公开(公告)号：US20230167131A1

公开(公告)日：2023-06-01

申请号：US17799028

申请日：2021-02-11

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Kumaravel Selvakumar ,  Venkatram Paidi ,  Srinivasan Thangathirupathy ,  Vijaya Kumar Cm ,  Tirupathi Rao Alajangi ,  Mallikarjun Reddy Sura ,  Krishna Mahadevu ,  Ramesh Kumar Sistla ,  Piyush Agarwal ,  Arul Mozhi Subbiah Karuppiah ,  Jalathi S. Nair ,  Ooha Morampudi ,  Manoranjan Panda ,  Joseph A. Tino ,  Robert J. Cherney ,  John V. Duncia ,  Daniel S. Gardner ,  T. G. Murali Dhar ,  Audrey Graham Ross ,  Paul E. Gormisky ,  Xiao Zhu ,  Boris M. Seletsky ,  Alyssa H. Antropow ,  Deqiang Niu ,  Zhengdong Zhu ,  Guobin Miao ,  Julio Herman Cuervo

IPC: C07D519/00 ,  C07D471/04 ,  C07D487/04 ,  C07D409/14 ,  C07D405/14 ,  C07D413/14

CPC classification number: C07D519/00 ,  C07D471/04 ,  C07D487/04 ,  C07D409/14 ,  C07D405/14 ,  C07D413/14

Abstract: The disclosure generally relates to substituted heterocyclic compounds of Formula (Ia), which are inhibitors of PAD4, method for preparing these compounds, pharmaceutical compositions comprising these compounds and use of these compounds in the treatment of a disease or a disorder associated with PAD4 enzyme activity.

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：US10166249B2

公开(公告)日：2019-01-01

申请号：US15648250

申请日：2017-07-12

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 ,  C07C215/42 ,  C07C217/52 ,  C07C217/58 ,  C07C219/24 ,  C07C233/41 ,  C07C251/52 ,  C07C251/54 ,  C07C271/34 ,  C07C317/28 ,  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 ,  C07F9/62 ,  C07F9/655 ,  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

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：US10035790B2

公开(公告)日：2018-07-31

申请号：US14436355

申请日：2013-10-17

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  EXELIXIS, INC.

Inventor： Wei Xu ,  Yong Wang ,  Sunghoon Ma ,  Elena S. Koltun ,  Byung Gyu Kim ,  Joon Won Jeong ,  T. G. Murali Dhar ,  Lynne Canne Bannen

IPC: C07D403/04 ,  C07D403/14 ,  C07D401/04 ,  C07D401/14 ,  C07D413/14 ,  C07D405/14 ,  C07D417/14

CPC classification number: C07D403/04 ,  C07D401/04 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14

Abstract: Described are RORy modulators of the formula (I), and N-oxides thereof, and pharmaceutically acceptable salts thereof, and solvates and hydrates thereof, wherein R1, R2, R3, R4, R5, R6, Ra, x, y, L, G, Z, the bond denoted by “q”, the ring system denoted by “A” and the ring system denoted by “B” are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORy 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 RORy activity, for example, autoimmune and/or inflammatory disorders.

公开(公告)号：US11701373B2

公开(公告)日：2023-07-18

申请号：US17307138

申请日：2021-05-04

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 ,  A61K31/135 ,  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 ,  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 ,  C07F9/117 ,  C07F9/62 ,  C07F9/6503 ,  C07F9/6509 ,  C07F9/655 ,  C07F9/6553 ,  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 ,  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 ,  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 ,  C07F7/08 ,  C07F7/081 ,  C07F9/091 ,  C07F9/117 ,  C07F9/5442 ,  C07F9/5728 ,  C07F9/62 ,  C07F9/65031 ,  C07F9/65522 ,  C07F9/650952 ,  C07F9/655345 ,  C07B2200/05 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2602/10 ,  C07C2603/74

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：US10711020B2

公开(公告)日：2020-07-14

申请号：US16295378

申请日：2019-03-07

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Jingwu Duan ,  T. G. Murali Dhar ,  David Marcoux ,  Robert J. Cherney

IPC: 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

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：US10709719B2

公开(公告)日：2020-07-14

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 ,  A61K31/135 ,  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 ,  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 ,  C07F9/117 ,  C07F9/62 ,  C07F9/6503 ,  C07F9/6509 ,  C07F9/655 ,  C07F9/6553 ,  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

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：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：US09637455B2

公开(公告)日：2017-05-02

申请号：US15109727

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

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

CPC classification number: C07D211/54 ,  C07D211/96 ,  C07D309/08 ,  C07D401/06 ,  C07D405/06

Abstract: 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：US09458171B2

公开(公告)日：2016-10-04

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: 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 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.