公开(公告)号：US09770459B2

公开(公告)日：2017-09-26

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: C07D217/00 ,  A61K31/695 ,  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 ,  C07D217/24 ,  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 ,  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

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.

公开(公告)号：US09359286B2

公开(公告)日：2016-06-07

申请号：US14798498

申请日：2015-07-14

Applicant: Bristol-Myers Squibb Company

Inventor： Hai-Yun Xiao

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（例如自身免疫性疾病和血管疾病）中的疾病或病症的进展。

公开(公告)号：US20210147361A1

公开(公告)日：2021-05-20

申请号：US16636662

申请日：2018-08-08

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Alaric J. Dyckman ,  Ling Li ,  T.G. Murali Dhar ,  Hai-Yun Xiao

IPC: C07D213/53 ,  C07D207/12 ,  C07D211/40 ,  C07D211/96 ,  A61P37/06

Abstract: Disclosed are compounds of Formula (I): (I) or a salt thereof, wherein: X is CH or N; Y is CH or N; R1 is —OH or —OP(O)(OH)2; L1 is —CR3═N—O—CRaRa— or CRaR—O—N═CR3; L2 is a bond, —C(O)—, or S(O)2—; and R2, R3, Ra, m, and n 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.

公开(公告)号：US10934286B2

公开(公告)日：2021-03-02

申请号：US16341474

申请日：2017-10-12

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Qingjie Liu ,  T. G. Murali Dhar ,  Lan-ying Qin ,  Lyndon A. M. Cornelius ,  Hai-Yun Xiao ,  Jianqing Li ,  Robert J. Cherney

IPC: C07D471/04 ,  C07D491/147

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 Gamma 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 Gamma activity, for example, autoimmune and/or inflammatory disorders.

公开(公告)号：US20190300523A1

公开(公告)日：2019-10-03

申请号：US16341474

申请日：2017-10-12

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Qingjie LIU ,  T.G. Murali Dhar ,  Lan-ying Qin ,  Lyndon A.M. Cornelius ,  Hai-Yun Xiao ,  Jianqing Li ,  Robert J. Cherney

IPC: C07D471/04 ,  C07D491/147

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 Gamma 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 Gamma activity, for example, autoimmune and/or inflammatory disorders.

公开(公告)号：US20150315128A1

公开(公告)日：2015-11-05

申请号：US14798498

申请日：2015-07-14

Applicant: Bristol-Myers Squibb Company

Inventor： Hai-Yun Xiao

IPC: C07C215/42

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。

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：US10435369B2

公开(公告)日：2019-10-08

申请号：US15806554

申请日：2017-11-08

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： David Marcoux ,  Myra Beaudoin Bertrand ,  T. G. Murali Dhar ,  Michael G. Yang ,  Zili Xiao ,  Hai-Yun Xiao ,  Yeheng Zhu ,  Carolyn A. Weigelt ,  Douglas G. Batt

IPC: C07C317/12 ,  C07C317/44 ,  A61K31/10 ,  C07D211/48 ,  A61P37/00 ,  C07D205/04 ,  C07D205/08 ,  C07D207/10 ,  C07D207/16 ,  C07D207/277 ,  C07D211/96 ,  C07D213/40 ,  C07D213/75 ,  C07D231/08 ,  C07D241/08 ,  C07D257/04 ,  C07D295/195 ,  C07D307/22 ,  C07D309/10 ,  C07D333/48 ,  C07D335/02 ,  C07D471/04 ,  C07D471/10 ,  C07D213/81 ,  C07D215/36 ,  C07D231/06 ,  C07D231/18 ,  C07D233/64 ,  C07D233/76 ,  C07D233/78 ,  C07D233/90 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07C317/20 ,  C07C317/24 ,  C07C317/30 ,  C07D405/12 ,  C07D249/12 ,  C07D261/18 ,  C07D263/20 ,  C07D207/09 ,  C07D207/28 ,  C07D285/06 ,  C07D211/62 ,  C07D295/16 ,  C07D211/78 ,  C07D213/56 ,  C07D305/08 ,  C07F9/09

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：US20190076450A1

公开(公告)日：2019-03-14

申请号：US16188444

申请日：2018-11-13

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 ,  C07F7/08 ,  A61K31/505 ,  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 ,  A61K31/661 ,  C07F9/09 ,  C07F9/572 ,  C07F9/54 ,  C07C235/46 ,  C07C323/25 ,  C07C217/74 ,  C07C275/26 ,  C07D213/38 ,  C07D209/46 ,  C07C251/44 ,  C07C251/42 ,  C07C251/38 ,  C07C323/29 ,  C07D241/04 ,  C07D215/14 ,  A61K31/135 ,  C07D213/69 ,  C07D213/32 ,  C07C251/54 ,  C07C219/24 ,  C07C217/52 ,  C07D333/16 ,  C07D319/20 ,  C07D311/76 ,  C07D311/58 ,  C07D309/12 ,  C07D309/06 ,  C07D277/24 ,  C07D239/26 ,  C07D231/12 ,  C07D217/24 ,  C07C317/28 ,  C07C271/34 ,  C07C251/52 ,  C07C233/41 ,  C07C217/58 ,  C07C215/42 ,  C07F9/655 ,  C07F9/62 ,  C07D305/08 ,  C07D241/12 ,  C07D231/20 ,  C07D215/12 ,  C07D213/70

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.

公开(公告)号：US10189840B2

公开(公告)日：2019-01-29

申请号：US15558692

申请日：2016-03-17

Applicant: BRISTOL-MYERS SQUIBB COMPANY

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

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

Abstract: 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.