公开(公告)号：EP1590335A2

公开(公告)日：2005-11-02

申请号：EP04708546.9

申请日：2004-02-05

Applicant: Bristol-Myers Squibb Company

Inventor： CHEN, Bang-Chi ,  ZHAO, Rulin ,  SUNDEEN, Joseph, Edward ,  LEFTHERIS, Katerina ,  HYNES, John ,  WROBLESKI, Stephen, T.

IPC: C07D253/08 ,  C07D487/04 ,  A61K31/53 ,  A61P29/00

CPC classification number: C07D487/04

Abstract: An improved process for the preparation of certain pyrrolotriazine compounds is disclosed. The compounds exhibit utility as kinase inhibitors.

Abstract translation: 公开了一种制备某些吡咯并三嗪化合物的改进方法。 该化合物表现出作为激酶抑制剂的用途

公开(公告)号：EP2046779B1

公开(公告)日：2011-05-18

申请号：EP07813363.4

申请日：2007-07-26

Applicant: Bristol-Myers Squibb Company

Inventor： CARTER, Percy, H. ,  DUNCIA, John, V. ,  MUDRYK, Boguslaw, M. ,  RANDAZZO, Michael, E. ,  XIAO, Zili ,  YANG, Michael, G. ,  ZHAO, Rulin

IPC: C07D403/12 ,  C07D207/273 ,  A61K31/4025

CPC classification number: C07D403/12 ,  C07D207/273 ,  C07D317/72

Abstract: The present invention provides a novel antagonist or partial agonists/antagonist of MCP-I receptor activity: N-((lR,2S,5R)-5-(tert-butylamino)-2- ((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-l- yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. 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 is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((lR,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6- (trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-l-yl)cyclohexyl)acetamide: wherein R1, R8, R9, R10, and 'HET' are as described herein. Compounds that are useful intermediates of the process are also provided herein.

公开(公告)号：EP1805176A2

公开(公告)日：2007-07-11

申请号：EP05805626.8

申请日：2005-09-27

Applicant: Bristol-Myers Squibb Company

Inventor： MUDRYK, Boguslaw, M. ,  CUNIERE, Nicolas ,  HSIEH, Dau-Ming ,  ROSSANO, Lucius ,  LIANG, Jing ,  CHEN, Bang-Chi ,  ZHANG, Huiping ,  ZHAO, Rulin ,  WANG, Bei ,  DAVID, Adrian

IPC: C07D471/04 ,  A61K31/437 ,  A61P7/02

CPC classification number: C07D471/04

Abstract: A novel process and intermediates thereof for making 4,5-dihydro-pyrazolo[3,4-c]pyrid-2-ones of the type shown below from appropriate phenyl hydrazines is described. Formula (I). These compounds can be useful as factor Xa inhibitors.

公开(公告)号：EP1303512B1

公开(公告)日：2005-07-20

申请号：EP01931013.5

申请日：2001-05-02

Applicant: Bristol-Myers Squibb Company

Inventor： CHEN, Bang-Chi ,  KIM, Kyoung, S. ,  KIMBALL, S., David ,  MISRA, Raj, N. ,  SUNDEEN, Joseph, E. ,  ZHAO, Rulin

IPC: C07D417/12 ,  C07D417/14 ,  C07C69/618 ,  C07C67/343 ,  C07C59/74 ,  C07C51/373 ,  C07C69/73 ,  C07C67/31 ,  C07C67/333

CPC classification number: C07D417/12 ,  A61K31/427 ,  A61K31/454 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D417/14

Abstract: The present invention relates to new, efficient processes for the preparation of 5-(2-oxazolylalkylthio)-2-arylacetylaminothiazole compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R?1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13¿ and X are as defined in the specification. Compounds of formula (I) are novel, potent inhibitors of cyclin dependent kinases (cdks). The present invention also concerns a new process for the preparation of formylarylacetates and formylarylacetic acids.

公开(公告)号：EP3487862A1

公开(公告)日：2019-05-29

申请号：EP17746324.7

申请日：2017-07-21

Applicant: Bristol-Myers Squibb Company

Inventor： CHENG, Peter T. W. ,  MENG, Wei ,  LIU, Mark ,  WANG, Bei ,  ZHAO, Rulin

IPC: C07F9/40 ,  A61K31/675 ,  A61P3/00

公开(公告)号：EP1303514B9

公开(公告)日：2006-11-08

申请号：EP01932879.8

申请日：2001-05-02

Applicant: Bristol-Myers Squibb Company

Inventor： CHEN, Bang-Chi ,  KIM, Kyoung, S. ,  KIMBALL, S., David ,  MISRA, Raj, N. ,  SALVATI, Mark, E. ,  SUNDEEN, Joseph, E. ,  XIAO, Hai-Yun ,  ZHAO, Rulin

IPC: C07D417/14 ,  C07D487/18 ,  C07D263/32 ,  C07D251/00

CPC classification number: C07D417/12 ,  A61K31/427 ,  A61K31/454 ,  C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D417/14

Abstract: The present invention relates to new, efficient processes for the preparation of 5-(2-oxazolylalkylthio)-2-azacycloalkanoylaminothiazole compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R, R?1, R2, R3, R4, R5, R6, R7, R8¿, m and n are as defined in the specification. The compounds formula (I) are potent inhibitors of cyclin dependent kinases (cdks). The present invention further concerns new key intermediate compounds, a quaternary ammonium salt of formula (III') and a 2-oxazolylalkyl derivative of formula (IX).

公开(公告)号：EP1322603A1

公开(公告)日：2003-07-02

申请号：EP01975752.5

申请日：2001-09-17

Applicant: Bristol-Myers Squibb Company

Inventor： CHEN, Bang-Chi ,  SUNDEEN, Joseph, E. ,  ZHAO, Rulin

IPC: C07C317/46 ,  C07C315/02 ,  C07C323/62 ,  C07C319/14 ,  C07D303/48 ,  C07D301/16 ,  C07C255/66 ,  C07C253/30 ,  C07C231/08

CPC classification number: C07D303/48 ,  C07C253/30 ,  C07C315/02 ,  C07C319/14 ,  C07C317/46 ,  C07C323/60 ,  C07C255/60

Abstract: The present invention provides an improved process for the preparation of N-(substituted phenyl)-3-alkyl-, aryl- and heteroarylsulfonyl-2-hydroxy-2-alkyl- and haloalkylpropanamide compounds of formula I (I), The formula I compounds exhibit antiandrogenic activity and are useful in the treatment of malignant or benign prostatic disease or of androgen dependent disease conditions such as acne, hirsutism or seborrhoea.

公开(公告)号：EP2280956A2

公开(公告)日：2011-02-09

申请号：EP09759418.8

申请日：2009-06-04

Applicant: Bristol-Myers Squibb Company ,  Albany Molecular Research, Inc.

Inventor： LOBBEN, Paul ,  ZHAO, Rulin ,  WANG, Bei ,  CHEN, Bang-chi ,  LIU, Shuang ,  HU, Min ,  YANG, Yuh-Lin, Allen ,  ISHERWOOD, Matthew ,  AMIN, Rasidul ,  CUI, Wenge

IPC: C07D401/04

CPC classification number: C07F5/04 ,  C07C215/20 ,  C07C217/58 ,  C07C223/02 ,  C07D217/04 ,  C07D237/20 ,  C07D401/04 ,  C07D413/10 ,  C07F5/022 ,  C07F5/025

Abstract: Disclosed are processes for preparing tetrahydroisoquinolines, intermediates useful in the preparation of tetrahydroisoquinolines, processes for preparing such intermediates, and a crystalline form of 6-[(4S)-2-methyl-4-(naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine. Also disclosed are pharmaceutical compositions comprising tetrahydroisoquinolines, methods of using tetrahydroisoquinolines in the treatment of depression and other conditions and methods for obtaining the crystalline form.

公开(公告)号：EP1618092B1

公开(公告)日：2010-09-22

申请号：EP04751133.2

申请日：2004-05-03

Applicant: Bristol-Myers Squibb Company

Inventor： DYCKMAN, Alaric ,  DAS, Jagabandhu ,  LEFTHERIS, Katerina ,  LIU, Chunjian ,  ZHAO, Rulin ,  CHEN, Bang-Chi ,  WROBLESKI, Stephen, T.

IPC: C07D231/18 ,  A61K31/4155 ,  A61P37/00

CPC classification number: C07D231/14 ,  C07D231/12 ,  C07D231/40 ,  C07D401/12 ,  C07D413/12

Abstract: The present invention relates to compounds having the formula (I), and pharmaceutically-acceptable salts, prodrugs, solvates, isomers, and/or hydrates thereof, wherein Q is an optionally-substituted phenyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl ring; R2 is alkyl or an amino group as defined herein; and Z is optionally-substituted oxadiazolyl or -C(=O)NR6, wherein R6 is lower alkyl or cyclopropyl. The compounds are surprisingly advantageous in preparing medicaments for treating p38 kinase related conditions and/or in preparing medicaments for use in treating inflammatory disorders or conditions in a patient.

公开(公告)号：EP2046779A2

公开(公告)日：2009-04-15

申请号：EP07813363.4

申请日：2007-07-26

Applicant: Bristol-Myers Squibb Company

Inventor： CARTER, Percy, H. ,  DUNCIA, John, V. ,  MUDRYK, Boguslaw, M. ,  RANDAZZO, Michael, E. ,  XIAO, Zili ,  YANG, Michael, G. ,  ZHAO, Rulin

IPC: C07D403/12 ,  C07D207/273 ,  A61K31/4025

CPC classification number: C07D403/12 ,  C07D207/273 ,  C07D317/72

Abstract: The present invention provides a novel antagonist or partial agonists/antagonist of MCP-I receptor activity: N-((lR,2S,5R)-5-(tert-butylamino)-2- ((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-l- yl)cyclohexyl)acetamide, or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having an unexpected combination of desirable pharmacological characteristics. Crystalline forms of the present invention are also provided. 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 is also an objective of this invention. The present disclosure also provides a process for preparing compounds of Formula (I), including N-((lR,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6- (trifluoromethyl)quinazolin-4-ylamino)pyrrolidin-l-yl)cyclohexyl)acetamide: wherein R1, R8, R9, R10, and 'HET' are as described herein. Compounds that are useful intermediates of the process are also provided herein.

Abstract translation: N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S）-2-氧代-3 - （6-（三氟甲基）喹唑啉-4-基氨基）吡咯烷-1-基）环己基）乙酰胺，或其药学上可接受的盐，溶剂化物或前药，其具有理想药理学特性的意想不到的组合。 还提供了本发明的晶体形式。 含有其的药物组合物及其作为治疗炎性疾病，变应性疾病，自身免疫疾病，代谢疾病，癌症和/或心血管疾病的药物的方法也是本发明的目的。 本发明还提供了制备式（I）化合物的方法，其包括N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S）-2-氧代-3- （三氟甲基）喹唑啉-4-基氨基）吡咯烷-1-基）环己基）乙酰胺：其中R 1，R 8，R 9，R 10和'HET'如本文所述。 本文还提供了作为该方法的有用中间体的化合物。