Imidazole derivativesThe invention provides compounds of formula (1), wherein R, R, R, and R are as defined, and their pharmaceutically acceptable salts. Compounds of formula (1) are indicated to have activity inhibiting cdk5, cdk2, and GSK-3. Pharmaceutical compositions and methods comprising compounds of formula (1) for treating and preventing diseases and conditions comprising abnormal cell growth, such as cancer, and neurodegenerative diseases and conditions and those affected by dopamine neurotransmission. Also described are pharmaceutical compositions and methods comprising compounds of formula (1) for treating male fertility and sperm motility; diabetes mellitus; impaired glucose tolerance; metabolic syndrome or syndrome X; polycystic ovary syndrome; adipogenesis and obesity; myogenesis and frailty, for example age-related decline in physical performance; acute sarcopenia, for example muscle atrophy and/or cachexia associated with burns, bed rest, limb immobilization, or major thoracic, abdominal, and/or orthopedic surgery; sepsis; hair loss, hair thinning, and balding; and immunodeficiency.Formula 1 compound and pharmacologically acceptable salt thereof r wherein 1be straight or branched (c 1-c 8) alkyl, straight or branched (c 2-c 8) alkenyl, straight or branched (c 2-c 8) alkynyl, (c 3-c 8) cycloalkyl, (c 4-c 8) cycloalkenyl group, (3-8 unit) heterocyclylalkyl, (c 5-c 11) bicyclic alkyl, (c 7-c 11) the assorted bicyclic alkyl of bicycloenyl, (5-11 unit), (c 6-c 14) aryl or (5-14 unit) heteroaryl; r wherein 1can choose wantonly by 1-6 and be independently selected from following substituent r 5replace: f, cl, br, i, nitro, cyano group ,-cf 3,-nr 7r 8,-nr 7c (=o) r 8,-nr 7c (=o) or 8,-nr 7c (=o) nr 8r 9,-nr 7s (=o) 2r 8,-nr 7s (=o) 2nr 8r 9,-or 7,-oc (=o) r 7,-oc (=o) or 7,-c (=o) or 7,-c (=o) r 7,-c (=o) nr 7r 8,-oc (=o) nr 7r 8,-oc (=o) sr 7,-sr 7,-s (=o) r 7,-s (=o) 2r 7,-s (=o) 2nr 7r 8,-o-s (=o) 2r 7,-n 3and r 7r 2be h, f, ch 3, cn or c (=o) or 7r 3be-c (=o) nr 9-,-c (=o) o-,-c (=o) (cr 10r 11) n-or-(cr 10r 11) n-; r 4be straight or branched (c 1-c 8) alkyl, straight or branched (c 2-c 8) alkenyl, straight or branched (c 2-c 8alkynyl), (c 3-c 8) cycloalkyl, (c 4-c 8) cycloalkenyl group, (3-8 unit) heterocyclylalkyl, (c 5-c 11) bicyclic alkyl, (c 7-c 11) the assorted bicyclic alkyl of bicycloenyl, (5-11 unit), (c 6-c 14) aryl or (5-14 unit) heteroaryl; r wherein 4can choose wantonly by 1-3 and be independently selected from following substituent r 6replace: f, cl, br, i, nitro, cyano group ,-cf 3,-nr 7r 8,-nr 7c (=o) r 8,-nr 7c (=o) or 8,-nr 7c (=o) nr 8r 9,-nr 7s (=o) 2r 8,-nr 7s (=o) 2nr 8r 9,-or 7,-oc (=o) r 7,-oc (=o) or 7,-c (=o) or 7,-c (=o) r 7,-c (=o) nr 7r 8,-oc (=o) nr 7r 8,-oc (=o) sr 7,-sr 7,-s (=o) r 7,-s (=o) 2r 7,-s (=o) 2nr 7r 8, or r 7r 7, r 8, and r 9be independently selected from h, straight or branched (c respectively 1-c 8) alkyl, straight or branched (c 2-c 8) alkenyl, straight or branched (c 2-c 8alkynyl), (c 3-c 8) cycloalkyl, (c 4-c 8) cycloalkenyl group, (3-8 unit) heterocyclylalkyl, (c 5-c 11) bicyclic alkyl, (c 7-c 11) the assorted bicyclic alkyl of bicycloenyl, (5-11 unit), (c 6-c 14) aryl and (5-14 unit) heteroaryl, wherein r 7, r 8, and r 9choose wantonly independently respectively by 1-6 and be independently selected from following substituting group replacement: f, cl, br, i, no 2,-cn ,-cf 3,-nr 10r 11,-nr 10c (=o) r 11,-nr 10c (=o) or 11,-nr 10c (=o) nr 11r 12,-nr 10s (=o) 2r 11,-nr 10s (=o) 2nr 11r 12,-or 10, oc (=o) r 10,-oc (=o) or 10,-oc (=o) nr 10r 11,-oc (=o) sr 10,-sr 10,-s (=o) r 10,-s (=o) 2r 10,-s (=o) 2nr 10r 11,-c (=o) r 10,-c (=o) or 10,-c (=o) nr 10r 11, and r 10or work as r 7and r 8at nr 7r 8in the time, they can choose wantonly connection with its nr that is connected 7r 8nitrogen form 3-7 unit heterocyclylalkyl, described heterocyclylalkyl can be chosen wantonly and comprise 1 or 2 other heteroatoms that is independently selected from n, o and s; r 10, r 11, and r 12be independently selected from h, straight or branched (c respectively 1-c 8) alkyl, straight or branched (c 2-c 8) alkenyl, straight or branched (c 2-c 8alkynyl), (c 3-c 8) cycloalkyl, (c 4-c 8) cycloalkenyl group, (3-8 unit) heterocyclylalkyl, (c 5-c 11) bicyclic alkyl, (c 7-c 11) the assorted bicyclic alkyl of bicycloenyl, (5-11 unit), (c 6-c 14) aryl and (5-14 unit) heteroaryl, wherein r 10, r 11, and r 12choose wantonly independently respectively by 1-6 and be independently selected from following substituting group replacement: f, cl, br, i, no 2,-cn ,-cf 3,-nr 13r 14,-nr 13c (=o) r 14,-nr 13c (=o) or 14,-nr 13c (=o) nr 14r 15,-nr 13s (=o) 2r 14,-nr 13s (=o) 2nr 14r 15,-or 13, oc (=o) r 13,-oc (=o) or 13,-oc (=o) nr 13r 14,-oc (=o) sr 13,-sr 13,-s (=o) r 13,-s (=o) 2r 13,-s (=o) 2nr 13r 14,-c (=o) r 13,-c (=o) or 13,-c (=o) nr 13r 14, and r 13r 13, r 14, and r 15be independently selected from h, straight or branched (c respectively 1-c 8) alkyl, straight or branched (c 2-c 8) alkenyl, straight or branched (c 2-c 8alkynyl), (c 3-c 8) cycloalkyl, (c 4-c 8) cycloalkenyl group, (3-8 unit) heterocyclylalkyl, (c 5-c 11) bicyclic alkyl, (c 7-c 11) the assorted bicyclic alkyl of bicycloenyl, (5-11 unit), (c 6-c 14) aryl and (5-14 unit) heteroaryl, wherein r 13, r 14, and r 15choose wantonly independently respectively by 1-6 and be independently selected from following substituting group replacement: f, cl, br, i, no 2,-cn ,-cf 3,-nr 16r 17,-nr 16c (=o) r 17,-nr 16c (=o) or 17,-nr 16c (=o) nr 17r 8,-nr 16s (=o) 2r 17,-nr 16s (=o) 2nr 17r 18,-or 16, oc (=o) r 16,-oc (=o) or 16,-oc (=o) nr 16r 17,-oc (=o) sr 16,-sr 16,-s (=o) r 16,-s (=o) 2r 16,-s (=o) 2nr 16r 17,-c (=o) r 16,-c (=o) or 16,-c (=o) nr 16r 17, and r 16r 16, r 17, and r 18be independently selected from h, straight or branched (c respectively 1-c 8) alkyl, straight or branched (c 2-c 8) alkenyl, straight or branched (c 2-c 8alkynyl), (c 3-c 8) cycloalkyl, (c 4-c 8) cycloalkenyl group, (3-8 unit) heterocyclylalkyl, (c 5-c 11) bicyclic alkyl, (c 7-c 11) the assorted bicyclic alkyl of bicycloenyl, (5-11 unit), (c 6-c 1...
이미다졸 유도체 본 발명은 하기 화학식 1의 화합물 및 그의 제약상 허용되는 염을 제공한다. 화학식 1의 화합물은 cdk5, cdk2 및 GSK-3을 억제하는 활성을 갖는 것으로 나타났다. 화학식 1의 화합물을 포함하는, 암과 같은 비정상적 세포 성장 및 신경퇴행성 질병 및 질환, 및 도파민 신경전달에 의해 영향받는 질병 및 질환을 포함하는 질병 및 질환의 치료 및 예방용 제약 조성물, 및 치료 및 예방 방법이 제공된다. 또한, 화학식 1의 화합물을 포함하는, 남성 생식능 및 정자 운동; 당뇨병; 손상된 글루코스 내성; 대사 증후군 또는 증후군 X; 다낭성 난소 증후군; 지방발생 및 비만; 근육발생 및 약함, 예를 들어 나이 관련 신체 성능 저하; 급성 근감소증, 예를 들어 화상, 침상 요양, 사지 고정, 또는 흉부, 복부 및(또는) 정형 외과 대수술과 연관된 근위축증 및(또는) 악액질; 패혈증; 모발 손실, 모발 연화 및 대머리; 및 면역결핍증의 치료용 제약 조성물 및 치료 방법이 기재되어 있다. <화학식 1>  상기 식에서, R1, R2, R3 및 R4는 정의된 바와 같다.하기 화학식 1의 화합물 또는 그의 제약상 허용되는 염. <화학식 1> [이미지] 상기 식에서, R1은 직쇄 또는 분지쇄 (C1-C8)알킬, 직쇄 또는 분지쇄 (C2-C 8)알케닐, 직쇄 또는 분지쇄 (C2-C8)알키닐, (C3-C8)시클로알킬, (C4-C 8)시클로알케닐, (3 내지 8원)헤테로시클로알킬, (C5-C11)비시클로알킬, (C7-C11)비시클로알케닐, (5 내지 11원)헤테로비시클로알킬, (C6-C14)아릴 또는 (5 내지 14원)헤테로아릴이고, 여기서 R1 은 F, Cl, Br, I, 니트로, 시아노, -CF3, -NR7R8, -NR7C(=O)R8 , -NR7C(=O)OR8, -NR7C(=O)NR8R9, -NR7S(=O)2R8, -NR7 S(=O)2NR8R9, -OR7, -OC(=O)R7, -OC(=O)OR 7, -C(=O)OR7, -C(=O)R7, -C(=O)NR7R8, -OC(=O)NR7R 8, -OC(=O)SR7, -SR7, -S(=O)R7, -S(=O)2R7, -S(=O)2NR7R8, -O-S(=O)2R 7, -N3 및 R7에서 독립적으로 선택된 1 내지 6개의 치환기 R5로 임의로 치환되고; R2는 H, F, -CH3, -CN 또는 -C(=O)OR7이고; R3은 -C(=O)NR9-, -C(=O)O-, -C(=O)(CR10R11)n- 또는 -(CR10R11)n-이고; R4는 직쇄 또는 분지쇄 (C1-C8)알킬, 직쇄 또는 분지쇄 (C2-C 8)알케닐, 직쇄 또는 분지쇄 (C2-C8)알키닐, (C3-C8)시클로알킬, (C4-C 8)시클로알케닐, (3 내지 8원)헤테로시클로알킬, (C5-C11)비시클로알킬, (C7-C11)비시클로알케닐, (5 내지 11원)헤테로비시클로알킬, (C6-C14)아릴 또는 (5 내지 14원)헤테로아릴이고, 여기서 R4 는 F, Cl, Br, I, 니트로, 시아노, -CF3, -NR7R8, -NR7C(=O)R8 , -NR7C(=O)OR8, -NR7C(=O)NR8R9, -NR7S(=O)2R8, -NR7 S(=O)2NR8R9, -OR7, -OC(=O)R7, -OC(=O)OR 7, -C(=O)OR7, -C(=O)R7, -C(=O)NR7R8, -OC(=O)NR7R 8, -OC(=O)SR7, -SR7, -S(=O)R7, -S(=O)2R7, -S(=O)2NR7R8 또는 R7에서 독립적으로 선택된 1 내지 3개의 치환기 R6으로 임의로 치환되고; 각 R7, R8 및 R9는 독립적으로 H, 직쇄 또는 분지쇄 (C1-C8 )알킬, 직쇄 또는 분지쇄 (C2-C8)알케닐, 직쇄 또는 분지쇄 (C2-C8)알키닐, (C 3-C8)시클로알킬, (C4-C8)시클로알케닐, (3 내지 8원)헤테로시클로알킬, (C5-C11)비시클로알킬, (C7-C 11)비시클로알케닐, (5 내지 11원)헤테로비시클로알킬, (C6-C14)아릴 및 (5 내지 14원)헤테로아릴에서 선택되고, 여기서 R7, R8 및 R9는 각각 독립적으로 F, Cl, Br, I, NO2, -CN, -CF3, -NR10R11, -NR10C(=O)R11, -NR10 C(=O)OR11, -NR10C(=O)NR11R12, -NR10S(=O) 2R11, -NR10S(=O)2NR11R12, -OR10, -OC(=O)R10, -OC(=O)OR10, -OC(=O)NR10R11, -OC(=O)SR10, -SR10, -S(=O)R10, -S(=O)2R10, -S(=O)2NR10 R11, -C(=O)R10, -C(=O)OR10, -C(=O)NR10R11 및 R10에서 독립적으로 선택된 1 내지 6개의 치환기로 임의로 치환되거나; R7과 R8이 NR7R8로서 존재하는 경우, 이들은 대신에 이들이 결합한 NR7R8의 질소와 함께 임의로 N, O 및 S에서 독립적으로 선택된 1 또는 2개의 추가 헤테로원자를 함유하는 3 내지 7원 고리의 헤테로시클로알킬 잔기를 임의로 형성할 수 있으며; 각 R10, R11 및 R12는 독립적으로 H, 직쇄 또는 분지쇄 (C1-C 8)알킬, 직쇄 또는 분지쇄 (C2-C8)알케닐, 직쇄 또는 분지쇄 (C2-C8)알키닐, (C 3-C8)시클로알킬, (C4-C8)시클로알케닐, (3 내지 8원)헤테로시클로알킬, (C5-C11)비시클로알킬, (C7-C 11)비시클로알케닐, (5 내지 11원)헤테로비시클로알킬, (C6-C14)아릴 및 (5 내지 14원)헤테로아릴에서 선택되고, 여기서 R10, R11 및 R12는 각각 독립적으로 F, Cl, Br, I, -NO2, -CN, -CF3, -NR13R14, -NR13C(=O)R14, -NR13 C(=O)OR14, -NR13C(=O)NR14R15, -NR13S(=O) 2R14, -NR13S(=O)2NR14R15, -OR13, -OC(=O)R13, -OC(=O)OR13, -OC(=O)NR13R14, -OC(=O)SR13, -SR13, -S(=O)R13, -S(=O)2R13, -S(=O)2NR13 R14, -C(=O)R13, -C(=O)OR13, -C(=O)NR13R14 및 R13에서 독립적으로 선택된 1 내지 6개의 치환기로 임의로 치환되고; 각 R13, R14 및 R15는 독립적으로 H, 직쇄 또는 분지쇄 (C1-C 8)알킬, 직쇄 또는 분지쇄 (C2-C8)알케닐, 직쇄 또는 분지쇄 (C2-C8)알키닐, (C 3-C8)시클로알킬, (C4-C8)시클로알케닐, (3 내지 8원)헤테로시클로알킬, (C5-C11)비시클로알킬, (C7-C 11)비시클로알케닐, (5 내지 11원)헤테로비시클로알킬, (C6-C14)아릴 및 (5 내지 14원)헤테로아릴에서 선택되고, 여기서 R13, R14 및 R15는 각각 독립적으로 F, Cl, Br, I, -NO2, -CN, -CF3, -NR16R17, -NR16C(=O)R17, -NR16 C(=O)OR17, -NR16C(=O)NR17R18, -NR16S(=O) 2R17, -NR16S(=O)2NR17R18, -OR16, -OC(=O)R16, -OC(=O)OR16, -OC(=O)NR16R17, -OC(=O)SR16, -SR16, -S(=O)R16, -S(=O)2R16, -S(=O)2NR16 R17, -C(=O)R16, -C(=O)OR16, -C(=O)NR16R17 및 R16에서 독립적으로 선택된 1 내지 6개의 치환기로 임의로 치환되고; 각 R16, R17 및 R18은 독립적으로 H, 직쇄 또는 분지쇄 (C1-C 8)알킬, 직쇄 또는 분지쇄 (C2-C8)알케닐, 직쇄 또는 분지쇄 (C2-C8)알키닐, (C 3-C8)시클로알킬, (C4-C8)시클로알케닐, (3 내지 8원)헤테로시클로알킬, (C5-C11)비시클로알킬, (C7-C 11)비시클로알케닐, (5 내지 11원)헤테로비시클로알킬, (C6-C13)아릴 및 (5 내지 12원)헤테로아릴에서 선택되고; n은 0, 1, 2 또는 3이고; 여기서, -C(=O)(CR10R11)n- 및 -(CR10R11)n - 중의 R10 및 R11은 반복된 n 각각에 대하여 상기와 같이 독립적으로 정의된다.