H，m，CH₂-benzyl), 4.90(1H, m, CH α Trp), 5.65(1H, d, J ═ 18Hz, CH ₂-naphthyl), 5.81(1H, d, J ═ 18Hz, CH ₂Naphthyl), 6.12(1H, d, J)_o＝7Hz，H₂Naphthyl), 6.38(1H, t, J)_o＝7Hz，H₅ Trp)，6.47(1H，d，J_o＝8Hz，H₄ Trp)，6.85(1H，t，J_o＝8Hz，H₆ Trp)，7.03(1H，d，J_m＝2Hz，H₂Trp), 7.05-7.12(5H, m, CHar benzyl), 7.15(1H, d, J)_o＝8Hz，H₇ Trp)，7.19(1H，d，J_o＝8Hz，H₃Naphthyl), 7.58(2H, m, H)₆And H₇Naphthyl), 7.81(1H, d, J)_o＝8Hz，H₄Naphthyl), 7.89-8.01(5H, m, NH)₂ Aib，H₅And H₈Naphthyl), 8.92(1H, d, J ═ 8Hz, NH amide), 10.73(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃ Aib)，23.6(CH₃ Aib)，29.2(CH₂ βTrp)，30.5(CH₂-benzyl), 44.0(CH₂Naphthyl), 45.6 (CH. alpha. Trp), 56.6(Cq Aib), 109.7 (C)₃ Trp)，111.7(C₇ Trp)，117.9(C₄ Trp)，118.4(C₅ Trp)，121.1(C₆ Trp)，122.1(C₂Naphthyl), 122.8 (C)₈Naphthyl), 124.9 (C)₂ Trp)，125.7 (C₃Naphthyl), 126.7 (C)₆Naphthyl), 126.9 (C)₉ Trp)，127.0(C₇Naphthyl), 128.2 (C)₄Benzyl), 128.7 to 129.1 (C)₂，C₃，C₅And C₆Benzyl radical, C₄And C₅Naphthyl), 129.9 (C)₉Naphthyl), 131.5 (C)₁Naphthyl), 133.5 (C)₁₀Naphthyl), 136.2 (C)₁Benzyl), 136.4 (C)₈Trp), 154.2(Cq triazole), 155.7(Cq triazole), 171.9 (COAib).

ESI-MS: actually measuring: m/z 543.4[ M + H ]]⁺Calculating: 542.2g/mol

Example 3:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 5)

Compound 5 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), naphthalen-1-yl-methylamine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 33% after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶，300°K)：

δ(ppm)1.25(3H，s，CH₃ Aib)，1.28(3H，s，CH₃ Aib)，2.93(2H，m，CH ₂-CH₂Indole), 3.01(2H, m, CH)₂-CH ₂Indole), 3.30(1H, dd,³j ═ 14.3 and 5.8Hz, CH₂ βTrp)，3.40(1H，dd，³J ═ 14.3 and 8.8Hz, CH₂ βTrp)，5.03(1H，m，CH αTrp)，5.62(1H，d，J＝18.0Hz，CH₂-naphthyl), 5.76(1H, J ═ 18.0Hz, CH₂Naphthyl), 3.36(1H, d, J)_o＝7.2Hz，H₂Naphthyl), 6.51(1H, t, J)_o＝7.4Hz，H₅ Trp)，6.72(1H，d，J_o＝7.9Hz，H₄ Trp)，6.76(1H，t，J_o＝7.5Hz，H₅Indole), 6.92(1H, t, J)_o＝7.5Hz，H₆ Trp)，7.0(1H，t，J_o＝7.5Hz，H₆Indole), 7.02(1H, d, J ═ 2.0Hz, H)₂Indole), 7.09(1H, d, J ═ 2.0Hz, H)₂ Trp)，7.13(1H，d，J_o＝7.9Hz，H₄Indole), 7.26(1H, J)_o＝7.9Hz，H₇ Trp)，7.27(1H，t，J_o＝8.2Hz，H₃Naphthyl), 7.29(1H, d, H)₇Indole), 7.58-7.64(2, m, H)₆And H₇Naphthyl), 7.88(1H, d, J)_o＝8.2Hz，H₄Naphthyl), 7.93(1H, d, J)_o＝ 7.9Hz，H₈Naphthyl), 7.98(3H, brs, NH)₂ Aib)，8.03(1H，d，J_o＝8.2Hz，H₅Naphthyl), 8.96(1H, d, J)_o7.9Hz, NH Trp), 10.75(1H, brs, NH indole), 10.77(1H,brs, NH indole Trp).

¹³C NMR(100MHz，DMSO-d⁶，300°K)：

δ(ppm)22.6(CH₂-CH₂-indole), 23.1 (CH)₃ Aib)，23.2(CH₃ Aib)，25.3(CH₂-CH₂Indole), 28.8 (CH)₂ βTrp)，43.3(CH₂Naphthyl), 45.3 (CH. alpha. Trp), 56.2(Cq Aib), 109.4 (C)₃ Trp)，111.2(C₇Indole and C₇ Trp)，112.9(C₃Indole), 117.5 (C)₄ Trp)，117.8(C₄Indole), 118.0 (C)₅ Trp)，118.1(C₅Indole), 120.7 (C)₆ Trp)，120.8(C₆Indole), 121.6 (C)₂Naphthyl), 122.5 (C)₂Indole and C₈Naphthyl), 124.4 (C)₂ Trp)，125.4(C₃Naphthyl), 126.3 (C)₆Naphthyl), 126.6 (C)₉Indole, C₉Trp and C₇Naphthyl), 127.9 (C)₄Naphthyl), 128.6 (C)₅Naphthyl), 129.5 (C)₉Naphthyl), 131.4 (C)₁Naphthyl), 133.1 (C)₁₀Naphthyl), 135.9 (C)₈Trp)，136.1(C₈Indole), 154.7(2Cq triazole), 171.4(CO Aib).

ESI-MS: actually measuring: m/z 596.4[ M + H ] ]⁺Calculating: 595.3g/mol

Example 4:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 6)

Compound 6 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), (3-methoxyphenyl) -methylamine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 25% after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.28(3H，s，CH₃ Aib)，1.30(3H，s，CH₃ Aib)，2.92(2H，m，CH ₂-CH₂Indole), 2.98(2H, m, CH)₂-CH ₂-indole), 3.33(1H, dd, J ═ 14.5, J ═ 6.2, 1 hch)₂ βTrp)，3.40(1H，dd，J＝14.5，J＝8.8，1H CH₂ βTrp)， 3.66(3H，s，OCH₃)，5.09(2H，m，CH₂m-methoxybenzyl), 5.22(1H, m, ca H Trp), 6.38(1H, d, J ═ 7.5, H₆m-methoxybenzyl), 6.59(1H, s, H)₂m-methoxybenzyl), 6.86(1H, t, H)₅ Trp)，6.87(1H，d，H₄m-methoxybenzyl), 6.92(1H, t, J ═ 7.5, H)₅Indole), 7.03(1H, t, J ═ 7.9, H)₆ Trp)，7.05(1H，t，H₆Indole), 7.07(1H, s, H)₂Indole), 7.11(1H, s, H)₂ Trp)，7.18(1H，t，H₅m-methoxybenzyl), 7.19(1H, d, H)₄ Trp)，7.31(1H，H₄Indole), 7.32(2H, H)₇ Trp，H₇Indole), 8.00(2H, s, NH)₂Aib), 8.96(1H, d, J ═ 8.1, NH Trp), 10.78(1H, s, NH indole), 10.80(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)22.4(CH CH₂Indole), 23.1 (CH)₃ Aib)，23.3(CH₃ Aib)，25.4(CH₂-CH₂Indole), 28.7 (C.beta.Trp), 45.3 (CH)₂m-methoxybenzyl), 45.4 (C.alpha.Trp), 55.0 (OCH) ₃)，56.3(Cq Aib)，109.5(C₃ Trp)，111.3(C₇ Trp，C₇Indole), 112.0 (C)₂m-methoxybenzyl), 113.0 (C)₄m-methoxybenzyl, C₃Indole), 117.8 (C)₄ Trp，C₆m-methoxybenzyl), 118.0 (C)₄Indole), 118.2 (C)₅Indole), 118.3 (C)₅ Trp)，120.8(C₆Indole), 120.9 (C)₆ Trp)，122.4(C₂Indole), 124.3 (C)₂Trp)，126.7(C₉Indole), 126.9 (C)₉ Trp)，130.0(C₅m-methoxybenzyl), 136.0 (C)₈Indole), 136.1 (C)₈Trp)，137.2(C₁m-methoxybenzyl), 154.3(2Cq triazole), 159.6 (C)₃m-methoxybenzyl), 171.4(CO Aib).

ESI-MS: actually measuring: m/z 576.6[ M + H ]]⁺Calculating: 575.3g/mol

Example 5:

(R) -N- (1- (4- (3-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 7)

Compound 7 was obtained according to the-general synthetic scheme from Boc- (D) -Trp (10mmoles), (3-methoxyphenyl) -methylamine, 2-phenylacethydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 30% after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.25(3H，s，CH₃ Aib)，1.29(3H，s，CH₃ Aib)，3.24(1H，dd，J＝14.3，J＝5.8，1H CH₂ βTrp)，3.38(1H，dd，J＝14.3，J＝9.1，1H CH₂ βTrp)，3.61(3H，s，m-OCH₃)，4.04(2H，m，CH₂Benzyl), 5.07(1H, d, J ═ 17.4, 1 hch)₂m-methoxybenzyl), 5.13(1H, d, J ═ 17.4, 1 HCH)₂m-methoxybenzyl), 5.14(1H, m, ca H Trp), 6.32(1H, d, J ═ 7.8, H)₆m-methoxybenzyl), 6.40(1H, m, H)₂m-methoxybenzyl), 6.82(1H, t, H)₅Trp)，6.83(1H，d，J＝7.8，H₄m-methoxybenzyl), 7.01(1H, t, J ═ 8.2, H) ₆ Trp)，7.04(1H，d，J＝8.2，H₄ Trp)，7.06(1H，d，J＝2.0，H₂ Trp)，7.12(2H，m，H₂，H₆Benzyl), 7.13(1H, t, J ═ 7.9, H)₅m-methoxybenzyl), 7.20(1H, m, H)₄Benzyl), 7.24(2H, m, H)₃，H₅Benzyl), 7.29(1H, d, J ═ 8.2, H)₇ Trp)，7.99(2H，s，NH₂Aib), 8.92(1H, d, J ═ 8.2, NHTrp), 10.77(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)23.0(CH₃ Aib)，23.3(CH₃ Aib)，28.6(CβTrp)，30.1(CH₂Benzyl), 45.2 (C.alpha.Trp), 45.6 (C.alpha.Trp) ((C.alpha.)CH₂-m-methoxybenzyl), 54.9 (m-OCH)₃)，56.2(Cq Aib)，109.4(C₃ Trp)，111.2(C₇ Trp)，111.7(C₂m-methoxybenzyl), 113.1 (C)₄m-methoxybenzyl), 117.9 (C)₄ Trp，C₆m-methoxybenzyl), 118.2 (C)₅ Trp)，120.8(C₆ Trp)，124.3(C₂ Trp)，126.6(C₄Benzyl), 126.8 (C)₉ Trp)，128.3(C₃，C₅Benzyl), 128.4 (C)₂，C₆Benzyl), 129.9 (C)₅m-methoxybenzyl), 135.9 (C)₁Benzyl radical, C₈Trp)，137.0(C₁m-methoxybenzyl), 153.5(Cq triazole), 154.8(Cq triazole), 159.5 (C)₃m-methoxybenzyl), 171.3(CO Aib).

ESI-MS: actually measuring: m/z 523, 3[ M + H ]]⁺Calculating: 522.3g/mol

Example 6:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 8)

Compound 8 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), phenylmethylamine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 45% after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.29(3H，s，CH₃Aib)，1.30(3H，s，CH₃Aib)，2.88(2H，m，CH ₂-CH₂Indole), 2.97(2H, m, CH)₂-CH ₂Indole), 3.37(2H, m, CH) ₂ βTrp)，5.11(2H，s，CH₂Benzyl), 5.21(1H, m, C α H Trp), 6.86(1H, t, J ═ 7.4, H)₅Trp)，6.88(2H，H₂，H₆Benzyl), 6.92(1H, t, J ═ 7.6, H)₅Indole), 7.03(1H, t, J ═ 7.6, H)₆Trp)，7.05(2H，H₆Indole, H₂Indole), 7.09(1H, d, J ═ 1.8, H)₂Trp)，7.17(1H，d，J＝7.9，H₄Trp)，7.26(2H，H₃，H₅Benzyl), 7.27(1H, H)₄Benzyl), 7.30(1H, H)₄Indole), 7.32(2H, H)₇Trp，H₇Indole), 8.03(2H, brs, NH)₂Aib), 8.95(1H, d, J ═ 8.1, NH Trp), 10.77(1H, s, NH indole), 10.81(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)22.4(CH₂-CH₂Indole), 23.1 (CH)₃Aib)，23.3(CH₃Aib)，25.4(CH₂-CH₂Indole), 28.7(C β Trp), 45.3(C α Trp,CH₂-benzyl), 56.3(Cq Aib), 109.5 (C)₃Trp)，111.3(C₇Trp，C₇Indole), 113.0 (C)₃Indole), 117.8 (C)₄Trp)，118.0(C₄Indole), 118.2 (C)₅Indole), 118.3 (C)₅ Trp)，120.9(C₆Trp，C₆Indole), 122.4 (C)₂Indole), 124.3 (C)₂Trp)，125.9(C₂，C₆Benzyl), 126.7 (C)₉Indole), 126.9 (C)₉Trp)，127.6(C₄Benzyl), 128.8 (C)₃，C₅Benzyl), 135.7 (C)₁Benzyl), 136.0 (C)₈Trp)，136.1(C₈Indole), 154.3(Cq triazole), 154.5(Cq triazole), 171.4(CO Aib).

ESI-MS: actually measuring: m/z 546.3[ M + H]⁺Calculating: 545.3g/mol

Example 7:

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 9)

Compound 9 was obtained according to the-general synthetic scheme from Boc- (D) -Trp (10mmoles), phenylmethylamine, 4- (1H-indol-3-yl) butyrhydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 38% after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.29(3H，s，CH₃Aib)，1.31(3H，s，CH₃Aib)，1.90(2H，m，CH₂-CH ₂-CH₂Indole), 2.61(2H, m,CH ₂-CH₂-CH₂indole), 2.69(2H, m, CH)₂-CH₂-CH ₂Indole), 3.37(2H, m, CH)₂βTrp)，5.09(2H，s，CH₂Benzyl), 5.20(1H, m, C.alpha.H Trp), 6.85(3H, m, H)₂，H₆Benzyl radical, H₅Trp)，6.94(1H，t，J＝7.5，H₅Indole), 7.01(1H, s, H)₂Indole), 7.02(1H, t, J ═ 7.8, H)₆Trp)，7.05(1H，t，J＝8，H₆Indole), 7.08(1H, d, J ═ 2.0, H)₂Trp)，7.14(1H，d，J＝8.0，H₄Trp)，7.25(3H，m，H₃，H₄，H₅Benzyl), 7.31(1H, d, J ═ 8.0, H)₇Trp)，7.32(1H，d，J＝8.0，H₇Indole), 7.42(1H, d, J ═ 7.8, H)₄Indole), 8.03(2H, s, NH)₂Aib), 8.95(1H, d, J ═ 8.1, NH Trp), 10.73(1H, s, NH indole), 10.80(1H, d, J ═ 2.0, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)23.1(CH₃Aib)，23.3(CH₃Aib)，23.8(CH₂-CH₂-CH₂Indole), 24.1 (CH)₂-CH₂-CH₂-indole), 27.2 (CH)₂-CH₂-CH₂Indole), 28.7 (C.beta.Trp), 45.4 (C.alpha.Trp), 45.5 (CH)₂Benzyl), 56.3(Cq Aib), 109.4 (C)₃ Tr p)，111.3(C₇Trp，C₇Indole), 113.6 (C)₃Indole), 117.8 (C)₄Trp)，118.0(C₅Indole), 118.2 (C)₄Indole), 118.3 (C)₅Trp)，120.8(C₆Indole, C₆Trp)，122.2(C₂Indole), 124.3 (C)₂Trp)，125.9(C₂，C₆Benzyl), 126.8 (C)₉Trp)，127.0(C₉Indole), 127.7 (C)₄Benzyl), 128.7 (C)₃，C₅Benzyl), 135.5 (C)₁Benzyl), 136.0 (C)₈Trp)，136.2(C₈Indole), 154.3(Cq triazole), 154.7(Cq triazole), 171.4(CO Aib).

ES I-MS: actually measuring: m/z 560.4[ M + H ]]⁺Calculating: 559.3g/mol

Example 8:

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 10)

Compound 10 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), (3-methoxyphenyl) -methylamine, 4- (1H-indol-3-yl) butyrhydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 25% after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.30(3H，s，CH₃Aib)，1.92(2H，m，CH₂-CH ₂-CH₂Indole), 2.62(2H, m,CH ₂-CH₂-CH₂indole), 2.68(2H, m,CH₂-CH₂-CH ₂-indole), 3.24(1H, dd, J ═ 14.5, J ═ 5.8, 1 hch)₂ βTrp)，3.39(1H，dd，J＝14.5，J＝9.0，1H CH₂βTrp)，3.66(3H，s，m-OCH₃)，5.07(2H，s，CH₂m-methoxybenzyl), 5.18(1H, m, ca H Trp), 6.35(1H, d, J ═ 7.5, H₆m-methoxybenzyl), 6.54(1H, bs, H)₂m-methoxybenzyl), 6.84(1H, t, J ═ 7.5, H)₅Trp)，6.87(1H，dd，J＝8.0，J＝2.1，H₄m-methoxybenzyl), 6.94(1H, t, J ═ 7.3, H)₅Indole), 7.02(1H, t, H)₆ Trp)，7.02(1H，s，H₂Indole), 7.05(1H, t, J ═ 7.8, H)₆Indole), 7.08(1H, d, J ═ 2.1, H)₂Trp)，7.13(1H，d，J＝8.1，H₄Trp)，7.17(1H，t，J＝8.1，H₅m-methoxybenzyl), 7.30(1H, d, H)₇Trp)，7.32(1H，d，J＝8，H₇Indole), 7.42(1H, d, J ═ 7.6, H)₄Indole), 7.98(2H, s, NH)₂Aib), 8.93(1H, d, J ═ 8.2, NH Trp), 10.71(1H, s, NH indole), 10.77(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)23.1(CH₃Aib)，23.3(CH₃Aib)，23.9(CH₂-CH₂-CH₂Indole), 24.3 (CH)₂-CH₂-CH₂-indole), 27.4 (CH)₂-CH₂-CH₂Indole), 28.8 (C.beta.Trp), 45.2 (C.beta.. Trp.), (C.beta.)CH₂-m-methoxybenzyl), 45.4 (C.alpha.Trp), 55.1 (m-OCH)₃)， 56.3(Cq Aib)，109.5(C₃Trp)，111.3(C₇Trp，C₇Indole), 111.8 (C)₂m-methoxybenzyl), 113.0 (C)₄m-methoxybenzyl), 113.8 (C)₃Indole), 117.8 (C) ₆m-methoxybenzyl), 117.9 (C)₄Trp)，118.1(C₅Indole), 118.2 (C)₅Trp，C₄Indole), 120.8 (C)₆Trp)，120.9(C₆Indole), 122.2(C₂Indole), 124.3 (C)₂Trp)，126.8(C₉Trp)，127.0(C₉Indole), 130.0 (C)₅m-methoxybenzyl), 136.0 (C)₈Trp)，136.2(C₈Indole), 137.4 (C)₁m-methoxybenzyl), 154.3(Cq triazole), 154.6(Cq triazole), 159.7 (C)₃m-methoxybenzyl), 171.4(CO Aib).

ESI-MS: actually measuring: m/z 590.3[ M + H ]]⁺Calculating: 589.3g/mol

Example 9:

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 11)

Compound 11 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), naphthalen-1-ylmethylamine, 4- (1H-indol-3-yl) butyrhydrazide and Boc-2-amino-2-methylpropionic acid in 22% overall yield after HPLC purification.

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.20(3H，s，CH₃Aib)，1.25(3H，s，CH₃Aib)，1.93(2H，m，CH₂-CH₂-CH ₂Indole), 2.66(4H, m, C)H ₂-CH₂-CH ₂-indole), 3.25(1H, dd, J ═ 14Hz and 5Hz, CH)₂β Trp), 3.40(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，4.95(1H，m，CH αTrp)，5.66(1H，d，J＝18Hz，CH₂-naphthyl), 5.81(1H, d, J ═ 18Hz, CH₂Naphthyl), 6.37(1H, d, J)_o＝7Hz，H₂Naphthyl), 6.43(1H, t, J)_o＝7Hz，H₅Trp)，6.59(1H，d，J_o＝8Hz，H₄Trp)，6.86(3H，m，H₅And H₆Indole, H₆Trp)，6.95(1H，d，J＝2Hz，H₂Indole), 7.00(1H, d, J)_o＝8Hz，H₄Indole), 7.06(1H, d, J ═ 2Hz, H)₂Trp)，7.20-7.33(4H，m，H₄And H₇Indole, H₇Trp，H₃Naphthyl), 7.60 (2H, m, H)₆And H₇Naphthyl), 7.87(1H, d, J) _o＝8Hz，H₄Naphthyl), 7.99(5H, m, NH)₂Aib，H₅And H₈Naphthyl), 8.95(1H, d, J ═ 8Hz, NH amide), 10.70(1H, s, NH indole), 10.77(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.6(CH₃Aib)，24.1(CH₂-CH₂-CH₂Indole), 24.5 (CH)₂-CH₂-CH₂-indole), 27.6 (CH)₂-CH₂-CH₂Indole), 29.1 (CH)₂ βTrp)，44.1(CH₂Naphthyl), 45.7 (CH. alpha. Trp), 56.7(Cq Aib), 109.7 (C)₃Trp)，111.7(C₇Indole and C₇Trp)，113.9(C₃Indole), 117.9 (C)₄Trp)，118.5(C₄Indole, C₅Trp)，118.6(C₅Indole), 121.1 (C)₆Trp)，121.2(C₆Indole), 122.1 (C)₂Naphthyl), 122.7 (C)₂Indole), 122.9 (C)₈Naphthyl), 125.0 (C)₂Trp)，125.9(C₃Naphthyl), 126.8 (C)₆Naphthyl), 127.O (C)₉Indole), 127.1 (C)₇Naphthyl), 127.4 (C)₉Trp)，128.5(C₄Naphthyl), 129.2 (C)₅Naphthyl), 129.9 (C)₉Naphthyl), 131.6 (C)₁Naphthyl), 133.6 (C)₁₀Naphthyl), 136.4 (C)₈Trp)，136.7(C₈Indole), 155.4(Cqs triazole), 171.9(CO Aib).

ESI-MS: actually measuring: m/z 610.3[ M + H ]]⁺Calculating: 609.3g/mol

Example 10:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 12)

Compound 12 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), (4-methoxyphenyl) -methylamine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in 28% overall yield after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.30(3H，s，CH₃Aib)，1.33(3H，s，CH₃Aib)，2.91(2H，m，CH ₂-CH₂Indole), 2.97(2H, m, CH) ₂-CH ₂Indole), 3.37(2H, d, CH)₂ βTrp)，3.71(3H，s，OCH₃)，5.02(2H，s，CH₂p-methoxybenzyl), 5.23 (1H, m, C α H Trp), 6.78(4H, m, CHa rp-methoxybenzyl), 6.87(1H, t, J ═ 7.5, H₅Trp)，6.93(1H，t，J＝7.5，H₅Indole), 7.03(1H, t, H)₆Trp)，7.05(1H，t，H₆Indole), 7.07(1H, s, H)₂Indole), 7.09(1H, s, H)₂Trp)，7.21(1H，d，J＝8，H₄Trp)，7.32(3H，H₄Indole, H₇Trp，H₇Indole), 8.02(2H, s, NH)₂Aib), 8.97(1H, d, J ═ 8.1, NH Trp), 10.77(1H, s, NH indole), 10.80(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)22.4(CH₂-CH₂Indole), 23.1 (CH)₃Aib)，23.4(CH₃Aib)，25.5(CH₂-CH₂Indole), 28.9 (C.beta.Trp), 44.9 (CH)₂p-methoxybenzyl), 45.3 (C.alpha.Trp), 55.0 (OCH)₃)，56.3(Cq Aib)，109.5(C₃Trp)，111.3(C₇Trp，C₇Indole), 113.0 (C)₃Indole), 114.1 (C)₃，C₅p-methoxybenzyl), 117.9 (C)₄Trp)，118.0(C₄Indole), 118.2 (C)₅Indole), 118.3 (C)₅Trp)，120.9(C₆Indole, C₆ Trp)，122.0(C₂Indole), 124.4 (C)₂Trp)，126.7(C₉Indole), 126.9 (C)₉ Trp)，127.3(C₂，C₆p-methoxybenzyl), 127.4 (C)₁p-methoxybenzyl), 135.9 (C)₈Trp)，136.1(C₈Indole), 154.2(Cq triazole), 154.5(Cq triazole), 158.4C₄p-methoxybenzyl), 171.4(CO Aib).

ESI-MS: actually measuring: m/z 576.3[ M + H ]]⁺Calculating: 575.3g/mol

Example 11:

(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 13)

Following the general synthetic scheme, compound 13 was obtained from Boc- (D) -Trp (10mmoles), (4-methoxyphenyl) -methylamine, 2-phenylacethydrazide and Boc-2-amino-2-methylpropionic acid in 37% overall yield after HPLC purification.

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.24(3H，s，CH₃Aib)，1.28(3H，s，CH₃Aib)，3.26(1H，dd，³J-14 Hz and 6Hz, CH₂βTrp)，3.31(1H，dd，³J-14 Hz and 9Hz, CH₂βTrp)，3.67(3H，s，OCH₃)，3.99(2H，s，CH₂-benzyl), 4.99(2H, s, C)H ₂-p-methoxybenzyl), 5.12(1H, m, CH. alpha. Trp), 6.67(4H, m, CHarp-methoxybenzyl), 6.80(1H, t, J)_o＝8Hz，H₅Trp)，6.98(1H，t，J_o＝8Hz，H₆Trp)，7.02-7.06(4H，m，H₂And H₆Benzyl radical, H₂And H₄Trp)，7.12-7.25(3H，m，H₃，H₄And H₅Benzyl), 7.26(1H, d, J)_o＝8Hz，H₇Trp)，8.01(3H，brs，NH₂Aib)，8.92(1H，d，J＝8Hz，NH Trp), 10.77(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.7(CH₃Aib)，29.1(CH₂βTrp)，30.6(CH₂-benzyl), 45.7(CH₂-p-methoxybenzyl), 45.7 (CH. alpha. Trp), 55.5 (OCH)₃)，56.7(Cq Aib)，109.8(C₃Trp)，111.7(C₇Trp)，114.5(C₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.8(C₂Trp)，127.1(C₂And C₆Benzyl), 127.3 (C)₉Trp)，127.6(C₁p-methoxybenzyl), 127.8 (C)₂And C₆p-methoxybenzyl), 128.8 (C)₃，C₄And C₅p-methoxybenzyl), 136.3 (C)₁Benzyl), 136.4 (C)₈Trp), 153.8(Cq triazole), 155.2(Cq triazole), 159.1 (C)₄p-methoxybenzyl), 171.9(CO Aib).

ESI-MS: actually measuring: m/z 524.1[ M + H ]]⁺Calculating: 522.3g/mol

Example 12:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 15)

Following the general synthetic scheme, compound 15 was obtained from Boc- (D) -Trp (10mmoles), hexane-1-amine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in 28% overall yield after HPLC purification.

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)0.77(3H，t，J＝7.2(CH₂)₅-CH ₃)，1.01(4H，m，2CH₂)，1.11(2H，m，CH ₂-CH₃)，1.14(1H，m，1H N-CH₂-CH ₂)，1.33(1H，m， 1H N-CH₂-CH ₂)，1.40(3H，s，CH₃Aib)，1.42(3H，s，CH₃Aib)，3.05(2H，m，CH ₂-CH₂Indole), 3.10(2H, m, CH) ₂-CH ₂-indole), 3.37(1H, dd, J ═ 14.2, J ═ 7.6, 1 hch)₂βTrp)，3.44(1H，dd，J＝14.2，J＝7.6，1HCH₂βTrp)，3.58(1H，m，1H N-CH₂)，3.71(1H，m，1H N-CH₂)，5.21(1H，m，CαH Trp)，6.96(1H，H₅Trp)，6.97(1H，H₅Indole), 7.06(2H, H)₆Trp，H₆Indole), 7.09(1H, s, H)₂Trp)，7.13(1H，s，H₂Indole), 7.34(2H, H)₇ Trp，H₇Indole), 7.48(1H, d, H)₄Indole), 7.50(1H, H)₄ Trp)，8.14(2H，s，NH₂Aib), 9.08(1H, d, J ═ 7.8, NH Trp), 10.84(1H, s, NH indole), 10.88(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)13.7(CH₂)₅-CH ₃)，21.7(CH ₂-CH₃)，22.4(CH₂-CH _□Indole), 23.1 (CH)₃Aib)，23.3(CH₃Aib)，25.1(CH ₂-CH_□Indole), 25.5 (CH)₃-CH₂-CH₂-CH ₂)，29.1(CβTrp)，29.3(N-CH₂-CH ₂)，30.4(CH₃-CH₂-CH ₂)，42.6(N-CH ₂-CH₂)，45.6(CαTrp)，56.3(Cq Aib)，109.2(C₃Trp)，111.4-111.5(C₇Trp，C₇Indole), 112.8 (C)₃Indole), 117.7 (C)₄Trp)，118.0(C₅Indole), 118.2 (C)₄Indole), 118.4 (C)₅Trp)，120.9(C₆Indole, C₆Trp)，122.6(C₂Indole), 124.3 (C)₂Trp)，126.8(C₉Trp)，126.9(C₉Indole), 136.0 (C)₈Trp)，136.2(C₈Indole), 154.0(Cq triazole), 154.1(Cq triazole), 171.4 (COAib). ESI-MS: actually measuring: m/z540.3[ M + H ]]⁺Calculating: 539.3g/mol

Example 13:

(S) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 18)

Compound 18 was obtained according to the general synthetic scheme from Boc- (L) -Trp (10mmoles), (2, 4-dimethoxyphenyl) -methylamine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 30% after HPLC purification.

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.31(3H，s，CH₃Aib)，2.89(2H，m，CH ₂CH₂Indole), 2.93(2H, m, CH)₂CH ₂Indole), 3.27(2H, m, CH)₂βTrp)，3.62(3H，s，o-OCH₃)，3.68(3H，s，p-OCH₃)，4.89(1H，d，³J＝17Hz，CH₂-o, p-dimethoxybenzyl), 5.06(1H, d, ³J＝17Hz，CH ₂-o, p-dimethoxybenzyl), 5.18(1H, m, CH. alpha. Trp), 6.27(1H, dd, J)_o8Hz and J_p＝2Hz，H₅o, p-dimethoxybenzyl), 6.40(1H, d, 8Hz, H₆o, p-dimethoxybenzyl), 6.56(1H, d, J)_p＝2Hz，H₃o, p-dimethoxybenzyl), 6.83(1H, t, J)_o＝7Hz，H₅Trp)，6.90(1H，t，J_o＝7Hz，H₅Indole), 7.02(1H, t, H)₆Trp)，7.04(1H，t，H₆Indole), 7.07(1Hs, H)₂Indole), 7.08(1H, s, H)₂Trp)，7.12(1H，d，J_o＝8Hz，H₄Trp)，7.29(3H，H₄And H₇Indole, H₇Trp)，8.00(3H，brs，NH₂Aib), 8.93(1H, d, J ═ 8Hz, NH amide), 10.76(1H, s, NH indole), 10.79(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)22.9(CH₂ CH₂-indole), 23.6 (CH)₃Aib)，23.7(CH₃Aib)，25.8(CH₂CH₂Indole), 29.2 (CH)₂βTrp)，41.4(CH₂-o, p-dimethoxybenzyl), 45.7 (C.alpha.Trp), 55.7 (p-OCH)₃)，55.9(o-OCH₃)，56.7(CqAib)，99.0(C₃o, p-dimethoxybenzyl), 105.1 (C)₅o, p-dimethoxybenzyl), 109.9 (C)₃Trp)，111.8(C₇Trp，C₇Indole), 113.4 (C)₃Indole), 115.6 (C)₁o, p-dimethoxybenzyl), 118.3 (C)₄Indole), 118.4 (C)₄Trp)，118.6(C₅Trp，C₅Indole), 121.3 (C)₆Trp，C₆Indole), 122.6 (C)₂Indole), 124.4 (C)₂Trp)，127.2(C₉Indole), 127.3 (C)₉Trp)，128.0(C₆o, p-dimethoxybenzyl), 136.4 (C)₈Trp)，136.6(C₈Indole), 155.0(2Cq triazole), 157.7 (C)₂o, p-dimethoxybenzyl), 160.9 (C)₄o, p-dimethoxybenzyl), 171.6(CO Aib).

ESI-MS: actually measuring: m/z 606.2[ M + H ]]⁺Calculating: 605.3g/mol

Example 14:

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 23)

Compound 23 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), (4-methoxyphenyl) -methylamine, 4- (1H-indol-3-yl) butyrhydrazide and Boc-2-amino-2-methylpropionic acid in a total yield of 25% after HPLC purification.

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.30(3H，s，CH₃Aib)，1.84(2H，m，CH₂CH ₂CH₂Indole), 2.58(2H, m, C)H ₂CH₂CH₂Indole), 2.65(2H, m, CH)₂CH₂CH ₂Indole), 3.34(2H, d,³J＝7Hz，CH₂βTrp)，3.67(3H，s，OCH₃)，4.96(2H，s，CH₂-p-methoxybenzyl), 5.19(1H, m, CH. alpha. Trp), 6.71(4H, s, CHar p-methoxybenzyl), 6.89(1H, t, J)_o＝7Hz，H₅Trp)，6.92(1H，t，J_o＝7Hz，H₅Indole), 7.02(1H, s, H)₂Indole), 7.05(1H, s, H)₂Trp)，7.14(1H，d，J_o＝8Hz，H₄Trp)，7.33(3H，H₄Indole, H₇Trp，H₇Indole), 8.02(3H, brs, NH)₂Aib), 7.90(1H, d, J ═ 8Hz, NH amide), 10.73(1H, s, NH indole), 10.79(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.8(CH₃Aib)，24.3(CH₂CH₂ CH₂Indole), 24.8 (CH)₂ CH₂CH₂-indole), 27.7(CH₂CH₂CH₂Indole), 29.1 (C.beta.Trp), 45.5(N-CH₂-p-methoxybenzyl), 45.8 (C.alpha.Trp), 55.5 (OCH)₃)，56.8(Cq Aib)，109.8(C₃Trp)，111.7(C₇Trp，C₇Indole), 114.0 (C)₃Indole), 114.5 (C)₃，C₅p-methoxybenzyl), 118.3 (C)₄Indole, C₄Trp)，118.5(C₅Indole), 118.8 (C)₅Trp)，121.3(C₆Indole, C₆Trp)，127.3(C₉Indole), 127.4 (C)₉Trp)，127.6(C₁p-methoxybenzyl), 127.9 (C)₂，C₆p-methoxybenzyl, C₂Trp，C₂Indole), 136.1 (C)₈Indole), 136.4 (C)₈Trp), 154.7(Cq triazole), 155.1(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 171.9(CO Aib).

ESI-MS: actually measuring: m/z 590.0[ M + H ] ]⁺Calculating: 589.3g/mol

Example 15:

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2-methoxy) benzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 25)

Compound 25 was obtained according to the general synthetic scheme from Boc- (D) -Trp (10mmoles), (2-methoxyphenyl) -methylamine, 3- (1H-indol-3-yl) propane hydrazide and Boc-2-amino-2-methylpropionic acid in 28% overall yield after HPLC purification.

¹H NMR(300 MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.29(3H，s，CH₃Aib)，2.90(2H，m，CH ₂-CH₂Indole), 2.96(2H, m, CH)₂-CH ₂Indole), 3.29(2H, m, CH)₂ βTrp)，3.65(3H，s，OCH₃)，5.09(3H，m，CH ₂-o-methoxybenzyl and CH α Trp), 6.49(1H, d, J)_o＝8 Hz，H₃o-methoxybenzyl), 6.76(1H, t, J)_o＝8Hz，H₅Trp)，6.81(1H，t，J_o＝8Hz，H₅Indole), 6.89(1H, t, J)_o＝7Hz，H₆Trp)，6.96(1H，t，J_o＝8Hz，H₆Indole), 6.98(1H, s, H)₂Indole), 7.02(3H, m, H)₄，H₅And H₆o-methoxybenzyl), 7.07(1H, d, J)_o＝6Hz，H₄Trp)，7.18(1H，m，H₄Indole), 7.29(2H, m, H)₇Indole and H₇Trp)，8.07(3H，brs，NH₂Aib), 8.97(1H, d, J ═ 8Hz, NH amide), 10.80(1H, s, NH indole), 10.82(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)22.8(CH₂-CH₂-indole), 23.6 (CH)₃Aib)，23.7(CH₃Aib)，25.8(CH₂-CH₂Indole), 29.1 (CH)₂βTrp)，42.3(CH₂-o-methoxybenzyl), 45.7 (CH. alpha. Trp), 55.8 (OCH)₃)，56.7(Cq Aib)，109.8(C₃Trp)，111.5(C₃o-methoxybenzyl), 111.8 (C)₇Indole and C₇Trp)，113.2(C₃Indole), 118.2 (C)₄Trp)，118.4(C₄Indole), 118.7 (C)₅Indole and C₅Trp)，121.0(C₆Indole), 121.3 (C)₆Trp)，121.4(C₅o-methoxybenzyl), 123.0 (C)₂Indole and C ₂Trp)，123.3(C₁o-methoxybenzyl), 127.0 (C)₄o-methoxybenzyl), 127.1 (C)₉Indole), 127.3 (C)₉Trp)，129.8(C₆o-methoxybenzyl), 136.4 (C)₈Indole), 136.6 (C)₈Trp), 155.2(Cq triazole), 171.9 (COAib).

ESI-MS: actually measuring: m/z 576.1[ M + H ]]⁺Calculating: 575.3g/mol

The following compiles data of further exemplary embodiments of the synthesis according to the general synthesis scheme (see also table 1):

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 3):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.32(s，3H，CH₃ Aib)，1.37(s，3H，CH₃ Aib)，1.86(2H，m，CH₂-CH ₂-CH₂indole), 2.38(2H, m, C)H ₂-CH₂-CH₂Indole), 2.65(4H, m, CH)₂-CH₂-CH ₂-indole and CH₂-CH ₂Phenyl), 3.38(2H, m, C)H ₂-CH₂Phenyl), 3.74(1H, m, CH)₂ βTrp)，3.92(1H，m，CH₂ βTrp)，5.23(1H，m，CHαTrp)，6.78(2H，m，H₅Indole and H₅ Trp)，6.93(1H，t，J_o＝8Hz，H₆ Trp)，7.01(3H，m，H₆Indole, H₂And H₆Phenyl), 7.05(1H, d, J ═ 2Hz, H)₂Trp)，7.08(1H，d，J＝2Hz，H₂Indole), 7.15(3H, m, H)₃，H₄And H₅Phenyl), 7.29(1H, d, J)_o＝8Hz，H₄Trp)，7.31(1H，d，J_O＝8Hz，H₇ Trp)，7.44(1H，d，J_o＝8Hz，H₇Indole), 7.46(1H, d, J)_o＝8 Hz，H₄Indole), 8.06(3H, brs, NH)₂Aib), 9.05(1H, d, 8Hz, NH amide), 10.76(1H, s, NH indole), 10.85(1H, d, J ═ 2Hz, NH indole Trp).

¹³C NMR(75 MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.6(CH₂-CH₂-CH₂-indole), 23.9 (CH)₃Aib)，24.5(CH₂-CH₂-CH₂-indole), 27.3 (CH)₂-CH₂-CH₂Indole), 29.4 (CH)₂βTrp)，35.7(CH₂-CH₂-phenyl), 44.5(CH₂-CH₂Phenyl), 46.1 (CH. alpha. Trp), 56.8(CqAib), 109.6 (C)₃Trp)，111.8(C₇Indole), 111.9 (C) ₇Indole), 113.9 (C)₃Indole), 118.3 (C)₄Trp)，118.6(C₅Indole), 118.7 (C)₄Indole), 118.9 (C)₅Trp)，121.3(C₆Trp)，121.4(C₆Indole), 122.8 (C)₂Indole and C₂Trp)，127.1(C₄Phenyl), 127.3 (C)₉Trp)，127.5(C₉Indole), 128.8 (C)₂And C₆Phenyl), 129.1 (C)₃And C₅Phenyl), 136.5 (C)₁Phenyl), 136.8 (C)₈Trp)，137.2(C₈Indole), 154.7(Cq triazole), 172.0(CO Aib).

(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 16):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)0.74(3H，t，J＝6Hz，CH ₃-CH₂-CH₂-CH₂-CH₂-CH₂)，0.95(4H，brs，CH₃-CH₂-CH ₂-CH ₂-CH₂-CH₂)，1.06(3H，m，CH₃-CH ₂-CH₂-CH₂-CH₂ -CH₂and 1H N-CH₂-CH ₂)，1.38(7H，s，CH₃Aib and 1HN-CH₂-CH ₂)，1.97(2H，m，CH₂-CH ₂-CH₂Indole), 2.71(4H, m, C)H ₂-CH₂-CH ₂Indole), 3.37(2H, m, CH)₂βTrp)，3.56(2H，m，N-CH ₂)，5.15(1H，m，CH αTrp)，6.91(2H，m，H₅Indole and H₅Trp)，7.00(2H，m，H₆Indole and H₆Trp)，7.07(2H，s，H₂Indole and H₂Trp)，7.29(2H，d，J_o＝8Hz，H₇Indole and H₇Trp)，7.45(2H，d，J_O＝7Hz，H₄Indole and H₄Trp)，8.15(3H，brs，NH₂Aib), 9.10(1H, d, J ═ 6Hz, NH amide), 10.77(1H, s, NH indole), 10.85(1H, s,NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)14.2(CH₃-CH₂-CH₂-CH₂-CH₂-CH₂)，22.2(CH₃-CH₂-CH₂-CH₂ -CH₂-CH₂And CH₂-CH₂-CH₂-indole), 23.6 (CH)₃Aib)，23.7(CH₃Aib)，24.5(CH₂-CH₂-CH₂Indole), 25.9 (CH)₃-CH₂-CH₂-CH₂-CH₂-CH₂)，27.5(CH₂Beta Trp and CH₂-CH₂-CH₂Indole), 29.7 (N-CH)₂-CH₂)，30.8(CH₃-CH₂-CH₂-CH₂-CH₂ -CH₂)，43.2(N-CH₂)，46.1(CHαTrp)，56.8(Cq Aib)，109.5(C₃Trp)，111.8(C₇Trp)，111.9(C₇Indole), 113.9 (C)₃Indole), 118.1 (C)₄Trp)，118.5(C₅Indole), 118.6 (C)₄Indole), 118.9 (C)₅Trp)，121.3(C₆Indole and C₆Trp)，122.8(C₂Indole and C₂Trp)，127.3(C₉Trp)，127.4(C₉Indole), 136.5 (C)₈Trp)，136.8(C₈Indole), 154.7(Cq triazole), 172.0(CO Aib).

(R) -N- (1- (4, 5-bis (2- (1H-indol-3-yl) ethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 17):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.30(3H，s，CH₃Aib)，1.37(3H，s，CH₃Aib)，2.50(2H，m，N-CH₂-CH ₂indole), 2.68(2H, t, J) _o＝8Hz，C-CH₂-CH ₂Indole), 2.91(2H, t, J)_o＝8Hz，C-CH₂-CH ₂Indole), 3.34(2H, m, N-C)H ₂-CH₂Indole), 3.93(2H, m, CH)₂βTrp)，5.25(1H，m，CHαTr p)，6.72-6.94(4H，m，H₅And H₆Trp，H₅Indoles from C-CH₂-CH₂-indole and H₅Indoles from N-CH₂-CH₂Indole), 6.98-7.04(4H, m, H)₂Trp，H₆Indoles from C-CH₂-CH₂-indole, H₂And H₆Indoles from N-CH₂-CH₂Indole), 7.11(1H, s, H)₂Indoles from C-CH₂-CH₂Indole), 7.19(1H, d, J)_o＝8Hz，H₄Indoles from N-CH₂-CH₂Indole), 7.28(3H, m, H)₄And H₇Trp，H₇Indoles from N-CH₂-CH₂Indole), 7.40(1H, d, J)_o＝8Hz，H₇Indoles from C-CH₂-CH₂Indole), 7.44(1H, d, J)_o＝8Hz，H₄Indoles from C-CH₂-CH₂Indole), 8.04(3H, brs, NH)₂Aib), 9.69(1H, d, J ═ 8Hz, NH amide), 10.73(1H, s, NH indole from C-CH)₂-CH₂-indole), 10.82(1H, d, J ═ 2Hz, NH indole Trp), 10.84(1H, s, NH indole from N-CH)₂-CH₂-indoles).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)22.7(C-CH₂-CH₂-indole), 23.6 (CH)₃Aib)，23.8(CH₃Aib)，25.4(C-CH₂-CH₂Indole), 26.0 (N-CH)₂-CH₂Indole), 29.6 (CH)₂βTrp)，43.9(N-CH₂-CH₂Indole), 46.0 (CH. alpha. Trp), 56.8(Cq Aib), 109.5 (C)₃Indoles from N-CH₂-CH₂Indole), 109.9 (C)₃Trp)，111.7(C₇Trp)，111.9(C₇Indoles from N-CH₂-CH₂-indole and C₇Indoles from C-CH₂-CH₂Indole), 113.5 (C)₃Indoles from C-CH₂-CH₂Indole), 118.3 (C)₄Indoles from N-CH₂-CH₂Indole), 118.4 (C)₄Trp)，118.5(C₅Indoles from C-CH₂-CH₂Indole), 118.7 (C)₄Indoles from C-CH₂-CH₂Indole), 118.9 (C)₅Trp)，119.0(C₅Indoles from N-CH ₂-CH₂Indole), 121.3 (C)₆Trp)，121.5(C₆Indoles from C-CH₂-CH₂-indole and C₆Indoles from N-CH₂-CH₂Indole), 122.8 (C)₂Trp，C₂Indoles from C-CH₂-CH₂-indoles and indoles from N-CH₂-CH₂Indole), 127.1 (C)₉Trp)，127.2(C₉Indoles from C-CH₂-CH₂Indole), 127.4 (C)₉Indoles from N-CH₂-CH₂Indole), 136.5 (C)₈Trp and C₈Indoles from C-CH₂-CH₂-indole), 136.6 (C)₈Indoles from N-CH₂-CH₂Indole), 154.5(Cq triazole), 154.8(Cq triazole), 171.8(CO amide).

(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 19):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.24(3H，s，CH₃Aib)，1.27(3H，s，CH₃Aib)，2.82(4H，m，CH ₂-CH ₂phenyl), 3.32(2H, m, CH)₂βTrp)，3.63(3H，s，OCH₃)，5.08(2H，m，CH ₂-m-methoxybenzyl), 5.18(1H, m, CH. alpha. Trp), 6.35(1H, d, J)_o＝8Hz，H₆m-methoxybenzyl), 6.57(1H, s, H)₂m-methoxybenzyl)，6.82(1H，t，J_o＝8Hz，H₅Trp)，6.84(1H，d，J_o＝8Hz，H₄m-methoxybenzyl), 6.99(1H, t, J)_o＝8Hz，H₆Trp)，7.08(1H，m，H₄Phenyl), 7.11-7, 16(5H, m, H)₂And H₄Trp，H₂And H₆Phenyl radical, H₅m-methoxybenzyl), 7.20(2H, m, H)₃And H₅Phenyl), 7.27(1H, d, J)_o＝8Hz，H₇Trp)，8.01(3H，br s，NH₂Aib), 8.96(1H, d, J ═ 8Hz, NH amide), 10.81(1H, d, J ═ 2Hz, NH indole).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，26.4(CH₂-CH₂-phenyl), 29.1 (CH)₂βTrp)，32.7(CH₂-CH₂Phenyl), 45.7 (CH. alpha. Trp), 45.8 (CH)₂-m-methoxybenzyl), 55.5 (OCH)₃)，56.7(Cq Aib)，109.8(C₃Trp)，111.8(C₇Trp)，112.5(C₂m-methoxybenzyl), 113.5 (C)₄m-methoxybenzyl), 118.2 (C)₄Trp)，118.4(C₆m-methoxybenzyl), 118.7 (C) ₅Trp)，121.3(C₆Trp)，124.8(C₂Trp)，126.5(C₄Phenyl), 127.3 (C)₉Trp)，128.7(C₂，C₃，C₅And C₆Phenyl), 130.5 (C)₅m-methoxybenzyl), 136.4 (C)₈Trp)，137.7(C₁m-methoxybenzyl), 170.9 (C)₁Phenyl), 154.6(Cq triazole), 154.9(Cq triazole), 160.1 (C)₃m-methoxybenzyl), 171.9(CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 20):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.28(3H，s，CH₃Aib)，1.32(3H，s，CH₃Aib)，2.46(2H，m，CH ₂-CH₂phenyl), 2.82(2H, m, CH)₂-CH ₂-phenyl), 3.35(2H, d, J ═ 7Hz, CH)₂βTrp)，3.68(3H，s，OCH₃)，5.02(2H，s，CH ₂-p-methoxybenzyl), 5.22(1H, m, CH. alpha. Trp), 6.73-6.81(4H, m, CHar p-methoxybenzyl), 6.84(1H, t, J)_o＝7Hz，H₅Trp)，7.00(1H，t，J_o＝7Hz，H₆ Trp)，7.05-7.11(4H，m，H₂And H₆Phenyl radical, H₂And H₄Tr p)，7.14-7.22(3H，m，H₃，H₄And H₅Phenyl), 7.29(1H, d, J)_o＝8Hz，H₇Trp)，8.09(3H，brs，NH₂Aib), 8.99(1H, d, J ═ 8Hz, NH amide), 10.83(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，26.5(CH₂-CH₂-phenyl), 29.1 (CH)₂βTrp)，32.6(CH₂-CH₂-phenyl), 45.5(CH₂-p-methoxybenzyl), 45.7 (CH. alpha. Trp), 55.5 (OCH)₃)，56.8(Cq Aib)，109.7(C₃Trp)，111.8(C₇Trp)，114.6(C₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.7(C₅ Trp)，121.3(C₆Trp)，124.9(C₂Trp)，126.6(C₂And C₆Phenyl), 127.3 (C)₉Trp)，127.6(C₁p-methoxybenzyl), 128.0 (C)₂And C₆p-methoxybenzyl), 128.7 (C)₃，C₄And C₅Phenyl), 136.4 (C)₈Trp)，140.8(C₁Phenyl), 154.5(Cq triazole), 154.8(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 172.0 (COAib).

(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 22):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.31(3H，s，CH₃Aib)，1.73(2H，m，CH₂-CH ₂-CH₂Phenyl), 2.47(2H, m, C)H ₂-CH₂-CH₂Phenyl), 2.52(2H, t,³J＝7Hz，CH₂-CH₂-CH ₂-phenyl), 3.35(2H, d, J ═ 7Hz, CH)₂βTrp)，3.68(3H，s，OCH₃)，4.98(2H，s，CH₂-P-methoxybenzyl), 5.20(1H, m, CH. alpha. Trp), 6.75(4H, m, CHar P-methoxybenzyl), 6.82(1H, t, J)_o＝7Hz，H₅Trp)，6.99(1H，t，J_o＝7Hz，H₆Trp)，7.04-7.07(4H，m，H₂And H₆Phenyl radical, H₂And H₄Trp)，7.13-7.24(3H，m，H₃，H₄And H₅Phenyl), 7.29(1H, d, J)_o＝8Hz，H₇Trp)，8.03(3H，brs，NH₂Aib), 8.96(1H, d, J ═ 8Hz, NH amide), 10.80(1H, d, J ═ 2Hz, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.6(CH₃Aib)，24.06(CH₂-CH₂-CH₂-phenyl), 28.5(CH₂-CH₂-CH₂-phenyl), 29.2 (CH)₂βTrp)，34.7(CH₂-CH₂-CH₂-phenyl), 45.5(CH₂-p-methoxybenzyl), 45.8 (CH. alpha. Trp), 55.5 (OCH)₃)，56.8(Cq Aib)，109.8(C₃Trp)，111.8(C₇Trp)，114.6(C₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.9(C₂Trp)，126.2(C₂And C₆Phenyl), 127.3 (C)₉Trp)，127.8(C₁p-methoxybenzyl), 127.9 (C)₂And C₆p-methoxybenzyl), 128.7 (C)₃，C₄And C₅Phenyl), 136.4 (C)₈Trp)，141.7(C₁Phenyl), 154.8(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 171.9 (COAib).

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 24):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.29(3H，s，CH₃Aib)，1.35(3H，s，CH₃Aib)，1.78(2H，m，CH₂-CH ₂-CH₂indole), 2.34(2H, m, C)H ₂-CH₂-CH₂Indole), 2.48(2H, m, N-CH)₂-CH ₂Indole), 2.80(2H, m, CH)₂-CH₂-CH ₂Indole), 3.34(2H, m, N-C)H ₂-CH₂Indole), 3.94(2H, m, CH)₂βTrp)，5.27(1H，m，CHαTrp)，6.73-6.94(4H，m，H₅And H₆Trp，H₅Indoles from N-CH₂-CH₂-indole and H₅Indole is from CH₂-CH₂-CH₂Indole), 6.99-7.04(5H, m, H) ₂Trp，H₂And H₆Indoles from N-CH₂-CH₂-indole, H₂And H₆Indole from CH₂-CH₂-CH₂Indole), 7.20(1H, d, J)_o＝8Hz，H₄Indoles from N-CH₂-CH₂Indole), 7.29(3H, m, H)₄And H₇Trp，H₇Indoles from N-CH₂-CH₂Indole), 7.40(1H, d, J)_o＝8Hz，H₇Indole from CH₂-CH₂-CH₂Indole), 7.44(1H, d, J)_o＝8Hz，H₄Indole from CH₂-CH₂-CH₂Indole), 8.05(3H, brs, NH)₂Aib), 9.07(1H, d, J ═ 8Hz, NH amide), 10.75(1H, s, NH indole from CH), 8.8₂-CH₂-CH₂Indole), 10.86(1H, s, NH indole Trp), 10.90(1H, s, NH indole from N-CH)₂-CH₂-indoles).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.8(CH₃Aib)，24.5(CH₂-CH₂-CH₂Indole), 25.8 (CH)₂-CH₂-CH₂-indole), 27.2 (CH)₂-CH₂-CH₂Indole), 29.4 (CH)₂ βTrp)，44.1(N-CH₂-CH₂Indole), 46.0 (CH. alpha. Trp), 52.9(N-CH₂-CH₂Indole), 56.8(Cq Aib), 109.7 (C)₃Trp and C₃Indoles from N-CH₂-CH₂-indole), 111.8 (C)₇Tr p)，111.9(C₇Indoles from N-CH₂-CH₂-indole and C₇Indole from CH₂-CH₂-CH₂Indole), 114.0 (C)₃Indole from CH₂-CH₂-CH₂Indole), 118.2 (C)₄Indoles from N-CH₂-CH₂Indole), 118.3 (C)₄Trp)，118.5(C₅Indole from CH₂-CH₂-CH₂Indole), 118.6 (C)₄Indole from CH₂-CH₂-CH₂Indole), 118.9 (C)₅Trp)，119.0(C₅Indoles from N-CH₂-CH₂Indole), 121.3 (C)₆Trp)，121.4(C₆Indole from CH₂-CH₂-CH₂Indole), 121.6 (C)₆Indoles from N-CH₂-CH₂Indole), 122.7 (C)₂Trp，C₂Indoles from N-CH₂-CH₂-indole and C₂Indole from CH₂-CH₂-CH₂Indole), 127.1(C₉Trp)，127.4(C₉Indoles from N-CH₂-CH₂-indole and C₉Indole from CH₂-CH₂-CH₂Indole), 136.4 (C) ₈Trp)，136.5(C₈Indole from CH₂-CH₂-CH₂-indole), 136.7 (C)₈Indoles from N-CH₂-CH₂Indole), 154.7(2Cq triazole), 171.9(CO amide).

(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 26):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.26(3H，s，CH₃Aib)，1.29(3H，s，CH₃Aib)，2.78-2.92 (4H，m，CH ₂-CH ₂-phenyl), 3.29(2H, m, CH)₂βTrp)，3.65(3H，s，OCH₃) 4.97-5.21(3H, m, CH. alpha. Trp and CH)₂-o-methoxybenzyl), 6.52(1H, d, J)_o＝7Hz，H₃o-methoxybenzyl), 6.78(1H, t, J)_o＝7Hz，H₅Trp)，6.82(1H，t，J_o＝8Hz，H₆Trp)，6.84-7.04(3H，m，H₄，H₅And H₆o-methoxybenzyl), 7.15(1H, d, J)_o＝7Hz，H₄Trp)，7.19-7.29(4H，m，H₃，H₄And H₅Phenyl radical, H₇Trp)，8.03(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 8Hz, NH amide), 10.82(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.7(CH₃Aib)，26.3(CH₂-CH₂-phenyl), 29.0 (CH)₂βTrp)，32.5(CH₂-CH₂-phenyl), 42.3 (CH)₂-o-methoxybenzyl), 45.7 (CH. alpha. Trp), 55.8 (OCH)₃)，56.7(Cq Aib)，109.7(C₃Trp)，111.5(C₇Trp)，111.8(C₃o-methoxybenzyl), 118.2 (C)₄Trp)，118.7(C₅Trp)，121.0(C₆Trp)，121.3(C₅o-methoxybenzyl), 123.2 (C)₁o-methoxybenzyl), 124.9 (C)₂Trp)，126.6(C₂And C₆Phenyl), 127.2 (C)₉Trp and C₄o-methoxybenzyl), 128.7 (C)₃，C₄And C₅Phenyl), 129.9 (C)₆o-methoxybenzyl), 136.4 (C)₈Trp)，140.6(C₁Phenyl), 154.8(Cq triazole), 155.2(Cq triazole), 156.7 (C)₂o-methoxybenzyl), 171.9(CO Aib).

(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 27):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.21(3H，s，CH₃Aib)，1.25(3H，s，CH₃Aib)，2.46(2H，m，CH ₂-CH₂Phenyl), 2.88(2H, m, CH)₂-CH ₂Phenyl), 3.26(2H, dd,³j-14 Hz and 6Hz, CH₂βTrp)，3.36(2H，dd，³J-14 Hz and 9Hz, CH₂βTrp)，4.99(1H，m，CH αTr p)，5.65(1H，d，³J＝18Hz，CH ₂Naphthyl), 5.78(1H, d,³J＝18Hz，CH ₂naphthyl), 6.29(1H, d, J)_o＝7Hz，H₂Naphthyl), 6.45(1H, t, J)_o＝7Hz，H₅Trp)，6.62(1H，d，J_o＝8Hz，H₄Trp)，6.88(1H，t，J_o＝8Hz，H₆Trp)，7.04-7.06(4H，m，H₂And H₇Trp，H₂And H₆Phenyl), 7.07-7.25 (H)₃Naphthyl, H₃，H₄And H₅Phenyl), 7.57-7.60(2H, m, H)₆And H₇Naphthyl), 7.86(1H, d, J)_o＝8Hz，H₄Naphthyl), 7.98-8.00(4H, m, H)₅And H₈Naphthyl, NH₂Aib), 8.96(1H, d, J ═ 8Hz, NH amide), 10.77(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.6(CH₃Aib)，26.3(CH₂CH₂-phenyl), 29.2 (CH)₂βTrp)，32.6(CH₂-CH₂-phenyl), 43.8(CH₂Naphthyl), 45.6 (CH. alpha. Trp), 56.7(Cq Aib), 109.7 (C)₃Trp)，111.7(C₇Trp)，117.9(C₄ Trp)，118.4(C₅Trp)，121.1(C₆Trp)，122.1(C₂Naphthyl), 123.0 (C)₈Naphthyl), 124.9 (C)₂Trp)，125.9(C₃Naphthyl), 126.5 (C)₆Naphthyl), 126.9 (C)₂And C₆Phenyl), 127.0 (C)₉Trp and C₇Naphthyl), 127.1 (C)₄Naphthyl), 128.4 (C)₅Naphthyl), 128.7 (C)₃，C₄And C₅Phenyl), 130.0 (C)₉Naphthyl), 131.7 (C)₁Naphthyl), 133.6 (C)₁0 naphthyl), 136.4 (C)₈Trp)，140.8(C₁Phenyl), 154.8(Cq triazole), 155.3(Cq triazole), 171.9(CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3, 4-dichlorobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 28):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.26(6H，s，CH₃Aib)，2.87(2H，m，CH ₂-CH₂indole), 2.96(2H, m, CH)₂-CH ₂Indole), 3.32(2H, m, CH)₂β Trp), 5.13(3H, m, CH α Trp and CH) ₂-m, p-dichlorobenzyl), 6.58(1H, d, J)_o＝8Hz，H₆m, p-dichlorobenzyl), 6.85(1H, t, J)_o＝7Hz，H₅Trp)，6.96(1H，t，J_o＝7Hz，H₅Indole), 7.01(2H, m, H)₆Indole and H₆Trp)，7.04(1H，s，H ₂Trp)，7.08(1H，s，H₂Indole), 7.13(1H, d, J)_o＝8Hz，H₅m, p-dichlorobenzyl), 7.20-7.30(4H, m, H)₄And H₇Indole, H₇Trp and H₂m, p-dichlorobenzyl), 7.36(1H, d, J)_o＝8Hz，H₄Trp)，8.08(3H，brs，NH₂Aib), 8.98(1H, d, J ═ 8Hz, NH amide), 10.80(1H, s, NH indole), 10.82(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)22.8(CH₂-CH₂-indole), 23.4 (CH)₃Aib)，23.8(CH₃Aib)，25.8(CH₂-CH₂Indole), 29.0 (CH)₂βTrp)，44.8(CH₂-m, p-dichlorobenzyl), 45.6 (CH. alpha. Trp), 56.8(Cq Aib), 109.7 (C)₃Indole), 111.8 (C)₇Indole and C₇Trp)，118.1(C₄Trp)，118.4(C₅Indole), 118.6 (C)₄Indole and C₅Trp)，121.3(C₆Indole and C₆Trp)，123.0(C₂Indole and C₂Trp)，126.4(C₆m, p-dichlorobenzyl), 127.1 (C)₉Trp)，127.3(C₉Indole), 128.6 (C)₂m, p-dichlorobenzyl), 130.9 (C)₄m, p-dichlorobenzyl), 131.3 (C)₅m, p-dichlorobenzyl), 132.0 (C)₃m, p-dichlorobenzyl), 136.4 (C)₈Trp)，136.6(C₈Indole), 137.2 (C)₁m, p-dichlorobenzyl), 154.7(Cq triazole), 155.1(Cq triazole), 172.0 (COAIb).

(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 30):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.29(3H，s，CH₃Aib)，3.33(2H，m，CH₂βTrp)，4.02(2H，s，CH₂-benzyl), 5.10(3H, m, CH)₂-p-fluorobenzyl and CH α Trp), 6.71(2H, m, H)₃And H₅p-fluorobenzyl), 6.80(1H, t, J) _o＝8Hz，H₅Trp)，6.90(2H，d，J_o＝8Hz，H₂And H₆p-fluorobenzyl), 6.94(1H, t, J)_o＝8Hz，H₆Trp)，6.99-7.10(4H，m，H₂And H₄Trp，H₂And H₆Benzyl), 7.20(3H, m, H)₃，H₄And H₅Benzyl), 7.27(1H, d, J)_o＝8Hz，H₇Trp)，8.09(3H，brs，NH₂Aib), 8.97(1H, d, J ═ 8Hz, NH amide), 10.79(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d₆，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，29.0(CH₂βTrp)，31.1(CH₂-benzyl), 45.7 (CH)₂-p-fluorobenzyl), 45.8 (CH. alpha. Trp), 56.8(Cq Aib), 109.6 (C)₃Trp)，111.8(C₇Trp), 115.6 and 115.9 (C)₃And C₅p-fluorobenzyl), 118.2 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.8(C₂Trp)，127.1(C₄Benzyl), 127.2 (C)₉Trp), 128.8 and 128.9 (C)₂And C₆p-fluorobenzyl), 129.4 (C)₂，C₃，C₅And C₆p-fluorobenzyl), 131.6 (C)₁p-fluorobenzyl), 135.9 (C)₁Benzyl), 136.4 (C)₈Trp)，154.0(C₄p-fluorobenzyl), 155.3(Cq triazole), 172.0(CO amide).

(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 33):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.25(3H，s，CH₃Aib)，1.28(3H，s，CH₃Aib)，1.73(2H，m，CH₂-CH ₂-CH₂phenyl), 2.23(3H, s, CH)₃P-methylbenzyl), 2.49-2.54(4H, m, C)H ₂-CH₂-CH ₂Phenyl), 3.33(2H, m, CH)₂βTrp)，5.04(2H，s，CH₂-p-methylbenzyl), 5.16(1H, m, CH. alpha. Trp), 6.74(2H, d, J)_o＝8Hz，H₃And H₅p-methylbenzyl), 6.80(1H, t, J)_o＝7Hz，H₅Trp)，6.98(1H，t，J_o＝7Hz，H₆Trp)，7.03(1H，d，J＝2Hz，H₂Trp), 7.06(5H, m, CHa r phenyl), 7.14(1H, d, J)_o＝7Hz，H₄Trp)，7.20(2H，d，J_o＝7Hz，H₂And H₆p-methylbenzyl), 7.27(1H, d, J)_o＝8Hz，H₇Trp)，8.01(3H，brs，NH₂Aib), 8.95(1H, d, J ═ 8Hz, NH amide), 10.80(1H, d, J ═ 2Hz, NH indole Trp),

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)21.0(CH₃p-methylbenzyl), 23.5 (CH) ₃Aib)，23.8(CH₃Aib)，24.0(CH₂-CH₂-CH₂-phenyl), 28.5(CH₂-CH₂-CH₂-phenyl), 29.1 (CH)₂βTrp)，34.7(CH₂-CH₂-CH₂Phenyl), 45.7 (CH. alpha. Trp), 45.8 (CH)₂-p-methylbenzyl), 56.8(Cq Aib), 109.8 (C)₃Trp)，111.8(C₇Trp)，118.3(C₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.9(C₂Trp)，126.2(C₄Phenyl), 126.4 (C)₃And C₅p-methylbenzyl), 127.3 (C)₉Trp)，128.7(C₂，C₃，C₅And C₆Phenyl), 129.8 (C)₂And C₆p-methylbenzyl), 133.0 (C)₁p-methylbenzyl), 136.4 (C)₈Trp)，137.5(C₄p-methylbenzyl), 141.7 (C)₁Phenyl), 154.8(Cq triazole), 171.9(CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 34):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.25(3H，s，CH₃Aib)，1.28(3H，s，CH₃Aib)，2.23(3H，s，CH ₃-p-methylbenzyl), 2.84-2.97(4H, m, C)H ₂-CH ₂Indole), 3.32(2H, m, CH)₂βTrp)，5.04(2H，s，CH ₂-p-methylbenzyl), 5.16(1H, m, CH. alpha. Trp), 6.79-6.86(4H, m, CH ar p-methylbenzyl), 6.99-7.05(4H, m, H₅And H₆Indole, H₅And H₆Trp)，7.08(3H，m，H₂Indole, H₂And H₄Trp)，7.25-7.30(3H，m，H₄And H₇Indole, H₇Trp)，8.00(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 8Hz, NH amide), 10.76(1H, s, NH indole), 10.78(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d ⁶，300°K)：

δ(ppm)21.0(CH₃-p-methylbenzyl), 22.8 (CH)₂-CH₂-indole), 23.8 (CH)₃ Aib)，23.9(CH₃Aib)，25.9(CH₂-CH₂Indole), 28.5 (CH)₂βTrp)，45.7(CH₂-p-methylbenzyl and CH α Trp), 56.7(Cq Aib), 109.9 (C)₃Trp)，111.8(C₇Indole and C₇Trp)，113.4(C₃Indole), 118.1 (C)₄Trp)，118.3(C₄Indole), 118.5 (C)₅Indole), 118.7 (C)₅Trp)，120.9(C₆Indole and C₆Trp)，121.3(C₂Indole and C₂Trp)，126.3(C₃And C ₅p-methylbenzyl), 127.2 (C)₉Indole), 127.3 (C)₉Trp)，129.8(C₂And C₆p-methylbenzyl), 133.1 (C)₁p-methylbenzyl), 135.8 (C)₈Indole, C₈Trp)，136.4(C₄p-methylbenzyl), 154.8(Cq triazole), 155.0(Cq triazole), 171.9(CO Aib).

(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 37):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.25(3H，s，CH₃Aib)，1.28(3H，s，CH₃Aib)，2.23(3H，s，CH₃p-methylbenzyl), 2.83(4H, m, C)H ₂-CH ₂Phenyl), 3.32(2H, m, CH)₂ βTrp)，5.05(2H，s，CH₂-p-methylbenzyl), 5.18(1H, m, CH. alpha. Trp), 6.75(2H, d, J)_o＝8Hz，H₃And H₅p-methylbenzyl), 6.82(1H, t, J)_o＝8Hz，H₅ Trp)，6.99(1H，t，J_o＝8Hz，H₆Trp)，7.02-7.11(6H，m，H₂Trp and CHa r phenyl), 7.15(1H, d, J)_o＝7Hz，H₄Trp)，7.20(2H，d，J_o＝7Hz，H₂And H₆p-methylbenzyl), 7.28(1H, d, J)_o＝8Hz，H₇Trp)，8.01(3H，brs，NH₂Aib), 8.93(1H, d, J ═ 8Hz, NH amide), 10.77(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)21.0(CH₃p-methylbenzyl), 23.6 (CH)₃Aib)，23.8(CH₃Aib)，26.5(CH₂-CH₂-phenyl), 29.1 (CH)₂βTrp)，32.7(CH₂-CH₂Phenyl), 45.7 (CH. alpha. Trp and CH)₂-p-methylbenzyl), 56.8(Cq Aib), 109.8 (C)₃Trp)，111.8(C₇Trp)，118.3(C₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.8(C₂Trp)，126.4(C₃And C₅p-methylbenzyl), 126.6 (C)₄Phenyl), 127.3 (C)₉ Trp)，128.7(C₂，C₃，C₅And C₆Phenyl), 129.8 (C)₂And C₆p-methylbenzyl), 133.0 (C)₁p-methylbenzyl), 136.4 (C)₈Trp)，137.5(C₄p-methylbenzyl), 140.9 (C)₁Phenyl), 154.5(Cq triazole), 154.9(Cq triazole), 171.9(CO amide).

(R) -N- (1- (5-benzyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 39):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.23(3H，s，CH₃Aib)，1.27(3H，s，CH₃Aib), 3.34(1H, dd, J ═ 14Hz and 6Hz, CH)₂β Trp), 3.43(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，4.13(2H，s，CH ₂-benzyl), 5.22(1H, s, CH. alpha. Trp), 5.35(2H, s, CH)₂-o-pyridyl), 6.80(1H, t, J)_o＝8Hz，H₅Trp)，6.92(1H，t，J_o＝8Hz，H₅Pyridyl), 6.97(1H, t, J)_o＝8Hz，H₆Trp)，7.04(1H，d，J_o＝8Hz，H₄Trp)，7.07(1H，d，J＝2Hz，H₂Trp), 7.10-7.16(5H, m, CHar benzyl), 7.19(1H, s, H)₃o-pyridyl), 7.26(1H, d, J)_o＝8Hz，H₇Trp)，7.57(1H，t，J_o＝9Hz，H₄o-pyridyl), 8.16(3H, brs, NH)₂Aib)，8.36(1H，d，J_αβ＝5Hz，H₆o-pyridyl), 9.01(1H, d, J ═ 8Hz, NH amide), 10.85(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.4(CH₃Aib)，23.7(CH₃Aib)，28.6(CH₂βTrp)，30.4(CH₂-benzyl), 45.7(CH α Trp), 47.7(CH α Trp), 2₂-o-pyridyl), 56.7(Cq Aib), 109.8 (C)₃Trp)，111.8(C₇Trp)，118.3(C₄Trp)，118.6(C₅Trp)，121.2(C₆Trp)，121.7(C₃o-pyridyl), 123.3 (C)₅o-pyridyl), 124.8 (C)₂Trp)，127.1(C₄Benzyl), 127.3 (C)₉Trp)，128.8(C₂And C₆Benzyl), 129.0 (C)₃And C₅Benzyl), 135.6 (C)₁Benzyl), 136.4 (C)₈Trp)，137.5(C₄o-pyridyl), 149.5 (C)₆o-pyridyl), 154.1(Cq triazole), 154.2(Cq triazole), 155.7 (C)₂o-pyridyl), 172.0(CO amide).

(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 43):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.10(3H，t，J＝8Hz，CH ₃-CH₂p-ethylbenzyl), 1.25(3H, s, CH)₃Aib)，1.28(3H，s，CH₃Aib)，2.53(2H，q，J＝8Hz，CH₃-CH ₂P-ethylbenzyl), 2.83(4H, m, C)H ₂-CH ₂Phenyl), 3.34(2H, m, CH)₂βTrp)，5.07(2H，s，CH ₂-p-ethylbenzyl), 5.19(1H, m, CH. alpha. Trp), 6.77(2H, d, J) _o＝8Hz，H₃And H₅p-ethylbenzyl), 6.81(1H, t, J)_o＝7Hz，H₅Trp)，6.99(1H，t，J_o＝8Hz，H₆Trp), 7.05-7.10(7H, m, CHar phenyl, H)₂And H₆p-ethylbenzyl), 7.13(1H, d, J ═ 2Hz, H)₂Trp)，7.20(1H，d，J_o＝7Hz，H₄Trp)，7.28(1H，d，J_o＝8Hz，H₇Trp)，8.03(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 8Hz, NH amide), 10.79(1H, s NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)15.9(CH₃-CH₂p-ethylbenzyl), 23.5 (CH)₃Aib)，23.8(CH₃ Aib)，26.5(CH₂-CH₂-phenyl), 28.1 (CH)₃-CH₂p-ethylbenzyl), 29.1 (CH)₂ βTrp)，32.7(CH₂-CH₂-phenyl), 45.7(CH α Trp), 45.8 (c) (CH₂-p-ethylbenzyl), 56.8(Cq Aib), 109.8 (C)₃Trp)，111.8(C₇Trp)，118.3(C₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.9(C₂Trp)，126.5(C₃And C₅p-ethylbenzyl), 126.6 (C)₄Phenyl), 127.3 (C)₉Trp)，128.6(C₂And C₆p-ethylbenzyl, C₂，C₃，C₅And C₆Phenyl), 133.1 (C)₁p-ethylbenzyl), 136.5 (C)₈ Trp)，140.8(C₁Phenyl), 143.8 (C)₄p-ethylbenzyl), 154.6(Cq triazole), 154.9(Cq triazole), 171.9(CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide (compound 44):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)1.42(m，2H，H₃and H₅Piperidinyl), 1.55(m, 1H, H)₅Piperidinyl), 2.23(m, 1H, H)₄Piperidinyl), 2.75(m, 5H, H)₂Piperidinyl and CH ₂-CH ₂Phenyl), 3.04(m, 1H, H)₆Piperidinyl), 3.13(m, 1H, H)₂Piperidinyl) group, 3.32(m，2H，CH₂βTrp)，3.66(s，3H，OCH₃)，4.97(m，2H，CH₂-p-methoxybenzyl), 5.23(m, 1H, CH. alpha. Trp), 6.70(s, 4H, CHar p-methoxybenzyl), 6.87(t, 1H, J_o＝8Hz，H₅Trp)，7.00(m，2H，H₂And H₆Trp)，7.07(d，2H，J_o＝8Hz，H₂And H₆Phenyl), 7.14(d, 1H, J) _o＝7Hz，H₄ Trp)，7.18-7.30(m，4H，H₇Trp，H₃，H₄And H₅Phenyl), 8.16 and 8.46(2m, 2H, NH piperidinyl TFA salt), 8.66(d, 1H, J ═ 8Hz, NH amide), 10.75(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)24.9(C₃Piperidinyl), 25.4 (C)₅Piperidinyl), 26.5(CH₂-CH₂-phenyl), 29.2 (CH)₂βTrp)，32.7(CH₂-CH₂-phenyl), 38.7 (C)₄Piperidinyl), 42.7 (C)₂And C₆Piperidinyl), 44.7(CH Trp), 45.3 (CH)₂-p-methoxybenzyl), 55.5 (OCH)₃)，110.2(C₃Trp)，111.7(C₇Trp)，114.4(C₃And C₅p-methoxybenzyl), 118.5 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.4(C₂Trp)，126.5(C₂And C₆Phenyl), 127.5 (C)₉Trp)，127.8(C₁，C₂And C₆p-methoxybenzyl), 128.7 (C)₃，C₄And C₅Phenyl), 136.4 (C)₈Trp)，140.8(C₁Phenyl), 155.3(Cq triazole), 155.4(Cq triazole), 159.1 (C)₄p-methoxybenzyl), 173.1(CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide (compound 45):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)1.41(m，2H，H₃and H₅Piperidinyl), 1.54(dd, 1H, J ═ 13Hz and 2Hz, H)₅Piperidinyl), 2.23(m, 1H, H)₄Piperidinyl), 2.72(m, 2H, H)₂And H₆Piperidinyl), 2.77-2.93(m, 4H, C)H ₂-CH ₂Indole), 3.06(m, 2H, H)₂And H₆Piperidinyl), 3.32(m, 2H, CH)₂βTrp)，3.65(s，3H，OCH₃)，4.94(s，2H，CH₂-p-methoxybenzyl), 5.22(m, 1H, CH. alpha. Trp), 6.68(s, 4H, CHar p-methoxybenzyl), 6.87(m, 3H, H)₅And H₆Trp，H₅Indole), 6.98(m, 4H, H)₂And H₆Indole, H₂And H ₄Trp)，7.20-7.33(m，3H，H₄And H₇Indole, H₇Tr p), 8.15 and 8.46(2m, 2H, NH piperidinyl TFA salt), 8.64(d, 1H, J ═ 8Hz, NH amide), 10.74(s, 2H, NH indole and NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.9(CH₂-CH₂Indole), 24.9 (C)₃Piperidinyl), 25.4 (C)₅Piperidinyl), 26.0: (CH₂-CH₂Indole), 29.3 (CH)₂βTrp)，39.1(C₄Piperidinyl), 42.7 (C)₂And C₆Piperidinyl), 44.7 (CH. alpha. Trp), 45.3 (CH)₂-p-methoxybenzyl), 55.5 (OCH)₃)，109.5(C₃Trp)，111.7(C₇Indole and C₇Trp)，113.5(C₃Indole), 114.4 (C)₃And C₅p-methoxybenzyl), 118.5 (C)₄Indole and C₄Trp)，118.6(C₅Indole and C₅Trp)，121.2(C₆Indole), 121.3 (C)₆Trp)，122.9(C₂Indole and C₂Trp)，127.2(C₉Indole), 127.6 (C)₉Trp，C₂And C₆p-methoxybenzyl), 127.9 (C)₁p-methoxybenzyl), 136.4 (C)₈Trp)，136.6(C₈Indole), 154.9(Cq triazole), 155.2(Cq triazole), 159.0 (C)₄p-methoxybenzyl), 173.0(CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide (compound 50):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.78(m，4H，CH ₂-CH ₂-phenyl), 3.26(1H, dd, J ═ 14Hz and 7Hz, CH₂βTrp)，3.39(m，3H，CH₂Beta Trp and CH ₂-NH₂)，3.65(s，3H，OCH₃)，4.95(m，2H，CH₂-p-methoxybenzyl), 5.20(m, 1H, CH. alpha. Trp), 6.63(s, 4H, CHar p-methoxybenzyl), 6.86(t, 1H, J_o＝7Hz，H₅Trp)，6.99(s，1H，H₂Trp)，7.02(t，1H，J_o＝7Hz，H₆Trp)，7.10(m，2H，H₂And H₆Phenyl), 7.15(d, 1H, J)_o＝7Hz，H₄Trp)，7.23(m，3H，H₃，H₄And H₅Trp)，7.31(d，1H，J_o＝8Hz，H₇Trp)，7.95(brs，3H，NH₂Gly, TFA salt), 9.20(d, 1H, J ═ 8Hz, NH amide), 10.82(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)26.5(CH₂-CH₂-phenyl), 29.8 (CH)₂βTrp)，32.7(CH₂-CH₂-phenyl), 39.0(CH₂-NH₂)，45.3(CH₂-p-methoxybenzyl), 45.4 (CH. alpha. Trp), 55.4 (OCH)₃)，109.7(C₃Trp)，111.8(C₇Trp)，114.5(C₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.9(C₅Trp)，121.4(C₆Trp)，124.6(C₂Trp)，126.5(C₂And C₆Phenyl), 127.3 (C)₉Trp)，127.7(C₁p-methoxybenzyl), 127.8 (C)₂And C₆p-methoxybenzyl), 128.7 (C)₃，C₄And C₅Phenyl), 136.4 (C)₈Trp)，140.9(C₁Phenyl), 154.3(Cq triazole), 154.8(Cq triazole), 159.0 (C)₄p-methoxybenzyl), 166.1(CO amide).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide (compound 51):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.77-2，88(m，4H，CH ₂-CH ₂phenyl), 3.37(m, 2H, CH)₂ βTrp)，3.64(s，3H，OCH₃)，3.74(m，2H，CH₂-o-pyridyl), 5.03(m, 2H, CH)₂-p-methoxybenzyl), 5.24(m, 1H, CH. alpha. Trp), 6.65(s, 4H, CHarp-methoxybenzyl), 6.85(t, 1H, J)_o＝7Hz，H₅Trp)，7.01(m，2H，H₂And H₆Trp)，7.08(d，2H，J_o＝7Hz，H₂And H₆Phenyl), 7.15(d, 1H, J)_o＝7Hz，H₄Trp)，7.21(m，3H，H₃，H₄And H₅Phenyl), 7.27-7.36(m, 2H, H)₇Trp and H₃o-pyridyl), 7.58(t, 1H, J ═ 6Hz, H)₅o-pyridyl), 8.04(t, 1H, J)_o＝8Hz，H₄o-pyridyl), 8.62(d, 1H, J)_αβ＝5Hz，H₆o-pyridyl), 9.17(d, 1H, J ═ 8hz, NH amide), 10.81(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)26.4(CH₂-CH₂-phenyl), 29.2 (CH)₂βTrp)，32.4(CH₂-CH₂-phenyl), 41.7 (CH)₂-o-pyridyl), 45.3(CH αTrp)，45.7(CH₂-p-methoxybenzyl), 55.5 (OCH)₃)，109.7(C₃Trp)，111.8(C₇Trp)，114.4(C₃And C₅p-methoxybenzyl), 118.4 (C)₄Trp)，118.8(C₅Trp)，121.4(C₆Trp)，124.1(C₃o-pyridyl), 124.6 (C) ₂Trp)，126.4(C₅o-pyridyl), 126.6 (C)₂And C₆Phenyl), 127.2 (C)₉Trp)，127.4(C₁p-methoxybenzyl), 127.9 (C)₂And C₆p-methoxybenzyl), 128.7 (C)₃，C₄And C₅Phenyl), 136.4 (C)₈Trp)，140.5(C₁Phenyl), 142.1 (C)₄o-pyridyl), 145.3 (C)₆o-pyridyl), 153.0 (C)₂o-pyridyl), 154.5(Cq triazole), 155.3(Cq triazole), 159.1 (C)₄p-methoxybenzyl), 167.9(CO amide).

(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide (Compound 64):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.83(m，2H，CH ₂-CH₂phenyl), 2.90(m, 2H, CH)₂-CH ₂Phenyl), 3.48(m, 2H, CH)₂βTrp)，3.57(s，3H，OCH₃)，3.61(s，3H，OCH₃)，4.97(d，1H，J＝17Hz，CH₂-o, p-dimethoxybenzyl), 5.09(d, 1H, J ═ 17Hz, CH₂-o, p-dimethoxybenzyl), 5.56(m, 1H, CH. alpha. Trp), 6.18(dd, 1H, J)_o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.41(d, 1H, J)_m＝2Hz，H₃o, p-dimethoxybenzyl), 6.55(d, 1H, J)_o＝8Hz，H₆o, p-dimethoxybenzyl), 6.87(t, 1H, J)_o＝8Hz，H₅Trp)，7.01(t，1H，J_o＝8Hz，H₆Trp)，7.08(m，3H，H₂Trp，H₂And H₆Phenyl radical)，7.14(d，1H，J_o＝7Hz，H₄Trp)，7.19-7.31(m，4H，H₇Trp，H₃，H₄And H₅Phenyl), 7.56(t, 1H, J ═ 8Hz, NH amide), 7.91(m, 2H, H)₄And H₅o-pyridyl), 8.57(d, 1H, J)_αβ＝5Hz，H₆o-pyridyl), 9.16(d, 1H, J)_o＝8Hz，H₃o-pyridyl), 10.80(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)26.2(CH₂-CH₂-phenyl), 28.8 (CH)₂βTrp)，32.1(CH₂-CH₂-phenyl), 43.0 (CH)₂-o, p-dimethoxybenzyl), 45.5 (CH. alpha. Trp), 55.6 (OCH) ₃)，55.8(OCH₃)，98.9(C₃o, p-dimethoxybenzyl), 105.0 (C)₅o, p-dimethoxybenzyl), 109.5 (C)₃Trp)，111.8(C₇Trp)，114.4(C₁o, p-dimethoxybenzyl), 118.4 (C)₄Trp)，118.8(C₅Trp)，121.4(C₆Trp)，122.4(C₃o-pyridyl), 124.4 (C)₂Trp)，126.7(C₆o, p-dimethoxybenzyl), 127.2 (C)₅o-pyridyl), 127.5 (C)₉Trp)，128.6-128.8(C₂，C₃，C₄，C₅And C₆Phenyl), 136.4 (C)₈Trp)，138.1(C₄o-pyridyl), 140.2 (C)₁Phenyl), 148.8 (C)₆o-pyridyl), 149.3 (C)₂o-pyridyl), 155.2(Cq triazole), 155.4(Cq triazole), 157.9 (C)₂o, p-dimethoxybenzyl), 161.0 (C)₄o, p-dimethoxybenzyl), 163.9(CO amide).

(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide (Compound 66):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.87(m，4H，CH ₂-CH ₂phenyl), 3.51(m, 2H, CH)₂βTrp)，3.58(s，3H，OCH₃)，3.59(s，3H，OCH₃)，4.97(d，1H，J＝17Hz，CH₂-o, p-dimethoxybenzyl), 5.08(d, 1H, J ═ 17Hz, CH₂-o, p-dimethoxybenzyl), 5.56(s, 1H, CH. alpha. Trp), 6.10(dd, 1H, J)_o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.36(d, 1H, Jm ═ 2Hz, H₃o, p-dimethoxybenzyl), 6.40(d, 1H, J)_o＝8Hz，H₆o, p-dimethoxybenzyl), 6.87(t, 1H, J)_o＝8Hz，H₅Trp)，7.00(t，1H，J_o＝7Hz，H₆Trp)，7.09(m，3H，H₂Trp，H₂And H₆Phenyl), 7.15(d, 1H, J)_o＝7Hz，H₄Trp)，7.19-7.28(m，3H，H₃，H₄And H₅Phenyl), 7.36(d, 1H, J)_o＝8Hz，H₇Trp)，8.61(t，1H，J＝2Hz，H₃o-pyrazinyl), 8.78(d, 1H, J ═ 2Hz, H)₅o-pyrazinyl), 8.94(d, 1H, J ═ 1Hz, H)₆o-pyrazinyl), 9.26(d, 1H, J ═ 8Hz, NH amide), 10.78(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)26.1(CH₂-CH₂-phenyl), 28.4 (CH)₂βTrp)，32.1(CH₂-CH₂-phenyl), 42.9(CH₂-o, p-dimethoxybenzyl), 45.5 (CH. alpha. Trp), 55.5 (OCH)₃)，55.8(OCH₃)，98.7(C₃o, p-dimethoxybenzyl), 104.9 (C)₅o, p-dimethoxybenzyl), 109.7 (C)₃o, p-dimethoxybenzyl), 111.8 (C)₇Trp)，114.5(C₁o, p-dimethoxybenzyl), 118.5 (C)₄Trp)，118.8(C₅Trp)，121.4(C₆Trp)，124.4(C₂Trp)，126.7(C₆o, p-dimethoxybenzyl), 127.5 (C)₉Trp)，128.1(C₄Phenyl), 128.7-128.8 (C)₂，C₃，C₅And C₆Phenyl), 136.4 (C)₈Trp)，140.3(C₁Phenyl), 141.2 (C)₆o, p-dimethoxybenzyl), 144.2 (C)₂o-pyrazinyl), 144.3 (C)₃o-pyrazinyl), 146.8 (C)₅o-pyrazinyl), 155.2(Cqs triazole), 157.7 (C)₂o, o-dimethoxybenzyl), 160.7(CO amide), 162.9 (C)₄o, p-dimethoxybenzyl).

(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide (compound 70):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)1.40(m，1H，H₃Pro)，1.53(m，1H，H₄Pro)，1.71(m，1H，H₄Pro)，2.09(m，1H，H₃Pro)，2.90(m，4H，CH ₂-CH ₂-indole), 3.06(t, 2H, J ═ 6Hz, H)₅Pro)，3.28(m，2H，CH₂βTrp)，3.40(s，3H，OCH₃)，3.80(s，3H，OCH₃)，3.80(m，1H，CH αPro)，4.80(d，1H，J＝17Hz，CH₂-o, p-dimethoxybenzyl), 5.4(d, 1H, J ═ 17Hz, CH₂-o, p-dimethoxybenzyl), 5.1(m, 1H, CH. alpha. Trp), 6.26(dd, 1H, J)_o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.38(d, 1H, J)_o＝8Hz，H₆o, p-Dimethoxybenzyl), 6.53(d, 1H, J)_m＝2Hz，H₃o, p-dimethoxybenzyl), 6.84(t, 1H, H)₅Indole), 6.91(t, 1H, J) _o＝8Hz，H₅Trp)，6.93-7.07(m，4H，H₂And H₆Indole, H₂And H₆Trp)，7.16(d，1H，J_o＝8Hz，H₄Trp)，7.29(m，3H，H₄And H₇Indole, H₇Trp), 8.39 and 9.10(2m, 2H, NH Pro TFA salt), 9.22(d, 1H, J ═ 8Hz, NH amide), 10.76 (r), (ls, 1H, NH indole), 10.80(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.9(CH₂-CH₂-indole), 23.5 (C)₄Pro)，25.8(CH₂-CH₂Indole), 29.6 (CH)₂βTrp)，29.8(C₃Pro)，41.9(CH₂-o, p-dimethoxybenzyl), 45.2 (CH. alpha. Trp), 46.0 (C)₅Pro)，55.7(OCH₃)，55.9(OCH₃)，59.3(CH αPro)，99.0(C₃o, p-dimethoxybenzyl), 105.1 (C)₅o, p-dimethoxybenzyl), 109.7 (C)₃Trp)，111.8(C₇Indole and C₇Trp)，113.4(C₃Indole), 115.6 (C)₁o, p-dimethoxybenzyl), 118.4 (C)₄Indole and C₄Trp)，118.7(C₅Indole and C₅Trp)，121.4(C₆Indole and C₆Trp)，123.0(C₂Indole and C₂Trp)，127.2(C₉Indole), 127.3 (C)₉Trp)，128.1(C₆o, p-dimethoxybenzyl), 136.5 (C)₈Trp)，136.6(C₈Indole), 155.0(Cq triazole), 157.8 (C)₂o, p-dimethoxybenzyl), 160.9 (C)₄o, p-dimethoxybenzyl), 168.1(CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide (compound 71):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)3.01(m，2H，CH₂-CH₂indole), 3.10(m, 2H, CH)₂-CH ₂Indole), 3.51(m, 2H, CH)₂βTrp)，3.55(s，3H，OCH₃)，3.57(s，3H，OCH₃)，5.15(d，2H，J＝7Hz，CH₂-o, p-dimethoxybenzyl), 5.63(m, 1H, CH. alpha. Trp), 6.08(dd, 1H, J)_o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.35(d, 1H, J)_m＝2Hz，H₃o, p-Dimethoxybenzyl), 6.53(d, 1H, J)_o＝8Hz，H₆o, p-dimethoxybenzyl), 6.89(m, 2H, H) ₅Indole and H₅Trp)，6.99(m，2H，H₆Indole and H₆Trp)，7.08(m，2H，H₂Indole and H₂Trp)，7.29(m，3H，H₄Trp，H₄And H₇Indole), 7.41(d, 1H, J)_o＝8Hz，H₇Trp)，8.61(t，1H，J＝2Hz，H₃o-pyrazine), 8.79(d, 1H, J ═ 2Hz, H)₅o-pyrazine), 8.94(d, 1H, J ═ 1Hz, H)₆o-pyrazine), 9.43(d, 1H, J ═ 8Hz, NH amide), 10.84(s, 2H, NH indole and NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.0(CH₂-CH₂-indole), 25.3(CH₂-CH₂-indole), 27.9 (CH)₂ βTrp)，44.1(CH₂-o, p-dimethoxybenzyl), 45.5 (CH. alpha. Trp), 55.5 (OCH)₃)，55.8(OCH₃)，98.8(C₃o, p-dimethoxybenzyl), 104.9 (C)₅o, p-dimethoxybenzyl), 109.3 (C)₃Trp)，111.8(C₇Indole and C₇Trp)，112.1(C₃Indole), 113.4 (C)₁o, p-dimethoxybenzyl), 118.4 (C)₄Indole), 118.5 (C)₄Trp)，118.8(C₅Indole and C₅Trp)，121.5(C₆Indole and C₆Trp)，127.0(C₉Indole), 127.4 (C)₉Trp)，136.4(C₈Trp)，136.6(C₈Indole), 141.2 (C)₆o-pyrazine), 144.1 (C)₂o-pyrazine), 144.3 (C)₃o-pyrazine), 146.8 (C)₅p-pyrazine), 155.4(Cq triazole), 156.0(Cq triazole), 157.8 (C)₂o, p-dimethoxybenzyl), 161.0(CO amide), 163.2 (C)₄o, p-dimethoxybenzyl).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide (Compound 73):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.94(m，4H，CH ₂-CH ₂indole), 3.47(m, 2H, CH)₂βTrp)，3.57(s，3H，OCH₃)，3.60(s，3H，OCH₃)，5.05(m，2H，CH₂-o, P-dimethoxybenzyl), 5.56(m, 1H, CH. alpha. Trp), 6.14(dd, 1H, J)_o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.41(d, 1H, J) _m＝2Hz，H₃o, p-dimethoxybenzyl), 6.52(d, 1H, J)_o＝8Hz，H₆o, p-dimethoxybenzyl), 6.88(t, 2H, J)_o＝7Hz，H₅Indole and H₅Trp)，6.99(t，1H，J_o＝8Hz，H₆Trp)，7.01(t，1H，J_o＝8Hz，H₆Indole), 7.04(d, 1H, J ═ 2Hz, H)₂Trp)，7.07(d，1H，J＝2Hz，H₂Indole), 7.27-7.33(m, 4H, H)₄And H₇Trp，H₄And H₇Indole), 7.55(m, 1H, NH amide), 7.90(m, 2H, H)₄And H₅o-pyridyl), 8.57(d, 1H, J)_αβ＝4Hz，H₆o-pyridyl), 9.15(d, 1H, J ═ 8Hz, H)₃o-pyridyl), 10.78(brs, 2H NH indole and NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.3(CH₂-CH₂Indole), 25.6(CH₂-CH₂Indole), 28.9 (CH)₂ βTrp)，43.1(CH₂-o, p-dimethoxybenzyl), 45.5 (CH. alpha. Trp), 55.5 (OCH)₃)， 55.8(OCH₃)，98.9(C₃o, p-dimethoxybenzyl), 105.0 (C)₅o, p-dimethoxybenzyl), 109.5 (C)₃Trp)，111.8(C₇IndolesAnd C₇Trp)，112.8(C₃Indole), 114.4 (C)₁o, p-dimethoxybenzyl), 118.4 (C)₄Indole and C₄Trp)，118.7(C₅Indole), 118.8 (C)₅Trp)，121.4(C₆Indole and C₆Trp)，122.5(C₂Indole and C₃o-pyridyl), 123.1 (C)₂Trp)，127.1(C₅o-pyridyl), 127.2 (C)₉Indole), 127.5 (C)₉Tr p)，128.6(C₆o, p-dimethoxybenzyl), 136.4 (C)₈ Tr p)，136.6(C₈Indole), 139.1 (C)₄o-pyridyl), 146.6 (C)₆o-pyridyl), 150.6 (C)₂o-pyridyl), 155.5(Cq triazole), 155.6(Cq triazole), 157.8 (C)₂o, p-dimethoxybenzyl), 161.0 (C)₄o, p-dimethoxybenzyl), 163.9(CO amide).

(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethylamine (Compound 74):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.79(m，2H，CH ₂-CH₂Indole), 2.86(m, 2H, CH)₂-CH ₂Indole), 3.30(dd, 1H,³j-14 Hz and 5Hz, CH ₂βTrp)，3.38(dd，1H， ³J-14 Hz and 6Hz, CH ₂βTrp)，3.62(s，3H，OCH₃)，3.63(s，3H，OCH₃)，4.47(d，1H，³J＝17Hz，CH ₂-o, p-dimethoxybenzyl), 4.59(d, 1H,³J＝17Hz，CH ₂-o, p-dimethoxybenzyl), 6.11(dd, 1H, J)_o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.20(d, 1H, J)_o＝8Hz，H₆o, p-dimethoxybenzyl), 6.45(d, 1H, J)_m＝2Hz，H₃o, p-dimethoxybenzyl), 6.87(t, 1H, J)_o＝8Hz，H₅Trp)，6.91(t，1H，J_o＝8Hz，H₅Indoles)，7.00-7.04(m，2H，H₆Indole and H₆Trp)，7.07(s，1H，H₂Indole), 7.09(s, 1H, H)₂Trp)，7.17-7.35(m，4H，H₄And H₇Indole, H₄And H₇Trp)，8.75(brs，3H，NH₂TFA salt), 10.78(s, 1H, NH indole), 11.00(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.9(CH₂-CH₂-indole), 25.7(CH₂-CH₂Indole), 29.9(CH₂ βTrp)，41.5(CH₂-o, p-dimethoxybenzyl), 46.5 (CH. alpha. Trp), 55.6 (OCH)₃)，55.9(OCH₃)，98.8(C₃o, p-dimethoxybenzyl), 105.0 (C)₅o, p-dimethoxybenzyl), 107.4 (C)₃Trp)，111.8(C₇Indole and C₇Trp)，113.4(C₃Indole), 115.1 (C)₁o, p-dimethoxybenzyl), 118.0 (C)₄Indole), 118.4 (C)₄Trp)，118.6(C₅Trp)，119.0(C₅Indole), 121.3 (C)₆Trp)，121.6(C₆Indole), 122.9 (C)₂Indole), 125.4 (C)₂Trp)，127.1(C₉Indole and C₉Trp)，128.5(C₆o, p-dimethoxybenzyl), 136.5 (C)₈Trp)，136.6(C₈Indole), 152.3(Cq triazole), 155.6(Cq triazole), 157.6 (C)₂o, p-dimethoxybenzyl), 160.8 (C)₄o, p-dimethoxybenzyl).

(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide (compound 79):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.85(m，4H，CH ₂-CH ₂Phenyl), 3.51(m, 2H, CH)₂βTrp)，3.59(s，3H，OCH₃)，5.11(d，1H，J＝17Hz，CH₂-p-methoxybenzyl), 5.23(d, 1H, J ═ 17Hz, CH)₂-p-methoxybenzyl), 5.51(m, 1H, CH. alpha. Trp), 6.59(d, 2H, J)_o＝8Hz，H₃And H₅p-methoxybenzyl), 6.73(d, 2H, J)_o＝8Hz，H₂And H₆p-methoxybenzyl), 6.87(t, 1H, J)_o＝8Hz，H₅Trp)，7.01(t，1H，J_o＝8Hz，H₆Trp)，7.06(m，2H，H₂And H₆Phenyl), 7.10(d, 1H, J ═ 2Hz, H)₂Trp)，7.14(d，1H，J_o＝7Hz，H₄Trp)，7.24(m，3H，H₃，H₄And H₅Phenyl), 7.34(d, 1H, J)_o＝8Hz，H₇Trp), 7.55(m, 1H, NH amide), 7.88(m, 2H, H)₄And H₅o-pyridyl), 8.56(d, 1H, J)_αβ4Hz, H6 o-pyridyl), 9.20(d, 1H, J)_o＝8Hz，H₃o-pyridyl), 10.80(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)26.2(CH₂-CH₂-phenyl), 28.6 (CH)₂βTrp)，32.1(CH₂-CH₂-phenyl), 45.5(CH α Trp), 46.2 (c: (c)CH₂-p-methoxybenzyl), 55.4 (OCH)₃)，109.6(C₃Trp)，111.8(C₇Trp)，114.3(C₃And C₅p-methoxybenzyl), 118.5 (C)₄Trp)，118.8(C₅Trp)，121.4(C₆Trp)，122.5(C₃o-pyridyl), 124.5 (C)₂Trp)，127.2(C₂And C₆Phenyl), 127.4 (C)₉Trp and C₁p-methoxybenzyl), 127.8 (C)₅o-pyridyl), 128.7 (C)₂And C₆p-methoxybenzyl), 128.8 (C)₃，C₄And C₅Phenyl), 136.4 (C)₈Trp)，138.1(C₄o-pyridyl), 140.3 (C)₁Phenyl), 148.7 (C)₆o-pyridyl), 149.3 (C)₂o-pyridyl), 155.0(Cq triazole), 155.3(Cq tris)Oxazole), 159.0 (C)₄p-methoxybenzyl), 164.1(CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide (compound 80):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)2.95(m，4H，CH ₂-CH ₂Indole), 3.48(m, 2H, CH)₂βTrp)，3.58(s，3H，OCH₃)，5.16(m，2H，CH₂-p-methoxybenzyl), 5.50(m, 1H, CH. alpha. Trp), 6.57(d, 2H, J)_o＝8Hz，H₃And H₅p-methoxybenzyl), 6.72(d, 2H, J)_o＝8Hz，H₂And H₆p-methoxybenzyl), 6.87(t, 2H, J)_o＝8Hz，H₅Trp and H₅Indole), 6.96-7.07(m, 5H, H)₂And H₆Indole, H₂，H₄And H₆Trp)，7.27-7.34(m，3H，H₄And H₇Indole, H₇Trp), 7.55(m, 1H, NH amide), 7.88(m, 2H, H)₄And H₅o-pyridyl), 8.56(d, 1H, J)_αβ＝4Hz，H₆o-pyridyl), 9.18(d, 1H, J)_o＝8Hz，H₃o-pyridyl), 10.77(brs, 2H, NH indole Trp and NH indole).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.4(CH₂-CH₂-indole), 25.7(CH₂-CH₂Indole), 28.9 (CH)₂ βTrp)，45.5(CHαTrp)，46.2(CH₂-p-methoxybenzyl), 55.4 (OCH)₃)，109.7(C₃Trp)，111.8(C₇Trp and C₇Indole), 112.6 (C)₃Indole), 114.3 (C)₃And C₅p-methoxybenzyl), 118.4 (C)₄Trp and C₄Indole), 118.7 (C)₅Indole), 118.8 (C)₅Trp)，121.4(C₆Trp and C₆Indole), 122.4 (C)₃o-pyridyl and C₂Indole), 124.5 (C)₂Trp)，126.7(C₉Indole), 127.1 (C)₉Trp)，127.2(C₅o-pyridyl), 127.5 (C)₁p-methoxybenzyl), 127.7 (C)₂And C₆p-methoxybenzyl), 136.4 (C)₈Trp)，136.6(C₈Indole), 138.1 (C)₄o-pyridyl), 148.7 (C)₆o-pyridyl), 149.3 (C)₂o-pyridyl), 155.3(Cq triazole), 159.0 (C)₄p-methoxybenzyl), 164.0(CO amide).

(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide (compound 81):

¹H NMR(300MHz，DMSO d⁶，300°K)：

Delta (ppm)2.18(m, 2H, NH piperazine), 2.96(m, 6H, H)₂，H₅And H₆Piperazine), 3.34(d, 2H, J ═ 7Hz, CH)₂βTrp)，3.57(m，4H，CH ₂-CH ₂Indole), 3.61(s, 3H, OMe), 3.64(m, 1H, H)₃Piperazine), 4.82(m, 2H, CH)₂-p-methoxybenzyl), 5.40(m, 1H, CH. alpha. Trp), 6.45(d, 2H, J)_o＝8Hz，H₃And H₅p-methoxybenzyl), 6.51(d, 2H, J)_o＝8Hz，H₂And H₆p-methoxybenzyl), 6.65-7.47(m, 10H, chra, indole and indole Trp), 8.95(m, 1H, NH amide), 10.88(d, 1H, J ═ 2Hz, NH indole), 10.91(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.5(CH₂-CH₂Indole), 25.6(CH₂-CH₂Indole), 31.3 (CH)₂ βTrp)，41.9(CH₂-p-methoxybenzyl), 47.7 (CH. alpha. Trp, C₅And C₆Piperazine), 55.5 (OCH)₃And C₂Piperazine), 61.1 (C)₃Piperazine), 109.3 (C)₃Trp)，111.7(C₇Indole and C₇Trp)，114.0(C₃Indole), 114.3 (C)₃And C₅p-methoxybenzyl), 118.6 (C)₄Indole), 118.7 (C)₄Trp)，118.9(C₅Indole and C₅Trp)，121.4(C₆Indole), 121.5 (C)₆Trp)，123.9(C₂Indole and C₂Trp)，127.0(C₉Indole), 127.2 (C)₉Trp)，127.7(C₁p-methoxybenzyl), 128.1 (C)₂And C₆p-methoxybenzyl), 136.3 (C)₈Trp)，136.5(C₈Indole), 155.5(Cq triazole), 162.2 (C)₄p-methoxybenzyl), 171.1(CO amide).

(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide (compound 89):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)1.42(m，1H，H₃Pro)，1.52(m，1H，H₄Pro)，1.72(m， 1H，H₄Pro)，2.07(m，1H，H₃Pro)，2.94(m，4H，CH ₂-CH ₂-indole), 3.05(t, 2H, J ═ 6Hz, H)₅Pro)，3.30(m，2H，CH₂βTrp)，3.67(s，3H，OCH₃)，3.96(m，1H，CH αPro)，5.02(s，2H，CH₂-p-methoxybenzyl), 5.19(m, 1H, CH. alpha. Trp), 6.73(s, 4H, CHarp-methoxybenzyl), 6.84(t, 1H, J)_o＝8Hz，H₅Indole), 6.90(t, 1H, J)_o＝8Hz，H₅Trp)，6.93-7.06(m，4H，H₂And H₆Indole, H₂And H₆Trp)，7.17(d，1H，J_o＝8Hz，H₄Trp)，7.29(d，3H，J_o＝8Hz，H₄And H₇Indole, H₇Trp), 8.39 and 9.10(2m, 2H, NH Pro TFA salt), 9.25(d, 1H, J ═ 8Hz, NH amide), 10.76(s, 1H, NH indole), 1.5 (r, g, H, n, g, n0.80(d, 1H, J ═ 2Hz, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.8(CH₂-CH₂-indole), 23.5 (C)₄Pro)，25.8(CH₂-CH₂Indole), 29.4 (CH)₂βTrp)，29.8(C₃Pro)，45.2(CH αTrp)，45.5(CH₂-p-methoxybenzyl), 46.0 (C)₅Pro)，55.5(OCH₃)，59.3(CH αPro)，109.6(C₃Trp)，111.8(C₇Indole and C₇Trp)，113.4(C₃Indole), 114.6 (C)₃And C₅p-methoxybenzyl), 118.4 (C)₄Indole), 118.5 (C)₄Trp)，118.7(C₅Indole and C₅Trp)，121.4(C₆Indole and C₆Trp)，123.0(C₂Trp)，124.7(C₂Indole), 127.2 (C)₉Indole), 127.3 (C)₉Trp)，127.7(C₁p-methoxybenzyl), 127.8 (C)₂And C₆p-methoxybenzyl), 126.5 (C)₈Trp)，136.6(C₈Indole), 154.8(Cq triazole), 154.9(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 168.2(CO amide).

(R) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide (compound 90):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)1.23(m，1H，H₃Pro)，1.52(m，1H，H₄Pro)，1.74(m，1H，H₄Pro)，2.08(m，1H，H₃Pro)，2.81(m，2H，H₅Pro)，2.90-3，14(m，4H，CH ₂-CH ₂-indole), 3.31(dd, 1H, J ═ 14Hz and 7Hz, CH₂β Trp), 3.41(dd, 1H, J ═ 14Hz and 8Hz, CH₂βTrp)，3.63(s，3H，OCH₃)， 4.05(m，1H，CHαPro)，4.86(s，2H，CH₂-p-methoxybenzyl), 5.21(m, 1H, CH. alpha. Trp), 6.63(s, 4H, CHarp-methoxybenzyl), 6.88(t, 2H, J) _o＝7Hz，H₅Indole and H₅Trp)，7.02(m，4H，H₂And H₆Indole, H₂And H₆Trp)，7.26-7.34(m，4H，H₄And H₇Indole, H₄And H₇Trp), 8.51 and 9.18(2m, 2H, NH Pro, TFA salt), 9.27(d, 1H, J ═ 8Hz, NH amide), 10.73(s, 1H, NH indole), 10.80(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)22.8(CH₂-CH₂-indole), 23.8 (C)₄Pro)，25.9(CH₂-CH₂Indole), 29.7 (CH)₂Beta Trp and C₃Pro)，45.4(CH₂-p-methoxybenzyl), 45.8 (CH. alpha. Trp), 46.1 (C)₅Pro)，55.5(OCH₃)，59.2(CHαPro)，109.7(C₃ Trp)，111.8(C₇Trp)，111.9(C₇Indole), 113.4 (C)₃Indole), 114.4 (C)₃And C₅p-methoxybenzyl), 118.3 (C)₄Indole), 118.5 (C)₄Trp)，118.6(C₅Indole), 118.9 (C)₅Trp)，121.4(C₆Indole and C₆Trp)，122.9(C₂Indole and C₂Trp)，127.2(C₉Indole), 127.4 (C)₉Trp)，127.6(C₁，C₂And C₆p-methoxybenzyl), 136.5 (C)₈Trp)，136.6(C₈Indole), 154.4(Cq triazole), 155.0(Cq triazole), 159.1 (C)₄p-methoxybenzyl), 168.3(CO amide).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 92):

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.28(3H，s，CH₃Aib)，1.30(3H，s，CH₃Aib)，2.90(2H，m，CH ₂-CH₂indole), 3.00(2H, m, CH)₂-CH ₂Indole), 3.37(2H, m, CH)₂ βTrp)，5.10(2H，s，CH₂4-bromobenzyl), 5.13(1H, m, ca H Trp), 6.75(2H, d, J ═ 8.1, H₂，H₆4-bromobenzyl), 6.88(1H, t, J ═ 7.3, H₅Trp)，6.93(1H，t，J＝7.5，H₅Indole), 7.03(1H, t, J ═ 7.0, H)₆Trp)，7.05(1H，H₆Indole), 7.07(1H, d, J ═ 1.7, H)₂Indole), 7.09(1H, d, J ═ 1.8, H)₂ Trp)，7.12(1H，d，J＝8.2，H₄Trp)，7.28(1H，d，J＝7.9，H₄Indole), 7.32(2H, d, J ═ 8.2, H) ₇Trp，H₇Indole), 7.41(2H, d, J ═ 8.1, H)₃，H₅4-bromobenzyl), 8.01(2H, s, NH)₂Aib), 8.95(1H, d, J ═ 7.9, NHTrp), 10.77(1H, brs, NH indole), 10.80(1H, brs, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)22.4(CH₂-CH_□Indole), 23.1 (CH)₃Aib)，23.4(CH₃Aib)，25.4(CH₂-CH_□Indole), 28.7 (C.beta.Trp), 44.8 (C.beta.Trp) ((R)CH₂4-bromobenzyl), 45.2 (C.alpha.Trp), 56.3(Cq Aib), 109.4 (C)₃Trp)，111.3(C₇Trp，C₇Indole), 113.0 (C)₃Indole), 117.8 (C)₄Trp)，118.0(C₄Indole), 118.2 (C)₅Indole), 118.3 (C)₅Trp)，120.8(C₄4-bromobenzyl), 120.9 (C)₆Trp，C₆Indole), 122.5 (C)₂Indole), 124.4 (C)₂Trp)，126.7(C₉Indole), 126.8 (C)₉ Tr p)，128.0(C₂，C₆4-bromobenzyl), 131.6 (C)₃，C₅4-bromobenzyl), 135.1 (C)₁4-bromobenzyl), 136.1 (C)₈Trp，C₈Indole), 154.2(Cq triazole), 154.5(Cq tris)Oxazole), 171.4(CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide (compound 93):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.18(3H，s，CH₃Aib)，1.27(3H，s，CH₃Aib)，2.91(4H，m，CH ₂-CH ₂indole), 3.19(2H, m, CH)₂βPhe)，3.69(3H，s，OCH₃)，5.05(2H，m，CH ₂-p-methoxybenzyl), 5.20(1H, m, CH. alpha. Phe), 6.82(2H, d, J)_o＝8Hz，H₃And H₅p-methoxybenzyl), 6.88(2H, d, J)_o＝8Hz，H₂And H₆p-methoxybenzyl), 6.92(1H, t, J)_o＝8Hz，H₅Indole), 7.02(1H, t, J)_o＝7Hz，H₆Indole), 7.03(1H, d, J ═ 2Hz, H)₂Indole), 7.11-7.20(5H, m, CHar Phe), 7.29(2H, d, J)_o＝8Hz，H₄And H₇Indole), 7.99(3H, brs, NH) ₂Aib), 8.93(1H, d, J ═ 8Hz, NH amide), 10.77(1H, s, NH indole).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)22.8(CH₂-CH₂-indole), 23.5 (CH)₃Aib)，23.9(CH₃Aib)，25.9(CH₂-CH₂Indole), 38.7 (CH)₂βPhe)，45.7(CH₂-p-methoxybenzyl), 46.4 (CH. alpha. Phe), 55.6 (OCH)₃)，56.8(Cq Aib)，111.8(C₇Indole), 113.4 (C)₃Indole), 114.7 (C)₃And C₅p-methoxybenzyl), 118.5 (C)₄Trp)，118.6(C₅Trp)，121.4(C₆Trp)，123.0(C₂Trp)，127.0(C₄Phenyl), 127.2 (C)₉Indole), 127.9 (C)₁p-methoxybenzyl group),128.1(C₂and C₆Phenyl), 128.5 (C)₃And C₅Phenyl), 129.8 (C)₂And C₆p-methoxybenzyl), 136.6 (C)₈Indole), 137.7 (C)₁Phenyl), 155.2(Cq triazole), 154.4(Cq triazole), 159.3 (C)₄p-methoxybenzyl), 171.7(CO Aib).

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 95):

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.29(3H，s，CH₃Aib)，1.35(3H，s，CH₃Aib)，2.85(1H，m，1H N-CH₂-CH ₂-In)，2.89(1H，m，1H，-N-CH₂-CH ₂-In)，3.28(1H，dd，J＝14.2，J＝6.8，1H CH₂βTrp)，3.40(1H，dd，J＝14.2，J＝8.4，1H CH₂βTrp)，4.10(2H，m，-N-CH ₂-CH₂-In)，5.25(1H，m，CHαTrp)，6.85(1H，d，J＝2.0，H₂indole), 6.90-6.98(2H, m, H)₅Indole), 7.01(1H, d, J ═ 2.0, H)₂Indole), 7.02-7.12(2H, m, H)₆Indole), 7.30(1H, d, J ═ 8.2, H)₇Indole), 7.33(1H, d, J ═ 8.3, H)₇Indole), 7.40(1H, d, J ═ 7.9, H)₄Indole), 7.47(1H, d, J ═ 7.8, H)₄Indole), 8.04(2H, brs, NH)₂Aib), 8.42(1H, s, H triazole), 9.01(1H, d, J ═ 8.0, NH Trp), 10.81(1H, s, NH indole), 10.90(1H, s, NH indole).

(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 96):

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.20(3H，s，CH₃Aib)，1.28(3H，s，CH₃Aib)，3.32(3H，d，N-CH₃)，3.30-3.45(2H，m，CH₂βTrp)，4.22(2H，s，-CH₂-In)，5.30(1H，m，CHαTrp)，6.91(1H，t，J＝7.5，H₅Indole), 6.94(1H, d, J ═ 7.5, H)₅Indole), 7.02(1H, t, J ═ 7.9, H)₆Indole), 7.05(1H, t, J ═ 7.9, H)₆Indole), 7.08(1H, d, J ═ 1.9, H)₂Indole), 7.12(1H, d, J ═ 1.9, H)₂Indole), 7.29(1H, d, J ═ 8.1, H)₇Indole), 7.33(1H, d, J ═ 8.2, H)₇Indole), 7.48(1H, d, J ═ 7.9, H)₄Indole), 7.57(1H, d, J ═ 7.9H)₄Indole), 8.00(2H, brs, NH)₂Aib), 8.85(1H, d, J ═ 8.2, NH Trp), 10.82(1H, s, NH indole), 10.98(1H, s, NH indole).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 97):

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.30(3H，s，CH₃Aib)，1.40(3H，s，CH₃Aib)，3.00-3.20(4H，m，-CH ₂-CH ₂-In)，3.36(3H，s，N-CH₃)，3.45-3.50(2H，m，CH₂βTrp)，5.30(1H，m，CHαTrp)，6.95-7.04(2H，t，H₅indole), 7.06-7.13(2H, m, H)₆Indole), 7.18(2H, brs, H)₂Indole), 7.34(1H, d, J ═ 8.0, H)₇Indole), 7.36(1H, d, J ═ 8.0, H)₇Indole), 7.48(1H, d, J ═ 7.8, H)₄Indole), 7.58(1H, d, J ═ 7.8, H)₄Indole), 8.10(2H, brs, NH)₂Aib), 8.95(1H, d, J ═ 8.1, NH Trp), 10.95(1H, s, NH indole), 10.96(1H, s, NH indole).

¹³C NMR(100MHz，DMSO-d⁶)：

δ(ppm)22.9-25.9(-CH₂-CH₂Indole), 24.1 (CH)₃Aib)，24.3(CH₃ Aib)，28.8(CH₂βTrp)，30.7(-NCH₃)，46.2(CHαTrp)，57.2(CqAib)，110.2(C₃Indole), 112.3 (2C)₇Indole), 113.5 (C)₃Indole), 118.9-119.2 (2C)₅，2C₄Indole), 121.9 (2C) ₆Indole), 123.6 (C)₂Indole), 125.3 (C)₂Indole), 127.7 (C)₉Indole), 128.0 (C)₉Indole), 136.9 (C)₈Indole), 137.1 (C)₈Indole), 155.3(Cq triazole), 155.8(Cq triazole), 172.2 (COAib).

(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 98):

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.31(3H，s，CH₃Aib)，1.42(3H，s，CH₃Aib)，3.19(1H，dd，J＝14.5，J＝9.6，1H CH₂βTrp)，3.35(1H，dd，J＝14.5，J＝5.3，1H CH₂βTrp)，4.15(2H，s，CH₂indole), 5.26(1H, m, C.alpha.H Trp), 6.95(1H, t, H)₅Trp)，6.96(1H，t，H₅Indole), 7.05(1H, t, H)₆Trp)，7.06(1H，s，H₂Trp)，7.07(1H，t，H₆Indole), 7.21(1H, s, H)₂Indole), 7.32(1H, d, H)₇Trp)，7.37(1H，d，H₇Indole), 7.51(1H, d, J ═ 7.8, H)₄Indole), 7.58(1H, d, J ═ 7.8, H)₄Trp)，8.00(2H，s，NH₂Aib), 8.64(1H, d, J ═ 8.7, NH Trp), 10.77(1H, s, NH indole Trp), 10.92(1H, s, NH indole).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)22.9(CH₂Indole), 23.2 (CH)₃Aib)，23.3(CH₃Aib)，29.4(CβTrp)，48.3(CαTrp)，56.3(Cq Aib)，109.7(C₃Indole), 110.3 (C)₃Trp)，111.2(C₇Trp)，111.3(C₇Indole), 118.1 (C)₄Trp，C₅Trp)，118.3(C₄Indole), 118.4 (C)₅Indole), 120.7 (C)₆Trp)，121.0(C₆Indole), 123.4 (C)₂Indole), 123.6 (C)₂Trp)，126.8(C₉Indole), 127.1 (C)₉ Trp)，136.0(C₈Trp)，136.2(C₈Indole), 157.5(Cq triazole), 161.7(Cq triazole), 170.8(CO Aib).

(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 99):

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.29(3H，s，CH₃Aib)，3.25(1H，dd，J＝14.3，J＝5.6，1H CH₂βTrp)，3.38(1H，dd，J＝14.3，J＝9.1，1H CH₂βTrp)，3.68(3H，s，OCH₃)，3.72(3H，s，OCH₃)，4.10(1H，d，J＝16.5，1H CH₂indole), 4.16(1H, d, J ═ 16.5, 1 hch) ₂Indole), 4.96(1H, d, J ═ 16.8, 1 hch)₂o, p-dimethoxybenzyl), 5.12(1H, d, J ═ 16.8, 1 hch)₂o, p-dimethoxybenzyl), 5.16(1H, m, ca H Trp), 6.21(1H, dd, J ═ 8.5, J ═ 2.1, H₅o, p-dimethoxybenzyl), 6.27(1H, d, J ═ 8.5, H)₆o, p-dimethoxybenzyl), 6.57(1H, d, J ═ 2.1, H₃o, p-dimethoxybenzyl), 6.83(1H, t, H)₅Trp)，6.94(1H，t，H₅Indole), 7.02(1H, t, H)₆Trp)，7.05(1H，t，H₂Indole), 7.06(1H, t, H)₆Indole), 7.07(1H, s, H)₂Trp)，7.07(1H，t，H₄Trp)，7.31(1H，d，H₇Trp)，7.33(1H，d，H₇Indole), 7.36(1H, d, J ═ 7.8, H)₄Indole), 8.00(2H, brs, NH)₂Aib)，8.92(1H, d, J ═ 8.2, NH Trp), 10.79(1H, s, NH indole Trp), 10.89(1H, s, NH indole).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)21.2(CH₂Indole), 23.1 (CH)₃Aib)，23.2(CH₃Aib)，28.6(CβTrp)，41.4(N-CH₂o, p-dimethoxybenzyl), 45.1 (C.alpha.Trp), 55.2 (OCH)₃)，55.4(OCH₃)，56.2(Cq Aib)，98.5(C₃o, p-dimethoxybenzyl), 104.6 (C)₅o, p-dimethoxybenzyl), 107.9 (C)₃Indole), 109.5 (C)₃Trp)，111.2(C₇Trp)，111.3(C₇Indole), 115.1 (C)₁o, p-dimethoxybenzyl), 117.8 (C)₄Trp)，118.1(C₅Trp)，118.3(C₄Indole), 118.4 (C)₅Indole), 120.8 (C)₆Trp)，121.1(C₆Indole), 123.5 (C)₂Indole), 124.3 (C)₂ Trp)，126.6(C₉Indole), 126.8 (C)₉Trp)，127.2(C₆o, p-dimethoxybenzyl), 136.0 (C)₈Trp)，136.2(C₈Indole), 157.5(Cq triazole), 154.9(Cq triazole), 157.2 (C)₂o, p-dimethoxybenzyl), 160.3 (C)₄o, p-dimethoxybenzyl), 171.2(CO Aib).

(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 101):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.22(3H，s，CH₃Aib)，1.25(3H，s，CH₃aib), 3.22(1H, dd, J ═ 14Hz and 6Hz, CH)₂β Trp), 3.34(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，3.68(3H，s，OCH₃)，4.11(2H，m，CH ₂Indole), 5.09(3H, m, CH. alpha. Trp and CH ₂-p-methoxybenzyl), 6.70(4H, s, CHarp-methylOxybenzyl), 6.78(2H, m, H)₅Indole and H₅Trp)，6.93(2H，m，H₆Indole and H₆Trp)，7.01-7，06(3H，m，H₂Indole, H₂And H₄Trp)，7.31(3H，m，H₄And H₇Indole, H₇Trp)，7.98(3H，brs，NH₂Aib), 8.92(1H, d, J ═ 8Hz, NH amide), 10.77(1H, s, NH indole), 10.89(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)21.7(CH₂-indole), 23.5 (CH)₃Aib)，23.7(CH₃Aib)，28.9(CH₂βTrp)，45.6(CH αTrp)，45.8(CH₂-p-methoxybenzyl), 55.5 (OCH)₃)，56.7(Cq Aib)，108.1(C₃Indole), 109.7 (C)₃Trp)，111.7(C₇Trp)，111.9(C₇Indole), 114.5 (C)₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.7(C₄Indole), 118.8 (C)₅Indole), 118.9 (C)₅Trp)，121.3(C₆Indole), 121.6 (C)₆Trp)，124.2(C₂Indole), 125.3 (C)₂Trp)，127.1(C₉Indole), 127.2 (C)₉Trp)，127.6(C₁p-methoxybenzyl), 127.8 (C)₂And C₆p-methoxybenzyl), 136.4 (C)₈Trp)，136.7(C₈Indole), 154.2(Cq triazole), 155.2(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 171.9(CO Aib).

(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 102):

¹H NMR(400MHz，DMSO-d⁶)：

δ(ppm)1.30(3H，s，CH₃Aib)，1.33(3H，s，CH₃Aib)，3.26(1H，dd，J＝14.2，J＝5.9，1H CH₂βTrp)，3.38(1H，dd，J＝14.2，J＝8.7，1H CH₂βTrp)，3.69(3H，s，OCH₃)，3.72(3H，s，OCH₃)，4.02(2H，s，CH₂Benzyl), 4.87(1H, d, J ═ 16.7, 1 hch)₂o, p-dimethoxybenzyl), 5.08(1H, d, J ═ 16.7, 1 hch)₂o, p-dimethoxybenzyl), 5.17(1H, m, ca H Trp), 6.24(1H, dd, J ═ 8.4, J ═ 1.7, H₅o, p-dimethoxybenzyl), 6.28(1H, d, J ═ 8.4, H₆o, p-dimethoxybenzyl), 6.56(1H, d, J ═ 1.7, H₃o, p-dimethoxybenzyl), 6.85(1H, t, J ═ 7.5, H₅Trp)，7.02(1H，t，H₆Trp)，7.07(2H，m，H₂，H₆Benzyl), 7.08(1H, s, H)₂Trp)，7.09(1H，d，H₄ Trp)，7.16-7.29(3H，m，H₃，H₄，H₅Benzyl), 7.31(1H, d, J ═ 8.2, H)₇ Trp)，8.01(2H，s，NH₂Aib), 8.92(1H, d, J ═ 7.9, NH Trp), 11.79(1H, s, NH indole Trp).

¹³C NMR(400MHz，DMSO-d⁶)：

δ(ppm)23.2(2CH₃Aib)，28.7(CβTrp)，30.2(CH₂-benzyl), 41.3(CH₂-o, p-dimethoxybenzyl), 45.2 (CaTrp), 55.2 (OCH)₃)，55.4(OCH₃)，56.2(Cq Aib)，98.5(C₃o, p-dimethoxybenzyl), 104.7 (C)₅o, p-dimethoxybenzyl), 109.5 (C)₃Trp)，111.3(C₇Trp)，115.1(C₁o, p-dimethoxybenzyl), 117.8 (C)₄Trp)，118.2(C₅Trp)，120.8(C₆Trp)，124.3(C₂Trp)，126.5(C₂，C₆Benzyl), 126.8 (C)₉Trp)，127.3(C₆o, p-dimethoxybenzyl), 128.3 (C)₃，C₄，C₅Benzyl), 135.8 (C)₁Benzyl), 136.0 (C)₈Trp), 153.4(Cq triazole), 155.0(Cq triazole), 157.2 (C)₂o, p-dimethoxybenzyl), 160.3 (C)₄o, p-dimethoxybenzyl), 171.3(CO Aib).

(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 104):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.29(3H，s，CH₃Aib)，2.39-2.53(4H，m，CH ₂-CH ₂Phenyl), 3.74(1H, m, CH)₂βTrp)，3.92(1H，m，CH ₂ βTr p)，3.99(2H，s，CH₂Indole), 5.21(1H, m, CH. alpha. Trp), 6.74(2H, m, H)₅Indole and H₅Trp)，6.90(1H，t，J_o＝8Hz，H₆Trp)，6.92(1H，t，J_o＝8Hz，H₆Indole), 7.01-7.06(4H, m, H)₂And H₆Phenyl radical, H₂Indole and H₂Trp)，7.16(3H，m，H₃，H₄And H₅Phenyl), 7.27(1H, d, J)_o＝8Hz，H₄Trp)，7.32(1H，d，J_o＝8Hz，H₇Trp)，7.36(1H，d，J_o＝8Hz，H₇Indole), 7.50(1H, d, J)_o＝8Hz，H₄Indole), 7.99(3H, brs, NH)₂Aib), 9.02(1H, s, J ═ 8Hz, NH amide), 10.79(1H, s, NH indole Tr p), 10.94(1H, s, NH indole).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)21.4(CH₂-indole), 23.5 (CH)₃Aib)，23.8(CH₃Aib)，29.5 (CH₂βTrp)，35.8(CH₂-CH₂-phenyl), 44.5(CH₂-CH₂-phenyl), 45.8 (CH. alpha. Trp), 56.7(Cq Aib), 108.5 (C)₃Indole), 109.9 (C)₃Trp)，114.0(C₇Indole and C₇Trp)，118.4(C₄Trp)，118.8(C₄Indole and C₅Trp)，119.0(C₅Indole), 121.4 (C)₆Trp)，121.7(C₆Indole), 124.0 (C)₂Indole and C₂ Tr p)，127.1(C₄Phenyl), 127.7 (C)₉Indole and C₉Trp)，128.8(C₂And C₆Phenyl), 129.1 (C)₃And C₅Phenyl), 136.5 (C)₈Trp)，136.6(C₈Indole), 137.5 (C)₁Phenyl), 153.6(Cq triazole), 155.0(Cq triazole), 171.8(CO Aib).

(R) -N- (1- (5-benzyl-4- (2, 2-diphenylethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 106):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.29(3H，s，CH ₃Aib)，1.34(3H，s，CH₃Aib)，3.37(4H，m，CH₂beta Trp and CH₂-benzyl), 3.74(1H, t, J ═ 7Hz, CH)₂-CH(Phe)₂) 4.21(1H, dd, J ═ 14Hz and 8Hz, CH ₂-CH(Phe)₂) 4.51(1H, dd, J ═ 14Hz and 8Hz, CH ₂-CH(Phe)₂)，5.08(1H，m，CHαTrp)，6.72(2H，m，H₂And H₆Benzyl), 6.86-6.93(5H, m, H)₃，H₄And H₅Benzyl radical, H₅And H₆Trp)，7.03(1H，s，H₂Trp), 7.06-7.25(CHar phenyl from CH (Phe) ₂)，7.33(1H，d，J_o＝8Hz，H₄Trp)，7.47(1H，d，J_o＝8Hz，H₇Indole), 8.10(3H, brs, NH)₂Aib), 8.98(1H, d, J ═ 8Hz, NH amide), 10.94(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.7(CH₃Aib)，29.4(CH₂βTrp)，30.1(CH₂-benzyl), 46.0(CH α Trp), 47.7 (c) (i)CH₂-CH(Phe)₂)，51.3(CH(Phe)₂)，56.8(Cq Aib)，109.8(C₃Trp)，112.0(C₇Trp)，118.5(C₄Trp)，119.0(C₅Trp)，121.5(C₆Trp)，124.8(C₂Trp)，127.1(C₄Phenyl is from CH (Phe)₂)，127.4(C₉Trp，C₂And C₆Benzyl), 128.3 (C)₂And C₆Phenyl is from CH (Phe)₂)，128.8-129.1(C₃And C₅Phenyl is from CH (Phe)₂，C₃，C₄And C₅Benzyl), 136.2 (C)₁Benzyl), 136.5 (C)₈Trp)，141.0(C₁Phenyl is from CH (Phe)₂) 153.5(Cq triazole), 155.1(Cq triazole), 172.0(CO Aib).

(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 2-diphenylethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 107):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.34(3H，s，CH₃Aib)，1.38(3H，s，CH₃Aib)，2.06(1H，m，CH₂-CH ₂indole), 2.30(1H, m, CH)₂-CH ₂Indole), 2.78(2H, m, C)H ₂-CH₂-indole), 3.35(1H, dd, J ═ 14Hz and 7Hz, CH)₂β Trp), 3.46(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，3.58(1H，t，J＝7Hz，CH₂-CH(Phe)₂) 4.14(1H, dd, J ═ 14Hz and 8Hz, CH ₂-CH(Phe)₂) 4.39(1H, dd, J ═ 14Hz and 7Hz, CH ₂-CH(Phe)₂)，5.12(1H，m，CHαTrp)，6.50(2H，m，H₅Indole and H₅Trp)，6.76(2H，m，H₆Indole and H₆Trp)，6.87(2H，m，H₂Indole and H₂Trp)，6.89-6.96(2H，m，H₄Phenyl), 7.03-7, 15(8H, m, H)₂，H₃，H₅And H₆Phenyl), 7.33(3H, m, H)₄Indole, H₄And H₇Trp)，7.47(1H，d，J＝8Hz，H₇Indole), 8.11(3H, brs, NH)₂Aib), 9.04(1H, d, J ═ 8Hz, NH amide), 10.76(1H, s, NH indole), 10.96(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)22.4(CH₂-CH ₂-indole), 23.6 (CH)₃Aib)，23.8(CH₃Aib)，24.9(CH₂-CH₂Indole), 29.6( CH₂βTrp)，46.1(CHαTrp)，47.5(CH₂-CH(Phe)₂)，51.5(CH₂-CH(Phe)₂)，56.8(Cq Aib)，109.8(C₃Trp)，111.8(C₇Trp)，112.1(C₇Indole), 113.5 (C)₃Indole), 118.4 (C)₄Trp)，118.7(C₄And C₅Indole), 119.0 (C)₅Trp)，121.4(C₆Indole and C₆Trp)，122.8(C₂Indole), 125.0 (C)₂Trp)，127.2(C₉Indole and C₉Trp)，127.3(C₄Phenyl), 128.2 (C)₂And C₆Phenyl), 128.7 (C)₃And C₅Phenyl), 136.6 (C)₈Indole and C₈Trp)，141.0(C₁Phenyl), 154.6(2Cq triazole), 172.0 (COAib).

(R) -N- (1- (4, 5-dibenzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 109):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.23(3H，s，CH₃Aib)，1.26(3H，s，CH₃aib), 3.23(1H, dd, J ═ 14Hz and 6Hz, CH)₂β Trp), 3.35(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，3.99(2H，s，C-CH ₂Phenyl), 5.10(3H, m, N-CH ₂Phenyl and CH α Trp), 6.77(3H, m, H)₅Trp，H₂And H₆Phenyl from N-CH₂-benzeneBase), 6.99(2H, m, H)₂And H₆Trp)，7.01-7.07(3H，m，H₄Trp，H₂And H₆From C-CH₂-phenyl), 7.15-7.23(6H, m, H)₃，H₄And H₅Phenyl from N-CH₂-phenyl and is derived from C-CH₂-phenyl), 7.25(1H, d, J ═ 8Hz, H₇Trp)，8.01(3H，brs，NH₂Aib), 8, 91(1H, d, J ═ 8Hz, NH amide), 10.78(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.7(CH₃Aib)，29.0(CH₂βTrp)，30.6(C-CH₂Phenyl), 45.7 (CH. alpha. Trp), 46.1(N-CH₂Phenyl), 56.7(Cq Aib), 109.8 (C)₃Trp)，111.7(C₇Trp)，118.3(C₄Trp)，118.7(C₅Trp)，121.2(C₆Trp)，124.8(C₂Trp)，126.3(C₂And C₆Phenyl from N-CH₂-phenyl), 127.0 (C)₂And C₆Phenyl is from C-CH₂-phenyl), 127.2 (C)₉Trp)，128.0(C₄Phenyl from N-CH₂-phenyl), 128.8 (C)₃，C₄And C₅Phenyl is from C-CH₂-phenyl), 128.9 (C)₃And C₅Phenyl from N-CH₂-phenyl), 135.8 (C) ₁Phenyl from N-CH₂-phenyl), 136.2 (C)₁Phenyl is from C-CH₂-phenyl), 136.4 (C)₈Trp), 153.9(Cq triazole), 155.3(Cq triazole), 171.9(CO Aib).

(R) -N- (1- (5-benzyl-4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 110):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)0.71(3H，t，³J＝7Hz，(CH₂)₅-CH ₃)，0.87(4H，m，2CH₂)，0.95(2H，m，CH ₂-CH₃)，1.00(2H，m，N-CH₂-CH ₂)，1.36(6H，s，CH₃ Aib)，3.36(1H，dd，³j-14 Hz and 7Hz, CH₂βTrp)，3.41(1H，dd， ³J-14 Hz and 7Hz, CH₂βTrp)，3.50(1H，m，N-CH ₂)，3.65(1H，m，N-CH ₂)，4.11(2H，s，CH ₂Benzyl), 5.14(1H, m, CH. alpha. Trp), 6.90(1H, t, J)_o＝7Hz，H₅Trp)，7.01(1H，t，J_o＝7Hz，H₆Trp)，7.04(1H，s，H₂Trp)，7.09(2H，m，H₂And H₆Benzyl), 7.17-7.29(4H, m, H)₄Trp，H₃，H₄And H₅Benzyl), 7.47(1H, d, J)_o＝8Hz，H₇Trp)，8.10(3H，brs，NH₂Aib), 9.05(1H, d, J ═ 7Hz, NH amide), 10.84(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)14.1((CH ₂)₅-CH₃)，22.1(CH₂-CH₃)，23.8(CH₃Aib)，23.5(CH₃Aib)，25.8(CH₃-CH₂-CH₂-CH₂)，29.5(CH₂βTrp)，30.3(N-CH₂-CH₂)，30.8(CH₂-benzyl and CH₃-CH₂-CH₂)，43.3(N-CH₂-CH₂)，46.1(CHαTrp)，56.8(Cq Aib)，109.6(C₃Trp)，111.9(C₇Trp)，118.2(C₄Trp)，118.8(C₅Trp)，121.4(C₆Trp)，124.7(C₂Trp)，127.2(C₂And C₆Benzyl), 127.3 (C)₉Trp)，128.8(C₃，C₄And C₅Benzyl), 136.2 (C)₁Benzyl), 136.5 (C)₈Trp), 153.1(Cq triazole), 155.1(Cq triazole), 171.9(CO Aib).

(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 111):

¹H NMR(400MHz，DMSO-d⁶，300°K)：

δ(ppm)1.31(3H，s，CH₃Aib)，1.35(3H，s，CH₃Aib)，2.51(2H，m，CH₂-CH ₂indole), 3.37(2H, m, CH)₂βTrp)，3.76-3.90(4H，m，CH ₂-benzyl and CH ₂-CH₂Indole), 5.25(1H, m, CH. alpha. Trp), 6.88(2H, t, J)_o＝7hz，H₅Indole and H₅Trp)，6.95(2H，t，J_o＝7Hz，H₆Indole and H₆Trp)，7.03(4H，m，H₂Trp，H₂Indole, H₂And H₆Benzyl), 7.16(2H, d, J)_o＝8Hz，H₄Indole and H₄Trp)，7.20-7，30(4H，3，H₇Indole, H₃，H₄And H₅Benzyl), 7.47(1H, d, J)_o＝8Hz，H₇Trp)，8.05(3H，brs，NH₂Aib), 9.05(1H, d, J ═ 8Hz, NH amide), 10.83(1H, s, NH indole), 10.88(1H, s, NH indole Trp).

¹³C NMR(100MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.7(CH₃Aib)，29.6(CH₂βTrp)，30.3(CH₂-benzyl and CH₂-CH₂Indole), 44.1(CH₂-CH₂Indole), 46.1 (CH. alpha. Trp), 56.8(Cq Aib), 109.8 (C)₃Trp)，109.9(C₃Indole), 111.9 (C)₇Indole and C₇Trp)，118.3(C₄Trp)，118.4(C₄Indole), 118.9 (C)₅Indole and C₅Trp)，121.3(C₆Trp)，121.5(C₆Indole), 123.7 (C)₂Indole), 124.7 (C)₂Trp)，127.0(C₉Indole), 127.2 (C)₂And C₆Benzyl), 127.4 (C)₉Trp)，128.8(C₃And C₅Benzyl), 129.0 (C)₄Benzyl), 136.3 (C)₁Benzyl), 136.4 (C)₈Indole and C₈Trp), 153.1(Cq triazole), 155.3(Cq triazole), 171.8(CO Aib).

(S) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 112):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.26(3H，s，CH₃Aib)，1.29(3H，s，CH₃aib), 3.24(1H, dd, J ═ 14Hz and 6Hz, CH)₂β Trp), 3.33(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，3.64(3H，s，OCH₃)，3.68(3H，s，OCH₃)，3.99(2H，s，CH₂Phenyl), 4.84(1H, d, J ═ 17Hz, CH)₂-o, p-dimethoxybenzyl), 5.05(1H, d, J ═ 17Hz, CH₂-o, p-dimethoxybenzyl), 5.13(1H, m, CH. alpha. Trp), 6.24(2H, m, H)₅And H₆o, p-dimethoxybenzyl), 6.52(1H, d, J)_m＝2Hz，H₃o, p-dimethoxybenzyl), 6.83(1H, t, J)_o＝7Hz，H₅Trp)，7.01(1H，t，J_o＝8Hz，H₆Trp)，7.04(1H，s，H₂Trp), 7.05-7.23(6H, m, H4Trp and CHar phenyl), 7.27(1H, d, J)_o＝8Hz，H₇Trp)，8.O1(3H，brs，NH₂Aib), 8.90(1H, d, J ═ 8Hz, NH amide), 10.77(1H, d, J ═ 2Hz, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，29.1(CH₂βTrp)，30.6(CH₂-phenyl), 41.9 (CH)₂-o, p-dimethoxybenzyl), 45.7 (CH. alpha. Trp), 55.7 (OCH) ₃)，55.9(OCH₃)，56.7(Cq Aib)，99.9(C₃o, p-dimethoxyBenzyl), 105.1 (C)₅o, p-dimethoxybenzyl), 109.9 (C)₃Trp)，111.7(C₇Trp)，115.5(C₁o, p-dimethoxybenzyl), 118.3 (C)₄Trp)，118.6(C₅Trp)，121.3(C₆Trp)，124.2 (C₂Trp)，127.0(C₆o, p-dimethoxybenzyl), 127.3 (C)₉Trp)，127.8(C₄Phenyl), 128.8 (C)₂，C₃，C₅And C₆Phenyl), 136.2 (C)₈Trp)，136.4(C₁Phenyl), 153.9(Cq triazole), 155.5(Cq triazole), 157.6 (C)₂o, p-dimethoxybenzyl), 160.8 (C)₄o, p-dimethoxybenzyl), 171.8(CO amide).

(R) -N- (1- (4- (3, 5-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 113):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.24(3H，s，CH₃Aib)，1.27(3H，s，CH₃Aib)，2.83(4H，s，CH ₂-CH ₂phenyl), 3.32(2H, m, CH)₂βTrp)，3.61(6H，s，OCH₃)，5.02(2H，m，CH₂-m-dimethoxybenzyl), 5.18(1H, m, CH. alpha. Trp), 6.07(2H, d, J)_m＝2Hz，H₂And H₆m-dimethoxybenzyl), 6.42(1H, brs, H)₄m-dimethoxybenzyl), 6.83(1H, t, J)_o＝7Hz，H₅Trp)，6.99(1H，t，J_o＝8Hz，H₆Trp)，7.08(1H，d，J＝2Hz，H₂Trp)，7.13(3H，t，J_o＝8Hz，H₃，H₄And H₅Phenyl), 7.20(3H, d, J)_o＝7Hz，H₂And H₆Phenyl radical, H₄Trp)，7.28(1H，d，J_o＝8Hz，H₇Trp)，7.99(3H，brs，NH₂Aib), 8.92(1H, d, J ═ 8Hz, NH amide), 10.77(1H, s, NH indole).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，26.5(CH₂-CH₂-phenyl), 29.2 (CH)₂βTrp)，32.7(CH₂-CH₂Phenyl), 45.6 (CH. alpha. Trp), 45.8 (CH)₂-m-dimethoxybenzyl), 55.6 (OCH)₃)，56.8(Cq Aib)，99.6(C₄m-dimethoxybenzyl), 104.6 (C)₂And C₆m-dimethoxybenzyl), 109.9 (C)₃Trp)，111.8(C₇Trp)，118.2(C₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.8(C₂Trp)，126.5(C₄Phenyl), 127.3 (C)₉Trp)，128.7(C₂，C₃，C₅And C₆Phenyl), 136.4 (C)₈Trp)，138.6(C₄m-dimethoxybenzyl), 140.9 (C)₁Phenyl), 154.6(Cq triazole), 154.8(Cq triazole), 161.4 (C) ₃And C₅m-dimethoxybenzyl), 171.8(CO amide).

(R) -N- (1- (4- (4-bromobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 114):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.23(3H，s，CH₃Aib)，1.25(3H，s，CH³Aib)，3.26(1H，dd，³j-14 Hz and 6Hz, CH₂Trp)，3.34(1H，dd，³J-14 Hz and 9Hz, CH₂βTrp)，4.01(2H，m，CH₂Benzyl), 5.01(1H, m, CH. alpha. Trp), 5.08(2H, s, CH)₂-p-bromobenzyl), 6.59(2H, d, J)_o＝8Hz，H₂And H₆p-bromobenzyl), 6.81(1H, t, J)_o＝7Hz，H₅Trp)，6.94(1H，s，H₂Trp)，6.98(1H，t，J_o＝7Hz，H₆Trp)，7.06(2H，m，H₂And H₆Benzyl), 7.12(1H, d, J)_o＝7Hz，H₄Trp)，7.16-7.20(3H，m，H₃，H₄And H₅Benzyl), 7.26(1H, d, J)_o＝8Hz，H₇Trp)，7.29(2H，d，J_o＝8Hz，H₃And H₅Benzyl), 8.00(3H, brs, NH)₂Aib), 8.92(1H, d, J ═ 8Hz, NH amide), 10.78(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23，5(CH₃Aib)，23，8(CH₃Aib)，29，0(CH₂βTrp)，30，5(CH₂-benzyl), 45, 6 (c)CH ₂-p-bromobenzyl), 45, 7 (CH. alpha. Trp), 56, 7(Cq Aib), 109, 7 (C)₃Trp)，111，8(C₇Trp)，118，2(C₄Tryptophan), 118, 7 (C)₅Trp)，121，2(C₄p-bromobenzyl), 121, 3 (C)₆Trp)，124，9(C₂Tryptophan), 127, 0 (C)₂And C₆Benzyl), 127, 2 (C)₉Trp)，128，4(C₂And C₆p-bromobenzyl), 128, 9 (C)₃，C₄And C₅Benzyl), 131, 9 (C)₃And C₅p-bromobenzyl), 135, 2 (C)₁p-bromobenzyl), 136, 2 (C)₈Trp)，136，4(C₁Benzyl), 153, 9(Cq triazole), 155, 3(Cq triazole), 171, 9(CO Aib).

(R) -N- (1- (4- (2-methoxybenzyl) -5-benzyl-4H 1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 115):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.24(3H，s，CH₃Aib)，1.27(3H，s，CH₃aib), 3.20(1H, dd, J ═ 14Hz and 5Hz, CH) ₂β Trp), 3.33(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，3.68(3H，s，OCH₃)，4.00(2H，s，CH₂-phenyl), 4.95(1H, d, J ═ 17Hz, CH)₂-o-methoxybenzyl), 5.07(1H, m, CH. alpha. Trp), 5.18(1H,d，J＝17Hz，CH₂-o-methoxybenzyl), 6.27(1H, d, J)_o＝8Hz，H₃o-methoxybenzyl), 6.67(1H, t, J)_o＝7Hz，H₅Trp)，6.77(1H，t，J_o＝6Hz，H₆Trp)，6.92-7.05(6H，m，H₂Trp，H₂And H₆Phenyl radical, H₄，H₅And H₆o-methoxybenzyl), 7.14-7.26(5H, m, H)₄And H₇Trp，H₃，H₄And H₅Phenyl), 8.03(3H, brs, NH)₂Aib), 8.91(1H, d, J ═ 8Hz, NH amide), 10.78(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.6(CH₃Aib)，29.1(CH₂βTrp)，30.5(CH₂-phenyl), 42.1 (CH)₂-o-methoxybenzyl), 45.7 (CH. alpha. Trp), 55.9 (OCH)₃)，56.7(Cq Aib)，109.8(C₃Trp)，111.3(C₃o-methoxybenzyl), 111.7 (C)₇Trp)，118.2(C₄Trp)，118.7(C₅Trp)，120.9(C₅o-methoxybenzyl), 121.2 (C)₆Trp)，123.3(C₁o-methoxybenzyl), 124.8 (C)₂ Trp)，126.6(C₂And C₆Phenyl), 127.1 (C)₄o-methoxybenzyl), 127.2 (C)₉ Trp)，128.8(C₃，C₄And C₅Phenyl), 129.5 (C)₆o-methoxybenzyl), 136.0 (C)₁Phenyl), 136.4 (C)₈Trp), 154.0(Cq triazole), 155.6(Cq triazole), 156.5 (C)₂o-methoxybenzyl), 171.8(CO Aib).

(S) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 116):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.28(3H，s，CH₃Aib)，1.32(3H，s，CH₃Aib)，2.81(4H，m，CH ₂-CH ₂phenyl), 3.30(2H, t, CH)₂βTrp)，3.61(3H，s，OCH₃)，3.69(3H，s，OCH₃)，4.87(1H，d，J＝17Hz，CH₂-o, p-dimethoxybenzyl), 5.03(1H, d, J ═ 17Hz, CH₂-o, p-dimethoxybenzyl), 5.20(1H, m, CH. alpha. Trp), 6.29(1H, dd, J) _o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.43(1H, d, J)_o＝8Hz，H₆o, p-dimethoxybenzyl), 6.55(1H, d, J)_m＝2Hz，H₃o, p-dimethoxybenzyl), 6.83(1H, t, J)_o＝8Hz，H₅Trp)，6.99(1H，t，J_o＝ 8Hz，H₆Trp)，7.06(1H，d，J＝2Hz，H₂Trp)，7.09-7.25(6H，m，H₄Trp and CHar phenyl), 7.28(1H, d, J)_o＝8Hz，H₇Trp)，8.04(3H，brs，NH₂Aib), 8.92(1H, d, J ═ 8Hz, NH amide), 10.79(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.7(CH₃Aib)，26.5(CH₂-CH₂-phenyl), 29.1 (CH)₂βTrp)，32.7(CH₂-CH₂-phenyl), 41.8 (CH)₂-o, p-dimethoxybenzyl), 45.7 (CH. alpha. Trp), 55.7 (OCH)₃)，55.9(OCH₃)，56.8(Cq Aib)，99.1(C₃o, p-dimethoxybenzyl), 105.2 (C)₅o, p-dimethoxybenzyl), 109.9 (C)₃Trp)，111.8(C₇Trp)，115.6(C₁o, p-dimethoxybenzyl), 118.3 (C)₄ Tr p)，118.7(C₅Trp)，121.3(C₆Trp)，124.4(C₂Trp)，126.6(C₄Phenyl), 127.3 (C)₉Trp)，128.2(C₆o, p-dimethoxybenzyl), 128.7 (C)₂，C₃，C₅And C₆Phenyl), 136.4 (C)₈Trp)，140.9(C₁Phenyl group),154.6(Cq triazole), 155.0(Cq triazole), 157.8 (C)₂o, p-dimethoxybenzyl), 160.9 (C)₄o, p-dimethoxybenzyl), 171.8(CO Aib).

(R) -N- (1- (4, 5-diphenylethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 117):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.32(3H，s，CH₃Aib)，1.37(3H，s，CH₃Aib)，2.59(4H，m，C-CH ₂-CH ₂-phenyl), 2.83(2H, t, J ═ 8Hz, N — CH)₂-CH ₂Phenyl), 3.38(2H, m, N-CH ₂-CH₂Phenyl), 3.84(1H, m, CH)₂βTrp)，3.94(1H，m，CH₂ βTrp)，5.23(1H，m，CHαTrp)，6.84(2H，m，H₄Phenyl is from C-CH₂-CH₂-phenyl and H₄Phenyl from N-CH₂-CH₂Phenyl), 6.93(1H, t, J)_o＝8Hz，H₅Trp)，7.00(1H，t，J_o＝8Hz，H₆Trp)，7.07(1H，d，J＝2Hz，H₂Trp)，7.11-7.27(9H，m，H₂，H₃，H₅And H₆Phenyl is from C-CH₂-CH₂-phenyl, H₂，H₃，H₅And H₆Phenyl from N-CH ₂-CH₂-phenyl and H₄Trp)，7.50(1H，d，J_o＝8Hz，H₇Trp)，8.07(3H，brs，NH₂Aib), 9.04(1H, d, J ═ 8Hz, NH amide), 10.85(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，25.9(C-CH₂-CH₂-phenyl), 29.5 (CH)₂βTrp)，32.4(C-CH₂-CH₂-phenyl), 35.8 (N-CH)₂-CH₂Phenyl), 44.2(N-CH₂-CH₂-phenyl), 45.9 (CH. alpha. Trp), 56.8(Cq Aib), 109.7 (C)₃Trp)，111.9(C₇Trp)，118.4(C₄Trp)，118.9(C₅Trp)，121.4(C₆Trp)，124.8(C₂Trp)，126.6(C₄Phenyl is from C-CH₂-CH₂-phenyl), 127.2 (C)₄Phenyl from N-CH₂-CH₂-phenyl), 127.4 (C)₉Trp)，128.7(C₂And C₆Phenyl is from C-CH₂-CH₂-phenyl radical, C₂And C₆Phenyl from N-CH₂-CH₂-phenyl), 128.8 (C)₃And C₅Phenyl is from C-CH₂-CH₂-phenyl radical, C₃And C₅Phenyl from N-CH₂-CH₂-phenyl), 136.5 (C)₁Phenyl from N-CH₂-CH₂-phenyl), 137.5 (C)₁Phenyl is from C-CH₂-CH₂-phenyl), 140.8 (C)₈Trp), 154.1(Cq triazole), 154.7(Cq triazole), 171.9(CO Aib).

(R) -N- (1- (4- (3, 4-dichlorobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 118):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.24(3H，s，CH₃Aib)，1.25(3H，s，CH₃Aib)，3.33(2H，m，CH₂βTrp)，4.04(2H，s，CH ₂benzyl), 5.05(1H, m, CH. alpha. Trp), 5.12(2H, s, CH)₂-m, p-dichlorobenzyl), 6.49(1H, dd, J)_o8Hz and J_m＝2Hz，H₆m, p-dichlorobenzyl), 6.80(1H, t, J)_o＝8Hz，H₅Trp)，6.87(1H，d，J_m＝2Hz，H₂Trp)，6.98(1H，t，J_o＝7Hz，H₆Trp)，7.02-7.10(3H，m，H₂And H₆Benzyl radical, H₅m, p-dichlorobenzyl), 7.18(3H, m, H)₃，H₄And H₅Benzyl), 7.26(2H, m, H)₄And H₇Trp)，8.04(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 9Hz, NH amide), 10.81(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.4(CH₃Aib)，23.8(CH₃Aib)，29.0(CH₂βTrp)，30.4(CH₂-benzyl), 45.1 (CH) ₂-m, p-dichlorobenzyl), 45.6 (CH. alpha. Trp), 56.7(CqAib), 109.6 (C)₃Trp)，111.8(C₇Trp)，118.1(C₄Trp)，118.6(C₅ Trp)，121.3(C₆Trp)，124.9(C₂Trp)，126.4(C₆m, p-dichlorobenzyl), 127.0 (C)₂m, p-dichlorobenzyl), 127.2 (C)₉Trp)，128.4(C₂And C₆Benzyl), 130.7 (C)₄And C₅m, p-dichlorobenzyl), 131.8 (C)₃m, p-dichlorobenzyl), 136.0 (C)₁Benzyl), 136.4 (C)₈Trp)，136.7(C₁m, p-dichlorobenzyl), 154.1(Cq triazole), 155.2(Cq triazole), 172.0(CO Aib).

(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide (compound 120):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.18(3H，s，CH₃Aib)，1.26(3H，s，CH₃aib), 3.09(1H, dd, J ═ 14Hz and 6Hz, CH)₂β Phe), 3.18(1H, dd, J ═ 14Hz and 9Hz, CH)₂βPhe)，3.99(2H，d，J＝4Hz，CH₂-phenyl), 4.95(1H, d, J ═ 16Hz, CH)₂-p-methoxybenzyl), 5.06(1H, d, J ═ 16Hz, CH)₂-p-methoxybenzyl), 5.13(1H, m, CH. alpha. Phe), 6.78(4H, s, CHarp-methoxybenzyl), 7.02-7.08(4H, m, H)₂And H₆Phenyl radical, H₂And H₆Phe)，7.12-7.25(6H，m，H₃，H₄And H₅Phenyl radical, H₃，H₄And H₅Phe)，7.99(3H，brs，NH₂Aib), 8.92(1H, d, J ═ 8Hz, NH amide).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.4(CH₃Aib)，23.8(CH₃Aib)，30.7(CH₂-phenyl), 38.7 (CH)₂βPhe)，45.9(CH₂-p-methoxybenzyl), 46.4 (CH. alpha. Phe), 55.6 (OCH)₃)，56.7(Cq Aib)，114.6(C₃And C₅p-methoxybenzyl), 126.9 and 127.1 (C)₄Phenyl and C₄Phe)，127.7(C₁p-methoxybenzyl), 128.2 (C)₂And C₆Phe)，128.5(C₃And C₅Phe)，128.9(C₂，C₃，C₅And C₆Phenyl), 129.7 (C)₂And C₆p-methoxybenzyl), 136.3 (C) ₁Phenyl), 137.6 (C)₁Phe), 154.0(Cq triazole), 154.9(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 171.7(CO amide).

(R) -N- (1- (4- (4-fluorobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 121):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.28(3H，s，CH₃Aib)，2.82(4H，m，CH ₂-CH ₂phenyl), 3.34(2H, m, CH)₂βTrp)，5.06(2H，s，CH₂-p-fluorobenzyl), 5.16(1H, m, CH. alpha. Trp), 6.85(3H, m, H)₅Trp，H₃And H₅p-fluorobenzyl), 6.98-7.04(4H, m, H)₂And H₆Tr p，H₂And H₆Phenyl), 7.09-7.11(2H, m, H)₂And H₆p-fluorobenzyl), 7.15(1H, d, J)_o＝6Hz，H₄Trp)，7.19(3H，t，J_o＝8Hz，H₃，H₄And H₅Phenyl), 7.29(1H, d, J)_o＝8Hz，H₇Trp)，8.01(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 8Hz, NH amide), 10.78(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，26.5(CH₂-CH₂-phenyl), 29.2 (CH)₂βTrp)，32.7(CH₂-CH₂-phenyl), 45.4 (CH)₂-p-fluorobenzyl), 45.7 (CH. alpha. Trp), 56.8(Cq Aib), 109.8 (C)₃Trp)，111.8(C₇Trp), 115.9 and 116.2 (C)₃And C₅p-fluorobenzyl), 118.3 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.8(C₂Trp)，126.5(C₄Phenyl), 127.3 (C)₉Trp)，128.5(C₂And C₆p-fluorobenzyl), 128.7 (C)₂，C₃，C₅And C₆Phenyl), 132.2 (C)₁p-fluorobenzyl), 136.4 (C)₈Trp)，140.9(C₁Phenyl), 154.5(Cq triazole), 154.7(Cq triazole), 160.3 (C)₄p-fluorobenzyl), 171.9(CO amide).

NMR¹⁹F(282MHz，DMSO-d⁶，300°K)：

Delta (ppm) -114.9(1F, m, p-fluorobenzyl).

(R) -N- (1- (4- (3, 4-dichlorobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 122):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.25(3H，s，CH₃Aib)，1.26(3H，s，CH₃Aib)，2.84(4H，m，CH ₂-CH ₂-phenyl), 3.34(2H, d, J ═ 7Hz, CH)₂β Trp), 5.11(3H, m, CH α Trp and CH₂-m, p-dichlorobenzyl), 6.63(1H, dd, J)_o8Hz and J_m＝2Hz，H₆m, p-dichlorobenzyl), 6.83(1H, t, J)_o＝8Hz，H₅Trp)，6.99(1H，t，J_o＝8Hz，H₆Trp)，7.05(1H，d，J＝2Hz，H₂Trp), 7.12(5H, m, CHar phenyl), 7.17(1H, d, J)_o＝8Hz，H₄Trp)，7.21(1H，s，H₂m, p-dichlorobenzyl), 7.27(1H, d, J)_o＝8Hz，H₅m, p-dichlorobenzyl), 7.39(1H, d, J)_o＝8Hz，H₇Trp)，8.02(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 8Hz, NH amide), 10.78(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，26.4(CH₂-CH₂-phenyl), 29.1 (CH)₂βTrp)，32.6(CH₂-CH₂-phenyl), 44.7 (CH)₂-m, p-dichlorobenzyl), 45.6 (CH. alpha. Trp), 56.7(Cq Aib), 109.7 (C)₃Trp)，111.8(C₇Trp)，118.1(C₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.9(C₂Trp)，126.5(C₄Phenyl and C₆m, p-dichlorobenzyl), 127.2 (C)₉Trp)，128.7(C₂，C₃，C₅And C₆Phenyl radical, C₂m, p-dichlorobenzyl), 130.9 (C)₄m, p-dichlorobenzyl), 131.4 (C)₅m, p-dichlorobenzyl), 132.0 (C)₃m, p-dichlorobenzyl), 136.4 (C)₈Trp)，137.2(C₁m, p-dichlorobenzyl), 140.8 (C)₁Phenyl), 154.5(Cq triazole), 154.7(Cq triazole), 171.9(CO amide).

(R) -N- (1- (4- (4-methylbenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 124):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.22(3H，s，CH₃Aib)，1.27(3H，s，CH₃Aib)，2.22(3H，s，CH₃p-methylbenzyl), 3.22(1H, dd, J ═ 14Hz and 6Hz, CH)₂β Trp), 3.33(1H, dd, J ═ 14Hz and 9Hz, CH)₂βTrp)，3.99(2H，s，CH₂-benzyl), 5.04(2H, s, CH)₂-p-methylbenzyl), 5.09(1H, m, CH. alpha. Trp), 6.64(2H, d, J) _o＝8Hz，H₃And H₅p-methylbenzyl), 6.78(1H, t, J)_o＝7Hz，H₅ Trp)，6.98(4H，t，J_o＝7Hz，H₆Trp，H₃，H₄And H₅Benzyl), 7.01(1H, d, J ═ 2Hz, H)₂Trp)，7.07(2H，d，J_o＝7Hz，H₂And H₆p-methylbenzyl), 7.20(3H, m, H)₄Trp，H₂And H₆Benzyl), 7.26(1H, d, J)_o＝8Hz，H₇Trp)，7.98(3H，brs，NH₂Aib), 8.89(1H, d, J ═ 8Hz, NH amide), 10.74(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)21.0(CH₃p-methylbenzyl), 23.5 (CH)₃Aib)，23.7(CH₃Aib)， 29.1(CH₂βTrp)，30.6(CH₂-benzyl), 45.7(CH α Trp), 46.0(CH α Trp), 4.0 (CH —)₂-p-methylbenzyl), 56.7(Cq Aib), 109.8 (C)₃Trp)，111.7(C₇Trp)，118.3(C₄Trp)，118.6(C₅Trp)，121.2(C₆Trp)，124.8(C₂Trp)，126.3(C₃And C₅p-methylbenzyl), 127.0 (C)₄Benzyl), 127.2 (C)₉Trp)，128.9(C₂，C₃，C₅And C₆Benzyl), 129.7 (C)₂And C₆p-methylbenzyl), 132.9 (C)₁p-methylbenzyl), 136.3 (C)₄p-methylbenzyl), 136.4 (C)₈Trp)，137.4(C₁Benzyl), 153.9(Cq triazole), 155.3(Cq triazole), 171.8(CO amide).

(S) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 125):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.31(3H，s，CH₃Aib)，1.74(2H，m，(CH₂-CH ₂-CH₂-phenyl), 2.52(4H, t, J ═ 7Hz, CH ₂-CH₂-CH ₂-phenyl), 3.35(2H, d, J ═ 7Hz, CH)₂βTrp)，3.68(3H，s，OCH₃)，4.98(2H，s，CH₂-p-methoxybenzyl), 5.20(1H, m, CH. alpha. Trp), 6.75(4H, s, CHarp-methoxybenzyl), 6.83(1H, t, J)_o＝8Hz，H₅Trp)，6.99(1H，t，J_o＝7Hz，H₆Trp)，7.06(3H，m，H₂And H₆Phenyl radical, H₂Trp)，7.14(1H，d，J_o＝7Hz，H₄Trp)，7.19(3H，t，J_o＝8Hz，H₃，H₄And H₅Phenyl), 7.29(1H, d, J)_o＝8Hz，H₇Trp)，8.01(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 8Hz, NH amide), 10.79(1H, d, J ═ 2Hz, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.8(CH₃Aib)，24.1(CH₂-CH₂-CH₂-phenyl), 28.5( CH₂-CH₂-CH₂-phenyl), 29.2 (CH)₂βTrp)，34.7(CH₂-CH₂-CH₂-phenyl), 45.5 (CH)₂-p-methoxybenzyl), 45.8 (CH. alpha. Trp), 55.5 (OCH)₃)，56.8(Cq Aib)，109.8(C₃Trp)，111.8(C₇Trp)，114.6(C₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆ Trp)，124.9(C₂Trp)，126.2(C₄Phenyl), 127.3 (C)₉Trp)，127.8(C₁p-methoxybenzyl), 127.9 (C)₃，C₄And C₅Phenyl), 128.7 (C)₂And C₆p-methoxybenzyl), 136.4 (C)₈Trp)，141.7(C₁Phenyl), 154.7(Cq triazole), 154.8(Cq triazole), 159.2 (C)₁p-methoxybenzyl), 171.9(CO amide).

(S) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 126):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.25(3H，s，CH₃Aib)，1.28(3H，s，CH₃aib), 3.26(1H, dd, J ═ 14Hz and 6Hz, CH)₂β Trp), 3.34(1H, dd, J ═ 14Hz and 8Hz, CH)₂βTrp)，3.99(2H，s，CH₂Phenyl), 4.98(2H, s, CH)₂-p-methoxybenzyl), 5.13(1H, m, CH. alpha. Trp), 6.68(4H, s, CHarp-methoxybenzyl), 6.80(1H, t, J)_o＝8Hz，H₅Trp)，6.99(1H，t，J_o＝8Hz，H₆Trp)，7.02-7.06(4H，m，H₂And H₄Trp，H₂And H₆Phenyl), 7.20(3H, m, H)₃，H₄And H₅Phenyl), 7.27(1H, d, J)_o＝8Hz，H₇Trp)，8.00(3H，s，NH₂Aib), 8.91(1H, d, J ═ 8Hz, NH amide), 10.76(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.7(CH₃Aib)，29.1(CH₂βTrp)，30.6(CH₂-phenyl), 45.7 (CH. alpha. Trp andCH₂-p-methoxybenzyl), 55.5 (OCH)₃)，56.7(Cq Aib)，109.8(C₃Trp)，111.7(C₇Trp)，114.5(C₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.8(C₂Trp)，127.1(C₄Phenyl), 127.3 (C)₉Trp)，127.6(C₁p-methoxybenzyl), 127.8 (C)₂And C₆p-methoxybenzyl), 128.8 (C)₂And C₆Phenyl), 128.9 (C) ₃And C₅Phenyl), 136.3 (C)₈Trp)，136.4(C₁Phenyl), 153.8(Cq triazole), 155.2(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 171.9(CO amide).

N- ((R-1- (4- (4-nitrobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 128):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.28(3H，s，CH₃Aib)，1.29(3H，s，CH₃Aib)，2.77-2.94 (4H，m，CH ₂-CH ₂phenyl), 3.28(1H, dd,³j-14 Hz and 8Hz, CH₂βTrp)，3.43(1H，dd，³J-14 Hz and 7Hz, CH₂βTrp)，5.05(1H，m，CHαTrp)，5.25(2H，d，J＝7Hz，CH ₂-p-nitrobenzyl), 6.72(1H, t, J)_o＝7Hz，H₅Trp)，6.89(2H，d，J_o＝9Hz，H₂And H₆p-nitrobenzyl), 6.92(1H, t, J)_o＝7Hz，H₆Trp)，7.00(1H，d，J_m＝2Hz，H₂Trp)，7.08-7.15(4H，m，H₄And H₇Trp，H₂And H₆Phenyl), 7.17(2H, J)_o＝7hz，H₃And H₅Phenyl), 7.24(1H, t, J)_o＝8Hz，H₄Phenyl), 7.92(2H, d, J)_o＝9Hz，H₃And H₅p-nitrobenzyl), 8.06(3H, brs, NH)₂Aib), 8.98(1H, d, J ═ 8Hz, NH amide), 10.79(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，26.4(CH₂-CH₂-phenyl), 29.1 (CH)₂βTrp)，32.6(CH₂-CH₂-phenyl), 45.3(CH₂-p-nitrobenzyl), 45.7 (CH. alpha. Trp), 56.8(Cq Aib), 109.6 (C)₃Trp)，111.8(C₇Trp)，118.1(C₄Trp)，118.5(C₅Trp)，121.2(C₆Trp)，124.1(C₂And C₅p-nitrobenzyl), 124.8 (C)₂Trp)，126.5(C₂And C₅Phenyl), 127.2 (C)₉Trp，C₁And C₆p-nitrobenzyl), 128.7 (C)₃，C₄And C₅Phenyl), 136.4 (C)₈Trp)，140.8(C₁Phenyl), 143.5 (C)₁p-nitrobenzyl), 154.5(Cq triazole), 154.8(Cq triazole), 172.0(CO Aib).

(S-N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 129):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.27(3H，s，CH₃Aib)，1.30(3H，s，CH₃Aib)，2.81(4H，m，CH ₂-CH ₂-phenyl), 3.34(2H, d, J ═ 7Hz, CH)₂βTrp)，3.68(3H，s，OCH₃)，4.99(2H，s，CH ₂-p-methoxybenzyl), 5.20(1H, m, CH. alpha. Trp), 6.75(4H, m, CHarp-methoxybenzyl), 6.83(1H, t, J)_o＝7Hz，H₅Trp)，7.03(1H，t，J_o＝8Hz，H₆Trp)，7.04(1H，d，J＝2Hz，H₂Trp)，7.10(2H，d，J_o＝7Hz，H₂And H₆Phenyl), 7.13(1H, d, J)_o＝8Hz，H₄ Tr p)，7.19(3H，t，J_o＝7Hz，H₃，H₄And H₅Phenyl), 7.29(1H, d, J)_o＝ 8Hz，H₇Trp)，8.01(3H，brs，NH₂Aib), 8.94(1H, d, J ═ 8Hz, NH amide), 10.78(1H, d, J ═ 2Hz, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.8(CH₃Aib)，26.6(CH₂-CH ₂-phenyl), 29.2 (CH)₂βTrp)，32.7(CH₂-CH₂-phenyl), 45.3(CH₂-p-methoxybenzyl), 45.7 (CH. alpha. Trp), 55.5 (OCH)₃)，56.8(Cq Aib)，109.9(C₃Trp)，111.8(C₇Trp)，114.6(C₃And C₅p-methoxybenzyl), 118.3 (C)₄Trp)，118.7(C₅ Trp)，121.3(C₆Trp)，124.8(C₂Trp)，126.5(C₄Phenyl), 127.3 (C)₉Trp and C₁p-methoxybenzyl), 127.9 (C)₂And C₆p-methoxybenzyl), 128.7 (C)₂，C₃，C₅And C₆p-methoxybenzyl), 136.5 (C)₈Trp)，140.9(C₁Phenyl), 154.4(Cq triazole), 154.7(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 171.9(CO amide).

(R-N- (1- (4- (4-methoxyphenethyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 130):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.30(3H，s，CH₃Aib)，1.35(3H，s，CH₃Aib)，2.55(4H，m，CH ₂-CH₂-phenyl and CH₂-CH ₂-p-methoxybenzyl), 2.83(2H, t, J ═ 8Hz, CH₂-CH ₂Phenyl), 3.37(2H, m, C)H ₂-CH₂-p-methoxybenzyl), 3.65(3H, s, OCH)₃)，3.77(1H，m，CH₂βTrp)，3.89(1H，m，CH₂βTrp)，5.20(1H，m，CH α Trp), 6.72(4H, s, chrap-methoxybenzyl), 6.94(1H, t, J)_o＝7Hz，H₅Trp)，7.02(1H，t，J_o＝8Hz，H₆Trp)，7.05(1H，d，J＝2Hz，H₂Trp)，7.11(2H，d，J_o＝7Hz，H₂And H₆Phenyl), 7.16(1H, d, J)_o＝7Hz，H₄Trp)，7.25(3Hm，H₃，H₄，H₅Phenyl), 7.50(1H, d, J) _o＝8Hz，H₇Trp)，8.05(3H，brs，NH₂Aib), 9.02(1H, d, J ═ 8Hz, NH amide), 10.83(1H, d, J ═ 2Hz, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.5(CH₃Aib)，23.8(CH₃Aib)，26.0(CH₂-CH₂-phenyl), 29.5 (CH)₂βTrp)，32.5(CH₂-CH₂-phenyl), 35.0 (CH)₂-CH₂-p-methoxybenzyl), 44.4(CH₂-CH₂-p-methoxybenzyl), 45.8 (CH. alpha. Trp), 55.4 (OCH)₃)，56.8(Cq Aib)，109.9(C₃Trp)，111.9(C₇Trp)，114.2(C₃And C₅p-methoxybenzyl), 118.4 (C)₄Trp)，118.9(C₅Trp)，121.4(C₆Trp)，124.7(C₂Trp)，126.5(C₄Phenyl), 127.4 (C)₉Trp)，128.7(C₂，C₃，C₅And C₆Phenyl), 129.4 (C)₁p-methoxybenzyl), 130.3 (C)₂And C₆p-methoxybenzyl), 136.5 (C)₈Trp)，141.0(C₁Phenyl), 154.0(Cq triazole), 154.5(Cq triazole), 158.6 (C)₄p-methoxybenzyl), 171.8(CO amide).

(R-N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide (Compound 132):

¹H NMR(300MHz，DMSO-d⁶，300°K)：

δ(ppm)1.26(3H，s，CH₃Aib)，1.29(3H，s，CH₃Aib)，2.95(4H，m，CH ₂-CH ₂phenyl), 3.40(2H, m, CH)₂βTrp)，5.26(1H，m，CH αTrp)，5.37(2H，s，CH₂-o-pyridyl), 6.83(1H, t, J)_o＝7Hz，H₅Trp)，6.98(1H，t，J_o＝8Hz，H₆Trp)，7.11-7.30(10H，m，H₂，H₄And H₇Trp, CHar phenyl, H₃And H₅o-pyridyl), 7.71(1H, t, J)_o＝7Hz，H₄o-pyridyl), 8.22(3H, brs, NH)₂Aib)，8.42(1H，d，J_αβ＝4Hz，H₆o-pyridyl), 9.05(1H, d, J ═ 8Hz, NH amide), 10.87(1H, s, NH indole Trp).

¹³C NMR(75MHz，DMSO-d⁶，300°K)：

δ(ppm)23.4(CH₃Aib)，23.7(CH₃Aib)，26.4(CH₂-CH₂-phenyl), 28.6 (CH)₂βTrp)，32.5(CH₂-CH₂Phenyl), 45.7 (CH. alpha. Trp), 47.6 (CH)₂o-pyridyl), 56.8(Cq Aib), 109.8 (C)₃Trp)，111.8(C₇Trp)，118.3(C₄Trp)，118.6(C₅Trp)，121.2(C₆Trp)，122.0(C₃o-pyridyl), 123.6 (C)₅o-pyridyl), 126.3 (C)₂Trp)，126.6(C₄Phenyl), 127.3 (C)₉ Trp)，128.7(C₂，C₃，C₅And C₆Phenyl), 136.4 (C)₈Tryptophan), 137.7 (C) ₄o-pyridyl), 140.7 (C)₁Phenyl), 150.1 (C)₆o-pyridyl), 154.9(Cq triazole), 155.2(Cq triazole), 158.7 (C)₂o-pyridyl), 172.0(CO amide).

N ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 179):

¹H NMR(300MHz，DMSO d ⁶，300°K)：

δ(ppm)1.26(s，3H，CH₃Aib)，1.30(s，3H，CH₃Aib)，2.82(m，4H，CH ₂-CH ₂-phenyl), 3.29(t, 2H, J ═ 8Hz, CH₂βTrp)，3.61(s，3H，OCH₃)，3.68(s，3H，OCH₃)，4.85(d，1H，J＝17Hz，CH₂-o, p-dimethoxybenzyl), 5.02(d, 1H, J ═ 17Hz, CH₂-o, p-dimethoxybenzyl), 5.18(m, 1H, CH. alpha. Trp), 6.29(dd, 1H, J)_o8Hz and J_m＝2Hz，H₅o, p-dimethoxybenzyl), 6.40(d, 1H, J)_o＝8Hz，H₆o, p-dimethoxybenzyl), 6.55(d, 1H, J)_m＝2Hz，H₃o, p-dimethoxybenzyl), 6.82(t, 1H, J)_o＝8Hz，H₅Trp)，6.99(t，1H，J_o＝8Hz，H₆Trp)，7.05(s，1H，H₂Trp)，7.09-7.24(m，6H，H₄Trp and CHar phenyl), 7.27(d, 1H, J)_o＝8Hz，H₇Trp)，7.99(s，3H，large，NH₂Aib TFA salt), 8.89(d, 1H, J ═ 8Hz, NH amide), 10.77(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)23.6(CH₃Aib)，23.7(CH₃Aib)，26.5(CH₂-CH₂-phenyl), 29.2 (CH)₂βTrp)，32.7(CH₂-CH₂-phenyl), 41.6 (CH)₂-o, p-dimethoxybenzyl), 45.7 (CH. alpha. Trp), 55.7 (OCH)₃)，55.9(OCH₃)，56.7(Cq Aib)，99.1(C₃o, p-dimethoxybenzyl), 105.2 (C)₅o, p-dimethoxybenzyl), 110.0 (C)₃Tr p)，111.8(C₇Tr p)，115.7(C₁o, p-dimethoxybenzyl), 118.3 (C)₄ Trp)，118.7(C₅Trp)，121.3(C₆Trp)，126.5(C₂Trp and C₆o, p-dimethoxyBenzylyl), 127.3 (C)₉Trp)，128.1(C₄Phenyl), 128.7 (C)₂，C₃，C₅And C₆Phenyl), 136.4 (C)₈Trp)，140.9(C₁Phenyl), 154.5(Cq triazole), 155.0(Cq triazole), 157.8 (C) ₂o, p-dimethoxybenzyl), 160.9 (C)₄o, p-dimethoxybenzyl), 171.7(CO amide).

N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -tetrahydro-2H-pyran-4-carboxamide (compound 184):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)1.20(m，1H，H₅tetrahydropyran), 1.30(m, 3H, H)₃And H₅Tetrahydropyran), 2.17(m, 1H, H)₄Tetrahydropyran), 2.82(m, 4H, C)H ₂-CH ₂Phenyl), 3.16(m, 2H, H)₂And H₆Tetrahydropyran), 3.31(dd, 1H, J ═ 14Hz and 8Hz, CH)₂β Trp), 3.35(dd, 1H, J ═ 14Hz and 7Hz, CH₂βTrp)，3.66(s，3H，OCH₃)，3.72(m，2H，H₂And H₆Tetrahydropyran), 5.08(m, 2H, CH)₂-p-methoxybenzyl), 5.26(m, 1H, CH. alpha. Trp), 6.73(s, 4H, CHarp-methoxybenzyl), 6.87(t, 1H, J)_o＝8Hz，H₅Trp)，7.02(m，2H，H₂And H₆Trp)，7.07(d，2H，J_o＝7Hz，H₂And H₆Phenyl), 7.18(m, 3H, H)₃，H₄And H₅Phenyl), 7.30(m, 2H, H)₄And H₇Trp), 8.52(d, 1H, J ═ 8Hz, NH amide), 10.77(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)26.3(CH₂-CH₂-phenyl), 28.8 (C)₃And C₅Tetrahydropyran), 29.2 (CH)₂ βTrp)，32.2(CH₂-CH₂-phenyl), 40.7 (C)₄Tetrahydropyran), 44.8 (CH. alpha. Trp), 45.9 (CH)₂-p-methoxybenzyl), 55.5 (OCH)₃)，66.6(C₂And C₆Tetrahydropyran), 109.8 (C)₃Trp)，111.7(C₇Trp)，114.5(C₃And C₅p-methoxybenzyl), 118.4 (C)₄Trp)，118.7(C₅Trp)，121.3(C₆Trp)，124.5(C₂Trp)，126.7(C₄Phenyl), 127.2 (C)₉Trp)，127.5(C₁p-methoxybenzyl), 128.8 (C)₂And C₆Phenyl), 128.7 (C)₃And C₅Phenyl), 127.9 (C) ₂And C₆p-methoxybenzyl), 136.4 (C)₈Trp)，140.4(C₁Phenyl), 154.7(Cq triazole), 155.7(Cq triazole), 159.2 (C)₄p-methoxybenzyl), 174.2(CO amide).

N- ((R) -1- (5- ((1H-indol-3-yl) methyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide (compound 185):

¹H NMR(300MHz，DMSO d⁶，300°K)：

δ(ppm)1.19(s，3H，CH₃Aib)，1.23(s，3H，CH₃aib), 3.14(dd, 1H, J ═ 14Hz and 5Hz, CH₂β Trp), 3.34(dd, 1H, J ═ 14Hz and 9Hz, CH₂βTrp)，3.46(s，3H，OCH₃)，3.72(m，2H，CH ₂Indole), 5.06(m, 1H, CH. alpha. Trp), 5.14(m, 2H, CH)₂-m-methoxybenzyl), 6.31(s, 1H, H)₂m-methoxybenzyl), 6.32(d, 1H, J)_o＝7Hz，H₆m-methoxybenzyl), 6.77(m, 3H, H)₅Indole, H₅Trp and H₄m-methoxybenzyl), 6.92(m, 2H, H)₆Indole and H₆Trp)，7.02(m，2H，H₂Indole and H₂Trp)，7.26-7.30(m，3H，H₅m-methoxybenzyl, H₄And H₇Indole, H₄Trp)，7.41(d，1H，J_o＝8Hz，H₇Trp)，7.94(brs，3H，NH₂Aib TFA salt), 8.87(d, 1H, J ═ 8Hz, NH amide), 10.73(d, 1H, J ═ 2Hz, NH indole), 10.85(s, 1H, NH indole Trp).

¹³C NMR(75MHz，DMSO d⁶，300°K)：

δ(ppm)21.7(CH₂-indole), 23.5 (CH)₃Aib)，23.7(CH₃Aib)，28.9(CH₂βTrp)，45.5(CH αTrp)，46.2(CH₂-m-methoxybenzyl), 55.2 (OCH)₃)，56.7(Cq Aib)，108.2(C₃Indole), 109.8 (C)₃Trp)，111.7(C₇Trp)，111.9(C₇Indole and C₂m-methoxybenzyl), 113.7 (C)₄m-methoxybenzyl), 118.2 (C)₆m-methoxybenzyl), 118.4 (C)₄Trp)，118.6(C₄Indole), 118.9 (C)₅Indole and C₅Trp)，121.2(C₆Indole), 121.6 (C)₆Trp)，127.1(C₉Indole), 127.2 (C)₉Trp)，136.4(C₈Trp)，136.7(C₈Indole), 137.5 (C) ₁m-methoxybenzyl), 154.2(Cq triazole), 155.3(Cq triazole), 160.0 (C)₃m-methoxybenzyl), 171.8(CO amide).

Table 1: further exemplary embodiments with synthesis and MS data (Compounds No.2, 3, 14, 16, 17, 19-22, 24, 26-35, 36-122, 124-:

No.	chemical name (Chem Draw Ultra 8)	ESI-MS (calculation)	ESI-MS [ actually measured (M + H) +]
				2	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	559.3	560.4
3	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	573.3	574.3
				14	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-bromobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	637.2	638.1
16	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	553.3	554.4
				17	(R) -N- (1- (4, 5-bis (2- (1H-indol-3-yl) ethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	598.3	599.2
19	(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	536.3	537.1
				20	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	536.3	537.3
21	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3, 5-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	605.3	606.4
				22	(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	550.3	551.3

24	(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	612.3	612.8
				26	(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	536.3	537.1
27	(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide	556.3	557.2
				28	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3, 4-dichlorobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	613.2	614.2
29	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-fluorobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	563.3	564.1
				30	(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	510.3	511.0
31	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide	631.3	632.0
				32	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine	631.3	631.8

	Pyridine-3-carboxamides
				33	(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indolidin-3-yl) ethyl) -2-amino-2-methylpropanamide	534.3	535.4
34	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	559.7	559.9
				36	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide	631.3	631.8
37	(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	520.3	521.0
				38	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide	639.3	639.8
39	(R) -N- (1- (5-benzyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	493.3	493.9
				40	(2S, 4R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-hydroxypyrrolidine-2-carboxamide	564.3	565.0
41	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide	562.3	563.0

42	(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide	562.3	562.9
				43	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	534.3	535.0
44	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide	562.3	563.0
				45	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide	601.3	602.0
46	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide	548.3	548.9
				47	(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide	548.3	548.9
48	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide	562.3	563.0
				49	(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide	562.3	562.9
50	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide	508.3	508.9
				51	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl)	570.3	571.2

	Yl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide
				52	N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide	570.3	570.9
53	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole)-3-yl) ethyl) cyclohexanecarboxamide	561.3	562.4
				54	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide	571.3	572.5
55	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide	571.3	572.4
				56	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3-aminopropionamide	522.3	523.3
57	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopropionamide	522.3	523.3
				58	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide	570.3	571.2
59	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3- (pyridin-3-yl) propanamide	584.3	585.3
				60	(R)-N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide	579.3	580.2
61	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide	639.3	640.5
				62	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-	592.3	593.3

	phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
				63	(R) -N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide	592.3	593.3
64	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide	586.3	587.2
				65	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide	586.3	587.2
66	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide	587.3	588.2
				67	(R) -N-1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) piperazine-2-carboxamide	593.3	594.2
68	(S) -N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1,2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide	578.3	579.4
				69	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide	577.3	578.0
70	(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide	617.3	618.0
				71	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide	626.3	627.2
72	(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide	632.3	633.2
				73	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) acetate	625.3	626.3

	4- (2, 4-Dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyri-dinamide
				74	(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethylamine	520.3	520.8
75	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide	538.3	539.3
				76	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenylethyl)-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide	557.3	558.0
77	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide	556.3	556.9
				78	(R) -N-1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide	563.3	564.0
79	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide	556.3	557.3
				80	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide	595.3	596.2
81	(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide	602.3	603.3
				82	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide	568.3	569.3
83	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide	560.3	561.3
				84	(R) -N-1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperazine-2-carboxamide	561.3	562.2
85	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenylethyl)	555.3	556.2

	-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide
				86	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-cis-aminocyclohexanecarboxamide	645.3	646.2
87	(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide	601.3	601.9
				88	(R) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide	601.3	602.2
89	(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl)Pyrrolidine-2-carboxamides	587.3	588.2
				90	(R) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide	587.3	588.0
91	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide	609.3	610.0
				92	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	623.2	624.1
93	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide	536.3	536.9
				94	(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl)Yl-4- (thien-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-carboxamide	538.3	538.8
95	(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indole	455.2	456.2

	-3-yl) ethyl) -2-amino-2-methylpropanamide
				96	(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	455.2	456.4
97	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropionamide	469.3	470.2
				98	(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	441.3	442.1
99	(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	591.3	592.1
				100	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-methyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) -2-amino-2-methylpropanamide	476.3	477.4
101	(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	561.3	562.3
				102	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazole-3-yl) -2- (1H-indole-3-yl) ethyl) -2-amino-2-methylpropanamide	552.3	553.2
103	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	619.3	620.2
				104	(R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	545.3	546.4
105	(R) -N- (1- (5-benzyl-4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	506.3	507.4
				106	(R) -N- (1- (5-benzyl-4- (2, 2-diphenylethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indole)	582.3	583.3

	-3-yl) ethyl) -2-amino-2-methylpropanamide
				107	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 2-diphenylethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	635.3	636.4
108	(R) -N- (1- (4- (3, 5-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) -2-amino-2-methylpropanamide	552.3	553.3
				109	(R) -N- (1- (4, 5-dibenzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	492.3	493.3
110	(R) -N- (1- (5-benzyl-4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropionamide	486.3	487.4
				111	(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	545.3	546.2
112	(S) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) -2-amino-2-methylpropanamide	552.3	553.1
				113	(R) -N- (1- (4- (3, 5-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	566.3	567.3
114	(R) -N- (1- (4- (4-bromobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	570.2	571.0
				115	(R) -N- (1- (4- (2-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl ester2-amino-2-methylpropanamide	522.3	523.0
116	(S) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	566.3	567.0
				117	(R) -N- (1- (4, 5-diphenylethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	520.3	521.1
118	(R) -N- (1- (4- (3, 4-dichlorobenzyl) -5-benzyl)	560.2	561.3

	-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
				119	(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethylamine	451.3	452.1
120	(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2-phenylethyl) -2-amino-2-methylpropanamide	483.3	484.0
				121	(R) -N- (1- (4- (4-fluorobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	524.3	524.9
122	(R) -N- (1- (4- (3, 4-dichlorobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	574.2	574.9
				124	(R) -N- (1- (4- (4-methylbenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	506.3	507.3
125	(S) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	550.3	551.3
				126	(S) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	522.3	523.4
128	(R) -N- (1- (4- (4-nitrobenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	551.3	551.9
				129	(S) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	536.3	537.0
130	(R) -N- (1- (4- (4-methoxyphenethyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indolin-3-yl) ethyl) -2-amino-2-methylpropanamide	550.3	551.0
				131	(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (thiophen-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide	512.2	512.8
132	(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide	507.3	508.4

133	(R) -N- (-2- (1H-indol-3-yl) -1- (5-phenethyl-4- (pyridin-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-3-carboxamide	533.3	534.0
				134	(S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) pyrrolidine-2-methylAmides of carboxylic acids	546.3	547.3
135	N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide	506.3	507.3
				136	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide	609.3	610.4
137	(2R) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) piperidine-2-amide	560.3	561.3
				138	N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide	554.3	555.3
139	N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopyridine-3-amide	569.3	570.3
				140	(2S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indolidin-3-yl) ethyl) -2-aminopropionamide	520.3	521.2
141	N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide	554.3	555.4
				142	N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-amide	518.3	519.3
143	(2S) -N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) pyrrolidine-2-amide	504.3	505.1
				144	N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-aminoacetamide	464.3	465.1
145	N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethane	526.3	527.2

	2- (pyridin-2-yl) acetamides
				146	N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide	512.3	513.4
147	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide	579.3	580.1
				148	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide	593.3	594.2
149	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide	531.3	532.2
				150	(2S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide	571.3	572.4
152	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide	547.3	548.0
				153	N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-trans-aminocyclohexanecarboxamide	576.3	577.2
154	N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide	568.3	569.3
				155	(3S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indolidin-3-yl) ethyl) piperidine-3-carboxamide	560.3	561.5
156	N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide	568.3	569.1
				157	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazole-3-)	551.3	552.2

	2- (1H-indol-3-yl) ethyl) picolinamide
				158	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide	557.3	558.1
159	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide	572.3	573.4
				160	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide	586.3	587.3
161	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) pyrazine-2-carboxamide	573.3	574.2
				162	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-aminoacetamide	524.3	525.3
163	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-carboxamide	578.3	579.4
				164	N- ((R) -1- (5-benzyl-4- ((pyridin-2-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide	513.3	514.3
165	N- ((R) -1- (5-benzyl-4- ((pyridin-2-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-acetamide	465.3	466.4
				166	N- ((R) -1- (5-benzyl-4- ((pyridin-2-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide	519.3	520.2
167	N- ((R) -1- (5-benzyl-4- ((pyridin-4-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	493.3	494.3
				168	N- ((R) -1- (5- (4-methoxybenzyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	536.3	537.3
169	N- ((R) -1- (5-benzyl-4- ((pyridin-4-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide	513.3	514.2
				170	N- ((R) -1- (5-benzyl-4- ((pyridine-4-yl) methyl)	465.3	466.1

	Radical) -4H-1, 24-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) 2-amino-acetamide
				171	(R) -benzyl-3- (2-aminoisobutyrylamino) -3- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -propionate	594.3	595.2
172	N- ((R) -1- (5-benzyl-4- ((pyridin-3-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	493.3	494.3
				173	N- ((R) -1- (4-benzyl-5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	506.3	507.3
174	N- ((R) -2- (1H-indol-3-yl) -1- (4-methyl-5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide	450.3	451.3
				175	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl)-2-amino-2-methylpropionamide	531.3	532.4
176	N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) benzamide	555.3	556.2
				177	(R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-phenylmethanesulfonyl amine	635.3	637.0
178	(R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-toluenesulfonylethylamine	635.3	636.3
				179	N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	566.3	567.2
180	N-1- ((R) -1- (4- (2, 4-Dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) Ethane-1, 2-diamine	524.3	525.2
				181	N- ((R) -1- (4- ((furan-2-yl) methyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) -2-amino-2-methylpropanamide	496.3	497.1

182	N- ((R) -1- (4- ((furan-2-yl) methyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) picolinamide	516.3	517.1
				183	N- ((R) -1- (4- ((furan-2-yl) methyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indole-3-yl) ethyl) piperidine-4-carboxamide	522.3	523.2
184	N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl)yl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -tetrahydro-2H-pyran-4-carboxamide	563.3	564.2
				185	N- ((R) -1- (5- ((1H-indol-3-yl) methyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide	561.3	562.2
186	(2S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-3-phenylpropionamide	598.3	599.1
				187	(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-toluenesulfonylethylamine	674.3	675.0
188	N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-azidobenzamide	626.3	627.3
				189	N-benzyl- (R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethylamine	571.3	572.3
190	(2S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2, 5-dihydro-1H-pyrrole-2-carboxamide	585.3	586.2

II) GHS-R1 a receptor-ligand binding assay (Membrane preparations from transfected LLC PK-1 cells)

GHS-R1 a receptor binding/affinity studies were performed according to Guerlavais et al.

The isolated plasma membranes were derived from LLC PK-1 cells, a renal epithelial cell line (ECACC No.86121112) (10. mu.g protein) originally derived from porcine kidney, transiently transfected with human GHS-R1 a cDNA (Guerlavais et al, J.Med.chem.2003, 46: 1191-₂2, 5mM EDTA and 30. mu.g/mL bacitracin (Sigma)]Neutral 60pM¹²⁵I-His⁹Ghrelin (Amersham) incubation for 60 min.

With increasing concentrations of test compound (10)^-11M to 10^-2M) displacement of the radiolabeled ghrelin, the binding affinity of each test compound to human GHS-R1 a was measured (three replicates per experiment).

Use of excess (10)^-6M) restricted non-specific binding. KnotThe synthesis reaction was terminated by the addition of 4mL of ice cold HB, followed by rapid filtration through a Whatman GP/C filter, pre-impregnated with 0.5% polyethyleneimine to prevent excessive binding of the radioligand to the filter. The filter was washed with 3mL of ice-cold wash buffer [50mM Tris (pH7.3), 10mM MgCl ₂2.5mM EDTA and 0.015% (w/v) X-100Triton) were washed three times and the radioactivity bound to the membrane was measured in a Gamma-counter (Kontron Analytical Gamma Matic, Automatic Gamma counting system).

The concentration of test compound (IC) required to inhibit radiolabelled ghrelin binding by 50% was determined by fitting a competition binding curve using non-linear regression (PRISM 3.0, Graph Pad San Diego, USA)₅₀)。

The results obtained with selected compounds of the invention are listed in table 2 below, in comparison with the examples of the prior art. Given IC₅₀Values are the average of at least two independent experiments performed in triplicate.

Shown in FIGS. 1-13 for¹²⁵I-His⁹Ghrelin and GHS-R1 a receptor-ligand binding assay competition patterns determined for selected compounds 9, 31, 39, 45, 50, 62, 64, 71, 73, 74, 79, 81 and 90.

Table 2: GHS-R1 a receptor-ligand binding assay results (IC of some selected exemplary Compounds)₅₀Value)

No.	GHS-R 1a IC₅₀[nM]	Chemical name
			1	160	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
2	81	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			3	14	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
4	220	(R) -N- (1- (5-benzyl-4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			5	125	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
6	18	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			7	120	(R) -N- (1- (4- (3-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
8	18	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			9	46	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
10	32	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (3-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			11	137	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
12	6	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazole-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide

13	138	(R) -N- (1- (4- (4-methoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			14	150	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-bromobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
15	120	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			16	240	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4-hexyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
17	156	(R) -N- (1- (4, 5-bis (2- (1H-indol-3-yl) ethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			18	83	(S) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
19	78	(R) -N- (1- (4- (3-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			20	14	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
21	203	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3, 5-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			22	12	(R) -N- (1- (4- (4-methoxybenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
23	37	(R) -N- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			24	29	(R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
25	96	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2-methoxy) benzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl-

		Yl) ethyl) -2-amino-2-methylpropanamide
			26	56	(R) -N- (1- (4- (2-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
27	126	(R) -N- (2- (1H-indol-3-yl) -1- (4- (naphthalen-1-ylmethyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2-amino-2-methylpropanamide
			28	79	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (3, 4-dichlorobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
29	66	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-fluorobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			30	171	(R) -N- (1- (4- (4-fluorobenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
31	0，5	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dime thoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
			32	10，3	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-diMethoxybenzyl) -4H1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide
33	30	(R) -N- (1- (4- (4-methylbenzyl) -5- (3-phenylpropyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			34	28	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methylbenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
36	53	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dime thoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide
			37	136	(R) -N- (1- (4- (4-methylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
38	112	(R) -N- (1- (5- (2- (11-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminobenzamide

40	249	(2S, 4R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-hydroxypyrrolidine-2-carboxamide
			41	16	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide
42	7	(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide
			43	44	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
44	0，6	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
			45	0，3	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
46	12	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide
			47	27	(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide
48	11	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide
			49	23	(R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide
50	56	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide
			51	3	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide
53	18	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) cyclic

		Hexane formamide
			54	35	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
55	11	(R) -N-1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide
			56	59	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3-aminopropionamide
57	140	(S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminopropionamide
			58	29	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-3-yl) acetamide
59	173	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -3- (pyridin-3-yl) propanamide
			60	61	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide
61	34	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide
			62	0，9	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
63	210	(R) -N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide
			64	1，1	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyri-dinamide
65	58	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide

66	8	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide
			67	35	(R) -N-1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -piperazine-2-carboxamide
68	44	(S) -N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide
			69	38	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dime thoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide
70	6	(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide
			71	19	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dime thoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide
72	32	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dime thoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -piperazine-2-carboxamide
			73	1，8	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dime thoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
75	140	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide
			76	14	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide
77	119	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) isonicotinamide
			78	54	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -piperazine-2-carboxamide
79	0，7	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyri-dine

		Pyridinamides
			80	1，9	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
81	18	(R) -N- (1- (5- ((1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -piperazine-2-carboxamide
			82	51	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide
83	19	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
			84	247	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -piperazine-2-carboxamide
85	89	(R) -N- (1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrazine-2-carboxamide
			86	143	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dime thoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-cis-aminocyclohexanecarboxamide
87	10	(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide
			88	29	(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-2-carboxamide
89	9	(S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide
			90	28	(R) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-carboxamide
91	11	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide

92	200	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-bromobenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			94	255	(R) -N- (2- (1H-indol-3-yl) -1- (5-phenethyl-4)- (thien-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-carboxamide
108	250	(R) -N- (1- (4- (3, 5-dimethoxybenzyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			136	106	(R) -N- (1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-4-yl) acetamide
138	44	N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
			146	105	N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide
147	49	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
			148	96	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl)) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide
152	138	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide
			155	188	(3S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide
157	160	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
			158	70	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide
159	33	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) picolinamide

160	121	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) -2- (pyridin-2-yl) acetamide
			163	63	N- ((R) -2- (1H-indol-3-yl) -1- (4- (2, 4-dimethoxyphenyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) ethyl) piperidine-4-carboxamide
164	207	N- ((R) -1- (5-benzyl-4- ((pyridin-2-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide
			173	114	N- ((R) -1- (4-benzyl-5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
175	140	N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4-phenyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			176	80	N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) benzamide
179	62	N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			180	189	N-1- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) ethane-1, 2-diamine
182	81	N- ((R) -1- (4- ((furan-2-yl) methyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyridine amide
			184	5，9	N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -tetrahydro-2H-pyran-4-carboxamide
186	175	(2S) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-3-phenylpropanamide
			187	66	(R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (2, 4-dimethoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-toluenesulfonylethylamine
188	87	N- ((R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl

		Yl) -4-azidobenzamide
			190	12	(2S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2, 5-dihydro-1H-pyrrole-2-carboxamide
WO 00/54729A 2 example 39	ca.5000	(R) -N- (1- (5- (tert-butylsulfanyl) -4- (furan-2-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropaneAmides of carboxylic acids
			WO 00/54729A 2 example 8	ca. 20000	(S) -N- (1- (4-benzyl-5- (tert-butylsulfanyl) -1, 2, 4-triazol-3-yl) -2- (benzyloxy) ethyl) -2-amino-2-methylpropanamide
WO 00/54729A 2 example 3	ca.3000	(R) -N- (1- (1-methylpropionate-tetrazol-5-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide
			WO 00/54729 Page a2175 example	ca. 25000	(S) -N- (1- (1-benzyl-tetrazol-5-yl) -2- (benzyloxy) ethyl) -2-amino-2-methylpropanamide

III) in vitro intracellular calcium Release assay Using human GHS-R1 a transfected CHO cells

The potential of the compounds of the invention to modulate the activity of the GHS receptor was assessed using an in vitro intracellular calcium release assay using CHO cells transfected with human GHS-R1 a.

Intracellular calcium release or inhibition thereof was measured using a fluorescent calcium indicator assay (FLIPR) and Fluo-4 AM.

CHO cells (CHO-KI Chinese hamster ovary cell line, ATCC No. CCL-61) were transiently transfected with human GHS-R1 a cDNA by electroporation and plated into 96-well black-bottom plates (Corning 3603) (80,000 cells/well). Transient transfections were performed using an EasyjectOptima Electroporator (Equibio) according to the manufacturer's instructions.

At 37 deg.C, 5% CO₂Transfected cells were grown in Dulbecco's modified Eagle medium without phenol red, supplemented with 10% (v/v) non-essential amino acids, 2nM glutamine and streptomycin-penicillin (250. mu.g/ml-250 u/ml) (both from Cambrex) for 24 hours under humidified atmosphere.

After incubation, transfected cells were treated with 150. mu.l buffer A [ Hanks Balanced salt solution (Sigma H-6648), 0.5% (v/v) BSA (Sigma A-7906), 20mM CaCl₂2.5mM probenecid (pH7.4, dissolved in 1M NaOH) (Sigma P-8761) ]Washed and then loaded with Fluo-4AM (10) containing a fluorescent calcium indicator^-6M) (Interchim UP72972) additionally containing 0.06% pluronic acid (Molecular probes P-6867) (a mild ionic detergent which facilitates loading of Fluo-4AM ester). (Loading: 100. mu.l per well of buffer A containing 120. mu.l/ml Pluronic Acid and 1. mu.M Fluo-4AM was added to the cells.

After loading with Fluo-4AM, transfected cells were incubated for 1 hour at 37 ℃ in the dark.

Test compounds were dissolved in buffer A in triplicate at a concentration of 10^-6M, and distributed to another 96-well plate (Fisher Labosi A1210500).

After incubation, excess Fluo-4AM was removed and 100. mu.l buffer A was added to each well at room temperature and immediately removed by aspiration. The process was then repeated, after which 50. mu.l of buffer A was added to each well.

Transfected cells were further incubated at room temperature for 30min to complete the de-esterification of intracellular Fluo-4AM ester.

Subsequently, both the black matrix plate containing transfected cells and the microtiter plate containing test compounds were placed in a temperature-regulated (25 ℃) FlexStation machine (desk-top scanning fluorometer Flex Station II, Molecular Devices, Sunnyvale, California, USA) and the fluorescence output was measured.

Since Fluo-4AM shows a large increase in fluorescence intensity after calcium binding, the fluorescence output can be directly used as a corresponding measure of intracellular calcium release.

The basal fluorescence output from transfected cells was measured for 15 seconds, and then 50 μ l of test compound was automatically dispensed into wells containing transfected cells. The fluorescence output was then recorded for an additional 45 seconds.

Excitation and emission wavelengths were 485nm and 525nm, respectively. The basal fluorescence intensity of transfected cells loaded with Fluo-4AM varied between 800-1200 arbitrary units in the absence of test compound, while the maximum fluorescence output of transfected cells loaded with stain varied between 5000-7000 arbitrary units after incubation with test compound and corresponded to that of 10-7000 cells^-6M ghrelin stimulates the maximum fluorescence output obtained from transfected cells loaded with stain.

For each test compound, the change in fluorescence output after addition of each compound was compared to the basal fluorescence output measured with a negative control, i.e., 50. mu.l of buffer A was added to transfected cells only.

The ability and extent of each test compound to cause calcium release was determined relative to basal levels (0%) and maximum levels achieved with 1 μ M ghrelin (100%).

For test compounds identified as GHS receptor agonists, EC is determined using a dose-response curve₅₀And a KI value.

For test compounds identified as GHS receptor antagonists, at 10^-7Determination of IC Using an antagonist inhibition Curve in the Presence of M ghrelin (sub-maximal concentration)₅₀And Kb (antagonist dissociation constant). Computing IC₅₀Values, as GHS receptor antagonist, reduce the maximal response of ghrelin by 50% molar concentration. Kb values were estimated using the Cheng-Prusoff equation (Lazarenos and Birdsall NJ, Trends Pharmacol Sci.1993, 14 (6): 237-.

FIGS. 14-40 show selected chemomes calculated for CHO cells transfected with human GHS-R1 aIn vitro intracellular calcium release assay dose-response profiles of compounds 1, 9, 12, 20, 22, 31, 39, 41, 42, 45, 46, 47, 48, 49, 50, 51, 55, 62, 64, 67, 71, 73, 74, 79, 81, 90 and ghrelin, as well as EC of agonistic compounds₅₀And KI value and IC of antagonistic compounds₅₀And Kb value.

IV) in vivo determination of GH concentration in plasma of young male rats

Plasma concentrations of GH in young male rats are measured to identify the modulating effects (antagonism or agonism) of the compounds of the present invention as ligands for the GHs receptor analogs.

In principle, GH concentration determination in plasma of rats in vivo was carried out in accordance with Torsello et al (Eur.J.Pharmacol.1998, 360: 123-129).

Juvenile male Sprague-Dawley rats (Charles River, Calco, Italy) were separated from their mothers on the seventh postnatal day and randomly re-assigned to the dams for each care of ten to twelve pups. On the tenth day after birth, young mice were again separated from their mothers.

Test compounds were dissolved in solvent (DMSO (0.4% of total volume), distilled water (4% of total volume), added to final volume with physiological saline).

One hour after separation from their mothers, the pups were given an equal volume of test compound (160 μ g/kg body weight s.c.) at-10 min, followed by hexarelin (80 μ g/kg body weight s.c.) or solvent at 0min, and sacrificed after 15min by decapitation. Trunk blood was collected, immediately centrifuged, plasma samples stored at-20 ℃ and GH concentrations determined.

Plasma GH concentrations were measured using a rat growth hormone enzyme immunoassay kit (SPIbio, France, cat. No.589601) according to the manufacturer's instructions. Values were expressed as NIDDK rat-GH-RP 2 standard (potency 2IU/mg) in ng/mL plasma.

Calculating the concentration that produces 15% of the initial tracer displacement as the detection limit, and is 0.5 ng/mL; the intra-measurement and inter-measurement variation coefficients were 4% (n-24) and 14% (n-9).

The results obtained for selected compounds of the invention are listed in table 3 below.

Table 3: relative GH concentration in rat plasma after treatment with selected compounds of the invention (160. mu.g/kg body weight s.c.) and/or hexarelin (80. mu.g/kg body weight s.c.) and/or solvents

Treatment of	GH concentration (ng/mL)
		Solvent(s)	4,008±0,469
hexarelin	162,839±21,095
		Compound 1	n.d.
Compound 1+ hexarelin	80.22±18.66
		Compound 12	4.0±0.12
Compound 12+ hexarelin	200.0±19.7
		Compound 20	5.27±0.59
Compound 20+ hexarelin	220.51±15.52
		Compound 22	4.88±0.33
Compound 22+ hexarelin	239.91±19.75
		Compound 47	5,658±1,192
Compound 47+ hexarelin	160,857±13,52

Compound 39	5,509±1,950
		Compound 39+ hexarelin	82,481±11,530
Compound 31	119,937±33,054
		Compound 31+ hexarelin	103,528±14,094
Compound 48	6,096±2,091
		Compound 48+ hexarelin	145,946±12,159
Compound 44	87,520±15,066
		Compound 44+ hexarelin	100,52±12,112
Solvent(s)	2,237±0,073
		hexarelin	170,101±13,226
Compound 9	13,016±1,960
		Compound 9+ hexarelin	183.562±16.729
Compound 39	5.509±1.95
		Compound 39+ hexarelin	82.481±11.53
Compound 50	9.852±1.040
		Compound 50+ hexarelin	164.459±4.443
Compound 64	13.056±2.169
		Compound 64+ hexarelin	138.394±14.580
Solvent(s)	10,729±2,027
		hexarelin	253,820±12,268
Compound 71	15,326±1,355
		Compound 71+ hexarelin	173,611±18,444
Compound 74	10,571±0,791
		Compound 74+ hexarelin	194,564±7,658
Compound 81	18,634±2,933
		Compound 81+ hexarelin	216,575±19,734
Compound 90	16,857±2,152
		Compound 90+ hexarelin	218,844±19,723

V) measurement of eating behavior (food intake) in young-adult rats

The effect of the compounds of the invention as GHS receptor analogue ligands on feeding behaviour, i.e. food intake, in young-adult male rats was determined.

In principle, the feeding behavior (food intake) assay was performed in young-adult male rats according to T0rsello et al (Eur. J. Pharmacol.1998, 360: 123-129).

For the assay, young-adult male Sprague-Dawley rats (Charles River, Calco, Italy) weighing 200-.

Rats were acclimated to their respective cage and animal chamber conditions for 1 week (22. + -. 2 ℃, 65% humidity, artificial light from 08.00 to 20.00 h). The next week they were trained daily to simulate the experimental procedure. Rats had free access to dry pellets and tap water throughout the experimental period. At the end of the training, the test compounds (160 μ g/kg body weight) and/or hexarelin (80 μ g/kg body weight) and/or solvents (DMSO (0.4% of total volume), distilled water (4% of total volume), added to the final volume with physiological saline, were administered subcutaneously to the rats (around 10.00-11.00 a.m.).

Hexarelin was used to study the effect of test compounds on stimulated feeding behavior. Immediately after injection, the animals were returned to their cages containing known amounts of standard rat feed and unlimited amounts of water. The remaining food was carefully collected every hour for the next 6 hours and weighed to the nearest 0.1 g. Food intake was normalized to rat body weight, expressed as grams of food ingested per 100g of rat body weight.

The results obtained for selected compounds of the invention are listed in table 4 below.

Table 4: cumulative food intake (g food/100 g body weight) in young-adult rats after 2 and 6 hours treatment with selected compounds of the invention (160. mu.g/kg body weight s.c.) and/or hexarelin (80. mu.g/kg body weight s.c.) and/or solvents

Treatment of	Cumulative food intake (after 2 hours)	Cumulative food intake (after 6 hours)
			Solvent(s)	0,003±0,0015	0,017±0,0026
hexarelin	0,533±0,194	1,0014±0,1973
			Compound 1	0.02±0.002	0.06±0.03
Compound 1+ hexarelin	0.06±0.02	0.33±0.21
			Compound 12	0.034±0.011	0.06±0.019

Compound 12+ hexarelin	0.13±0.07	0.48±0.22
			Compound 20	0.01	0.2±0.19
Compound 20+ hexarelin	0.53±0.21	0.63±0.19
			Compound 22	0.01	0.44±0.2
Compound 22+ hexarelin	0.67±0.12	0.86±0.18
			Compound 47	0,006±0,002	0,02±0
Compound 47+ hexarelin	0,35±0,201	0,47±0,1943
			Compound 44	0,43±0,0721	0,7075±0,1471
Compound 44+ hexarelin	1,2667±0,1319	1,4033±0,1177
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,536±0,176	0,594±0,169
			Compound 9	0,01±0	0,01±0
Compound 9+ hexarelin	0,0104±0,0032	0,0231±0,0032
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	1,060±0,143	1,138±0,114
			Compound 13	0,057±0,057	0,167±0,167
Compound 13+ hexarelin	0,731±0,318	0,792±0,337
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	1,060±0,143	1,138±0,114
			Compound 17	0,001±0,001	0,2661±0,166
Compound 17+ hexarelin	0,0501±0,049	0,846±0,411
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,428±0,192	0,588±0,303
			Compound 24	0,008±0,008	0,215±0,200
Compound 24+ hexarelin	0,586±0,252	0,912±0,359
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,627±0,211	0,778±0,218
			Compound 30	0,264±0,244	0,277±0,246
Compound 30+ hexarelin	1,350±0,177	1,449±0,213
			Solvent(s)	0,184±0,018	0,399±0,201

hexarelin	0,278±0,078	0,883±0,259
			Compound 38	0,001±0	0,076±0,096
Compound 38+ hexarelin	0,002±0,002	0,478±0,141
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,26±0,13	0,78±0,25
			Compound 49	0,004±0,004	0,004±0,004
Compound 49+ hexarelin	0,057±0,037	0,558±0,212
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,536±0,176	0,594±0,169
			Compound 50	0,012±0,008	0,039±0,011
Compound 50+ hexarelin	0,003±0,002	0,017±0,001
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,427±0,16	0,688±0,203
			Compound 64	0,012±0,008	0,039±0,011
Compound 64+ hexarelin	0,012±0,004	0,021±0,007
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,696±0,267	0,74±0,27
			Compound 71	0,522±0,283	0,53±0,28
Compound 71+ hexarelin	0,117±0,074	0,20±0,01
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,70±0,116	1,221±0,06
			Compound 72	0,008±0,003	0,011±0
Compound 72+ hexarelin	0,634±0,33	0,746±0,31
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	1,031±0,219	1,455±0,192
			Compound 80	0,145±0,143	0,346±0,159
Compound 80+ hexarelin	0,475±0,196	0,733±0,238
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,696±0,267	0,74±0,27
			Compound 81	0,017±0,004	0,03±0

Compound 81+ hexarelin	0,024±0,0101	0,116±0,077
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,412±0,173	0,68±0,29
			Compound 81	0,034±0,003	0,346±0,179
Compound 81+ hexarelin	1,4±0,35	1,665±0,345
			Solvent(s)	0,184±0,111	0,497±0,183
hexarelin	0,323±0,131	0,45±0,17
			Compound 90	0,014±0,001	0,035±0,003
Compound 90+ hexarelin	0,054±0,041	0,069±0,041

VI) motilin receptor-ligand binding assay (using human recombinant HEK-293 cells)

Motilin receptor binding/affinity studies were performed as described in Feighner SD et al (Science1999, 284: 2184-2188). The measurement was carried out under the following conditions:

the source is as follows: human recombinant HEK-293 cell [ motilin-receptor 1a (MTL-R1a) ]

Ligand: 0.1nM [ alpha ], [ beta ], [ alpha¹²⁵I]Motilin (pig, human)

Carrier: 1% DMSO

Incubation time/temperature: 2,5 hours, 25 deg.C

Incubation buffer: 50mM Tris, pH 7,4, 10mM MgCl₂，0，5％BSA

Non-specific ligand: 1 μ M motilin (human, pig)

Compounds of the invention were tested at concentrations comprising 0.01. mu.M, 0.1. mu.M, 1. mu.M and 10. mu.M.

IC was determined by means of nonlinear least squares regression Analysis using a Data Analysis Toolbox (MDL Information Systems, USA) ₅₀The value is obtained.

The results obtained for selected compounds of the invention are listed in table 5 below.

Table 5: results of motilin receptor-ligand binding assay (IC of some selected exemplary Compounds)₅₀Value)

No.

MTL-R1a IC₅₀[μM]

Chemical name

44	1,61	(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazole-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-4-carboxamide,
			64	1,39	(R) -N- (1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-Triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

VII) study of the anti-cachexia Effect in an adjuvant-induced arthritis model System

The effectiveness of the compounds of the invention in the treatment of cachexia was investigated in accordance with Ibanez de CaCeres I, etc., using the cachexia model system (Roubenoff R et al, Arthritis Rheum.1997, 40 (3): 534-.

Table 6 shows the anti-cachexia effect of compound 44(0.1 μ g/kg/day s.c. injection) in arthritic rats compared to adjuvant-induced arthritis without medical treatment.

Table 6: grams of body weight change (average of 6 animals per group)

	Day 3	Day 6	Day 10	Day 13	Day 15	Day 17
							Adjuvant-induced arthritis rats + vehicle	-3,02	2,95	11,97	9,32	-2,78	-8,27
Arthritic rats + compound 44 treatment (0.1 μ g/kg/day s.c.)	-5,32	2,98	14,92	19,08	7,05	1,47

VIII) study of the anti-suppressive Effect of isoproterenol-induced lipolysis in an adipocyte model

The efficacy of the compounds of the invention in inhibiting the inhibition of non-acylated ghrelin-induced isoproterenol-induced lipolysis was investigated using an adipocyte model.

Isolation of Primary mouse adipocytes

Mice were fed a high-fat diet to induce obesity (60% lipid), starting at 4 weeks of age for 12 and 18 weeks.

Cutting white adipose tissue from epididymal fat and applying CO₂Saturated Krebs-Ringer-Bicarbonate-Hepes (KRBH) buffer (20mM Hepes pH 7.4, 120mM NaCl, 4.7mM KCl, 1.2mM K)₂HPO₄，2.5mM CaCl₂，1.2mM MgSO₄，24mM NaHCO₃) Medium digest containing glucose (1mg/mL), 1% BSA and collagenase (2mg/g tissue). Digestion was performed by constant shaking (250rpm) for 45 minutes at 37 ℃.

The cell suspension was filtered through a nylon mesh, the adipocytes were separated from the tissue debris and washed three times in 3mL of warm KRBH 1% BSA.

Cells were resuspended in KRBH 1% BSA and incubated for 30 min at 37 ℃ on a shaker (75 rpm).

Lipolysis assay

Primary adipocytes were induced to lipolysis by incubation with 30nM isoproterenol in KRBH 4% BSA for 90 minutes at 37 ℃ with shaking at a constant rate (125 rpm).

Lipolysis of differentiated cells was induced with DMEM containing 30nM isoproterenol (the DMEM does not contain FBS) at 37 ℃ for 90 minutes while shaking every 15 minutes.

The inhibitory effect of unacylated ghrelin (UAG) on isoproterenol-induced lipolysis was demonstrated in the presence or absence of 10^-7In the presence of the compound of the invention selected by M, the concentration of UAG is from 10^-11M increases to 10^-6M。

The lipolytic index was assessed by measuring glycerol release after hydrolysis of triglycerides.

The antagonistic effect was determined as follows:

wherein

Figures 41-46 show the effect of selected compounds 9, 38, 50, 64, 74, 81 on the lipolytic inhibition curve of isoproterenol-induced unacylated ghrelin (uag) in primary adipocytes of diet-induced obese mice.

Claims

1. Use of a compound of formula (I) for the preparation of a medicament for the treatment or prevention of a physiological and/or pathophysiological condition mediated by GHS receptors in a mammal selected from the group consisting of: growth retardation, cachexia, regulation of energy balance, regulation of food intake, adipogenesis and/or obesity, weight gain and/or reduction,

wherein:

r1 is selected from the group consisting of: "hydrogen atom, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl", optionally substituted in the alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/or heterocyclylalkyl groups with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

r2 is selected from the group consisting of: "alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl", optionally substituted in the alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/or heterocyclylalkyl groups with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N ₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

one of the radicals R3 and R4 is a hydrogen atom and the other radical is selected from the group consisting of: "hydrogen atom, alkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -alkyl-O-aryl, -alkyl-O-arylalkyl, -alkyl-O-heteroaryl, -alkyl-O-heteroarylalkyl, -alkyl-O-heterocyclyl, alkyl-O-heterocyclylalkyl, -alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, -alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, -alkyl-C (O) O-arylalkyl, alkyl-C (O), aryl, heteroaryl, heterocyclyl, heteroaryl-CO-heterocyclylalkyl, heteroaryl-C (O), -alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O-heterocyclyl, -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH₂-alkyl-CO-OH, -alkyl-NH₂-alkyl-NH-C (NH) -NH₂Alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, alkyl-S-alkyl, alkyl-S-H ", optionally substituted in aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and/or heterocyclylalkyl with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N ₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

r5 is selected from the group consisting of: "Hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, -CO-alkyl, -CO-cycloalkyl, -CO-cycloalkylalkyl, -CO-aryl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, -CO-heterocyclylalkyl, -CO-C^＊(R9R10)-NH₂、-CO-CH₂-C^＊(R9R10)-NH₂、-CO-C^＊(R9R10)-CH₂-NH₂Alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl ", optionally substituted with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

r6 is selected from the group consisting of: "hydrogen atom, alkyl group, cycloalkyl group, cycloalkylalkyl group";

r7 and R8 are independently selected from the group consisting of: "hydrogen atom, alkyl group, cycloalkyl group, cycloalkylalkyl group";

r9 and R10 are independently selected from the group consisting of: "hydrogen atom, alkyl group, natural alpha-amino acid side chain, unnatural alpha-amino acid side chain";

m is 0, 1 or 2; and is

^＊Represents a carbon atom of R or S configuration when chiral;

wherein the content of the first and second substances,

The term "alkyl" refers to acyclic saturated hydrocarbons having C1-C12 carbon atoms;

the term "alkenyl" refers to acyclic unsaturated or partially unsaturated hydrocarbons having C2-C12 carbon atoms that contain one or more double bonds;

the term "alkynyl" refers to acyclic unsaturated or partially unsaturated hydrocarbons containing one or more triple bonds having from C2 to C12 carbon atoms;

the term "cycloalkyl" refers to (C3-C8) -cycloalkyl;

the term "aryl" refers to phenyl, biphenyl, naphthyl, anthracenyl, indanyl, indenyl, or 1, 2, 3, 4-tetrahydronaphthyl;

the term "heteroaryl" refers to pyrrolyl, thienyl, furyl, imidazolyl, thiazolyl, isothiazolyl, thiazolyl,Azolyl radical, isoOxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, indolyl, quinolinyl or isoquinolinyl; and

the term "heterocyclyl" means pyrrolidinyl, thiapyrrolidinyl, piperidinyl, piperazinyl, oxapiperazinyl, oxapiperidinyl orA diazolyl group.

2. Use of a compound according to formula (I) as claimed in claim 1, wherein

R3 is selected from the group consisting of: "-alkyl-CO-aryl, -alkyl-CO-arylalkyl, -alkyl-CO-heteroaryl, -alkyl-CO-heteroarylalkyl, -alkyl-CO-heterocyclyl, alkyl-CO-heterocyclylalkyl, -alkyl-C (O) O-aryl, -alkyl-C (O) O-arylalkyl, -alkyl-C (O) O-heteroaryl, -alkyl-C (O) O-heteroarylalkyl, -alkyl-C (O) O-heterocyclyl, -alkyl-C (O) O-heterocyclylalkyl, -alkyl-CO-NH-alkyl ₂-alkyl-CO-OH, -alkyl-NH-C (NH) -NH₂alkyl-S-alkyl, alkyl-S-H ".

3. Use of a compound according to formula (I) as claimed in claim 1, wherein

R4 is a hydrogen atom;

with the proviso that if R5 is "-CO-heteroarylalkyl", "heteroaryl" is not imidazole;

with the proviso that if R5 is "-CO-heterocyclyl", and "heterocyclyl" contains only nitrogen atoms as heteroatoms, at least two nitrogen atoms are contained in "heterocyclyl";

Wherein "alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, -CO-cycloalkyl, -CO-cycloalkylalkyl, -CO-aryl, -CO-arylalkyl, -CO-heteroaryl, -CO-heteroarylalkyl, -CO-heterocyclyl, and/or-CO-heterocyclylalkyl" is optionally substituted with up to 3 substituents independently selected from the group consisting of: "halogen, -F, -Cl, -Br, -I, -N₃、-CN、-NR7R8、-OH、-NO₂Alkyl, aryl, arylalkyl, -O-alkyl, -O-aryl, -O-arylalkyl,;

with the proviso that if R5 is "-CO-cycloalkyl" or "-CO-cycloalkylalkyl", R5 is not directly connected at the 1-position of "cycloalkyl" to the C atom of "cycloalkyl" which is substituted by NR7R8 with carbonyl "-CO-" in the case of R5 ═ CO-cycloalkyl "or" alkyl "in the case of R5 ═ CO-cycloalkylalkyl";

r6 is a hydrogen atom;

r7 and R8 are independently selected from the group consisting of: "hydrogen atom, alkyl group, cycloalkyl group, cycloalkylalkyl group"; and is

m is 0, 1 or 2.

4. Use of a compound according to formula (I) as claimed in claim 1, wherein

R3 is selected from the group consisting of: "hydrogen atom, methyl group, propan-2-yl group, 2-methyl-propan-1-yl group, butan-2-yl group, butan-1-yl group, -CH₂-SH、-(CH₂)₂-S-CH₃1H-indol-3-yl-methyl, phenyl-methyl, 2-phenyl-ethylradical-CH₂-O-CH₂-phenyl, -CH₂-CO-CH₂-phenyl, - (CH)₂)₂-CO-CH₂-phenyl, -CH₂-C (O) O-phenyl, - (CH)₂)₂-C (O) O-phenyl, hydroxy-methyl, 1-hydroxy-ethan-1-yl, -CH₂-CO-NH₂、-(CH₂)₂-CO-NH₂(1-hydroxy-phen-4-yl) -methyl, -CH₂-CO-OH、-(CH₂)₂-CO-OH、-(CH₂)₄-NH₂(1H-imidazol-5-yl) -methyl, - (CH)₂)₃-NH-C(NH)-NH₂、-(CH₂)₃-NH₂、-(CH₂)₃-NH-CO-NH₂”；

R4 is a hydrogen atom;

r5 is selected from the group consisting of: "Hydrogen atom, -CO-CH₂-NH₂(Gly residue), -CO-CH₂-CH₂-NH₂(beta-Ala residue), -CO-CHCH₃-NH₂(D-and/or L-alpha-Ala residue), -CO- (pyrrolidin-2-yl) (D-and/or L-Pro residue), 2-amino-2-carbonyl-propane (2-amino-isobutyric acid/Aib residue), 4-carbonyl-1H-piperidine, 3-carbonyl-1H-piperidine, R- (3-carbonyl-1H-piperidine), S- (3-carbonyl-1H-piperidine), 2-carbonyl-1H-piperidine, R- (2-carbonyl-1H-piperidine), S- (2-carbonyl-1H-piperidine), 1-amino-2-carbonyl-benzene, L-amino-2-carbonyl-propane, L-isobutyric acid/Aib residue, 4-carbonyl-1H-piperidine, 3-carbonyl-1H-piperidine, L-carbonyl-1, Carbonyl-cyclohexane, 2-acetyl-pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine, 4-propionyl-pyridine, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-1H-imidazole, 2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-pyrazine, 2-carbonyl-4-hydroxy-1H-pyrrolidine, 4-carbonyl-1H, 3H-diazacyclohexane, methylsulfonyl, phenylsulfonyl, 1-carbonyl-1-amino-2-phenylethane, phenylmethyl, 1-carbonyl-4-azide-benzene, 2-carbonyl-2, 5-dihydro-1H-pyrrole, 2-carbonyl-piperazine, 2-carbonyl-1H-pyrrolidine, 2-aminoethane, carbonyl-benzene, 2-carbonyl-pyrazine, 3-carbonyl-pyrazine, 4-carbonyl-oxacyclohexane, 4-methyl-phenylsulfonyl, phenylmethyl-sulfonyl ";

R6 is a hydrogen atom; and is

m is 0.

5. Use of a compound according to formula (I) as claimed in claim 4 wherein R3 is selected from the group consisting of: "-CH₂-CO-CH₂-phenyl, - (CH)₂)₂-CO-CH₂-phenyl, -CH₂-CO-NH₂、-(CH₂)₂-CO-NH₂、-CH₂-CO-OH、-(CH₂)₂-CO-OH、-(CH₂)₃-NH-C(NH)-NH₂、-CH₂-SH、-(CH₂)₂-S-CH₃”。

6. Use of a compound according to formula (I) as claimed in claim 4 wherein R5 is selected from the group consisting of: "hydrogen atom, methylsulfonyl group, phenylsulfonyl group, carbonyl-cyclohexane, (R-1-amino) -2-carbonyl-cyclohexane, (S-1-amino) -2-carbonyl-cyclohexane, 2-carbonyl-pyridine, 3-carbonyl-pyridine, 4-carbonyl-pyridine, 2-acetyl-pyridine, 3-acetyl-pyridine, 4-acetyl-pyridine, 2-propionyl-pyridine, 3-propionyl-pyridine, 4-propionyl-pyridine, 2-amino-3-carbonyl-pyridine, 2-carbonyl-1H-imidazole, 2-carbonyl-pyrazine, 4-carbonyl-1H, 3H-diazacyclohexane ".

7. Use as claimed in any one of claims 1 to 6 wherein the compound is selected from the group consisting of:

The compound 11(R) -H- (1- (5- (3- (1H-indol-3-yl) propyl) -4- (naphthalen-1-ylmethyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

Compound 40(2S, 4R) -N- ((R) -1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -4-hydroxypyrrolidine-2-carboxamide,

compound 113 (R) -N- (1- (4- (3, 5-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 135N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-aminoacetamide,

the compound 138N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) picolinamide,

compound 143 (2S) -N- ((R) -2- (1H-indol-3-yl) -1- (5-phenethyl-4-phenyl-4H-1, 2, 4-triazol-3-yl) ethyl) pyrrolidine-2-carboxamide,

the compound 150(2S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-ethylphenyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) pyrrolidine-2-amide,

Compound 155 (3S) -N- ((R) -1- (4- (4-ethylbenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) piperidine-3-carboxamide,

the compound 177(R) -1- (4- (2, 4-dimethoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) -N-phenylmethanesulfonyl amine,

the compound 190(2S) -N- ((R) -1- (5- (2- (1H-indol-3-yl) ethyl) -4- (4-methoxybenzyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2, 5-dihydro-1H-pyrrole-2-carboxamide.

8. Use as claimed in any one of claims 1 to 6 wherein the compound is selected from the group consisting of: compound 1, 3, 12, 13, 14, 18, 20, 22, 23, 33, 36, 37, 38, 41, 46, 47, 48, 49, 50, 51, 52, 53, 57, 58, 59, 60, 61, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 79, 80, 82, 85, 86, 87, 88, 89, 90, 91, 93, 101, 102, 109, 114, 116, 119, 134, 135, 136, 137, 138, 139, 140, 145, 146, 147, 148, 150, 152, 153, 154, 156, 157, 159, 160, 161, 164, 171, 174, 176, 178, 179, 182, 184, 186, 188 and/or compound 190.

9. Use as claimed in any one of claims 1 to 6 wherein the compound is selected from the group consisting of: compound 2, 4, 5, 6, 7, 8, 9, 10, 11, 15, 16, 17, 19, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 39, 40, 42, 43, 44, 45, 54, 55, 56, 62, 67, 78, 81, 83, 84, 87, 92, 94, 99, 103, 104, 105, 106, 107, 108, 110, 111, 115, 117, 118, 121, 122, 124, 130, 131, 142, 155, 158, 163, 173, 175, 180, 181, 183, 185 and/or compound 187.

10. The use as claimed in claim 1 wherein the GHS receptor is selected from the group consisting of "GHS type 1 receptor, GHS-R1 a, GHS-R1 b, motilin receptor 1a, neurotensin receptor, TRH receptor, GPR38, GPR39, FM3, GHS-R subtype, GHS binding site, cardiac GHS-R and mammary GHS-R".

11. The use as claimed in claim 10 wherein the GHS receptor is selected from the group consisting of "GHS type 1 receptor, GHS-R1 a and GHS-R1 b".

12. The use as claimed in claim 10 wherein the GHS receptor is GHS-R1 a.

13. A triazole compound selected from the group consisting of:

compound 24) (R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5- (3- (1H-indol-3-yl) propyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

The compound 53(R) -N- (1- (4- (4-methoxybenzyl) -5-phenethyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) cyclohexanamide,

the compound 98 (R) -N- (1- (5- ((1H-indol-3-yl) methyl) -4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

compound 111 (R) -N- (1- (4- (2- (1H-indol-3-yl) ethyl) -5-benzyl-4H-1, 2, 4-triazol-3-yl) -2- (1H-indol-3-yl) ethyl) -2-amino-2-methylpropanamide,

14. A pharmaceutical composition comprising a pharmacologically active amount of at least one compound as claimed in claim 13.

15. A pharmaceutical composition as claimed in claim 14 wherein the compound is present in a unit dose of from 0.001 mg to 100 mg per kg body weight of the patient.

16. A pharmaceutical composition as claimed in any one of claims 14 to 15 wherein the composition additionally comprises at least one pharmaceutically acceptable carrier and/or excipient.