公开(公告)号：US20140256700A1

公开(公告)日：2014-09-11

申请号：US14190477

申请日：2014-02-26

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Michael A. Poss ,  David R. Tortolani ,  Dharmpal S. Dodd ,  Christopher P. Mussari ,  John S. Tokarski ,  Ashvinikumar V. Gavai ,  Yufen Zhao ,  George V. Delucca ,  Daniel O'Malley ,  Derek J. Norris ,  Patrice Gill ,  Claude A. Quesnelle ,  Wen-Ching Han

IPC: A61K31/553 ,  A61K31/5377 ,  C07D417/14 ,  C07D413/14 ,  A61K31/422 ,  A61K31/4192 ,  A61K31/496 ,  A61K31/427 ,  A61K31/5355 ,  A61K31/541 ,  C07D405/14 ,  C07D413/04 ,  A61K31/454

CPC classification number: A61K31/553 ,  A61K31/4192 ,  A61K31/422 ,  A61K31/427 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5355 ,  A61K31/5377 ,  A61K31/541 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention is directed to carbazole compounds, pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

Abstract translation: 本发明涉及咔唑化合物，包含本发明化合物的药学上可接受的组合物和使用所述组合物治疗各种疾病的方法。

公开(公告)号：US09725449B2

公开(公告)日：2017-08-08

申请号：US15150492

申请日：2016-05-10

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Derek J. Norris ,  Wayne Vaccaro ,  Mikkel V. DeBenedetto ,  Andrew P. Degnan ,  George V. Delucca ,  Jeffrey A. Deskus ,  Wen-Ching Han ,  Godwin Kwame Kumi ,  William D. Schmitz ,  John E. Starrett, Jr. ,  Matthew D. Hill ,  Hong Huang

IPC: C07D471/14 ,  A61K31/4375 ,  A61K31/439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/554 ,  A61K31/675 ,  A61K31/683 ,  C07D519/00 ,  C07F9/6561

CPC classification number: C07D471/14 ,  A61K31/4375 ,  A61K31/439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/554 ,  A61K31/675 ,  A61K31/683 ,  C07D519/00 ,  C07F9/6561

Abstract: The present invention is directed to tricyclic compounds of the formula wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

公开(公告)号：US09427442B2

公开(公告)日：2016-08-30

申请号：US14429958

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Yufen Zhao ,  Ashvinikumar V. Gavai ,  Patrice Gill ,  Soong-Hoon Kim ,  Brian E. Fink ,  Libing Chen ,  Mark G. Saulnier ,  Wen-Ching Han

IPC: C07D243/24 ,  A61K31/5513 ,  A61K45/06

CPC classification number: A61K31/5513 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/555 ,  A61K45/06 ,  C07D243/18 ,  C07D243/24 ,  C07D243/26 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I): (Formula (I)) wherein: R1 is —CH2CH2CF3; R2 is —CH2CH2CH2F, —CH2CF2CH3, —CH2CH2CF3, —CH2CH(CH3)CF3, —CH2CH2CF2CH3, (Formulae (II), (III), (IV), (V) or (VI): R3 is H or —CH3; Ring A is phenyl or pyridinyl; and Rx, Ry, Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, 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 cancer.

Abstract translation: 公开了式（I）的化合物：（式（I））其中：R 1是-CH 2 CH 2 CF 3; R2是-CH2CH2CH2F，-CH2CF2CH3，-CH2CH2CF3，-CH2CH（CH3）CF3，-CH2CH2CF2CH3，（式（Ⅱ），（Ⅲ），（Ⅳ），（Ⅴ）或（Ⅵ）：R3是H或-CH3; 环A是苯基或吡啶基; Rx，Ry，Ra，Rb，y和z在本文中定义。还公开了使用这些化合物抑制Notch受体的方法，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（例如癌症）中的疾病或病症的发展。

公开(公告)号：US20150231152A1

公开(公告)日：2015-08-20

申请号：US14429958

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Yufen Zhao ,  Ashvinikumar V. Gavai ,  Patrice Gill ,  Soong-Hoon Kim ,  Brian E. Fink ,  Libing Chen ,  Mark G. Saulnier ,  Wen-Ching Han

IPC: A61K31/5513 ,  A61K45/06 ,  C07D243/24

CPC classification number: A61K31/5513 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/555 ,  A61K45/06 ,  C07D243/18 ,  C07D243/24 ,  C07D243/26 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I): (Formula (I)) wherein: R1 is —CH2CH2CF3; R2 is —CH2CH2CH2F, —CH2CF2CH3, —CH2CH2CF3, —CH2CH(CH3)CF3, —CH2CH2CF2CH3, (Formulae (II), (III), (IV), (V) or (VI): R3 is H or —CH3; Ring A is phenyl or pyridinyl; and Rx, Ry, Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, 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 cancer.

Abstract translation: 公开了式（I）的化合物：（式（I））其中：R 1是-CH 2 CH 2 CF 3; R2是-CH2CH2CH2F，-CH2CF2CH3，-CH2CH2CF3，-CH2CH（CH3）CF3，-CH2CH2CF2CH3，（式（Ⅱ），（Ⅲ），（Ⅳ），（Ⅴ）或（Ⅵ）：R3是H或-CH3; 环A是苯基或吡啶基; Rx，Ry，Ra，Rb，y和z在本文中定义。还公开了使用这些化合物抑制Notch受体的方法，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（例如癌症）中的疾病或病症的发展。

公开(公告)号：US20150218111A1

公开(公告)日：2015-08-06

申请号：US14429941

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Ashvinikumar V. Gavai ,  Weifang Shan ,  James Aaron Balog ,  Claude A. Quesnelle ,  Wen-Ching Han ,  George V. DeLucca ,  Daniel O'Malley ,  Brian E. Fink

IPC: C07D243/24 ,  C07D413/12 ,  A61K45/06 ,  C07D413/14 ,  C07D401/04 ,  C07D491/056 ,  A61K31/5513 ,  C07D401/12

CPC classification number: C07D243/24 ,  A61K31/5513 ,  A61K45/06 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14 ,  C07D491/04 ,  C07D491/056

Abstract: Disclosed are compounds of Formula (I): wherein: R2 is phenyl, fluorophenyl, chlorophenyl, trifluorophenyl, methylisoxazolyl, or pyridinyl; R3 is H, CH3, CH2(cyclopropyl), pyridinyl, chloropyridinyl, or methoxypyridinyl: and Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, 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 cancer.

Abstract translation: 公开了式（I）的化合物：其中：R 2是苯基，氟苯基，氯苯基，三氟苯基，甲基异恶唑基或吡啶基; R 3是H，CH 3，CH 2（环丙基），吡啶基，氯吡啶基或甲氧基吡啶基：和R a，R b，y和z在本文中定义。 还公开了使用这些化合物抑制Notch受体的方法，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（例如癌症）中疾病或病症的发展。

公开(公告)号：US10174024B2

公开(公告)日：2019-01-08

申请号：US15573151

申请日：2016-05-11

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Wen-Ching Han ,  Andrew P. Degnan ,  Jeffrey A. Deskus ,  Ashvinikumar V. Gavai ,  Patrice Gill ,  William D. Schmitz ,  John E. Starrett, Jr.

IPC: C07D471/04

Abstract: The present invention is directed to tricyclic compounds of formula (I), pharmaceutically acceptable compositions comprising compounds of the invention and said compositions for use in methods for the treatment of various disorders in particular cancer.

公开(公告)号：US09133139B2

公开(公告)日：2015-09-15

申请号：US14429941

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Ashvinikumar V. Gavai ,  Weifang Shan ,  James Aaron Balog ,  Claude A. Quesnelle ,  Wen-Ching Han ,  George V. DeLucca ,  Daniel O'Malley ,  Brian E. Fink

IPC: C07D413/14 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D243/24 ,  A61K31/5513 ,  C07D491/056 ,  A61K45/06

CPC classification number: C07D243/24 ,  A61K31/5513 ,  A61K45/06 ,  C07D401/04 ,  C07D401/12 ,  C07D413/12 ,  C07D413/14 ,  C07D491/04 ,  C07D491/056

Abstract: Disclosed are compounds of Formula (I): wherein: R2 is phenyl, fluorophenyl, chlorophenyl, trifluorophenyl, methylisoxazolyl, or pyridinyl; R3 is H, CH3, CH2(cyclopropyl), pyridinyl, chloropyridinyl, or methoxypyridinyl: and Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, 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 cancer.

Abstract translation: 公开了式（I）的化合物：其中：R 2是苯基，氟苯基，氯苯基，三氟苯基，甲基异恶唑基或吡啶基; R 3是H，CH 3，CH 2（环丙基），吡啶基，氯吡啶基或甲氧基吡啶基：和R a，R b，y和z在本文中定义。 还公开了使用这些化合物抑制Notch受体的方法，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（例如癌症）中疾病或病症的发展。

公开(公告)号：US20150246892A1

公开(公告)日：2015-09-03

申请号：US14429945

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Wen-Ching Han ,  Patrice Gill ,  Ashvinikumar V. Gavai ,  Claude A. Quesnelle

IPC: C07D243/16 ,  A61K45/06 ,  C07D401/04 ,  C07D491/056 ,  A61K31/5513

CPC classification number: C07D243/16 ,  A61K31/138 ,  A61K31/337 ,  A61K31/506 ,  A61K31/5513 ,  A61K31/555 ,  A61K31/573 ,  A61K45/06 ,  C07D243/18 ,  C07D243/26 ,  C07D401/04 ,  C07D491/04 ,  C07D491/056 ,  A61K2300/00

Abstract: Disclosed are compounds of Formula (I): wherein: R1 is —CH2CH2CF3; R2 is —CH2CH2CF3, or —CH2CH2CH2CF3; R3 is —CH2CF3, —CH2CN, —CH2(cyclopropyl), pyridinyl, chloropyridinyl, or tetrahydropyranyl; Ring A is phenyl or pyridinyl; Ra, Rb, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, 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 cancer.

Abstract translation: 公开了式（I）的化合物：其中：R1是-CH2CH2CF3; R2是-CH2CH2CF3或-CH2CH2CH2CF3; R3是-CH2CF3，-CH2CN，-CH2（环丙基），吡啶基，氯吡啶基或四氢吡喃基; 环A是苯基或吡啶基; Ra，Rb，y和z在本文中定义。 还公开了使用这些化合物抑制Notch受体的方法，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（例如癌症）中疾病或病症的发展。

公开(公告)号：US20150239851A1

公开(公告)日：2015-08-27

申请号：US14429935

申请日：2013-09-20

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Ashvinikumar V. Gavai ,  Yufen Zhao ,  Daniel O'Malley ,  Claude A. Quesnelle ,  Brian E. Fink ,  Derek J. Norris ,  Wen-Ching Han ,  George V. DeLucca

IPC: C07D243/24 ,  A61K45/06 ,  A61K31/675 ,  C07D403/12 ,  A61K31/5513 ,  C07F9/645

CPC classification number: C07D243/24 ,  A61K31/5513 ,  A61K31/675 ,  A61K45/06 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07F9/12 ,  C07F9/645

Abstract: Disclosed are compounds of Formula (I) and/or salts thereof: (I) wherein: R1 is CH2CH2CF3; R2 is CH2(cyclopropyl), CH(CH3)(cyclopropyl), or CH2CH2CH3; R3 is H, CH3, or Rx; R4 is H or Ry; and Rx, Ry, Ra, Rb, Rc, y, and z are defined herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, 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 cancer. The compounds of Formula (I) also include prodrugs of the Notch inhibitor compounds.

Abstract translation: 公开了式（I）和/或其盐的化合物：（I）其中：R 1是CH 2 CH 2 CF 3; R2是CH2（环丙基），CH（CH3）（环丙基）或CH2CH2CH3; R3是H，CH3或Rx; R4是H或Ry; 并且Rx，Ry，Ra，Rb，Rc，y和z在本文中定义。 还公开了使用这些化合物抑制Notch受体的方法，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（例如癌症）中疾病或病症的发展。 式（I）的化合物还包括Notch抑制剂化合物的前药。