公开(公告)号：US10214537B2

公开(公告)日：2019-02-26

申请号：US15521202

申请日：2015-10-21

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Rajeev S. Bhide ,  Douglas G. Batt ,  Robert J. Cherney ,  Lyndon A. M. Cornelius ,  Qingjie Liu ,  David Marcoux ,  James Neels ,  Michael A. Poss ,  Zheming Ruan ,  Qing Shi ,  Anurag S. Srivastava ,  Lan-ying Qin ,  Joseph A. Tino ,  Scott Hunter Watterson

IPC: C07D487/04 ,  C07D491/08 ,  A61K31/53 ,  A61K31/541 ,  A61P29/00

Abstract: Disclosed are compounds of Formula (I) or a salt thereof; wherein: X is N or CH; Q1 is: (i) Cl, Br, I, —CN, —CH3, or —CF3; (ii) a 5-membered heteroaryl selected from pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, and thiadiazolyl; (iii) a 6?membered heteroaryl selected from pyridinyl, pyridazinyl, and pyrimidinyl; or (iv) a bicyclic heteroaryl selected from indolyl, pyrrolopyridinyl, pyrazolopyridinyl and benzo[d]oxazolyl; wherein each of said 5-membered, 6-membered, and bicyclic heteroaryl is substituted with zero to 1 Ra and zero to 1 Rb; and R1, R2, R3, R4, R5, R6, Ra, and Rb are defined herein. Also disclosed are methods of using such compounds as modulators of PI3K, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases.

公开(公告)号：US20180002358A1

公开(公告)日：2018-01-04

申请号：US15701818

申请日：2017-09-12

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Jingwu Duan ,  T.G. Murali Dhar ,  David Marcoux ,  Qing Shi ,  Douglas G. Batt ,  Qingjie Liu ,  Robert J. Cherney ,  Lyndon A.M. Cornelius ,  Anurag S. Srivastava ,  Myra Beaudoin Bertrand ,  Carolyn A. Weigelt

IPC: C07F9/6574 ,  C07D209/30 ,  C07D493/08 ,  C07D491/107 ,  C07D491/052 ,  C07D471/04 ,  C07D417/14 ,  C07D417/12 ,  C07D417/06 ,  C07D417/04 ,  C07D413/12 ,  C07D413/10 ,  C07D413/06 ,  C07D409/06 ,  C07D409/04 ,  C07D405/06 ,  C07D403/12 ,  C07D403/06 ,  C07D401/12 ,  C07D401/06 ,  C07D221/10 ,  C07D215/36 ,  C07D209/70 ,  C07D209/60 ,  C07D495/04 ,  C07D495/08

CPC classification number: C07F9/65742 ,  C07D209/30 ,  C07D209/60 ,  C07D209/70 ,  C07D215/36 ,  C07D221/10 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07D413/06 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/052 ,  C07D491/107 ,  C07D493/08 ,  C07D495/04 ,  C07D495/08

Abstract: There are described RORγ modulators of the formula (I), and formula (II) 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：US20170355707A1

公开(公告)日：2017-12-14

申请号：US15521202

申请日：2015-10-21

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Rajeev S. Bhide ,  Douglas G. Batt ,  Robert J Cherney ,  Lyndon A.M. Cornelius ,  Qingjie Liu ,  David Marcoux ,  James Neels ,  Michael A. Poss ,  Zheming Ruan ,  Qing Shi ,  Anurag S. Srivastava ,  Lan-ying Qin ,  Joseph A. Tino ,  Scott Hunter Watterson

IPC: C07D491/08 ,  C07D487/04

CPC classification number: C07D491/08 ,  C07D487/04

Abstract: Disclosed are compounds of Formula (I) or a salt thereof; wherein: X is N or CH; Q1 is: (i) Cl, Br, I, —CN, —CH3, or —CF3; (ii) a 5-membered heteroaryl selected from pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, and thiadiazolyl; (iii) a 6?membered heteroaryl selected from pyridinyl, pyridazinyl, and pyrimidinyl; or (iv) a bicyclic heteroaryl selected from indolyl, pyrrolopyridinyl, pyrazolopyridinyl and benzo[d]oxazolyl; wherein each of said 5-membered, 6-membered, and bicyclic heteroaryl is substituted with zero to 1 Ra and zero to 1 Rb; and R1, R2, R3, R4, R5, R6, Ra, and Rb are defined herein. Also disclosed are methods of using such compounds as modulators of PI3K, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases.

公开(公告)号：US09815859B2

公开(公告)日：2017-11-14

申请号：US15148209

申请日：2016-05-06

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Jingwu Duan ,  T. G. Murali Dhar ,  David Marcoux ,  Qing Shi ,  Douglas G. Batt ,  Qingjie Liu ,  Robert J. Cherney ,  Lyndon A. M. Cornelius ,  Anurag S. Srivastava ,  Myra Beaudoin Bertrand ,  Carolyn A. Weigelt

IPC: A61K31/437 ,  C07F9/6574 ,  C07D215/36 ,  C07D409/04 ,  C07D417/04 ,  C07D209/30 ,  C07D209/60 ,  C07D209/70 ,  C07D221/10 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D409/06 ,  C07D413/06 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/052 ,  C07D491/107 ,  C07D493/08 ,  C07D495/04 ,  C07D495/08

CPC classification number: C07F9/65742 ,  C07D209/30 ,  C07D209/60 ,  C07D209/70 ,  C07D215/36 ,  C07D221/10 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07D413/06 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/052 ,  C07D491/107 ,  C07D493/08 ,  C07D495/04 ,  C07D495/08

Abstract: There are described RORγ modulators of the formula (I), and formula (II) 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：US20170042917A1

公开(公告)日：2017-02-16

申请号：US15337843

申请日：2016-10-28

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: A61K31/695 ,  A61K31/351 ,  A61K31/415 ,  A61K31/381 ,  A61K31/44 ,  A61K31/137 ,  A61K31/166 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4402 ,  A61K31/4965 ,  A61K31/165 ,  A61K31/4174 ,  A61K31/426 ,  A61K31/337 ,  A61K31/47 ,  A61K31/505 ,  A61K31/27 ,  A61K31/17 ,  A61K31/352 ,  A61K31/15 ,  A61K31/661 ,  A61K31/222 ,  A61K31/24 ,  A61K31/135

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：US20160326195A1

公开(公告)日：2016-11-10

申请号：US15148209

申请日：2016-05-06

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Jingwu Duan ,  T.G. Murali Dhar ,  David Marcoux ,  Qing Shi ,  Douglas G. Batt ,  Qingjie Liu ,  Robert J. Cherney ,  Lyndon A.M. Cornelius ,  Anurag S. Srivastava ,  Myra Beaudoin Bertrand ,  Carolyn A. Weigelt

IPC: C07F9/6574 ,  C07D221/10 ,  C07D401/06 ,  C07D209/70 ,  C07D409/06 ,  C07D491/052 ,  C07D401/12 ,  C07D403/06 ,  C07D417/06 ,  C07D493/08 ,  C07D405/06 ,  C07D413/10 ,  C07D413/06 ,  C07D471/04 ,  C07D417/14 ,  C07D495/04 ,  C07D495/08 ,  C07D417/12 ,  C07D413/12 ,  C07D403/12 ,  C07D491/107 ,  C07D209/60

CPC classification number: C07F9/65742 ,  C07D209/30 ,  C07D209/60 ,  C07D209/70 ,  C07D215/36 ,  C07D221/10 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07D413/06 ,  C07D413/10 ,  C07D413/12 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/052 ,  C07D491/107 ,  C07D493/08 ,  C07D495/04 ,  C07D495/08

Abstract: There are described RORγ modulators of the formula (I), and formula (II) 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: 或其立体异构体，互变异构体，其药学上可接受的盐，溶剂合物或前药，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。