公开(公告)号：US20090088441A1

公开(公告)日：2009-04-02

申请号：US12238982

申请日：2008-09-26

申请人： Leifeng Cheng ,  Michael Karle

发明人： Leifeng Cheng ,  Michael Karle

IPC分类号： A61K31/496 ,  C07D215/14 ,  C07D401/10 ,  A61K31/47

CPC分类号： C07D215/18 ,  C07D215/38 ,  C07D215/54 ,  C07D401/06 ,  C07D401/12

摘要： The present invention relates to novel compounds of the general formula (I) wherein R1, R4, R5 and X are as defined, having a positive allosteric GABAB receptor (GBR) modulator effect, methods for the preparation of said compounds and to their use, optionally in combination with a GABAB agonist, for the inhibition of transient lower esophageal sphincter relaxations, for the treatment of gastroesophageal reflux disease, as well as for the treatment of functional gastrointestinal disorders and irritable bowel syndrome (IBS).

摘要翻译： 本发明涉及通式（I）的新化合物，其中R 1，R 4，R 5和X如上定义，具有正变构GABA B受体（GBR）调节剂作用，制备所述化合物的方法及其用途， 任选地与GABAB激动剂组合，用于抑制短暂的食管下括约肌松弛，用于治疗胃食管反流疾病，以及治疗功能性胃肠道疾病和肠易激综合征（IBS）。

公开(公告)号：US08415378B2

公开(公告)日：2013-04-09

申请号：US12755010

申请日：2010-04-06

申请人： Jonas Boström ,  Leifeng Cheng ,  Tomas Fex ,  Michael Karle ,  Daniel Pettersen ,  Peter Schell

发明人： Jonas Boström ,  Leifeng Cheng ,  Tomas Fex ,  Michael Karle ,  Daniel Pettersen ,  Peter Schell

IPC分类号： A01N43/40 ,  A01N43/80 ,  A61K31/445 ,  A61K31/42 ,  C07D401/00 ,  C07D405/00 ,  C07D409/00 ,  C07D411/00 ,  C07D413/00 ,  C07D417/00 ,  C07D419/00 ,  C07D421/00 ,  C07D261/00 ,  C07D307/02 ,  C07D315/00 ,  C07D407/00

CPC分类号： C07D413/04

摘要： or a pharmaceutically suitable salt thereof, wherein, R1 and R2 independently are hydrogen, deuterium, aryl, hetero aryl, C1-C8 alkyl, optionally being substituted with one or more substituents independently being R3, R3 is an aryl, hetero aryl, fluorine(s), a C1-C6 alkyl containing one or more fluorine, a C1-C6 alkyl containing one or more deuterium, a C1-C6 alkyl containing hydroxy, the aryl and heteroaryl optionally being substituted with one or more halogen, a fluorinated alkoxy, a fluorinated alkyl, a sulfonyl, one or more deuterium, a C1-6 alkyl, a C1-6 alkoxy, a nitrile, or R3 is a C1-6 alkyl optionally substituted with one or more of the following groups: COOR4, OCOR4, CONR5R6, NR5COR6, OR4; wherein, R4 is a C1-10 alkyl optionally substituted with one or more fluorine, deuterium, alkoxy, arylcarboxylate, alkyl carboxylate; R5 and R6 are independently selected from hydrogen, alkyl or they may together form a 4-8 membered carbon ring; or R1 and R2 form a 3-10 membered carbon ring optionally comprising O or N and optionally substituted with a C1-10 alkyl or aryl, hetero aryl optionally substituted with R3.

摘要翻译： 或其药学上合适的盐，其中R 1和R 2独立地是氢，氘，芳基，杂芳基，任选被一个或多个取代基独立地被R 3取代的C 1 -C 8烷基，R 3是芳基，杂芳基，氟（ 含有一个或多个氟的C 1 -C 6烷基，含有一个或多个氘的C 1 -C 6烷基，含羟基的C 1 -C 6烷基，任选被一个或多个卤素取代的芳基和杂芳基，氟化烷氧基， 氟化烷基，磺酰基，一个或多个氘，C 1-6烷基，C 1-6烷氧基，腈或R 3是任选被一个或多个下列基团取代的C 1-6烷基：COOR 4，OCOR 4， CONR5R6，NR5COR6，OR4; 其中，R4为任选被一个或多个氟，氘，烷氧基，芳基羧酸酯，羧酸烷基酯取代的C 1-10烷基; R 5和R 6独立地选自氢，烷基或它们可以一起形成4-8元碳环; 或R 1和R 2形成任选地包含O或N并任选被C 1-10烷基或芳基取代的3-10元碳环，任选被R 3取代的杂芳基。

公开(公告)号：US20100261755A1

公开(公告)日：2010-10-14

申请号：US12755010

申请日：2010-04-06

申请人： Jonas BOSTRÖM ,  Leifeng Cheng ,  Tomas Fex ,  Michael Karle ,  Daniel Pettersen ,  Peter Schell

发明人： Jonas BOSTRÖM ,  Leifeng Cheng ,  Tomas Fex ,  Michael Karle ,  Daniel Pettersen ,  Peter Schell

IPC分类号： A61K31/454 ,  C07D401/04 ,  A61P1/16 ,  A61P9/10 ,  A61P7/04

CPC分类号： C07D413/04

摘要： or a pharmaceutically suitable salt thereof, wherein, R1 and R2 independently are hydrogen, deuterium, aryl, hetero aryl, C1-C8 alkyl, optionally being substituted with one or more substituents independently being R3, R3 is an aryl, hetero aryl, fluorine(s), a C1-C6 alkyl containing one or more fluorine, a C1-C6 alkyl containing one or more deuterium, a C1-C6 alkyl containing hydroxy, the aryl and heteroaryl optionally being substituted with one or more halogen, a fluorinated alkoxy, a fluorinated alkyl, a sulfonyl, one or more deuterium, a C1-6 alkyl, a C1-6 alkoxy, a nitrile, or R3 is a C1-6 alkyl optionally substituted with one or more of the following groups: COOR4, OCOR4, CONR5R6, NR5COR6, OR4; wherein, R4 is a C1-10 alkyl optionally substituted with one or more fluorine, deuterium, alkoxy, arylcarboxylate, alkyl carboxylate; R5 and R6 are independently selected from hydrogen, alkyl or they may together form a 4-8 membered carbon ring; or R1 and R2 form a 3-10 membered carbon ring optionally comprising O or N and optionally substituted with a C1-10 alkyl or aryl, hetero aryl optionally substituted with R3.

摘要翻译： 或其药学上合适的盐，其中R 1和R 2独立地是氢，氘，芳基，杂芳基，任选被一个或多个取代基独立地被R 3取代的C 1 -C 8烷基，R 3是芳基，杂芳基，氟（ 含有一个或多个氟的C 1 -C 6烷基，含有一个或多个氘的C 1 -C 6烷基，含羟基的C 1 -C 6烷基，任选被一个或多个卤素取代的芳基和杂芳基，氟化烷氧基， 氟化烷基，磺酰基，一个或多个氘，C 1-6烷基，C 1-6烷氧基，腈或R 3是任选被一个或多个下列基团取代的C 1-6烷基：COOR 4，OCOR 4， CONR5R6，NR5COR6，OR4; 其中，R4为任选被一个或多个氟，氘，烷氧基，芳基羧酸酯，羧酸烷基酯取代的C 1-10烷基; R 5和R 6独立地选自氢，烷基或它们可以一起形成4-8元碳环; 或R 1和R 2形成任选地包含O或N并任选被C 1-10烷基或芳基取代的3-10元碳环，任选被R 3取代的杂芳基。