公开(公告)号：US20130158039A1

公开(公告)日：2013-06-20

申请号：US13746389

申请日：2013-01-22

Applicant: Bristol-Myers Squibb Company

Inventor： Percy H. Carter ,  Robert J. Cherney

IPC: A61K31/53

CPC classification number: A61K31/53 ,  C07D487/04

Abstract: The present invention provides a novel antagonist: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide: or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having unexpected dual CCR-2 and CCR-5 receptor activity. Crystalline forms, metabolites, pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases are also disclosed. The present disclosure also provides processes for preparing compounds of Formula (I) as provided herein, including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide. Compounds that are useful intermediates of the process are also provided herein.

Abstract translation: 本发明提供新的拮抗剂：N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S）-3-（7-叔丁基吡唑并[1,5-a] 1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺：或其药学上可接受的盐，溶剂合物或前药，具有意想不到的双重CCR-2和CCR-5受体活性。 还公开了结晶形式，代谢物，含有其的药物组合物和使用其作为治疗炎性疾病，过敏性，自身免疫性，代谢性，癌症和/或心血管疾病的药剂的方法。 本公开还提供了制备本文提供的式（I）化合物的方法，包括N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S） 叔丁基吡唑并[1,5-a] [1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺。 本文还提供了该方法有用中间体的化合物。

公开(公告)号：US20140309265A1

公开(公告)日：2014-10-16

申请号：US14356911

申请日：2012-11-09

Applicant: Ensemble Therapeutics ,  Bristol-Myers Squibb Company

Inventor： Benjamin Adam Seigal ,  Nicholas Terrett ,  Percy H. Carter ,  Robert M. Borzilleri ,  Yong Zhang ,  Michael M. Miller

IPC: C07D498/22 ,  C07D498/16

CPC classification number: C07D498/22 ,  A61K38/00 ,  C07D249/04 ,  C07D498/16 ,  C07K5/1008 ,  C07K7/56 ,  Y02A50/411 ,  Y02A50/414

Abstract: The invention relates generally to macrocyclic compounds and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of inhibitors of apoptosis (IAPs) and/or are useful in the treatment of medical conditions, such as cancer.

Abstract translation: 本发明一般涉及大环化合物及其治疗用途。 更具体地，本发明涉及调节凋亡抑制剂（IAP）的活性的大环化合物和/或可用于治疗诸如癌症的医学病症。

公开(公告)号：US20140088109A1

公开(公告)日：2014-03-27

申请号：US14091388

申请日：2013-11-27

Applicant: Bristol-Myers Squibb Company

Inventor： Percy H. Carter ,  Robert J. Cherney

IPC: C07D487/04

CPC classification number: A61K31/53 ,  C07D487/04

Abstract: The present invention provides a novel antagonist: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin -1-yl)cyclohexyl)acetamide: or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having unexpected dual CCR-2 and CCR-5 receptor activity. Crystalline forms, metabolites, pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases are also disclosed. The present disclosure also provides processes for preparing compounds of Formula (I) as provided herein, including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide. Compounds that are useful intermediates of the process are also provided herein.

Abstract translation: 本发明提供新的拮抗剂：N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S）-3-（7-叔丁基吡唑并[1,5-a] 1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺：或其药学上可接受的盐，溶剂合物或前药，具有预期的双重CCR-2和CCR-5受体活性。 还公开了结晶形式，代谢物，含有其的药物组合物和使用其作为治疗炎性疾病，过敏性，自身免疫性，代谢性，癌症和/或心血管疾病的药剂的方法。 本公开还提供了制备本文提供的式（I）化合物的方法，包括N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S） 叔丁基吡唑并[1,5-a] [1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺。 本文还提供了该方法有用中间体的化合物。

公开(公告)号：US08906920B2

公开(公告)日：2014-12-09

申请号：US14091388

申请日：2013-11-27

Applicant: Bristol-Myers Squibb Company

Inventor： Percy H. Carter ,  Robert J. Cherney

IPC: C07D487/04 ,  A61K31/53 ,  A61P13/12

CPC classification number: A61K31/53 ,  C07D487/04

Abstract: The present invention provides a novel antagonist: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide: or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having unexpected dual CCR-2 and CCR-5 receptor activity. Crystalline forms, metabolites, pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases are also disclosed. The present disclosure also provides processes for preparing compounds of Formula (I) as provided herein, including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide. Compounds that are useful intermediates of the process are also provided herein.

Abstract translation: 本发明提供新的拮抗剂：N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S）-3-（7-叔丁基吡唑并[1,5-a] 1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺：或其药学上可接受的盐，溶剂合物或前药，具有意想不到的双重CCR-2和CCR-5受体活性。 还公开了结晶形式，代谢物，含有其的药物组合物和使用其作为治疗炎性疾病，过敏性，自身免疫性，代谢性，癌症和/或心血管疾病的药剂的方法。 本公开还提供了制备本文提供的式（I）化合物的方法，其包括N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S） 叔丁基吡唑并[1,5-a] [1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺。 本文还提供了该方法有用中间体的化合物。

公开(公告)号：US08618101B2

公开(公告)日：2013-12-31

申请号：US13746389

申请日：2013-01-22

Applicant: Bristol-Myers Squibb Company

Inventor： Percy H. Carter ,  Robert J. Cherney

IPC: C07D487/04 ,  A61K31/53 ,  A61P19/02 ,  A61P35/00

CPC classification number: A61K31/53 ,  C07D487/04

Abstract: The present invention provides a novel antagonist: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide: or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having unexpected dual CCR-2 and CCR-5 receptor activity. Crystalline forms, metabolites, pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases are also disclosed. The present disclosure also provides processes for preparing compounds of Formula (I) as provided herein, including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide. Compounds that are useful intermediates of the process are also provided herein.

Abstract translation: 本发明提供新的拮抗剂：N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S）-3-（7-叔丁基吡唑并[1,5-a] 1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺：或其药学上可接受的盐，溶剂合物或前药，具有意想不到的双重CCR-2和CCR-5受体活性。 还公开了结晶形式，代谢物，含有其的药物组合物和使用其作为治疗炎性疾病，过敏性，自身免疫性，代谢性，癌症和/或心血管疾病的药剂的方法。 本公开还提供了制备本文提供的式（I）化合物的方法，包括N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S） 叔丁基吡唑并[1,5-a] [1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺。 本文还提供了该方法有用中间体的化合物。

公开(公告)号：US11479581B2

公开(公告)日：2022-10-25

申请号：US16618847

申请日：2018-06-08

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Gardner S. Creech ,  Mahboubeh Kheirabadi ,  Martin D. Eastgate ,  David S. Nirschl ,  Percy H. Carter

IPC: C07K1/04 ,  C07K1/113 ,  C07K7/64 ,  C07C309/75 ,  C07C309/77 ,  C07D225/08 ,  C07K1/107 ,  C07K17/08

Abstract: The disclosure is directed to compounds and methods for preparing purified macrocyclic peptide using “catch-release” methods. These methods comprise reacting a free amino group of a resin-bound linear peptide with an azide- or alkyne-functionalized cap to form a resin-bound capped linear peptide having an azide- or alkyne-functionalized cap; cleaving the capped linear peptide from the resin to form a free capped linear peptide having an azide- or alkyne-functionalized cap; reacting the free capped linear peptide having an azide-functionalized cap with an alkyne-functionalized catch resin, or reacting the free capped linear peptide having an akynyl-functionalized cap with an azide functionalized catch resin, to form a catch-resin bound capped linear peptide; reacting the catch-resin bound capped linear peptide under conditions sufficient to effect macrocyclization of the linear peptide and release of the macrocyclic peptide from the catch resin.

公开(公告)号：US20130178444A1

公开(公告)日：2013-07-11

申请号：US13785039

申请日：2013-03-05

Applicant: Bristol-Myers Squibb Company

Inventor： John Hynes ,  Percy H. Carter ,  Lyndon A.M. Cornelius ,  T.G. Murali Dhar ,  John V. Duncia ,  Satheesh K. Nair ,  Joseph B. Santella ,  Jayakumar S. Warrier ,  Hong Wu

IPC: C07D211/60 ,  C07F9/59

CPC classification number: C07D211/60 ,  C07D211/52 ,  C07F9/59

Abstract: The present application describes prodrugs of the compound of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis using the prodrug compounds of the invention are disclosed.

Abstract translation: 本申请描述了式（I）化合物的前药或其立体异构体或其药学上可接受的盐。 此外，公开了使用本发明的前药化合物治疗和预防炎症性疾病如哮喘和过敏性疾病以及自身免疫性病症如类风湿性关节炎的方法。