公开(公告)号：WO2019046498A1

公开(公告)日：2019-03-07

申请号：PCT/US2018/048662

申请日：2018-08-30

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： QIN, Lan-Ying ,  RUAN, Zheming ,  CHEN, Libing ,  WATTERSON, Scott Hunter ,  FINK, Brian E.

IPC分类号： C07H21/02 ,  A61P35/00

摘要： The present invention is directed to compounds of the formula (I) 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：WO2016064957A1

公开(公告)日：2016-04-28

申请号：PCT/US2015/056576

申请日：2015-10-21

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： BHIDE, Rajeev S. ,  BATT, Douglas G. ,  CHERNEY, Robert J. ,  CORNELIUS, Lyndon A.M. ,  LIU, Qingjie ,  MARCOUX, David ,  NEELS, James ,  POSS, Michael A. ,  QIN, Lan-ying ,  RUAN, Zheming ,  SHI, Qing ,  SRIVASTAVA, Anurag S. ,  TINO, Joseph A. ,  WATTERSON, Scott Hunter

IPC分类号： C07D487/04 ,  C07D491/08 ,  A61K31/4985 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/541 ,  A61P29/00

CPC分类号： C07D491/08 ,  C07D487/04

摘要： Disclosed are compounds of Formula (I) or a salt thereof; wherein: X is N or CH; Q 1 is: (i) C1, Br, I, -CN, -CH 3 , or -CF 3 ; (ii) a 5-membered heteroaryl selected from pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, and thiadiazolyl; (iii) a 6?membered heteroaryl selected from pyridinyl, pyridazinyl, and pyrimidinyl; or (iv) a bicyclic heteroaryl selected from indolyl, pyrrolopyridinyl, pyrazolopyridinyl and benzo[d]oxazolyl; wherein each of said 5-membered, 6-membered, and bicyclic heteroaryl is substituted with zero to 1 R a and zero to 1 R b ; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R a , and R b are defined herein. Also disclosed are methods of using such compounds as modulators of PI3K, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases.

摘要翻译： 公开了式（I）的化合物或其盐; 其中：X为N或CH; Q1是：（i）C1，Br，I，-CN，-CH3或-CF3; （ii）选自吡咯基，吡唑基，咪唑基，恶唑基，噻唑基，三唑基，恶二唑基和噻二唑基的5元杂芳基。 （iii）选自吡啶基，哒嗪基和嘧啶基的6元杂芳基; 或（iv）选自吲哚基，吡咯并吡啶基，吡唑并吡啶基和苯并[d]恶唑基的双环杂芳基; 其中所述5元，6元和双环杂芳基中的每一个被0至1个Ra和0至1个Rb取代; 并且R 1，R 2，R 3，R 4，R 5，R 6，R a和R b在本文中定义。 还公开了使用这种化合物作为PI3K的调节剂的方法和包含这些化合物的药物组合物。 这些化合物可用于治疗，预防或减缓炎症和自身免疫性疾病。

公开(公告)号：WO2019023459A1

公开(公告)日：2019-01-31

申请号：PCT/US2018/043907

申请日：2018-07-26

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： FINK, Brian E. ,  DODD, Dharmpal S. ,  QIN, Lan-ying ,  RUAN, Zheming ,  ZHAO, Yufen ,  HARIKRISHNAN, Lalgudi S. ,  KAMAU, Muthoni G.

IPC分类号： C07H19/20 ,  C07H19/14 ,  C07H19/207 ,  C07H19/23 ,  A61P35/00 ,  A61P35/02 ,  A61K31/706 ,  A61K31/7064 ,  A61K31/7076 ,  A61K31/708

摘要： The present invention is directed to compounds of the formulae I, II and III as shown below (I) (II) (III) wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and said compositions for use in the treatment of various disorders.

公开(公告)号：WO2006113261A2

公开(公告)日：2006-10-26

申请号：PCT/US2006/013610

申请日：2006-04-12

申请人： BRISTOL-MYERS SQUIBB COMPANY ,  LI, James, J. ,  HAMANN, Lawrence, G. ,  RUAN, Zheming ,  COOPER, Christopher, B. ,  WU, Shung, C. ,  SIMPKINS, Ligaya, M. ,  WANG, Haixia ,  NAYEEM, Akbar ,  KRYSTEK, Stanley, R., Jr.

发明人： LI, James, J. ,  HAMANN, Lawrence, G. ,  RUAN, Zheming ,  COOPER, Christopher, B. ,  WU, Shung, C. ,  SIMPKINS, Ligaya, M. ,  WANG, Haixia ,  NAYEEM, Akbar ,  KRYSTEK, Stanley, R., Jr.

IPC分类号： C07D401/12 ,  C07D401/14 ,  C07D401/04 ,  A61K31/444

CPC分类号： C07D213/70 ,  A61K31/421 ,  A61K31/426 ,  A61K31/4439 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/506 ,  C07D213/71 ,  C07D213/81 ,  C07D213/82 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D413/14 ,  C07D487/04 ,  C07D487/08

摘要： Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure: (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein G, L, Q, Z, R 6 , R 7 , and R 8 are defined herein.

摘要翻译： 提供了新的化合物，其为11-β-羟基类固醇脱氢酶I型抑制剂。 11-β-羟基类固醇脱氢酶I型抑制剂可用于治疗，预防或减缓需要11-β-羟基类固醇脱氢酶I型抑制剂治疗的疾病进展。 这些新化合物具有以下结构：（I）或其立体异构体或前药或其药学上可接受的盐，其中G，L，Q，Z，R 6，R 7和 本文定义R 8。

公开(公告)号：WO2021026179A1

公开(公告)日：2021-02-11

申请号：PCT/US2020/044918

申请日：2020-08-05

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： HARIKRISHNAN, Lalgudi S. ,  PARK, Peter Kinam ,  RUAN, Zheming ,  WEI, Donna D. ,  O'MALLEY, Daniel ,  WAN, Honghe ,  PURANDARE, Ashok Vinayak ,  FINK, Brian E.

IPC分类号： C07D211/52 ,  A61K31/445 ,  A61P35/00 ,  C07D205/04 ,  C07D207/27 ,  C07D211/18 ,  C07D211/26 ,  C07D211/34 ,  C07D211/42 ,  C07D211/46 ,  C07D211/54 ,  C07D211/56 ,  C07D211/88 ,  C07D211/96 ,  C07D213/12 ,  C07D213/56 ,  C07D213/61 ,  C07D213/69 ,  C07D213/71 ,  C07D213/75 ,  C07D213/82 ,  C07D217/02 ,  C07D217/04 ,  C07D217/06 ,  C07D231/12 ,  C07D231/18 ,  C07D233/60 ,  C07D233/61 ,  C07D233/64 ,  C07D235/18 ,  C07D239/26 ,  C07D241/12 ,  C07D241/16 ,  C07D241/24 ,  C07D249/08 ,  C07D261/08 ,  C07D263/20 ,  C07D263/24 ,  C07D277/64 ,  C07D295/125 ,  C07D295/145 ,  C07D295/15 ,  C07D295/192 ,  C07D295/215 ,  C07D295/26 ,  C07D309/04 ,  C07D335/02 ,  C07D401/06 ,  C07D401/12 ,  C07D471/04 ,  C07D471/10 ,  C07D487/10

摘要： The present invention is directed to compounds of the formula (I) 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：WO2016064958A1

公开(公告)日：2016-04-28

申请号：PCT/US2015/056577

申请日：2015-10-21

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： BHIDE, Rajeev S. ,  RUAN, Zheming ,  CHERNEY, Robert J. ,  CORNELIUS, Lyndon A.M. ,  DHAR, T.G. Murali ,  GONG, Hua ,  MARCOUX, David ,  POSS, Michael A. ,  QIN, Lan-ying ,  SHI, Qing ,  TINO, Joseph A.

IPC分类号： C07D487/04 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/541 ,  A61P29/00

CPC分类号： C07D487/04

摘要： Disclosed are compounds of Formula (I); or a salt thereof; wherein Qi is (i) C1, Br, I, -CN, -CH 3 , or -CF 3 ; or (ii) pyrazole, triazole, or pyridinyl, each substituted with R 1 ; Q 2 is pyridinyl, indazolyl, isoquinolinyl, or benzo[d]imidazolyl substituted with R 2 and R 3 ; and R 1 , R 2 , and R 3 are defined herein. Also disclosed are methods of using such compounds as modulators of PI3K, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing inflammatory and autoimmune diseases.

摘要翻译： 公开了式（I）的化合物; 或其盐; 其中Qi是（i）C1，Br，I，-CN，-CH3或-CF3; 或（ii）各自被R 1取代的吡唑，三唑或吡啶基; Q2是被R2和R3取代的吡啶基，吲唑基，异喹啉基或苯并[d]咪唑基; 并且R1，R2和R3在本文中定义。 还公开了使用这种化合物作为PI3K的调节剂的方法和包含这些化合物的药物组合物。 这些化合物可用于治疗，预防或减缓炎症和自身免疫性疾病。

公开(公告)号：WO2007082264A2

公开(公告)日：2007-07-19

申请号：PCT/US2007/060383

申请日：2007-01-11

申请人： BRISTOL-MYERS SQUIBB COMPANY ,  HAQUE, Tasir Shamsul ,  EWING, William R. ,  MAPELLI, Claudio ,  LEE, Ving G. ,  SULSKY, Richard B. ,  RIEXINGER, Douglas James ,  MARTINEZ, Rogelio L. ,  ZHU, Yeheng ,  RUAN, Zheming

发明人： HAQUE, Tasir Shamsul ,  EWING, William R. ,  MAPELLI, Claudio ,  LEE, Ving G. ,  SULSKY, Richard B. ,  RIEXINGER, Douglas James ,  MARTINEZ, Rogelio L. ,  ZHU, Yeheng ,  RUAN, Zheming

IPC分类号： C07K14/43

CPC分类号： C07K14/605 ,  A61K38/26 ,  A61K38/28 ,  C07C271/16 ,  C07C2603/18 ,  A61K2300/00

摘要： The present invention provides novel human glucagon-like peptide-1 (GLP-1)-receptor modulators that have biological activity similar or superior to native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. Further, the present invention provides novel, chemically modified compounds that not only stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 receptor modulators exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration. The compounds of this invention show desirable pharmacokinetic properties and desirable potency in efficacy models of diabetes.

摘要翻译： 本发明提供了具有与天然GLP-1肽相似或优于天然GLP-1肽的生物活性的新型人胰高血糖素样肽-1（GLP-1） - 受体调节剂，因此可用于治疗或预防与GLP活性相关的疾病或病症 。 此外，本发明提供新颖的化学修饰的化合物，其不仅刺激II型糖尿病患者的胰岛素分泌，而且产生其它有益的促胰岛素反应。 这些合成肽GLP-1受体调节剂表现出增加的蛋白水解切割的稳定性，使其成为口服或肠胃外给药的理想治疗候选物。 本发明的化合物在糖尿病的功效模型中显示出所需的药代动力学性质和期望的效力。

公开(公告)号：WO2006135795A1

公开(公告)日：2006-12-21

申请号：PCT/US2006/022576

申请日：2006-06-08

申请人： BRISTOL-MYERS SQUIBB COMPANY ,  LI, James J. ,  HAMANN, Lawrence G. ,  WANG, Haixia ,  RUAN, Zheming ,  COOPER, Christopher B. ,  LI, Jun ,  ROBL, Jeffrey A.

发明人： LI, James J. ,  HAMANN, Lawrence G. ,  WANG, Haixia ,  RUAN, Zheming ,  COOPER, Christopher B. ,  LI, Jun ,  ROBL, Jeffrey A.

IPC分类号： C07D471/04 ,  A61K31/435 ,  A61P3/00

CPC分类号： C07D471/04

摘要： Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure:(I) or stereoisomers or pharmaceutically acceptable salts thereof, wherein W, L, R 3 , R 3a , R 3b and R 4 are defined herein.

摘要翻译： 提供了新的化合物，其为11-β-羟基类固醇脱氢酶I型抑制剂。 11-β-羟基类固醇脱氢酶I型抑制剂可用于治疗，预防或减缓需要11-β-羟基类固醇脱氢酶I型抑制剂治疗的疾病进展。 这些新化合物具有以下结构：其中W，L，R 3，R 3a，R 3b，R 3，R 3， SUB＆gt;和R 4＆gt;在本文中定义。

公开(公告)号：WO2004106296A2

公开(公告)日：2004-12-09

申请号：PCT/US2004/016713

申请日：2004-05-27

申请人： BRISTOL-MYERS SQUIBB COMPANY ,  YANG, Wu ,  DICKSON, John, K. ,  COOPER, Christopher, B. ,  DODD, Dharmpal, S. ,  RUAN, Zheming ,  SCHNUR, Dora, M.

发明人： YANG, Wu ,  DICKSON, John, K. ,  COOPER, Christopher, B. ,  DODD, Dharmpal, S. ,  RUAN, Zheming ,  SCHNUR, Dora, M.

IPC分类号： C07D

CPC分类号： C07D239/42 ,  C07D401/04 ,  C07D403/04 ,  C07D405/12 ,  C07D405/14

摘要： Trisubstituted heteroaromatic compounds having the structure Formula (I) are provided, wherein X is C or N; A and B are each independently CH or N, with the proviso that A and B cannot both be CH; R 1 is Ar-L-; R 2 is hydrogen or alkyl; or R 1 and R 2 can be joined together to form a 4- to 7-membered cycloheteroalkyl ring; R 3 to R 8 , Ar and L are as defined herein. A method for using these compounds to treat diseases associated with abnormal bone or mineral homeostasis is also provided.

摘要翻译： 提供具有结构式（I）的三取代杂芳族化合物，其中X是C或N; A和B各自独立地为CH或N，条件是A和B不能都是CH; R 1是Ar-L-; R 2是氢或烷基; 或R 1和R 2可以连接在一起形成4-至7-元环杂烷基环; R 3至R 8中，Ar和L如本文所定义。 还提供了使用这些化合物治疗与异常骨或矿物质内稳态相关疾病的方法。

公开(公告)号：WO2022192794A1

公开(公告)日：2022-09-15

申请号：PCT/US2022/020239

申请日：2022-03-14

申请人： BRISTOL-MYERS SQUIBB COMPANY

发明人： FINK, Brian Edward ,  CHERNEY, Robert Joseph ,  NGU, Khehyong ,  VELAPARTHI, Upender ,  VACCARO, Wayne David ,  RUAN, Zheming ,  QIN, Lan-Ying ,  SHIRUDE, Pravin A. ,  RAHAMAN, Hasibur

IPC分类号： C07D487/08 ,  A61K31/4995 ,  A61P35/00

摘要： The present disclosure relates to KRAS inhibitors. Methods of treating cancers using the compounds are also provided.