Benzamide derivatives and uses related theretoBenzamide derivatives of formulae I and II, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof, and pharmaceutical compositions comprising the same, are described and have therapeutic utility, particularly in the treatment of diabetes, obesity, and related conditions and disorders: wherein R, R, R, R, R, R, R, R, R, R, R, and Rare defined as provided herein.Compound with formula (i):or its pharmaceutically acceptable salt, solvate, steric isomer or prodrug, wherein:r 1be to be selected from by-oh, halogen and (c 1-c 6) member of the group that forms of haloalkyl; r 2and r 3be the member who is independently selected from the group that forms by following each base: halogen, (c 1-c 8) alkyl, (c 2-c 8) thiazolinyl, (c 2-c 8) alkynyl, (c 1-c 8) alkoxyl group, (c 1-c 6) haloalkyl, (c 2-c 8) hydroxyalkyl and (c 3-c 8) cycloalkyl, wherein r 1, r 2and r 3in to be no more than two be halogen; r 4be to be selected from by hydrogen, halogen, (c 1-c 8) alkyl and (c 3-c 8) member of the group that forms of cycloalkyl; r 5be selected from the group that forms by following each base: halogen ,-cn ,-no 2, (c 1-c 8) alkyl, (c 2-c 8) thiazolinyl, (c 2-c 8) alkynyl, (c 1-c 6) haloalkyl, (c 2-c 8) hydroxyalkyl, (c 3-c 8) cycloalkyl, (c 3-c 8) heterocyclylalkyl, (c 3-c 8) cycloalkyl (c 1-c 6) alkyl, (c 3-c 8) cycloalkyl (c 1-c 6) alkoxyl group, (c 3-c 8) heterocyclylalkyl (c 1-c 6) alkyl, heteroaryl (c 1-c 6) alkyl, aryl, aryl (c 1-c 6) alkyl ,-c (o) r ' ,-c (o) or ' ,-nr ' c (o) or ' ,-or ' ,-oc (o) r ' ,-c (o) n (r ') 2,-s (o) r ' ,-so 2r ' ,-so 2n (r ') 2,-n (r ') 2,-nr ' c (o) r ' ,-nr ' so 2r ' ,-x-c (o) r ' ,-x-c (o) or ' ,-x-nr ' c (o) or ' ,-x-or ' ,-x-oc (o) r ' ,-x-c (o) n (r ') 2,-x-s (o) r ' ,-x-so 2r ' ,-x-so 2n (r ') 2,-x-n (r ') 2with-x-nr ' c (o) r '; r 6be selected from the group that forms by following each base: halogen ,-cn ,-no 2, methyl, ethyl, straight or branched butyl, straight or branched amyl group, straight or branched hexyl, straight or branched heptyl, straight or branched octyl group, (c 2-c 8) thiazolinyl, (c 2-c 8) alkynyl, (c 1-c 6) haloalkyl, (c 2-c 8) hydroxyalkyl, (c 3-c 8) cycloalkyl, (c 3-c 8) heterocyclylalkyl, (c 3-c 8) cycloalkyl (c 1-c 6) alkyl, (c 3-c 8) cycloalkyl (c 1-c 6) alkoxyl group, (c 3-c 8) heterocyclylalkyl (c 1-c 6) alkyl, aryl, heteroaryl (c 1-c 6) alkyl, aryl (c 1-c 6) alkyl ,-c (o) r ' ,-c (o) or ' ,-nr ' c (o) or ' ,-or ' ,-oc (o) r ' ,-c (o) n (r ') 2,-s (o) r ' ,-so 2r ' ,-so 2n (r ') 2,-n (r ') 2,-nr ' c (o) r ' ,-nr ' so 2r ' ,-x-c (o) r ' ,-x-c (o) or ' ,-x-nr ' c (o) or ' ,-x-or ' ,-x-oc (o) r ' ,-x-c (o) n (r ') 2,-x-s (o) r ' ,-x-so 2r ' ,-x-so 2n (r ') 2,-x-n (r ') 2with-x-nr ' c (o) r '; any cycloalkyl moiety, heterocyclylalkyl part, aryl moiety or heteroaryl moieties replace through 1-4 the member who is selected from the group that is made up of following each base according to circumstances: halogen ,-cn ,-no 2, (c 1-c 8) alkyl, (c 2-c 8) thiazolinyl, (c 2-c 8) alkynyl, (c 1-c 8) alkoxyl group, (c 1-c 6) haloalkyl, (c 2-c 8) hydroxyalkyl ,-c (o) r ' ,-c (o) or ' ,-nr ' c (o) or ' ,-or ' ,-sr ' ,-oc (o) r ' ,-c (o) n (r ') 2,-s (o) r ' ,-so 2r ' ,-so 2n (r ') 2,-n (r ') 2,-nr ' c (o) r ' and-nr ' so 2r '; x is side chain or straight chain (c 1-c 8) alkylidene group; be h or the member who is unsubstituted who is selected from the group that forms by following each base independently when r ' occurs at every turn:(c 1-c 8) alkyl, (c 2-c 8) thiazolinyl, (c 2-c 8) alkynyl, (c 1-c 4) alkoxyl group (c 1-c 4) alkyl, (c 1-c 6) haloalkyl, (c 2-c 8) hydroxyalkyl, (c 3-c 8) cycloalkyl, (c 3-c 8) heterocyclylalkyl, heteroaryl, aryl, (c 3-c 8) cycloalkyl (c 1-c 6) alkyl, (c 3-c 8) heterocyclylalkyl (c 1-c 6) alkyl, heteroaryl (c 1-c 6) alkyl, aryl (c 1-c 6) alkyl, or when two r ' groups were connected with same nitrogen-atoms, it can be combined to form heterocyclic radical or heteroaryl with the nitrogen-atoms that it connected; and r ' is the member who is unsubstituted who is selected from the group that is made up of following each base when occurring: (c at every turn independently 1-c 8) alkyl, (c 2-c 8) thiazolinyl, (c 2-c 8) alkynyl, (c 1-c 4) alkoxyl group (c 1-c 4) alkyl, (c 1-c 6) haloalkyl, (c 2-c 8) hydroxyalkyl, (c 3-c 8) cycloalkyl, (c 3-c 8) heterocyclylalkyl, heteroaryl, aryl, (c 3-c 8) cycloalkyl (c 1-c 6) alkyl, heterocyclic radical (c 1-c 6) alkyl, heteroaryl (c 1-c 6) alkyl or aryl (c 1-c 6) alkyl; its restricted condition is to work as r 1be-during oh, r so 2and r 3two not all is cf 3
벤자미드 유도체 및 그것에 관련된 사용화학식 I과 II의 벤자미드 유도체, 그리고 약리학적으로 허용가능한 그것의 염, 용매화합물, 입체이성질체, 및 프로드러그, 그리고 그것을 포함하는 약제학적 조성물이 기술되며, 특히 당뇨병, 비만 및 관련 상태 및 장애의 치료에서 치료 효용성을 갖는다: 상기식에서 R1, R2, R3, R4, R5, R6, R7, R9, R10, R11, 및 R12 은 본원에서 제공된 바와 같이 정의된다. 하기 화학식 I을 갖는 화합물 또는 약리학적으로 허용가능한 그것의 염, 용매화합물, 입체이성질체, 또는 프로드러그. (화학식 I) [이미지] 상기 식에서: R1은 -OH, 할로겐 및 (C1-C6)할로알킬로 구성되는 군으로부터 선택된 구성원이고; R2 및 R3 은 할로겐, (C1-C8)알킬, (C2-C8)알케닐, (C2-C8)알키닐, (C1-C8)알콕시, (C1-C6)할로알킬, (C2- C8)하이드록시알킬 및 (C3-C8)시클로알킬로 구성되는 군으로부터 독립적으로 선택된 구성원이며, 이때 R1, R2 및 R3 의 2개 이하는 할로겐이고; R4 는 수소, 할로겐, (C1-C8)알킬 및 (C3-C8)시클로알킬로 구성되는 군으로부터 선택된 구성원이고; R5 는 할로겐, -CN, -NO2, (C1-C8)알킬, (C2-C8)알케닐, (C2-C8)알키닐, (C1-C6)할로알킬, (C2-C8)하이드록시알킬, (C3-C8)시클로알킬, (C3-C8)헤테로시클로알킬, (C3-C8)시클로알킬(C1-C6)알킬, (C3-C8)시클로알킬(C1-C6)알콕시, (C3-C8)헤테로시클로알킬(C1-C6)알킬, 헤테로아릴(C1-C6)알킬, 아릴, 아릴(C1-C6)알킬, -C(O)R', -C(O)OR', -NR'C(O)OR", -OR", -OC(O)R', -C(O)N(R')2, -S(O)R", -SO2R", -SO2N(R')2, -N(R')2, -NR'C(O)R', -NR'SO2R", -X-C(O)R', -X-C(O)OR', -X-NR 'C(O)OR", -X-OR", -X-OC(O)R', -X-C(O)N(R')2, -X-S(O)R", -X-SO2R", -X-SO2N(R')2, -X-N(R')2 및 -X-NR'C(O)R'으로 구성되는 군으로부터 선택되고; R6은 할로겐, -CN, -NO2, 메틸, 에틸, 직선 또는 분지 부틸, 직선 또는 분지 펜틸, 직선 또는 분지 헥실, 직선 또는 분지 헵틸, 직선 또는 분지 옥틸, (C2-C8)알케닐, (C2-C8)알키닐, (C1-C6)할로알킬, (C2-C8)하이드록시알킬, (C3-C8)시클로알킬, (C3-C8)헤테로시클로알킬, (C3-C8)시클로알킬(C1-C6)알킬, (C3-C8)시클로알킬(C1-C6)알콕시, (C3-C8)헤테로시클로알킬(C1-C6)알킬, 아릴, 헤테로아릴(C1-C6)알킬, 아릴(C1-C6)알킬, -C(O)R', -C(O)OR', -NR'C(O)OR", -OR", -OC(O)R', -C(O)N(R')2, -S(O)R", -SO2R", -SO2N(R')2, -N(R')2, -NR'C(O)R', -NR'SO2R", -X-C(O)R', -X-C(O)OR', -X-NR'C(O)OR", -X-OR", -X-OC(O)R', -X-C(0)N(R')2, -X-S(O)R", -X-SO2R", -X-SO2N(R')2, -X-N(R')2 및 -X-NR'C(O)R'로 구성되는 군으로부터 선택되고; 어떠한 시클로알킬 부분, 헤테로시클로알킬 부분, 아릴 또는 헤테로아릴 부분은 할로겐, -CN, -NO2, (C1-C8)알킬, (C2-C8)알케닐, (C2-C8)알키닐, (C1-C8)알콕시, (C1-C6)할로알킬, (C2-C8)하이드록시알킬, -C(O)R', -C(O)OR' , -NR'C(O)OR", -OR', -SR', -OC(O)R', -C(0)N(R')2, -S(O)R", -SO2R", -SO2N(R')2, -N(R')2, -NR'C(O)R' 및 -NR'SO2R"으로 구성되는 군으로부터 선택된 1 내지 4 구성원으로 선택적으로 치환되고 ; X 는 분지 또는 직쇄 (C1-C8)알킬렌 기이고; R'의 각각의 존재는 독립적으로 H 또는 (C1-C8)알킬, (C2-C8)알케닐, (C2-C8)알키닐, (C1-C4)알콕시(C1-C4)알킬, (C1-C6)할로알킬, (C2-C8)하이드록시알킬, (C3-C8)시클로알킬, (C3-C8)헤테로시클로알킬, 헤테로아릴, 아릴, (C3-C8)시클로알킬(C1-C6)알킬, (C3-C8)헤테로시클로알킬(C1-C6)알킬, 헤테로아릴(C1-C6)알킬, 아릴(C1-C6)알킬로 구성되는 군으로부터 선택된 미치환 구성원이거나, 또는 두개의 R'기가, 동일한 질소 원자에 부착될 때, 그들이 부착되는 질소 원자와 결합되어 헤테로고리 또는 헤테로아릴 기를 형성할 수 있고 ; R"의 각각의 존재는 독립적으로 (C1-C8)알킬, (C2-C8)알케닐, (C2-C8)알키닐, (C1-C4)알콕시(C1-C4)알킬, (C1-C6)할로알킬, (C2-C8)하이드록시알킬, (C3-C8)시클로알킬, (C3-C8)헤테로시클로알킬, 헤테로아릴, 아릴, (C3-C8)시클로알킬(C1-C6)알킬, 헤테로시클릴(C1-C6)알킬, 헤테로아릴(C1-C6)알킬 또는 아릴(C1-C6)알킬로 구성되는 군으로부터 선택된 미치환 구성원이고; 단, R1이 -OH일 때, 그러면 R2과 R3는 둘다 CF3은 아니라는 조건을 만족시킨다. 