首页>
外国专利>
New 2,5-disubstituted benzimidazole derivatives, are gonadotropin releasing hormone antagonists useful e.g. for treating endometriosis, breast or prostate cancer or precocious puberty
New 2,5-disubstituted benzimidazole derivatives, are gonadotropin releasing hormone antagonists useful e.g. for treating endometriosis, breast or prostate cancer or precocious puberty
2-(Alkylamino or alkylthio)-5-(aminocarbonyl or aminomethyl)-benzimidazole derivatives (I) are new. 2-(Alkylamino or alkylthio)-5-(aminocarbonyl or aminomethyl)-benzimidazole derivatives of formula (I), in racemic or enantiomer form or any combination of these forms, and their salts are new. A = CH2 or CO; Y = S or NH; R1, R2 = H, 1-8C alkyl, 5-9C bicycloalkyl (optionally substituted (os) by one or more T) or -(CH2)a-X; or NR1R2 = heterocycloalkyl, heterobicycloalkyl or a spiro or fused piperidine group of formula (i), (ii), (iii) or (iv) (all os by one or more of -(CH2)c-X''-Y'', oxo, hydroxy, halo, nitro or cyano); T = 1-6C alkyl; X = NH2, NHT, NT2, adamantyl, arylcarbonyl, 1,4-benzodioxanyl, 1,3-benzodioxolyl, indanyl or tetralinyl or 3-7C cycloalkyl, heterocycloalkyl, aryl or heteroaryl (os by one or more of -(CH2)b-X'-Y', halo, oxo, NO2, CN, NH2, NHT, NT2, OH or N3); X' = O, S, C(O), C(O)O, NHC(O), NHSO2 or direct bond; Y' = T (os by one or more halo) or heteroaryl, aryl or heterocycloalkyl (all os by one or more of T, OT, halo, NO2, CN, NH2, CF3, OCF3, OH, N3, NHT or NT2); X'' = O, C(O), C(O)O or direct bond; Y'' = T, NH2, NHT, NT2, 3-7C cycloalkyl, heterocycloalkyl or aralkyl; aryl or heteroaryl (both os by one or more of T, OT, COT, halo, OH, NO2, CN, CF3, OCF3, NH2, NHT or NT2); or 1,4-benzodioxanyl, 1,3-benzodioxolyl or benzimidazol-2-on-1-yl; a = 0-6; b = 0-2; c = 0-4; R3 = -(CH2)c-W3-(CH)2d-Z3; W3 = direct bond, CH(OH) or C(O); Z3 = T, adamantyl, aryl, heteroaryl, 1,4-benzodioxanyl, 1,3-benzodioxolyl or anthraquinonyl (where all aryl groups are os by one or more of -(CH2)e-V3-Y3, halo, NO2, CN, N3 or OH; V3 = O, S, C(O), C(O)O, SO2 or direct bond; Y3 = T, os by one or more halo, NH2, NHT, NT2, CH2COPh, heterocycloalkyl or aryl; c, d, e = 0-4; R4 = -(CH2)f-R''4; R''4 = heterocycloalkyl containing at least one N (os by T or aralkyl); heteroaryl containing at least one N (os by T); or -NW4W'4; W4 = H, T or cycloalkyl; W'4 = -(CH2)g-Q4-Z4; Q4 = -CH2CH(OH)-(CH2)h-(O)i-(CH2)j or -C(O)O; Z4 = H, 1-8C alkyl (os by one or more of OT, ST, SST and OH), 2-6C alkenyl, 2-6C alkynyl, 3-7C cycloalkyl (os by one or more alkyl, COOT or -T-OH), cyclohexenyl, adamantyl, heteroaryl, aryl (os by one or more of -(CH2)k-V4-Y4, OH, NO2, halo or CN), 1,4-benzodioxanyl or 1,3-benzodioxolyl; V4 = O, S, NHC(O) or direct bond; Y4 = T (os by NT2 or one or more halo), NH2, NHT, NT2, aralkyl or heterocycloalkyl; f, g = 0-4; h, i, j = 0 or 1; and k = 0-4.
展开▼
机译：2-（烷基氨基或烷硫基）-5-（氨基羰基或氨基甲基）-苯并咪唑衍生物（I）是新的。外消旋或对映体形式或这些形式的任何组合的式（I）的2-（烷基氨基或烷硫基）-5-（氨基羰基或氨基甲基）-苯并咪唑衍生物，以及它们的盐是新的。 A = CH2或CO; Y = S或NH; R1，R2 ＝ H，1-8C烷基，5-9C双环烷基（任选地被一个或多个T取代的（os））或-（CH2）a-X;或NR1R2 =式（i），（ii），（iii）或（iv）的杂环烷基，杂二环烷基或螺或稠合的哌啶基团（全部os带有-（CH2）c-X''-Y'中的一个或多个'，氧代，羟基，卤素，硝基或氰基）; T = 1-6C烷基; X = NH 2，NHT，NT 2，金刚烷基，芳基羰基，1,4-苯并二恶烷基，1,3-苯并二恶唑基，茚满基或四氢萘基或3-7C环烷基，杂环烷基，芳基或杂芳基（os-（CH2）b中的一个或多个-X'-Y'，卤素，氧代，NO2，CN，NH2，NHT，NT2，OH或N3）; X′＝ O，S，C（O），C（O）O，NHC（O），NHSO 2或直接键; Y'= T（一个或多个卤素的os）或杂芳基，芳基或杂环烷基（所有os均为T，OT，卤素，NO2，CN，NH2，CF3，OCF3，OH，N3，NHT或NT2中的一个或多个） ; X''= O，C（O），C（O）O或直接键; Y''= T，NH2，NHT，NT2、3-7C环烷基，杂环烷基或芳烷基;芳基或杂芳基（两者均为T，OT，COT，卤素，OH，NO2，CN，CF3，OCF3，NH2，NHT或NT2中的一个或多个）; 1，4-苯并二恶烷基，1，3-苯并二恶唑基或苯并咪唑-2-基-1-基; a = 0-6; b = 0-2; c = 0-4; R3 ＝-（CH2）c-W3-（CH）2d-Z3; W3 ＝直接键，CH（OH）或C（O）; Z3 = T，金刚烷基，芳基，杂芳基，1,4-苯并二恶烷基，1,3-苯并二恶唑基或蒽醌基（其中所有芳基均为-（CH2）e-V3-Y3，卤素，NO2，CN中的一个或多个为os的基团） ; N 3或OH; V 3 ＝ O，S，C（O），C（O）O，SO 2或直接键; Y 3 ＝ T，具有一个或多个卤素的NH 3，NHT，NT 2，CH 2 COPh，杂环烷基或芳基; c，d，e ＝ 0-4; R 4 ＝-（CH 2）f -R″ 4; R″ 4 ＝含有至少一个N的杂环烷基（通过T或芳烷基的os）;含有至少一个N的杂芳基（os）通过T）;或-NW4W'4; W4 = H，T或环烷基; W'4 =-（CH2）g-Q4-Z4; Q4 = -CH2CH（OH）-（CH2）h-（O）i- （CH2）j或-C（O）O; Z4 = H，1-8C烷基（由OT，ST，SST和OH中的一个或多个组成的os），2-6C烯基，2-6C炔基，3-7C环烷基（由一个或多个烷基，COOT或-T-OH形成的os），环己烯基，金刚烷基，杂芳基，芳基（由-（CH2）k-V4-Y4，OH，NO2，卤素或CN中的一个或多个组成的os），1 ，4-苯并二恶烷基或1,3-苯并二恶唑基; V4 = O，S，NHC（O）或直接键; Y4 = T（由NT2或一个或多个卤素取代），NH2，NHT，NT2，芳烷基或杂环烷基; f ， G = 0-4; h，i，j = 0或1;并且k = 0-4。
展开▼
