AU2012211458A1 - Amine derivative having NPY Y5 receptor antagonist activity - Google Patents

Abstract

C \NRPorhl)CC\DAR14'4117 IDOC -X/2012 This invention provides a compound of the formula (1): R1-Y-N-X-N-Z (I) I I a pharmaceutically acceptable salt or solvate thereof, wherein R' is optionally substituted lower alkyl, Y is -S(O)n- wherein n is I or 2, or -CO-, R2 is hydrogen or lower alkyl, R 7 is hydrogen or lower alkyl, X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, and Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like.

Description

Australian Patents Act 1990 - Regulation 3.2A ORIGINAL COMPLETE SPECIFICATION STANDARD PATENT Invention Title "Amine derivative having NPY Y5 receptor antagonist activity" The following statement is a full description of this invention, including the best method of' performing it known to us: C\NRPortb1\DCC\DAR\4494054 I DOC C:NRPonlh\DCC\DAR\J94117_. DOC-K/09/2012 AMINE DERIVATIVE HAVING NPY Y5 RECEPTOR ANTAGONISTIC ACTIVITY This application is a divisional of Australian Patent Application No. 2007244358, the entire content of which is incorporated herein by reference. Field of the Invention [0001] This invention relates to a new compound having NPY Y5 receptor antagonistic activity. The compound is useful as a pharmaceutical composition. especially an anti-obesity agent. Background Art [0002] Neuropeptide Y (hereinafter referred to as NPY) is a peptide which consists of 36 amino acid residues and was isolated from porcine brain in 1982. NPY is widely distributed in the central nervous system and peripheral tissues of humans and animals. [00031 It has been reported that NPY possesses a stimulating activity of food intake, an anti seizure activity, a learning-promoting activity, an anti-anxiety activity, an anti-stress activity etc. in central nervous system, and it may be pivotally involved in the central nervous system diseases such as depression, Alzheimer's disease and Parkinson's disease. NPY is thought to be associated with the cardiovascular diseases, since it induces a contraction of smooth muscles such as blood vessels or cardiac muscles in the peripheral tissues. Furthermore, NPY is also known to be involved in the metabolic diseases such as obesity. diabetes and hormone abnormalities (Non-patent Document I). Therefore, an NPY receptor antagonist is expected as a medicine for preventing or treating various diseases involved in the NPY receptor like the above. [0004] Subtypes of Y 1, Y2, Y3, Y4, Y5, and Y6 have now been identified as the NPY receptor (Non-patent Document 2). It has been suggested that the Y5 receptor is at least involved in the feeding behavior and its antagonist is expected as an anti-obesity agent (Non patent Document 3). [0005] Amine derivatives having sulfonyl group and similar structures to compounds of the present invention and exhibiting NPY Y5 receptor antagonistic activity arc disclosed -1lin Patent Document 1, 2, 3, 4 and the like. Amide derivatives having sulfonyl group and exhibiting NPY Y5 receptor antagonistic activity are disclosed in Patent Document 5, 8, 9, 10 and 11. Derivatives having sulfonyl group and exhibiting NPY Y5 receptor antagonistic activity are disclosed in Patent Document 12. The structures of these compounds are different from those of the compounds of the present invention. [00061 Furthermore, although compounds having similar structures to compounds of the present invention are disclosed in Patent Document 6, 7, 13, 14 and the like, the activities of their compounds are quite different from those of the compounds of the present invention and these documents do not suggest the present invention. [Non-patent Document 1] Tends in Pharmacological Sciences, Vol.15, 153(1994) [Non-patent Document 2] Trends in Pharmacological Sciences, Vol.18, 372(1997) [Non-patent Document 3] Peptides, Vol.18, 445(1997) [Patent Document 1] WOO1/002379 [Patent Document 2] WOOO/064880 [Patent Document 31 W099/055667 [Patent Document 4] WOOO/068197 [Patent DQcument 5] W001/037826 [Patent Document 6] W02006/014482 [Patent Document 71 W02005/097738 [Patent Document 8] W097/20823 [Patent Document 91 US2006/293341 [Patent Document 101 W02007/002126 [Patent Document 11] W02006/001318 [Patent Document 12] W02005/080348 [Patent Document 131 US2007/060598 [Patent Document 141 W02005/121107 Disclosure of Invention [0007] The present invention advantageously provides excellent new compounds having NPY Y5 receptor antagonistic activity. In our examination, compounds in Patent Document 1 or 2 showed the strong induction of a drug-metabolizing enzyme and some compounds in Patent Document 10 showed toxicity such as anemia induction. 2 [0008] The present inventors have intensively studied to synthesize the following excellent new compounds having NPY Y5 receptor antagonistic activity. Patent Document 5 disclosed that amide derivatives having sulfonyl group are compounds having NPY Y5 receptor antagonistic activity. However, the present inventors found that transportability of compounds which the aide is substituted with the amine through the blood-brain barrier is much higher than that of the unsubstituted compounds. Furthermore, the inventors found that compounds of the present invention have less the induction of a drug-metabolizing enzyme compared to compounds described in Patent Document 1 or 2. [0009] The present invention includes the followings. (1) A compound of the formula (I): [Formula 1]

R

1 -Y-N-X-N-Z (I) I I R2 R7 a pharmaceutically acceptable salt or solvate thereof, wherein RI is optionally substituted lower alkyl, Y is -S(O)n- wherein n is 1 or 2, or -CO-,

R

2 is hydrogen or optionally substituted lower alkyl, R1 and R 2 taken together may form lower alkylene,

R

7 is hydrogen or optionally substituted lower alkyl, X is optionally substituted lower alkylene, optionally substituted lower alkenylene, optionally substituted -CO-lower alkylene, optionally substituted -CO-lower alkenylene or a group of the formula: [Formula 2] -(CR 3

R

4 )p-- (CR 5 'R)q wherein R 8 , R 4 , R5 and R 6 are each independently hydrogen or optionally substituted 3 lower alkyl, a group of the formula: [Formula 3] 5 is optionally substituted cycloalkylene, optionally substituted cycloalkenylene, optionally substituted bicycloalkylene, optionally substituted arylene or optionally substituted heterocyclyldiyl, p and q are each independently an integer between 0 and 2, either p or q is not 0, and provided that a group of the formula: 10 [Formula 4] is not a group of the formula: [Formula 51 15 wherein R 14 is optionally substituted phenyl,

-NR

2 -X- may be a group of the formula: [Formula 61 -N U 20 wherein a group of the formula: [Formula 71 - N is piperidinediyl, piperazinediyl, pyridindiyl, pyrazinediyl, pyrrolidinediyl or pyrrolediyl, and U is lower alkylene or lower alkenylene, 25 Z is optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted amino, optionally substituted lower alkoxy, optionally substituted carbocyclyl or optionally substituted heterocyclyl, provided that Z is not fused heterocyclyl consisting of three rings, optionally substituted thiazolyl or optionally substituted quinazolinyl, and 4 provided that a compound wherein X is a group of the formula: [Formula 8] -(CPIR )p- A (CR5R)q wherein a group of the formula: [Formula 9] is optionally substituted cycloalkylene, q is 1, p is 0 and Z is optionally substituted pyrimidinyl is excluded. (2) The compound, pharmaceutically acceptable salt or solvate thereof of (1), wherein R1 is lower alkyl. (3) The compound, pharmaceutically acceptable salt or solvate thereof of (1), wherein Y is -S(0) 2 -. (4) The compound, pharmaceutically acceptable salt or solvate thereof of (1), wherein Z is optionally substituted carbocyclyl or optionally substituted heterocyclyl. (5) The compound, pharmaceutically acceptable salt or solvate thereof of (1), wherein X is a group of the formula: [Formula 101 -(CR 3

R

4 )p

(CR

5 R)q- , and

R

1 is optionally substituted C2 to C10 alkyl. 0 (6) The compound, pharmaceutically acceptable salt or solvate thereof of (5), wherein Z is optionally substituted heterocyclyl. (7) The compound, pharmaceutically acceptable salt or solvate thereof of (5), wherein a group of the formula: [Formula 111 5 0( is optionally substituted cycloalkylene, optionally substituted cycloalkenylene, optionally substituted bicycloalkylene or optionally substituted piperidinylene. (8) The compound, pharmaceutically acceptable salt or solvate thereof of (5), wherein a group of the formula: 30 [Formula 12]

-

A is optionally substituted cyclohexylene or optionally substituted piperidinylene, p and q are each independently 0 or 1, either p or q is not 0. (9) The compound, pharmaceutically acceptable salt or solvate thereof of (7) or (8), 5 wherein Z is optionally substituted lower alkyl, optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyrazolyl, optionally substituted isoxazolyl, optionally substituted oxadiazolyl, optionally substituted pyridazinyl, optionally substituted pyrazinyl, optionally substituted pyrimidinyl or optionally substituted fused heterocyclyl consisting of two rings. 10 (10) The compound, pharmaceutically acceptable salt or solvate thereof of (1), wherein X is a group of the formula: [Formula 13] 3 4 5 6 -(CR R )p- A (CR R )q ,and p+q is I or 2. 15 (11) The compound, pharmaceutically acceptable salt or solvate thereof of (10), wherein p+q is 1. (12) A compound of the formula (I): [Formula 14]

R

1 -Y-N-X-N-Z (I) R2 R 20 a pharmaceutically acceptable salt or solvate thereof, wherein RI is optionally substituted lower alkyl, Y is -S(O)2-,

R

2 is hydrogen or optionally substituted lower alkyl, 25 R 7 is hydrogen or optionally substituted lower alkyl, X is a group of the formula: [Formula 15] -(CR3 R )p- A (CR5R )q wherein R5 and R 6 are each independently hydrogen, 30 a group of the formula: 6 [Formula 16] is optionally substituted cycloalkylene, p is 0, and q is 1 or 2, Z is optionally substituted carbocyclyl or optionally substituted heterocyclyl, and provided that a compound wherein Z is fused heterocyclyl consisting of three rings or optionally substituted pyrimidinyl is excluded. (13) The compound, pharmaceutically acceptable salt or solvate thereof of (12), wherein Z is optionally substituted phenyl, optionally substituted indanyl, optionally substituted pyridyl, optionally substituted pyrindazinyl, optionally substituted pyrimidinyl, optionally substituted pyrazolyl, optionally substituted isoxazolyl, optionally substituted oxadiazolyl or optionally substituted fused heterocyclyl consisting of two rings. (14) The compound, pharmaceutically acceptable salt or solvate thereof of (12), wherein Z is optionally substituted isoquinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzopyridyl, optionally substituted benzopyridazinyl, optionally substituted benzimidazolyl, optionally substituted thiazolopyridyl, optionally substituted benzisoxazolinonyl, optionally substituted benzoxazolinonyl, optionally substituted benzoxadinonyl or optionally substituted benzoxyazepinonyl. (15) A compound of the formula (I): [Formula 17] R'-Y-N-X-N-Z (1) I I R2 R 7 a pharmaceutically acceptable salt or solvate thereof, wherein

R

1 is optionally substituted lower alkyl, Y is -S(0)r,

R

2 is hydrogen or optionally substituted lower alkyl,

R

7 is hydrogen or optionally substituted lower alkyl, X is a group of the formula [Formula 18] -(CR 3

R

4 )p- A (CR 5

R

6 )q wherein R 3 and R 4 are each independently hydrogen, a group of the formula: [Formula 19] 5 is optionally substituted cycloalkylene, p is 1 or 2, and q is 0, provided that 10 [Formula 20] is not [Formula 21] 15 wherein R1 4 is optionally substituted phenyl, Z is optionally substituted carbocyclyl or optionally substituted heterocyclyl, and provided that a compound wherein Z is fused heterocyclyl consisting of three rings, optionally substituted thiazolyl or optionally substituted quinazolinyl is excluded. (16) The compound, pharmaceutically acceptable salt or solvate thereof of (15), wherein 20 Z is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyridazinyl, optionally substituted pyrazinyl, optionally substituted pyrimidinyl, optionally substituted quinolyl, optionally substituted isoquinolyl, optionally substituted benzothiazolyl, optionally substituted benzimidazolyl, optionally substituted benzoxazolyl, optionally substituted thiazolopyridyl or optionally substituted 25 oxazolopyridyl. (17) A compound of the formula (I): [Formula 221

R

1 -Y-N-X-N-Z (I) R 2 R 7 8 a pharmaceutically acceptable salt or solvate thereof, wherein R1 is optionally substituted lower alkyl, Y is -S(O) 2 -,

R

2 is hydrogen or optionally substituted lower alkyl,

R

7 is hydrogen or optionally substituted lower alkyl, X is a group of the formula: [Formula 23] -(CR3 R )p- (CRR )q wherein R 3 and R 4 are each independently hydrogen, a group of the formula: [Formula 24] is optionally substituted cycloalkylene, p is 1 or 2, and q is 0, and Z isloptionally substituted phenyl, optionally substituted pyridyl, optionally substituted pyridazinyl, optionally substituted pyrazinyl, optionally substituted pyrimidinyl, optionally substituted quinolyl, optionally substituted isoquinolyl, optionally substituted benzothiazolyl, optionally substituted benzimidazolyl, optionally substituted benzoxazolyl, optionally substituted thiazolopyridyl or optionally substituted oxazolopyridyl. (18) A pharmaceutical composition comprising the compound, pharmaceutically acceptable salt or solvate thereof of any one of (1) to (17) as an active ingredient. (19) A NPY Y5 receptor antagonist comprising the compound, pharmaceutically acceptable salt or solvate thereof of any one of (1) to (17) as an active ingredient. (20) A compound of the formula: [Formula 25] H S H 2

NH

2 02 a salt or solvate thereof, wherein RI is ethyl or tert-butyl.

(21) A compound of the formula: [Formula 26) 0 R I NH 0-tert-Bu 02 H a salt or solvate thereof, wherein RI is ethyl, isopropyl or tert-butyl. (22) A compound of the formula: [Formula 27] H 2 H

N

3 -C N-Z a salt or solvate thereof, wherein Z is optionally substituted carbocyclyl or optionally substituted heterocyclyl. (23) A compound of the formula: [Formula 28]

H

2 H R15-C2 -Z a salt or solvate thereof, wherein R5 is NH2or OK, and Z is optionally substituted pyridyl, optionally substituted pyridazinyl, optionally substituted pyrazinyl, optionally substituted pyrimidinyl, optionally substituted quinolyl, optionally substituted isoquinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzopyridyl, optionally substituted benzopyridazinyl, optionally substituted benzimidazolyl, optionally substituted benzoxazolyl, optionally substituted thiazolopyridy optionally substituted benzisoxazolinonyl, optionally substituted benzoxazolinonyl, optionally substituted benzoxadinonyl or optionally substituted benzoxyazepinonyl. Effect of the Invention [00101 A compound of the present invention exhibits NPY Y5 receptor antagonistic activity and are very useful as a medicine especially for preventing and/or treating feeding disorder, obesity, hyperorexia, sexual disorder, impaired fertility, depression, epileptic seizure, hypertension, cerebral hemorrhage, congestive heart failure or sleep disorders. 5 Best Mode for Carrying Out the Invention 10011) Each term used in this description is explained below. The each term has the same meaning in this description both when it is used alone each term and when it is 10 used with the other term. [0012) The term "halogen" includes fluorine, chlorine, bromine and iodine. Especially, fluorine or chlorine is preferable. [0013) 15 The term "protective group" in "optionally protected hydroxyl" and "optionally protected hydroxy lower alkyl" includes all of hydroxy protecting groups usually used. For example, acyl such as acetyl, trichloroacetyl and benzoyl, lower alkoxycarbonyl such as t-butoxycarbonyl, lower alkylsulfonyl such as methane sulfonyl, lower alkoxy(lower)alkyl such as methoxymethyl and trialkylsilyl such as t-butyldimethylsilyl 20 are included. [00141 The term "lower alkyl" includes Cl to C1O straight or branched alkyl. Examples are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-buthyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl, n 25 decyl and the like. "Lower alkyl" represented by R1 is preferably C2 to C1O, more preferably C2 to C6 alkyl and most preferably ethyl, isopropyl or t-butyl. [00151 "Lower alkyl" in other cases is preferably C1 to C6 and more preferably C1 to C4 30 alkyl. [0016] The examples of substituents of "optionally substituted lower alkyl" represented by Z are, (1) halogen; (2) cyano; (3) the following groups (i) to (xvi), which are optionally substituted with one or more 35 substituents selected from "a substituents group 6" defined below, 11 (i) hydroxy, (ii) lower alkoxy, (iii) mercapto, (iv) lower alkylthio, (v) acyl, (vi) acyloxy, (vii) carboxy, (viii) lower alkoxycarbonyl, (ix) imino, (x) carbamoyl, (xi) thiocarbamoyl, (xii) lower alkylcarbamoyl, (xiii) lower alkylthiocarbamoyl, (xiv) amino, (xv) lower alkylamino or (xvi) heterocyclylcarbonyl; 5 or (4) a group of the formula: [Formula 29] -W -(CR 10

R

1 1 )s wherein RI 0 and R" are each independently hydrogen or lower alkyl and when this 10 group has two or more of RIO and/or two or more of R", each RIO and/or each R' 2 may be different, W is single bond, 0, S or NR 12 , R1 2 is hydrogen, lower alkyl or phenyl, a group of the formula: 15 [Formula 30] is cycloalkyl, bicycloalkyl, cycloalkenyl, aryl or heterocyclyl, each of which is optionally substituted with one or more of substituents selected from "a substituents group a" defined below and 20 s is an integer of 0 to 4. [0017] In the present specification, "a substituents group a" is a group constituting of (1) halogen; (2) oxo; (3) cyano; (4) nitro; (5) imino optionally substituted with lower alkyl or hydroxy; 25 (6) the following groups (i) to (xxi), which are optionally substituted with one or more of groups selected from the substituents group B, (i) hydroxy, (ii) lower alkyl, (iii) lower alkenyl, (iv) lower alkoxy, (v) carboxy, (vi) lower alkoxycarbonyl, (vii) acyl, (viii) acyloxy, (ix) imino, (x) mercapto, (xi) lower alkylthio, (xii) carbamoyl, (xiii) lower alkylcarbamoyl, (xiv) cycloalkylcarbamoyl, (xv) thiocarbamoyl, 30 (xvi) lower alkylthiocarbamoyl, (xvii) lower alkylsulfinyl, (xviii) lower alkylsulfonyl, (xix) sulfamoyl, (xx) lower alkylsulfamoyl and (xxi) cycloalkylsulfamoyl; (7) the following groups (i) to (v), which are optionally substituted with the substituent:3 group 8, lower alkyl, lower alkoxy(lower)alkyl, optionally protected hydroxy(lower)alkyl, 12 halogeno(lower)alkyl, lower alkylsulfonyl and/or arylsulfonyl, (i cycloalkyl, (ii) cycloalkenyl, (iii)cycloalkyloxy, (iv) amino and (v) alkylenedioxy; and (8) the following groups (i) to (xii), which are optionally substituted with the 5 substituents group 8, lower alkyl, halogeno(lower)alkyl and/or oxo, (i) phenyl, (ii) naphthyl, (iii) phenoxy, (iv) phenyl(lower)alkoxy, (v) phenylthio, (vi) phenyl(lower)alkylthio, (vii) phenylazo, (viii) heterocyclyl, (ix) heterocyclyloxy, (x) heterocyclylthio, (xi) heterocyclylcarbonyl and (xii) heterocyclylsulfonyl. [0018] 10 The preferable examples of the substituents group a as substituents for Ring B are halogen; nitro; hydroxy; optionally substituted lower alkyl wherein the substituent(s) is halogen, cyano, phenyl, carboxy and/or lower alkoxycarbonyl; lower alkenyl; lower alkoxycarbonyl(lower)alkenyl; 15 optionally substituted lower alkoxy wherein the substituent(s) is halogen, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkylamino and/or cyano; acyl; hydroxyimino; lower alkylthio; lower alkylsulfinyl; sulfamoyl; optionally substituted amino wherein the substituent(s) is lower alkyl, optionally protected hydroxy(lower)alkyl, phenyl and/or acyl; 20 alkylenedioxy; cyanophenyl; heterocyclylphenyl; biphenylyl; phenoxy; phenylazo optionally substituted with lower alkyl; or optionally substituted heterocyclyl wherein the substituent(s) is optionally protected hydroxy, mercapto, halogen, lower alkyl, cycloalkyl, lower alkoxycarbonyl, amino, lower alkoxycarbonyl amino, carbamoyl, oxo, phenyl, lower alkoxyphenyl or heterocyclyl. 25 More preferable examples are halogen; lower alkyl optionally substituted with halogen; or lower alkoxy optionally substituted with halogen. [00191 "A substituents group B" is a group consisting of halogen, optionally protected hydroxy, mercapto, lower alkoxy, lower alkenyl, amino, lower alkylamino, lower 30 alkoxycarbonylamino, lower alkylthio, acyl, carboxy, lower alkoxycarbonyl, carbamoyl, cyano, cycloalkyl, phenyl, phenoxy, lower alkylphenyl, lower alkoxyphenyl, halogenophenyl, naphthyl and heterocyclyl. [0020] Examples of the substituents for "optionally substituted lower alkyl" represented 35 by any other than Z (e.g., RI) are one or more substituents selected from the 13 substituents group B. The lower alkyl may be substituted with these substituents at any possible positions. [0021] The lower alkyl part in "lower alkoxy", "lower alkoxycarbonyl", "lower 5 alkoxycarbonyl(lower)alkyl", "lower alkylphenyl", "lower alkoxyphenyl", "lower alkylcarbamoyl", "lower alkylthiocarbamoyl", "lower alkylamino", "halogeno(lower)alkyl", "hydroxy(lower)alkyl", "phenyl(lower)alkoxy", "lower alkylthio", "phenyl(lower)alkylthio", "lower alkoxycarbonylamino", "lower alkoxycarbonyl(lower)alkenyl", "lower alkylsulfinyl", "lower alkylsulfonyl", 10 "aryl(lower)alkoxycarbonyl", "lower alkylbenzoyl" and "lower alkoxybenzoyl" is the same as defined in the above "lower alkyl". [0022] Examples of the substituent(s) for "optionally substituted lower alkoxy" are one or more substituents selected from the -substituents group B. Preferable examples are 15 phenyl, lower alkylphenyl, lower alkoxyphenyl, naphthyl and heterocyclyl. [0023] The term "cycloalkyl" includes C3 to C8 and preferably C5 to C6 cyclic alkyl. Examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. [0024] 20 Examples of the substituent(s) for "optionally substituted cycloalkyl" are one or more substituents selected from the substituents group a and the cycloalkyl may be substituted with these substituents at any possible positions. [00251 The term "bicycloalkyl" includes a group which is formed by excluding one 25 hydrogen atom from a C5 to C8 aliphatic cycle containing two rings which possess two or more of atoms in common. Examples are bicyclo[2.1.0]pentyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl and bicyclo[3.2.Iloctyl. [0026] The term "lower alkenyl" includes C2 to C10, preferably C2 to C8 and more 30 preferably C3 to C6 straight or branched alkenyl having one or more double bonds at any possible positions. Examples are vinyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl. heptenyl, octenyl, nonenyl and decenyl. [00271 35 The "lower alkenyl" part in "lower alkoxycarbonyl(lower)alkenyl" is the same as 14 the above "lower alkenyl". [0028] Examples of the substituent(s) for "optionally substituted lower alkenyl" are halogen, lower alkoxy, lower alkenyl, amino, lower alkylamino, lower 5 alkoxycarbonylamino, lower alkylthio, acyl, carboxy, lower alkoxycarbonyl, carbamoyl, cyano, cycloalkyl, phenyl, lower alkylphenyl, lower alkoxyphenyl, naphthyl and/or heterocyclyl. [0029] The term "acyl" includes (1) C1 to C10, preferably Cl to C6 and more preferably 10 CI to C4 straight or branched alkylcarbonyl or alkenylcarbonyl, (2) C4 to C9 and preferably C4 to C7 cycloalkylcarbonyl and (3) C7 to C11 arylcarbonyl. Examples are formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, pivaloyl, hexanoyl, acryloyl, propioloyl, methacryloyl, crotonoyl, cyclopropylcarbonyl, cyclohexylcarbonyl, cyclooctylcarbonyl and benzoyl. 15 [0030] The "acyl" part in "acyloxy" is the same as the above. [00311 The term "cycloalkenyl" includes a group having at least one double bond at any possible positions in the above cycloalkyl. Examples are cyclopropenyl, cyclobutenyl, 20 cyclopentenyl, cyclohexenyl and cyclohexadienyl. [00321 Examples of substituents for "optionally substituted cycloalkenyl" are one or more substituents selected from the substituents group B. [0033] 25 Examples of the substituent(s) for "optionally substituted amino" are the substituents group 8, optionally substituted benzoyl and/or optionally substituted heterocyclylcarbonyl wherein the substituents is hydroxy, lower alkyl, lower alkoxy and/or lower alkylthio. (0034] 30 The term "aryl" includes a monocyclic of polycyclic aromatic carbocyclyl group and examples are phenyl, naphthyl, anthryl and phenanthryl. "Aryl" includes aryl fused with other a non-aromatic carbocyclyl group, for example, indanyl, indenyl, biphenylyl, acenaphthyl, tetrahydronaphthyl and fluorenyl. Phenyl is preferable. [0035] 35 The aryl part in "aryl (lower) alkoxycarhonyl" is the same as the above. 15 The term "optionally substituted aryl" and "optionally substituted phenyl" represented by Z include the above "aryl" and "phenyl" respectively, which may be substituted with the substituents group a or lower alkyl which may be substituted with one or more group selected from the substituents group a. 5 [00361 Examples of the substituent(s) for "optionally substituted aryl" and "optionally substituted phenyl" represented by any other than Z are one or more groups selected from the substituents group B. [00371 10 The term "carbocyclyl" includes the above "cycloalkyl", "cycloalkenyl", "bicycloalkyl" and "aryl". [00381 The term "non-aromatic carbocyclyl" includes the above "cycloalkyl", "cycloalkenyl" and "bicycloalkyl". 15 [00391 The term "optionally substituted carbocyclyl" includes the above "optionally substituted cycloalkyl", "optionally substituted cycloalkenyl", "optionally substituted bicycloalkyl" and "optionally substituted aryl". [00401 20 The term "heterocyclyl" includes a heterocyclic group containing at least one heteroatom arbitrarily selected from 0, S and N. For example, 5- or 6-membered heteroaryl such as pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazolyl, triazinyl, tetrazolyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl, furyl and thienyl; fused heterocyclyl consisting of two rings such 25 as indolyl, isoindolyl, indazolyl, indolizinyl, indolinyl, isoindolinyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzopyranyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benbzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazoropyridyl, imidazothiazolyl, 30 pyrazinopyridazinyl, tetrahydroquinolyl, tetrahydrobenzothienyl, oxazolopyridyl, thiazolopyridyl (e.g., thiazolo[5,4-b]pyridin-2-yl, thiazolo[5,4-clpyridin-2-yl, thiazolo[4,5 blpyridin-2-yl and thiazolo[4,5-clpyridin-2-yD, benzoxazolinonyl, benzisoxazolinonyl, benzoxazinonyl, benzoxyazepinonyl, oxazolopyridinonyl and benzodioxolyl; fused heterocyclyl consisting of three rings such as carbazolyl, acridinyl, xanthenyl, 35 phenothiazinyl, phenoxathiinyl, phenoxazinyl and dibenzofuryl; and non-aromatic 16 heterocyclyl such as dioxanyl, thiiranyl, oxiranyl, oxathiolanyl, azetidinyl, thianyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, dihydropyridyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiazolyl and 5 tetrahydroisothiazolyl. [0041) "Fused heterocyclyl" fused with a ring other than a heterocycle (e.g., benzothiazolyl), may connect at any possible position. [0042) 10 The substituent(s) for "optionally substituted heterocyclyl" and "optionally substituted fused heterocyclyl consisting of two rings" are the same as those for the above "optionally substituted aryl". [0043] Heterocyclyl parts in "heterocyclylcarbonyl", "heterocyclyloxy", "heterocyclylthio" 15 and "heterocyclyl substituted phenyl" are the same as the above "heterocyclyl". [00441 The term "lower alkylene" includes a bivalent group comprising 1 to 6 of methylene, preferably 2 to 6 of methylene and more preferably 3 to 6 of methylene. For example, methylene, ethylene, trimethylene, tetramethylene, pentamethylene and 20 hexamethylene are included. Tetramethylene is preferable. [0045] "RI and R 2 taken together may form lower alkylene" includes the case [Formula 311 RIS-N- is (Q)n R//S-N (O)n 25 Preferable examples are [Formula 32] and [0046] Lower alkylene part in "lower alkylenedioxy" is the same as the above "lower 30 alkylene". Methylenedioxy or ethylenedioxy is preferable. [00471 17 The term "lower alkenylene" includes a bivalent group comprising 2 to 6 of methylene, preferably 3 to 6 of methylene and more preferably 4 to 5 of methylene and including at least one double bond. [0048] The term "cydoalkylene" includes a bivalent group which is formed by excluding one hydrogen atom from the above "cycloalkyl". A preferable example of cycloalkylene represented by X is 1, 4-cyclohexanediyl. [00491 The term "cycloalkenylene" includes a group containing at least one double bonds in the above cycloalkylene. [0050] The term "bicycloalkylene" includes a group which is formed by excluding one hydrogen atom from the above "bicycloalkyl". Examples are bicyclo[2. 1. 0]pentylene, bicyclo[2. 2. 1]heptylene, bicyclo[2. 2. 2]octylene and bicyclo[3. 2. 1]octylene. [0051] The term "heterocyclediyl" includes a bivalent group which is formed by excluding one hydrogen atom from the above "heterocyclyl". Piperidinediyl, piperazinediyl, pyridinediyl, pyrimidinediyl, pyrazinediyl, pyrrolidinediyl or pyrrolediyl is preferable. Piperidinediyl is more preferable. [0052] The term "arylene" includes a bivalent group which is formed by excluding one hydrogen atom from the above "aryl". Phenylene is preferable. [0053] The term "heteroarylene" includes aromatic groups in the above "heterocyclediyl". Examples are pyrrolediyl, imidazolediyl, pyrazolediyl, pyridinediyl, pyridazinediyl, pyrimidinediyl, pyrazinediyl, triazolediyl, triazinediyl, isoxazolediyl, oxazolediyl, oxadiazolediyl isothiazolediyl, thiazolediyL thiadiazolediyl, furandiyl and thiophenediyl. [0054] One or more groups selected from the substituents group B are examples of ) substituents for "optionally substituted lower alkylene", "optionally substituted lower alkenylene", "optionally substituted cycloalkylene", "optionally substituted cyclohexylene", "optionally substituted bicycloalkylene", "optionally substituted cycloalkenylene", "optionally substituted phenylene", "optionally substituted heterocyclyldiyl" and "optionally substituted piperidinylene". Halogen, hydroxy, lower alkyl, halogeno(lower)alkyl, lower alkoxy, amino, lower alkylamino, acyl, carboxy or lower alkoxycarbonyl is preferable. These substituents may attach to any possible positions. When -NR2-X- is a group of the formula: [Formula 331 5

-

No- U is preferably methylene or ethylene. More preferred is a group of the formula: [Formula 34]

H

2 rC C: -N - -N jC/ -NJ>- or -N

H

2 , H 2 [0055] 10 The compounds of the present invention include any formable and pharmaceutically acceptable salts thereof. Examples of "the pharmaceutically acceptable salt" are salts with mineral acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid; salts with organic acids such as para-toluenesulfonic acid, methanesulfonic acid, oxalic acid and citric acid; salts with organic bases such as 15 ammonium, trimethylammonium and triethylammonium; salts with alkaline metals such as sodium and potassium; and salts with alkaline earth metals such as calcium and magnesium. [00561 The compounds of the present invention include solvates thereof. Hydrate is 20 preferable and arbitrary numbers of water molecules may coordinate to the compound of the present invention. [00571 When Compound (I) of the present invention has an asymmetric carbon atom, it includes racemates, all of enantiomers and all of stereoisomers such as diastereomer, 25 epimer and enantiomer thereof. When Compound (I) of the present invention having one or more double bonds forms an E isomer or Z isomer, Compound (I) includes both isomers. When X is cycloalkylene, Compound (I) includes both of cis isomer and trans isomer. [00581 30 For example, Compound (I) of the present invention can be synthesized by the following methods. Hereinafter, X will be described as -CH2G- or -G-CH2r. 19 [0059] [Compounds wherein Y=S(O)n] [Formula 35]

R

2 1 R2 R2 I R -SO2-Hal 2 i HN .,C0 2

R

1 3 - R I IN ,C0 2

R

13 , R ,,N -CO 2 H Step A 0 0 Step D 0 0 1 3 O Step B 1R2 / Step C R Ha , G c02R3 0 5 R 2 R 2 0 R2 R .,CO2H RHN-Z 7 R, S' ' R G 'GZ R , , I 0 0 Step E 0 0 R7 Step F 0 0 R7 6 8 (I-A) ep G 2R 7 HN-Z 7

R

1 N R 1 N ,C HO -G OH'0S 'G 0 0 Step H 0 0 9 10 5 wherein Hal is halogen, -G-CH2- is the same as -X- in the formula (I), R's is lower alkyl and the other symbols are the same as the above. Step A 10 Compound 1 is reacted with Sulfonyl Halide 2 having the desired substituent RI in a suitable solvent at 0 *C to 50 *C for several minutes to several hours to give Compound 3 wherein n is 2. Examples of the solvent are tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, 15 dioxane, acetone, acetonitrile, water and a mixture thereof. Step B Compound 5 wherein n is 1 can be synthesized by reacting Compound 1 and Sulfinyl Halide 4 having substituent RI. The conditions for the reaction are the same 20 as those of the above Step A. Step C Compound 5 obtained in Step B is oxidized by the usual method to give 5 Compound 3 wherein n is 2. Examples of an oxidizer are m-Chloroperbenzoic acid, peracetic acid, hydrogen peroxide, trifluoroperacetic acid, sodium periodate, sodium hypochlorite and potassium permanganate. The reaction may be carried out at 0 *C to 50 *C. Examples of solvents are tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl 10 acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile, water, methanol, ethanol, isopropanol and mixture thereof. Step D Compound 3 obtained from Step A or C is treated in a suitable solvent and base to 15 give Compound 6. Examples of the base are barium hydroxide, sodium hydroxide, potassium hydroxide, hydrazine, lithium salt of propanethiol. Examples of the solvent are tetrahydrofuran, dimethylformamide, dioxane, acetone, acetonitrile, methanol, ethanol, propanol, water and a mixed solvent thereof. The reaction may be carried out at 0 *C to 100 *C for several minutes to tens of hours. 20 Step E Compound 6 obtained form Step D is reacted with Amino Compound 7 having the desired substituent Z and R 7 in a suitable solvent at 0 *C to 50 *C for several minutes to several hours to give Compound 8. Examples of the solvent are 25 tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile, water and a mixed solvent thereof. An activator such as thionyl chloride, acid halide, acid anhydride and activated ester can be used, if necessary. 30 Step F The obtained Compound 8 is treated in a suitable solvent with a suitable reducing agent to give Compound (I-A). Examples of the reducing agent are sodium borohydride, lithium boron hydride and lithium aluminum hydride. Examples of the 35 solvent are tetrahydrofuran, dimethylformamide, dioxane, acetonitrile, methanol, 21 ethanol, propanol, acetic acid and a mixed solvent thereof. The reaction may be carried out at 0 *C to 100 *C for several minutes to tens of hours. Step G 5 Compound 6 obtained from Step D is treated in a suitable solvent with a reducing agent to give Compound 9. Examples of reducing agent are sodium borohydride, lithium boron hydride, lithium aluminum hydride and diborane. Examples of the solvent are tetrahydrofuran, dimethylformamide, dioxane, acetonitrile, methanol, ethanol, propanol and a mixed solvent thereof. The reaction may be carried out at 0 *C 10 to 100 *C for several minutes to tens of hours. Compound 9 can be obtained through the intermediate such as acid halide, acid anhydride and activated ester, if necessary. Step H Compound 9 obtained from Step G is oxidized by the usual method to give 15 Compound 10. Examples of an oxidizer are m-Chloroperbenzoic acid, peracetic acid, hydrogen peroxide, pertrifluoroacetic acid, sodium periodate, sodium hypochlorite, potassium permanganate, Dess-Martin periodinane, dimethylsulfoxide/oxalyl chloride (Swern oxidation) and ruthenium-catalyst. The reaction may be carried out at -80 *C to 50 *C. Examples of the solvent are tetrahydrofuran, dimethylformamide, diethyl 20 ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile, water, methanol, ethanol, isopropanol and a mixed solvent thereof. Step J 25 The obtained Compound 10 and Amino Compound 7 having the desired substituent Z and R 7 are subjected to reductive amination reaction by a ordinary method to give Compound (I-A). Examples of the reducing agent are sodium borohydride, triacetoxy sodium borohydride and cyano sodium borohydride. The reaction may be carried out at 0 "C to 50 *C. Examples of the solvent are tetrahydrofuran, 30 dimethylformamide, dioxane, acetonitrile, methanol, ethanol, propanol, acetic acid, hydrochloric acid and a mixed solvent thereof. [00601 [Compounds wherein Y=COI [Formula 361 22 R2 R-CO-Ha

R

2 R2 HN ,CO 2

R

13 R N, .,CO 2

R

1 3 R N, ,CO 2 H G G G< Step K Step D Step G 1 12 13 R2 R2 R2

R

1 N1 iR 7 HN -Z 7 1 "0" R G N O, R 'fN I CHO ,R YN 10 ,Z-IN ~G OH - - 'G' 'GCN O Step H O Step J

R

7 14 15 (I-8) wherein each of the symbols is the same as the above and -G-CH2- is the same as -X- in the formula(I). 5 Step K Compound 1 is reacted with Acyl Halide 11 having the desired substituent RI in a suitable solvent at -20 *C to 50 *C for several minutes to several hours to give Compound 12. Examples of the solvent are tetrahydrofuran, dimethylformamide, 10 diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane, acetone, acetonitrile, water and a mixed solvent thereof. Step D, G, H and J 15 The obtained Compound 12 is subjected to the similar method to the above Step D, G, H and J to give Compound (I-B) of the present invention. [00611 [Formula 371 23 0 H Step L 0 H Step M 0 Z N 1 7N RO G H RO G R 7 RO G R7 16 17 18 Step N Z Step 0 Z Step P on- HO G N R7 N G 'N* 19 20 Z Step 0 Z Step R N I

H

2 N G '-'R 7 N N G N H 21 22 z R N G N R2 (I-C) wherein each of the symbols is the same as the above, -CH2-G- is the same as -X- in the formula (I) and R is alkyl. 5 Step L This is the step to introduce substituent RI into Compound 16. For example, Compound 16 is reacted with R 7 X' wherein XI is halogen under the presence of a base to give Compound 17. Examples of the solvent are tetrahydrofuran and 10 dimethylformamide. The reaction may be carried out at a room temperature. Examples of the base are triethylamine, pyridin and dimethylamino pyridin. The compound wherein R 7 is hydrogen in formula (I-C) do not need this step. Step M 15 This is the step to introduce substituent Z into Compound 17. For example, Compound 17 is reacted with ZXI wherein XI is halogen under the presence of a base to give Compound 18. Examples of the solvent are methanol, ethanol, isopropanol and dimethylformamide. The reaction may be carried out at a room temperature or under heating. For example, it can be carried out in a sealed tube by a microwave reactor. 24 An example of the base is N,N-diisopropyl ethyl amine. Step N This is the step to reduce Compound 18 to give Compound 19. An example of 5 reducing agent is lithium aluminum hydride. An example of the solvent is tetrahydrofuran. The reaction may be carried out at a room temperature. Step 0 This is the step to give Compound 20 by azidation of Compound 19. For 10 example, methanesulfonyl chloride is reacted with Compound 19 by using triethylamine as a base to give mesylate. Chloroform can be used as the solvent for the mesylation. Sodium azide is reacted with the obtained compound and azidation is carried out in dimethylformamide or the like at room temperature or under warming to give Compound 20. 15 Step P This is the step to reduce Compound 20 to give Compound 21. It can be carried out by catalytic reduction. An example of the catalyst is 10 % palladium carbon. An example of the solvent is ethanol. 20 Step Q This is the step to a compound of the formula: R'-Y-X 1 wherein X1 is halogen or the like, and Y is S, SO, SO2 or CO is reacted with Compound 21 to give Compound 22. Examples of a compound of the formula: R'-Y-X 1 are various sulfonyl chloride and acyl 25 chloride. Examples of the solvent are tetrahydrofuran and dimethylamide. The reaction may be carried out at a room temperature or under heating. The reaction is preferably carried out under a base. Examples of the base are pyridin and triethylamine. A compound wherein R 2 is hydrogen in the formula (I-C) do not need the subsequent Step R and Compound 22 is a final target compound. This reaction car 30 be carried out with a compound of the formula: RI-Y-XI wherein Y=S or SO to give Compound 22, and then the oxidation can be carried out to transform to a compound wherein Y is S02 used for the next step. Step R 35 This is the step to introduce substituent R 2 into Compound 22. R 2 XI wherein X' 25 is halogen or the like is reacted with Compound 22 under the presence of a base to give Compound (I-C). An example of base is sodium hydride. An example of the solvent is dimethylformamide. (0062) 5 The following intermediates are useful in the above steps. [Formula 381 0 Z Z RO NR7 HO G NR7 18 19 z z N3 N NR7 H 2 N 'N - N-R7 20 21 wherein 10 R is optionally substituted lower alkyl,

R

7 is hydrogen or optionally substituted lower alkyl, G is 1,4-cycloalkylene, and Z is optionally substituted carbocyclyl or optionally substituted heterocyclyl. R is preferably lower alkyl and more preferably methyl and ethyl. Ethyl is 15 especially preferable. Preferable R 7 is hydrogen. Preferable Z is optionally substituted heterocyclyl. The following compounds are especially preferable. A compound of the formula: 20 [Formula 39]

H

2 H

R

1 5 -C N-Z wherein RIO is NH 2 or OH, and 25 Z is optionally substituted pyridyl, optionally substituted pyridazinyl, optionally 26 substituted pyrazinyl, optionally substituted pyrimidinyl, optionally substituted quinolyl, optionally substituted isoquinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzopyridyl, optionally substituted benzopyridazinyl, optionally substituted benzimidazolyl, optionally substituted benzoxazolyl, optionally substituted thiazolopyridyl optionally substituted benzisoxazolinonyl, optionally substituted benzoxazolinonyl, optionally substituted benzoxazinonyl or optionally substituted benzoxyazepinonyl. [0063] [Formula 40] 0 H Step S 0 Pro Stp TPro RO G N R7 RO G R HO G R 17 23 24 Pro t Pro Step W Step~te W tp I N __

N

3 G R7 26 25 Pro H Step X Step Y NlY, 1 GoN, , R N Ry ep R N G R _ H

R

2 27 28 z R 1 N _ _-N -R7 R2 (I-D) wherein each of the symbols is the same as the above, -CHrG- is the same as -X- in the formula (I), R is alkyl and Pro is amino protecting group. 5 Step S This is the step to introduce a protecting group into Compound 17. As a protecting group, the protecting group described in Protective Groups in Organic Synthesis (Theodra W. Greene) or the like can be used. The amino protecting groups which can be removed under the acid condition are preferable. Examples are benzyloxycarbonyl and tert-butyloxycarbonyl. For example, ProXI wherein XI is halogen or the like and Pro is benzyloxycarbonyl, tert-butyloxycarbonyl or the like and Pro-O-Pro wherein Pro is benzyloxycarbonyl, tert-butyloxycarbonyl or the like are 5 reacted under the presence of the base to give Compound 23. Examples of the solvent are tetrahydrofuran and dimethylformamide. The reaction may be carried out at a room temperature. Examples of the base are triethylamine, pyridin and dimethyl amino pyridin. The reaction also can be carried out with a compound wherein R 7 is hydrogen. 10 Step T This is the step to reduce Compound 23 to give Compound 24. Lithium aluminum hydride can be used as the reducing agent. An example of the solvent is tetrahydrofuran. The reaction may be carried out at a room temperature. 15 Step U This is the step to give Compound 25 by azidation of Compound 24. For example, methanesulfonyl chloride is reacted with Compound 24 by using triethylamine as a base to give mesylate. Chloroform can be used as the solvent for the mesylation. 20 Sodium azide is reacted with the obtained compound and azidation is carried out in dimethylformamide or the like at room temperature or under warming to give Compound 25. Step V 25 This is the step to reduce Compound 25 to give Compound 26. Compound 25 is reduced with triphenylphosphine and water to give Compound 26. The reaction may be carried out under heating. An example of the solvent is tetrahydrofuran. Except for the reduction method with triphenylphosphine, the catalytic reduction can be used. For the catalytic reduction, 10 % palladium carbon or the like can be used as catalyst. 30 An example of the solvent is ethanol. The reduction method can be suitably selected depending on the used protecting group. Step W This is the step to react a compound of the formula: R1-Y-XI wherein XI is halogen 35 or the like, Y is S, SO, S02 or CO with Compound 26 to give Compound 27. Examples 28 of the compound of the formula: RI-Y-XI wherein X1 is halogen or the like are various sulfonyl chloride and acyl chloride. Examples of the solvent are tetrahydrofuran and dimethylamide. The reaction may carry out at a room temperature or under heating. The reaction is preferably carried out under a base. Examples of the base are pyridin 5 and triethylamine. This reaction can be carried out with a compound of the formula: R'-Y-X1 wherein Y=S or SO to give Compound 27, and then the oxidation can be carried out to transform to a compound wherein Y is S02 used for the next step. Step X 10 This is the step to remove the protecting group of Compound 27. The method for removing the protecting group can be used by selecting various conditions depending on the protecting group. For example, tert-butyloxycarbonyl can be removed with acid. Benzyloxycarbonyl can be removed by catalytic reduction or the like. 15 Step Y This is the step to introduce substituent Z into Compound 28. For example, ZX' wherein X1 is halogen is reacted under the presence of the base to give Compound (I-D). Examples of the solvent are methanol, ethanol, isopropanol and dimethylformamide. The reaction may carry out at a room temperature or under heating. For example, it 20 can be carried out in a sealed tube by a microwave reactor. An example of the base is N,N-diisopropyl ethyl amine. In the above steps, the following intermediates are useful. A compound of the formula: 25 [Formula 41] 0 Pro Pro Pro RO G 'R7 HO G R7 N 3 G R 7 23 24 25 Pro Pro H N 1 1 1 N NR lY*N ",R7

H

2 N G ''R 7 R N G R R N G N 7 H 26 27 20 wherein 29 R is optionally substituted lower alkyl, Pro is a protecting group,

R

7 is hydrogen or optionally substituted lower alkyl, G is 1,4-cycloalkylene, 5 Y is SO2 or SO, RI is optionally substituted lower alkyl, and

R

2 is hydrogen or optionally substituted lower alkyl. R is preferably lower alkyl and more preferably methyl and ethyl. Ethyl is especially preferable. 10 Preferable Pro is amino protecting group which can be removed under the acid condition. Examples of Pro are the formula: -(C=)-0-R, wherein R is optionally substituted lower alkyl, optionally substituted lower alkenyl. Tert-butyloxycarbonyl is especially preferable. Preferable R 7 is hydrogen. 15 Preferable Y is S02.

R

1 is preferably lower alkyl and more preferably isopropyl and ethyl. Ethyl is especially preferable. Preferable R 2 is hydrogen. The following compounds are especially preferable. 20 A compound of the formula: [Formula 421 H R' N-- NH S / C NH2 02 wherein RI is ethyl or tert-butyl. 25 A compound of the formula: [Formula 431 0 H I R N NH O-tert-Bu 02 wherein RI is ethyl, isopropyl or tert-butyl. 30 A compound of the formula: 30 [Formula 44]

H

2 H

N

3 -C N-Z wherein Z is optionally substituted carbocyclyl or optionally substituted heterocyclyl. 5 [00641 All of the compounds of the present invention have an NPY Y5 antagonistic activity and the following compounds are especially preferable. [00651 In the formula (I), 10 a compound wherein R' is optionally substituted lower alkyl (hereinafter referred to as "R1 is R1 -1"), a compound wherein RI is C1 to C10 alkyl optionally substituted with halogen (hereinafter referred to as "RI is R1-2"), a compound wherein R 1 is C1 to C10 alkyl optionally substituted with halogen 15 (hereinafter referred to as "R1 is Rl-3"), a compound wherein R 1 is isopropyl or t-butyl (hereinafter referred to as "RI is R1-4"), a compound wherein R 2 is hydrogen or C1 to C3 alkyl (hereinafter referred to as "R 2 is R2- 1"), 20 a compound wherein R 2 is hydrogen (hereinafter referred to as "R 2 is R2-2"), a compound wherein X is optionally substituted lower alkylene, optionally substituted lower alkenylene or a group of the formula: [Formula 451 25 wherein a group of the formula: [Formula 461 is optionally substituted cycloalkylene, optionally substituted cycloalkenylene, 30 optionally substituted bicycloalkylene, optionally substituted phenylene or option y substituted heterocyclediyl (hereinafter referred to as "X is X-1"), 31 a compound wherein X is C2 to C6 alkylene, C3 to C6 alkenylene or a group of the formula: [Formula 471 5 wherein a group of the formula: [Formula 48] is optionally substituted cycloalkylene, optionally substituted cycloalkenylene, optionally substituted bicycloalkylene, optionally substituted phenylene, optionally 10 substituted piperidinylene, optionally substituted thiophenediyl or optionally substituted furandiyl (hereinafter referred to as "X is X-2"), a compound wherein X is C2 to C6 alkylene or a group of the formula: [Formula 49] 15 wherein a group of the formula: [Formula 50]

-A

wherein is optionally substituted cycloalkylene, optionally substituted phenylene, optionally substituted piperidinylene, optionally substituted thiophenediyl or optionally 20 substituted furandiyl (hereinafter referred to as "X is X-3"), a compound wherein X is (i) C2 to C6 alkylene or (ii) cycloalkylene or phenylene, each of which is optionally substituted with halogen, hydroxy, lower alkyl or halogeno(lower)alkyl (hereinafter referred to as "X is X-4"), a compound wherein X is C2 to C6 alkylene or to C5 to C6 cycloalkylene (hereinafter 25 referred to as "X is X-5"), a compound wherein X is C3 to C6 alkylene or 1,4-cyclohexylene (hereinafter referred to as "X is X-6"), a compound wherein Y is -SO- (hereinafter referred to as "Y is Y- 1"), 30 a compound wherein Y is -S02- (hereinafter referred to as "Y is Y-2"), a compound wherein Y is -CO- (hereinafter referred to as "Y is Y-3"), 32 a compound wherein Z is optionally substituted lower alkyl, optionally substituted carbocyclyl or optionally substituted heterocyclyl (hereinafter referred to as "Z is Z- 1"), 5 a compound wherein Z is a group of the formula:-(CR R9)r-W-(CRIRI)s-V wherein R8, R 9 , RIO and R" are each independently hydrogen or lower alkyl and when Z has two or more of R 8 , two or more of R 9 , two or more of RIO and/or two or more of R", each of R 8 ,

R

9 , RIO and R" may be different, 10 W is single bond, 0, S or NR 12 ,

R

12 is hydrogen, lower alkyl or phenyl, V is hydrogen, optionally substituted cycloalkyl, optionally substituted bicycloalkyl, optionally substituted aryl or optionally substituted heterocyclyl, r is an integer of 1 to 4 and 15 s is an integer of 0 to 4 (hereinafter referred to as " Z is Z-2"), a compound wherein Z is a group of the formula:-(CH2)r-W-(CH2)s-V wherein 20 W is single bond, 0, S or NR12,

RI

2 is hydrogen or lower alkyl, V is optionally substituted aryl or optionally substituted heterocyclyl wherein the substituent(s) is halogen, hydroxy, lower alkyl, halogeno(lower)alkyl, lower alkoxy, lower alkenyl, amino, lower alkylamino, acyl, carboxy, lower alkoxycarbonyl, 25 phenyl or monocyclic heteroaryl, r is an integer of 1 to 4 and s is an integer of 0 to 4 (hereinafter referred to as "Z is Z-3"), 30 a compound wherein Z is a group of the formula:-(CH2)r-W-(CH2)s-V wherein W is single bond, 0, S, NH or NMe, V is optionally substituted phenyl or optionally substituted heteroaryl wherein the substituents is halogen, lower alkyl, halogeno(lower)alkyl, lower alkoxy, 35 amino or lower alkylamino, 33 r is an integer of I to 3 and s is an integer of 0 or 1 (hereinafter referred to as "Z is Z-4"), 5 a compound wherein Z is optionally substituted carbocyclyl, wherein the substituent is halogen; hydroxy; optionally substituted lower alkyl wherein the substituent(s) is halogen, hydroxy, carboxy, lower alkoxycarbonyl, cyano and/or phenyl; lower alkenyl optionally substituted with lower alkoxycarbonyl; 10 optionally substituted lower alkoxy wherein the substituent(s) is halogen, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkylamino, cycloalkyl, cyano and /or heterocyclyl; cycloalkyl; cycloalkyloxy; acyl; lower alkylthio; carbamoyl; lower alkylcarbamoyl; cycloalkylcarbamoyl; hydroxy imino; 15 optionally substituted amino wherein the substituent(s) is lower alkyl, optionally protected hydroxy(lower)alkyl, lower alkoxy(lower)alkyl, acyl, lower alkylsulfonyl, arylsulfonyl and/or phenyl; phenyl optionally substituted with halogen, cyano, phenyl and/or heterocyclyl; lower alkylsulfinyl; lower alkylsulfamoyl; cycloalkylsulfamoyl; 20 nitro; cyanos alkylenedioxy; phenylazo optionally substituted with lower alkyl; phenoxy; oxo; optionally substituted heterocyclyl wherein the substituent(s) is optionally protected hydroxy, mercapto, halogen, lower alkyl, cycloalkyl, lower alkoxycarbonyl, acyl, amino, lower alkoxycarbonylamino, carbamoyl, oxo, phenyl, lower alkoxyphenyl, 25 halogenophenyl, heterocyclyl and/or oxo; heterocyclylsulfonyl optionally substituted with lower alkyl; heterocyclyloxy; heterocyclylcarbonyl optionally substituted with lower alkyl (hereinafter referred to as "Z is Z-5"), 30 a compound wherein Z is optionally substituted phenyl wherein the substituent(s) is halogen; hydroxy; lower alkyl optionally substituted with halogen, hydroxy, lower alkoxycarbonyl, cyano and/or phenyl; lower alkoxycarbonyl(lower)alkenyl; lower alkoxy optionally substituted with halogen, lower alkoxy, lower alkoxycarbonyl, cycloalkyl and/or heterocyclyl; cycloalkyl; cycloalkyloxy; 35 acyl; lower alkylthio; carbamoyl; lower alkycarbamoyl; amino optionally substituted 34 with lower alkyl, hydroxy(lower)alkyl, acyl, lower alkylsulfonyl and /or phenyl; phenyl optionally substituted with halogen, cyano, phenyl and /or heterocyclyl; lower alkyl sulfamoyl; cycloalkylsulfamoyl; nitro; alkylenedioxy; phenylazo optionally substituted with lower alkyl; phenoxy; oxo; 5 heterocyclyl optionally substituted with hydroxy, halogen, lower alkyl, lower alkoxycarbonyl, amino, carbamoyl, phenyl, halogenophenyl, heterocyclyl and /or oxo; heterocyclyloxy; and/or heterocyclylsulfonyl optionally substituted with lower alkyl (hereinafter referred to as "Z is Z-61, 10 a compound wherein Z is optionally substituted phenyl wherein the substituent(s) is halogen; lower alkyl optionally substituted with halogen, hydroxy, lower alkoxycarbonyl and/or phenyl; lower alkoxy optionally substituted with halogen and/or cycloalkyl; cycloalkyl; cycloalkyloxy; acyl; lower alkylthio; lower alkylcarbamoyl; amino optionally substituted with lower alkyl, hydrcxy(lower)alkyl, acyl 15 and/or phenyl; phenyl optionally substituted with piperidyl; cycloalkylsulfamoyl; alkylenedioxy; phenoxy; morpholinyl or morpholino, each of which is optionally substituted with lower alkyl; piperidyl optionally substituted with hydroxy, lower alkyl, lower alkoxycarbonyl, phenyl, halogenophenyl and/or oxo; pyrrolidinyl optionally substituted with hydroxy, 20 carbamoyl and/or oxo; piperazinyl optionally substituted with phenyl or pyrimidinyl; dihydropyridyl; pyrrolyl; pyrrolinyl; imidazolyl optionally substituted with halogen and/or lower alkyl; pyrazolyl; thienyl; thiadiazolyl; furyl; oxazolyl; isoxazolyl; tetrazolyl optionally substituted with lower alkyl and/or phenyl; indolinyl; indolyl; tetrahydroquinolyl; benzothiazolyl optionally substituted with lower alkyl; 25 tetrahydroisothiazolyl optionally substituted with oxo; benzopyranyl optionally substituted with oxo; tetrahydropyranyloxy; tetrahydrofuryloxy; morpholinosulfonyl optionally substituted with lower alkyl; and/or piperidylsulfonyl optionally substituted with lower alkyl (hereinafter referred to as "Z is Z-7"), 30 a compound wherein Z is optionally substituted phenyl wherein the substituent(s) is halogen, lower alkyl, halogenolower)alkyl, lower alkoxy, cycloalkyloxy, lower alkylcarbamoyl, phenyl, lower alkyl morpholino and/or tetrahydropyranyloxy 35 (hereinafter referred to as "Z is Z-8"), 35 a compound wherein Z is optionally substituted heterocyclyl wherein the substituent(s) is halogen, hydroxy, lower alkyl, halogeno(lower)alkyl, lower alkoxy, mercapto, lower alkylthio, acyl, carboxy, lower alkoxycarbonyl, amino, lower 5 alkylamino, phenyl, naphthyl, phenylthio optionally substituted with halogen, phenoxy optionally substituted with halogen, oxo, and/or heterocyclyl optionally substituted with lower alkyl (hereinafter referred to as "Z is Z-9"), 10 a compound wherein Z is thienyl, pyrazolyl, thiazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, indolyl, isoindolyl, indolinyl, isoindolinyl, indazolyl, benzopyranyl, benzoxazolyl, benzothienyl, benzothiazolyl, benzothiazolinyl, benzothiadiazolyl, benzimidazolyl, quinolyl, isoquinolyl, dihydrobenzofuryl, carbazolyl, acridinyl, dibenzofuryl or thiazolopyridyl, each of which is optionally substituted with 15 substituents selected from the group of lower alkyl; halogeno(lower)alkyl; lower alkoxy; lower alkoxycarbonyl; acyl; lower alkoxycarbonyl(lower)alkyl; mercapto; phenyl, naphthyl, phenylthio or phenoxy, each of which is optionally substituted with halogen; furyl; nitro; oxo; and morpholino optionally substituted with lower alkyl) (hereinafter referred to as "Z is Z- 10"), 20 a compound wherein Z is thienyl, thiazolyl, thiadiazolyl, pyridyl, pyrazinyl, indolyl, isoindolinyl, benzopyranyl, quinolyl, carbazolyl, dibenzofuryl, benzopyranyl, benzothienyl or benzothiazolyl, each of which is optionally substituted with one or more substituent(s) selected from the group of lower alkyl, halogeno(lower)alkyl, lower alkoxy, 25 lower alkoxycarbonyl, acyl, phenyl, naphthyl, phenylthio, lower alkyl morpholino and oxo) (hereinafter referred to as "Z is Z-11"), a compound wherein RI is R1-2, R 2 is R2-2, n is 2 and a combination of X, Y and Z, i.e., (X, Y, Z), is any one of the followings. 30 (X,Y,Z)=(X-3,Y-2,Z- 1),(X-3,Y-2,Z-2),(X-3,Y-2,Z-3),(X-3,Y-2,Z-4),(X-3,Y-2,Z-5),(X-3,Y-2,Z 6),(X-3,Y-2,Z-7),(X-3,Y-2,Z-8),(X-3,Y-2,Z-9),(X-3,Y-2,Z-10),(x-3,Y-2,Z- 11), (X-3,Y-3,Z- 1),(X-3,Y-3I,Z-2),(X-3,Y-3,Z-3),(X-3,Y-3,Z-4),(X-3,Y-3,Z-5),(X-3,Y-3,Z-6),(X-3,Y 3,Z-7),(X-3,Y-3,Z-8),(X-3,Y-3,Z-9),(X-3,Y-3,Z- 10),(X-3,Y-3,Z- 11), (X-4,Y-2,Z- 1),(X-4,Y-2,Z-2),(X-4,Y-2,Z-3),(X-4,Y-2,Z-4),(X-4,Y-2,Z-5),(X-4,Y-2,Z-6),(X-4,Y 35 2,Z-7),(X-4,Y-2,Z-8),(X-4,Y-2,Z-9),(X-4,Y-2,Z- 10),(X-4,Y-2,Z- 11), 36 (X-4,Y-3,Z- 1), (X-4,Y-3,Z-2),(X-4,Y-3,Z-3),(X-4,Y-3,Z-4),(X-4,Y-3,Z-5),(X-4,Y-3,Z-6),(,X- 4,Y 13,Z-7),(X-4,Y-3,Z-8),(X-4.Y-3,Z-9),(X-4,Y-3,Z-10),(X-4,Y-3,Z-11), )(X-5,Y-2,Z- 1), (X-5,Y-2,Z-2),(X-5,Y-2,Z-3),(XK-5,Y-2,Z-4), (X-5,Y-2,Z-5), (X-59,Y-2,Z-6),(X- 5,Y 2,Z-7),(X-5,Y-2,Z-8),(X-5,Y-2,Z-9),(X-5,Y-2,Z-10),(X-5,Y-2,Z-11), (X-5,Y-3,Z-1),(X-5,Y-3,Z-2),(X-5,Y-3,Z-3),(X-5,Y-3,2-4),(X-5,Y-3,Z-5),(X-5,Y-3,Z-6),(X-5,Y 3,Z-7),(X-5,Y-3,Z-8),(X-5,Y-3,Z-9),(X-5,Y-3,Z-10)or (X-5,Y-3,Z-11) the pharmaceutically acceptable salt or solvate thereof [0066] The NPY Y5 receptor antagonist of the present invention is effective for all of the diseases in which NPY Y5 is involved and it is especially useful for preventing and/or treating obesity and suppressing food intake. Moreover, the antagonist is effective for preventing and/or treating the diseases in which obesity acts as a risk factor, for example, diabetes, hypertension, hyperlipemia, atherosclerosis and acute coronary syndrome. Furthermore, a compound of the present invention has not only NPY Y5 receptor antagonistic activity but also any or all good characters as a medicine selected from the followings. a) weak CYP enzyme inhibition b) less induction of a drug-metabolizing enzyme. c) good drug disposition such as high bioavailability. d) low toxicity of anemia-inducing activity or the like. e) high metabolic stability. ) high selectivity for Y5 receptor. g) high water solubility. h) high transportability through the blood-brain barrier. [00671 In addition, the NFY Y5 receptor antagonist of the present invention has a low affinity for NPY Y1 and Y2 receptors, and has a high selectivity for NPY Y5 receptor. NPY causes a sustained vasoconstrictive action in the periphery and this action is p mainly via Y1 receptor. Since Y5 receptor is not involved in this action at all, the NPY Y5 receptor antagonist has a low risk of inducing side effects based on the peripheral vasoconstriction, and is expected to be suitably used as a safe medicine. [00681 The NPY Y5 receptor antagonist shows an anti-obesity effect by suppressing food intake. Therefore, it is one of the features of the present antagonist not to induce side effects such as dyspepsia caused by an anti-obesity agent which inhibits digestion and absorption, or central nervous system side-effects such as an anti-depressant effect due to a serotonin transporter inhibitor that shows an anti-obesity effect. [0069] A compound of the present invention can be administered orally or parenterally as an anti-obesity agent or anorectic agent. In the case of oral administration, it may be in any usual form such as tablets, granules, powders, capsules, pills, solutions, syrups, buccal tablets and sublingual tablets. When the compound is parenterally administered, any usual form is preferable, for example, injections (e.g., intravenous, intramuscular), suppositories, endermic agents and inhalations. Oral administration is especially preferable because the compounds of the present invention show a high oral absorbability. [0070] A pharmaceutical composition may be manufactured by mixing an effective amount of a compound of the present invention with various pharmaceutical additives suitable for the administration form, such as excipients, binders, moistening agents, disintegrants, lubricants and diluents. When the composition is of an injection, an active ingredient together with a suitable carrier can be sterilized to give a pharmaceutical composition. [0071] Examples of the excipients include lactose, saccharose, glucose, starch, calcium carbonate and crystalline cellulose. Examples of the binders include methylcellulose, carboxymethylcellulose, hydroxypropylcellulose, gelatin and polyvinylpyrrolidone. Examples of the disintegrants include carboxymethylcellulose, sodium carboxymethylcellulose, starch, sodium alginate, agar and sodium lauryl sulfate. Examples of the lubricants include talc, magnesium stearate and macrogol. Cacao oil, macrogol, methylcellulose or the like may be used as base materials of suppositories. When the composition is manufactured as solutions, emulsified injections or suspended injections, solubilizing agents, suspending agents, emulsifiers, stablilizers, preservatives, isotonic agents and the like which are usually used may be added. For oral administration, sweetening agents, flavors and the like which are usually used may be added. [0072] Although the dosage of a compound of the present invention as an anti-obesity agent or anorectic agent should be determined in consideration of the patient's age and body weight, the type and degree of diseases, the administration route and the like, a usual oral dosage for an adult is 0.05 to 100 mg/kg/day and preferable is 0.1 to 10 mg/kg/day. For parenteral administration, although the dosage highly varies with administration routes, a usual dosage is 0.005 to 10 mg/kg/day and preferably 0.01 to 1 5 mg/kg/day. The dosage may be administered in one to several divisions per day. [0073] The present invention is further explained by the following Examples, which are not intended to limit the scope of the present invention. The abbreviations used in the present description stand for the following 10 meanings. Me: methyl Et: ethyl i-Pr: isopropyl DMSO: dimethylsulfoxide 15 Pd-C: palladium carbon THF: tetrahydrofuran DMF: N,N-dimethylformamide mCPBA: meta-Chloroperoxybenzoic acid Example 20 [0074] Example 1 Synthesis of Compound (Ii-1) Step 1 [Formula 51] HN 02K 2 C 0 2 N N DMSO CeH4FN0 2

C

13 HjsN 2 0 2 Mot. VL : 141.1 Mot WI. : 234.29 25 3-fluoronitrobenzene (2.00 g, 14.2 mmol) was dissolved in dimethylsulfoxide (15 ml). 3,5-dimethylpiperidine (3.21 g, 28.4 mmol) and potassium carbonate (3.92 g, 28.4 mmol) were added thereto and the mixture was stirred for 3 hours at 150 "C. The reactant was poured into water and extracted with ethyl acetate. The organic layer 30 was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure. Ethyl acetate and hexane were added to the residue. 39 The precipitated crystals were collected with filtration to give the desired substituted nitrobenzene (2.05 g, 62 % yield). 1H-NMR (CDC13) 6ppm: 0.76 (q, 1H, J= 12.0 Hz), 0.96 (d, 6H, J= 6.3 Hz), 1.70-1.91 (m, 3H), 2.32 (t, 2H, J = 12.0 Hz), 3.62-3.72 (m, 21), 7.17-7.25 (m, 1H), 7.34 (t, 1H, J= 8. 1 Hz), 7.59 (d, 1H, J = 8.1 Hz), 7.71 (a, 1H). Step 2 [Formula 52] 2H, Pd-C H2N EtO H

C

13

HION

2 0 2 0 13 H2 0

N

2 MoI l. t.: 234.29 M ol. Wt : 204.31 The compound obtained in Step 1 (2.05 g, 8.75 mmol) was dissolved in ethanol (25 ml) and 10 % Pd-C (0.20 g) was added thereto to carry the hydrogenation reaction for 12 hours. Pd-C was removed by celite filtration and the filtrate was condensed under reduced pressure. The residue was purified by silica gel chromatography to give the desired aniline (1.62 g, 90 % yield). 1H-NMR (CDC13) 8ppm: 0.69 (q, 1H, J = 12.0 Hz), 0.92 (d, 6H, J = 6.3 Hz), 1.75-1.98 (m, 3H), 2.22 (t, 2H, J = 12.0 Hz), 3.53-3.62 (m, 2H), 6.21 (d, 1H, J= 7.5 Hz), 6.38 (s, IH), 6.42 (d, 1H, J = 8.1 Hz), 7.04 (t, 1H, J = 8.1 Hz). Step 3 [Formula 53) UAH4 002H HF 0 O

C

11

H

21

NO

4 S

CI

1

H

23 N0 3 8 Mol.Wt :263.35 Mol. Wt : 249.37 Carboxylic acid (the synthesis method was described in W001/037826) (5.04 g, 19.1 mmol) was suspended in tetrahydrofuran (50 ml) and lithium aluminum hydride (0.726 g, 19.1 mmol) was added thereto under ice-cooling. The mixture was stirred at room temperature for 1 hour and under ice-cooling and water (1.5 mL) was carefully added dropwise. After that, the mixture was stirred at room temperature for 5 minutes and the generated deposit was removed by filtration. The filtrate was condensed under reduced pressure. Ethyl acetate and hexane were added to the residue. The precipitated crystals were collected with filtration to give the desired alcohol (3.15 g, 66 % yield). 5 1H-NMR (DMSO-d6) 8ppm: 0.88 (q, 2H, J = 11.6 Hz), 1.25 (8, 9H), 1.15-1.30 (m, 3H), 1.67-1.76 (m, 2H), 1.83-1.92 (m, 2H), 2.97 (m, 1H), 3.13-3.20-(m, 2H), 4.35 (t, 1H, J = 5.2 Hz), 6.71 (d, 1H, J = 8.8 Hz). Step 4 10 [Formula 541 H~ H N Dess-Martin Ox. N 00 OH CHC1 3 ,.'CHO

C

11

H

2 3

NO

3 S C 11

H

21 NO3S Mol. V .: 249.37 Mol. WI. : 247.35 The compound obtained in Step 3 (500 mg, 2.01 mmol) was dissolved in chloroform (5 ml) and Dess-Martin periodinane (893 mg, 2.11 mmol) was added thereto. 15 The mixture was stirred at room temperature for 1 hour. The deposit was removed by filtration, the filtrate was condensed under reduced pressure. The residue was purified by silica gel chromatography to give the desired aldehyde (385 mg, 77 % yield). 1H-NMR (DMSO-d6) Sppm: 1.26 (s, 9H), 1.13-1.38 (m, 4H), 1.85-1.98 (m, 4H), 2.16 (m, 1H), 3.01 (m, 1H), 6.80 (d, 1H, J 8.0 Hz), 9.54 (s, 1H). 20 Step 5 [Formula 55]

H

2 N N >jH 'O HO THF C I H 21 NOS

C

2 6H 4 IN o 2 S Mol. VIA. : 247.35 MolIWt.: 435.67 25 Aniline obtained in Step 2 (107 mg, 0.523 mmol) was dissolved in tetrahydrofuran (3 ml). Aldehyde obtained in Step 4 (130 mg, 0.523 mmol) was added thereto and the mixture was stirred at room temperature for 1 hour. To the reactant, 41 was added sodium borohydride (23.7mg, 0.628 mmol) and the mixture was stirred at room temperature for 3 hours. The reactant was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure and the residue 5 was purified by silica gel chromatography to give the desired compound (99.3 mg, yield 43 %). 1H-NMR (DMSO-d6) 6ppm: 0.64 (q, 1H, J = 11.6 Hz), 0.87 (d, 6H, J = 6.0 Hz), 0.92-1.08 (m, 2H), 1.25 (a, 9H), 1.15-1.32 (m, 2H), 1.41 (in, IH), 1.58-1.95 (in, 7H), 2.08 (t, 2H, J = 11.6 Hz), 2.75-2.82 (m, 2H), 3.00 (m, 1H), 3.48-3.55 (m, 2H), 5.31 (m, 1H), 5.94 (d, 1H, J 10 = 8.5 Hz), 6.08-6.13 (m, 2H), 6.71 (d, 1H, J 8.5 Hz), 6.85 (t, 1H, J = 8.5 Hz). Melting point: 161 to 162 *C [0075] Example 2 Synthesis of Compound (Ij-1) Step 1 15 [Formula 561 Me 2C ci Me0 2 C ''N CF 3 (,-Pr) 2 NE1

NH

2 i-PrOH N N TsOH H

C

11

H

2 1

NO

4 S

C

14

H

7 FAN0 2 Mol.Wt. : 263.35 Mol. Wt : 302.29 Amine (1.20 g, 3.64 mmol) and 2-chloro-5-trifluoromethylpyridin (727 mg, 4.01 mmol) was suspended in isopropanol (4 ml) and N, N-diisopropyl ethyl amine (1.87 ml, 20 10.9 mmol) was added thereto. After the mixture was in sealed tubes and the reaction was carried out by a microwave reactor for 1 hour at 160 "C. The reactant was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography to give the desired 25 ester (222 mg, 20 % yield). Step 2 [Formula 57] 42 Me 2 Ce CF LAlH Ho c)F i ) MsCl. EtN NCry N TH F N ii) NaNI / D MF H c gH nF3N202 C :H l FN2O C qH 1 6 FaNS MCl. Wt. : 302.29 Mol. WI. : 274.28 M O I. Wt. : 299.29 Ester obtained in Step 1 (207 mg, 0.685 mmol) was dissolved in tetrahydrofuran (3 ml). Lithium aluminum hydride (31.1 mg, 0.822 mmol) was added thereto under ice 5 cooling and the mixture was stirred at room temperature for 0.5 hour. The reactant was poured into iced water and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure to give alcohol. The obtained alcohol was dissolved in chloroform (3 ml). Triethylamine (0.28 ml, 2.04 mmol) was added thereto and 10 methanesulfonyl chloride (0.12 ml, 1.64 mmol) was added dropwise under ice-cooling. The mixture was stirred at room temperature for 1 hour. The reactant was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure to give mesylate. The obtained mesylate was dissolved in dimethylformamide 15 (3 ml) and sodium azide (221 mg, 3.40 mmol) was added thereto. The mixture was stirred for 3 hours at 100 "C. The reactant was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the desired azide (178 mg, 87 % yield). 20 Step 3 [Formula 58] a CFa H2N CF Er5 2 CI 0 .OCF3 H EtOH THF ,H H C lHZLF 3 NOZS C 1 4 IF 3 N5 M ol. W. : 379 44 Mo1. VA : 299.29 25 Azide (178 mg, 0.595 mmol) obtained in Step 2 was dissolved in ethanol (3 mD and 10 % Pd-C (30 mg) was added thereto to carry the hydrogenation reaction for 4 hours. Pd-C was removed by sellite filtration and the filtrate was condensed under reduced pressure to give amine. 43 The obtained amine was dissolved in tetrahydrofuran (3 ml) and triethylamine (0.28 ml, 0.714 mmol) was added thereto. Isopropyl sulfonyl chloride (0.10 ml, 1.64 mmol) was added dropwise under ice-cooling and the mixture was stirred for 1 hour. The reactant was poured into water and extracted with ethyl acetate. The organic 5 layer was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure. The residue was purified by silica gel chromatography to give the desired compound (64.8 mg, 29 % yield). 1H-NMR (DMSO-d6) 6: 0.92-1.06 (m, 2 H), 1.10-1.25 (m, 2H,), 1.22 (d, 6H, J = 6.4 Hz), 1.38 (m, iH), 1.76-1.84 (m, 2H), 1.93-2.02 (m, 2H), 2.81 (t, 2H, J = 6.0 Hz), 3.08-3.19 (m, 10 1H), 3.69 (m, 1H), 6.53 (d, 1H, J = 8.8 Hz), 6.95 (t, 1H, J = 5.6 Hz), 7.16 (d, 1H, J= 7.6 Hz), 7.58 (d, 1H, J = 8.8 Hz), 8.26 (s, 1H) Melting point: 155 to 156 0 C [00761 Example 3 Synthesis of Compound (Ij-1) Step 1 15 [Formula 591 Me0 2 C (Boc)20 Me0 2 C EtbN 'N H 2 C H CH TsOH

C

15 H3NO 5 S C 13

H

23 NO4 Mol. Wt. . 329 41 Mol. Wt.: 257.33 Amine (132 g, 401 mmol) was suspended in dichloromethane (1000 ml under ice cooling. Triethylamine (123 ml, 882 mmol) and (Boc)20 (101 ml, 440 mmoD were 20 sequentially added thereto and stirred for 10 minutes. After that, the mixture was stirred at room temperature for 2 hours and the solvent was removed. The residue wai poured into aqueous citric acid (citric acid. monohydrate 50 g in water 400 ml) to become pH4 and extracted with ethyl acetate. The organic layer was washed with water and dried over magnesium sulfate anhydrous. The solvent was removed under reduced 25 pressure to quantitatively give the target compound. 1H-NMR (DMSO-d6) Sppm: 1.06-1.25 (m, 2H), 1.25-1.43 (m, 2H), 1.37 (s, 9H), 1.75-1.94 (m, 4H), 2.19 (tt, 1H, J = 11.7, 3.9 Hz), 3.07-3.24 (m, 1H), 3.58 (8, 3H), 6.74 (d, 1H, J = 6.6 Hz). 30 Step 2 [Formula 601 44 MeO 2 C~ M.B2C L IH 4 HO H THF H

C

13

H

23 N0 4

C

12

H

23 NO3 Mol. Wt. : 257. 33 Mol. Wt. :229.32 Lithium aluminum hydride (18.3 g, 483 mmol) was suspended in tetrahydrofuran (800 ml) and ester in tetrahydrofuran (300 ml) obtained in Step 1 was slowly added 5 thereto under ice-cooling with stirring over 1 hour. The mixture was stirred under ice cooling for 10 minutes and at room temperature for 2.5 hours. The reactant was ice cooled and the mixture of water and tetrahydrofuran (1:1, 36 ml), 2N aqueous sodium hydroxide (18 ml) and water (18 ml) were sequentially added thereto. The mixture was stirred for 20 minutes and at room temperature for 1.5 hours. The deposit was 10 removed by filtration, the filtrate was condensed under reduced pressure. Ethyl acetate and hexane was added to the residue. The precipitated crystals were collected with filtration to give the desired alcohol (79.5 g, 87 % yield)(through Step 1 to 2). 1H-NMR (DMSO-d6) 8ppm: 0.78-1.00 (m, 2H), 1.00-1.32 (m, 3H), 1.37 (, 9H), 1.65-1.84 (m, 4H), 3.04-3.24 (m, 3H), 4.32-4.42 (in, 1H), 6.66 (d, 1H, J = 7.8 Hz). 15 Step 3 [Formula 611 i) M sCI I THF HO 'N BoC i) NaN 3 /DMF H H

C

12

H

23

NO

3

C

12

H

22

N

4 0 2 Mol. Wt.: 229.32 Mol. Wt. : 254.33 20 Alcohol (79.5 g, 347 mmol) was dissolved in tetrahydrofuran (800 ml). Triethylamine (72.5 ml, 520 mmol) and methanesulfonyl chloride (32.2 ml, 416 mmol) were sequentially added thereto under ice-cooling with stirring and the mixture was stirred for 1.5 hours. The reactant was poured into aqueous citric acid (citric acid monohydrate 30 g in water 500 ml) to become pH4 and extracted with ethyl acetate. 25 The organic layer was washed with water and dried over magnesium sulfate anhydrous. The solvent was removed under reduced pressure. The crystal deposited in the removal process was collected by filtration and washed with hexane to give mesylate (100 g). The obtained mesylate was dissolved in dimethylformamide (100 ml) and sodium azide (63.7 g, 980 mmol) was added thereto and reacted at 80 "C for 2 hours. 45 The reactant was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over magnesium sulfate anhydrous and the solvent was removed under reduced pressure to quantitatively give the desired azide (the crude weight is 85.4 g). 5 1H-NMR (DMSO-d6) 6ppm: 0.90-1.21 (m, 4H), 1.32-1.50 (m, 1H), 1.37 (s, 911), 1.65-1.84 (m, 4H), 3.06-3.24 (m, 3H), 6.71 (d, 1H, J = 8.1 Hz). Step 4 [Formula 62] .BOc H H2N .Boc H THF

C

1 2 1- 2

N

4 0 2

C

1 2

H

24

N

2 0 2 10 Mol. Wt.: 254.33 Mol. Wt : 228.33 Azide obtained in Step 3 was dissolved in tetrahydrofuran (900 ml) at room temperature. Triphenylphosphine (103 g, 392 mmol) and water (90 ml) were sequentially added thereto and stirred at 80 *C for 1.5 hours. The solvent (770 ml) was 15 removed and water (300 ml), ethyl acetate (400 ml) and 2N hydrochloric acid (150 ml) were sequentially added to become pH 2.5 and liquid-liquid extraction was carried out. The organic layer was extracted with 2N hydrochloric acid and the water layer was added thereto. The mixture was washed with ethyl acetate and 2N sodium hydroxide was added to alkalinize and repeatedly extracted with ethyl acetate and chloroform. 20 The organic layer was added thereto and dried over magnesium sulfate anhydrous. The solvent was removed under reduced pressure and hexane was added to the residue. The precipitated crystals were collected with filtration and washed with hexane to give the desired amine (41.7 g, 53 % yield) (through Step 3 to 4 ). 1H-NMR (DMSO-d6) 8ppm: 0.77-0.96 (m, 2H), 1.00-1.18 (m, 3H), 1.37 (s, 91H), 1.67-1.82 25 (m, 4H), 2.30-2.38 (m, 2H), 2.90-3.60 (m, 2H), 3.05-3.22 (m, 1H), 6.66 (d, 1H, J = 7.2 Hz). Step 5 [Formula 63] 46 0 0 0 0 F N C . cI >tN ) ,. 'N 8 Q H2N NBoc HEtaN H THF H C12H24N202

C

1

OH

30

N

2 0 4 S Mol. Wt. : 228.33 Mol. Wt.: 334.47 Amine (37.5 g, 164 mmol) was suspended in tetrahydrofuran (400 mo. Triethylamine (91.7 ml, 656 mmol) and isopropyl sulfonyl chloride (32.2 ml, 416 mmol) 5 were slowly and sequentially added thereto at -55 to -40 "C with stirring. The mixture was stirred for 6 hours with gradually warming to 0 C. The reactant was poured into the ice-cooled dilute aqueous acid and extracted with ethyl acetate. The organic layer was washed with water and dried over magnesium sulfate anhydrous. The solvent was removed under reduced pressure and isopropyl ether was added to the residue. The 10 precipitated crystals were collected with filtration and washed with isopropyl ether to give the desired sulfonamide (43.1 g, 79 % yield). 1H-NMR (DMSO-d6) 6ppm: 0.79-0.98 (m, 2H), 1.00-1.36 (m, 3H), 1.20 (d, 6H, J = 6.6 Hz), 1.37 (a, 9H), 1.70-1.84 (m, 4H), 2.72-2.80 (m, 2H), 3.04-3.22 (m, 2H), 6.68 (d, IH, J 8.1 Hz), 6.94 (t, 1H, J = 6.0 Hz). 15 Step 6 [Formula 64] 0 0 0 0 N HCIIdiaxane N . *9C MeOH H K)**H H HCI

C

1 5

I-IN

2 0 4 S ClOH 23

CIN

2 0 2 S Mol. Wt.: 334.47 M ol. Wt : 270.82 20 Boc-protected amine (43.0 g, 128 mmol) was suspended in methanol (200 ml) and 4N hydrochloric acid in dioxane (96 ml, 384 mmol) was added thereto under ice-cooling with stirring for 20 minutes and at room temperature for 3 hours. The reactant was ice-cooled and isopropyl ether (220 ml) was added thereto. After stirring for 30 minutes, the precipitated crystals were collected with filtration and washed with 25 isopropyl ether to give the desired amine hydrochloride (30.8 g, 89 % yield). 1H-NMR (DMSO-d6) 6ppm: 0.85-1.02 (m, 2H), 1.20 (d, 6H, J = 6.6 Hz), 1.20-1.40 (m, 3H), 1.75-1.84 (m, 2H), 1.90-2.00 (m, 2H), 2.73-2.82 (m, 2H), 2.83-2.97 (m, 1H), 3.08-3.20 47 (m, 1H), 7.01 (t, 1H, J = 5.7 Hz), 8.01 (s, 3H). Step 7 [Formula 65] -4 O O cCF3 0 > 0 0 0i t N (6Pr)2NEt N C Wj NMP H N HCI O ClOH 23

CIN

2 02S CsH2 4

F

3

N

3 0 2 S Mol. Wt.: 270.82 Mo1. W.: 379.44 Amine (190 mg, 0.700 mmol) and 2-chloro-5-trifuluoromethyl pyridin (1.27 g, 7.00 immol) were suspended in N-methyl pyrrolidone (4 ml) and N,N-diisopropyl ethyl amine (1.25 ml, 7.00 mmol) was added thereto. After the mixture was in sealed tubes and the reaction was carried out by a microwave reactor for 20 minutes at 210 *C. The reactant was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulphate anhydrous. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography to give the desired Compound (Ij-1) (158 mg, 60 % yield). (0077) In Step 5, ethanesulfonyl chloride instead of isopropyl sulfonyl chloride was reacted to give the following compound wherein R' is ethyl. [Formula 661 0 0 N H

C

1 4

H

28

N

2 0 4 6 Mof. Wt.: 320.45 20 1H-NMR (DMSO-d6) Sppm: 0.80-0.98 (m, 2H), 1.02-1.18 (m, 2H), 1.17 (t, 3H, J = 7.2 Hz), 1.22-1.34 (m, 1H), 1.37 (s, 9H), 1.68-1.82 (m, 4H), 2.68-2.78 (m, 2H), 2.96 (q, 2H, J = 7.2 Hz), 3.04-3.22 (m, 1H), 6.68 (d, 1H, J = 8.1 Hz), 6.94 (t, 1H, J = 6.0 Hz). [00781 .5 In Step 5, tert-butyl sulfinylchloride instead of isopropyl sulfonyl chloride was reacted and the oxidation with mCPBA was carried out to give the following compound wherein R1 is tert-butyl (W02001037826, Example 3). 48 [Formula 67] 0 0 0 rrCPBA >rH N. Boc *H ,*-N'BOC H H

C

1 8

N

32

N

2 0 4 6 Mol. VV. :346.5 1H-NMR (DMSO-d6) 6ppm: 0.79-1.00 (m, 2H), 1.01-1.20 (m, 2H), 1.22-1.34 (m, IH), 1.25 5 (s, 9H), 1.37 (s, 9H), 1.70-1.86 (m, 4H), 2.81-2.90 (m, 2H), 3.04-3.22 (m, IH), 6.68 (d, 1H, J = 8.1 Hz), 6.83 (t, 1H, J = 6.0 Hz). [0079] The following compounds wherein RI is ethyl or tert-butyl was obtained in Step 6 by using the above compound. 10 A compound wherein RI is ethyl. [Formula 68] 0 0 H 4N -NH2 HCI C H 21 ClN 2 0 2 6 Mol. W .: 256.79 H-NMR (DMSO-d6) 6ppm: 0.84-1.02 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.20-1.40 (m, 3H), 15 1.74-1.82 (m, 2H), 1.90-2.00 (m, 2H), 2.72-2.80 (m, 2H), 2.83-2.96 (m, iH), 2.97 (q, 2H, J = 7.5 Hz), 7.04 (t, 1H, J = 6.0 Hz), 8.03 (s, 3H). A compound wherein RI is tert-butyl [Formula 691 0 O , NH2 HCI CjI H4CIN 2 026 20 Mc1. Wt.: 284.85 H-NMR (DMSO-d6) 6ppm: 0.84-1.04 (m, 2H), 1.16-1.38 (m, 3H), 1.26 (s, 9H), 1.74-1.84 (m, 2H), 1.92-2.02 (m, 2H), 2.82-2.98 (m, 3H), 6.90 (d, 1H, J = 6.0 Hz), 8.01 (s, 3H). 49 (0080] The following compounds synthesized in similar methods also include the present invention. [0081) 5 [Formula 70] 50 H 1-12 H H - a N N Me 2 N 1-2 C 1-13 H 00 H H H I-3 1-14 N - N 1..4 ,L1-15 H H 1-5 S 1-16 s HHH -6 L N 1-17 O H o I-8 1-19 AN N O '. HH H I-9 I-20 NN I-10 N1-216 I-11 N1-22 [Formula 71] 51 H oo 1-23 -IS N-% 1-34 00N 000 1 000 I-24., I-35 X H 1-25 H -36

O

0 0 H 1-26 >rS N N 1-37 N H 0%0 1-27 N 1-38 N H H OMe s N <H 1-28 >lN N 1-39 0N o0 ,LH H H Ci N H 1 .2 9 N - - - N C1 - 4 0 o b NN 1-30 os 141 -,N > ,O H N 1-30 0 SN 1-41 ob 0", 1-31 s I-42 0 H1Q 1-2N I-32 00 1 -43 db N mm CN 1-33 SNK NbN H [Formula 721 52 HH '04H 1-56 H OMe 1-47 1-57 , N-48 1-59 1-47 11-60 I-SO "N j 10-61 T 1-53, ' H 1 -59 N HH 1-49 AS N 1-605 N H 1-51 000 H 1-62 -,4,L 0 _N 0 1-53 , 1-6 53 Nl I-68 H I-8 1-69 6b -0 H NT NN 1-68 e1-81 _) .H I-71 .N I-83 N

NH

2 - 7 2 ' : b ~ H- 8 4N I-73 )N NmN 1 -85 H~1.NM NM I-74 ~ ~ ~ -HCI 8 H -NH2 I -7 5 6 N O H H N I-76 o2H H 1- 0 HO1 2 e'., 117I-90 6N

NH

2 ,)_N H [Formula 741 54 1-91 ST s N 1-103 00 1-92 C 6 N 1-104 N 1-93 6SHN N SO N Me H I-4 c N I-106 Cl N I-95 I-1Me07S~ I-9 6 00N 1-10 6 N NF N I-9 0 N N -1 1-99 O N' I-100 H I 1-101 1-1 i H 1-102 UN H 00 N [Formula 751 H )~~~~~ I-1H NI-2 -. H H H 1-115 L N N 1-127 00 .. N ob 0 H H LN O O32H SMe 1-117 - 1-12 H H 1.118 N N1-130 00 - N CN H Me 1-119 N N Cl 1-131 0B I-120 HI0-132 00 O >LH H N F H I118 N 1-133 d0 -A c I-122 1-134 0 -N O doC I-123 I -135 00 CC H S 1-125 I0 0 N 0 N S H 1-13 1 0 N C N H 1-126 N CF 2

CHF

2 1-13 [Formula 76] 56 H H 1-139 1-151 >'H J_151I ci H H CF 1-140 ) 1-152 rN 0 o N 52s 1-141 PN.r S JC 1-153 H 00 .lN) N' W OH OMe M e 1-142 >' Q sjO 1-154 O(Q .NH

HN

F Fo -4 >Le ~ 1 -1586 oO..~ NNHp 9 1-143 6 D OMs 1-158 OMe ,~H H j 1-148 -160 4 9 Q L70 1-161 o o HjH 11450 oO L-N 1-162 N I-150 I-162 [Formula 771 57 1-163 Li ., H -173 I-164 1174 6C 2 1A65 OH 1-175 HO 1-166 OH -176N HO I-167 1-177 N 0C02H I-169 N N O 790 N O CN I-10 N-178 0 1-16 N db 0 1-179 b N 0,0M 1-172 0 1-182 N 1-171 ~ f J~2 N NO0 >1-sr HO 1-168 >L1N18 1-179 NH0 2 -,-C 1-17 00 N 0 1-182 00 C0-Ne [Formula 78] 58 1-183 I -193 OMe 1- 1 8 4 I H N 1-1 9 4 N Oe 1-185 1-195 N

C

2 Me I-186 I-196 o~~Et 00 --- N K>0Et H 1-1867 , ~bc~.c 0 ~1-196 o&.,,NOK 1-189 .e2 1-199 LH0 N _>Iao 1 I-190 I-200 Ss > II~ CN I-191 0v- 0I-0 1-192 0Q HI-202 N OC 9 N HOCH 3 [Formula 79] 59 1-20 b 111NKCONH, 1-211 N 1-204 ->IN H1-212 11 N -\ H H -- \HH 1-205 1.N -1 00b (N C0H 1-214 0'0 H H 1-207 NS.. Q~Q~ H 1-215 Hb 1-208 2~N d'NH 00K2HN~ 1-216 N H N~ SN N 1-209 6 1-2 17 0'b "OS0 2

NH

2 NI O H Hy 1-210 e ,.N1-218 o b a N H 1-219H 1-220N [Formula 80] 60 1-227 QF 1-228 0 H -j-S N I-229 6 N 1-230 1-231 L-N,, 1-232 N 1-233 N H ~No 1-234 N N ON H y~ 1-235 N N H OMe 1-236 H:Me H 01OEt 1-237 0 KN [Formula 81] 61 H H 1-238 6 N-249 6 H 1-29 1-239 6 I-250 H H H N NH 2 I-240 61-251 N 0 0 '~NN NH2 N~ H I-243 6 -254 0 N I-245 6 1-246 1-257 0 H NH I-247 4- I258 H HN 1-248 I-259 0 b"- ~1-259NO [Formula 821 62 H I-261 N -272 Me N 00 H2 H H I-263 0-24 N00O I-264 S N Me-O7e KOTB HH I-265 N 1-273 0 0 1-261 H O 1-27N H 'QNJ 00 \N H H 1-266 NN 1-277 00 CO2 1 Me SHO H-6 H H I-267 H 1-278 00 H CO2H N 1-268 I-279 N H H 0 0 1-269 OHb 1-27 N SMe NQOH I-270 1-7 [Formula 83] 63 1-282 H 1-293 tS N H S 00 C 0 0CI, '\ 00e 00 H N OMe H C N 'gN 1-283 N Me 1-294 0 0 H crr H 1-284 SN 1-295 N M Hb-- Ome 00 N eC 2 Me 1-285 S H H 1-296 0 1-286 H -297 >N 00 S N 0 NNH H 1-299 H I-288 0S N 00 H H N O0M -289 0 H -300 H 0 N NNU 1-290 HN -301 00 H s H I-291 s 1-302 00o H 00 H 0 NmN HH 1-292 1-303 'HSN 00 0 H tFormnula 84] 64 HH >LSN CF 3 S H 1-304 0o0 -, 1-315 00 1.305 00 N I-316 00 N I-306 1 -317 NO H~s H I-307 0 I-318 0 N H 1-308 00 H 1-319 0 0 N OH NN Me I-313 N 1 -324 0 HoNH N MO 1-303 00 H 1-3174 00 H N 0C 2 M [Formula 85] 65 1-30 00 0 1318 .C1 -N -- \-Nw1 1-326 00 H 1-337 00o H N (> C0 2 H N 2 1-327 N1-338 00N 1-328 0 0 OQ.0CozMe 1-339 o o ~ i 00 \ H )-34 ~ N OM@M 1-329 N O&0C0 2 H 00O-~ Me -30NO N e 2 1-3401 0 -\ , c(:(NMe2 H :SN )H 1-3N0 1-343 )L6 1-3 00 H OC 1-342 wL H 1-3 3 LN HH-4 0 y~ 1-332 N 1-343 00 -- , 1-336 \ 1-344 0NCM [Fomul 86] 66 0 1-348 00 N H I-357 s N CONH N OEt I-349 000I-38 I-350 'OH -359 H H sN 1SO2 2 0 CN^Y N N SN 0 C S I-3550 N C I-364 o" ba HOCH N I -35 N o'b H 0 N 1-3 521 00 ~ -6 H SOe H N H 1-353 Io H HH 1-354~~ 0 1-l cI:) 1-363 N :sNCI H 8 H

H

3 0b N DC0NH 2 H N 1-355 ->L6 N' 1-356 N~~ H 00 1-365N H o'b N1

G

N N [Formula 871 67 'I H H H H db O,'b HH H 1-367 N YQ 1-378 _SH HHH 1-3 68 N 1-379 I I 0C 0 'LSH 1-37H 1-380 1 N 00O' _H H 1-3702 1-3813 HH 1373 0 1-3842o' N 1-34 H H 135KA~ N ~ ~ ~ K 1-8 t 1-375- 1-8 bH H' H 1 0 1-38 )~N NZ0M 1-376 H 00N [Formula385 0, b 0 ' b 68 1-38 b 1-399 b b NN 1-389 s ca N b 1-400 tN-N OMe ~b-sJ 0 OMe I-390 H H c5 O'( 1-401 bN) OEt H 0 H H 1-391 N C-402 H H 1-392 H H H H N N 403 0N N NH 2 1- ~H H -393 Ls N ci' >NCQ 1-404 T H H 1 -3 9 4 - N N 'O 0b N I-405 N H H I-395 NN N N ' N N cl cl0 1-396 H r S H-~ -N ~ 2HCI s' -408 00 N&N8 H H 1-397 H1-408, -398 1-409 60 6 b lo (Formula 89] 69 H H H H H IH 1-410 Ob ~ 1-421 b N C ON2H , ' HN H -0 N-O NH2 1-412 s 1-423 1-413 - 1-424 H H~M e I-415 H NJOTBS O-2 H~. Me OTBS 1-416 L, 1-425 HCI-,-N a H H I-417 N I-418 N N Me I-419 1-2 H H H 1 -4 2 0 H N C 2 [Formula 90] 70 H H ,JSN N CI H H 0 1-432 IA la 1-44 sN N H H H I-433 00 N N N 1-445 N O0O 1-43 H HH H 1- 34 0 0N -1H4CN I-35 s CF 2

CHF

2 14 00 s 00 H H 1-436 L N N CC2H21447g 00 00N,,, I-437 IH S~ -449 I-438 H IA450 N 00 00 I-439 H 451sN CN H H NN H H CO 2 Me 1-440 N I-452 SN N CO 2 Me 00 00 44 H HOH eJ 1-441 S N N 1-453 H HO 00 N N0 IA442 0H0 1-454 s I-443 0 1-455 0 00 NN [Formula 911 7] H H H) 1-456 N 1-467 0 0 ~OMe H H H H -4 SN N O 1-457 S 1-468 00 00 0 H H~ 1-458 S 1-469 OS O,-O4 HCI 0NN0OH H H c 1-461 N0-472 0O H H~~ OiHH 1-462 SO OH 00 SMe0 1-463 H 1-474 N N O H 00 0 H HOH H O H 1-464 SN N N -475' SN 00 H OH0 H HH I-465 N N-476 00 0 1-466 N N N 1-477 0tS,^J-iN 0 00 [Formula 92] 72 1478 NP ,N01489 t Me 1-479 tS NO2 1-490 H H 0 N N 1-480 00 -491 N OO I-482 00 CO2M I9 N I-482C02H 1-493 00b I-483 H 1494s OMe I-484 s ~N y Oo.C2Me I-495 I-485 N 0SC 2 H H96 H N e2 1-486 0S N( O NMe 1-497 H N I-487 N O8CN 1-488 1 N-499 iSN [Formula 931 73 IH H fOME 1-500 N N 1-510 , ~ ' *I1% H HQOe 0-H H 1-5012 ,,, I 1-5112 L -- _ OH 0' r~OMe 0b H HOH-1 1521-5 15 " ~H HH b'N H H N- H 1-515N6, 1-505 H H~' OC H 3 0 HH 1-507 0, b CCN 1-518 oO(b

CF

3 H HH H N-o j~N-N 0 151N - z"& 112150-58 1-509 _ N--- H(yCONH2 1-520 b [Formula 941 74 I-521 I~ -532 s Hm I-532 H sm AN H H 1-525 1-536 )sNQ H H 1-525 N N 1-537 H H N N 1-528 d N -539N H H 1-524 _SCN ,L H-3 N I-529 -540 H 1-5359 b a N S d b 3o N HKO 1-5259* 1-5460 1-530 1 N N I-531 7 [ Formula 95] 75 HH N OS N NCOMe 1-545 N O 1-556 N O~t H H a -546N 1-547 s1-558 N N I-5 8 sN -559 NH2~ N N I-549 I-560 sa t,_N Y'e -500N I-56 C151 1 HN 1-551 0 N OI 2H HH N NH2 HP H 0. I-552 1-53 O N -0 N N 00 I-553 -sN I-564 . N bFormula 96) 76 1-565 N I ( H H NN0 1-566 I- 1-577 b N SNH2 I-567 M 1-568 s I-579 -Y NN H H H I-6 1 -580 - N Me I-570 N.~~ OTBS I-581 S ~H, OMe H y,~OTBS H HC 1-571 O - Id -582 N H N H I-572 b N1-583 S H N N I-573 O' ~N N Me I-584 I-574 N'.0 1-585 H QN~OHO~YQ~~Nc1OMe HOH 1-575 f N [Formula 97] 77 H H 1-587 L0 N 1-599 sN H I-58 EO H I6 00 0 N H H 1-589 -LsN H 1-600 H 00 N H C I-592 00N 1-601 H 1-590 N,ON 1-591 N 1-602 0 00 ON CF2CHF2 I-9 H I-606 1-592 SN 1-603 H S -59 7 H 1 -60 8 iS N CO2M S0 N-60 0 N0 N 1-5935 S 1-606 "LSN<H S 00a CNe N fX)r 1-594 H Me1-6057N ,IS N H&00 ON.0 1-595 -0 8Sa 00609 00 -N [Formula 98] 78 HH 1-610 s 621 sO OSOQNI 1-6 0021 0O N O e 1 0 H~ H 1-611 H 1-622 S N H C F3 I-28N N-NH H 1-612 H 1-623 0 N I-618 OH OON OMe H H I-63 N H 1-613 N H OO N 00 NQO' 0 1-614 S H 1-625 O O N O O H N0 N N O OO~NNJO 1-615 "L N' H K ci 1-62 6 "Ls N H 00 Ns0 0 a-&No,-- 1-616 H 1-627 S a 00 OHN CI 00 OONQOOMe H S -N, H C F 3 1-628 LN H 1-617 ), H (N0 , ~ 1-629 1-618 tsN H00 SMe H H1-630 , 5 NaH OH 1-619 N H0 H1-631 'J N H 1-620 OO1ts N H 00 N, OH H S-N [Formula 991 79 Ha NN ~ h I-31 -644 0N ,CN N O I-634 I-646 H Me I-635 00 aNnOI670 H MeN OJ 1-6457 1-636 00 N O 1-648 S 0 >HST N T0 0 KKNA2 I-637 O "j1NH 2 I-649 I-638 O1OM -650 )%SKJ' N 1-639 0 C2 1-651 I-640 0 I-652 00 H H0 0 Me I - 6 4 1 O ON C 2 M e I - 5 3 ee 1-642 0SO CO 2 H 1-654 0 NMe2 1-643 00 2 N lO -NMe 1-655 N ,)IS H [Formula 100] 80 , 1-656 00 1 I-668 d 6 CONH 2 1-657 o o 1-669 I-658 0N H Me

ONH

1-65 00O NN1-670 o b H UH 1-659 O e 1-671 1-660 0 N 1-672 N N O2Me N 1-661 0 0 1-673 N N 1-662 o 0 1-674 o N "LSM u , ,-, SO2NH2 1-663 000 1-675 H NOH 0 HiH I-664 0 a (^0 I[-676 db N,,j 60 0 K.A-N Q i - OCH 3 IrOCH 3 OCH3 1-665 1-677 O'bO c F 3 1-6 6 6 N ' Y 1-67 8 O N F NN 1-667 6b Ocioj 1-679 NH [Formula 101] 81 1-680 >j1-690 Na,.H J~OAc Me 1 H s 1-68 a <H) 1- 691 > H 1-682 . NNaHO H-9 00686 1-696 , ~OtN~N H~ NHMe 1-683 00 ~a H 1-698 Nc i 1-6939 L 1-684 ~ N O0E [Frml 10218M H8 1-700 N F 1-710 I-70 S N O- ONH2 HH 1-701 -'2k [-711c1.NJhs C1-71 H OEt H Me 1-702 S ' JN jO I-712 SN H COOH H 1-7 0 3 0 N I-7 13 N S S 00 N N NH 00 S S I-705 0 Et I-715 s H iPrH I-706 N-716 NQ LEt I-707 00 I-717 N CH2OH 1-708 1-718 00 M SNH 2 1-7096 L I-719 [Formula 103] 83 060 RN O kNcJC02Et N O'- 1-722 1-7320 HH 1-723 LSNaH 1-733 -, s N H 0-0 N N 00 O N O CNMe - 7 2 5 N, S N I -72 NH S-3 0 H O C -72 7 N 1-734 00 00 1-728 H 1-738 N 00 NON~ a N 0 0-0 1-724 1-73471 HCr 1-725 IaJ 1-7358_ Sa 00 N 00 J0-- 1-729 N1739 [Formula1041 84 H H 1-740 - O HO 1-5 ,>Na H Me 1-750-- -CO 1-741 H1-751 HH~

O

2 NXCN ON CONMe, N 0-' 1-742 H 752 00 O N SH -73 H H_ 173 N H1-753 > SNN~ 0 1-744 H1-754 N2::H No74 N N L) 0( 1 0 0 1-745 H1-7 55 H No, GYOO

M

e 1-746 H H-5 ~ s aN 00 QaN N 0 1-747 > N1-7 57 ,~,.NF 1-70 1-75 00 F>~ N hJ~ 1-748 H 159H N3 N - ,-N~ ci e [Formula 105] 85 HH H Ia-12 d~ Ib Ia-2 Ia-13 IN F 't'1 Ia-N 00 OC O NQCF Ia-15 H Ia-5 H Aa6 N 0' 'b N10 N00o [o r Ia- 1 H Ia- HN8 SH H Ia-1 H la-6 b N Ia-7 l S Ia-22 d 'b H [Formul 1061,, H F) 86 ~ H ),H Ia-23 S Ia-35 Me SH H CI N NT Ia-24 -s HF Ia-36 N Nc H N N OMe Ia-25 00O N Ia0 S-37 Ia-26 doy -4 Ia3S F Ia-39 H Ia-27 ,O CN Ia-4 N NN Ia-2 O .- ,N CI Ia-44 H SN 1 Ia-28 db NN SN HON [Formul 107 Ia-30 d ~ b N F Ia-42H FN 00N . >LS H Ia-31 b , ,I Ia-4 H K .>j H NH L T Ia-3H dbQ.&CI Ia-44 Ia-33 00 H S~ dFrml 107) I a -3 2 -8 7 ) Ia4A5 N 0N- Ia-56 7 0 6 N( HHH IaA6 H 0 H H N H Ia-47 N H C H NIa-58 sN. IaA8 0 0 NN Ia-59 -S NH 00 Ia-50 C H Ia-61 0 0H Ia-51 00-MH Ia-52 00 N H HIa-63 SN H Ia-5 N N

HNHSO

2 Me Ia-54 0I N NN N >-s-i 0 D H ,IN F Ia-60 Ia-55 00 Ia-66 [Formula 108] 88 HH H Ia-69 - Ia-78 F1s -, H Ia-60 Ha-8 110 O b H HH cc,7 HIa-84 C Ia7 H H H F Ia-77 H H a8 H T Formulaa 109 Ia-71 0 0 Ia 89 H H Ia-122 Ia-89 N N 'N J NY a-90H H Ia-123 ; 0 Ia-9 N N Oa 6 Na, Ia-124 H Ia-91 N CH N 0 NY Ia-104 H Ia-125 H 0 O> N N H Ia-105 HNIa-126 H N'b H -)S -., N N0 - Na S Ia-106 H Ia-127 ) IS N 0 Ia-128 H Ia-107 N Ia-108 H N N N ' CF 3 Ia-109 Ia-1 30 Ia-110 N I3 b ~N I-1a-13_H Ia-ilIa-132 N CrZK0,QCOHHH [Formula 110] 90 00 >LH Ia-134 S-eN~ a15 H H Ia-135 SNe H Ia-146 N 0L H 00 F ) HL H Ia-139 0

S

6 N. ~ H Ia-1570 0 Ia-14 F H I a -1 3 7 0 0 H FI a -1 5 1 ? S ' , A H Ia-141 0 0 Hii Ha19>S N H Fa I5 00 N , CH Ia-13 H Ia-154 )L -N,4i 0 00 N 00 [Fomul Ili N )-S9H Ia-155

H

3 C H Ia-166 0 ,,N CF3 00 .. N: Ia-156 H3H CIa-167 H N H

.-

Ndo NN H3 C H SCF3 Ia-157 H N H Ia-168 H Ia-158 Ia-169 S-N Ia-159 S Ia-171 HH 00N N Ia-160 N6~1)

CF

3 Ia-172 )SN H N Ia-161 S'-NJ HN 00 NCF Ia-173 N H

CH

3 N Ia-162 S N NCF Ia-174 S-H Ia-163 S-N H 0 H H 00H Ia-164 S -N 00

-

N O HH 00Ia-176 / -S0 Ia-165 00 000 [Formula 1121 92 Ia-177 H H Sa19 Os6NOH Ia-190 -N-L Ia19H N 10PC 000J (C I17 SN H Ia-192 Ia-ISO~0 H0~I-9 la-17J 00 Ia-192 4 --- -NN Ia-180 H0~ ~H .N0.,N os6ND Ia-180 0S6NQ H ~ H Ia-196 H obS H 0,H Na18 00 H HH H H H- ON H1 Ia-182 0C ONH 19 Ab" . Na20 _CON 00 [Formua 113 -S93 Ia-203 >L N Ia-216 S H H ON CF Ia-204 db I0 H a-219 -N N b"'b O O H NHJ Ia-205 NIa-220 0 Ia2 6 0 Ia22 N3 N O0 H Ia-221 Ia-20? SN O N yO bb~H )----. k H 0 Ia-22 3 N 0O p Ia-20 8 d 0 Ia-224 S HN H C3 Ia-209 CNd H Ia-225 N 0 H N: Ia-210 6 S- H H Ia-226 N H OH Hb Ia-211 N N O Ia-227 H 0 Ia-212 N OOa NH H "-.O-' H H CH 3 SIa-229 N .N Ia-214 0 ' Na- H 'N Ia-230 >- H Ia-215 (:T N

CF

3 .. [Formula 114] 94 Ia-231 0 N 0 H0 ,KJSN Ia-232 N N 0 Ia-233 SN _,-,-N H H0O a-234 - .N N.- N H H 08 Ia-235 0 0 )H N Ia-236 Oib ..,N IIN H H D02 I a - 2 3 7 S N NO 0 2 00 H H 10 I a -2 3 8 N N C 6"0

N-

1 OCF, H Ia-239 0 -.. N 0 H

H

3 Ia-240 H H N Ia-241 N HO H HCo Ia -2 4 3 s N N H H Ia-244 N N [Formula 115] 95 H5- 9 b1-14 lbIN ~ 0 N QH O& Q N O Me Ib-7 Ib--17 N 0 0 N FD N CCF Ib-8 t15I-18H 15- N519FO 1 H Ho 66 IN 0 .N F Ib-12 o Ib-22 H 0o N W 1-22 H Ib-13 [Formula 116] 96 b5-23 H F Ib-35 e Ib-24 H F Ib-36 N H Ib-25 'I-37 6 N 0,-2 -.

4 6N 15 -37 6 ON H F Ib-28 o,6N H § Ib-40 H 15N H Ib-2 O bF1-49 N lb-2N O H 10-31 > HYF F H F N 0 NH H Ib 2 ,,NIb-31 O'-1 .,NON 15-3 2t 1b-44 'N N Ib3HO Me [Formula 1171 97 Ib-45 Sb-56 )S. I-46 Ib-57 o N&CH H lbH4 C 0 I-47 N I-58 H N Ib-48 I-59 )oC LH H Ib-49 Ib-60 Ib-50 I b-61 H H Ib-51 o I-62 Ib-52 Ib 1-63 4j 0 7 H

HSO

2 Me 15.53 Co~ CJ(> HS 2 Ph Ib-54 IbN 1-65 X H }O Ib -55 N 00 15-66 H CH N N [Formula 1181 98 HIb-78 SN-,,N Ib-68 N 00 lb1-69 Ib-79 H 1 5 -6 9 /' - o'Hu -I o N , H NH 8 N O Ib-70 O Ib-81 Ib-72 N lbSN)' 00 0 0 , 7H HH H I-73 NON N Ib-74 Ib-84 6 0a Ib-85 N F OH H H H H 8 Ni N CI lb7 H C I8 15-7 O Ib -8 HH N.-StH lb-S4 b-88 s [Formula 1191 99 Ib-89 Ib-100 16-90 to l b-101 HQ0H 6606 "N OC Ib-91 iHIb-102 Ib-92 Ib-103 H Ib93

O'O.N

0

CONH

2 16-N0N H N' b ._N107 HC~ Ib-97 Ib-105 H CN 6N N~ I-98 H H N S HH Ib-99 N

OIH

2 N [Formula 120] 100 b - 1 1 1 Ib -1 2 2 N' O K Ib- 112 N Ib-113 Ib12 Ib-114 Fa Ib-125 -115s Ib-126 Ib-116 Ib-127 Ib-1 17 Ib-128 I b -1 1 8 H Ib-119 " H Ib-130 Ib-120 N ^Yb-1 H db .,.o N CON Ib-1 17 H ~yCN [Formula 1211 101 Ib1-133 6 I-144 IsNCN Ib-134 N Ib-145 -135 Ib-14 (Yb NFF F3 I-148 jH FN Ib-138 Iby 1-149 s H OC0 Ib-139 Nb-150 b>OCof Ib-140 b-151 Ib-141 H -152 N b-142 1b-153 *N 61N-143 Ib-154 N0 00OI9CF 3 ) o0bD.Y [Formula 122) 102 Ib-155 'O 1b-166 H 0O F C ~.(>i40 FN N 15H5 '~O YF 15-1H 0 0 ).,15-169 1,yH b-156 H Ib-1576F0~ H N Ib-158 9 H N H C; Ib-153 Ib-17 H OY ON Ib-160 hN cF17 F H 6 N F O N N lb 1 5 * H H61 7 H 0 ;b Ib-174 H ~H O Y N Ib-164 Ib-175 , A Ib-165 S QH H517 O6 ..,N 0 - 76 N 06 0 [Formula 123] H 03 > Ib-177 H Ib-188 H 0 'HtA ON H I Ib-189 ),N b-179 FN O _ Ib-18 0 Ib-191 s OFH H O 1b-181 b s Ib-19 2 6 c 0161101.C ONN H' Ib-182 Ib-193 N b-183 N H 0 H6 N SN O H 6 N Ib-184 H H 10 H5-195 H Ib-185 H 1518 6 OoN.Q 2 ND 15 7 H .S NO ,HIb19 S g N HH 0 [Formula 124] 104 Ib-199 ) Ib-212 Ib-200 NIb-213 H Ib-201 Ib-214 N Ib-202 H Ib-215 H I)ICFj Ib-203 N C0a 0 6 Nao Ib-216 N H o'b N fb20 6KAN~ Ib-219 N Ib-204 N aj H Ib-205 N H NY 'CFa Ib-220 A H ) OJ O-b , Ib-206 11sN H'F b-207 b N HIb-222 Ib-208 H Ib-223 H H H OS 0N0 -N C Ib-209 6TIb-224 AN Ib-210 Ib-225 lb-211 H b-22 6 N O N 0)0 N CF No0b 0 }C F 3 0 [Formula 125] 105 ) IC-1 Ic-13 O'b06 0 H H H H Ic-2 SN N IC-14 ,N-CN 0 O Q CN 6 6 OM e CIa H H AH Ic-5 N N Ic-16 >L&~N>NA06 H HH IC-9 Nc N IC-19, I-17 y~~~ IC-0 b C-0 o Nb

HF

Ic-9 o' c-1N H H Ic-ID )LS N -N~ ~ Hc2 >j H F H H Ic-12 >N Nc-22 [Formula 126] 106 ) Ic-23 s NHN Ic-35 N c I H H F H H Ic-24 00 Ic-36 OO H H Ic-25 6N N N ( Ic-3 6N Ic-38 N H H I Ic-2'7 N3N F Me F FN Ic-40 N Ic-29 t Ic-30 HF F Ic-42 H N FoOO Ic-31 Ic-43 H IC-32 NO Ic-44T Ic-33 NN e 107 Ic-45 N HN -56 H b OH Ic-46 gH H o06 LssIc-57 N Ic -47 N N H Oc NIc-58 Ic-48 - N Ic-59 N N N O b N H

H

Ic-49 N N Ic-62 H H Icc-6 NN O H H ' Ic-5 H Ic-6 I C -5 b N Ic -6 3 N HNl N KAN H SOH Ic-S53 N Ic-64 H H !aoNHSOph Ic-54 Ic-65 N H H iH Ic -5N Ic-66 [Formula 1281 108 HH H H Ic-67 N N Ic-78 L,_N Ic-68 60Ic-79 N Ic-80 H 0 Ic-69 N MeO o Ic-8 0 1 40 H 0 N H H ~NIc-82 N N Me0 ~-N N -O Ic-70 Ic-84 N Ic-7 4 c -8 5 NN H -Y Ic-7 5 b Ic-8 6 N H HOF Ic-76 6 o .IIc-87 N H H0 Ic -77 [Formula 129] 109 Ic-89 NIc-100 N N H rHn H H Ic-90 I ICUI-101 2"N .',sN OCHJ 00 KtOCH 3

OCH

3 Ic-91 Ic-102 o5N CF 0 6~ Ic-92 H H Ic-103 N N N N NN c-93 N N CNH 2 Ic-104 N 0 b fl N Ic-94 Ic-105 N N N 0ob H C-5 N ONH- Ic-1 06 H H Ic-96 Ic-107 N N o'b H Ic-97 bH H N-S O6 Ic-108 N -,,N N o'6 Ic-98 s Ic-109 Ic-99 02H Ic-110 N"6 H [Formula 130] 110 HH Ic-111 Ic-122 0 0 IC-12 6 ~td NPr NN N ? H HH Hi Ic-113 KI$F3 Ic-124 Wrri Ic- Ic-125 Ic-115 Ic-126 Ic-116 Ic-127 Ic-117 Ic-128 00-118N - Ic-129 N N Ic-119 6Ic-130 6 Ic62 06>$4 .N Ic-1 N Ic-131 Ic-121-25 ob -121Ic-132 [Formula 131] 111 Ic-133 Ic-144 N N Fj jH H .H HA>, Ic-134 .N -,N Ic-145 > N-,.r-N H6 H H HC Ic-135 & F Ic-146 00 F

CS

H HH H Ic-136 Ic-147 Ic10 b Fv IC15 F Ic-137 1 Ic-148 F 00 00 6-O Ic-13 Ic-153 Ic-14 -CF3 Ic-154 N Ic- 140 )Zt NCC,,NICF Ic -151 H [Formula 1321 112 H jH H 0 Ic-155 FF Ic-166 N-0 I1 6CFj IH H H FiH H Ic-15 6LN N Ic-167 9 IN , N N Ic-1597 c-7 6 F, IC-17 Ic-161 CF Ic-168 N N Ic-163 A H H Ic-164 N ,,, Ic-16 IN -- , VIc-165 H [Formul 1331]@ H H iH H H6 H Ic12 H0 HO l Ic-162 Ic..174n H Ic-175 N 1 164 )- 1176 6 bi~ [Formula 133] 113 H HH H Ic-177 ) . N N Ic-188 N 00 -CO ~ 0 0 Ic-178 F Ic-189 N N H~i H H Ic-179 T C_-190 ^ O 0,"N o6 U H H ;-H" Ic-I180 N - IN Ic-191 N N o6 O 2 NHN ,- N 10-181 N- N 802 H H oI Ic-192 N , % 4 N CONH H H Ic- 182 0 .Q[ONO \ Ic-193 H Ic-183 N 0014 N N Ic-184 >1srN -,,-N O Ic-195 H IH H NZ 1 Ic-185 N H Sib' 10-196 0 Ic-86 N S2ND Ic-197 N 0,>! Ic- 187 10ND -198 , 00c

H

0 ON H [Formula 134] 114 Ic-199 0 Ic-212 Ic-200 IcH b ( 1-213NN Ic-201 CH ~HIc-214

N'

1 '~( 1. 2H H b Ic-202 H H Ic-215 N Ic-203 N N,,N H H N-1 I-204 N N F0 H' N Ic-219 04 b o O c H I 2 N F F H H 0 Ic-206 NIc-221 H H Ic-222 N N 11-20 H ~ct Ic-208 00 N I c-223 CF Ic-209 Ic-224 N Ic-20 Ic-225 H H H 0H o6 .. j-j2j6 I H-2 H!% ~ ~ r 0 0 Ic-20 JbI-2N,-N CF [Formula 135] 115 Id- H H Id-2 N ,N Id-14 N O'bo'b Id-2 Hrt Hl ASN 0 N.A,,- Id- 146 H H Id-4 )SN N N M Id-7 Id-17 Id-8A6 Id-18 Id-9 6Id-19 Id-10 H H

-

NId-20 Id-11 Id-21 Id-12 HF I-d2 NNN [Formula 136] 116 FF _H H OMe Id-23 I Id Id-24 N 1 F Hd3 H~ Id-25 c Id-37H H H HH Id-27 Id-39 N O 2b N 0 0 Id2 N F HH ~~NId-41 ,,N Id- 3 0 H Id-"IT0 0 I Id-43 N NC F O Id-30 C _s~,J' b F H F Id-44 Id-31 NC,-,- H 0d-3 H IN Id-44 A)-J .ic H~ H FNK Id-33 N FMe 0F 0M [Formula 137] 117 Id-45 NO.Id-56 6 OH Id4 N -ON6 N1 C O H H 0 Id-50 NN tJId-6 N 1N6Ne Id- o 6 1 N1 6 HH O 18.63 N Id-57 O N Nd5 I O ,-, HOf H H H H Id-5ON N H H N H cd4 06 146 c bN 4 M H H H Id-SI N' 6 ,,, M r 14-62 00 ;N , H H obH NH S 0 Id-54 Id-65 N N NA Id-55 N N O -6N C [Formula 1381 118 H H Id-67 N Id-78 0 Id-79 <H IH 00 Id-68 N H H Id-80 N N H H 0 Id-69 N N Me H H 0 05 Id-81 N 1)4 0 H H H H _--N I HS H N Id-70 %$6 Id-82 ^-tN Id-71 Id-83 .3H~ Id-73 NbY16~54 O H Id-76 Id-8 c o b )-H H Hi H, O OH 1d-77 00 [Formula 1391 119 Id-89 >Id-10 0 H Id-90 Id-101 ~Nr y CH3 0 HO O CH. H H Id-92 HId-103 N N HS Id-93 )N.-rN.nCONH 2 Id-104 N S.1NN Id-94 Id -105N0N Id-95 0 I-16I obb Id-lC 6 Id-96 N H H 0OC~ 9Id-107 N N 6 N Id-99 02NAO 9

H

2 IdO [Formula 140] 120 1-J" Id-111 Id-122 00 00 Id-112 06 LN Id-123 Id-136 F6 Id-I114 N Id- 125 N N Id- 115 - N s,, Idt-1256 -,,N Id-116 Id-127 Id -1 1 7 d - 2 H H H'I I d -1 1 8 I d - 1 2 6 c, N 06 N ~ 06'# Id-116 -b J Id-127 , H H Id-120 Id-131 Id-121 Id-132 N CONH Hb H51 o b p [Formula 1411 121 Id-133 Id-144 N N F: Id-134 Id-145 Id-135 FN F6-146 00 F o6F Id-136 Id-147 N F H H FH H Id-137 -N -N F-148 N N CH Id-13 ^ ] Id-150 Id-13 6 F Id-149

(CH

3 Id-139 Id-2I O NQ Id-142 Id-153 'c N N Id-143 N F 6Id-154 N HV [Formula 1421 122 Id-155 Id-166 Id-156 HF 0, 6Id- 1 ? )%NrNY N N Id-157 F 00

CF

3 'H H Id_0N I d -1 5 1 6 N, , , , H N H H Id~ H Id- 159 N N HN O'bH H H Id-169 Id- 161 N FN0 7 N H Id 16 NH Id- 17 3 N 00 O Id-160 L Wd -17 4 H 6 Id-16 F Id-172 b Id- 162 N N Jd173 ,Ji WH H Id-163 0617 0 0 Id- 164 Id-17 (-jD 66 b [Formula 1431 123 Id-177 N Id-188 Id-178 0 6 c 16I-189 N N Id1 0 6 sc: O ~0 6l C Id-181 N -, N SO3 Id-192 IN , N CN I I NZFO0 Id-183 N ---- Id194

-

Id18 N N O Id-95N H H H Id-185 N N H -180 s NN -196N I 6

NSO

2 io197 Id- 181 H so$ 0 16HI-1 92 A-S>N ycoN 0 0y H Id-184 N 1 1 H0 Q0N 6 K#-.3 H H 50 [Fomu 1844] 121854 60 totD 1-1 96N Id- 186 ,-N '~02Q 16 i-197 >0 0 1d- 187 H H H19 [Formula 144] 124 Id-199 Id-212 at Hb ~ ' &1 Id-200 IN-213 00 d'M H H CHH I 1-201 oN s0 Id-215 N N F -203 0 & -21 H H Id-204 ISN,,-N HH H6H NDI I-21 F Id-205 )d-220 O D F Id-206 o d1-221 N Id-207 N IH N 1 22 HL HI H bcF Id28 N 16_223 N0N OC Id-209 Id-22 HH Id-210 I.N N Id-225 ^ bH H 0r Id-211 N .N Id-226 F Nj> [Formula 145] 125 Ig-1 Ig-13 I,, 2H Ig-14 0 Ig-7 HgI t>NH F 0 0- Ny J I g -1 9 F 0 Ig-4 9gI Ig-21 0 F H Ct Ig- 1 1 Ig-22 Nin [Formula 146] 126 Ig-3 %~41~~JjFIg-35 >H ~OMe H Ig-2 >NQ F g3 C ,bfH 06-3 F~ )2 H oN 1Me O QN C Ig-37 N H N. Ig-26 )S F O 4 N HIg-39t 0 HOz Ig-28 Ig-29 FXF Ig-32H N Ig 0 N CI Ig-33 FY F H F N OQW29 N Ig'T-O1 F C 3 H C AOCe H 4 [Formula 1471 127 HH Ig-4 5 Ig-56 00 OH Ig-46 0Ig-57H Ha N Ig-46 H Ig-58 H.7 N OH Ig-48 6NIg-59 N) N NH N H NqF Ig-60 I N Ig-61 0 O H &N O Ig-52 Ig-63t$ A R Ig-53 NS NHSH HH H H HNHS0fh -54 N Ig-6 5 00 H <"' I N)A Me g-5i H Ig-6 00 H 00 g63 /0 , N5 00 O H ~~ H&12 N Ig-66 00-1 K SN N S [Formula 148] 128 Ig-67 Ig-79 0 Ig-68 H H 0 N I80 N 0 Ig-69 g- NyHi H g SNOKI N Ig-82 F N Ig-71 Ig-83 F OKF 6 Ig-84 N Y H 4T Ig-75 6 H Ig-87 N H Ig-76Y H S H O N O I 7 Ig-8 Ig-78 6 Ig-88 [Formula 149] 129 Ig-89 Ig-100 t Ig-90 Tg N - H OQC CH 3 Ig-91 6 N g-102 H Ig -92 6 NNY " H g- 1 3 F 06 NN Ig-93 Ig-105 6

CONH

2 6 N pr toH Ig-94 Ig-10 H 0 N Ig-H10 Ig-98 6> O N Ig-109 N Ig-99 J d 6 N,,),-co'6 A IgIg-11O10\

ONNH

2 N [Formula 150] 130 Ig-Ill H Nt x Ig-122 &NY N Ob0 016 , Ig1 Ig-123 N .O Ig-115 Ig-1264 ~-115 ? b Ig-127 Ig-117 Ig-11 7 Ig-128 N 00 H HNF H1 N '>g-129C I1Ig-19 H Ig-120 c Ig-1 ~~g132 >%NON [Formula 151] 131 Ig-133 ) I-144 POX-X145N QC Ig-134 I g4 Cd Ig-13 7 Ig-14 5 FQWS 4 § F OCS H Ig-139 Ig-14 H F obtsKN->$b Ig-147 1 Ig-152 ~& 0 F6 H Ig-138142 Ig-140 Ig-15 6 &F Ig6F1 Ig-142 cbJ{6c> Ig-153 QN

M

C 0615 N 0A. Ig-143 4s > N-9-CFJ05 [Formula 152] 132 H t' Ig -16 6 Ny0 Ig-155 NQYF g& Hg-156 Fa Ig-167 N Ig -1 5 6 > F Ny

S

4 CF , Ig15 6Ig-169 0 Ig-159 Ig-1 7 1 H Ig-160 N F Ig-161 F -1 O0 6l N H 6 HH Ig-163 O Ig-174 NO 0 0 N N Ig-14 Ng-175 Ig-165 N HN 'b N F18I-176 H O N [Formula 1531 133 Ig-17 7 )1>Q1 Ig-188 H O Ig-1 7 8 N N H Ig-189-FH SIg-190 NCr Ig-10S Ig-191 NH Ig-I7 18 N 'OtQ80 g-9 HO 0 N O HH H Ig-1 Ig-194 N x g-184 0 fI H O19Ig-95 N Ig18 N N H ) O Ig-186 > NQ4C SO2ND Ig-19 Ig-186 H O 6 N SO2No,, _ 67 6 CON I8 5-19H O Ob ON 0 f [Formula 1541 134 Ig-199 0 Ig-212> Ig-200 0 H -0 Q Ig-213 N H6 ON- H Ig-2012 I-1 S20 ONH Ig 215 0Q Ig-203 N Ig-216 H Ig-2174SH Ng2000 N F H&O OH F Ig-206 Ig-2 Ho F Ig-201I-22 -).S H" HCH g -207 O1N ' O 8O Ig20 bIg-2223y~ o 6 C Ig-209 Ig-224 I 210 Ig-225 Ig-211Ig-26 Ig-226 ,CJNCF [Formula 155] 135 Ih -2 N h -14 N Ih-4 6 h6Oj6 Ih-7 N 4h 17 N 0h-8 6 N h-18 H F6 FO Ih- n H CF 0 0 NP-t H 1() J F 66 IJh-22 N HF Ih-9 )-sNh 11> 19 Ns H F 11>10 H Ih-[ 1 56 Ih-21 36N Ih-12 CNQJH h-22H Y [Formula 1561 136 Ih-23 FF1-35 Oe 0 0 H OJ d Ih-24 N F36 cI 0h2 b% C]J-Fih-6 H F 00N Ih-25 0-6 4 H OMe U -37 0 N Ih-26 H F HN Ih-28 N^Y Ih40 NN? Th-29 0 6 FO Ih-30 O N >F 1-42 (>2' I-31 N~'.IC 63 6O CJ ' 143c 1h-32 0 Ih_44 cNH Ih-33 o N Me 013 0 H~ [Formula 1571 137 Ih-45 Nh-56 ) Ih-46 H 0 (h-57 H N-J CH, Ih-47 H H OH hNIh-58 H Ih48 b N Ih-59 N H NI Ih-49 )0 F Ih-60 H H F 0 Ih-50 o0 Hlh-61 H Me Ih-51 o Ih-62 is6N 0 N H Ih-52 )0 N Ih-63 is-N -53 N H NHSO0le Ih53 XH- Ih-64 40 C4 , 00 CLL NH SO2P h Ih-54 S-Nr 0 Ih-65 00 %YOH Jh -5 5 NO- 00 Th-5 H 00 Ih-66 N~ySNJ0 0 [Formula 158] 138 Ih-67 Ih-78 Ih-68 N Ih-79 HH Ih-69 6 N M 0 -0 6 N Y m80 Ih-70 N Ih-81 N H Ih-82 N mm JJN(X 0,Y6 H 5 c NIh-84 Ih-74 H O N Ih -7 5 6 fI -6 N NH H ]h.84 H H N O C KI Ih-7 oh8 o* H Or? Th-88 N 6 Th -86 I17 Th-87 O [Formula 1591 139 Ih-89 H HIh-100 N Ih-90 fo Ih-101 H H N OCHJ ]h-91 0 Ih_10 OCHH Ih O N O 69 N O ]_03 F H-I 6- ONH2 Ih-104 - N H N Hh-105 N N h-95 'N Q N CONHN -106 N h-66 1( ,H H 1-107 N lh-97 6 HN h H - N Ih-98 N H H b]NIh-109 N 0 2

NH

2 N [Formula 1601 140 Ih-l11 J Ih-122 b h-1 12 N h123 H Ih-2I h-1 Ih-115 6 NIh-126 Ih-1 16 N h -17N Ih-128 cs 6-Ih-129 N X CF ]h19 g(H fNY13 I 0h- 131 Ih-121 Ih-132 [Formula 1611 141 N F Ih-133 I-F I Q 6H CF3 Ih-134 7 I,,N H Ih-145 F H ()H Ih-135 F F Ih-15 N h-141 Ih-14 N FaD 06 NXC Ih-13 N Ih-153 O-%t F o'6 H

CH

3 fh - 139 SNj(,' F lh-14 )O "-H H CF Ih-154 Nh14 H h- 149 As 3 H HN H Jh- 143 1)1 o 0 o b 'IZQ(..F 6h15 0C [Formula 162] 142 0 6 [)-N H 16 -( r)| Th- 155 PNnF 1 S6 N S HIh-157l~ 68 S0I1F bT,,,N F N,-,,SAN-0~ HN Ih-159 HnFk-6 N,%S .F Hh.-172 Ih-161N Th" -168 ShH700 -0 H,. N h- "a4 Ih- 158 00kl H [Formul 1631 143, N

S

Di-177 iL-NiH > b Ih-188 s H HCON Ih-178 N Ih-189 H H N,)CF3 H O lh-179 N Ih-190 Na NcN Ih -18 2 N O H 0O I 1 HN Ho b h-184 Hbh-195 4 N S02N Ih-186 ICi N O'b N( SO N h-9 7 N Ih-186 H 11-193 oN'b - 187 ON Ih-198 N [Formula 164] 1 44 Ih-199 SNIIh-212 ,H HO Ih-200 N Ih-213 N Ih-201 s CH Ih-214 N Ih-202 Ih-215 ASNo H H CFa Ih-203 Ih-216 ICI,,N a Ih111Y Ih-204 I-1 N H 205 Ih-221 F 0 t N HF Ih-209 Ih-224 ~CQ~ h-20 h >225 Ih-211 Jh-226 ~ NN 15OCF3 Ih-Th- 225 6h21 b Ih226 HL 11>211 IjI-21 N~ N,,::0 Ih-20 Ls' h-N2 66 0 145 [0082] Compound I-72 [Formula 1651 H NQ 5 1H-NMR (DMSO-d6) 6: 0.90-1.05 (m, 2 H), 1.05-1.15 (m, 6H), 1.25 (s, 9H,), 1.15-1.32 (m, 3H), 1.41 (m, 1H), 1.75-1.98 (m, 4H), 2.11 (m, 1H), 2.58-3.38 (m, 5H), 3.58-3.76 (m, 2H), 5.17 (m, 1H), 6.25-6.92 (m, 5H) Melting point: 147 to 149 0 C 10 Compound Ia-140 [Formula 166]

CF

3 1H-NMR (CDCl3) 6:1.02-1.20 (m, 2 H), 1.17-1.32 (m, 2 H), 1.37 (d, 6H, J = 6.9 Hz), 1.46 15 1.70 (6, 4H), 1.86-1.95 Cm, 2H), 2.08-2.18 (m, 2H), 3.01 (d, 2H, J = 6.9 Hz), 3.13 (m, 1H), 3.25 (m, 1H), 3.87 (d, 1H, J= 8.4 Hz), 6.61(d, 2H, J = 8.7 Hz), 7.39 (d, 2H, J = 8.7 Hz) Compound Ia-141 [Formula 167] 20 1H-NMR (CDCl3) 6:1.00-1.30 (m, 4 H), 1.37 (d, 6H, J = 6.9 Hz), 1.59 (m, 1H), 1.87-1.98 (m, 2H), 1.99-2.18 (m, 5H), 2.85 (q, 3H, J = 7.5 Hz), 2.97 (d, 2H, J = 6.9 Hz), 3.12 (m, 1H), 3.23 (m, IH), 3.88 (d, 1H, J = 8.1 Hz), 6.53 (d, 1H, J = 7.8 Hz), 6.63 (brs, 1H), 7.04 25 (d, 1H, J = 7.8 Hz) Mass: 351(M+Hl 146 Compound Ia-178 [Formula 1681 ~JN

CF

3 5 1H-NMR (CDC13) 6:1.08-1.36 (m, 4 H), 1.39 (s, 9H), 1.59 (m, 1H), 1.90-1.99 (m, 2H), 2.16-2.26 (m, 2H), 3.17-3.34 (m,3H), 3.69 (d, 1H, J = 9.3 Hz), 6.68 (d, 1H, J = 9.3 Hz), 7.77 (dd, 1H, J = 2.1 Hz and 9.3 Hz), 8.49 (brs, 1H) Mass:394[M+H]+ 10 Compound Ib-138 [Formula 169] N .. , H F 1H-NMR (CDCl3) 6:1.02-1.34 (m, 4 H), 1.37 (d, 6H, J = 6.6 Hz), 1.57 (m, 1H), 1.87-1.97 15 (m, 2H), 2.07-2.18 (m, 2H), 2.93 (d, 2H, J = 6.6 Hz), 3.13 (m, 1H), 3.25 (m, 1H), 3.99 (d, 1H, J = 8.4 Hz), 6.38 (m, 1H), 6.49 (brs, 1H), 6.97 (q, 1H, J= 9.3 Hz) Mass:3471M+H) Compound Ii-2 [Formula 170] d'bI N 20 F 1H-NMR (DMSO-d6) 8: 0.91-1.06 (m, 2H), 1.12-1.28 (m, 11H), 1.31-1.47 (m, IH), 1.75 1.94 (m, 4H), 2.19 (t, 2H, J = 11.3 Hz), 2.79 (t, 2H, J = 6.0 Hz), 2.93-3.08 (m, 1H), 2.97 (q. 2H, J = 7.42 Hz), 3.46 (m, 2H), 3.57-3.69 (m, 2H), 5.71 (t, 1H, J = 5.2 Hz), 5.77 (d, 1H, J 25 11.5 Hz), 5.88-5.96 (m, 2H), 7.01 (d, 1H, J = 7.4 Hz). 147 Compound Ii-3 [Formula 171] N 5 1H-NMR (DMSO-d6) 6: 0.90-1.07 (m, 2 H), 1.15-1.21 (m, 1H), 1.27 (s, 9H), 1.40-1.49 (m, 2H), 1.82 (d, 2H, J= 11.6 Hz), 1.92 (d, 2H, J = 11.6 Hz), 2.79-2.84 (m, 2H), 2.97-3.10 (m, 1H), 3.24 (s, 3H), 3.55-3.62 (m, 2H), 3.84-3.91 (m, 2H), 5.50-5.59 (m, 1H), 6.40 (d, 1H, J = 8.0 Hz), 6.56 (s, 1H), 6.72 (d, 1H, J = 8.4 Hz), 6.97 (d, IH, J = 8.4 Hz). Melting point: 166 to 168 0C 10 Compound Ii-4 [Formula 172] 0", H C0 yN 0 15 1H-NMR (DMSO-d6) 6: 0.87 (t, 3H, J 7.2 Hz), 0.93-1.06 (m, 2H), 1.13-1.21 (m, 1H), 1.26 (s, 9H), 1.37-1.49 (m, 2H), 1.61-1.72 (m, 2H), 1.82 (d, 2H, J = 12.0 Hz), 1.91 (d, 2H,.J = 12.0 Hz), 2.78-2.84 (m, 2H), 2.97-3.08 (m, 1H), 3.61-3.71 (m, 2H), 5.52-5.60 (m, 1H), 6.40 (d, 1H, J = 8.4 Hz), 6.56 (a, 1H), 6.73 (d, 1H, J = 8.8 Hz), 6.97 (d, 1H, J = 8.8 Hz). Melting point: 185 to 186 *C 20 Compound Ii-5 [Formula 173] INN 0 C 0 14 148 1H-NMR (DMSO-d6) 6: 0.90-1.05 (m, 2H), 1.26 (s, 9H), 1.28-1.31 (m, 1H), 1.35-1.47 (m, 8H), 1.81 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.77-2.84 (m, 2H), 2.96-3.07 (m, IH), 4.30-4.42 (m, 1H), 5.51-5.64 (m, 1H), 6.39 (d, 1H, J = 8.0 Hz), 6.55 (s, 1H), 6.72 (d, 1H, J = 8.8 Hz), 7.07 (d, 1H, J = 8.8 Hz). Melting point: 156 to 157 *C 5 Compound Ii-6 [Formula 174] N 10 1H-NMR (DMSO-d6) 6: 0.91-1.07 (m, 2H), 1. 19-1.25 (m, 4H), 1.26 (s, 9H), 1.38-1.49 (m, 2H), 1.82 (d, 2H, J = 8.8 Hz), 1.91 (d, 2H, J = 8.8 Hz), 2.79-2.84 (m, 2H), 2.97-3.07 (m, 1H), 3.69-3.80 (m, 2H), 5.51-5.63 (m, 1H), 6.41 (d, 1H, J = 8.0 Hz), 6.56 (s, 1H), 6.72 (d, 1H, J = 8.8 Hz), 6.97 (d, 1H, J = 8.8 Hz). Melting point: 178 to 179 00 15 Compound Ii-7 [Formula 1751 N - 0 N 1H-NMR (DMSO-d6) 6: 0.92-1.07 (m, 2H), 1.19-1.22 (m, IH), 1.26 (s, 9H), 1.38-1.48 (m, 20 2H), 1.82 (d, 2H, J = 11.6 Hz), 1.91 (d, 2H, J = 11.6 Hz), 2.79-2.84 (m, 2H), 2.95-3.09 (m, 1H), 3.25 (s, 3H), 5.52-5.60 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.56 (s, IH), 6.72 (d, IH, J:: 8.4 Hz), 6.92 (d, 1H, J = 8.4 Hz). Melting point: 206 to 207 00 Compound li-8 25 [Formula 176] H 149 1H-NMR (DMSO-d6) 5: 0.91-1.05 (m, 211), 1.16-1.24 (m, 1H), 1.26 (s, 9H), 1.37-1.47 (m, 2H), 1.81 (d, 2H, J = 12.8 Hz), 1.90 (d, 2H, J = 12.8 Hz), 2.75-2.81 (m, 2H), 2.96-3.08 (m, 1H), 5.45-5.52 (m, 1H), 6.33 (d, 1H, J = 8.4 Hz), 6.50 (a, 1H), 6.68-6.80 (m, 2H), 11.02 5 (bra, 1H). Melting point: 213 to 214 "C Compound Ii-9 [Formula 177] N d'b O H N 10 1H-NMR (DMSO-d6) 5: 0.91-1.08 (m, 2 H), 1.17-1.30 (m, 8H), 1.44 (bra, 1H), 1.82 (d, 2H, J = 12.4 Hz), 1.89 (d, 2H, J = 12.4 Hz), 2.78-2.82 (m, 2H), 2.97-3.15 (m, 2H), 3.23 (a, 3H), 3.55-3.62 (m, 2H), 3.83-3.90 (m, 2H), 5.52-5.59 (m, 1H), 6.40 (d, 1H, J = 8.0 Hz), 6.55 (a, 1H), 6.92 (d, 1H, J = 8.0 Hz), 6.97 (d, 1H, J= 8.4 Hz). Melting point: 120 to 121 *C 15 Compound li-10 [Formula 1781 o aN .,QN N 0 N 20 1H-NMR (DMSO-d6) 6: 0.88 (t, 3H, J= 7.2 Hz), 0.93-1.08 (m, 2H), 1.17-1.30 (m, 8H), 1.44 (bra, 1H), 1.52-1.61 (m, 2H), 1.83 (d, 2H, J = 12.0 Hz), 1.90 (d, 2H, J = 12.0 Hz), 2.78-2.84 (m, 2H), 2.98-3.15 (m, 2H), 3.62-3.71 (m, 2H), 5.52-5.60 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.57 (a, 1H), 6.92 (d, 1H, J = 8.0 Hz), 6.97 (d, 1H, J = 8.4 Hz). Melting point: 144 to 145 *C 25 Compound li-11 [Formula 1791 150 H |N

/I

1H-NMR (DMSO-d6) 6: 0.90-1.08 (m, 2H), 1.15-1.30 (m, 8H), 1.33-1.50 (m, 7H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 2.78-2.86 (m, 2H), 2.96-3.14 (m, 2H), 4.30 5 4.45 (m, 1H), 5.50-5.61 (m, iH), 6.40 (d, 1H, J= 7.6 Hz), 6.55 (s, 1w, 6.92 (d, IH, J= 7.2 Hz), 7.07 (d, 1H, J = 7.6 Hz). Melting point: 137 to 138 "C Compound li-12 [Formula 180] H H N N 10 1H-NMR (DMSO-d6) 6: 0.92-1.07 (m, 2H), 1.14-1.30 (m, 11H), 1.36-1.50 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 2.78-2.85 (m, 2H), 2.97-3. 15 (m, 2H), 3.69 3.79 (m, 2H), 5.52-5.60 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.56 (s, 1H), 6.92 (d, 1H, J = 7.2 15 Hz), 6.98 (d, 1H, J = 8.4 Hz). Melting point: 158 to 159 "C Compound Ii- 13 [Formula 181] H -ON 20 1H-NMR (DMSO-d6) 8: 0.90-1.06 (m, 2H), 1.12-1.30 (m, 8H), 1.34-1.51 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.88 (d, 2H, J = 12.0 Hz), 2.77-2.83 (m, 2H), 2.95-3.12 (m, 2H), 3.25 (s, 3H), 5.51-5.59 (m, 1H), 6.41 (d, 1H, J = 8.8 Hz), 6.56 (, 1H), 6.86-6.97 (m, 2H). Melting point:157 to 158 C 25 151 Compound Ii- 14 [Formula 182] H ~H 5 1H-NMR (DMSO-d6) 8: 0.91-1.08 (m, 2 H), 1.12-1.30 (m, 5H), 1.38-1.50 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.88 (d, 2H, J = 12.0 Hz), 2.77-2.85 (m, 2H), 2.90-3.09 (m, 3H), 3.23 (s, 3H), 3.55-3.61 (m, 2H), 3.84-3.91 (m, 2H), 5.52-5.60 (m, IH), 6.40 (d, 1H, J = 8.4 Hz), 6.55 (s, 1H), 6.89-7.00 (n, 2H). Melting point:150 to 151 00 10 Compound Ii-15 (Formula 183] -CN 1H-NMR (DMSO-d6) 6: 0.88 (s, 3H), 0.90 (s, 3H), 0.92-1.08 (m, 2H), 1.12-1.30 (m, 5H), 15 1.35-1.51 (m, 1H), 1.83 (d, 2H, J = 12.4 Hz), 1.89 (d, 2H, J = 12.4 Hz), 2.00-2.16 (m, 1H), 2.77-2.84 (m, 2H), 2.90-3.10 (m, 3H), 3.42-3.55 (m, 2H), 5.50-5.65 (m, 1H), 6.40 (d, IH, J = 8.4 Hz), 6.56 (s, 1H), 6.88-7.01 (m, 2H) Melting point: 132 to 133 C Compound Ii- 16 20 [Formula 184] H 1H-NMR (DMSO-d6) 5: 0.87 (t, 3H, J = 6.8 Hz), 0.90-1.08 (m, 2H), 1.10-1.28 (m, 511), 1.35-1.50 (m, 1H), 1.59-1.72 (m, 2H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 25 2.77-2.85 (m, 2H), 2.90-3.09 (m, 3H), 3.61-3.71 (m, 2H), 5.52-5.61 (m, 1H), 6.40 (d, 1H, J = 8.0 Hz), 6.56 (s, 1H), 6.97 (d, 2H, J = 8.0 Hz). Melting point: 136 to 137 *C 152 Compound i-17 [Formula 1851 H N N 5 1H-NMR (DMSO-d6) 5: 0.92-1.06 (m, 2H), 1.12-1.28 (m, 5H), 1.33-1.50 (m, 7H), 1.81 (d, 2H, J = 12.0 Hz), 1.88 (d, 2H, J = 12.0 Hz), 2.78-2.84 (m, 2H), 2.90-3.08 (m, 3H), 4.28 4.44 (m, IH), 5.49-5.79 (m, 1H), 6.39 (d, 1H, J = 8.0 Hz), 6.55 (s, 1H), 6.97 (d, 1H, J = 7.6 Hz), 7.07 (d, 1H, J = 8.0 Hz). Melting point: 124 to 125 *C 10 Compound Ii- 18 [Formula 186] H N 15 1H-NMR (DMSO-d6) 5: 0.90-1.07 (m, 2H), 1.12-1.29 (m, 8H), 1.36-1.51 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 2.78-2.86 (m, 2H), 2.90-3.09 (m, 3H), 3.68 3.80 (m, 2H), 5.51-5.61 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.57 (s, 1H), 6.97 (d, 2H, J = 8.4 Hz). Melting point: 163 to 164 *C 20 Compound Ii-19 [Formula 187) H ,CC N 0 N 1H-NMR (DMSO-d6) 5: 0.89-1.08 (m, 2H), 1.11-1.30 (m, 5H), 1.35-1.51 (m, 1H), 1.82 (d, 25 2H, J =10.8 Hz), 1.89 (d, 2H, J = 10.8 Hz), 2.75-2.88 (m, 2H), 2.89-3.10 (m, 3H), 3.25 (s, 3H), 5.48-5.60 (m, 1H), 6.42 (d, 1H, J = 7.6 Hz), 6.56 (s, 1H), 6.92 (d, 1H, J = 7.6 Hz), 153 6.98 (d, 111, J = 5.6 Hz). Melting point: 189 to 190 *C Compound Ii-20 [Formula 188] 5 1H-NMR (DMSO-d6) 6: 0.95-1.13 (m, 2H), 1.31-1.59 (m, 10H), 1.73-1.92 (m, 4H), 2.12 2.26 (m, 2H), 2.84 (d, 2H, J = 6.0 Hz), 3.07-3.30 (m, 4H), 4.30-4.46 (m, 1H), 5.64 (brs, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.57 (a, 1H), 7.08 (d, 1H, J 8.4 Hz). Melting point: 165 to 10 166 *C Compound Ii-21 [Formula 1891 HCI N 0 15 1H-NMR (DMSO-d6) 6: 0.86-1.25 (m, 10H), 1.40 (d, 3H, J = 6.9Hz), 1.52 (m, 1H), 1.82 1.93 (m, 4H), 2.95-3.00 (m, 5H), 3.63-3.91 (m, 2K), 4.61-4.68 (m, 1H), 6.73 (bra, 2H), 7.01 (d, 2H, J = 7.8Hz), 7.11 (d, 1H, J = 8.1Hz,). 20 Compound Ii-22 [Formula 1901 HCI 0N 0 1H-NMR (DMSO-d6) 6: 0.98-1.10 (m, 2 H), 1.15-1.34 (m, 5H), 1.36-1.43 (m, 9H), 1.53 (m, 25 1H), 1.82.1-93 (m, 4H), 2.94-3.01 (m, 6H), 4.52 (m, 1H), 4.63 (m, 1H), 6.73 (bra, 2H), 7.02 154 (d, 1H, J = 7.5Hz), 7.21-7.25 (m, 1H). Compound Ii-23 [Formula 1911 NHC 5 1H-NMR (DMSO-d6) 5: 0.86-1.04 (m, 4 H), 1.25 (s, 10H), 1.30 (s, 6H), 1.38 (s, 3H), 1.40 (a, 3H), 178-1.92 (m 4H), 2.76-2.80 (m, 2H), 3.03 (m, 1H), 4.54-4.63 (in, IH), 5.57 (m, 1H), 6.16 (a, 1H), 6.22 (d, 1H, J = 8.4Hz), 6.76 (d, 1H, J = 8.4Hz), 6.98 (d, 1H, J= 8.4Hz). 10 Compound 1i-24 [Formula 1921 H. .

HOI N 15 1H-NMR (DMSO-d6) 5: 0.98-1.11 (m, 5 H), 1. 15-1.31 (m, 20H), 1.57 (m, IH), 1.82.1-93 (m, 4H), 2.74-2.81 (m, iH), 3.01-3.06 (m, 2H), 3.35 (m, 1H), 3.40 (m, 1H), 4.04-4.17 (m, 3H), 6.77 (d, 1H, J = 9.0Hz), Compound Ii-25 20 [Formula 1931 H -N HOHC N .N N 1H-NMR (DMSO-d6) 6: 0.98-1.20 (m, 13 H), 1.30 (d, 3H, J = 3H), 1.59 (m, 1H), 1.81-1.91 (m, 4H), 2.73-2.83 (m, 1H), 2.94-3.04 (m, 4H), 3.35-3.45 (m, 2H), 4.08-4.19 (m, 3H), 6.88 25 (bra, 3H), 7.03 (d, 1H, J = 8.4Hz). 155 Compound Ii-26 [Formula 1941 H 2 HCI HN N 5 1H-NMR (DMSO-d6) 6:1.02-1.10 (m, 2H), 1.19-1.32 (m, 2H), 1.26 (s, 9H), 1.55 (m, 1H), 1.86-1.93 (in, 4H), 3.01-3.04 (m, 3H), 6.76 (d, 1H, J= 8.7 Hz), 7.03 (m, 1H), 7.37-7.43 (m, 3H), 7.76-7.80 (m, IH), 8.20-8.23 (m, 1H), 8.34-8.40 (m, 1H), 8.78-8.79 (m, 1H) Compound Ii-27 10 [Formula 195] 1H-NMR (DMSO-d6) 6:1.03-1.10 (m, 2H), 1.20-1.30 (m, 2H), 1.21 (d, 6H, J = 6.9 liz), 1.53 (m, 1H), 1.88 (m, 4H), 2.99-3.15 (m, 3H), 7.33-7.35 (m, 3H), 7.71-7.75 (m, 1H), 8.16 15 8.18 (m, 1H), 829-8.32 (m, 1H), 8.76-8.78 (m, 1H) Compound Ii-28 [Formula 196] H ~-~N 2 2HCI 0 0~.... N 20 1H-NMR (DMSO-d6) 6: 1.04-1.11 (m, 2H), 1.15-1.28 (m, 2H), 1.19 (t, 3H, J =7.2 Hz), 1.59 (m, 1H), 1.87-1.91 (m, 4H), 2.93-3.08 (m, 2H), 2.97 (q, 2H, J =7.2 Hz), 3.06-3.08 (m, 2H), 7.01 (m, 1H), 7.17 (d, 1H, J =7.5Hz), 7.43 (d, 1H, J =7.5Hz), 7.50-7.57 (m, 2H), 7.80-7.84 (in, 1H), 8.25-8.27 (m, 1H), 8.39-8.44 (m, 1H), 8.80-8.82 (m, 1H) 25 Compound Ii-29 156 [Formula 197] H N HCI 1H-NMR (DMSO-d6) 6:0.99-1.10 (m, 2H), 1.15-1.28 (m, 2H), 1.19 (t, 3H, J=7.5 Hz), 1.52 5 (m, 1H), 1.84-1.91 (m, 4H), 2.94-3.01 (m, 5H), 6.88 (m, 1H), 7.00 (d, 1H, J =7.8 Hz), 7.26 7.28 (m, 2H), 7.38 (m, IH), 7.76 (d, 1H, J = 3.3. Hz), 7.90 (d, 1H, J =3.3 Hz) Compound Ii-30 [Formula 1981 2 H CI 0 CN 10 1H-NMR (DMSO-d6) 6: 0.93-1.08 (m, 2 H), 1.18-1.33 (m, 2H), 1.26 (s, 9H), 1.45 (m, 1H), 1.78-1.97 (m, 4 H), 2.86-2.94 (m, 2H), 2.95-3.10 (m, 1H), 5.91 (m, 1H), 6.55 (d, 1H, J = 7.13 Hz), 6.63-6.71 (m, 2H), 6.73 (d, 1H, J 8.0 Hz), 7.06 (s, 1H), 7.15 (t, 1H, J= 8.0 Hz), 7.60 15 (s, 1H), 8.11 (a, 1H), 8.31 (s, IH) Compound li-31 [Formula 1991 N>H 2 H C I N 0 0 N 20 1H-NMR (DMSO-d6) 6: 0.93-1.08 (m, 2 H), 1.13-1.28 (m, 2H), 1.26 (s, 9H), 1.43 (m, 1H), 1.76-1.97 (m, 4 H), 2.83-3.18 (m, 3H), 5.79 (m, 1H), 6.21 (s, 2H), 6.44 (d, 1H, J = 6.8 Hz), 6.58-6.67 (m, 2H), 6.73 (d, 1H, J= 8.0 Hz), 7.10 (t, lH.,J = 8.0 Hz), 7.21 (s, 2H) Melting point: 205 to 206 *C 25 Compound Ii-32 157 [Formula 200] 1H-NMR (DMSO-d6) 6: 0.90-1.05 (m, 2 H), 1.05-1.28 (m, 11H), 1.41 (m, 1H), 1.75-1.92 5 (m, 4 H), 2.11 (t, 2H, J = 10.0 Hz), 2.73-2.82 (m, 2H), 2.91-3.08 (m, 3H), 3.24 (d, 2H, J= 11.2 Hz), 3.62-3.72 (m, 2H), 5.07 (m, 1H), 6.47 (d, 2H, J = 7.2 Hz), 6.72 (d, 2H, J = 7.2 Hz), 6.97 (d, 1H, J = 7.6 Hz) Melting point: 165 to 166 "C Compound Ii-33 10 [Formula 201] H MCI 1H-NMR (DMSO-d6) 8: 0.91-1.06 (m, 2H), 1.15-1.26 (m, 8H), 1.33-1.48 (m, 1H), 1.71-1.93 (m, 4H), 2.88 (d, 2H, J = 6.5 Hz), 2.93-3.15 (m, 2H), 5.70 (bra, 2H), 6.63 (d, 2H, J = 9.1 15 Hz), 6.93-6.96 (m, 1H), 7.38-7.42 (m, 2H), 7.57 (d, 2H, J = 9.1 Hz), 7.88-7.93 (m, 2H) Compound Ii-34 [Formula 202] H HCI ob6 20 1H-NMR (DMSO-d6) 6: 0.98-1.02 (m, 2H), 1.16-1.18 (m, 5H), 1.42 (s, 1H), 1.75-1.91 (m, 4H), 2.88 (d, 2H, J = 6.6 Hz), 2.96 (q, 3H, J = 7.3 Hz), 6.63 (d, 2H, J = 8.9 Hz), 6.99-7.02 (m, 1H), 7.38-7.41 (m, 2H), 7.57 (d, 2H, J = 8.9 Hz), 7.89-7.92 (m, 2H). 25 Compound Ii-35 158 [Formula 2031 H N H 0,., NI 1H-NMR (DMSO-d6) 8 0.90-1.52 (m, 5H), 1.19 (t, 3H, J = 7.2 Hz), 1.75-1.96 (m, 4H), 5 2.50-3. 10 (m, 3H), 2.62 (q, 2H, J = 7.2 H z), 5.55-5.70 (m, 1H), 6.57 (d, 2H, J = 8.7 H z), 6.80-7.04 (m, 4H), 7.01 (d, 1H, J= 7.8 Hz), 7.34 (d, 2H, J = 8.7 Hz) Compound Ii-36 [Formula 2041 H 10 1H-NMR (DMSO-d6) 6: 0.90-1.50 (m, 5H), 1.19 (t, 3H, J = 7.2 Hz), 1.75-1.95 (m, 411), 2.70-3.10 (m, 3H), 2.97 (q, 2H, J = 7.2 Hz), 3.70 (s, 3H), 5.40-5.50 (m, 1H ), 6.53 (d, 2H, J = 8.7 Hz), 6.74 (d, 2H, J = 8.7 Hz), 6.78-6.90 (m, 4H), 6.99 (d, 1H, J = 7.8 Hz) 15 Compound Ii-37 (Formula 205]

CF

3 20 1H-NMR (CDC13) 8:1.02-1.32 (m, 4 H), 139 (s, 9H,), 1.58 (m, 1H), 1.86-1.96 (m, 2H), 2.12-2.22 (m, 2H), 3.02 (d, 2H, J = 6.6 Hz), 3.25 (m, 111), 3.67 (d, 1H, J = 9.3 Hz), 6.67(d, 2H, J = 8.7 Hz), 7.41 (d, 2H, J = 8.7 Hz) Mass:393[M+H] Compound Ii-38 25 [Formula 2061 159 H Qa CF 3 1H-NMR (DMSO-d6) 5: 0.93-1.07 (m, 2H), 1.17-1.26 (m, 2H), 1.19 (t, 3H, J = 7.1 Hz), 1.43 (9, 1H), 1.77-1.85 (m, 2H), 1.85-1.94 (m, 2H), 2.82 (t, 1H, J = 5.8 Hz), 2.98 (m, 1H), 5 2.97 (q, 2H, J = 7.1 Hz), 5.87 (m, 1H), 6.56 (d, 2H, J = 8.6 Hz), 6.98 (d, 1H, J = 7.6 Hz), 7.02 (d, 2H, J = 8.6 Hz). Compound Ii-39 [Formula 2071 d-,b '12I o '' .- N 10 CF 3 1H-NMR (DMSO-d6) 5: 0.98-1.10 (m, 2H), 1.19-1.35 (m, 2H), 1.29 (s, 9H), 1.46 (s, IH), 1.73-1.98 (m, 4H), 2.93 (m, 1H), 3.04 (m, 1H), 6.60-6.69 (m, 2H), 6.75 (d, 1H, J = 8.8 Hz), 6.97 (d, 1H, J = 7.6 Hz), 7.49 (d, 1H, J = 8.8 Hz), 8.05 (s, 1H). 15 Compound Ii-40 [Formula 208]

CF

3 20 1H-NMR (DMSO-d6) 6: 0.96-1.09 (m, 2H), 1.16-1.29 (m, 2H), 1.19 (t, 3H, J = 7.3 Hz), 1.45 (s, IH), 1.76-1.94 (m, 4H), 1.76 (s, 2H), 2.93 (t, 2H, J = 5.8 Hz), 2.97 (q, 2H, J = 7.3 Hz), 6.66 (s, 1H), 6.94-7.01 (m, 2H), 7.49 (d, 1H, J = 8.6 Hz), 8.04 (s, 1H). Compound Ii-41 25 [Formula 2091 160 H 0 NN 1-11N , kIN Me 1H-NMR (DMSO-d6) 5: 0.91-1.05 (m, 2H), 1.17-1.33 (m, 2H), 1.26 (s, 9H), 1.35-1.48 (m, 1H), 1.76-1.86 (m, 2H), 1.86-1.95 (m, 2H), 2.76-2.82 (m, 1H), 2.96-3.08 (m, iH), 3.71 (s, 5 3H), 5.21-5.30 (m, 1H), 6.57 (d, 1H, J = 8.6 Hz), 6.73 (d, 1H, J = 8.6 Hz), 7.02 (dd, 1H, J = 8.6, 2.3 Hz), 7.44 (d, 1H, J = 2.3 Hz). Compound Ii-42 [Formula 210] 13.,b N 10 GMe 1H-NMR (DMSO-d6) 8: 0.98-1.01 (m, 2H), 1.18-1.28 (m, 2H), 1.19 (t, 3H, J = 7.1 Hz), 1.42 (s, 1H), 1.76-1.85 (m, 2H), 1.85-1.93 (m, 2H), 2.79 (t, 2H, J = 5.9 Hz), 2.97 (q, 2H, J = 7.1 Hz), 3.02 (m, 1H), 3.71 (s, 3H), 5.26 (m, 1H), 6.58 (d, 1H, J = 8.6 Hz), 6.98 (d, 2H, J 15 = 7.8 Hz), 7.02 (d, 2H, J = 8.6 Hz), 7.44 (br s, 1H). Compound Ii-43 [Formula 211] H H Me 20 1H-NMR (DMSO-d6) 6: 0.98-1.06 (m, 2H), 1.16-1.25 (m, 2H), 1.18 (t, 3H, J =7.5 Hz), 1.51 (m, 1H), 1.83-1.91 (m, 4H), 2.85 (t, 2H, J = 6.3 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.04(m, 1H), 3.56 (s, 3H), 5.46 (t, 1H, J = 6.3 Hz), 5.76 (s, 1H), 6.49 (d, 1H, J = 7.8 Hz), 7.21 (t, 1H, J = 7.5Hz), 7.32 (t, 2H, J = 7.5 Hz), 7.68 (d, 2H, J = 7.5 Hz) 25 Compound li-44 161 [Formula 2121 H T H HCI N 1H-NMR (DMSO-d6)6: 0.96-1.05 (m, 2H), 1.18 (t, 3H, J= 7.2 Hz), 1.24 (m, 2H), 1.48 (m, 5 1H), 1.76-1.91 (m, 4H), 2.91 (d, 2H, J = 6.6 Hz), 2.97 (q, 2H, J = 7.2 Hz), 6.35 (B, 1H), 6.99 (d, 1H, J = 7.8 Hz), 7.46-7.49 (m, 3H), 7.73-7.76 (m, 2H) Compound Ii-45 [Formula 2131 HH 10 F 1H-NMR (DMSO-d6) 5: 0.92-1.08 (m, 2H), 1.15-1.22 (m, 1H), 1.26 (s, 9H), 1.37-1.51 (m, 2H), 1.81 (d, 2H, J = 11.6 Hz), 1.91 (d, 2H, J = 11.6 Hz), 2.76-2.86 (m, 2H), 2.97-3.08 (m, 1H), 3.35 (a, 3H), 5.82-5.91 (m, 1H), 6.26 (d, 1H, J = 13.6 Hz), 6.39 (B, 1H), 6.73 (brs, 1H). 15 Melting point: 215 to 216 *C Compound Ii-46 [Formula 2141 F 20 1H-NMR (CDC13) 5: 1.02-1.32 (m, 4H), 1.24 (d, 6H, J 6.0 Hz), 1.39 (a, 9H), 1.54 (m, 1H), 1.84-1.94 (m, 2H), 2.12-2.22 (m, 2H), 2.39 (t, 2H, J = 10.5 Hz), 2.94 (d, 2H, J = 6.9 Hz), 3.24 (m, IH), 3.38 (d, 1H, J = 9.6 Hz), 3.61 (d, 1H, J = 9.6 Hz), 3.72-4.00 (m, 2H), 5.83-5.94 (m, 1H), 5.96-6.10 (m, 2H). 25 Compound Ii-47 [Formula 2151 162 F 1H-NMR (DMSO-d6) 6: 0.91-1.07 (m, 2H), 1.16-1.34 (m, 11H), 1.40 (m, 1H), 1.79 (d, 2H, J = 12.5 Hz), 1.90 (d, 2H, J = 11.9 Hz), 2.82 (t, 2H, J = 5.5 Hz), 3.01 (m, 1H), 6.12-6.18 5 (m, 3H), 6.30 (t, 1H, J = 5.5 Hz), 6.76 (d, 1H, J = 8.7 Hz). Compound li-48 [Formula 216] H , $~N~QN 10 1H-NMR (CDC13) 6: 1.00-1.28 (m, 4H), 1.39 (s, 9H), 1.56 (m, 1H), 1.91 (d, 2H, J = 12.4 Hz), 2.08-2.21 (m, 4H), 2.58 (t, 2H, J = 8.1 Hz), 2.97 (d, 2H, J = 6.0 Hz), 3.23 (m, 1H), 3.70 (d, 1H, J = 9.4 Hz), 3.80 (t, 2H, J = 7.1 Hz), 6.66 (d, 2H, J = 8.7 Hz), 7.36 (d, 2H, J = 8.7 Hz). 15 Compound Ii-49 [Formula 217] OF 20 1H-NMR (DMSO-d6) 6: 0.92-1.06 (m, 2H), 1.17-1.33 (m, 11H), 1.41 (m, 1H), 1.80 (d, 2H, J = 12.9 Hz), 1.90 (d, 211, J= 11.4 Hz), 2.82 (t, 2H, J= 6.1 Hz), 3.01 (m, 1H), 6.07 (t, 1H. J = 5.3 Hz), 6.34-6.43 (m, 2H), 6.51 (dd, IH, J1 = 8.2 Hz, J2 = 1.8 Hz), 6.75 (d, 1H, J = 8.5 Hz), 7.11 (t, 1H, 8.2 Hz). 163 Compound Ii-50 (Formula 2181 ) H 5 1H-NMR (DMSO-d6) 6: 0.92-1.08 (m, 2H), 1.14-1.31 (m, 8H), 1.43 (m, 1H), 1.76-1.94 (m, 4H), 2.82 (t, 2H, J = 6.0 H z), 2.95-3.16 (m, 2H), 5.90 (t, 1H, J = 5.5 Hz), 6.56 (d, 2H, J = 8.7 Hz), 6.95 (d, 1H, J = 7.9 Hz), 7.03 (d, 2H, J = 8.6 Hz). Compound Ii-51 10 (Formula 219] cr~b F 1H-NMR (DMSO-d6) 5: 0.90-1.08 (m, 2H), 1.13-1.31 (m, 8H), 1.42 (m, 1H), 1.76-1.94 (m, 411), 2.83 (t, 2H, J = 6.0 Hz), 2.95-3.16 (m, 2H), 6.07 (t, 1H, J = 5.4 Hz), 6.36-6.46 (m, 15 2H), 6.53 (dd, 111, J1 = 8.1 Hz, J2= 1.9 Hz), 6.95 (d, 1H, J 7.9 Hz), 7.12 (d, 1H, J = 8.1 H z). Compound Ii-52 [Formula 2201 SN O 20 1H-NMR (DMSO-d6) 5: 0.91-1. 10 (m, 2H), 1.19-1.37 (m, 11H), 1.45 (m, 1H), 1.78-1.90 (m, 4H), 2.84 (t, 2H, J = 6.0 Hz), 3.04 (m, 1H), 4.64 (q, 2H, J = 9.0 Hz), 5.73 (t, 1H, J = 5.4 Hz), 6.13-6.21 (m, 2H), 6.26 (d, 1H, J = 7.2 Hz), 6.78 (d, 1H, J = 8.4 Hz), 6.99 (t, 1H, 25 8.0 Hz). 164 Compound Ii-53 [Formula 221] _O F 5 1H-NMR (DMSO-d6) 6: 0.90-1.06 (m, 2H), 1.13-1.30 (m, 8H), 1.42 (m, 1H), 1.75-1.93 (m, 411), 2.80 (t, 2H, J = 6.2 Hz), 2.93-3.16 (m, 2H), 5.66 (t, 1H, J = 5.5 Hz), 6.53 (d, 2H, J = 9.1 Hz), 6.89 (d, 2H, J = 8.8 Hz), 6.92 (t, 1H, JH-F = 75 Hz), 6.94 (d, 1H, J = 8.0 Hz). Compound Ii-54 10 [Formula 222] HH F 1H-NMR (DMSO-d6) 5: 0.88-1.05 (m, 2H), 1.14-1.32 (m, 11H), 1.41 (m, 1H), 1.75-1.94 (m, 4H), 2.77 (t, 2H, J = 6.0 Hz), 3.01 (m, iH), 4.54 (q, 2H, J = 9.0 Hz), 5.33 (t, 1H, J = 15 5.8 Hz), 6.49 (d, 2H, J = 8.8 Hz), 6.75 (d, 1H, J = 8.8 Hz), 6.80 (d, 2H, J = 8.8 Hz). Compound Ii-55 [Formula 223] AH 20 1H-NMR (DMSO-d6) 6: 0.90-1.06 (m, 2H), 1.14-1.31 (m, 8H), 1.40 (m, 1H), 1.74-1.93 (m, 4H), 2.79 (t, 2H, J = 5.9 Hz), 2.94-3.15 (m, 6H), 3.69 (t, 4H, J = 4.8 Hz), 5.70-5.94 (m, 4H), 6.94 (d, 1H, J= 8.0 Hz). 165 Compound 1i-56 [Formula 2241 H , N 5 1H-NMR (DMSO-d6) 6: 0.98-1.14 (m, 2H), 1.15-1.32 (m, 5H), 1.54 (m, 1H), 1.83-1.96 (m, 4H), 2.89-3.10 (m, 5H), 6.17 (t, 1H, J = 5.2 Hz), 6.63 (d, 1H, J = 2.2 Hz), 7.02 (d, 1H, J = 7.7 Hz), 7.21 (dd, IH, J1 = 9.1 Hz, J2 = 2.5 Hz), 7.27 (dd, 1H, JI = 8.2 Hz, J2 = 4.4 Hz), 7.67 (d, 1H, J = 9.1 Hz), 7.97 (d, 1H, J= 8.2 Hz), 8.45 (dd, 1H, J1 = 4.3 Hz, J2 = 1.5 Hz). 10 Compound Ii-57 [Formula 2251 15 1H-NMR (DMSO-d6) 8: 0.97-1.14 (m, 2H), 1.17-1.34 (m, 8H), 1.54 (m, 1H), 1.83-1.96 (m, 4H), 2.94 (t, 2H, J = 6.0 Hz), 2.99-3.18 (m, 2H), 6.17 (t, 1H, J 5.4 Hz), 6.63 (d, 1H, J= 2.5 Hz), 6.96 (d, 1H, J = 7.7 Hz), 7.21 (dd, 1H, J1 = 9.1 Hz, J2 = 2.5 Hz), 7.27 (dd, 1H, J1 = 8.2 Hz, J2 = 4.1 Hz), 7.67 (d, 1H, J 9.1 Hz), 7.97 (d, 1H, J = 8.0 Hz), 8.45 (dd, 1H, 3 1 = 4.3 Hz, J2 = 1.5 Hz). 20 Compound Ii-58 [Formula 226] H b q,,N N F 166 1H-NMR (DMSO-d6) 8: 0.90-1.07 (m, 2H), 1.12-1.29 (m, 5H), 1.40 (m, 1H), 1.74-1.93 (m, 4H), 2.80 (t, 2H, J = 5.9 Hz), 2.92-3.07 (m, 7H), 3.69 (t, 4H, J = 4.8 Hz), 5.69-5.95 (m, 4H), 6.99 (d, 1H, J = 7.7 Hz). 5 Compound li-59 [Formula 227] H N~ H 10 1H-NMR (DMSO-d6) 5: 0.94-1.11 (m, 2H), 1. 14-1.30 (m, 5H), 1.47 (m, 1H), 1.78-1.95 (m, 4H), 2.88-3.09 (m, 5H), 3.80 (s, 3H), 6.09 (t, 1H, J = 5.6 Hz), 6.81-6.86 (m, 1H), 6.96 (dd, 1H, J1 = 8.8 Hz, J2 = 2.8 Hz), 7.01 (d, 1H, J = 7.4 Hz), 7.29 (t, 1H, J = 8.0 Hz), 7.45-7.51 (m, 2H), 7.66 (d, 1H, J = 8.5 Hz), 8.04 (d, 1H, J = 2.8 Hz). 15 Compound li-60 [Formula 2281 H N N 1H-NMR (DMSO-d6) 6: 1.03 (m, 2H), 1.19 (t, 2H, J = 7.8 Hz), 1.21 (m, 2H), 1.46 (m, 1HI), 20 1.76-1.95 (m, 4H), 2.90 (t, 2H, J = 5.8 Hz), 2.97 (q, 2H, J = 7.3 Hz), 3.03 (m, 1H), 3.80 (a, 3H), 5.95 (m, IH), 6.90 (m, 1H), 6.98 (d, 1H, J = 7.8 Hz), 6.98 (dd, 1H, J = 7.8, 7.8 Hz), 7.06 (d, 1H, J = 8.6 Hz), 7.26 (dd, 1H, J = 7.8, 7.8 Hz), 7.61 (d, 1H, J = 8.6 Hz), 7.69 (d, 1H, J = 7.8 Hz), 8.03 (s, 1H). 25 Compound li-61 [Formula 2291 167 H NN ;N 1H-NMR (DMSO-d6) 6: 0.96-1.09 (m, 2H), 1.18-1.29 (m,2H), 1.19 (t, 3H, J = 7.6 Hz), 1.47 (m, 1H), 1.87 (m, 5H), 2.90 (t, 2H, J = 6.3 Hz), 2.97 (q, 2H, J = 7.6 Hz), 3.02 (m, 1H), 5.98 5 (m, 1H), 6.63 (d, 2H, J = 8.3 Hz), 6.98 (d, 1H, J = 7.3 Hz), 7.14 (m, 1H), 7.73 (s, 2H), 7.83 (d, 2H, J = 8.3 Hz), 8.52 (d, 1H, J = 4.0 Hz). Compound Ii-62 [Formula 230] 10~~ 00, 10 1H-NMR (DMSO-d6) 6: 0.98-1.01 (m, 2H), 1.20 (s, 9H), 1.20-1.37 (m, 2H), 1.42 (m, 1H), 1.76-1.96 (m, 4H), 2.28-2.37 (m, 2H), 2.75-2.85 (m, 2H), 3.02 (m, 1H), 3.36 (t, 2H, J = 7.8 Hz), 3.57 (t, 2H, J = 6.3 Hz), 5.66 (m, 1H), 6.54 (d, 2H, J 8.0 Hz), 6.73 (d, 1H, J = 8.6 15 Hz), 7.00 (d, 1H, J= 8.0 Hz). Compound Ii-63 [Formula 2311 H NN O H 20 1H-NMR (DMSO-d6) 6: 0.96-1.14 (m, 2H), 1. 14-1.32 (m, 21H), 1.19 (t, 3H, J = 7.2 Hz), 1.50 (m, 1H), 1.76-1.96 (m, 4H), 2.91-3.10 (m, 311), 2.97 (q, 2H, J = 7.2 Hz), 6.28 (m, 1H), 7.02 (d, 1H, J = 7.8 H z), 7.32-7.46 (m, 3H), 8.20 (d, 1H, J = 6.9 Hz), 8.22 (s, 2H). 25 Compound Ii-64 168 [Formula 232) s 1H-NMR (DMSO-d6) 8:1.03-1.15 (m, 2H), 1.18-1.29 (m, 2H), 1.24 (d, 6H, J = 6.3 Hz), 5 1.52 (m, 1H), 1.86-1.94 (m, 2H), 2.10-2.19 (m, 2H), 2.40 (t, 2H, J = 6.0 Hz), 2.95 (d, 2H, J = 6.0 Hz), 3.23 (m, 1H), 3.40 (d, 2H, J = 11.4 Hz), 3.75-3.85 (m, 2H), 3.86 (d, 1H, J = 9.3 Hz), 6.14 (d, 1H, J 8.5 Hz), 6.15 (s, 1H), 6.29 (d, 1H, J= 8.5 Hz), 7.06 (d, 1H, J= 8.5 Hz). 10 Compound Ii-65 [Formula 2331 1H-NMR (CDCl3) 8:1.08-1.16 (m, 2H), 1.14 (d, 6H, J = 6.8 Hz), 1.21-1.30 (m, 2H), 1.29 (8, 15 9H), 1.78 (t, 2H, J = 10.6 Hz), 1.83-1.92 (m, 2H), 2.11-2.19 (m, 2H), 2.78 (d, 2H, J = 10.6 Hz), 3.06 (a, 2H), 3.23 (m, 1H), 3.38 (s, 2H), 3.70-3.80 (m, 2H), 4.02 (d, 1H, J= 9.9 Hz), 5.37 (s, 1H), 6.30 (s, 1H). Compound Ii-66 20 [Formula 234] >~ N 1H-NMR (DMSO-d6) 8:1.01-1.12 (m, 2H), 1.20-1.34 (m, 2H), 1.27 (s, 9H), 1.54 (m, 1H), 1.82-1.99 (m, 4H), 2.91-2.98 (m, 2H), 3.06 (m ,1H), 6.17 (a, 1H), 6.63 (s, 1H), 6.78 (d, 1H, 25 J = 9.0 Hz), 7.20 (m, 1H), 7.27 (m, 1H), 7.77 (d, 1H, J = 9.0 Hz), 7.98 (d, 1H, J = 9.0 Hz), 8.54 (a, IH). 169 Compound li-67 [Formula 235] 5 1H-NMR (DMSO-d6) 8: 0.92-1.06 (mn, 2H1), 1.20-1.32 (mn, 2H1), 1.26 (s, 9H1), 1.42 (mn, 1H), 1.78-1.88 (mn, 2H), 1.88-1.96 (in, 2H), 2.78-2.86 (mn, 2H), 3.02 (mn ,1H), 5.89 (s, 1H), 6.56 (d, 1H, J = 8.4 Hz), 6.76 (d, 1H, J = 8.4 Hz), 7.02 (d, 1H, J = 8.4 H z). Compound Ii-68 10 [Formula 236] H S 0 .. 1H-NMR (DMSO-d6) 6: 0.92-1.05 (m, 2H), 1.19 (s, 9H), 1.20-1.32 (m, 2H), 1.26 (m, 9H), 1.42 (m, 1H), 1.80-1.96 (m, 4H), 2.77 ((, 2H), 3.04 (m, 1H), 5.29 (s, 1H), 6.44 (d, 1H, J = 15 7.2 H z), 6.68 (d, 1H, J = 7.2 Hz), 6.75 (d, 1H, J = 8.4 Hz). Compound Ii-69 [Formula 2371 HH 0 .' N 20 1H-NMR (DMSO-d6) 6: 0.95-1.10 (m, 211), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.47 (m, 1H), 1.80-1.88 (m , 2H), 1.88-1.95 (mi(s,H), 2.88-2.95 (m, 2H), 3.02 (a, 1H), 6.07 (, 1H), 6.77 (d, 1H, J = 8.4 H z), 6.97 (d, 1H1, J = 7.6 H z), 7.26 (t, 1H1, J = 7.6 H z), 7.35-7.42 (mn, 211), 7.46 (d, 1H, J = 8.4 Hz), 7.91 (d. 1H, J = 7.6 Hz), 8.04 (s, 1H). 25 Compound li-70 170 [Formula 238] H N ko H F F 1H-NMR (DMSO-d6) 5: 0.93-1.05 (m, 2H), 1.10-1.32 (M, 2H), 1.26 (s, 9H), 1.42 (m, 1H), 5 1.78-1.86 (m, 2H), 1.86-1.95 (m, 2H), 2.78-2.83 (m, 2H), 3.03 (m, 1H), 4.80 (q, 2H, J = 9.2 Hz), 5.48 (t, 1H, J = 5.6 Hz), 6.69-6.76 (m, 2H), 7.08 (dd, 1H, J = 8.8, 2.4 Hz), 7.45 (d, 1H, J= 2.4 Hz). Compound Ii-71 10 [Formula 2391 SH NN 1H-NMR (DMSO-d6) 8: 0.96-1.10 (m, 2H), 1.20-1.32 (m, 2H), 1.27 (s, 9H), 1.82-1.88 (m, 2H), 1.88-1.97 (m, 2H), 2.83-2.88 (m, 2H), 3.04 (m, IH), 5.82 (s, 1H), 6.69 (m, 1H), 6.76 15 (d, 1H, J= 8.8 Hz), 7.12 (dd, 1H, J = 9.2, 8.8 Hz), 7.37 (m, 1H), 7.87 (d, 1H, J = 2.8 Hz), 7.99 (s, 1H). Compound Ii-72 [Formula 2401 H d0 N 20 -N Compound Ii-73 [Formula 2411 H ao . "NN 25 171 Compound Ii-74 [Formula 242] N1 5 Compound li-75 [Formula 243] 0H N N Compound li-76 10 [Formula 2441 H N N Compound li-77 [Formula 245] 15 Compound Ii-78 [Formula 246] H N 20 172 Compound li-79 (Formula 2471 H O0 .. ,,, N 5 Compound Ii-80 [Formula 248] H N N F Compound Ii-81 10 [Formula 2491 H N H N' FL Compound Ii-82 [Formula 2501 0 NI 15F ) Compound Ii-83 [Formula 251] H 'N 15o F H 0 H N' No173 Compound i-84 [Formula 252] H NNYH c b ..,, NF 5 1H-NMR (DMSO-d6) 5: 0.91-1.08 (m, 2H), 1.14-1.30 (t, 3H, J = 7.5 Hz), 1.41 (m, 1H), 1.73-1.94 (m, 4H), 2.34-2.46 (m, 2H), 2.85 (t, 2H, J= 6.6 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.00 (m, 1H), 3.25 (t, 2H, J = 7.5 Hz), 3.53 (t, 2H, J = 6.6 Hz), 6.27 (d, 2H, J = 11.7 Hz), 6.52 (t, 1H, J = 5.1 Hz), 7.00 (d, 1H, J = 7.2 Hz). 10 Compound Ii-85 [Formula 253]

-

0 F F 15 Compound 1-86 [Formula 254] N N, N H 0 F Compound Ii-87 20 [Formula 255] O 0 F O1F 174 Compound Ii-88 [Formula 256) H N F N 5 Compound 11-89 [Formula 257] H ,--' s -N 0I H S'N CI Compound li-90 10 [Formula 258] HH N HCI F Compound li-91 [Formula 2591 H d'b ? N 15 1H-NMR (DMSO-d6) 8: 0.92-1.05 (m, 2H), 1.13 (d, 6H, J= 6.0 Hz), 1.18-1.30 (m, 2H), 1.21 (d, 6H, J = 6.4 Hz), 1.40 (m, 1H), 1.76-1.83 (m, 2H), 1.83-1.93 (m, 2H), 2.19 (dd, 1H, J= 11.2, 11.2 Hz), 2.76-2.82 (m, 2H), 3.01 (m, 1H), 3.09 (m, 1H), 3.45 (d, 2H, J = 11.2 20 Hz), 3.58-3.69 (m, 2H), 5.67 (m, 1H), 5.77 (d, 1H, J = 12.0 Hz), 5.90 (s, 1H), 5.91 (m, 1H), 6.91 (d, 1H, J = 7.6 H z). 175 Compound Ii-92 [Formula 260] H N H o'-b N C| 5 1H-NMR (DMSO-d6) 5: 0.90-1.07 (m, 2H), 1.14-1.30 (m, 2H), 1.21 (d, 6H, J 6.6 Hz), 1.32-1.46 (m, 1H), 1.75-1.92 (m, 4H), 2.78-2.83 (m, 2H), 2.95-3.18 (m, 6H), 3.66-3.72 (m, 4H), 5.75 (brs, 1H), 6.00 (s, 1H), 6.04 (s, 1H), 6.11 (s, iH), 6.95 (d, 1H, J = 9.0 Hz). 10 Compound li-93 [Formula 261] H N . NQ HCI F 1H-NMR (DMSO-d6) 5: 0.90-1.08 (m, 2H), 1.13-1.27 (m, 5H), 1.42 (m, 1H), 1.74-1.93 (m, 15 4H), 2.30-2.40 (m, 2H), 2.81 (d, 2H, J = 6.6 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.00 (m, 1H), 3.49 (t, 2H, J = 7.5 Hz), 3.66 (t, 2H, J = 6.6 Hz), 5.00-5.50 (brs, 2H), 6.07-6.15 (m, 2H), 6.25(s, 1H), 7.00 (d, 1H, J = 6.6Hz). Compound Ii-94 20 [Formula 262] NN HCI F 1H-NMR (DMSO-d6) 5: 0.92-1.07 (m, 211), 1.15-1.32 (m, 5H), 1.21 (d, 6H, J= 6.9 Hz), 1.42 (m, 1H), 1.74-1.93 (m, 4H), 2.30-2.42 (m, 2H), 2.81 (d, 2H, J = 6.6 Hz), 2.92-3.18 (m, 25 2H), 3.49 (t, 2H, J = 7.5 Hz), 3.66 (t, 2H, J = 6.6 Hz), 4.70-5.30 (brs, 2H), 6.05-6.16 (m, 211), 6.25 (s, 1H), 6.95 (d, 111, J = 8.1Hz). 176 Compound Ii-95 [Formula 263] F N 5 1H-NMR (DMSO-d6) 6: 0.90-1.06 (m, 2H), 1.16-1.31 (d, 6H, J = 6.9 Hz), 1.40 (m, 1H), 1.73-1.94 (m, 4H), 2.34-2.46 (m, 2H), 2.84 (t, 2H, J = 6.0 Hz), 2.94-3.16 (m, 2H), 3.28 (t, 2H, J = 7.5 Hz), 3.53 (t, 2H, J= 6.6 Hz), 6.27 (d, 2H, J = 11.7 Hz), 6.52 (t, 1H, J 5.4 Hz), 6.94 (d, 1H, J = 7.8 Hz). 10 Compound li-96 [Formula 2641 H N No F 15 1H-NMR (DMSO-d6) 5: 0.91-1.04 (m, 2H), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.40 (m, IH), 1.76-1.95 (m, 4H), 2.77-2.83 (m, 2H), 2.99-3.04 (m, 5H), 3.67-3.72 (m, 4H), 5.71 (n, 1H), 5.79 (d, 1H, J = 11.7 Hz), 5.89 (a, 1H), 5.90 (m, 1H), 6.72 (d, 1H, J = 8.4 Hz). Compound Ii-97 20 [Formula 2651 N H, 1H-NMR (DMSO-d6) 6: 0.92-1.03 (m, 2H), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.41 (m, IH), 1.77-1.93 (m, 4H), 2.78-2.83 (m, 2H), 2.97-3.05 (m, 5H), 3.68-3.72 (m, 4H), 5.36 (m, IH), 25 6.04 (d, 1H, J = 8.0 Hz), 6.10 (a, 1H), 6.11 (d, 1H, J = 8.0 Hz), 6.72 (d, 1H, J = 8.0 Hz), 6.89 (dd, 1H, J = 8.0, 8.0 Hz). 177 Compound li-98 [Formula 266] H N N- N 5 1H-NMR (DMSO-d6) 6: 0.92-1.04 (m, 2H), 1.17-1.29 (m, 2H), 1.21 (d, 6H, J = 6.4 Hz), 1.41 (m, 1H), 1.75-1.92 (m, 4H), 2.77-2.83 (m, 2H), 2.95-3.05 (m, 5H), 3.09 (m, 1H), 3.67 3.72 (m, 4H), 5.36 (m, 1H), 6.04 (d, 1H, J = 8.0 Hz), 6.10 (s, 1H), 6.11 (d, 1H, J = 8.0 Hz), 6.89 (dd, 1H, J = 8.0, 8.0 Hz), 6.92 (d, 1H, J = 8.0 Hz). 10 Compound li-99 [Formula 2671 N N 15 1H-NMR (DMSO-d6) 5: 0.90-1.06 (m, 2H), 1.15-1,31 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.47-1.62 (m, 6H), 1.74-1.94 (m, 4H), 2.78 (t, 2H, J = 6.0 Hz), 2.93-3.16 (m, 6H), 5.64-5.76 (m, 2H), 5.83-5.92 (m, 2H), 6.94 (d, 1H, J = 7.8 Hz). Compound li-100 20 [Formula 268] H~ NN 1H-NMR (DMSO-d6) 5: 0.90-1.06 (m, 2H), 1.15-1.30 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.40 (m, IH), 1.74-1.96 (m, 8H), 2.79 (t, 2H, J = 6.0 Hz), 2.93-3.18 (m, 6H), 5.48-5.67 (m, 25 4H), 6.94 (d, 1H, J = 8.1 Hz). Compound Ii-101 178 [Formula 269] F 1H-NMR (DMSO-d6) 6: 0.90-1.06 (m, 2H), 1.13-1.29 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 5 1.39 (m, 1H), 1.47-1.62 (m, 6H), 1.75-1.94 (m, 4H), 2.79 (t, 2H, J = 6.0 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.03-3.10 (m, 4H), 5.64-5.75 (m, 2H), 5.83-5.91 (m, 2H), 7.00 (d, 1H, J= 7.8 Hz). Compound 1i-102 10 [Formula 270] H d, 6N _ ND F 1H-NMR (DMSO-d6) 6: 0.90-1.07 (m, 2H), 1.13-1.29 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.41 (m, 1H), 1.74-1.96 (m, 8H), 2.79 (t, 2H, J = 6.0 Hz), 2.97 (q, 2H, J 7.5 Hz), 3.00 (m. 15 IH), 3.09-3.19 (m, 4H), 5.46-5.66 (m, 4H), 6.99 (d, 1H, J = 7.2 Hz). Compound Ii- 103 [Formula 271] NN d' ** .,AWNq N F 20 1H-NMR (DMSO-d6) 5: 0.91-1.03 (m, 2H), 1.16-1.29 (m, 2H), 1.21 (d, 6H, J = 6.8 Hz), 1.40 (m, IH), 1.75-1.92 (m, 4H), 2.20 (a, 3H), 2.35-2.43 (m, 4H), 2.75-2.82 (m, 2H), 2.88 3.13 (m, 6H), 5.67 (m, IH), 5.76 (d, 1H, J = 11.2 Hz), 5.82-5.92 (m, 2H), 6.91 (d, 1H, J = 8.0 Hz). 25 Compound li- 104 179 [Formula 2721 H rN F 1H-NMR (DMSO-d6) 5: 0.92-1.02 (m, 2H), 1. 19-1.32 (m, 2H), 1.26 (s, 9H), 1.39 (m, 1H), 5 1.75-1.95 (m, 4H), 2.19 (s, 3H), 2.38-2.42 (m, 4H), 2.77-2.83 (m, 5H), 2.98-3.09 (m, 5H), 5.67 (m, 1H), 5.76 (d, 1H, J = 11.2 Hz), 5.88 (m, IH), 5.88 (a, 1H), 6.72 (d, 1H, J = 8.8 Hz). Compound Ii-105 10 [Formula 273] N H N F 1H-NMR (DMSO-d6) 6: 0.95-1.09 (m, 2H), 1.18-1.31 (m, 2H), 1.22 (d, 6H, J = 6.8 Hz), 1.44 (m, 1H), 1.78-1.93 (m, 4H), 2.87-2.92 (m, 2H), 3.03 (m, 1H), 3.10 (m, 1H), 6.13 (m, 15 1H), 6.21 (m, IH), 6.22 (8, 2H), 6.51 (s, 1H), 6.52 (d, 1H, J = 8.0 Hz), 6.92 (d, 1H, J = 8.0 Hz), 7.26 (s, 2H). Compound Ii-106 [Formula 2741 H ,N 20 F 1H-NMR (DMSO-d6) 6: 0.97-1.08 (m, 2H), 1.17-1.29 (m, 5H), 1.40-1.68 (m, 3H), 1.80-1.92 (m, 2H), 2.90 (t, 2H, J = 6.0 Hz), 2.94-3.06 (m, 3H), 6.12-6.22 (m, 4H), 6.50-6.54 (m, 2H), 6.94-7.00 (m, 1H), 7.26-7.27 (m, 2H). 25 Compound Ii-107 180 [Formula 2751 N H I c'b N qN . F 1H-NMR (DMSO-d6) 5: 0.91-1.03 (m, 2H), 1. 16-1.29 (m, 2H), 1.21 (d, 6H, J = 6.4 Hz), 5 1.40 (m, 1H), 1.74-1.92 (m, 4H), 2.75-2.81 (m, 2H), 2.84 (a, 3H), 3.00 (m, 1H), 3.09 (m, 1H), 3.25 (s, 3H), 3.35-3.47 (m, 4H), 5.59-5.67 (m, 4H), 6.91 (d, 1H, J = 8.0 Hz). Compound li-108 [Formula 2761 HH N N I 10 1H-NMR (DMSO-d6) 5: 0.92-1.03 (m, 2H), 1. 18-1.32 (m, 2H), 1.26 (s, 9H), 1.40 (m, 1H), 1.75-1.94 (m, 4H), 2.75-2.81 (m, 2H), 2.83 (s, 3H), 3.01 (m, 1H), 3.25 (8, 3H), 3.34-3.47 (m, 4H), 5.58-5.70 (m, 4H), 6.72 (d, 1H, J = 8.4 Hz). 15 Compound 1i-109 [Formula 277] N N o F 20 1H-NMR (DMSO-d6) 6: 0.90-1.51 (m, 10H), 1.21 (d, 6H, J = 6.9 Hz), 1.56-1.67 (m, 3H), 1.71-1.93 (m, 6H), 2.64 (s, 3H), 2.78 (t, 2H, J = 6.0 Hz), 2.93-3.17 (m, 2H), 3.44 (m, 1H1), 5.56-5.77 (m, 4H), 6.94 (d, 1H, J = 7.8 Hz). Compound li-110 25 [Formula 278] 181 Hg 1Q0 N F 1H-NMR (DMSO-d6) 5: 0.83-1.01 (m, 2H), 1.00-1.40 (m, 3H), 1.21 (d, 6H, J = 6.9 Hz), 1.68-1.91 (m, 4H), 2.73 (t, 2H, J= 6.0 Hz), 2.90-3.15 (m, 2H), 2.95 (s, 3H), 4,48 (s, 2H), 5 5.60-5.72 (m, 4H), 6.94 (d, 1H, J= 7.8 Hz), 7.15-7.35 (m, 5H). Compound li-111 [Formula 2791 H 10 1H-NMR (DMSO-d6) 6: 0.97-1.14 (m, 2H), 1.14-1.33 (m, 5H), 1.45-1.61 (m, 1H), 1.81-1.96 (m, 4H), 2.90-3.10 (m, 5H), 6.34 (t, 1H, J = 5.2 Hz), 6.51 (d, 1H, J = 2.2 Hz), 6.99-7.07 (m, 2H), 7.36 (dd, 1H, J = 8.2, 4.1 Hz), 8.02 (d, 1H, J = 8.5 Hz), 8.48 (dd, 1H, J = 4.1, 1.4 Hz). 15 Compound Ii-112 [Formula 280] F IH-NMR (DMSO-d6) 5: 0.97-1.13 (m, 2H), 1.17-1.34 (m, 8H), 1.45-1.59 (m, 111), 1.81-1.99 20 (m, 4H), 2.94 (t, 2H, J = 5.9 Hz), 2.99-3.21 (m, 2H), 6.33 (t, 1H, J = 5.4 Hz), 6.51 (d, 1H, J = 2.2 Hz), 6.96 (d, 1H, J = 7.7 Hz), 7.02 (dd, 111, J = 13.5, 2.2 Hz), 7.36 (dd, 1H, J = 8.2, 4.1 Hz), 8.02 (d, 1H1, J = 8.5 Hz), 8.48 (dd, 111, J = 4.1, 1.4 Hz). Compound li-113 25 [Formula 2811 182 1H-NMR (DMSO-d6) 6: 0.93-1.13 (m, 2H), 1.15-1.34 (m, 8H), 1.39-1.57 (m, 1H), 1.79-1.95 (m, 4H), 2.87 (t, 2H, J = 6.2 Hz), 2.94-3.16 (m, 2H), 3.54 (a, 3H), 5.66 (t, 1H, J = 5.5 Hz), 5 6.49 (d, 1H, J = 9.6 Hz), 6.73 (d, 1H, J = 2.8 Hz), 6.91-7.02 (m, 2H), 7.29 (d, 1H, J = 9.3 Hz), 7.72 (d, 1H, J= 9.3 Hz). Compound Ii-114 [Formula 282] 10 N 1H-NMR (DMSO-d6) 6: 0.93-1.10 (m, 2H), 1.14-1.33 (m, 8H), 1.41-1.56 (m, 1H), 1.79-1.94 (m, 4H), 2.89 (t, 2H, J = 6.0 Hz), 2.95-3.16 (m, 2H), 6.00 (t, 1H, J = 5.4 Hz), 6.84 (dd, 1H, J = 8.8, 2.2 Hz), 6.95 (d, 1H, J = 8.0 Hz), 7.07 (d, 1H, J = 2.2 Hz), 7.72 (d, 1H, J = 8.8 Hz), 15 8.86 (s, 1H). Compound Ii-115 [Formula 2831 20 1H-NMR (DMSO-d6) 8: 0.94-1.06 (m, 4H), 1.26 (s, 9H), 1.40-1.51 (m, 1H), 1.84 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.85-2.90 (m, 2H), 2.97-3.06 (m, 1H), 5.93-5.99 (in, 1H), 6.63-6.79 (m, 3H), 7.40 (d, 1H, J = 8.8 Hz), 8.32 (s, 1H). 25 Compound Ii-116 [Formula 2841 183 1H-NMR (DMSO-d6) 6:0.95-1.07 (m, 4H), 1.26 (s, 9H), 1.39-1.47 (m, IH), 1.80 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.87-2.93 (m, 2H), 2.98-3.06 (m, 1H), 3.37 (s, 3H), 5 6.27 (s, 1H), 6.55 (d, 1H, J = 8.8 Hz), 6.73 (d, 1H, J = 8.8 Hz), 6.80 (t, 1H, J = 5.2 Hz), 7.32 (d, 1H, J = 8.8 Hz). Compound Ii-117 [Formula 285] 10 1H-NMR (DMSO-d6) 5:0.94-1.08 (m, 4H), 1.20 (a, 3H), 1.22 (s, 3H), 1.39-1.51 (m, 1H), 1.80 (d, 2H, J = 12.4 Hz), 1.88 (d, 2H, J= 12.4 Hz), 2.87-2.94 (m, 2H), 2.97-3.07 (m, 1H), 3.08-3.14 (m, 1H), 3.37 (a, 3H), 6.27 (s, 1H), 6.55 (d, 1H, J = 8.4 Hz), 6.82 (t, 1H, J = 5.6 15 Hz), 6.94 (d, 1H, J = 8.0 Hz), 7.32 (d, 1H, J = 8.4 Hz). Compound Ii-118 [Formula 286] > I " N 20 1H-NMR (DMSO-d6) 6: 0.92-1.06 (m, 4H), 1.26 (s, 9H), 1.38-1.50 (m, IH), 1.83 (d, 2H, J - 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.80-2.86 (m, 2H), 2.96-3.06 (m, 1H), 3.26 (a, 3H), 5.58-5.65 (m, 1H), 6.27 (d, 1H, J = 8.4 Hz), 6.38 (s, 1H), 6.75 (d, 1H, J = 8.4 Hz), 6.99 (d, 1H, J= 8.4 Hz). 25 Compound Ii-119 [Formula 287] 184 HI IH-NMR (DMSO-d6) 8:0.94-1.06 (m, 4H), 1.26 (s, 9H), 1.39-1.50 (m, IH), 1.84 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.81-2.89 (m, 2H), 2.96-3.07 (m, IH), 3.51 (s, 3H), 5 5.79-5.84 (m, 1H), 6.60 (s, 1H), 6.75 (d, 1H, J = 8.8 Hz), 7.03 (d, 1H, J= 8.8 Hz), 7.19 (d, 1H, J = 8.8 Hz). Compound Ii-120 [Formula 288] 10 1H-NMR (DMSO-d6) 6: 0.93-1.10 (m, 4H), 1.26 (s, 9H), 1.37-1.40 (m, 1H), 1.42 (s, 3H), 1.44 (s, 3H), 1.83 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.79-2.96 (m, 2H), 2.97 3.07 (i, 1H), 4.33-4.46 (m, 1H), 5.50-5.59 (m, 1H), 6.25 (d, 1H, J= 8.8 Hz), 6.57 (s, 1H), 15 6.75 (d, 1H, J = 8.4 Hz), 7.00 (d, 1H, J = 8.4 Hz). Compound Ii-121 [Formula 2891 NN o>b No Cl 20 1H-NMR (DMSO-d6) 8: 0.90-1.06 (m, 41), 1.26 (s, 9H), 1.36-1.49 (m, 1H), 1.82 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.80-2.87 (m, 2H), 2.95-3.97 (m, 1H), 3.27 (s, 3H), 5.85-5.92 (m, 1H), 6.33 (s, 1H), 6.36 (s, 1H), 6.75 (d, 1H, J = 8.8 Hz). 25 Compound Ii-122 [Formula 2901 185 N H CI 1H-NMR (DMSO-d6) 8: 0.92-1.08 (m, 4H), 1.26 (s, 9H), 1.38-1.41 (m, 1H), 1.42 (s, 3H), 1.43 (s, 3H), 1.82 (d, 2H, J = 11.8 Hz), 1.90 (d, 2H, J = 11.8 Hz), 2.83-2.88 (m, 2H), 2.98 5 3.06 (m, 1H), 4.33-4.47 (m, IH), 6.35 (s, 1H), 6.54 (s, 1H), 6.76 (d, 1H, J= 8.4 Hz), 8.32 (s, 1H). Compound Ii- 123 [Formula 2911 0 10 1H-NMR (DMSO-d6) 6: 0.93-1.06 (m, 4H), 1.22 (s, 3H), 1.24 (s, 3H), 1.26 (a, 9H), 1.39 1.50 (m, 1H), 1.81 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.87-2.93 (m, 2H), 2.96 3.07 (m, 1H), 4.39-4.47 (m, 1H), 6.30 (a, 1H), 6.54 (d, 11H, J = 8.8 Hz), 6.77 (d, 1H, J 8.8 15 Hz), 6.86 (t, 1H, J = 5.2 Hz), 7.32 (d, 1H, J = 8.4 Hz). Compound Ii- 124 [Formula 2921 o'b 0 20 1H-NMR (DMSO-d6) 6: 0.90-1.05 (m, 411), 1.26 (s, 9H), 1.36-1.51 (m, 1H), 1.79 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.80-2.86 (m, 2H), 3.01 (s, 3H), 3.02-3.05 (m, 1H), 3.49 (t, 2H, J = 4.8 Hz), 4.26 (t, 2H, J = 4.8 Hz), 6.02 (s, 1H), 6.20 (t, 1H, J = 5.6 Hz), 6.31 (d, 1H, J = 8.8 Hz), 6.74 (d, 1H, J = 8.8 Hz), 7.43 (d, 1H, J = 8.4 Hz). 25 Compound Ii- 125 186 [Formula 2931 0 1H-NMR (DMSO-d6) 6: 0.92-1.02 (m, 4H), 1.08 (t, 3H, J= 7.2 Hz), 1.25 (s, 9H), 1.35-1.42 5 (m, 1H), 1.79 (d, 2H, J = 12.0 Hz), 1.90 (d, 2H, J = 12.0 Hz), 2.80-2.86 (m, 2H), 2.96-3.05 (m, 1H), 3.42-3.51 (m, 4H), 4.20-4.26 (m, 2H), 6.03 (a, 1H), 6.20 (s, 1H), 6.31 (d, 1H, J = 8.8 Hz), 6.75 (d, 1H, J = 8.8 Hz), 7.42 (d, 1H, J = 8.8 Hz). Compound Ii-126 10 [Formula 294] 1H-NMR (DMSO-d6) 6: 0.92-1.02 (m, 4H), 1.09 (s, 3H), 1.11 (s, 3H), 1.25 (s, 9H), 1.43 1.55 (m, 1H), 1.80 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.0 Hz), 2.84 (m, 2H), 2.97-3.08 15 (m, IH), 3.37 (t, 2H, J = 5.2 Hz), 4.18 (t, 2H, J = 5.2 Hz), 4.71-4.80 (m, 1H), 6.05 (8, 1H), 6.19 (t, 1H, J = 5.2 Hz), 6.32 (d, 1H, J = 8.8 Hz), 6.74 (d, 1H, J = 8.4 H z), 7.18 (d, 1H, J = 8.4 Hz). Compound Ii-127 20 [Formula 2951 H j~F C FF 'v N N 1H-NMR (DMSO-d6) 5: 0.94-1.12 (in, 2H), 1.14-1.39 (m, 5H), 1.34-1.56 (m, 1H), 1.70-1.97 (m, 4H), 2.87-3.10 (m, 5H), 6.17 (t, 1H, J = 5.2 Hz), 6.94-7.06 (m, 2H), 7.35-7.47 (m, 4H), 25 7.75-7.80 (m, 1H), 8.07 (d, 1H, J = 3.0 Hz). 187 Compound li-128 [Formula 2961 H 0- F N 5 1H-NMR (DMSO-d6) 8: 0.96-1.12 (m, 2H), 1.14-1.31 (m, 5H), 1.31-1.55 (m, 1H), 1.70-1.96 (m, 4H), 2.89-3.09 (m, 5H), 6.24 (t, 1H, J = 5.4 Hz), 6.94-7.05 (m, 2H), 7.24 (d, 1H, J = 6.9 Hz), 7.52 (t, 1H, J = 8.0 Hz), 7.75 (d, 1H, J = 8.8 Hz), 7.88-7.97 (m, 2H), 8.07 (d, 1H, J = 2.5 Hz). 10 Compound li-129 [Formula 2971 H N 1H-NMR (DMSO-d6) 5: 0.98-1.12 (m, 2H), 1.18-1.30 (m, 2H), 1.19 (t, 3H, J = 6.8 H z), 15 1.48 (m, 1H), 1.79-1.95 (m, 4H), 2.92-3.09 (m, 3H), 2.97 (q, 2H, J = 6.8 Hz), 6.27 (m, 1H), 7.01 (d, 1H, J = 8.0 Hz), 7.39-7.47 (m, 2H), 7.56 (m, 1H), 8.18-8.25 (m, 2H), 8.23 (a, 2H). Compound Ii-130 [Formula 2981 H N 20 1H-NMR(DMSO-d6) 6:0.96-1.12 (m, 2H), 1.15-1.30 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.45-1.64 (m, 1H), 1.78-1.96 (m, 4H), 2.97 (q, 2H, J = 7.2 Hz), 2.95-3.15 (m, 1H), 3.22 3.28 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 6.94-7.02 (m, 2H), 7.38 (t, 1H, J = 6.0 Hz), 7.46 (t, 25 2H, J = 7.5 Hz), 7.78 (d, 1H, J = 9.0 Hz), 7.96 (d, 2H, J = 9.0 Hz). 188 Compound li-131 [Formula 2991 H N. F 5 1H-NMR (DMSO-d6) 6: 0.96-1.12 (m, 2H), 1.15-1.30 (m, 2H), 1.18 (t, 3H, J= 7.2 Hz), 1.48-1.62 (m, 1H), 1.78-1.96 (m, 4H), 2.98 (q, 2H, J = 7.2 Hz), 2.94-3. 10 (m, 1H), 3.22 3.28 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 7.02 (d, 1H, J = 9.0 Hz), 7.10 (t, 1H, J = 5.4 Hz), 7.22 (td, 1H, J = 9.0, 3.0 Hz), 7.47-7.56 (m, 1H), 7.77-7.88 (m, 3H). 10 Compound li-132 [Formula 3001 H __.s N / N'N 1H-NMR (DMSO-d6) 6: 0.96-1.13 (m, 2H), 1.15-1.32 (m, 2H), 1.19 (t, 3H, J = 7.5 Hz), 15 1.48-1.65 (m, 1H), 1.78-1.96 (m, 4H), 2.98 (q, 2H, J = 7.2 Hz), 2.94-3.12 (m, 1H), 3.22 3.28 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 7.01 (d, 1H, J = 6.0 Hz), 7.09 (t, 1H, J = 5.4 Hz), 7.27-7.35 (m, 2H), 7.42-7.50 (m, IH), 7.57 (dd, IH, J = 9.0, 3.0 Hz), 7.86 (td, 1H, J = 7.5, 3.0 Hz). 20 Compound Ii-133 [Formula 301] 1H-NMR (DMSO-d6) 6: 0.92-1.08 (m, 2H), 1.15-1.30 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 25 1.42-1.58 (m, 1H), 1.72-1.94 (m, 4H), 2.95-3.20 (m, 4H), 4.89-4.98 (m, 2H), 6.65 (brs, 1H), 189 6.92 (d, 1H, J = 9.0 Hz), 6.91-6.98 (m, 1H), 7.03 (d, 1H, J = 9.0 Hz). Compound li-134 [Formula 302] 5 N6 ,,F 1H-NMR (DMSO-d6) 5:0.90-1.08 (m, 2H), 1.15-1.30 (m, 2H), 1.21 (d, 6H, J 6.6 Hz), 1.42-1.58 (m, 1H), 1.72-1.94 (m, 4H), 2.92-3.20 (m, 4H), 6.74 (t, 1H, J = 6.0 Hz), 6.94 (t, 1H, J = 6.0 Hz), 6.97 (s, 1H), 7.08-7.24 (in, 5H). 10 Compound Ii-135 [Formula 303] H N .. N 15 1H-NMR (DMSO-d6) 6: 0.95-1.10 (m, 2H), 1.12-1.30 (m, 2H), 1.19 (t, 3H, J= 7.2 Hz), 1.48-1.60 (m, 1H), 1.76-1.94 (m, 4H), 2.92-3.10 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.18 3.30 (m, 2H), 6.89 (d, 1H, J = 9.6 Hz), 7.02 (brs, 1H), 7.11 (t, 1H, J = 5.4 Hz), 7.42-7.56 (m, 2H), 7.85 (d, 1H, J = 9.6 Hz), 7.93 (d, 1H, J = 7.5 Hz), 8.03 (s, 1H). 20 Compound Ii-136 [Formula 304] N C1 Cl 1H-NMR (DMSO-d6) 5: 0.98-1.12 (m, 2H), 1.13-1.30 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 25 1.48-1.62 (m, 1H), 1.78-1.96 (m, 4H), 2.92-3.12 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.22 190 3.32 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 7.01 (d, 1H, J = 7.5 Hz), 7.20 (t, 1H, J = 6.0 Hz), 7.62 (s, 1H), 7.91 (d, 1H, J = 9.0 Hz), 8.02 (s, 2H). Compound Ii- 137 5 [Formula 305] H ,,-sN F F 1H-NMR (DMSO-d6) 6: 0.95-1.12 (m, 2H), 1.13-1.30 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.65-1.95 (m, 5H), 2.93-3.12 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.25-3.40 (m, 2H), 5.07 10 5.16 (m, 2H), 7.01 (d, 1H, J= 7.5 Hz), 7.25 (t, 1H, J = 6.0 Hz), 7.92-8.03 (m, 3H), 8.33 (d, 1H, J= 6.0 Hz). Compound Ii- 138 [Formula 3061 H F 1H-NMR (DMSO-d6) 5: 0.91-1.26 (m, 4H), 1.19 (t, 3H, J= 7.5 Hz), 1.36-1.43 (m, 1H), 1.78-1.90 (m, 4H), 2.90-3.07 (m, 3H), 2.96 (q, 2H, J = 7.5 Hz), 5.69 (t, 1H, J = 5.7 Hz), 5.81 (d, 1H, J = 2.4 Hz), 7.00 (d, 1H, J = 7.8 Hz), 7.16-7.39 (m, 3H), 7.73-7.79 (m, 1H), 20 7.86-7.88 (m, 1H). Compound li- 139 [Formula 307] N F 25 1H-NMR (DMSO-d6) 6: 0.90-1.06 (m, 4H), 1.20 (s, 3H), 1.22 (s, 3H), 1.40-1.52 (m, IH), 1.81 (d, 2H, J= 12.4 Hz), 1.88 (d, 2H, J = 12.4 Hz), 2.90-2.98 (m, 2H), 2.99-3.13 (m, 2H), 5.68 (t, 1H, J = 5.6 Hz), 5.81 (s, 1H), 6.93 (d, 1H, J = 8.8 Hz), 7.16-7.40 (m, 3H), 7.76 (t, 191 1H, J = 8.0 Hz), 7.87 (s, 1H). Compound Ii-140 [Formula 308] >N N ~NQ 1H-NMR (DMSO-d6) 5: 0.90-1.06 (m, 4H), 1.26 (s, 9H), 1.40-1.49 (m, 1H), 1.82 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.90-2.99 (m, 2H), 3.01-3.06 (m, 1H), 5.67 (t, 1H, J = 6.0 Hz), 5.81 (s, 1H), 6.74 (d, 1H, J = 8.4 Hz), 7.14-7.40 (m, 3H), 7.76 (t, 1H, J = 8.4 10 Hz), 7.87 (s, 1H). Compound Ii- 141 [Formula 309] 0, H ,,N 15 1H-NMR (DMSO-d6) 6: 0.97-1.06 (m, 2H), 1.18-1.27 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.45-1.59 (m, 1H), 1.76-1.81 (m, 2H), 1.87-1.91 (m, 2H), 2.97-3.09 (m, 1H), 3.10-3.13 (m, 1H), 3.17-3.22 (m, 2H), 6.94-7.02 (m, 2H), 6.98 (td, 1H, J = 7.8, 1.2 Hz), 7.36 (dd, 1H, J = 7.8, 0.6 Hz), 7.65 (dd, 1H, J = 7.8, 0.6 Hz), 8.00-8.05 (m, 1H). 20 Compound li-142 [Formula 3101 N 25 1H-NMR (DMSO-d6) 6: 0.96-1.04 (m, 2H), 1. 18-1.28 (m, 2H), 1.20 (d, 6H, J = 6.9 Hz), 1.43-1.59 (m, IH), 1.74-1.79 (m, 2H), 1.85-1.90 (m, 2H), 2.92-3.07 (m, 1H), 3.09-3.18 (m, 3H), 6.92-6.99 (m, 2H), 7.10 (td, 1H, J = 7.8, 1.2 Hz), 7.21 (dd, 1H, J = 7.8, 0.6 Hz), 7.31 192 (dd, 1H, J = 7.8, 0.6 Hz), 7.89-7.97 (m, 1H). Compound Ii-143 [Formula 311] H 1H-NMR (DMSO-d6)6: 0.97-1.07 (m, 2H), 1.17-1.23 (m; 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.42-1.57 (m, 1H), 1.73-1.78 (m, 2H), 1.86-1.90 (m, 2H), 2.93-3.02 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.11 (t, 2H, J = 6.3 Hz), 6.91-7.02 (m, 2H), 7.19 (dd, 1H, J 8.4, 4.8 Hz), 7.34 10 (dd, 1H, J = 9.3, 2.4 Hz), 8.00 (t, 1H, J 6.0 Hz). Compound Ii-144 [Formula 3121 H N 15 1H-NMR (DMSO-d6)6: 0.97-1.08 (m, 2H), 1.16-1.24 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.42-1.59 (m, IH), 1.74-1.80 (m, 2H), 1.85-1.90 (m, 2H), 2.92-3.03 (m, 1H), 2.97 (q, 2H, J = 7.5 Hz), 3.18 (t, 2H, J = 6.3 Hz), 6.99-7.07 (m, 2H), 7.33 (dd, 1H, J = 9.0, 4.8 Hz), 7.58 (dd, 1H, J = 8.7, 2.7 Hz), 8.00 (t, 1H, J = 5.4 Hz). 20 Compound Ii-145 (Formula 313] 0, s N 25 1H-NMR (DMSO-d6) 6: 0.97-1.09 (m, 2H), 1.17-1.23 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.43-1.59 (m, 1H), 1.72-1.81 (m, 2H), 1.85-1.92 (m, 2H), 2.95-3.06 (m, 1H), 2.97 (q, 2H, J 193 = 7.5 Hz), 3.19 (t, 2H, J = 6.0 Hz), 7.01 (d, 1H, J = 8.1 Hz), 7.20-7.23 (m, 1H), 7.33 (dd, 1H, J = 8.7, 0.6 Hz), 7.58 (dd, 1H, J= 2.1, 0.9 Hz), 8.11-8.18 (m, 1H). Compound Ii- 146 5 (Formula 3141 H N 1H-NMR (DMSO-d6) 6: 0.98-1.06 (m, 2H), 1.15-1.21 (m, 2H), 1.18 (t, 3H, J 7.2 Hz), 1.42-1.58 (m, 1H), 1.70-1.81 (m, 2H), 1.82-1.96 (m, 2H), 2.93-3.00 (m, 3H), 3.13-3.19 (m, 10 2H), 6.98-7.02 (m, 2H), 7.26-7.27 (m, 1H), 7.32-7.35 (m, 1H), 8.18-8.21 (m, 1H). Compound Ii-147 [Formula 315] H N F 15 1H-NMR (DMSO-d6) 6: 0.98-1.04 (m, 2H), 1.16-1.23 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.43-1.59 (m, 1H), 1.73-1.78 (m, 2H), 1.86-1.89 (m, 2H), 2.93-3.00 (m, 3H), 3.11-3.15 (m, 2H), 6.72-6.79 (m, 1H), 7.00-7.08 (m, 2H), 7.29-7.34 (m, 1H), 8.13-8.16 (m, 1H). 20 Compound Ii- 148 [Formula 316] H NN 1H-NMR (DMSO-d6) 5: 0.94-1.06 (m, 2H), 1.15-1.26 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 25 1.45-1.58 (m, 1H), 1.72-1.80 (m, 2H), 1.84-1.92 (m, 2H), 2.96 (q, 2H, J = 7.2 Hz), 2.96 3.05 (m, 1H), 3.09-3.16 (m, 2H), 6.99 (d, 1H, J = 8.0 Hz), 7.13 (dd, 1H, J = 8.0, 2.0 Hz), 194 7.20 (d, 1H, J = 8.4 Hz), 7.49 (d, 1H, J = 2.0 Hz), 8.11 (t, 1H, J = 6.0 Hz). Compound Ii-149 [Formula 3171 H N5 N 1H -NMR (DMSO-d6) 8: 0.96-1.08 (m, 2H), 1.12-1.24 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.43-1.59 (m, 1H), 1.74-1.80 (m, 2H), 1.86-1.91 (m, 2H), 2.93-3.01 (m, 3H), 3.17-3.22 (m, 2H), 7.00-7.05 (m, 2H), 7.37-7.39 (m, 1H), 7.65-7.68 (m, 1H), 8.22-8.26 (m, 1H). 10 Compound Ii-150 (Formula 3181 N F 15 1H-NMR (DMSO-d6) 5: 0.98-1.08 (m, 2H), 1.15-1.29 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.44-1.60 (m, 1H), 1.74-1.80 (m, 2H), 1.86-1.91 (m, 2H), 2.95-3.17 (m, 2H), 3.21-3.27 (m, 2H), 6.95-6.98 (m, 1H), 8.10 (dd, 1H, J = 8.4, 2.7 Hz), 8.19 (dd, 1H, J = 3.0, 1.5 Hz), 8.44 8.47 (m, 1H). 20 Compound Ii-151 [Formula 3191 N Nc 1H-NMR (DMSO-d6) 6: 0.99-1.04 (m, 2H), 1.15-1.23 (m, 2H), 1.21 (d, 6H, J = 6.3 Hz), 25 1.43-1.59 (m, 1H), 1.73-1.81 (m, 2H), 1.85-1.91 (m, 2H), 2.97-3.18 (m, 2H), 3.21-3.29 (m, 2H), 6.95-6.98 (m, 1H), 8.20-8.23 (m, 2H), 8.58-8.61 (m, 11). 195 Compound li-152 [Formula 320] 5 1H-NMR (DMSO-d6) 8: 0.96-1.04 (m, 2H), 1.15-1.26 (m, 2H), 1.25 (s, 9H), 1.56-1.62 (m, 1H), 1.78-1.83 (m, 2H), 1.87-1.93 (m, 2H), 2.98-3.08 (m, 1H), 3.17 (t, 2H, J = 6.3 Hz), 3.48 (s, 311), 6.47 (d, 2H, J = 8.7 Hz), 6.89-6.96 (m, 2H), 7.11-7.19 (m, 2H). 10 Compound Ii-153 [Formula 321] H S'N H 0 0 -. ~ N F 00 1H-NMR (DMSO-d6) 6: 0.95-1.04 (m, 2H), 1.13-1.30 (m, 2H), 1.18 (t, 3H, J= 7.5 Hz), 15 1.41 (m, 1H), 1.71-1.94 (m, 4H), 2.80-2.89 (m, 2H), 2.92-3.10 (m, 2H), 2.97 (q, 2H, J = 7.5 Hz), 3.21-3.30 (m, 2H), 6.25-6.35 (m, 2H), 6.39 (dd, 1H, J= 8.4, 2.1 Hz), 7.01 (d, 1H, J = 7.5 Hz), 7.01 (dd, 1H, J = 8.4, 8.4 Hz). Compound Ii-154 20 [Formula 322] H N 1H-NMR (DMSO-d6) 6: 0.91-1.09 (m, 2H), 1.16-1.28 (m, 2H), 1.18 (t, 3H, J 7.5 Hz), 1.42 (m, 1H), 1.74-1.95 (m, 4H), 2.80-3.16 (m, 9H), 2.97 (q, 2H, J = 7.5 Hz), 6.24-6.36 (m. 196 2H), 6.30 (dd, 1H, J= 8.4, 2.1 Hz), 7.10 (dd, 1H, J = 8.4, 2.1 Hz), 7.05 (d, 1H, J = 8.4 Hz). Compound Ii-155 [Formula 3231 H N N 5 F 0 Compound Ii-156 (Formula 3241 H DN N F 0 10 Compound i-157 [Formula 3251 a N~ c N 15 Compound Ii-158 [Formula 3261 H N 01 Fk 1H-NMR (DMSO-d6) 6: 0.91-1.07 (m, 2H), 1.10-1.30 (m, 5H), 1.41 (m, 1H), 1.76-1.94 (m, 20 4H), 2.74-2.83 (m, 2H), 2.83 (s, 3H), 2.90-3.08 (m, 3H), 2.96 (s, 3H), 5.68 (m, 1H), 6.39 (m, 1H), 6.58 (m, 1H), 6.95 (dd, 1H, J = 8.4, 8.4 Hz), 7.00 (d, 1H, J = 7.8 Hz). 197 Compound Ii-159 [Formula 327] 0 ~H F 5 Compound Ii-160 [Formula 3281 H IINH 00 N F 10 Compound Ii-161 [Formula 329] H N

F

3 Compound Ii-162 15 [Formula 330] H N 0

CF

3 Compound Ii-163 [Formula 331] 198 AH NN Fo -N 0 Compound Ii-164 [Formula 332] AN F N, 5 0 Compound li- 165 [Formula 333] NN F . N F 0 10 Compound li-166 [Formula 334] NKF F 0 15 Compound Ii-167 [Formula 335] 199 Compound Ii- 168 [Formula 3361 S' ., 0 5 Compound i- 169 [Formula 3371 O O N F 10 Compound 1- 170 [Formula 3381 0N F 15 Compound li-171 [Formula 3391 N N N~No

CF

3 200 Compound Ii-172 [Formula 3401 H H N

CF

3 5 Compound Ii-173 [Formula 341] H ,N H1 r . N N C F 3 10 1H-NMR (DMSO-d6) 8: 0.95-1.08 (m, 2H), 1.15-1.28 (m, 2H), 1.19 (t, 3H, J = 7.2 H z),1.43 (m, 1H), 1.76-1.85 (m, 2H), 1.85-1.93 (m, 2H), 2.76-2.82 (m, 2H), 2.88 (t, 2H, ,J = 6.0 Hz), 2.97 (t, 2H, J = 7.2 Hz), 3.00 (m, 11), 3.64-3.70 (m, 4H), 6.33 (m, 1H), 6.37 (d, 1H, J 8.4 Hz), 6.56 (8, 1H), 7.00 (d, 1H, J = 7.8 Hz), 7.28 (d, 1H, J = 8.4 Hz). 15 Compound li-174 [Formula 342] , N O .,,N ND C F3 Compound Ii-175 20 [Formula 343] H N H

CF

3 201 Compound Ii- 176 [Formula 3441 H N O O ,.,,C F3 5 Compound Ii-177 [Formula 3451 H 0 0 .,,N C F3 N0 Compound Ii- 178 10 [Formula 3461 -H 0 0..,N C F3 N'N Compound Ii-179 [Formula 3471 0 i0 .. N CN 15 Compound li- 180 [Formula 348] 202 H %0 .H N CN Compound 1i- 181 [Formula 349] 'il'HH0 00 N N 5 CF3 Compound li- 182 [Formula 350] N N

CF

3 10 Compound Ii- 183 [Formula 3511 N' 0 .. , 2 IN.N C F 15 Compound Ii- 184 [Formula 3521 00..,N, CF3 N Compound Ii- 185 203 [Formula 3531 H NN Compound Ii-186 5 (Formula 3541 N' N Compound li-187 [Formula 3551 H N 10 Compound Ii-188 [Formula 3561 NN C N 15 Compound Ii-189 [Formula 3571 204 NI F N Compound Ii-190 [Formula 358] S , N F 5 0 Compound li-191 [Formula 3591 9H .N F NN F 0 10 Compound Ii-192 [Formula 3601 SH .. NF F 0 15 Compound Ii-193 [Formula 3611 205 HH -NN Compound Ii- 194 [Formula 3621 00 N N 5 F Compound li-195 [Formula 363] 0 NG F 10 Compound li-196 [Formula 3641 NN N N F 15 Compound Ii-197 [Formula 365] 206 HH 0 0..,N N

CF

3 Compound li- 198 [Formula 3661 SN N 5 CF, Compound li-199 [Formula 367] SNIN I1ZC F 3 10 Compound Ii-200 [Formula 3681 NIN

CF

3 15 Compound li-201 [Formula 369] N 2CF3 CN 207 Compound Ii-202 [Formula 370) HH N C F3 No 5 Compound li-203 [Formula 371] HH N CH N'N Compound li-204 10 [Formula 372] ~ C N 1, No Compound Ii-205 [Formula 373] .. , N N 15 1::ICN Compound Ii-206 [Formula 3741 208 N ~ N'

CF

3 [00831 Compound Ij-2 5 [Formula 3751 H I 1H-NMR (DMSO-d6) 5: 0.98-1.24 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.40 (m, 1H), 1.78 1.88 (m, 2H), 2.02-2.14 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 2.86 (q, 2H, J = 7.2 Hz), 3.64 10 3.82 (m, 1H), 6.40 (d, 2H, J = 8.1 Hz), 7.01 (d, 2H, J = 7.2 Hz), 7.32-7.50 (m, 4H), 7.99 (d, 2H, J = 6.9 Hz) Compound Ij-3 [Formula 3761 15H 1H-NMR (DMSO-d6) 6: 0.96-1.26 (m, 4H), 1.18 (t, 3H, J= 7.5 Hz), 1.40 (m, 1H), 1.78 1.88 (m, 2H), 2.02-2.14 (m, 211), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60 3.78 (m, 1H), 6.40-6.50 (m,2H), 6.85-6.92 (m, 1H), 6.97-7.03 (m, 1H), 7.22-7.35 (m, 2H), 20 7.36-7.46 (m, 2H), 7.88-7.96 (m, IH) Compound Ij-4 [Formula 3771 209 0 0 N 1H-NMR (DMSO-d6) 5: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.38 (m, 1H), 1.78 1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60 5 3.78 (m, 1H), 6.50 (t, 1H, J = 3.9 Hz), 6.53 (s, 1H), 7.00 (t, 1H, J = 5.7 Hz), 7.25 (t, 1H, J = 7.2 Hz), 7.34-7.45 (m, 2H), 7.55 (d, 2H, J = 7.2 Hz), 7.67 (dd, 1H, J = 8.7, 2.7 Hz), 8.29 (d, 1H, J = 2.7 Hz) Compound Ij-5 10 [Formula 3781 N 1H-NMR (DMSO-d6) 5: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.38 (m, IH), 1.78 1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60 15 3.78 (m, 1H), 6.52 (d, 1H, J = 8.4 Hz), 6.60 (d, 1H, J = 7.8 Hz), 7.01 (t, 1H, J = 5.7 Hz), 7.20-7.36 (m, 3H), 7.46 (t, 1H, J = 8.1 Hz), 7.55 (d, 1H, J = 8.7 Hz), 8.15 (8, 1H) Compound Ij-6 [Formula 3791 a0 F HL. 20 1H-NMR (DMSO-d6) 5: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.40 (m, 1H), 1.78 1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60 3.78 (m, 1H), 6.51 (d, 1H, J = 8.7 Hz), 6.60 (d, 1H, J = 7.5 Hz), 7.01 (t, 1H, J = 5.7 H z), 25 7.02-7.12 (m, 1H), 7.36-7.48 (m, 3H), 7.71 (dd, 1H, J 8.7, 2.1 Hz), 8.33 (d, 1H, J = 2.1 Hz) 210 Compound Ij-7 [Formula 3801 F 'N N H 5 1H-NMR (DMSO-d6) 5: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J= 7.2 Hz), 1.40 (m, 1H), 1.78 1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60 3.78 (m, 1H), 6.50 (d, 2H, J = 8.7 Hz), 6.99 (t, 1H, J = 6.0 Hz), 7.16-7.26 (m, 2H), 7.52 7.68 (m, 3H), 8.25 (s, 1H) 10 Compound lj-8 (Formula 381] a0 H ) N IOMc H 1H-NMR (CDC13) 6:1.15-1.26 (m, 4H), 1.40 (t, 3H, J = 7.5 Hz), 1.55-1.58 (m, 1H), 1.93 15 (d, 2H, J = 9.7 Hz), 2.23 (d, 2H, J = 9.7 Hz), 3.01-3.11 (m, 4H), 3.56-3.61 (m, 1H), 3.84 (8, 3H), 4.34 (t, 1H, J= 6.1 Hz), 4.83-4.86 (m, 1H), 6.46 (d, 1H, J = 8.6 Hz), 6.99 (d, 1H, J = 8.5 Hz), 7.05 (d, 1H, J = 8.5 Hz), 7.29 (s, 1H), 7.30-7.34 (m, IH), 7.69 (dd, 1H, J = 8.7, 2.4 Hz), 8.25 (s, 1H). 20 Compound Ij-9 [Formula 3821 "**I0 .,OMe o o H 1H-NMR (CDCl3) 5:1.16-1.24 (m, 4H), 1.40 (t, 3H, J = 6.2 Hz), 1.55-1.59 (m, 1H), 1.94 25 (d, 2H, J = 11.8 Hz), 2.23 (d, 2H, J = 11.8 Hz), 3.03-3.09 (m, 4H), 3.58-3.62 (m, 1H), 3.88 (s, 3H), 4.29 (t, 1H, J = 6.4 Hz), 4.85-4.89 (m, 1H), 6.49 (d, 1H, J = 8.7 Hz), 6.88 (dd, 1H, J = 8.7, 2.2 Hz), 7.04-7.06 (m, 1H), 7.10 (d, 1H, J = 8.7 Hz), 7.36 (t, 1H, J = 7.9 Hz), 7.70 (dd, 1H, J = 8.7, 2.2 Hz), 8.32 (s, IH). 211 Compound Ij-10 [Formula 3831 aMe o oN H H 5 1H-NMR (CDC13) 6:1.19-1.30 (m, 4H), 1.41 (t, 3H, J = 6.3 H z), 1.56-1.59 (m, 1H), 1.94 (d, 2H, J = 11.1 H z), 2.23 (d, 2H, J = 11.1 H z), 3.01-3.11 (m, 4H), 3.57-3.61 (m, 1H), 3.87 (s, 3H), 4.27 (t, 111, J = 6.4 Hz), 4.98 (s, 1H), 6.50 (dd, 1H, J = 8.7, 2.2 Hz), 6.99 (d, 2H, J = 8.9 Hz), 7.43 (d, 2H, J = 8.7 Hz), 7.68 (dd, 1H, J = 8.7, 2.2 Hz), 8.25 (s, 1H). 10 Compound Ij-11 [Formula 384] 00a NN H 15 1H-NMR (DMSO-d6) 6: 0.93-1.08 (m, 2H), 1.09-1.25 (m, 5H), 1.39 (m, 1H), 1.75-1.86 (m, 2H), 1.95-2.07 (m, 2H), 2.34 (s, 3H), 2.78 (t, 2H, J = 6.2 Hz), 2.98 (q, 2H, J = 7.3 Hz), 3.65 (m, 1H), 6.45-6.53 (m, 2H), 7.01 (t, 1H, J = 5.6 Hz), 7.07 (d, 1H, J = 7.1 Hz), 7.23-7.38 (m, 3H), 7.64 (dd, 1H, J1 = 8.8 Hz, J2 = 2.5 Hz), 8.26 (d, 1H, J = 2.5 Hz). 20 Compound Ij-12 [Formula 3851 0 N H 1H-NMR (DMSO-d6) 8:0.93-1.08 (m, 2H), 1.09-1.27 (m, 11H), 1.39 (m, 1H), 1.76-1.87 25 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.2 Hz), 2.84-3.03 (m, 3H), 3.66 (m, 1H), 6.45 6.54 (m, 2H), 7.01 (t, 1H, J = 5.8 Hz), 7.13 (d, 1H, J = 6.9 Hz), 7.27-7.41 (m, 3H), 7.66 (dd, 1H, J1 = 8.8 H z, J2 = 2.5 H z), 8.27 (d, 1H, J = 2.2 Hz). 212 Compound Ij-13 [Formula 386]

CF

3 H 5 1H-NMR (DMSO-d6) 6: 0.92-1.09 (m, 2H), 1.09-1.25 (m, 5H), 1.39 (m, 1H), 1.76-1.85 (m, 2H), 1.95-2.06 (m, 2H), 2.78 (t, 2H, J = 6.2 Hz), 2.98 (q, 2H, J = 7.3 Hz), 3.68 (m, 1H), 6.52 (d, 1H, J = 8.8 Hz), 6.66 (d, 1H, J = 8.0 Hz), 7.02 (t, 1H, J = 5.5 Hz), 7.23 (d, 1H, J = 8.1 Hz), 7.49-7.55 (m, 2H), 7.62 (d, 1H, JI = 8.5 Hz), 7.72 (dd, 1H, J1 = 8.8 Hz, J2 = 2.5 10 Hz), 8.35 (d, 1H, J= 2.5 Hz). Compound Ij-14 [Formula 3871 0 0 CF. N H 15 1H-NMR (DMSO-d6) 5: 0.92-1.22 (m, 4H), 1.22 (d, 6H, J = 6.4 Hz), 1.39 (m, 1H), 1.76 1.86 (m, 2H), 1.95-2.03 (m, 2H), 2.81 (t, 2H, J = 6.4 Hz), 3.10-3.20 (m, 1H), 3.60-3.75 (m, 1H), 6.65 (d, 1H, J = 4.8 Hz), 6.70 (s, 1H), 6.88-6.98 (m, 2H), 8.16 (d, 1H, J = 5.2 Hz). 20 Compound Ij-15 [Formula 3881 0 0 cI N H 1H-NMR (CDC13) 6:1.02-1.28 (m, 4H), 1.38 (d, 6H, J = 6.9 H z), 1.52 (m, 1H), 1.85-1.94 25 (m, 2H), 2.11-2.21 (m, 2H), 3.01 (t, 2H, J = 6.6 Hz), 3.10-3.25 (m, 1H), 3.38-3.54 (m, 1H). 4.22 (t, 1H, J = 6.3 Hz), 4.58 (d, 1H, J = 7.8 Hz), 6.34 (d, 1H, J = 1.8 Hz), 6.53 (dd, 1H, J = 5.4, 1.8 Hz), 7.93 (d, 1H, J = 5.4 Hz). 213 Compound lj-16 [Formula 389] a a 'NN Cl H 5 1H-NMR (CDC13) 8:1.03-1.28 (m, 4H), 1.37 (d, 6H, J = 6.9 Hz), 1.52 (m, 1H), 1.84-1.93 (m, 2H), 2.11-2.21 (m, 2H), 3.01 (t, 2H, J = 6.6 Hz), 3.09-3.24 (m, 1H), 3.40-3.54 (m, 1H), 4.26 (t, 1H, J = 6.6 Hz), 4.44 (d, 1H, J = 8.1 Hz), 6.29 (d, 1H, J = 8.7 Hz), 7.33 (dd, 1H, J = 8.7, 2.7 Hz), 7.99 (d, 1H, J = 2.7 Hz). 10 Compound Ij-17 [Formula 390] a a N N Cl H 15 1H-NMR (DMSO-d6) 5: 0.92-1.22 (m, 4H), 1.21 (d, 6H, J= 6.8 Hz), 1.36 (m, 1H), 1.76 1.84 (m, 2H), 1.92-2.00 (m, 2H), 2.80 (t, 2H, J = 6.4 Hz), 3.08-3.18 (m, 1H), 3.45-3.56 (m, 1H), 6.36 (d, 1H, J = 8.4 Hz), 6.43 (d, 1H, J = 7.2 Hz), 6.75 (d, 1H, J = 7.6 Hz), 6.94 (t, 1H, J = 6.0 Hz), 7.33 (t, 1H, J = 7.6 Hz). 20 Compound Ij-18 [Formula 391) > N 1H-NMR (DMSO-d6) 8: 0.98-1.24 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.40 (m, 1H), 1.78 25 1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.10-3.22 (m, iH), 3.64-3.82 (m, 1H), 6.40 (d, 2H, J = 8.4 Hz), 6.95-7.05 (m, 2H), 7.35-7.50 (m, 4H), 7.99 (d, 2H, J = 7.2 Hz) 214 Compound Ij-19 [Formula 392] NJ H 5 1H-NMR (CDCI3) 8:1.22-1.38 (m, 4H), 1.38 (d, 6H, J = 8.0 Hz), 1.54 (m, 1H), 1.86-1.95 (m, 2H), 2.18-2.26 (m, 2H), 3.03 (t, 2H, J = 6.0 Hz), 3.12-3.22 (m, 1H), 3.52-3.64 (m, 1H), 4.16 (t, 1H, J = 6.4 Hz), 4.82-4.92 (m, 1H), 6.46 (d, 1H, J = 8.0 Hz), 7.10-7.20 (m, 2H), 7.23-7.33 (m, 1H), 7.37 (t, 1H, J = 8.0 Hz), 7.65 (d, 1H, J = 8.7 Hz), 8.24 (6, 111). 10 Compound Ij-20 [Formula 393] 1H-NMR (CDCI3) 6:1.22-1.38 (m, 4H), 1.39 (d, 6H, J= 8.0 Hz), 1.54 (m, 1H), 1.86-1.95 15 (m, 2H), 2.18-2.26 (m, 2H), 3.03 (t, 2H, J = 6.0 Hz), 3.12-3.22 (m, 1H), 3.52-3.64 (m, 1H), 4.16 (t, 1H, J = 6.4 Hz), 4.78-4.88 (m, 1H), 6.46 (d, 1H, J = 8.0 Hz), 6.98(t, 1H, J = 5.7 Hz), 7.18 (d, 1H, J = 8.0 Hz), 7.23-7.29 (m, IH), 7.33-7.40 (m, 1H), 7.65 (d, 1H, J = 8.7 Hz), 8.29 (s, 1H). 20 Compound Ij-21 [Formula 394] F "N H 1H-NMR (CDCl3) 6:1.10-1.30 (m, 4H), 1.38 (d, 6H, J = 8.0 Hz), 1.54 (m, 1H), 1.86-1.95 25 (m, 2H), 2.18-2.26 (m, 2H), 3.03 (t, 2H, J = 6.0 Hz), 3.13-3.22 (m, 1H), 3.52-3.64 (in, 1H). 4.15 (t, 1H, J = 6.4 Hz), 4.78-4.88 (m, 1H), 6.46 (d, 1H, J = 8.0 Hz), 7.07-7.14 (m, 2H), 7.40-7.46 (m, 2H), 7.62 (d, 1H, J = 8.7 Hz), 8.23 (s, IH). 215 Compound Ij-22 [Formula 395] H 5 1H-NMR (DMSO-d6) 8: 0.95-1.25 (m, 4H), 1.22 (d, 6H, J 6.6 Hz), 1.25-1.50 (br, 1H), 1.81 (d, 2H, J = 11.4 Hz), 2.00 (d, 2H, J = 10.5 Hz), 2.81 (t, 2H, J = 6.6 Hz), 3.05-3.22 (m, 1H), 3.58-3.80 (m, 1H), 3.76 (s, 3H), 6.49 (d, 2H, J = 8.7 H z), 6.50-6.70 (br, 1H), 6.95-7.10 (m, 3H), 7.20-7.32 (m, 2H), 7.51 (d, 1H, J 7.2Hz), 8.05 (br, 1H). ESI(positive) 418.3 10 [M+Hl+ Compound Ij-23 [Formula 3961 OMe 15 1H-NMR (DMSO-d6) 6: 0.95-1.32 (m, 4H), 1.22 (d, 6H, J= 6.6 Hz), 1.25-1.55 (br, 1H), 1.82 (d, 2H, J = 11.4 Hz), 2.01 (d, 2H, J = 10.2 Hz), 2.81 (t, 2H, J = 6.6 H z), 3.05-3.22 (m, 1H), 3.58-3.78 (m, 1H), 3.80 (s, 3H), 6.59 (d, 2H, J = 9.6 Hz), 6.85 (dd, 1H, J = 8.4 Hz, 2.4 Hz), 6.99 (t, 3H, J = 5.7Hz), 7.05-7.18 (m, 2H), 7.32 (d, 1H, J = 7.8Hz), 7.76 (d, 1H, J = 20 8.4Hz), 8.27 (d, 1H, J = 2.1 Hz). ESI(positive) 418.3 [M+H]+ Compound Ij-24 [Formula 3971 OMe HH H 25 1H-NMR (DMSO-d6) 8: 0.92-1.25 (m, 4H), 1.22 (d, 6H, J= 6.6 Hz), 1.28-1.48 (m, 1H), 1.81 (d, 2H, J = 10.8 Hz), 2.00 (d, 2H, J = 9.6 Hz), 2.81 (t, 2H, J = 6.6 Hz), 3.08-3.22 (m, 1H), 3.58-3.74 (m, 1H), 3.77 (a, 3H), 6.51 (d, 2H, J = 8.7 Hz), 6.97 (d, 2H, J = 8.7 Hz), 216 6.98 (bra, 1H), 7.48 (d, 2H, J = 8.7 Hz), 7.63 (dd, 1H, J = 11.4H z, 2.4Hz), 8.21 (d, IH, J = 2.4 Hz). ESI(positive) 418.3[M+H]+ Compound Ij-25 5 [Formula 398] 00 CF 3 NN H .'N H 1H-NMR (DMSO-d6) 5: 0.92-1.22 (m, 4H), 1.27 (s, 9H), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 1.95-2.05 (m, 211), 2.88 (t, 2H, J = 6.0 Hz), 3.60-3.80 (m, 1H), 6.65 (d, 1H, J 5.4 Hz), 10 6.70 (s, IH), 6.87 (t, 1H, J = 6.0 Hz), 6.94 (d, 1H, J = 7.8 Hz), 8.16 (d, IH, J = 5.4 Hz) Compound Ij-26 (Formula 3991 O 0 N NCF H 15 1H-NMR (DMSO-d6) 8: 0.92-1.22 (m, 4H), 1.27 (s, 9H), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 1.94-2.04 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.60-3.80 (m, 1H), 6.53 (d, 1H, J = 8.7 Hz), 6.87 (t, 1H, J = 5.7 Hz), 7.19 (d, 1H, J = 7.5 Hz), 7.59 (dd, 1H, J = 9.0, 2.4 Hz), 8.26 (d, 1H, J = 2.4 Hz) 20 Compound Ij-27 [Formula 400] 0 0 ..'NC H 25 1H-NMR (DMSO-d6) 6: 0.92-1.22 (m, 4H), 1.26 (s, 9H), 1.38 (m, 1H), 1.76-1.86 (m, 2H), 1.92-2.02 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.40-3.60 (m, 1H), 6.36 (d, 1H, J = 8.1 Hz), 217 6.43 (d, 1H, J = 6.9 Hz), 6.80 (d, 1H, J = 7.5 Hz), 6.86 (t, 1H, J = 5.4 Hz), 7.34 (t, 1H, J = 8.4 Hz) Compound Ij-28 5 [Formula 401] 0 0 SO' CF3 H 1H-NMR ((DMSO-d6) 8: 0.93-1.18 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.75 1.86 (m, 2H), 1.94-2.05 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 3.09-3.27 (m, 2H), 6.19 (d, 1H, J 10 = 8.1 Hz), 6.64 (d, 2H, J = 8.7 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.33 (d, 2H, J = 8.7 Hz) Mass:379[M+H]+ Compound Ij-29 [Formula 4021 H N 15 1H-NMR (DMSO-d6) 5: 0.93-1.18 (m, 4H), 1.22 (s, 3H), 1.24 (s, 3H), 1.32-1.49 (m, 2H), 1.82 (d, 2H, J = 11.2 Hz), 2.04 (d, 2H, J = 11.2 Hz), 2.75-2.87 (m, 2H), 3.07-3.28 (m, 2H), 6.64 (s, 1H), 6.96 (s, 11), 7.10-7.22 (m, 2H), 7.25-7.39 (m, 2H), 7.77-7.90 (m, 2H), 8.63 (s, 20 1H). Melting point: 161 to 162 *C Compound Ij-30 [Formula 4031 0 0 .g CF 3 H 25 IH-NMR (DMSO-d6) 6: 0.92-1.22 (m, 4H), 1.27 (s, 9H), 1.37 (m, 1H), 1.76-1.86 (m, 2H), 1.94-2.05 (m, 2H), 2.88 (t, 2H, J = 6.3 Hz), 3.19 (m, 1H), 6.19 (d, 1H, J = 7.5 Hz), 6.64 (d, 2H, J = 8.7 Hz), 6.88 (d, 1H, J = 6.0Hz), 7.33 (d, 2H, J = 8.7 Hz) Mass:392M+ 218 Compound Ij-31 [Formula 404] 00 F S. F H 5 1H-NMR (DMSO-d6) 6: 0.92-1.16 (m, 4H), 1.26 (s, 9H), 1,36 (m, 1H), 1.72-1.83 (m, 2H), 1.92-2.02 (m, 2H), 2.87 (t, 2H, J = 6.3 Hz), 3.12 (m, 1H), 6.09-6.23 (m, 4H), 6.87 (t, 1H, J = 6.0 Hz) Mass:361[M+H]+ 10 Compound Ij-32 [Formula 405] 00 F HO 'N F H 1H-NMR (CDCl3) 6:1.00-1.20 (m, 4H), 1.40 (s, 9H), 1.42-1.64 (m, 2H), 1.84-1.95 (m, 2H), 15 2.09-2.20 (m, 2H), 3.07 (m, IH), 3.07 (t, 2H, J= 6.3 Hz), 3.90 (m, 1H), 6.10 (dd, 2H, J 9.6, 5.4 Hz). Compound Ij-33 (Formula 4061 I 'N H 20 1H-NMR (DMSO-d6) 8: 0.93-1.21 (m, 5H), 1.28 (a, 9H), 1.33-1.46 (m, 1H), 1.82 (d, 2H, J = 11.6 Hz), 2.04 (d, 2H, J = 11.6 Hz), 2.86-2.95 (m, 2H), 3.03-3.29 (m, 1H), 6.59-6.71 (m, 1H), 6.80-6.92 (m, 1H), 7.09-7.21 (m, 2H), 7.27-7.37 (m, 2H), 7.77-7.88 (m, 2H), 8.58-8.67 25 (s, 1H). Melting point: 172 to 173 C 219 Compound Ij-34 [Formula 4071 N N CI H 5 1H-NMR (DMSO-d6) 6: 0.96-1.08 (m, 2H), 1.12-1.24(m, 2H), 1.21 (d, 6H, J = 6.4 H z), 1.38 (m, 1H), 1.76-1.86 (m, 2H), 1.92-2.00 (m, 2H), 2.80 (t, 2H, J = 6.4 Hz), 3.10-3.20 (m, 1H), 3.48-3.60 (m, 1H), 6.95 (t, 1H, J = 5.6 Hz), 7.41 (d, 1H, J = 7.6 Hz), 7.63 (s, 1H), 7.82 (8, 1H). 10 Compound Ij-35 [Formula 4081 00 N C H 1H-NMR (DMSO-d6) 6: 0.96-1.26 (m, 4H), 1.27 (s, 9H), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 15 1.92-2.02 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.48-3.62 (m, 1H), 6.87 (t, 1H, J = 6.0 Hz), 7.45 (d, 1H, J = 7.5 Hz), 7.63 (s, 1H), 7.82 (s, 1H) Compound Ij-36 [Formula 4091 00 CF] N N 20 H 1H-NMR (DMSO-d6) 6: 0.96-1.06 (m, 2H), 1.12-1.20 (m, 211), 1.21 (d, 6H, J = 6.6 Hz), 1.39 (m, 1H), 1.78-1.84 (m, 2H), 1.95-1.99 (m, 2H), 2.81 (t, 2H, J = 6.0 Hz), 3.10-3.20 (m, 1H), 3.74-3.88 (m, 1H), 6.80 (s, 1H), 6.98 (t, 1H, J = 6.0 Hz), 7.93 (d, 2H, J = 7.2 Hz), 8.53 25 (8, 1H). Compound Ij-37 [Formula 4101 220 NN HH 1H-NMR (DMSO-d6) 6: 0.96-1.30 (m, 4H), 1.19 (t, 3H, J= 7.2 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.72 5 3.90 (m, 1H), 6.85 (d, 1H, J = 9.6 Hz), 6.93 (d, 1H, J = 7.5 Hz), 7.04 (t, 1H, J = 5.7 Hz), 7.26-7.38 (m, 2H), 7.40-7.52 (m, 1H), 7.57 (d, 1H, J = 9.0 Hz), 7.85 (t, 1H, J =7.8 Hz) Compound Ij-38 [Formula 411] 0 a N PO N Me 10 H 1H-NMR (DMSO-d6) 6: 0.96-1.30 (m, 4H), 1.19 (t, 3H, J= 7.2 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 211), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.72 3.90 (m, 1H), 3.80 (s, 3H), 6.72 (d, 1H, J = 7.8 Hz), 6.77 (d, 1H, J = 9.0 Hz), 6.98-7.10 (m, 15 2H), 7.12 (d, 1H, J = 8.4 Hz), 7.38 (t, 1H, J = 8.1 Hz), 7.56 (d, 1H, J = 9.3 Hz), 7.61 (d, 111, J = 7.8 Hz) Compound Ij-39 [Formula 4121 00 20 1H-NMR (DMSO-d6) 6: 0.96-1.30 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.72 3.90 (m, 1H), 6.85 (d, 1H, J = 9.6 Hz), 6.92 (d, 1H, J = 7.5 Hz), 7.04 (t, 1H1, J = 5.7 Hz), 25 7.21 (t, 1H, J = 8.7 Hz), 7.46-7.56 (m, 1H), 7.75-7.88 (m, 311) Compound Ij-40 221 (Formula 413] 0 aI 1H-NMR (DMSO-d6) 5: 0.96-1.10 (m, 2H), 1.19 (t, 3H, J= 7.2 Hz), 1.15-1.26 (m, 2H), 5 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.76-3.87 (m, 1H), 6.85 (d, 1H, J = 9.6 Hz), 6.91 (d, 1H, J = 7.5 Hz), 7.01 (t, 1H, J = 5.7 Hz), 7.42-7.52 (m, 2H), 7.83 (d, 1H, J = 8.0 Hz), 7.93 (d, 1H, J = 8.0 Hz), 8.02 (s, 1H). 10 Compound Ij-41 [Formula 414] ao 0 CF3 1H-NMR (DMSO-d6) 5: 0.96-1.30 (m, 4H), 1.20 (t, 3H, J = 7.5 Hz), 1.42 (m, 1H), 1.78 15 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.76 3.90 (m, 1H), 6.88 (d, 1H, J = 9.3 Hz), 6.97 (d, 1H, J = 7.5 Hz), 7.03 (t, 1H, J = 5.7 Hz), 7.67-7.77 (m, 2H), 7.92 (d, 1H, J = 9.6 Hz), 8.26 (d, 1H, J = 6.9 Hz), 8.33(s, 1H) Compound Ij-42 20 [Formula 415] N OCF 3 H NN 1H-NMR (DMSO-d6) 5: 0.93-1.10 (m, 2H), 1.20 (t, 3H, J= 7.2 Hz), 1.22-1.28 (m, 1H), 1.35-1.50 (m, 2H), 1.84 (d, 2H, J = 12.0 Hz), 2.08 (d, 2H, J = 12.0 Hz), 2.63-2.76 (m, 2H), 25 2.91-3.03 (m, 2H), 3.75-3.90 (m, 1H), 6.86 (d, 1H, J = 9.2 Hz), 6.93 (d, 1H, J = 7.2 Hz), 6.98-7.07 (m, 1H), 7.36 (d, 1H, J = 7.2 Hz), 7.59 (t, 1H, J = 8.0 Hz), 7.85 (d, 1H, J = 9.2 Hz), 7.91-8.02 (m, 2H). Melting point: 144 to 145 *C 222 Compound Ij-43 [Formula 416] 0 0 .. N. C H 5 1H-NMR (DMSO-d6) 8 0.94-1.06 (m, 2H), 1.10-1.24 (m, 2H), 1.21 (d, 6H, J= 6.8 Hz), 1.39 (m, 1H), 1.76-1.86 (m, 2H), 1.98-2.06 (m, 2H), 2.81 (t, 2H, J = 6.4 Hz), 3.10-3.20 (m, 1H), 3.62-3.74 (m, 1H), 6.84 (d, IH, J =9.2 Hz), 6.88-6.98 (m, 2H), 7.31 (d, 1H, J = 9.6 Hz). 10 Compound Ij-44 [Formula 4171 H 1H-NMR (DMSO-d6) 8: 0.94-1.26 (m, 4H), 1.20 (d, 6H, J= 6.6 Hz), 1.40 (m, 1H), 1.78 15 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.06-3.20 (m, 1H), 3.72-3.90 (m, 1H), 6.75-6.88 (m, 2H), 6.97 (t, 1H, J = 6.0 Hz), 7.30-7.48 (m, 3H), 7.76 (d, 1H, J = 9.3 Hz), 7.94 (d, 2H, J =8.4 Hz) Compound Ij-45 20 [Formula 418] N H 1H-NMR (DMSO-d6) 8: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J 6.9 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.3 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 25 1H), 6.85 (d, 1H, J = 9.0 Hz), 6.91 (d, 1H, J = 7.5 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.25-7.36 (m, 2H), 7.40-7.50 (m, 1H), 7.57 (d, 1H, J = 6.9 Hz), 7.85 (t, 1H, J =8.1 Hz) 223 Compound Ij-46 [Formula 4191 00 N F 5 1H-NMR (DMSO-d6) 8: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.3 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, IH), 6.85 (d, 1H, J = 9.3 Hz), 6.90 (d, 1H, J = 7.5 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.21 (t, 1H, J = 7.8 Hz), 7.46-7.56 (m, 1H), 7.75-7.86 (m, 3H) 10 Compound Ij-47 [Formula 420] F 0 0

N

15 1H-NMR (DMSO-d6) 8: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 6.81 (d, 1H, J = 7.5 Hz), 6.84 (d, 1H, J = 9.3 Hz), 6.98 (t, 1H, J = 6.3 Hz), 7.25-7.35 (m, 2H), 7.77 (d, 1H, J = 9.3 Hz), 7.96-8.06 (m, 2H) 20 Compound Ij-48 [Formula 4211 N "%%C .'N N' OMe H 1H-NMR (DMSO-d6) 6: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.42 (m, 1H), 1.78 25 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.3 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 3.80 (s, 3H), 6.71 (d, 1H, J = 7.8 Hz), 6.76 (d, 1H, J = 9.3 Hz), 6.98 (t, 1H, J = 5.7 Hz), 7.05 (d, 1H, J = 7.2 Hz), 7.12 (d, 1H, J = 7.8 Hz), 7.38 (t, 1H, J = 8.4 Hz), 7.56 (d, 1H, J = 9.3 Hz), 7.62 (d, 1H, J = 6.9 Hz) 224 Compound Ij-49 [Formula 422] N OMe H 5 1H-NMR (DMSO-d6) 5: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.0 H z), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 3.82 (s, 3H), 6.78-6.88 (m, 211), 6.92-7.04 (m, 2H), 7.37 (t, 1H, J= 7.5 Hz), 7.46-7.58 (m, 2H), 7.79 (d, 1H, J = 9.3 Hz) 10 Compound Ij-50 [Formula 4231 nfl OMe ii N H 15 1H-NMR (DMSO-d6) 5: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J= 6.9 Hz), 1.42 (m, 1H), 1.78 1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.10-3.22 (6, 1H), 3.74-3.92 (m, IH), 3.80 (s, 3H), 6.70 (d, 1H, J = 7.8 Hz), 6.82 (d, 1H, J = 9.3 Hz), 6.95-7.05 (m, 3H), 7.72 (d, 1H, J = 9.3 Hz), 7.90 (d, 2H, J = 9.0 Hz). 20 Compound Ij-51 [Formula 4241 -N F NN H 1H-NMR (DMSO-d6) 5: 0.92-1.05 (m, 2H), 1.07-1.20 (m, 2H), 1.22 (d, 6H, J = 6.9 Hz), 25 1.39 (m, 1H-), 1.76-1.85 (m, 2H), 2.02-2.10 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.57-3.68 (m, 1H), 4.89-4.98 (m, 2H), 6.47 (d, 1H, J= 8.0 Hz), 6.88 (d, 1H, J = 7.5 Hz), 6.96 (t, 1H, J = 6.0 Hz), 7.02 (d, 1H, J = 7.5 Hz). Compound Ij-52 225 [Formula 4251 a a I 1O9N N .N H 1H-NMR (DMSO-d6) 6: 0.92-1.05 (m, 2H), 1.07-1.20 (m, 2H), 1.22 (d, 6H, J = 6.9 Hz), 5 1.39 (m, 1H), 1.52-1.74 (m, 6H), 1.77-1.85 (m, 2H), 1.87-1.97 (m, 2H), 2.02-2.09 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.55-3.65 (m, IH), 5.25-5.32 (m, 1H), 6.19 (d, 1H, J = 8.0 Hz), 6.77 (s, 2H), 6.95 (t, 1H, J = 6.0 Hz). Compound Ij-53 10 [Formula 426] 0 a NI No -NN H 1H-NMR (DMSO-d6) 6: 0.92-1.15 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.38 (m, iH), 1.77 1.85 (m, 2H), 1.88-1.95 (m, 4H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 3.09-3.20 Cm, 15 1H), 3.25-3.35 (m, 4H), 3.55-3.65 (m, 1H), 5.80-5.85 (m, 1H), 6.72 (d, 111, J = 8.0 Hz), 6.80 (d, 1H, J = 8.0 Hz), 6.96 (t, 1H, J = 6.0 Hz). Compound Ij-54 (Formula 4271 0 0 20 0 1H-NMR (DMSO-d6) 6: 0.92-1.20 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.38 (m, 1H), 1.77 1.85 (m, 2H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.58-3.65 (m, 1H), 6.56 (d, 1H, J = 8.0 Hz), 6.90-6.98 (m, 211), 7.03-7.10 (m, 3H), 7.15 (t, 1H, J = 8.0 25 Hz), 6.38 (t, 2H, J = 8.0 Hz). Compound Ij-55 [Formula 428] 226 0 0 N N' F H 1H-NMR (DMSO-d6) 6: 0.92-1.20 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.38 (m, 1H), 1.77 1.85 (m, 2H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.58-3.65 (m, 5 1H), 6.55 (d, 1H, J = 8.0 Hz), 6.90-6.98 (m, 2H), 7.05-7.15 (m, 3H), 7.21 (t, 2H, J = 8.0 Hz). Compound lj-56 [Formula 429) 10 1H-NMR (DMSO-d6) 8: 0.92-1.20 (in, 4H), 1.21 (d, 6H, J= 6.9 Hz), 1.38 (m, IH), 1.77 1.85 (m, 2H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 H z), 3.09-3.20 (m, 1H), 3.58-3.65 (m, 1H), 3.75 (s, 3H), 6.49 (d, 1H, J= 8.0 Hz), 6.87-6.98 (m, 4H), 7.00-7.07 (m, 3H). 15 Compound Ij-57 [Formula 4301 0 0 H 20 1H-NMR (DMSO-d6) 8: 0.96-1.28 (m, 4H), 1.27 (s, 9H), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.00-2.10 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.60-3.76 (m, 1H), 6.82-6.92 (m, 2H), 6.96 (d, 1H, J = 7.8 Hz), 7.32 (d, 1H, J = 9.6 Hz). Compound Ij-58 25 [Formula 4311 227 0 0 H 1H-NMR (DMSO-d6) 6: 0.99-1.28 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.78 1.86 (m, 2H), 2.04-2.10 (m, 2H), 2.82 (t, 2H, J = 6.1 Hz), 3.06-3.20 (m, 1H), 3.80-3.96 (m, 5 1H), 6.71 (d, 1H, J = 9.0 Hz), 6.76-6.86 (m, 1H), 6.90-6.98 (m, 1H), 7.10 (t, 1H, J = 8.1 Hz), 7.39-7.50 (m, 2H), 7.56 (d, 1H, J = 7.5 Hz), 7.78 (d, 1H, J = 7.5 Hz). Compound Ij-59 [Formula 4321 0 0 10 H 1H-NMR (DMSO-d6) 5: 0.99-1.28 (m, 4H), 1.27 (s, 9H), 1.40 (m, 1H), 1.80-1.85 (m, 2H), 2.04-2.09 (m, 2H), 2.91 (t, 2H, J= 6.1 Hz), 3.80-3.96 (m, 1H), 6.70 (d, 1H, J = 9.0 Hz), 6.81-6.87 (m, 2H), 7.10 (t, 1H, J = 8.1 Hz), 7.39-7.44 (m, 2H), 7.56 (d, 1H, J = 7.5 Hz), 15 7.79 (d, 1H, J = 7 5 Hz). Compound Ij-60 [Formula 433] NN H D 20 1H-NMR (DMSO-d6) 6: 0.97-1.09 (m, 2H), 1.23 (d, 6H, J = 6.9 Hz), 1.31-1.50 (m, 2H), 1.82-1.87 (m, 2H), 2.01-2.05 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.11-3.20 (m, 1H), 4.00-4.18 (m, 1H), 6.83 (d, 1H, J = 5.7 Hz), 6.90-7.06 (m, 2H), 7.45 (t, 1H, J = 6.9 Hz), 7.59 (t, 1H, J = 8.1 Hz), 7.67 (d, 1H, J = 8.4 Hz), 7.83 (d, 1H, J = 5.7 Hz), 8.27 (d, 1H, J = 7.5 Hz). 25 Compound Ij-61 228 [Formula 434] a 0 N 1H-NMR (DMSO-d6) 6: 0.96-1.09 (m, 2H), 1.28 (s, 9H), 1.29-1.50 (m, 2H), 1.82-1.87 (m, 5 2H), 2.01-2.05 (m, 2H), 2.91 (t, 2H, J = 7.8 Hz), 4.00-4.18 (m, 1H), 6.82-6.89 (m, 2H), 6.97 (d, 1H, J = 7.5 Hz), 7.45 (t, 1H, J = 7.2 Hz), 7.59 (t, 1H, J = 8.1 Hz), 7.67 (d, 1H, J = 7.8 Hz), 7.84 (d, 1H, J = 6.0 Hz), 8.27 (d, 1H, J = 8.4 Hz). Compound Ij-62 10 [Formula 4351 0 0 'N H 1H-NMR (DMSO-d6) 6: 0.96-1.14 (m, 2H), 1.18-1.30 (m, 2H), 1.22 (d, 6H, J 6.6 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.10-3.20 (m, 15 1H), 3.58-3.70 (m, 1H), 6.95-7.03 (m, 2H), 7.20 (t, 1H, J = 7.5 Hz), 7.37 (d, 1H, J = 8.1 Hz), 7.64 (d, 1H, J = 7.5 Hz), 7.92 (d, 1H, J = 7.8 Hz). Compound Ij-63 [Formula 436] S. 'N 20 H 1H-NMR (DMSO-d6) 8: 1.00 (dd, 2H, J = 24.8, 10.6 Hz), 1.15-1.22 (m, 2H), 1.18 (t, 3H, J = 7.6 Hz), 1.27 (s, 9H), 1.34-1.40 (m, 1H), 1.81 (d, 2H, J = 11.6 Hz), 2.07 (d, 2H, J = 11.6 Hz), 2.60 (q. 2H, J = 7.6 Hz), 2.89 (t, 2H, J = 6.3 Hz), 3.52-3.63 (m, 1H), 6.87 (t, 1H, J = 25 5.8 Hz), 7.04 (d, 1H, J = 7.9 Hz), 7.27 (d, 1H, J = 8.2 Hz), 7.47 (s, 1H), 7.80 (d, 1H, J = 7.6 Hz). 229 Compound Ij-64 [Formula 437] 00 F .N N H 5 1H-NMR (DMSO-d6) 5: 0.92-1.10 (m, 2H), 1.12-1.25 (m, 2H), 1.27 (s, 9H), 1.37 (m, IH), 1.76-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.89 (t, 2H, J = 6.0 Hz), 3.50-3.66 (m, 1H), 6.87 (t, 1H, J = 5.7 Hz), 7.03 (dd, 1H, J = 8.7, 2.7 Hz), 7.32-7.37 (m, 1H), 7.58 (dd, 1H, J 8.7, 2.7 Hz), 7.92 (d, 1H, J= 7.2 Hz). 10 Compound Ij-65 [Formula 4381 CI 0 0 .N N H 15 1H-NMR (DMSO-d6) 8: 1.01 (dd, 2H, J = 24.6, 10.2 Hz), 1.21 (dd, 2H, J= 24.6, 10.2 Hz), 1.27 (a, 9H), 1.34-1.40 (m, 1H), 1.82 (d, 2H, J = 11.2 Hz), 2.08 (d, 2H, J 11.2 Hz), 2.89 (t, 2H, J = 6.2 Hz), 3.59-3.65 (m, 1H), 6.87 (t, 1H, J = 5.8 Hz), 7.21 (dd, 1H, J = 8.6, 2.4 Hz), 7.34 (d, 1H, J = 8.6 Hz), 7.77 (d, 1H, J = 1.8 Hz), 8.06 (d, 1H, J = 7.6 Hz). 20 Compound Ij-66 [Formula 4391 CF 3 H 1H-NMR (CDC13) 6:1.09-1.46 (m, 4H), 1.41 (s, 9H), 1.54 (m, 1H), 1.90-2.00 (m, 2H), 25 2.24-2.34 (m, 2H), 3.09 (t, 2H, J = 6.6 Hz), 3.46-3.60 (m, 111), 3.99 (t, 1H, J = 6.6 Hz), 6.58 (bra, 1H), 7.58(s, 2H), 7.85 (a, 1H). 230 Compound Ij-67 [Formula 4401

DCF

3 NN N H 5 1H-NMR (DMSO-d6)8: 0.90-1.30 (m, 4H), 1.27 (s, 9H), 1.30-1.48 (m, 1H), 1.82 (d, 2H, J = 11.1 Hz), 2.08 (d, 2H, J = 9.6 Hz), 2.89 (t, 2H, J = 6.3 Hz), 3.55-3.70 (m, 1H), 6.87 (t, 1H, J = 5.7 Hz), 7.17 (m, 1H), 7.41 (d, 1H, J = 8.7 Hz), 7.77 (d, 1H, J = 1.5 Hz), 8.10 (d, 1H, J = 7.5 Hz). ESI(positive)m/z 466.2 [M+H]+ 10 Compound Ij-68 [Formula 4411 .'N N H 15 1H-NMR (DMSO-d6) 6: 0.90-1.28 (m, 4H), 1.25 (s, 9H), 1.32 (m, 1H), 1.76-1.82 (m, 2H), 2.00-2.10 (m, 2H), 2.87 (t, 2H, J = 6.6 Hz), 3.50-3.62 (m, 1H), 3.71 (s, 3H), 6.77 (dd, 1H, J = 8.7, 2.7 Hz), 6.84 (t, 1H, J = 5.7 Hz), 7.22-7.28 (m, 2H), 7.66 (d, 1H, J = 7.2 Hz). Compound Ij-69 20 [Formula 442] 0 0 N OMe H 1H-NMR (DMSO-d6) 8: 0.94-1. 10 (m, 2H), 1.12-1.25 (m, 2H), 1.27 (s, 9H), 1.37 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.90 (t, 2H, J = 6.0 Hz), 3.52-3.68 (m, 1H), 3.84 (s, 25 3H), 6.82 (d, 1H, J = 8.1 Hz), 6.88 (t, 1H, J = 5.4 Hz), 6.95 (t, 1H, J = 7.8 Hz), 7.23 (d, 1H, J = 7.8 Hz), 7.83 (d, 1H, J = 7.8 Hz). 231 Compound Ij-70 ) Formula 4431 CF 3

N

HH NN H 5 1H-NMR (DMSO-d6) 6: 0.98-1.10 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.17-1.32 (m, 2H), 1.40 (m, 1H), 1.76-1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.79 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.60-3.78 (m, 1H), 7.03 (t, 1H, J= 6.3 Hz), 7.45-7.54 (m, 2H), 8.10 (s, 111), 8.34 (d, 1H, J= 7.2 Hz). 10 Compound Ij-71 [Formula 444] 00N N/ H 1H-NMR (DMSO-d6) 6: 1.01 (dd, 2H, J= 26.1, 12.3 Hz), 1.16-1.22 (m, 2H), 1.22 (d, 6H, J 15 = 6.6 Hz), 1.35-1.41 (m, 1H), 1.70-1.77 (m, 1H), 1.82 (d, 2H, J = 11.6 Hz), 2.08 (d, 2H, J = 11.6 Hz), 2.81 (t, 2H, J= 6.3 Hz), 3.66-3.72 (m, 1H), 6.99 (t, 1H, J = 6.3 Hz), 7.23 (dd, 1H, J = 8.1, 4.7 Hz), 7.66 (d, 1H, J = 8.1 Hz), 8.07 (d, 1H, J = 4.7 Hz), 8.26 (d, 1H, J = 6.3 Hz). 20 Compound Ij-72 [Formula 4451 0 0 N H 1H-NMR (DMSO-d6) 5: 1.01 (dd, 2H, J = 24.8, 11.3 Hz), 1.18-1.23 (m, 2H), 1.27 (s, 9H), 25 1.36-1.39 (m, 1H), 1.82 (d, 2H, J = 11.5 Hz), 2.08 (d, 2H, J = 11.5 Hz), 2.89 (t, 2H, J = 6.1 Hz), 3.65-3.73 (m, 1H), 6.87 (t, 1H, J = 5.7 Hz), 7.23 (dd, 1H, J = 8.1, 4.8 Hz), 7.66 (d, iH, 232 J = 7.9 Hz), 8.07 (d, 1H, J = 4.7 Hz), 8.26 (d, 1H, J = 7.6 Hz). Compound Ij-73 [Formula 4461 CF3 5 H 1H-NMR (CDCl3)8: 1.09-1.46 (m, 4H), 1.41 (s, 9H), 1.55 (m, 1H), 1.92-2.02 (m, 2H), 2.24 2.34 (m, 2H), 3.09 (t, 2H, J = 6.3 Hz), 3.58-3.72 (m, 1H), 3.98 (t, 1H, J = 6.0 Hz), 6.30 (brs, 1H), 7.62(d, 1H, J = 8.1 Hz), 7.77 (d, 1H, J = 8.4 Hz). 10 Compound Ij-74 [Formula 4471 "N N HH 15 1H-NMR (DMSO-d6) 6: 0.90-1.08 (m, 2H), 1.12-1.40 (m, 3H), 1.25 (s, 9H), 1.76-1.86 (m, 2H), 1.98-2.10 (m, 2H), 2.87 (d, 2H, J = 6.3 H z), 3.40-3.56 (m, 1H), 6.85 (bre, 1H), 6.93 (t, 1H, J = 7.5 Hz), 7.07 (t, 1H, J = 7.5 Hz), 7.20 (d, 1H, J = 7.5 Hz), 7.29 (d, IH, J = 7.8 Hz), 7.79 (brs, 1H). 20 Compound Ij-75 [Formula 4481 Cl 0 0 N N H 1H-NMR (CDCl3) 6:1.08-1.26 (m, 2H), 1.36-1.60 (m, 3H), 1.40 (8, 9H), 1.92-2.02 (m, 2H), 25 2.22-2.32 (m, 2H), 3.08 (t, 2H, J = 6.6 Hz), 3.68-3.80 (m, 1H), 4.03 (t, IH, J = 6.0 Hz), 7.06 (brs, 1H), 7.20-7.36(m, 3H). 233 Compound Ij-76 [Formula 4491 N H 5 1H-NMR (DMSO-d6) 6:1.02 (dd, 2H, J = 25.2, 12.4 Hz), 1.17 (t, 3H, J = 7.1 Hz), 1.20 (t, 3H, J = 7.3 Hz), 1.26-1.35 (m, 2H), 1.37-1.42 (m, IH), 1.83 (d, 2H, J = 11.6 Hz), 2.05 (d, 2H, J = 11.6 Hz), 2.80 (t, 2H, J = 6.4 Hz), 2.99 (q, 2H, J = 7.3 Hz), 3.65-3.72 (m, 1H), 4.01 (q, 2H, J = 7.1 Hz), 6.32 (d, 1H, J = 7.9 Hz), 6.86-6.94 (m, 2H), 7.01 (t, 1H, J = 6.0 Hz), 7.12 (d, 1H, J = 6.9 Hz), 7.17 (d, 1H, J = 6.8 Hz). 10 Compound Ij-77 [Formula 450] 1 o, NH N H 15 1H-NMR (DMSO-d6) 6 1.02 (dd, 2H, J = 24.8, 10.8 Hz), 1.19-1.21 (m, 2H), 1.30 (s, 9H), 1.37-1.41 (m, 1H), 1.84 (d, 2H, J = 10.6 Hz), 2.06 (d, 2H, J = 10.6 Hz), 2.92 (t, 2H, J = 6.3 Hz), 3.50-3.52 (m, 1H), 6.42 (d, 1H, J = 8.1 Hz), 6.83 (d, 1H, J = 7.9 Hz), 6.88-6.92 (m, 2H), 7.11-7.14 (m, 2H), 10.58 (s, IH). 20 Compound Ij-78 [Formula 451] 0 1 NN H 1H-NMR (DMSO-d6) 8: 0.97-1.05 (m, 2H), 1.20-1.26 (m, 2H), 1.28 (s, 9H), 1.34-1.38 (m, 25 1H), 1.84 (d, 2H, J = 11.5 Hz), 2.07 (d, 2H, J = 11.5 Hz), 2.90 (t, 2H, J = 6.1 Hz), 3.47 (8, 3H), 3.63-3.69 (m, 111), 6.34 (d, 1H, J = 7.6 Hz), 6.87-6.93 (m, 3H), 7.11 (d, 1H, J = 8.4 Hz), 7.17 (d, 1H, J = 8.4 Hz). Compound Ij-79 234 [Formula 452] N N N H 1H-NMR (DMSO-d6) 8: 1.03 (dd, 2H, J = 23.6, 10.8 Hz), 1.18 (t, 3H, J = 7.5 Hz), 1.25 5 1.34 (m, 2H), 1.29 (s, 9H), 1.37-1.40 (m, 1H), 1.86 (d, 2H, J = 11.7 Hz), 2.07 (d, 2H, J = 11.7 Hz), 2.92 (t, 2H, J = 6.2 Hz), 3.67-3.73 (m, 1H), 4.03 (q, 2H, J = 7.1 Hz), 6.34 (d, 1H, J = 7.9 Hz), 6.87-6.96 (m, 3H), 7.14 (dd, 1H, J = 8.1, 1.2 Hz), 7.19 (dd, 1H, J = 8.1, 1.2 Hz). 10 Compound lj-80 [Formula 4531 N 1H-NMR (DMSO-d6) 5: 1.00 (dd, 2H, J = 23.2, 11.9 Hz), 1.19-1.25 (m, 2H), 1.28 (s, 9H), 15 1.33-1.38 (m, IH), 1.45 (s, 3H), 1.47 (s, 3H), 1.83 (d, 2H, J = 11.1 Hz), 2.07 (d, 2H, J = 11.1 Hz), 2.90 (t, 2H, J = 6.1 Hz), 3.62-3.70 (m, 1H), 4.57-4.66 (m, 1H), 6.21 (d, 1H, J = 7.9 Hz), 6.82-6.94 (m, 3H), 7.18 (d, 1H, J 7.6 Hz), 7.31 (d, 1H, J = 7.6 Hz). Compound Ij-81 20 [Formula 454] 0 0 N N H Compound Ij-82 [Formula 455] 0 0 > O.N nN HN 25 H 235 1H-NMR (DMSO-d6) 8: 0.90-1.19 (m, 4H), 1.28 (s, 9H), 1.32-1.45 (m, 1H), 1.80 (d, 2H, J = 11.2 Hz), 1.98 (d, 2H, J = 11.2 Hz), 2.84-2.93 (m, 2H), 3.26 (s, 3H), 3.40-3.53 (m, 1H), 6.29 (d, 1H, J = 8.0 Hz), 6.38 (d, 1H, J= 7.2 Hz), 6.86 (s, 1H), 7.33 (d, 1H, J= 8.4 Hz). 5 Compound Ij-83 [Formula 456] H| ..,N F Compound Ij-84 10 [Formula 4571 0 Q 1H-NMR (DMSO-d6) 5: 0.92-1.20 (m, 4H), 1.18 (t, 3H, J= 7.2 Hz), 1.40 (m, 1H), 1.75 1.85 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.60 15 3.78 (m, 1H), 6.38 (d, 1H, J = 8.1 Hz), 6.67 (s, 1H), 6.72 (d, 1H, J = 5.4 Hz), 7.00 (t, 1H, J = 6.0 Hz), 7.36-7.54 (m, 3H), 7.62 (d, 2H, J = 6.9 Hz), 8.00 (d, 1H, J = 5.4 Hz) Compound Ij-85 [Formula 458) oci F 20 1H-NMR (DMSO-d6) 6: 1.00-1.20 (m, 4H), 1.20 (t, 3H, J = 7.2 Hz), 1.43 (m, 1H), 1.80 1.88 (m, 2H), 2.03-2.13 (m, 2H), 2.81 (t, 3H, J = 6.0 Hz), 3.00 (q, 2H, J = 7.2 Hz), 3.26 (m, 1H), 6.17 (d, 1H, J= 7.6 Hz), 6.57 (s, 1H), 6.96-7.07 (m, 2H), 7.35 (dd, 1H, J= 8.4, 4.0 25 Hz), 8.02 (d, 1H, J = 8.4 Hz), 8.47 (d, 1H, J = 4.0 Hz). Compound Ij-86 236 [Formula 459] oo F 1H-NMR (DMSO-d6) 6:1.00-1.24 (m, 4H), 1.23 (d, 6H, J = 6.4 Hz), 1.42 (m, 1H), 1.80 5 1.88 (m, 2H), 2.03-2.12 (m, 2H), 2.79-2.87 (m, 2H), 3.16 (m, 1H), 3.27 (m, 1H), 6.17 (d, 1H, J = 8.0 Hz), 6.57 (s, 1H), 6.99 (d, 1H, J = 8.0 Hz), 7.01 (s, 1H), 7.35 (dd, 1H, J = 8.0, 4.0 Hz), 8.02 (d, 1H, J = 8.0 Hz), 8.47 (d, 1H, J = 2.8 Hz). Compound Ij-87 10 [Formula 460] N H 1H-NMR (DMSO-d6) 6: 0.95-1.08 (m, 2H), 1.11-1.25 (m, 2H), 1.20 (t, 3H, J = 7.2 Hz), 1.40 (m, 1H), 1.76-1.86 (m, 2H), 1.97-2.04 (m, 2H), 2.73-2.82 (m, 2H), 2.99 (q, 2H, J = 7.2 15 Hz), 3.70 (m, 1H), 6.53 (d, 1H, J = 8.8 Hz), 6.53 (d, 1H, J = 8.8 Hz), 7.01 (t, 1H, J = 6.0 Hz), 7.58 (d, 1H, J = 3.2 Hz), 7.79 (d, 1H, J = 3.2 Hz), 7.86 (d, 1H, J = 8.8 H z), 8.55 (s, 1H). Compound lj-88 20 [Formula 461] O H H 1H-NMR (DMSO-d6) 6: 0.92-1.07 (m, 2H), 1.09-1.20 (m, 2H), 1.19 (t, 6H, J = 7.2 Hz), 1.39 (m, 1H), 1.75-1.83 (m, 2H), 1.95-2.03 (m, 2H), 2.74-2.81 (m, 2H), 2.98 (q, 2H, J = 7.2 25 Hz), 3.66 (m, 1H), 6.48 (d, 1H, J = 8.4 Hz), 6.60 (d, 1H, J = 7.6 Hz), 7.00 (t, 1H, J = 5.6 Hz), 7.06 (dd, 1H, J = 4.8, 2.4 Hz), 7.25 (d, 1H, J = 2.4 Hz), 7.37 (d, 1H, J = 4.8 Hz), 7.60 (dd, 1H, J = 8.4, 2.0 Hz), 8.26 (s, 1H). Compound Ij-89 237 [Formula 4621 0,0 HN H 1H-NMR (DMSO-d6) 5: 0.93-1.07 (m, 2H), 1.10-1.20 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 5 1.39 (m, 1H), 1.76-1.84 (m, 2H), 1.96-2.04 (m, 2H), 2.73-2.81 (m, 2H), 2.98 (q, 2H, J= 7.2 Hz), 3.65 (m, iH), 6.41-6.50 (m, 2H), 7.01 (t, 1H, J = 6.0 Hz), 7.44 (d, 1H, J = 4.0 Hz), 7.58 (m, 1H), 7.59 (s, 1H), 7.68 (d, 1H, J = 8.0 Hz), 8.34 (a, 1H). Compound Ij-90 10 [Formula 463) 00NI o o N 1H-NMR (DMSO-d6) 8: 0.95-1.08 (m, 2H), 1.12-1.25 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.39 (m, 1H), 1.76-1.86 (m, 2H), 1.94-2.03 (m, 2H), 2.75-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 15 Hz), 3.71 (m, 1H), 6.54 (d, 1H, J= 8.8 Hz), 6.98-7.07 (m, 2H), 7.25 (a, 111), 7.85 (dd, 1H, J = 8.8, 2.0 Hz), 8.07 (s, 1H), 8.56 (d, 1H, J = 2.0 Hz). Compound Ij-91 [Formula 4641 00 Nj o o N 20 1H-NMR (DMSO-d6) 6: 0.93-1.07 (m, 2H), 1.11-1.22 (m, 2H), 1.21 (d, 6H, J = 6.8 Hz), 1.38 (m, 1H), 1.77-1.85 (m, 2H), 1.95-2.03 (m, 2H), 2.77-2.83 (m, 2H), 3.14 (m, 1H), 3.72 (m, 1H), 6.53 (d, 1H, J = 8.8 Hz), 6.97 (t, 1H, J = 6.0 Hz), 7.02 (d, 1H, J = 7.6 Hz), 7.25 (s, 25 1H), 7.84 (dd, 1H, J = 8.8, 2.0 Hz), 8.06 (s, 1H), 8.56 (d, 1H, J = 2.0 Hz). Compound Ij-92 [Formula 4651 238 0 0 CN 1H-NMR(DMSO-d6) 5:0.92-1.03 (m, 2H), 1.11-1.23 (m, 2H), 1.21 (d, 6H, J = 6.8 Hz), 1.37 (m, 1H), 1.75-1.83 (m, 2H), 1.91-1.99 (m, 2H), 2.36-2.42 (m, 2H), 3.12 (m, 1H), 3.70 5 (m, 1H), 6.49 (d, 1H, J = 9.2 Hz), 6.97 (t, 1H, J = 6.0 Hz), 7.47 (d, 1H, J = 8.0 Hz), 7.62 (d, 1H, J = 8.0 Hz), 8.36 (s, 1H). Compound Ij-93 [Formula 4661 0 0 10 H 1H-NMR (DMSO-d6) 5: 0.95-1.13 (m, 4H), 1.23 (d, 6H, J= 6.9 Hz), 1.31-1.44 (m, 1H), 1.78-1.82 (m, 2H), 2.03-2.06 (m, 2H), 2.76-2.82 (m, 2H), 3.10-3.19 (m, IH), 3.20-3.25 (m, 4H), 3.58-3.65 (m, 1H), 3.69-3.74 (m, 4H), 6.04 (d, 1H, J = 7.5 Hz), 6.72 (d, 1H, J = 9.6 15 Hz), 6.95-6.99 (m, 1H), 7.10 (d, 1H, J = 9.6 Hz). Compound Ij-94 [Formula 467] 00 pA -0Me H 20 1H-NMR (DMSO-d6) 5: 0.96-1.42 (m, 5H), 1.22 (d, 6H, J 6.9 Hz), 1.79-1.83 (m, 2H), 2.03-2.07 (m, 2H), 2.80 (d, 2H, J = 6.3 Hz), 3.10-3.19 (m, 1H), 3.54-3.70 (m, 1H), 3.74 (s, 3H), 6.57-6.64 (in, 3H), 6.72-6.75 (m, 1H), 6.90-7.09 (m, 3H), 7.24-7.30 (m, 1H). 25 Compound 1j-95 (Formula 468] 00 239 1H-NMR (DMSO-d6) 6: 0.93-1.04 (m, 2H), 1.10-1.18 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.34-1.44 (m, 1H), 1.78-1.87 (m, 2H), 2.02-2.12 (m, 2H), 2.77-2.84 (m, 2H), 3.10-3.20 (m, 1H), 3.52-3.70 (m, 1H), 6.64 (d, 1H, J = 8.0 Hz), 6.88-7.06 (m, 5H), 7.12 (d, 1H, J = 8.0 5 Hz), 7.37-7.46 (m, 1H). Compound Ij-96 [Formula 469] oo F H 10 1H-NMR (DMSO-d6) 6: 0.90-1.04 (m, 2H), 1.05-1.18 (m, 211), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.43 (m, 1H), 1.75-1.84 (m, 2H), 1.98-2.08 (m, 2H), 2.76-2.84 (m, 2H), 3.08-3.18 (m, 1H), 3.52-3.64 (m, 1H), 6.55 (d, 1H, J = 8.0 Hz), 6.91-7.00 (m, 2H), 7.15-7.38 (m, 511). 15 Compound Ij-97 [Formula 4701 H 1H-NMR (DMSO-d6) 6: 0.96- 1.08 (m, 2H), 1.12-1.25 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 20 1.35-1.47 (m, 1H), 1.78-1.87 (m, 2H), 2.02-2.10 (m, 2H), 2.78-2.83 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.70-3.82 (m, 1H), 6.82 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.0 Hz), 7.01 (t, 1H, J = 4.5 Hz), 7.13 (d, 1H, J = 4.0 Hz), 7.43 (d, 1H, J = 4.0 Hz), 7.76 (d, 1H, J = 8.0 Hz). Compound Ij-98 25 [Formula 4711 ci IJN H 1H-NMR (DMSO-d6) 5: 0.97-1.10 (m, 2H), 1.17-1.28 (m, 2H), 1.19 (t, 3H, J 7.2 Hz), 240 1.37-1.49 (m, 1H), 1.80-1.88 (m, 2H), 2.04-2.12 (m, 2H), 2.77-2.83 (m, 2H), 2.99 (q, 2H, J = 7.2 Hz), 3.76-3.88 (m, 1H), 6.85 (d, 1H, J = 8.0 Hz), 6.99-7.05 (m, 2H), 7.61 (, 1H), 7.90 (d, 1H, J = 8.0 Hz), 8.02 (, 2H). 5 Compound Ij-99 [Formula 472] Do %")V N N H 1H-NMR (DMSO-d6) 5: 0.98-1.10 (m, 2H), 1.14-1.26 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 10 1.37-1.48 (m, 1H), 1.80-1.88 (m, 2H), 2.04-2.13 (m, 2H), 2.77-2.83 (m, 2H), 2.96 (8, 6H), 2.99 (q, 2H, J = 7.2 Hz), 3.76-3.86 (m, 1H), 6.72-6.78 (m, 2H), 6.82 (d, 1H, J = 8.0 Hz), 7.02 (t, 1H, J = 4.5 Hz), 7.18 (d, 1H, J = 8.0 Hz), 7.26 (t, 1H, J = 8.0 Hz), 7.34 (s, 1H), 7.74 (d, 1H, J = 8.0 Hz). 15 Compound Ij-100 [Formula 473] 00 ", ' ;.0.0 H 1H-NMR (DMSO-d6)S: 0.98-1.10 (m, 2H), 1.16-1.27 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 20 1.37-1.48 (m, 1H), 1.80-1.88 (m, 2H), 2.04-2.13 (m, 2H), 2.77-2.83 (m, 2H), 2.99 (q, 2H, J = 7.2 Hz), 3.76-3.86 (m, 1H), 6.83 (d, 1H, J = 8.0 Hz), 6.89 (d, 1H, J = 8.0 Hz), 7.02 (t, 1H, J = 4.5 Hz), 7.42-7.50 (m, 3H), 7.53-7.59 (m, 2H). Compound Ij-101 25 [Formula 474] 00 'NN 1H-NMR (DMSO-d6)5: 0.92-1.05 (m, 2H), 1.08-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.36-1.43 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.09 (m, 2H), 2.77-2.83 (m, 2H), 3.10-3.20 (m. 241 1H), 3.56-3.68 (m, 1H), 6.62 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.0 Hz), 6.98 (t, IH, J = 4.5 Hz), 7.10-7.15 (m, 3H), 7.43 (d, 2H, J = 8.0 Hz). Compound Ij-102 5 [Formula 475] 00 H 1H-NMR (DMSO-d6) 6: 0.92-1.05 (m, 2H), 1.08-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.36-1.43 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.09 (m, 2H), 2.77-2.83 (m, 2H), 3.10-3.20 (m, 10 1H), 3.57-3.68 (m, 1H), 6.65 (d, 1H, J = 8.0 Hz), 6.94 (d, 1H, J = 8.0 Hz), 6.97 (t, 1H, J = 4.5 Hz), 7.06 (d, 1H, J = 8.0 Hz), 7.13 (d, 1H, J = 8.0 Hz), 7.18-7.26 (m, 2H), 7.41 (t, 1H, J = 8.0 Hz). Compound Ij-103 15 [Formula 476] 1H-NMR (DMSO-d6) 8: 0.88-1.04 (m, 2H), 1.05-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.43 (m, 1H), 1.77-1.82 (m, 2H), 2.00-2.07 (m, 2H), 2.76-2.82 (m, 2H), 3.08-3.20 (m, 20 1H), 3.52-3.64 (m, 1H), 6.57 (d, 1H, J = 8.0 Hz), 6.92-7.00 (m, 2H), 7.17 (d, 1H, J = 8.0 Hz), 7.23-7.28 (m, 2H), 7.38 (t, 1H, J = 8.0 Hz), 7.56 (d, 1H, J = 8.0 Hz). Compound Ij -104 [Formula 477] 25 1H-NMR (DMSO-d6) 6: 0.96-1.08 (m, 2H), 1.12-1.24 (m, 2H), 1.19 (t, 3H, J = 7.6 Hz), 1.35-1.46 (m, 1H), 1.78-1.86 (m, 2H), 2.04-2.12 (m, 2H), 2.76-2.82 (m, 2H), 2.98 (q, 2H, J = 7.6 Hz), 3.67-3.78 (m, 1H), 6.27 (s, 2H), 6.71 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.0 242 Hz), 7.02 (bre, 111), 7.52 (s, 2H), 7.67 (d, 1H, J = 8.0 Hz). Compound Ij-1 0 5 [Formula 478] Na 5 H. 'N . 1H-NMR (DMSO-d6) 6: 0.96-1.08 (m, 2H), 1.13-1.25 (m, 2H), 1.19 (t, 3H, J = 7.6 Hz), 1.35-1.46 (m, 1H), 1.78-1.87 (m, 2H), 2.04-2.12 (m, 2H), 2.76-2.83 (m, 2H), 2.99 (q, 2H, J = 7.6 Hz), 3.72-3.82 (m, 1H), 6.82 (d, 1H, J = 8.0 Hz), 6.85 (d, 1H, J = 8.0 Hz), 7.03 (t, 1H, 10 J = 4.5 Hz), 7.12 (t, 1H, J = 4.0 Hz), 7.51 (d, 1H, J = 4.0 Hz), 7.56 (d, 1H, J = 4.0 Hz), 7.76 (d, 1H, J = 8.0 Hz). Compound Ij-106 [Formula 4791 15 H 1H-NMR (DMSO-d6) 6: 0.88-1.02 (m, 2H), 1.07-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.45 (m, 1H), 1.76-1.85 (m, 2H), 2.02-2.08 (m, 2H), 2.76-2.83 (m, 2H), 3.10-3.20 (m, 1H), 3.57-3.67 (m, 1H), 6.63 (d, 1H, J = 8.0 Hz), 6.92-7.00 (m, 3H), 7.13 (d, 1H, J = 8.0 20 Hz), 7.29-7.36 (m, 1H), 7.42-7.50 (m, 1H). Compound Ij- 107 [Formula 4801 oF H 25 1H-NMR (DMSO-d6) 6: 0.88-1.02 (in, 2H), 1.07-1.20 (m, 2H), 1.21 (d, 6H, J 6.6 Hz), 1.33-1.43 (m, IH), 1.75-1.83 (m, 2H), 1.98-2.06 (m, 2H), 2.76-2.83 (m, 2H), 3.08-3.18 (m, 1H), 3.52-3.63 (m, 1H), 6.57 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H,*J = 8.0 Hz), 6.97 (t, 1H, J = 4.5 Hz), 7.12 (t, 1H, J = 4.0 Hz), 7.19 (d, 1H, J = 8.0 Hz), 7.33-7.47 (m, 2H). 243 Compound Ij-108 [Formula 4811 0, F 5 1H-NMR (DMSO-d6) 6: 0.88-1.02 (m, 2H), 1.07-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.43 (m, 1H), 1.75-1.83 (m, 2H), 1.98-2.07 (m, 2H), 2.76-2.83 (m, 2H), 3.08-3.18 (m, 1H), 3.54-3.63 (m, IH), 6.63 (d, 1H, J = 8.0 Hz), 6.93-7.00 (m, 2H), 7.14 (t, 1H, J = 8.0 Hz), 7.20-7.37 (m, 3H). 10 Compound Ij-109 [Formula 4821 00 15 1H-NMR (DMSO-d6) 6: 0.82-1.05 (m, 2H), 1.05-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.32-1.43 (m, IH), 1.76-1.83 (m, 2H), 2.00-2.08 (m, 2H), 2.29 (s, 3H), 2.76-2.83 (m, 2H), 3.08-3.18 (m, 1H), 3.56-3.66 (m, IH), 6.55 (d, 1H, J = 8.0 Hz), 6.90 (d, 1H, J = 8.0 Hz), 6.93-7.00 (m, 311), 7.05 (d, 1H, J = 8.0 Hz), 7.17 (d, 2H, J = 8.0 Hz). 20 Compound lj-110 [Formula 483] D D F H 1H-NMR (DMSO-d6) 6: 0.91-1.19 (m, 4H), 1.28 (s, 9H), 1.32-1.43 (m, 1H), 1.80 (d, 2H, J 25 = 12.0 Hz), 2.07 (d, 2H, J = 12.0 Hz), 2.88 (t, 2H, J = 6.4 Hz), 3.16-3.27 (m, 11), 5.47 (d, 1H, J = 7.6 Hz), 5.80 (s, 1H), 6.83 (d, 1H, J = 6.0 Hz), 7.15-7.40 (m, 3H), 7.75 (t, 1H, J 8.4 Hz), 7.86 (s, 1H). Compound Ij-111 244 [Formula 484) 0 F N 1H-NMR (DMSO-d6) 6: 0.91-1.19 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.32-1.43 (m, 1H), 5 1.76-1.82 (m, 2H), 2.02-2.12 (m, 2H), 2.77-2.83 (m, 2H), 3.08-3.27 (m, 2H), 5.48 (d, 1H, J = 8.1 Hz), 5.80 (d, 1H, J = 2.7 Hz), 6.95 (t, 1H, J = 6.0 Hz), 7.15-7.39 (m, 3H), 7.75 (td, 1H, J = 8.4, 1.8 Hz), 7.86 (t, 1H, J = 2.7 Hz). Compound Ij-112 10 [Formula 485] 00 F H 1H-NMR (DMSO-d6) 8: 0.91-1.19 (m, 4H), 1.18 (t, 3H, J = 7.2 Hz), 1.30-1.45 (m, 1H), 1.76-1.82 (m, 2H), 2.02-2.12 (m, 2H), 2.77-2.83 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz) 3.10-3.30 15 (m, 1H), 5.48 (d, 1H, J = 7.8 Hz), 5.80 (d, 1H, J = 2.7 Hz), 6.99 (t, 1H, J 6.0 Hz), 7.15 7.40 (m, 3H), 7.75 (td, 1H, J = 8.4, 1.8 Hz), 7.86 (t, 1H, J = 2.7 Hz). Compound Ij-113 [Formula 4861 00 F H N 20 H Compound Ij-1.14 [Formula 4871 N H 25 Compound Ij-115 [Formula 4881 245 00 F ) N --o H 1H-NMR (DMSO-d6) 5: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.30-1.45 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.74-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz) 3.15-3.30 5 (m, iH), 5.53 (d, 1H, J = 8.1 Hz), 5.80 (d, 1H, J = 2.4 Hz), 6.92 (t, 1H, J= 8.4 Hz), 7.01 (t, 1H, J= 6.0 Hz), 7.37-7.43 (m, 3H), 8.21 (d, 1H, J = 2.4 Hz). Compound Ij-116 [Formula 489] a 0 10 H Compound Ij-117 [Formula 4901 15 Compound Ij-118 [Formula 4911 0 a 0N -&F H 20 1H-NMR (DMSO-d6)8: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.30-1.45 (m, 1H), 1.75-1.86 (m, 2H), 2.02-2.12 (m, 2H), 2.74-2.83 (m, 2H), 2.97 (q, 2H, J = 7.5 Hz) 3.13-3.30 (m, 1H), 5.38 (d, 1H, J = 8.4 Hz), 5.75 (d, 1H, J = 2.7 Hz), 6.99 (t, 111, J = 6.3 Hz), 7.18 7.28 (m, 2H), 7.63-7.70 (m, 2H), 8.11 (d, 1H, J = 2.7 Hz). 25 Compound Ij-119 [Formula 4921 246 H 1H-NMR (DMSO-d6) 6: 0.88-1.19 (m, 4H), 1.18 (t, 3H, J = 7.5 Hz), 1.28-1.45 (m, 1H), 1.73-1.83 (m, 2H), 2.02-2.13 (m, 2H), 2.73-2.81 (m, 2H), 2.95 (q, 2H, J = 7.5 Hz) 3.12-3.30 5 (m, 1H), 5.36 (d, 1H, J = 7.5 Hz), 5.76 (d, 1H, J = 2.4 Hz), 6.98 (t, 1H, J = 6.0 H z), 7.30 (td, 1H, J = 7.5, 1.8 Hz), 7.42 (td, 1H, J = 7.8, 1.5 Hz), 7.53-7.60 (m, 2H), 7.84 (d, 1H, J = 2.7 Hz). Compound Ij-120 10 [Formula 4931 00 C mH 1H-NMR (DMSO-d6) 8: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.5 H z), 1.30-1.45 (m, 1H), 1.74-1.84 (m, 2H), 2.02-2.10 (m, 2H), 2.75-2.82 (m, 2H), 2.97 (q, 2H, J = 7.5 Hz) 3.20-3.30 15 (m, 1H), 5.52 (d, 1H, J = 7.8 H z), 5.80 (d, IH, J = 2.4 H z), 6.99 (t, 1 H, J = 6.0 H z), 7.13 (d, 1H, J = 8.1 Hz), 7.40 (t, 1H, J = 8.1 Hz), 7.62 (d, 1H, J = 8.4 Hz), 7.72 (s, 1H), 8.22 (d, 1H, J = 2.4 Hz). Compound Ij-121 20 [Formula 4941 00 1H-NMR (DMSO-d6) 6: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.30-1.45 (m, 1H), 1.74-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.75-2.82 (m, 2H), 2.98 (q, 2H, J = 7.5 Hz) 3.15-3.30 25 (m, 1H), 5.47 (d, 1H, J = 8.1 Hz), 5.78 (d, 1H, J = 2.4 Hz), 7.00 (t, 1H, J = 6.0 Hz), 7.43 (d, 2H, J = 7.8 Hz), 7.67 (d, 2H, J = 9.0 Hz), 8.17 (d, 1H, J = 2.4 Hz). Compound Ij-122 [Formula 4951 247 009 HN F 1H-NMR (DMSO-d6) 6: 0.94-1.07 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.32-1.50 (m, IH), 1.81-1.84 (m, 2H), 1.99-2.07 (m, 2H), 2.77-2.81 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.60 5 3.77 (m, IH), 7.01-7.05 (m, 1H), 7.22-7.40 (m, 4H), 7.81-7.87 (m, IH), 8.02 (s, 1H), 8.36 (s, 1H). Compound Ij-123 [Formula 4961 D o F F 10 H 1H-NMR (DMSO-d6) 6: 0.95-1.12 (m, 4H), 1.18 (t, 3H, J = 7.2 Hz), 1.32-1.50 (m, 1H), 1.77-1.81 (m, 2H), 1.96-1.99 (m, 2H), 2.74-2.78 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.54 3.70 (m, 1H), 4.81 (q, 2H, J = 9.0 Hz), 6.50-6.53 (m, 1H), 6.99-7.03 (m, 1H), 7.50 (d, 1H, J 15 =0.9 Hz) 7.83 (d, 1H, J = 0.9 Hz). Compound Ij-124 [Formula 4971 oa -'--' N N HH 20 1H-NMR (DMSO-d6) 6: 0.95-1.23 (m, 4H), 1.19 (t, 3H, J= 7.2 Hz), 1.32-1.50 (m, 1H), 1.77-1.81 (m, 2H), 2.03-2.07 (m, 2H), 2.74-2.80 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.61 3.73 (m, 1H), 7.00-7.04 (m, 1H), 7.09-7.12 (m, 1H), 7.29-7.37 (m, 2H), 7.45-7.52 (m, 1H), 7.88-7.94 (m, 2H), 8.04-8.05 (m, 1H). 25 Compound Ij- 1 2 5 [Formula 498] 248 0, o F 1H-NMR (DMSO-d6) 6: 0.94-1.14 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.32-1.50 (m, 1H), 1.79-1.83 (m, 2H), 1.97-2.03 (m, 2H), 2.76-2.81 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.50 5 3.63 (m, 1H), 4.43 (q, 2H, J = 9.0 Hz), 7.00-7.04 (m, 1H), 7.13-7.15 (m, 1H), 7.35 (s, 1H) 7.55 (a, 1H). Compound Ij- 126 [Formula 499] 00 10 H 1H-NMR (DMSO-d6) 6:1.02-1.08 (m, 2H), 1.17-1.29 (m, 2H), 1.19 (t, 3H, J = 7.5 Hz), 1.36-1.43 (m, 1H), 1.79-1.85 (m, 2H), 2.05-2.11 (m, 2H), 2.79 (t, 2H, J = 6.0 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.53-3.62 (m, 1H), 6.98 (t, 1H, J = 7.8 Hz), 7.03 (t, 1H, J = 6.3 Hz), 7.28 15 (dd, 1H, J = 7.5, 1.2 Hz), 7.63 (dd, 1H, J = 7.5, 1.2 Hz), 8.28 (d, 1H, J = 7.5 Hz). Compound Ij-127 [Formula 500] Cl H H H 20 1H-NMR (DMSO-d6) 5: 0.97-1.05 (m, 2H), 1.18-1.24 (m, 2H), 1.16 (t, 3H, J = 7.5 Hz), 1.34-1.41 (m, 1H), 1.77-1.81 (m, 2H), 2.02-2.08 (m, 2H), 2.76 (t, 2H, J = 6.0 Hz), 2.96 (q, 2H, J = 7.5 Hz), 3.55-3.64 (m, 1H), 7.00 (t, 1H, J = 7.8 Hz), 7.18 (dd, 1H, J = 8.4, 1.8 Hz), 7.32 (dd, 1H, J = 8.4, 0.6 Hz), 7.74 (d, 1H, J = 1.8 Hz), 8.04 (d, 1H, J = 7.8 Hz). 25 Compound Ij-128 [Formula 501] 249 00 o o~ H 1H-NMR (DMSO-d6) 6: 0.98-1.07 (m, 2H), 1.15-1.26 (m, 8H), 1.32-1.43 (m, 1H), 1.78-1.84 (m, 2H), 1.98-2.09 (m, 2H), 2.60 (q, 2H, J = 7.5 Hz), 2.78 (t, 2H, J = 6.3 Hz), 2.96 (q, 2H, 5 J = 7.5 Hz), 3.55-3.64 (m, 1H), 6.98-7.05 (m, 2H), 7.27 (dd, 1H, J = 7.8, 1.8 Hz), 7.47 (m, IH), 7.84 (d, 1H, J =7.5 Hz). Compound Ij-129 [Formula 5021 o o N 02 00N0 10 1H-NMR (DMSO-d6) 5: 0.92-1.15 (m, 2H), 1.15-1.35 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.48 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.78-2.84 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.62-3.80 (m, 1H), 7.02 (t, 1H, J = 6.0 Hz), 7.45 (d, 1H, J = 9.0 Hz), 8.09 (dd, 15 111, J = 9.0, 2.4 Hz), 8.68 (d, 1H, J= 2.4 Hz), 8.70 (bra, 1H). Compound Ij-130 [Formula 503] 20 1H-NMR (DMSO-d6) 6: 0.88-1.10 (m, 2H), 1.15-1.46 (m, 3H), 1.21 (d, 6H, J = 6.6 Hz), 1.78-1.88 (m, 2H), 1.98-2.08 (m, 2H), 2.76-2.86 (m, 2H), 3.10-3.20 (m, IH), 3.46-3.62 (m, 1H), 6.91-6.96 (m, 1H), 7.01 (brs, 1H), 7.64 (d, 1H, J = 7.8 Hz), 8.07 (d, 1H, J = 5.1 Hz), 8.35 (d, 1H, J = 7.8 Hz). 25 Compound Ij-131 [Formula 5041 250 aIe 1H-NMR (DMSO-d6) 8: 0.92-1.05 (m, 2H), 1.15-1.30 (m, 2H), 1.27 (s, 9H), 1.30-1.43 (m, 1H), 1.77-1.86 (m, 2H), 1.98-2.08 (m, 2H), 2.86-2.92 (m, 2H), 3.35-3.50 (m, 1H), 3.73 (s, 5 3H), 6.69 (dd, 1H, J = 8.4, 2.0 Hz), 6.86 (t, 1H, J = 6.0 Hz), 7.01 (d, 1H, J = 2.0 Hz), 7.10 (d, 1H, J = 8.4 Hz), 7.62 (d, 1H, J = 7.6 Hz). Compound Ij-132 [Formula 5051 cI 10 1H-NMR (DMSO-d6)6: 0.92-1.08 (m, 2H), 1.15-1.33 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.42 (m, 1H), 1.76-1.86 (m, 2H), 1.98-2.08 (m, 2H), 2.76-2.82 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.40-3.58 (m, 1H), 7.01 (t, 1H, J = 6.0 Hz), 7.13 (d, 1H, J = 8.4 Hz), 7.20 (d, 1H, 15 J = 8.4 Hz), 7.49 (s, 1H), 8.01 (d, 1H, J = 7.6 Hz). Compound Ij-133 [Formula 506] F 0 aF H 20 1H-NMR (DMSO-d6) 5: 0.96-1.10 (m, 2H), 1.16-1.28 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.46 (m, 1H), 1.78-1.85 (m, 2H), 2.04-2.12 (m, 2H), 2.76-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.55-3.70 (m, 1H), 7.01 (t, 1H, J = 6.0 Hz), 7.12 (t, 1H, J = 9.6 Hz), 7.48 (d, 1H, J = 7.6 Hz), 8.13 (d, 1H, J = 7.6 Hz). 25 Compound Ij-134 [Formula 5071 251 / N 1H-NMR (DMSO-d6) 8: 0.98-1.08 (in, 2H), 1.15-1.26 (m, 2H), 1.21 (d, 6H, J 6.9 Hz), 1.33-1.42 (m, 1H), 1.39-1.84 (m, 2H), 2.05-2.09 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.10-3.20 5 (m, iH), 3.61-3.75 (m, 1H), 6.98 (t, 1H, J = 6.0 Hz), 7.45 (dd, 1H, J = 7.5, 0.6 Hz), 7.60 (dd, 1H, J = 8.4, 1.5 Hz), 8.17 (d, 1H, J = 1.5 Hz), 8.50 (d, 1H, J = 7.5 Hz). Compound Ij-135 [Formula 508] 00 N 0 H 1H-NMR (DMSO-d6) 8: 0.98-1.08 (m, 2H), 1.15-1.25 (m, 2H), 1.21 (d, 6H, J= 6.6 Hz), 1.35-1.44 (m, 1H), 1.80-1.84 (m, 2H), 2.05-2.08 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.10-3.19 (m, 1H), 3.62-3.78 (m, 1H), 6.98 (t, 1H, J = 6.0 Hz), 7.79 (d, 1H, J 2.1 Hz), 8.10 (d, 1H, 5 J = 2.1, 1.5 Hz), 8.52 (d, 1H, J = 6.9 Hz). Compound Ij-136 [Formula 509] 00 H 20 1H-NMR (DMSO-d6) 5: 0.97-1.08 (m, 2H), 1.17-1.24 (m, 2H), 1.19 (t, 3H, J 7.5 Hz), 1.33-1.41 (m, 1H), 1.78-1.83 (m, 2H), 2.04-2.08 (m, 2H), 2.78 (t, 2H, J = 6.3 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.56-3.67 (m, 1H), 7.00-7.04 (m, 2H), 7.39 (d, 1H, J = 2.1 Hz), 7.66 (dd, 1H, J = 8.4, 1.8 Hz), 8.14 (d, 1H, J = 7.5 Hz). 25 Compound Ij-137 [Formula 510] H 1H-NMR (DMSO-d6) 6: 0.96- 1.10 (m, 2H), 1.12-1.28 (m, 2H), 1.21 (d, 6H, J= 6.9 Hz), 1.31 (t, 3H, J = 6.9 Hz), 1.33-1.46 (m, 1H), 1.76-1.85 (m, 2H), 2.02-2.16 (m, 2H), 2.78-2.84 5 (m, 2H), 3.10-3.22 (m, 1H), 3.50-3.64 (m, 1H), 3.98 (q, 2H, J = 6.9 Hz), 6.78 (dd, 1H, J = 8.7, 2.7 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.23-7.27 (m, 2H), 7.68 (d, 1H, J = 7.2 Hz). Compound Ij-138 [Formula 511] F H 0 0 1H-NMR (DMSO-d6) 5: 0.94-1.08 (m, 2H), 1.14-1.26 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.45 (m, 1H), 1.77-1.86 (m, 2H), 2.03-2.12 (m, 2H), 2.76-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.52-3.68 (m, 1H), 6.97-7.06 (m, 2H), 7.34 (dd, 1H, J = 8.4, 4.8 Hz), 7.56 (dd, 5 1H, J = 8.4, 2.4 Hz), 7.91 (d, 1H, J = 7.6 Hz). Compound Ij-139 [Formula 512] ci -N s 20 1H-NMR (DMSO-d6) 5: 0.96-1.12 (m, 2H), 1.16-1.32 (m, 2H), 1.21 (d, 6H, J= 6.6 Hz), 1.32-1.46 (m, 1H), 1.78-1.86 (m, 2H), 2.02-2.16 (m, 2H), 2.78-2.84 (m, 2H), 3.10-3.21 (m, 1H), 3.58-3.76 (m, 1H), 7.00 (t, 1H, J = 6.0 Hz), 8.19-8.23 (m, 2H), 8.52 (d, 1H, J = 6.9 Hz). 25 Compound Ij-140 [Formula 513] F 1H-NMR (DMSO-d6) 6: 0.96-1.12 (m, 2H), 1.12-1.30 (m, 2H), 1.21 (d, 6H, J= 6.6 Hiz), 1.32-1.46 (m, 1H), 1.78-1.86 (m, 2H), 2.02-2.16 (m, 2H), 2.78-2.84 (m, 2H), 3.10-3.20 (m, 5 1H), 3.58-3.78 (m, 1H), 7.01 (t, 1H, J = 6.0 Hz), 8.08 (dd, 1H, J = 8.4, 2.7 Hz), 8.19 (d, 1H, J = 2.7 Hz), 8.38 (d, 1H, J = 7.2 Hz). Compound Ij-141 [Formula 514] W~e Goo -VN 5 ci 0 H/ 1H-NMR (DMSO-d6) 6: 0.97-1.08 (m, 2H), 1.15-1.22 (m, 5H), 1.34-1.42 (m, IH), 1.78-1.83 (m, 2H), 2.04-2.08 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.53-3.62 (m, iH), 3.81 (s, 1H), 7.02 (t, 1H, J = 6.3 Hz), 7.41 (s, 1H), 7.53 (s, 1H), 7.88 (d, 1H, J = 7.5 .5 Hz). Compound Ij-142 [Formula 515] \/CI H 20 1H-NMR (DMSO-d6) 5: 0.94-1.06 (m, 2H), 1.17-1.30 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.32-1.41 (m, 1H), 1.79-1.84 (m, 2H), 2.01-2.05 (m, 2H), 2.77 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.41-3.58 (m, 1H), 6.97 (dd, 1H, J = 8.4, 2.4 Hz), 6.99-7.03 (m, 1H), 7.27 (d, 1H, J = 2.4 Hz), 7.34 (dd, 1H, J = 8.4, 0.3 Hz), 8.07-8.14 (m, 1H). 25 Compound Ij-143 [Formula 516] 1H-NMR (DMSO-de) 8: 0.94-1.08 (m, 21-), 1.1L-1.33 (m, 2K), 1.19 (t, 3H, J= 7.2 Hz), 1.33-1.45 (m, 1H), 1.77-1.86 (n, 2H), 2.00-2.08 (m, 2H), 2.74-2.82 (m, 2H), 2.98 (q, 2H, J 5 = 7.2 Hz), 3.38-3.54 (m, 1H), 6.90-7.00 (m, 1H), 7.02 (t, 1H, J = 4.5 Hz), 7.19 (dd, 1H, J = 8.4, 5.1 Hz), 7.33 (dd, 1H, J = 8.4, 2.7 Hz), 7.88 (d, 1H, J = 7.8 Hz). Compound Ij-144 [Formula 5171 F 0 H 1H-NMR (DMSO-d6) 6: 0.94-1.06 (m, 2H), 1.19-1.29 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.31-1.41 (m, 1H), 1.79-1.84 (m, 2H), 2.01-2.05 (m, 2H), 2.77 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 6.9 Hz), 3.41-3.57 (m, 1H), 6.71-6.79 (m, IH), 7.06-7.08 (m, 2H), 7.31 (dd, 1H, J= 5 8.7, 4.8 Hz), 8.03 (d, 1H, J = 7.8 Hz). Compound Ij-145 [Formula 518] 00 H 20 1H-NMR (DMSO-d6) 5: 0.95-1.16 (m, 2H), 1. 18-1.44 (m, 3H), 1.21 (d, 6H, J = 6.6 Hz), 1.78-1.86 (m, 2H), 2.02-2.12 (m, 2H), 2.78-2.84 (m, 2H), 3.10-3.20 (m, 1H), 3.40-3.58 (m, 1H), 6.95 (t, 1H, J = 7.8 Hz), 7.01 (brs, 1H), 7.09 (t, 1H, J = 6.9 Hz), 7.22 (d, 1H, J = 6.6 Hz), 7.31 (d, 1H, J = 7.8 Hz), 7.83 (d, 1H, J = 7.8 Hz). 25 Compound Ij-146 [Formula 519] '-' '~-f N' Compound Ij-147 [Formula 520] 0 0 0 N 'N N' 5 H Compound Ij-148 [Formula 521] -NN N H 0 [0084] Experiment 1 Transportability through the blood-brain barrier and potential for drug drug interactions through P-gp Transportability of the compounds of the present invention through the blood 15 brain barrier (blood-brain partition coefficient; Kp) in mice (Jcl;C57BL/6J mice, ce, 7 weeks) was defined from the difference in concentration of the compounds between in plasma and in brain after intravenous administration of the compounds (0.5 mg/2 mL/kg). The brain Kp value of Compound (1-72) (Kp cont.) was 1.29 showing high transportability through the blood-brain barrier. 20 To examine the potential for drug-drug interactions through P-gp in vivo, the Kp values of compounds of the present invention with (Kp cs.-) or without (Kp cont.) cyclosporin A (20 mg/kg), a P-gp inhibitor, were calculated. The Kp CSA value of Compound (I-72) was 1.14, and the calculated Kp CSA / Kp Cont. ratio was 0.9. The result indicate that Compound (1-72) has no significant potential for drug-drug interactions ?5 through P-gp in mice. [0085] On the other hand the potential for drug-drug interactions through P-pg of aide -OMflU 16LLLLL .I-1 TV £J.L~..~- The Kp ca. and Kp csA were 0.04 and 0.84, respectively. The Kp csA / Kp c.t ratio w as aore than 1.0 (i.e. 20.5), indicating that the compound is effectively excreted through P p from the brain to vessels, and that significant drug-drug interactions through P-gp ould be induced in mice. Formula 522]

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.

N Compound B 0086] Experiment 2 Affinity for NPY Y5 receptor cDNA sequence encoding a mouse NPY Y5 receptor (Biochim. Biophys. Acta 1328, 33-89, 1997) was cloned in a vector (pMEI 8S, Takebe et al. Mol. Cell. Biol. 8, 466-472). The obtained expression vector was transfected into CHO cells as a host by using Lipofect ,AMINE reagent (Trademark, Gico BRL Co., Ltd.) according to the instruction manual. The cells that stably express NPY Y5 receptor were obtained. The membranes prepared from the CHO cells expressing NPY Y5 receptor, the :ompound of the present invention and 80,000 cpm [51] peptide YY (60 pM of final :oncentration: Amersham) were incubated in the assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serum albumin, pH 7.4) at 25 "C for 2 hours, and then the membrane was filtered from the mixture through a glassfilter (GF/O) presoaked with 1 % polyethyleneimine. After washing with 50 mM Tria-HCl buffer (pH 7.4), radioactivity retained on the filters was quantified with a gamma counter. Nonspecific binding was defined as the amount of radioactivity bound to the membranes after incubation in the presence of 200 rM of peptide YY. The 50 % inhibitory concentration of the test compound against the specific peptide YY binding (ICao value) was calculated (InuL, A. et al. Endocrinology 131, 2090 - 2096 (1992)). The results are shown in Table 1. . The compounds of the present invention inhibited the binding of peptide YY (NPY homologue) to NPY Y5 receptor, indicating that the compounds of the present invention have an affinity for the NPY Y5 receptor. [Table 11 257 Com ound No. Binding IC5o(nM) 1i-i 0.10 Ii-16 1.2 Ii-34 11 Ii-44 3.4 1j-1 0.70 1-52 0.99 j-59 2.5 Ij-66 |0.39| [0087] Experiment 3 Inhibitory effect on cAMP production in CHO cells CHO cells expressing human NPY Y5 receptor were incubated in the presence of 2.5 mM isobutylmethylxanthine (SIGMA) at 37 0C for 20 min. After the incubation the compound of the present invention was added, and then the mixture was incubated for 5 min. Next, 50 nM NPY and 10 pM forskolin (SIGMA) were added, and the mixture was incubated for 30 min. After termination of the reaction by adding 1N HCl, the amount of cAMP in the supernatant was determined with an EIA kit (Amersham LIFE SCIENCE). The inhibitory activity of NPY against forskolin stimulated cAMP production was expressed as 100 % and the 50 % inhibitory concentration (ICBo value) of the compound of the present invention against the NPY activity was calculated. [0088] Experiment 4 Using the membranes prepared from Y1-expression cells (human neuroblastoma, SK-N-MC) and the membranes prepared from Y2-expression cells (human neuroblastoma, SMS-KAN), the experiment was carried out in a similar way as Experiment 2 to determine the aminity of the compounds for NPY Y1 and NPY Y2 receptor. The results showed that the compounds of the present invention had no 20 significant affinity for their receptors, indicating high selectivity for NPY Y5 receptor. (0089] Experiment 5 Under diethylether anesthesia the skull of male C57B1J6J mice (12-14 week old, 25-30g) was exposed by making an incision about 1-cm long from external occipital crest 25 to nasal dorsum, and drilled in the 1-mm lateral position to the left following 1-mm posterior from bregma. After recovery from anesthesia mice were dosed with either 0.5% hydroxypropylmethyl cellulose solution (Shin-Etsu Chemical Co., Ltd) or the compounds of the present invention suspended in the 0.5% hydroxymethylpropylmethyl cellulose solution. At one hour after the treatment, each animal received a NPY Y5 receptor specific agonist, [cPP'- 7 , NPY19 23 , Ala 31 , Aib 32 , Gln34] hPancreatic Polypeptide (0.1 nmol/1.5 L/mouse) through the skull opening using a canula. Residual food was measured at 2 and 4 hours after the treatment, and the difference in food intake between the compounds-treated mice and 0.5% hydroxypropylmethyl cellulose solution-treated mice was calculated. The compound at 6 mg/kg caused a significant reduction in food intake of mice compared to the treatment with 0.5% hydroxypropylmethyl cellulose solution. [0090] Formulation Example The following Formulation Examples are only exemplified and not intended to limit the scope of the present invention. Formulation Example 1 Tablets Compound (I-1) 15 mg Starch 15 mg Lactose 15 mg Crystalline cellulose 19 mg Polyvinyl alcohol 3 mg Distilled water 30 ml Calcium stearate 3 mg All of the above ingredients except for calcium stearate are uniformly mixed. Then the mixture was crushed, granulated and dried to obtain a suitable size of granules. Next, calcium stearate was added to the granules. Finally, tableting was !5 performed under a compression force. [0091] Formulation Example 2 Capsules Compound (1-2) 10 mg Magnesium stearate 10 mg 30 Lactose 80 mg The above ingredients were mixed uniformly to obtain powders or fine granules, and then the obtained mixture was filled in capsules. [0092] Formulation Example 3 Granules 35 Compound (1-3) 30 g Lactose 265 g Magnesium Stearate 5 g After the above ingredients are mixed uniformly the mixture was compressed. The compressed matters were crushed, granulated and sieved to obtain suitable size of granules. Industrial Applicability [0093] As shown in the above Experiments, the compounds of the present invention have a NPY Y5 receptor antagonistic activity. Therefore, the compounds of the present invention are very useful as an anti-obesity and anorectic agent. Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates. 260