公开(公告)号：US10189840B2

公开(公告)日：2019-01-29

申请号：US15558692

申请日：2016-03-17

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： Hai-Yun Xiao ,  Murali T. G. Dhar ,  Jingwu Duan ,  Bin Jiang ,  Andrew J. Tebben

IPC分类号： C07D471/14 ,  C07D487/06 ,  A61P37/00 ,  A61P29/00

摘要： Disclosed are compounds of Formula (I) or a salt thereof, wherein: X is N; W is: (i) —(CR3R3)1-4—; (ii) —(CR3R3)x—Y—(CR3R3)y—; Or (iii) —Y—(CR3R3)2—Y—; and Y, R1, R2, R3, R5, R6, R8, x, and y are defined herein. Also disclosed are methods of using such compounds as modulators of TNFα, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

公开(公告)号：US20180221344A1

公开(公告)日：2018-08-09

申请号：US15749611

申请日：2016-08-02

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： Hai-Yun Xiao ,  T.G. Murali Dhar ,  Bin Jiang ,  Jingwu Duan

IPC分类号： A61K31/4184 ,  A61K31/4188 ,  A61P37/02

CPC分类号： A61K31/4184 ,  A61K31/4188 ,  A61P37/02 ,  C07D487/04 ,  C07D487/14

摘要： Disclosed are compounds of Formula (I) or a salt thereof, wherein: Ring A is 3- to 6-membered carbocyclic or heterocyclic ring; X is CR1 or N; Y is —(CR5R5)m—; Z is —(CR5R5)n—; and q, R1, R2, R3, R4, R6, R7, R8, R9, and R10 are defined herein. Also disclosed are methods of using such compounds as modulators of TNFα, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

公开(公告)号：US20200024257A1

公开(公告)日：2020-01-23

申请号：US16348195

申请日：2017-11-08

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： Jingwu DUAN ,  Bin Jiang ,  T.G. Murali Dhar ,  Zhonghui LU ,  Arun Kumar Gupta ,  Ananta Karmakar

IPC分类号： C07D401/14 ,  C07D207/16 ,  C07D207/06 ,  C07D207/12 ,  C07D401/06 ,  C07D403/04 ,  C07D413/06 ,  C07D405/12

摘要： There are described RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

公开(公告)号：US09637455B2

公开(公告)日：2017-05-02

申请号：US15109727

申请日：2015-01-05

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： Jingwu Duan ,  T. G. Murali Dhar ,  Bin Jiang ,  Ananta Karmakar ,  Arun Kumar Gupta ,  Zhonghui Lu

IPC分类号： C07D211/54 ,  C07D309/08 ,  C07D401/06 ,  C07D405/06 ,  C07D211/96 ,  A61K31/352 ,  A61K31/4418

CPC分类号： C07D211/54 ,  C07D211/96 ,  C07D309/08 ,  C07D401/06 ,  C07D405/06

摘要： Described are RORγ modulators of the formula (I), [INSERT CHEMICAL STRUCTURE HERE] or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

公开(公告)号：US20160318870A1

公开(公告)日：2016-11-03

申请号：US14917420

申请日：2014-09-08

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： T.G Murali Dhar ,  Jingwu Duan ,  Hua Gong ,  Bin Jiang ,  Zhonghui Lu ,  David S. Weinstein

IPC分类号： C07D215/58 ,  C07D401/06 ,  C07D401/12 ,  C07D471/10 ,  C07D279/16 ,  C07D405/14 ,  C07D405/12 ,  C07D491/044 ,  C07D409/12 ,  C07D417/12 ,  C07D413/12 ,  C07D487/10

CPC分类号： C07D215/58 ,  C07D279/16 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/06 ,  C07D417/12 ,  C07D471/10 ,  C07D487/10 ,  C07D491/04 ,  C07D491/044 ,  C07D491/10

摘要： Described are RORγ modulators of the formula (I), or pharmaceutically acceptable salts thereof, wherein all substituents are defined herein. The invention includes stereoisomeric forms of the compounds of formula I, including stereoisomerically-pure, scalemic and racemic form, as well as tautomers thereof. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

摘要翻译： 描述了式（I）的RORγ调节剂或其药学上可接受的盐，其中所有取代基在本文中定义。 本发明包括式I化合物的立体异构体形式，包括立体异构纯，鳞片和外消旋形式及其互变异构体。 还提供了包含其的药物组合物。 这样的化合物和组合物可用于调节细胞中RORγ活性的方法和用于治疗受试者治疗受益于RORγ活性（例如自身免疫和/或炎症性疾病）的疾病或病症的受试者的方法。

公开(公告)号：US09458171B2

公开(公告)日：2016-10-04

申请号：US14590233

申请日：2015-01-06

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： Jingwu Duan ,  T. G. Murali Dhar ,  Bin Jiang ,  Zhonghui Lu ,  Hai-Yun Xiao

IPC分类号： C07D417/14 ,  C07D471/10 ,  C07D493/04 ,  C07D207/12 ,  C07D207/16 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D405/06 ,  C07D417/06 ,  C07D487/04 ,  C07D403/12 ,  C07D401/14 ,  C07D413/14 ,  C07D405/12 ,  C07D407/12 ,  C07D407/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D487/10

CPC分类号： C07D207/12 ,  C07D207/16 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D407/12 ,  C07D407/14 ,  C07D409/12 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/10 ,  C07D493/04 ,  C07D493/08

摘要： Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

公开(公告)号：US09708253B2

公开(公告)日：2017-07-18

申请号：US15109733

申请日：2015-01-05

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： Jingwu Duan ,  T. G. Murali Dhar ,  Bin Jiang ,  Ananta Karmakar ,  Arun Kumar Gupta ,  Zhonghui Lu ,  Carolyn A. Weigelt

IPC分类号： C07C317/20 ,  C07C317/24 ,  C07C317/30 ,  C07D205/04 ,  C07D207/27 ,  C07D211/46 ,  C07D211/78 ,  C07D213/30 ,  C07D231/12 ,  C07D213/81 ,  C07D213/82 ,  C07D309/08 ,  C07D231/14 ,  C07D231/56 ,  C07D401/04 ,  C07D403/04 ,  C07D237/08 ,  C07D237/20 ,  C07D237/24 ,  C07D405/04 ,  C07D239/28 ,  C07C317/46 ,  C07D241/24 ,  C07D249/04 ,  C07D471/04 ,  C07D207/277 ,  C07D277/60 ,  C07D295/096 ,  C07D211/48 ,  C07D211/62 ,  C07D295/185 ,  C07D213/56 ,  C07D213/71 ,  C07D213/75 ,  C07D309/04 ,  C07D335/02 ,  C07D401/06 ,  C07D401/12 ,  C07D295/205 ,  C07D213/40 ,  C07D231/54 ,  C07D237/22 ,  C07D249/06 ,  C07D277/82 ,  C07D295/16 ,  C07D295/195

CPC分类号： C07C317/20 ,  C07C317/24 ,  C07C317/30 ,  C07C317/46 ,  C07C2601/02 ,  C07C2601/14 ,  C07D205/04 ,  C07D207/27 ,  C07D207/277 ,  C07D211/46 ,  C07D211/48 ,  C07D211/62 ,  C07D211/78 ,  C07D213/30 ,  C07D213/40 ,  C07D213/56 ,  C07D213/71 ,  C07D213/75 ,  C07D213/81 ,  C07D213/82 ,  C07D231/12 ,  C07D231/14 ,  C07D231/54 ,  C07D231/56 ,  C07D237/08 ,  C07D237/20 ,  C07D237/22 ,  C07D237/24 ,  C07D239/28 ,  C07D241/24 ,  C07D249/04 ,  C07D249/06 ,  C07D277/60 ,  C07D277/82 ,  C07D295/096 ,  C07D295/16 ,  C07D295/185 ,  C07D295/195 ,  C07D295/205 ,  C07D309/04 ,  C07D309/08 ,  C07D335/02 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D405/04 ,  C07D471/04

摘要： Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

公开(公告)号：US20160229844A1

公开(公告)日：2016-08-11

申请号：US15022673

申请日：2014-09-18

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： T. G. Murali Dhar ,  Jingwu Duan ,  Hua Gong ,  Bin Jiang ,  Zhonghui Lu ,  David S. Weinstein

IPC分类号： C07D417/06 ,  C07D401/06 ,  C07D401/12 ,  C07D413/14 ,  C07D215/58 ,  C07D413/06

CPC分类号： C07D417/06 ,  C07D215/58 ,  C07D401/06 ,  C07D401/12 ,  C07D413/06 ,  C07D413/14

摘要： Described are RORγ modulators of the formula (I), or pharmaceutically acceptable salts thereof, wherein all substituents are defined herein. The invention includes stereoisomeric forms of the compounds of formula I, including stereoisomerically-pure, scalemic and racemic form, as well as tautomers thereof. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

摘要翻译： 描述了式（I）的RORγ调节剂或其药学上可接受的盐，其中所有取代基在本文中定义。 本发明包括式I化合物的立体异构体形式，包括立体异构纯，鳞片和外消旋形式及其互变异构体。 还提供了包含其的药物组合物。 这样的化合物和组合物可用于调节细胞中RORγ活性的方法和用于治疗受试者治疗受益于RORγ活性（例如自身免疫和/或炎症性疾病）的疾病或病症的受试者的方法。

公开(公告)号：US20150191483A1

公开(公告)日：2015-07-09

申请号：US14590233

申请日：2015-01-06

申请人： Bristol-Myers Squibb Company

发明人： Jingwu Duan ,  T. G. Murali Dhar ,  Bin Jiang ,  Zhonghui Lu ,  Hai-Yun Xiao

IPC分类号： C07D493/04 ,  C07D207/16 ,  C07D401/06 ,  C07D487/04 ,  C07D403/04 ,  C07D405/06 ,  C07D403/06 ,  C07D417/06 ,  C07D207/12 ,  C07D401/12

CPC分类号： C07D207/12 ,  C07D207/16 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D405/12 ,  C07D407/12 ,  C07D407/14 ,  C07D409/12 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/10 ,  C07D493/04 ,  C07D493/08

摘要： Described are RORγ modulators of the formula (I), or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

摘要翻译： 描述了式（I）的RORγ调节剂或其立体异构体，互变异构体，药学上可接受的盐，溶剂化物或前药，其中所有取代基均在本文中定义。 还提供了包含其的药物组合物。 这样的化合物和组合物可用于调节细胞中RORγ活性的方法和用于治疗受试者治疗受益于RORγ活性（例如自身免疫和/或炎症性疾病）的疾病或病症的受试者的方法。

公开(公告)号：US09725443B2

公开(公告)日：2017-08-08

申请号：US15022673

申请日：2014-09-18

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： T. G. Murali Dhar ,  Jingwu Duan ,  Hua Gong ,  Bin Jiang ,  Zhonghui Lu ,  David S. Weinstein

IPC分类号： A61K31/47 ,  C07D417/06 ,  C07D401/06 ,  C07D401/12 ,  C07D413/14 ,  C07D215/58 ,  C07D413/06

CPC分类号： C07D417/06 ,  C07D215/58 ,  C07D401/06 ,  C07D401/12 ,  C07D413/06 ,  C07D413/14

摘要： Described are RORγ modulators of the formula (I), or pharmaceutically acceptable salts thereof, wherein all substituents are defined herein. The invention includes stereoisomeric forms of the compounds of formula I, including stereoisomerically-pure, scalemic and racemic form, as well as tautomers thereof. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.