CYCLOPENTYLPYRAZOLES AS N-TYPE CALCIUM CHANNEL BLOCKERSDisclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, Q, and G are defined herein.A compound of Formula (I)Formula. (!)whereinR1 is selected from the group consisting of Chalky!, Cf^alkoxy, trifluoromethoxv, and trifluoromethyl:R' is hydrogen; or, R may be taken with R and the phenyl ring to which R3 and R2 are both attached to form 2,3-dihydrobenzofuran-7-yi;RJ is hydrogen, chloro, or fluoro;Q is selected from the group consisting of Q l , Q2, and Q3;Q1 Q2 Q3 whereinR4 is selected from the group consisting of hydrogen, Ci^alkyl, Q. 4alkoxy, cyano, fluoro, chloro, hydroxy, di(C1-4alkyl)amino, (Q.4alkyl)amino, amino, and C1-4alkylsuifonyl; R' and R are each independently selected from the group consisting of hydrogen, C^alkyl, C1-4alkoxy, cyano, chloro, and di(C1-4alk^'l)amino;G is selected from the group consisting of d-ealkyl, hydroxy(Cj-4)aikyl, d- 6alkoxy, hydroxy, ally!, 2-methylprop-l-enyl, cyano, oxime, phenoxy, d- 4alkoxycarbonyl, 4)alkyl, Cs-ecycioalkyloxy, d-ealkyicarbonyloxy, di(C1-4alkyl)aminocarbonyloxy, di(Ci_4a.lkyl)aminocarbonyloxy-Ci_4alkyl, C3-6cycloalkyl(Ci_4)alkoxy, d^cycloalkylearbonyloxy, di(d-4alkyl)aminosulfonyl- amino, di(C!_4alkyl)aminosulfonyl~(A7~methyl)amir!0, Ci-4alkylsulfonyl-(N- methyl)amino, d^alkyisulfonylamino, d-4alkylsulfonylammo-C] .4alkyl, d.. 4alkylcarbonylamino-Ci-4alkyl, diiCi^alkylJaminocarbonylamino-Ci^alkyl, trifluoromethylcarbonylamino, trifluoromethylcarbonylamino-C alkyl, 2,5-dioxo- pyrrolidin- 1 -yl, 2-oxo-pyrrolidin- 1 ~yl, 3,3-ditluoro-pyrrolidin- 1 -yl, 3,3-diethyl- pyrrolidin- 1 -yl, 3,3-dimethyl-pyrrolidin- 1 -yl, pyrrolidin- 1 -yl, pyridinyloxy, trimethylsilyloxy, oxo, (tetrahydro-2H-pyran-2-yl)oxy, nwpb.olin-4-yl, 2,6- dirneihyl-morpholin-4-yl, rnorpho!in-4-ylcarbonyloxy, moipholin-4-y]carbonyloxy- C1-4alkyl, 6~(moq:>holin-4-yl)-pyrimidir!-3-yl, 4-methyl-piperidin-l-yl, (1 ,2,4)- bicyclo[2.2.1 ]heptan-2-yloxy, tetrahydro-2H-pyran-4-ylcarbonyloxy, tetrahydro- 2H-pyran-4-yl(C1_4)a3koxy, l ,2,3,4-tetrahydroquinolm-3-yl, aminocarbonyl,pyridin-3-yl optionally substituted with one to two substituents each independently selected from the group consisting of chloro, cyclopropyl, ηιοφ1ιο1ίη-4-ν1, and d-4alkoxycarbonyl;lH- l ,2,3-triazol-l -yl optionally substituted with one to two substituents each independently selected from the group consisting of C^alkyl, 2- hydroxypropan-2-yl, methoxymethyl, C3-6cycloalkyl, d^alkoxycarbonyl, d- 4alkyIcarbonyloxy-d-4alkyI, and trimethyisilyi;lH-imidazol-l-yl optionally independently substituted with one to three d- 3 alky 1 substituents;and a spirofused heterocyclvl independently selected from the group consisting of 4,4,5,5-tetramethyl-l ,3-dioxolan-2-y[, 4,5-dimethyl- 1 ,3-dioxolan-2-yi, 1 ,3- dioxan-2-yl, 4,6-dimethyl-l ,3-dioxan-2-yl, (3a,6a)-tetrahydro-3aH- cyclopenta[d][l,3]dioxol-2-yl, 5,5-dimethyl-l ,3-dioxan-2-yl, and (3a,7a.)- hexa.hydrobenzo[d] [ 1 ,3]dioxol-2-yl;provided that a compound of Formula (I) is other thanN-[3-(4-chlorophenyl)-2-(2-methoxyphenyl)-2,4,5,6- tetrahydrocyciopenta[c]pyrazol-5-yi]-N,N',N'-trimethylsulfamide: or 3-(4-chlorophenyl)-2-(2-methoxyphenyl)-4',4',5',5,-tetramethyl-2,6-dihydro-4H- spiro[cyclopenta[c]pyrazole-5,2'-[l ,3]dioxolane];and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof.The compound of claim 1 wherein R1 is selected from the group consisting of 4alkyl, Ci.4alkoxy, and trifluoromethoxy.The compound of claim 2 wherein R* is selected from the group consisting of Q. 4alkoxy, and trifluoromethoxy;The compound of claim 3 wherein R2 is hydrogen.The compound of claim 3 wherein R ' is hydrogen or chloro.The compound of claim 5 wherein R' is hydrogen.The compound of claim 1 wherein R4 is selected from the group consisting of C]_ 4alkyl, C1-4alkoxy, cyano, chloro, and di(C1-4alkyl)amino.
N형 칼슘 채널 차단제로서의 사이클로펜틸피라졸통증을 포함하는 다양한 질환, 증후군, 상태 및 장애를 치료하기 위한 화합물, 조성물 및 방법이 개시된다. 그러한 화합물은 다음과 같이 화학식 (I)로 나타내어진다: [화학식 (I)] 상기 식에서, R1, R2, R3, Q및 G는 본 명세서 및 특허청구범위에 정의된 바와 같다.N-[3-(4-클로로페닐)-2-(2-메톡시페닐)-2,4,5,6-테트라하이드로사이클로펜타[c]피라졸-5-일]-N,N',N'-트라이메틸설파미드 또는 3-(4-클로로페닐)-2-(2-메톡시페닐)-4',4',5',5'-테트라메틸-2,6-다이하이드로-4H-스피로[사이클로펜타[c]피라졸-5,2'-[1,3]다이옥솔란] 이외의 화학식 (I)의 화합물, 및 이의 거울상 이성질체, 부분입체 이성질체 및 약제학적으로 허용가능한 염:[화학식 (I)]상기 식에서,R1은 C1-4알킬, C1-4알콕시, 트라이플루오로메톡시 및 트라이플루오로메틸로 이루어진 군으로부터 선택되고;R2는 수소이거나; R2는 R1과, R1 및 R2가 부착되어 있는 페닐 고리와 함께 2,3-다이하이드로벤조푸란-7-일을 형성할 수 있으며;R3는 수소, 클로로 또는 플루오로이고;Q는 Q1, Q2 및 Q3:로 이루어진 군으로부터 선택되며;여기서,R4는 수소, C1-4알킬, C1-4알콕시, 시아노, 플루오로, 클로로, 하이드록시, 다이(C1-4알킬)아미노, (C1-4알킬)아미노, 아미노, C1-4알킬카르보닐 및 C1-4알킬설포닐로 이루어진 군으로부터 선택되고;R5 및 R6는 각각 독립적으로 수소, C1-4알킬, C1-4알콕시, 시아노, 클로로 및 다이(C1-4알킬)아미노로 이루어진 군으로부터 선택되며;G는 C1-6알킬, 하이드록시(C1-4)알킬, C1-6알콕시, 하이드록시, 알릴, 2-메틸프로프-1-에닐, 시아노, 옥심, 페녹시, C1-4알콕시카르보닐, C3-6사이클로알킬, 4,4-다이메틸-사이클로헥실, C3-6사이클로알킬(C1-4)알킬, C3-6사이클로알킬옥시, C1-6알킬카르보닐옥시, 다이(C1-4알킬)아미노카르보닐옥시, 다이(C1-4알킬)아미노카르보닐옥시-C1-4알킬, C1-4알콕시카르보닐아미노-C1-4알킬, C3-6사이클로알킬(C1-4)알콕시, C3-6사이클로알킬카르보닐옥시, 다이(C1-4알킬)아미노설포닐-아미노, 다이(C1-4알킬)아미노설포닐-(N-메틸)아미노, C1-4알킬설포닐-(N-메틸)아미노, C1-4알킬설포닐아미노, C1-4알킬설포닐아미노-C1-4알킬, C1-4알킬카르보닐아미노-C1-4알킬, 다이(C1-4알킬)아미노카르보닐아미노-C1-4알킬, 트라이플루오로메틸카르보닐아미노, 트라이플루오로메틸카르보닐아미노-C1-4알킬, 2,5-다이옥소-피롤리딘-1-일, 2-옥소-피롤리딘-1-일, 3,3-다이플루오로-피롤리딘-1-일, 3,3-다이에틸-피롤리딘-1-일, 3,3-다이메틸-피롤리딘-1-일, 피롤리딘-1-일, 피리디닐옥시, 트라이메틸실릴옥시, 옥소, (테트라하이드로-2H-피란-2-일)옥시, 모르폴린-4-일, 2,6-다이메틸-모르폴린-4-일, 모르폴린-4-일카르보닐옥시, 모르폴린-4-일카르보닐옥시-C1-4알킬, 6-(모르폴린-4-일)-피리미딘-3-일, 4-메틸-피페리딘-1-일, (1,2,4)-바이사이클로[2.2.1]헵탄-2-일옥시, 테트라하이드로-2H-피란-4-일카르보닐옥시, 테트라하이드로-2H-피란-4-일(C1-4)알콕시, 1,2,3,4-테트라하이드로퀴놀린-3-일, 아미노카르보닐;C1-4알킬, C1-4알콕시, 클로로, 사이클로프로필, 모르폴린-4-일 및 C1-4알콕시카르보닐로 이루어진 군으로부터 각각 독립적으로 선택되는 1개 내지 2개의 치환기로 임의로 치환되는 피리딘-3-일;C1-4알킬, 2-하이드록시프로판-2-일, 메톡시메틸, C3-6사이클로알킬, C1-4알콕시카르보닐, C1-4알킬카르보닐옥시-C1-4알킬 및 트라이메틸실릴로 이루어진 군으로부터 각각 독립적으로 선택되는 1개 내지 2개의 치환기로 임의로 치환되는 1H-1,2,3-트라이아졸-1-일;1개 내지 3개의 C1-3알킬 치환기로 임의로 독립적으로 치환되는 1H-이미다졸-1-일; 및4,4,5,5-테트라메틸-1,3-다이옥솔란-2-일, 4,5-다이메틸-1,3-다이옥솔란-2-일, 1,3-다이옥산-2-일, 4,6-다이메틸-1,3-다이옥산-2-일, (3a,6a)-테트라하이드로-3aH-사이클로펜타[d][1,3]다이옥솔-2-일, 5,5-다이메틸-1,3-다이옥산-2-일 및 (3a,7a)-헥사하이드로벤조[d][1,3]다이옥솔-2-일로 이루어진 군으로부터 독립적으로 선택되는 스피로융합된 (spirofused) 헤테로사이클릴로 이루어진 군으로부터 선택된다.