公开(公告)号：US20100292273A1

公开(公告)日：2010-11-18

申请号：US12745708

申请日：2008-12-08

申请人： Jean Marie Receveur ,  Emelie Bjurling ,  Anthony Murray ,  Thomas Hoegberg ,  Peter Aadal Nielsen ,  Jean-Michel Linget ,  Pia Karina Noerregaard ,  Dorthe Almholt

发明人： Jean Marie Receveur ,  Emelie Bjurling ,  Anthony Murray ,  Thomas Hoegberg ,  Peter Aadal Nielsen ,  Jean-Michel Linget ,  Pia Karina Noerregaard ,  Dorthe Almholt

IPC分类号： A61K31/454 ,  C07D413/06 ,  A61K31/4245 ,  C07D413/14 ,  C07D409/06 ,  C07D231/24 ,  A61K31/415 ,  A61P3/00 ,  A61P3/04 ,  A61P3/10 ,  A61P9/00 ,  A61P1/16 ,  A61P15/10 ,  A61P25/00

CPC分类号： C07D413/06 ,  C07D231/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04

摘要： Compounds of formula (I) are modulators of cannabinoid receptor CB1, useful inter alia for treatment of obesity: Formula (I). Wherein: X is a bond, or a divalent radical selected from —C(R10)(R11)—*, —C(R10)(R11)—O—*, —C(R10)(R11)CH2—*, —C(R10)(R11)CH2—O—*, —CH2C(R10)(R11)—*, —CH2C(R10)(R11)—O—*. and —CH2—O—C(R10)(R11)—*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; Z is a carboxyl isostere radical selected from the group specified; R3 is hydrogen, (C1-C)alkyl or (C1C3)fluoroalkyl; R4 is a radical of formula -(Alk1)p-(Q1)r (L)s-Q2 wherein p, r, s, Alk1, L, Q1 and Q2 are as specified; or R3and R4 taken together with the nitrogen to which they are attached form a cyclic amino ring of 4 to 7 ring atoms which is optionally substituted by a radical of formula -(L)s-Q2 wherein s, L and Q2 are as defined above, or by an optional substituent selected from hydroxy, methoxy, —NH2—, or mono- or di-(C1C3)alkylamino; R5, R6, R7 and R8 are each independently selected from hydrogen —F, —Cl, —Br, —CN, (C1-C3)alkyl, (C1C3)fluoroalkyl, cyclopropyl, and —OR9; R10 is hydrogen, (C1C3)alkyl, hydroxyl or NH2, and R11 is hydrogen or (C1-C3)alkyl; or R10 and R11 taken together with the carbon atom to which they are attached form a (C3-C5)cycloalkyl ring.

摘要翻译： 式（I）化合物是大麻素受体CB1的调节剂，尤其用于治疗肥胖症：式（I）。 其中X为键或选自-C（R 10）（R 11） - *，-C（R 10）（R 11）-O- *，-C（R 10）（R 11）CH 2 - C（R10）（R11）CH2-O- *，-CH2C（R10）（R11） - *，-CH2C（R10）（R11）-O- *。 和-CH 2 -O-C（R 10）（R 11） - *，其中由星号表示的键连接到吡唑环上; Z是选自指定组的羧基等价基团; R3是氢，（C1-C）烷基或（C1C3）氟烷基; R4是式 - （Alk1）p-（Q1）r（L）s-Q2的基团，其中p，r，s，Alk1，L，Q1和Q2如所规定; 或R 3和R 4与它们所连接的氮一起形成4至7个环原子的环状氨基，其任选被式 - （L）s-Q 2的基团取代，其中s，L和Q2如上所定义 或选自羟基，甲氧基，-NH 2 - 或单 - 或二 - （C 1 -C 3）烷基氨基的任选取代基; R5，R6，R7和R8各自独立地选自-F，-Cl，-Br，-CN，（C1-C3）烷基，（C1C3）氟烷基，环丙基和-OR9; R 10是氢，（C 1 -C 3）烷基，羟基或NH 2，R 11是氢或（C 1 -C 3）烷基; 或R 10和R 11与它们所连接的碳原子一起形成（C 3 -C 5）环烷基环。

公开(公告)号：US08173680B2

公开(公告)日：2012-05-08

申请号：US12745708

申请日：2008-12-08

申请人： Jean-Marie Receveur ,  Emelie Bjurling ,  Anthony Murray ,  Thomas Hoegberg ,  Peter Aadal Nielsen ,  Jean-Michel Linget ,  Pia Karina Noerregaard ,  Dorthe Almholt

发明人： Jean-Marie Receveur ,  Emelie Bjurling ,  Anthony Murray ,  Thomas Hoegberg ,  Peter Aadal Nielsen ,  Jean-Michel Linget ,  Pia Karina Noerregaard ,  Dorthe Almholt

IPC分类号： A61K31/445 ,  A61K31/41 ,  A61K31/415 ,  C07D401/02 ,  C07D271/06 ,  C07D231/00

CPC分类号： C07D413/06 ,  C07D231/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04

摘要： Compounds of formula (I) are modulators of cannabinoid receptor CB1, useful inter alia for treatment of obesity: Formula (I). Wherein: X is a bond, or a divalent radical selected from —C(R10)(R11)—*, —C(R10)(R11)—O—*, —C(R10)(R11)CH2—*, —C(R10)(R11)CH2—O—*, —CH2C(R10)(R11)—*, —CH2C(R10)(R11)—O—*, and —CH2—O—C(R10)(R11)—*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; Z is a carboxyl isostere radical selected from the group specified; R3 is hydrogen, (C1-C)alkyl or (C1C3)fluoroalkyl; R4 is a radical of formula -(Alk1)p-(Q1)r (L)s-Q2 wherein p, r, s, Alk1, L, Q1 and Q2 are as specified; or R3and R4 taken together with the nitrogen to which they are attached form a cyclic amino ring of 4 to 7 ring atoms which is optionally substituted by a radical of formula -(L)s-Q2 wherein s, L and Q2 are as defined above, or by an optional substituent selected from hydroxy, methoxy, —NH2—, or mono- or di-(C1C3)alkylamino; R5, R6, R7 and R8 are each independently selected from hydrogen —F, —Cl, —Br, —CN, (C1-C3)alkyl, (C1C3)fluoroalkyl, cyclopropyl, and —OR9; R10 is hydrogen, (C1C3)alkyl, hydroxyl or NH2, and R11 is hydrogen or (C1-C3)alkyl; or R10 and R11 taken together with the carbon atom to which they are attached form a (C3-C5)cycloalkyl ring.

摘要翻译： 式（I）化合物是大麻素受体CB1的调节剂，尤其用于治疗肥胖症：式（I）。 其中X为键或选自-C（R 10）（R 11） - *，-C（R 10）（R 11）-O- *，-C（R 10）（R 11）CH 2 - C（R10）（R11）CH2-O- *，-CH2C（R10）（R11） - *，-CH2C（R10）（R11）-O- *和-CH2-O-C（R10）（R11） - *，其中由星号表示的键连接到吡唑环上; Z是选自指定组的羧基等价基团; R3是氢，（C1-C）烷基或（C1C3）氟烷基; R4是式 - （Alk1）p-（Q1）r（L）s-Q2的基团，其中p，r，s，Alk1，L，Q1和Q2如所规定; 或R 3和R 4与它们所连接的氮一起形成4至7个环原子的环状氨基，其任选被式 - （L）s-Q 2的基团取代，其中s，L和Q2如上所定义 或选自羟基，甲氧基，-NH 2 - 或单 - 或二 - （C 1 -C 3）烷基氨基的任选取代基; R5，R6，R7和R8各自独立地选自-F，-Cl，-Br，-CN，（C1-C3）烷基，（C1C3）氟烷基，环丙基和-OR9; R 10是氢，（C 1 -C 3）烷基，羟基或NH 2，R 11是氢或（C 1 -C 3）烷基; 或R 10和R 11与它们所连接的碳原子一起形成（C 3 -C 5）环烷基环。