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WO2003082833A1 - Derives de 1,2,4-triazol possedant des proprietes cannabinoides - Google Patents

Derives de 1,2,4-triazol possedant des proprietes cannabinoides Download PDF

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Publication number
WO2003082833A1
WO2003082833A1 PCT/ES2003/000126 ES0300126W WO03082833A1 WO 2003082833 A1 WO2003082833 A1 WO 2003082833A1 ES 0300126 W ES0300126 W ES 0300126W WO 03082833 A1 WO03082833 A1 WO 03082833A1
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WO
WIPO (PCT)
Prior art keywords
triazole
heptyl
chlorophenyl
series
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/ES2003/000126
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English (en)
Spanish (es)
Inventor
Nadine Jagerovic
María Pilar GOYA LAZA
Laura HERNÁNDEZ FOLGADO
Ivon José ALCORTA OSORO
María Isabel MARTIN FONTELLES
Margarita Linarejos SUARDIAZ GARCÍA
María Teresa DANNERT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Consejo Superior de Investigaciones Cientificas CSIC
Universidad Rey Juan Carlos
Original Assignee
Consejo Superior de Investigaciones Cientificas CSIC
Universidad Rey Juan Carlos
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Consejo Superior de Investigaciones Cientificas CSIC, Universidad Rey Juan Carlos filed Critical Consejo Superior de Investigaciones Cientificas CSIC
Priority to AU2003215687A priority Critical patent/AU2003215687A1/en
Publication of WO2003082833A1 publication Critical patent/WO2003082833A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention relates to novel triazole derivatives with cannabinoid properties, in particular 1,2,4-triazole derivatives with cannabinoid properties.
  • Cannabinoids are a group of natural or synthetic compounds, belonging to different chemical families (P. Goya et al., Exp. Opin. Ther.Pat., 2000, 10 1529-1538), which interact with the cannabinoid receptors CB1 and CB2. These receptors are involved in the modulation of different functions, such as memory, cognition, appetite, immune responses, pain, etc., and therefore the compounds that interact with them will be useful in those therapeutic fields where these receptors are involved (RG Pertwee , Exp. Opin. Invest. Drugs., 2000, 9 7-19).
  • cannabinoid properties is designated activity in isolated tissues classically used to evaluate cannabinoid agonists and antagonists.
  • the present invention has for OBJECT the compounds of formula A:
  • X a , X b are identical or different, and each independently represents a hydrogen atom or a halogen atom.
  • R represents an alkyl of (C2-C7) and R 2 represents a phenyl substituted in the ortho and / or para position by a hydrogen atom and / or a halogen atom
  • the (C2-C7) alkyl groups are linear and is understood to be a halogen atom, a chlorine, bromine, fluorine or iodine atom.
  • the compounds of formula A of the following series I, ⁇ , ni and IV are preferred: the compounds of the series I of the formula:
  • - R represents an alkyl of (C2-C7)
  • X a , X b , X c , X d are identical or different, and each independently represents a hydrogen atom or a halogen atom.
  • - R represents an alkyl of (C2-C7)
  • X a , X b , X c are identical or different, and each independently represents a hydrogen atom or a halogen atom;
  • - Y represents a carbon atom bound to a hydrogen or attached to a halogen atom, or a nitrogen atom; as well as the compounds of the EH series of formula:
  • - R represents an alkyl of (C2-C7)
  • - R represents an alkyl of (C2-C7); - X a , X b are identical or different, and each independently represents a hydrogen atom or a halogen atom.
  • the synthetic route shown in Figure 2 can be followed.
  • the N (l) H-triazoles are synthesized in a second step.
  • Heterocyclic Chem., 1988, 25 771-782 are used to alkylate the N (1) H-triazoles.
  • the respective isomers of these two series can be separated by chromatography on silica gel according to conventional methods and characterized by their NMR spectra, mainly by two-dimensional studies.
  • the methylation is carried out according to a procedure described for the alkylation of pyridine, by example, in Synthesis, 2000, 9 1229-1236, with excess of methyl iodide as alkylating agent, and dichloromethane as the solvent to give the pyridinium salts of formula corresponding to the series rv.
  • the characterization of the CANNABINOID ACTIVITY of the new compounds described in the present invention was carried out by analyzing their activity in isolated tissues classically used to evaluate cannabinoid agonists and antagonists. We used the mouse vas deferens (L. Lay et al, Eur. J.
  • Cannabinoid antagonists are capable of selectively blocking this effect (RG Pertwee et al, Eur. J. Pharmacol., 1996, 315 195-201; RG Pertwee et al, Br. J. Pharmacol., 1992, 105 980-984 ; RG Pertwee et al, Eur. J. Pharmacol., 1996, 296 169-172; RG Pertwee et al, Br. J. Pharmacol., 1997, 121 1716-1720; AA Izzo et al, Br. J. Pharmacol. , 1998, 124 1363-1368).
  • the antagonist used as control was AM 251.
  • the effect of WIN 55,212-2 was also blocked confirming that the effect is mediated by CB1 receptors. It is important to highlight the fact that the compound 5- (4-chlorophenyl) -l- (2,4-dichlorophenyl) -3-hexyl-lH-1, 2,4-triazole, example of the series I of the present invention , did not show any significant modification of the force of the contractions compared to the force registered in control tissues or incubated with the solvent, which shows that they lack intrinsic activity, do not behave as partial agonists or as inverse agonists, this differentiates them of other previously described antagonists, since most of them, such as AM 251, are not pure antagonists.
  • AM 251 is a widely used antagonist (S. J. Gatley et al, Eur. J. Pharmacol., 1996, 307 331; S. J. Gatley et al, Life Sci., 1997, 6_i 191). Despite this some data suggest that it can also behave as an inverse agonist, in the preparation of guinea pig ileum it was observed that it is capable of significantly increasing the strength of the contractions.
  • the compounds according to the invention can be used as active ingredients of medicaments for the treatment of disorders in which cannabinoid receptors are involved.
  • the compounds of the present invention can be used, for example for the treatment, prevention or improvement of glaucoma, of bronchial asthma and chronic bronchitis, of allergies such as contact dermatitis or allergic conjunctivitis, of arthritis, of pain , diseases associated with organ transplants, motor disorders associated with Tourette syndrome, Parkinson's disease or Huntingdon's disease, malignant gliomas, multiple sclerosis, emesis associated with anticancer chemotherapy, of appetite.
  • the main therapeutic applications of the compounds according to the invention and due to their antagonistic nature are the suppression of appetite, the reduction of dyskinesia caused by L-dopa in Parkinson's patients, the treatment of acute schizophrenia and an improvement of cognitive dysfunctions and of memory associated with Alzheimer's disease.
  • the compounds of the present invention as CB1 receptor antagonists can be used as pharmacological tools for pharmacological characterization of the receptor and confirmation of agonist activities.
  • Figure 1 represents the synthetic scheme of the preparation of the compounds of the present invention of the Series I
  • Figure 2 represents the synthetic scheme of the preparation of the compounds of the present invention of Series II and El;
  • Figure 3 illustrates the dose-dependent inhibition of guinea pig ileum contraction by the example compound of the present invention, 5- (4-chlorophenyl) -l- (2,4-dichlorophenyl) -3-hexyl-lH-1, 2,4-triazole, and by the pattern WIN 55,212-2, each point represents the mean standard error;
  • Figure 4 illustrates the response of mouse deferent contraction by the example compound of the present invention, 5- (4-chlorophenyl) -l- (2,4-dichlorophenyl) -3-hexyl-lH-1, 2, 4-triazole, and by the pattern WIN 55,212-2, each point represents the mean standard error
  • Figure 5 illustrates the contraction effect of the antagonist AM 251 and the example compound of the present invention, 5- (4-chlorophenyl) -l- (2,4-dichlorophenyl) -3-hexyl-lH-1, 2,4 -triazole, in the modification of the contractile response of the mouse vas deferens induced by WIN 55,212-2, each point represents the mean standard error.
  • Example 1 Preparation and preparation of 5- (4-chlorophenyl) -3-ethyl-l-phenyl-lH-l, 2,4-triazole
  • the desired compound is prepared according to the embodiment described in step B of Example 1, from 700 mg of compound obtained in step A above, 544 mg of 4-chlorophenylhydrazine, and 284 mg of NaOAc with a reaction time from 28 h.
  • the crude is purified by flash chromatography on silica gel (cyclohexane: AcOEt 7: 1). 113 mg of desired product is obtained.
  • the desired compound is prepared according to the embodiment described in step B of Example 1, from 700 mg of compound obtained in step A of Example 2, 442 mg of 2,4-dichlorophenylhydrazine, and 284 mg of NaOAc with a reaction time of 24 h.
  • the crude is purified by flash chromatography on silica gel (cyclohexane: dichloromethane 1: 1). 94 mg of desired product are obtained.
  • Mp 60-63 ° C.
  • Example 4.- Preparation and preparation of l, 5-Bis (2,4-dichlorophenyl) -3-hexyl-lH-l, 2,4-triazole
  • the desired compound is prepared according to the embodiment described in step B of Example 1, from 1.00 g of compound obtained in step A above, 595 mg of 2,4-dichlorophenylhydrazine, and 433 mg of NaOAc with a reaction time of 26 h.
  • the crude is purified by flash chromatography on silica gel (cyclohexane: AcOEt 9: 1). 84 mg of desired product is obtained.
  • Example 5 Preparation and preparation of l-Benzyl-3-phenyl-5-heptyl-lH-l, 2,4-triazole and l-benzyl-5-phenyl-3-heptyl-lH-l, 2,4- triazole
  • Example 6 Preparation and preparation of l- (4-Chlorobenzyl) -3-phenyl-5-heptyl-lH-l, 2,4-triazole and l- (4-chlorobenzyl) -5-phenyl-3-heptyl- lH-1, 2,4-triazole
  • the desired compounds are prepared according to the embodiment described in step B of Example 5, starting from 73 mg of compound obtained in step A of
  • the desired compounds are prepared according to the embodiment described in step B of Example 5, starting with 100 mg of the compound obtained in step A of Example 5, and 57 ⁇ l of 2,4-dichlorobenzyl chloride, with a time of reaction of 5 h.
  • Example 8 Preparation and preparation of l-Benzyl-3- (4-chlorophenyl) -5-heptyl-lH-l, 2,4-triazole and l-benzyl-5- (4-chlorophenyl) -3-heptyl- lH-l, 2,4-triazole
  • the desired compounds are prepared according to the embodiment described in step B of Example 5, starting with 80 mg of the compound obtained in stage B above, and 34 ⁇ l of benzyl bromide, with a reaction time of 20 min.
  • the residue is chromatographed on silica gel (cyclohexane: AcOEt 9: 1). The two isomers are separated: 94 mg of 1-benzyl-3- (4-chlorophenyl) -5-heptyl-1H-1, 2,4-triazole are obtained.
  • P.f. 4-chlorophenyl
  • step B of Example 5 The desired compounds are prepared according to the embodiment described in step B of Example 5, starting with 100 mg of the compound obtained in step B of Example 8, and 64 mg of 4-chlorobenzyl chloride, with a reaction time from 6 h.
  • the residue is chromatographed on silica gel (cyclohexane: AcOEt 9: 1). The two isomers are separated:
  • Example 10 Preparation and preparation of 3- (4-chlorophenyl) -l- (2,4-dichlorobenzyl) -5-heptyl-lH-l, 2,4-triazole and 5- (4-chlorophenyl) -l- (2,4-dichlorobenzyl) -3-heptyl-lH-l, 2,4-triazole
  • Example 8 and 45 ⁇ l of 2,4-dichlorobenzyl chloride with a reaction time of 6 h.
  • the residue is chromatographed on silica gel (cyclohexane: AcOEt 9: 1). The two isomers are separated:
  • the desired compound is prepared according to the embodiment described in step B of Example 5, from 150 mg of the compound obtained in step B above, and 57 ⁇ l of 2,4-dichlorobenzyl chloride with a reaction time of 5 h. The residue is chromatographed on silica gel (dichloromethane). 166 mg of the desired compound are obtained. MS (ES + ) m / z: 335. Anal. (C 2 ⁇ H 26 N 4 )% found (calculated%) C: 75.71 (75.41); H: 7.79 (7.84); N: 16.54 (16.75).
  • Example 12 Preparation and preparation of 4- (l-Benzyl-5-heptyl-lH-l, 2,4-triazol-3-yl) -l-methylpyridinium iodide
  • dichloromethane a solution of 15 mg of compound obtained in the Step C of Example 11 in 4 ml of dichloromethane is added in excess methyl iodide, and the mixture is stirred for 16 h. After this time the solvent is removed in vacuo, and the residue obtained is purified by flash chromatography (dichloromethane: methanol 9: 1). 14 mg of the desired compound are obtained.
  • Anal. (C 22 H 29 IN)% found (calculated%) C: 55.42 (55.47); H: 6.30 (6.14); N: 11.57 (11.76).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à de nouveaux dérivés de triazol possédant des propriétés cannabinoïdes, plus concrètement des dérivés de 1,2,4-triazol possédant des propriétés cannabinoïdes. De par leur nature antagoniste, les composés de cette invention trouvent des applications thérapeutiques principales qui sont, entre autres, la suppression de l'appétit, la réduction de la dyskinésie provoquée par L-dopa chez des malades atteints de Parkinson, le traitement de la schizophrénie aiguë ainsi qu'une amélioration des dysfonctionnements cognitifs et de mémoire associés à la maladie d'Alzheimer.
PCT/ES2003/000126 2002-03-27 2003-03-18 Derives de 1,2,4-triazol possedant des proprietes cannabinoides Ceased WO2003082833A1 (fr)

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ESP200200740 2002-03-27
ES200200740A ES2192494B1 (es) 2002-03-27 2002-03-27 Derivados de 1,2,4-triazol con propiedades cannabinoides.

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Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1623741A2 (fr) 2004-07-22 2006-02-08 Cadila Healthcare Ltd. LIGANDS DU RECEPTEUR CANNABINOIDE pour moduler LA POUSSE DES CHEVEUX
WO2006050842A1 (fr) 2004-11-09 2006-05-18 F. Hoffmann-La Roche Ag Derives dibenzosuberone
US7129239B2 (en) 2002-10-28 2006-10-31 Pfizer Inc. Purine compounds and uses thereof
US7141669B2 (en) 2003-04-23 2006-11-28 Pfizer Inc. Cannabiniod receptor ligands and uses thereof
US7145012B2 (en) 2003-04-23 2006-12-05 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7144890B2 (en) 2004-01-28 2006-12-05 Hoffman-La Roche Inc. Spiro-pentacyclic compounds
WO2006138657A1 (fr) * 2005-06-17 2006-12-28 Bristol-Myers Squibb Company Heterocycles bicycliques en tant que modulateurs de recepteur de cannabinoide 1
US7176210B2 (en) 2003-02-10 2007-02-13 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7232823B2 (en) 2003-06-09 2007-06-19 Pfizer, Inc. Cannabinoid receptor ligands and uses thereof
US7247628B2 (en) 2002-12-12 2007-07-24 Pfizer, Inc. Cannabinoid receptor ligands and uses thereof
US7268133B2 (en) 2003-04-23 2007-09-11 Pfizer, Inc. Patent Department Cannabinoid receptor ligands and uses thereof
US7329658B2 (en) 2003-02-06 2008-02-12 Pfizer Inc Cannabinoid receptor ligands and uses thereof
US7348456B2 (en) 2002-12-19 2008-03-25 Merck & Co., Inc. Substituted amides
WO2008081205A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr de type pipéridine
WO2008081208A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr pipéridiniques
WO2008081206A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr pipéridiniques
WO2008081204A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes du gpcr de pipéridine
WO2008081207A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr pipéridiniques
WO2009050523A1 (fr) 2007-10-18 2009-04-23 Prosidion Limited Agonistes du récepteur couplé à la protéine g de type azéditinyle
WO2009050522A1 (fr) 2007-10-18 2009-04-23 Prosidion Limited Agonistes du récepteur couplé a une protéine g de type azétidinyle
EP2308840A1 (fr) 2005-06-30 2011-04-13 Prosidion Limited Agonistes de GPCR
US8034949B2 (en) 2004-05-28 2011-10-11 Mitsubishi Tanabe Pharma Corporation Pyrrolidine compound and a process for preparing the same
US8293773B2 (en) 2008-12-04 2012-10-23 National Tsing Hua University 1, 2, 3-triazole derivatives as new cannabinoid-1 receptor antagonists

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Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7129239B2 (en) 2002-10-28 2006-10-31 Pfizer Inc. Purine compounds and uses thereof
US7247628B2 (en) 2002-12-12 2007-07-24 Pfizer, Inc. Cannabinoid receptor ligands and uses thereof
US7576239B2 (en) 2002-12-19 2009-08-18 Merck & Co., Inc. Substituted amides
US7348456B2 (en) 2002-12-19 2008-03-25 Merck & Co., Inc. Substituted amides
US7329658B2 (en) 2003-02-06 2008-02-12 Pfizer Inc Cannabinoid receptor ligands and uses thereof
US7176210B2 (en) 2003-02-10 2007-02-13 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7354929B2 (en) 2003-04-23 2008-04-08 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7268133B2 (en) 2003-04-23 2007-09-11 Pfizer, Inc. Patent Department Cannabinoid receptor ligands and uses thereof
US7145012B2 (en) 2003-04-23 2006-12-05 Pfizer Inc. Cannabinoid receptor ligands and uses thereof
US7141669B2 (en) 2003-04-23 2006-11-28 Pfizer Inc. Cannabiniod receptor ligands and uses thereof
US7232823B2 (en) 2003-06-09 2007-06-19 Pfizer, Inc. Cannabinoid receptor ligands and uses thereof
US7144890B2 (en) 2004-01-28 2006-12-05 Hoffman-La Roche Inc. Spiro-pentacyclic compounds
US8034949B2 (en) 2004-05-28 2011-10-11 Mitsubishi Tanabe Pharma Corporation Pyrrolidine compound and a process for preparing the same
EP1623741A2 (fr) 2004-07-22 2006-02-08 Cadila Healthcare Ltd. LIGANDS DU RECEPTEUR CANNABINOIDE pour moduler LA POUSSE DES CHEVEUX
WO2006050842A1 (fr) 2004-11-09 2006-05-18 F. Hoffmann-La Roche Ag Derives dibenzosuberone
US7220743B2 (en) 2004-11-09 2007-05-22 Hoffmann-La Roche Inc. Heterocyclic CB1 receptor antagonists
WO2006138657A1 (fr) * 2005-06-17 2006-12-28 Bristol-Myers Squibb Company Heterocycles bicycliques en tant que modulateurs de recepteur de cannabinoide 1
US7858639B2 (en) 2005-06-17 2010-12-28 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid-1 receptor modulators
US7632837B2 (en) 2005-06-17 2009-12-15 Bristol-Myers Squibb Company Bicyclic heterocycles as cannabinoid-1 receptor modulators
EP2308840A1 (fr) 2005-06-30 2011-04-13 Prosidion Limited Agonistes de GPCR
WO2008081207A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr pipéridiniques
WO2008081204A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes du gpcr de pipéridine
WO2008081206A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr pipéridiniques
WO2008081208A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr pipéridiniques
WO2008081205A1 (fr) 2007-01-04 2008-07-10 Prosidion Limited Agonistes de gpcr de type pipéridine
EP2377864A1 (fr) 2007-01-04 2011-10-19 Prosidion Limited Agonistes de GPCR piperidiniques
EP2377863A1 (fr) 2007-01-04 2011-10-19 Prosidion Limited Agonistes du GPCR de piperidine
EP2383270A1 (fr) 2007-01-04 2011-11-02 Prosidion Limited Agonistes de GPCR de type piperidine
WO2009050523A1 (fr) 2007-10-18 2009-04-23 Prosidion Limited Agonistes du récepteur couplé à la protéine g de type azéditinyle
WO2009050522A1 (fr) 2007-10-18 2009-04-23 Prosidion Limited Agonistes du récepteur couplé a une protéine g de type azétidinyle
US8293773B2 (en) 2008-12-04 2012-10-23 National Tsing Hua University 1, 2, 3-triazole derivatives as new cannabinoid-1 receptor antagonists

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Publication number Publication date
AU2003215687A1 (en) 2003-10-13
ES2192494B1 (es) 2005-02-16
ES2192494A1 (es) 2003-10-01

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