公开(公告)号：US20140343276A1

公开(公告)日：2014-11-20

申请号：US14448058

申请日：2014-07-31

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Mimi L. Quan ,  Carl P. Decicco ,  James R. Corte ,  Cailan Wang

IPC: C07D498/08 ,  C07D487/08

CPC classification number: C07D487/04 ,  C07D471/14 ,  C07D471/18 ,  C07D487/06 ,  C07D487/08 ,  C07D487/14 ,  C07D487/16 ,  C07D487/18 ,  C07D498/04 ,  C07D498/06 ,  C07D498/08

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Abstract translation: 本发明提供式（I）的化合物或其立体异构体，互变异构体或其药学上可接受的盐，其中所有变量如本文所定义。 这些化合物是选择性因子XIa抑制剂或fXIa和血浆激肽释放酶的双重抑制剂。 本发明还涉及包含这些化合物的药物组合物和使用其制备血栓栓塞和/或炎症性疾病的方法。

公开(公告)号：US20140113892A1

公开(公告)日：2014-04-24

申请号：US13891548

申请日：2013-05-10

Applicant: Bristol-Myers Squibb Company

Inventor： Donald J.P. Pinto ,  Mimi L. Quan ,  Michael J. Orwat ,  Yun-Long Li ,  Wei Han ,  Jennifer X. Qiao ,  Patrick Y.S. Lam ,  Stephanie L. Koch

IPC: C07D471/04 ,  A61K31/55 ,  A61K31/496 ,  A61K45/06 ,  A61K31/4545 ,  C07D401/12 ,  C07D401/14 ,  A61K31/444 ,  A61K31/437 ,  A61K31/513

CPC classification number: C07D471/04 ,  A61J1/00 ,  A61J1/03 ,  A61J1/05 ,  A61K31/4365 ,  A61K31/437 ,  A61K31/444 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/513 ,  A61K31/55 ,  A61K45/06 ,  B65D81/3216 ,  C07D213/75 ,  C07D213/81 ,  C07D213/82 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D409/12 ,  C07D413/14 ,  C07D417/14

Abstract: The present application describes lactam-containing compounds and derivatives thereof of Formula I: P4-P-M-M4  I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Abstract translation: 本申请描述了含有式I的化合物及其衍生物：P4-PM-M4 I或其药学上可接受的盐形式，其中环P（如果存在）为5-7元碳环或杂环，且环M为5- 7元碳环或杂环。 本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa。

公开(公告)号：US20230331693A1

公开(公告)日：2023-10-19

申请号：US18300315

申请日：2023-04-13

Applicant: Bristol-Myers Squibb Company

Inventor： Joshua Hansen ,  Mimi L. Quan

IPC: C07D401/04 ,  A61K45/06 ,  C07D401/14 ,  C07D405/14 ,  A61P35/00

CPC classification number: C07D401/04 ,  A61K45/06 ,  C07D401/14 ,  C07D405/14 ,  A61P35/00

Abstract: Provided herein are compounds having the formula I




for treating, preventing or managing cancer. Also provided are pharmaceutical compositions comprising the compounds and methods of use of the compounds and compositions. In certain embodiments, the methods encompass treating, preventing or managing cancer, including solid tumors and blood borne tumors using the compounds provided herein.

公开(公告)号：US11136327B2

公开(公告)日：2021-10-05

申请号：US16691099

申请日：2019-11-21

Applicant: Bristol-Myers Squibb Company

Inventor： James R. Corte ,  Tianan Fang ,  Carl P. Decicco ,  Donald J. P. Pinto ,  Karen A. Rossi ,  Zilun Hu ,  Yoon Jeon ,  Mimi L. Quan ,  Joanne M. Smallheer ,  Yufeng Wang ,  Wu Yang

IPC: C07D487/04 ,  C07D487/08 ,  C07D498/08 ,  C07D487/06 ,  C07D487/16 ,  C07D498/06 ,  C07D471/18 ,  C07D487/18 ,  C07D471/14 ,  C07D487/14 ,  C07D498/04

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

公开(公告)号：US10112936B2

公开(公告)日：2018-10-30

申请号：US15440346

申请日：2017-02-23

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Jon J. Hangeland ,  Mimi L. Quan ,  Joanne M. Smallheer ,  Gregory S. Bisacchi ,  James R. Corte ,  Todd J. Friends ,  Zhong Sun ,  Karen A. Rossi ,  Cullen L. Cavallaro

IPC: C07D263/32 ,  C07D417/14 ,  C07D235/16 ,  C07D231/12 ,  C07D233/64 ,  C07D233/68 ,  C07D249/08 ,  C07D249/12 ,  C07D263/14 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06 ,  C07D235/08 ,  C07D263/12 ,  C07D233/90 ,  C07D235/14 ,  C07D277/30 ,  C07D401/10 ,  C07D413/10

Abstract: The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, R4, R6, R11, X1, X2, and X3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

公开(公告)号：US09802939B2

公开(公告)日：2017-10-31

申请号：US14578846

申请日：2014-12-22

Applicant: Bristol-Myers Squibb Company

Inventor： James R. Corte ,  Tianan Fang ,  Carl P. Decicco ,  Donald J. P. Pinto ,  Karen A. Rossi ,  Zilun Hu ,  Yoon Jeon ,  Mimi L. Quan ,  Joanne M. Smallheer ,  Yufeng Wang ,  Wu Yang

IPC: C07D487/18 ,  C07D487/04 ,  C07D487/08 ,  C07D498/08 ,  C07D487/06 ,  C07D487/16 ,  C07D498/06 ,  C07D471/18 ,  C07D471/14 ,  C07D487/14 ,  C07D498/04

CPC classification number: C07D487/04 ,  C07D471/14 ,  C07D471/18 ,  C07D487/06 ,  C07D487/08 ,  C07D487/14 ,  C07D487/16 ,  C07D487/18 ,  C07D498/04 ,  C07D498/06 ,  C07D498/08

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective Factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

公开(公告)号：US09745313B2

公开(公告)日：2017-08-29

申请号：US15246813

申请日：2016-08-25

Applicant: Bristol-Myers Squibb Company

Inventor： Mimi L. Quan ,  Carl P. Decicco ,  James R. Corte ,  Cailan Wang

IPC: C07D487/18 ,  C07D487/04 ,  C07D487/08 ,  C07D498/08 ,  C07D487/06 ,  C07D487/16 ,  C07D498/06 ,  C07D471/18 ,  C07D471/14 ,  C07D487/14 ,  C07D498/04

CPC classification number: C07D487/04 ,  C07D471/14 ,  C07D471/18 ,  C07D487/06 ,  C07D487/08 ,  C07D487/14 ,  C07D487/16 ,  C07D487/18 ,  C07D498/04 ,  C07D498/06 ,  C07D498/08

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

公开(公告)号：US20170166560A1

公开(公告)日：2017-06-15

申请号：US15440346

申请日：2017-02-23

Applicant: Bristol-Myers Squibb Company

Inventor： Jon J. Hangeland ,  Mimi L. Quan ,  Joanne M. Smallheer ,  Gregory S. Bisacchi ,  James R. Corte ,  Todd J. Friends ,  Zhong Sun ,  Karen A. Rossi ,  Cullen L. Cavallaro

IPC: C07D417/14 ,  C07D233/68 ,  C07D403/04 ,  C07D233/90 ,  C07D405/14 ,  C07D403/14 ,  C07D401/14 ,  C07D401/12 ,  C07D403/12 ,  C07D401/10 ,  C07D409/14 ,  C07D401/04 ,  C07D409/04 ,  C07D403/10 ,  C07D413/10 ,  C07D263/32 ,  C07D249/08 ,  C07D231/12 ,  C07D401/06 ,  C07D417/04 ,  C07D413/04 ,  C07D405/04 ,  C07D235/14 ,  C07D277/30 ,  C07D233/64

CPC classification number: C07D417/14 ,  C07D231/12 ,  C07D233/64 ,  C07D233/68 ,  C07D233/90 ,  C07D235/08 ,  C07D235/14 ,  C07D235/16 ,  C07D249/08 ,  C07D249/12 ,  C07D263/12 ,  C07D263/14 ,  C07D263/32 ,  C07D277/30 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06

Abstract: The present invention provides a method for treating a thrombotic or an inflammatory disorder administering to a patient in need thereof a therapeutically effective amount of at least one compound of Formula (I) or Formula (V): or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, R3, R4, R6, R11, X1, X2, and X3 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also provides compounds within the scope of Formula I and relates to pharmaceutical compositions comprising these compounds.

公开(公告)号：US09453029B2

公开(公告)日：2016-09-27

申请号：US14733996

申请日：2015-06-09

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Mimi L. Quan ,  Carl P. Decicco ,  James R. Corte ,  Cailan Wang

IPC: C07D487/06 ,  C07D498/06 ,  C07D471/08 ,  C07D471/18 ,  C07D487/08 ,  C07D487/18 ,  C07D498/08 ,  C07D487/16

CPC classification number: C07D487/04 ,  C07D471/14 ,  C07D471/18 ,  C07D487/06 ,  C07D487/08 ,  C07D487/14 ,  C07D487/16 ,  C07D487/18 ,  C07D498/04 ,  C07D498/06 ,  C07D498/08

Abstract: The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

公开(公告)号：US20160152627A1

公开(公告)日：2016-06-02

申请号：US14900228

申请日：2014-07-01

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Mimi L. Quan ,  Zilun Hu ,  Cailan Wang

IPC: C07D491/052 ,  C07D471/04

CPC classification number: C07D491/052 ,  C07D471/04 ,  C07D498/04

Abstract: The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.