公开(公告)号：US09708253B2

公开(公告)日：2017-07-18

申请号：US15109733

申请日：2015-01-05

Applicant: BRISTOL-MYERS SQUIBB COMPANY

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

IPC: 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 classification number: 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

Abstract: 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

Applicant: BRISTOL-MYERS SQUIBB COMPANY

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

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

CPC classification number: C07D417/06 ,  C07D215/58 ,  C07D401/06 ,  C07D401/12 ,  C07D413/06 ,  C07D413/14

Abstract: 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.

Abstract translation: 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

Applicant: Bristol-Myers Squibb Company

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

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

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US11078186B2

公开(公告)日：2021-08-03

申请号：US16348195

申请日：2017-11-08

Applicant: BRISTOL-MYERS SQUIBB COMPANY

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

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

Abstract: 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：US09771320B2

公开(公告)日：2017-09-26

申请号：US15109741

申请日：2015-01-05

Applicant: BRISTOL-MYERS SQUIBB COMPANY

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

IPC: C07C317/14 ,  C07D213/81 ,  C07D401/04 ,  C07D237/08 ,  C07C317/20 ,  C07C317/30 ,  C07C317/46 ,  C07D471/04 ,  C07D213/30 ,  C07D213/56 ,  C07D309/04 ,  C07D309/14 ,  C07D317/44 ,  C07D231/12 ,  C07D239/38 ,  C07D241/12 ,  C07D471/10 ,  C07D257/04 ,  C07D261/08 ,  C07D263/32 ,  C07D271/06 ,  C07D211/36 ,  C07D295/16 ,  C07D295/20 ,  C07D303/06 ,  C07D305/14 ,  C07D205/04 ,  C07D211/62 ,  C07D213/40 ,  C07D213/75 ,  C07D295/155 ,  C07D295/108 ,  C07D319/20 ,  C07D285/06 ,  C07D295/18 ,  C07D295/22 ,  C07D303/34 ,  C07C317/22 ,  C07C317/44 ,  C07C317/32 ,  C07C317/50 ,  C07D213/85 ,  C07D295/185

CPC classification number: C07C317/14 ,  C07C317/20 ,  C07C317/22 ,  C07C317/30 ,  C07C317/32 ,  C07C317/44 ,  C07C317/46 ,  C07C317/50 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/16 ,  C07C2602/08 ,  C07D205/04 ,  C07D211/36 ,  C07D211/62 ,  C07D213/30 ,  C07D213/40 ,  C07D213/56 ,  C07D213/75 ,  C07D213/81 ,  C07D213/85 ,  C07D231/12 ,  C07D237/08 ,  C07D239/38 ,  C07D241/12 ,  C07D257/04 ,  C07D261/08 ,  C07D263/32 ,  C07D271/06 ,  C07D285/06 ,  C07D295/108 ,  C07D295/155 ,  C07D295/18 ,  C07D295/185 ,  C07D295/20 ,  C07D295/22 ,  C07D303/06 ,  C07D303/34 ,  C07D305/14 ,  C07D309/04 ,  C07D309/14 ,  C07D317/44 ,  C07D319/20 ,  C07D401/04 ,  C07D471/04 ,  C07D471/10

Abstract: 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：US09522888B2

公开(公告)日：2016-12-20

申请号：US14831439

申请日：2015-08-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Alaric J. Dyckman ,  T. G. Murali Dhar ,  Hai-Yun Xiao ,  John L. Gilmore ,  Michael G. Yang ,  Zili Xiao ,  David Marcoux

IPC: C07F9/02 ,  C07C211/00 ,  C07D217/24 ,  C07C215/42 ,  C07C217/52 ,  C07C217/58 ,  C07C219/24 ,  C07C233/41 ,  C07C233/65 ,  C07C251/50 ,  C07C251/52 ,  C07C251/54 ,  C07C271/34 ,  C07C317/28 ,  C07C317/32 ,  C07C321/16 ,  C07C321/22 ,  C07C321/28 ,  C07D213/32 ,  C07D213/69 ,  C07D213/70 ,  C07D215/12 ,  C07D231/12 ,  C07D231/20 ,  C07D239/26 ,  C07D241/12 ,  C07D277/24 ,  C07D305/08 ,  C07D309/06 ,  C07D309/12 ,  C07D311/58 ,  C07D311/76 ,  C07D319/20 ,  C07D333/16 ,  C07F7/08 ,  C07F9/117 ,  C07F9/62 ,  C07F9/6503 ,  C07F9/6509 ,  C07F9/655 ,  C07F9/6553 ,  A61K31/135 ,  C07D215/14 ,  C07D241/04 ,  C07C323/29 ,  C07C251/38 ,  C07C251/42 ,  C07C251/44 ,  C07D209/46 ,  C07D213/38 ,  C07C275/26 ,  C07C217/74 ,  C07C323/25 ,  C07C235/46 ,  C07F9/54 ,  C07F9/572 ,  C07F9/09

CPC classification number: A61K31/695 ,  A61K31/135 ,  A61K31/137 ,  A61K31/15 ,  A61K31/165 ,  A61K31/166 ,  A61K31/17 ,  A61K31/222 ,  A61K31/24 ,  A61K31/27 ,  A61K31/337 ,  A61K31/351 ,  A61K31/352 ,  A61K31/381 ,  A61K31/415 ,  A61K31/4174 ,  A61K31/426 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/47 ,  A61K31/4965 ,  A61K31/505 ,  A61K31/661 ,  C07B2200/05 ,  C07C215/42 ,  C07C217/52 ,  C07C217/58 ,  C07C217/74 ,  C07C219/24 ,  C07C233/41 ,  C07C233/65 ,  C07C235/46 ,  C07C251/38 ,  C07C251/42 ,  C07C251/44 ,  C07C251/50 ,  C07C251/52 ,  C07C251/54 ,  C07C271/34 ,  C07C275/26 ,  C07C317/28 ,  C07C317/32 ,  C07C321/16 ,  C07C321/22 ,  C07C321/28 ,  C07C323/25 ,  C07C323/29 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2602/10 ,  C07C2603/74 ,  C07D209/46 ,  C07D213/32 ,  C07D213/38 ,  C07D213/69 ,  C07D213/70 ,  C07D215/12 ,  C07D215/14 ,  C07D217/24 ,  C07D231/12 ,  C07D231/20 ,  C07D239/26 ,  C07D241/04 ,  C07D241/12 ,  C07D277/24 ,  C07D305/08 ,  C07D309/06 ,  C07D309/12 ,  C07D311/58 ,  C07D311/76 ,  C07D319/20 ,  C07D333/16 ,  C07F7/081 ,  C07F9/091 ,  C07F9/117 ,  C07F9/5442 ,  C07F9/5728 ,  C07F9/62 ,  C07F9/65031 ,  C07F9/650952 ,  C07F9/65522 ,  C07F9/655345

Abstract: Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): and/or a salt thereof, wherein R1 is —OH or —OP(O)(OH)2, and X1, X2, X3, R2, R2a, Ra, Rb, and Rc are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Abstract translation: 和/或其盐，其中R1是-OH或-OP（O）（OH）2，X1，X2，X3，R2，R2a，Ra，Rb和Rc在本文中定义。 还公开了使用这种化合物作为G蛋白偶联受体S1P1的选择性激动剂的方法，以及包含这些化合物的药物组合物。 这些化合物可用于治疗，预防或减缓各种治疗领域（例如自身免疫疾病和血管疾病）中的疾病或病症的进展。

公开(公告)号：US09487481B2

公开(公告)日：2016-11-08

申请号：US15148222

申请日：2016-05-06

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： T. G. Murali Dhar ,  Hai-Yun Xiao

IPC: C07C25/22 ,  C07C49/67 ,  C07D207/50

CPC classification number: C07D207/50 ,  C07B2200/07 ,  C07B2200/13 ,  C07C25/22 ,  C07C49/67 ,  C07C215/42 ,  C07C2601/08 ,  C07C2602/10 ,  C07F9/117

Abstract: Disclosed are compounds of Formula (I) and/or a salt thereof; wherein R is —OH or —OP(O)(OH)2. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

公开(公告)号：US09221819B2

公开(公告)日：2015-12-29

申请号：US14503456

申请日：2014-10-01

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： T. G. Murali Dhar ,  John V. Duncia ,  Daniel S. Gardner ,  Weiwei Guo ,  John Hynes

IPC: C07D471/10 ,  A61K31/4427 ,  C07D401/12 ,  C07D405/12 ,  C07D413/12 ,  C07D471/04

CPC classification number: C07D471/10 ,  A61K31/4427 ,  C07D401/12 ,  C07D405/12 ,  C07D413/12 ,  C07D471/04

Abstract: The present application describes modulators of chemokine receptor activity of formula I or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using modulators of formula (I) are disclosed.

Abstract translation: 本申请描述了式I的趋化因子受体活性的调节剂或其立体异构体或其药学上可接受的盐。 此外，公开了使用式（I）的调节剂治疗和预防炎性疾病如哮喘和过敏性疾病以及类风湿性关节炎和移植排斥反应的自身免疫病态的方法。

公开(公告)号：US09115054B2

公开(公告)日：2015-08-25

申请号：US14185164

申请日：2014-02-20

Applicant: Bristol-Myers Squibb Company

Inventor： T. G. Murali Dhar ,  Hai-Yun Xiao ,  Alaric J. Dyckman ,  Eric J. Chan ,  Marta Dabros ,  Daniel Richard Roberts

IPC: C07C215/42 ,  C07F9/117

CPC classification number: C07D207/50 ,  C07B2200/07 ,  C07B2200/13 ,  C07C25/22 ,  C07C49/67 ,  C07C215/42 ,  C07C2601/08 ,  C07C2602/10 ,  C07F9/117

Abstract: Disclosed are compounds of Formula (I) and/or a salt thereof; wherein R is —OH or —OP(O)(OH)2. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Abstract translation: 公开了式（I）和/或其盐的化合物; 其中R是-OH或-OP（O）（OH）2。 还公开了使用这种化合物作为G蛋白偶联受体S1P1的选择性激动剂的方法，以及包含这些化合物的药物组合物。 这些化合物可用于治疗，预防或减缓各种治疗领域（例如自身免疫疾病和血管疾病）中的疾病或病症的进展。