公开(公告)号：WO2005058884A2

公开(公告)日：2005-06-30

申请号：PCT/US2004041852

申请日：2004-12-14

Applicant: JAPAN TOBACCO INC ,  INABA TAKASHI ,  HAAS JULIA ,  SHIOZAKI MAKOTO ,  LITTMAN NICOLE M ,  YASUE KATSUTAKA ,  ANDREWS STEVEN W ,  SAKAI ATUSHI ,  FRYER ANDREW M ,  MATSUO TAKAFUMI ,  LAIRD ELLEN R ,  SUMA AKIRA ,  SHINOZAKI YUICHI ,  HORI YOSHIKAZU ,  IMAI HIROTO ,  NEGORO TAMOTSU

Inventor： INABA TAKASHI ,  HAAS JULIA ,  SHIOZAKI MAKOTO ,  LITTMAN NICOLE M ,  YASUE KATSUTAKA ,  ANDREWS STEVEN W ,  SAKAI ATUSHI ,  FRYER ANDREW M ,  MATSUO TAKAFUMI ,  LAIRD ELLEN R ,  SUMA AKIRA ,  SHINOZAKI YUICHI ,  HORI YOSHIKAZU ,  IMAI HIROTO ,  NEGORO TAMOTSU

IPC: A61K31/18 ,  A61K31/381 ,  A61K31/496 ,  C07C311/13 ,  C07C311/20 ,  C07C311/22 ,  C07C311/29 ,  C07C311/36 ,  C07C311/46 ,  C07D205/04 ,  C07D207/08 ,  C07D207/48 ,  C07D209/44 ,  C07D211/14 ,  C07D211/58 ,  C07D211/96 ,  C07D213/18 ,  C07D213/30 ,  C07D213/65 ,  C07D213/71 ,  C07D213/74 ,  C07D213/81 ,  C07D213/82 ,  C07D217/08 ,  C07D217/16 ,  C07D231/12 ,  C07D233/54 ,  C07D237/12 ,  C07D239/22 ,  C07D241/04 ,  C07D241/38 ,  C07D243/08 ,  C07D257/04 ,  C07D261/08 ,  C07D265/30 ,  C07D271/06 ,  C07D271/10 ,  C07D271/107 ,  C07D277/20 ,  C07D277/26 ,  C07D277/36 ,  C07D277/82 ,  C07D295/26 ,  C07D307/79 ,  C07D307/81 ,  C07D307/91 ,  C07D333/06 ,  C07D333/18 ,  C07D333/34 ,  C07D333/36 ,  C07D333/38 ,  C07D333/62 ,  C07D401/04 ,  C07D403/04 ,  C07D409/04 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D419/04 ,  C07D419/14 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04 ,  C07D513/06 ,  C07D409/00

CPC classification number: C07C311/29 ,  C07C311/13 ,  C07C311/20 ,  C07C311/22 ,  C07C311/46 ,  C07C2601/02 ,  C07C2601/14 ,  C07C2603/08 ,  C07C2603/18 ,  C07C2603/30 ,  C07D205/04 ,  C07D207/48 ,  C07D209/44 ,  C07D211/58 ,  C07D211/96 ,  C07D213/18 ,  C07D213/65 ,  C07D213/71 ,  C07D213/74 ,  C07D213/81 ,  C07D213/82 ,  C07D217/08 ,  C07D231/12 ,  C07D233/64 ,  C07D237/12 ,  C07D239/22 ,  C07D243/08 ,  C07D257/04 ,  C07D261/08 ,  C07D271/06 ,  C07D271/107 ,  C07D277/26 ,  C07D277/36 ,  C07D277/82 ,  C07D295/26 ,  C07D307/79 ,  C07D307/91 ,  C07D333/18 ,  C07D333/34 ,  C07D333/36 ,  C07D333/38 ,  C07D333/62 ,  C07D401/04 ,  C07D409/04 ,  C07D409/12 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D513/04

Abstract: The present invention provides a compound having aggrecanase inhibitory activity and MMP-13 inhibitory activity, and useful as a therapeutic agent for osteoarthritis, rheumatoid arthritis and the like, more specifically, a cyclopropane compound of formula (1): wherein R is - (CH2) m-X- (CH2)n-A etc., wherein m and n are the same or different and each is 0 to 6, X is a single bond, etc. and A is a substituted C3-14 hydrocarbon ring group, etc.; R and R are the same or different and each is a hydrogen atom, -(CH2)p-X1-(CH2)q-A , etc., wherein p and q are the same or different and each is 0 to 6, X1 is a single bond, etc. and A is an optionally substituted C3-14 hydrocarbon ring group, etc.; R is -C02R , etc., wherein R is a hydrogen atom, etc.; and R and R are the same or different and each is a hydrogen atom, - (CH2)m12-X12- (CH2)m12-R , etc., wherein m12 and m12 are the same or different and each is 0 to 6, X12 is a single bond, etc. and R is a hydrogen atom, etc.; or a prodrug thereof or a pharmaceutically acceptable salt thereof.

Abstract translation: 本发明提供具有聚集蛋白聚糖蛋白聚糖酶抑制活性和MMP-13抑制活性的化合物，可用作骨关节炎，类风湿性关节炎等的治疗剂，更具体地，可以使用式（1）的环丙烷化合物：其中R 1为 - （CH 2）m -X-（CH 2）n A 1等，其中m和n相同或不同，各自为0至6，X为单键等，A 1为取代的C 3 - 14烃环基等; R 2和R 3相同或不同，各自为氢原子， - （CH 2）p -X 1 - （CH 2）q A 2等，其中p和q相同或不同， 各自为0〜6，X1为单键等，A 2为任选取代的C3-14烃环基等。 R 4是-CO 2 R 9等，其中R 9是氢原子等; 和R 20和R 21相同或不同，各自为氢原子， - （CH 2）m 12 -X 12 - （CH 2）m 12 -R 30等，其中m12和m12相同 或不同，各为0〜6，X 12为单键等，R 30为氢原子等。 或其前药或其药学上可接受的盐。

公开(公告)号：WO2011025938A3

公开(公告)日：2011-05-05

申请号：PCT/US2010046952

申请日：2010-08-27

Applicant: ARRAY BIOPHARMA INC ,  GENENTECH INC ,  ALIAGAS IGNACIO ,  GRADL STEFAN ,  GUNZNER JANET ,  LEE WENDY ,  MATHIEU SIMON ,  RUDOLPH JOACHIM ,  WEN ZHAOYANG ,  ZHAO GUILING ,  BUCKMELTER ALEXANDRE J ,  GRINA JONAS ,  HANSEN JOSHUA D ,  LAIRD ELLEN ,  MORENO DAVID ,  REN LI ,  WENGLOWSKY STEVEN MARK

Inventor： ALIAGAS IGNACIO ,  GRADL STEFAN ,  GUNZNER JANET ,  LEE WENDY ,  MATHIEU SIMON ,  RUDOLPH JOACHIM ,  WEN ZHAOYANG ,  ZHAO GUILING ,  BUCKMELTER ALEXANDRE J ,  GRINA JONAS ,  HANSEN JOSHUA D ,  LAIRD ELLEN ,  MORENO DAVID ,  REN LI ,  WENGLOWSKY STEVEN MARK

IPC: C07D239/94 ,  A61K31/517 ,  A61K31/519 ,  A61P35/00 ,  C07D403/12 ,  C07D405/12 ,  C07D471/04

CPC classification number: C07D239/94 ,  C07D403/12 ,  C07D405/12 ,  C07D471/04

Abstract: Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract translation: 式I化合物可用于抑制Raf激酶。 公开了使用式I化合物及其立体异构体，互变异构体，前药和药学上可接受的盐在体外，原位和体内诊断，预防或治疗哺乳动物细胞中的这些病症或相关病理学病症的方法。

公开(公告)号：WO2009111278A2

公开(公告)日：2009-09-11

申请号：PCT/US2009035380

申请日：2009-02-27

Applicant: ARRAY BIOPHARMA INC ,  GENENTECH INC ,  AHRENDT KATERI A ,  BUCKMELTER ALEXANDRE J ,  GRINA JONAS ,  HANSEN JOSHUA D ,  LAIRD ELLEN R ,  MORENO DAVID ,  NEWHOUSE BRAD ,  REN LI ,  WENGLOWSKY STEVEN MARK ,  FENG BAINIAN ,  GUNZNER JANET ,  MALESKY KIM ,  MATHIEU SIMON ,  RUDOLPH JOACHIM ,  WEN ZHAOYANG ,  YOUNG WENDY B

Inventor： AHRENDT KATERI A ,  BUCKMELTER ALEXANDRE J ,  GRINA JONAS ,  HANSEN JOSHUA D ,  LAIRD ELLEN R ,  MORENO DAVID ,  NEWHOUSE BRAD ,  REN LI ,  WENGLOWSKY STEVEN MARK ,  FENG BAINIAN ,  GUNZNER JANET ,  MALESKY KIM ,  MATHIEU SIMON ,  RUDOLPH JOACHIM ,  WEN ZHAOYANG ,  YOUNG WENDY B

IPC: A61K31/4745

CPC classification number: C07D471/04 ,  C07C311/08

Abstract: Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract translation: 式I化合物可用于抑制Raf激酶。 公开了使用式I化合物和立体异构体，互变异构体，前药和其药学上可接受的盐在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：WO2007027855A3

公开(公告)日：2007-05-03

申请号：PCT/US2006033976

申请日：2006-08-31

Applicant: ARRAY BIOPHARMA INC ,  MIKNIS GREG ,  LYSSIKATOS JOSEPH P ,  LAIRD ELLEN ,  TARLTON EUGENE ,  BUCKMELTER ALEXANDRE J ,  REN LI ,  RAST BRYSON ,  SCHLACTER STEPHEN T ,  WENGLOWSKY STEVEN MARK

Inventor： MIKNIS GREG ,  LYSSIKATOS JOSEPH P ,  LAIRD ELLEN ,  TARLTON EUGENE ,  BUCKMELTER ALEXANDRE J ,  REN LI ,  RAST BRYSON ,  SCHLACTER STEPHEN T ,  WENGLOWSKY STEVEN MARK

IPC: C07D495/04 ,  A61K31/4355 ,  A61K31/4365 ,  A61P35/00 ,  C07D491/04

CPC classification number: C07D491/04 ,  C07D495/04

Abstract: Compounds of Formula I are useful for inhibiting Raf kinase and for treating disorders mediated thereby. Methods of using compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract translation: 式I化合物可用于抑制Raf激酶和治疗由其介导的病症。 使用式I化合物及其立体异构体，几何异构体，互变异构体，溶剂合物和药学上可接受的盐用于体外，原位和体内诊断，预防或治疗哺乳动物细胞中这些病症或相关病理学病症的方法是 披露。

公开(公告)号：WO2005058884A3

公开(公告)日：2005-06-30

申请号：PCT/US2004/041852

申请日：2004-12-14

Applicant: JAPAN TOBACCO INC. ,  INABA, Takashi ,  HAAS, Julia ,  SHIOZAKI, Makoto ,  LITTMAN, Nicole, M. ,  YASUE, Katsutaka ,  ANDREWS, Steven, W. ,  SAKAI, Atushi ,  FRYER, Andrew, M. ,  MATSUO, Takafumi ,  LAIRD, Ellen, R. ,  SUMA, Akira ,  SHINOZAKI, Yuichi ,  HORI, Yoshikazu ,  IMAI, Hiroto ,  NEGORO, Tamotsu

Inventor： INABA, Takashi ,  HAAS, Julia ,  SHIOZAKI, Makoto ,  LITTMAN, Nicole, M. ,  YASUE, Katsutaka ,  ANDREWS, Steven, W. ,  SAKAI, Atushi ,  FRYER, Andrew, M. ,  MATSUO, Takafumi ,  LAIRD, Ellen, R. ,  SUMA, Akira ,  SHINOZAKI, Yuichi ,  HORI, Yoshikazu ,  IMAI, Hiroto ,  NEGORO, Tamotsu

IPC: A61P19/02

Abstract: The present invention provides a compound having aggrecanase inhibitory activity and MMP-13 inhibitory activity, and useful as a therapeutic agent for osteoarthritis, rheumatoid arthritis and the like, more specifically, a cyclopropane compound of formula (1): wherein R 1 is - (CH 2 ) m -X- (CH 2 ) n -A 1 etc., wherein m and n are the same or different and each is 0 to 6, X is a single bond, etc. and A 1 is a substituted C 3-14 hydrocarbon ring group, etc.; R 2 and R 3 are the same or different and each is a hydrogen atom, -(CH 2 ) p -X 1 -(CH 2 ) q -A 2 , etc., wherein p and q are the same or different and each is 0 to 6, X 1 is a single bond, etc. and A 2 is an optionally substituted C 3-14 hydrocarbon ring group, etc.; R 4 is -C0 2 R 9 , etc., wherein R 9 is a hydrogen atom, etc.; and R 20 and R 21 are the same or different and each is a hydrogen atom, - (CH 2 ) m12- X 12- (CH 2 ) m12 -R 30 , etc., wherein m12 and m12 are the same or different and each is 0 to 6, X 12 is a single bond, etc. and R 30 is a hydrogen atom, etc.; or a prodrug thereof or a pharmaceutically acceptable salt thereof.

公开(公告)号：WO2013055645A1

公开(公告)日：2013-04-18

申请号：PCT/US2012/059282

申请日：2012-10-09

Applicant: ARRAY BIOPHARMA INC. ,  BOYS, Mark Laurence ,  BURGESS, Laurence E. ,  EARY, C. Todd ,  GRONEBERG, Robert ,  HACHE, Bruno P. ,  HARVEY, Darren ,  HICKEN, Erik James ,  KRASER, Christopher F. ,  LAIRD, Ellen ,  MORENO, David A. ,  MUNSON, Mark C. ,  REN, Li ,  ROBINSON, John E. ,  SCHLACHTER, Stephen T.

Inventor： BOYS, Mark Laurence ,  BURGESS, Laurence E. ,  EARY, C. Todd ,  GRONEBERG, Robert ,  HACHE, Bruno P. ,  HARVEY, Darren ,  HICKEN, Erik James ,  KRASER, Christopher F. ,  LAIRD, Ellen ,  MORENO, David A. ,  MUNSON, Mark C. ,  REN, Li ,  ROBINSON, John E. ,  SCHLACHTER, Stephen T.

IPC: C07D487/04 ,  A61K31/519 ,  A61P29/00 ,  A61P37/00

CPC classification number: C07D487/04

Abstract: Compounds of Formula I: and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X 1 and X 2 have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.

Abstract translation: R 1，R 2，R 3，R 4，R 5，R 6，X 1和X 2具有本说明书中给出的含义的式I化合物及其立体异构体及其药学上可接受的盐和溶剂合物是一种或多种JAK激酶的抑制剂，并且是有用的 治疗自身免疫性疾病，炎症性疾病，移植器官，组织和细胞排斥，以及血液系统疾病和恶性肿瘤及其并发症。

公开(公告)号：WO2011130146A1

公开(公告)日：2011-10-20

申请号：PCT/US2011/031896

申请日：2011-04-11

Applicant: ARRAY BIOPHARMA INC. ,  BOYS, Mark Laurence ,  BURGESS, Laurence, E. ,  GRONEBERG, Robert, D. ,  HARVEY, Darren, M. ,  HUANG, Lily ,  KERCHER, Timothy ,  KRASER, Christopher, F. ,  LAIRD, Ellen ,  TARLTON, Eugene ,  ZHAO, Qian

Inventor： BOYS, Mark Laurence ,  BURGESS, Laurence, E. ,  GRONEBERG, Robert, D. ,  HARVEY, Darren, M. ,  HUANG, Lily ,  KERCHER, Timothy ,  KRASER, Christopher, F. ,  LAIRD, Ellen ,  TARLTON, Eugene ,  ZHAO, Qian

IPC: C07D487/04 ,  A61P29/00 ,  A61P37/00 ,  A61K31/519

CPC classification number: C07D487/04 ,  C07D498/04

Abstract: Compounds of Formula I: (Formula should be inserted here) and stereoisomers and pharmaceutically acceptable salts and solvates thereof in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X 1 and X 2 have the meanings given in the specification, are inhibitors of one or more JAK kinases and are useful in the treatment of autoimmune diseases, inflammatory diseases, rejection of transplanted organs, tissues and cells, as well as hematologic disorders and malignancies and their co-morbidities.

Abstract translation: 式I化合物（此处应该插入式）及其其中R 1，R 2，R 3，R 4，R 5，R 6，R 7，X 1和X 2具有本说明书中给出的含义的立体异构体及其药学上可接受的盐和溶剂化物是抑制剂 的一种或多种JAK激酶，并且可用于治疗自身免疫性疾病，炎性疾病，移植器官，组织和细胞的排斥，以及血液系统疾病和恶性肿瘤及其并发症。

公开(公告)号：WO2011025940A1

公开(公告)日：2011-03-03

申请号：PCT/US2010/046955

申请日：2010-08-27

Applicant: ARRAY BIOPHARMA INC. ,  GENENTECH, INC. ,  ALIAGAS, Ignacio ,  GRADL, Stefan ,  GUNZNER, Janet ,  MATHIEU, Simon ,  PULK, Rebecca ,  RUDOLPH, Joachim ,  WEN, Zhaoyang ,  GRINA, Jonas ,  HANSEN, Joshua D. ,  LAIRD, Ellen ,  MORENO, David ,  REN, Li ,  WENGLOWSKY, Steven Mark

Inventor： ALIAGAS, Ignacio ,  GRADL, Stefan ,  GUNZNER, Janet ,  MATHIEU, Simon ,  PULK, Rebecca ,  RUDOLPH, Joachim ,  WEN, Zhaoyang ,  GRINA, Jonas ,  HANSEN, Joshua D. ,  LAIRD, Ellen ,  MORENO, David ,  REN, Li ,  WENGLOWSKY, Steven Mark

IPC: C07D487/04 ,  C07D495/04 ,  C07D513/04 ,  A61K31/38 ,  A61P35/00

CPC classification number: C07D487/04 ,  C07D495/04 ,  C07D513/04

Abstract: Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro , in situ , and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract translation: 式I化合物可用于抑制Raf激酶。 公开了使用式I化合物和立体异构体，互变异构体，前药和其药学上可接受的盐在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：WO2009111280A1

公开(公告)日：2009-09-11

申请号：PCT/US2009/035383

申请日：2009-02-27

Applicant: ARRAY BIOPHARMA INC. ,  GENENTECH, INC. ,  AHRENDT, Kateri A. ,  BUCKMELTER, Alexandre J. ,  GRINA, Jonas ,  HANSEN, Joshua D. ,  LAIRD, Ellen R. ,  NEWHOUSE, Brad ,  REN, Li ,  WENGLOWSKY, Steven Mark ,  FENG, Bainian ,  MALESKY, Kim ,  MATHIEU, Simon ,  RUDOLPH, Joachim ,  WEN, Zhaoyang ,  YOUNG, Wendy B. ,  MORENO, David, A.

Inventor： AHRENDT, Kateri A. ,  BUCKMELTER, Alexandre J. ,  GRINA, Jonas ,  HANSEN, Joshua D. ,  LAIRD, Ellen R. ,  NEWHOUSE, Brad ,  REN, Li ,  WENGLOWSKY, Steven Mark ,  FENG, Bainian ,  MALESKY, Kim ,  MATHIEU, Simon ,  RUDOLPH, Joachim ,  WEN, Zhaoyang ,  YOUNG, Wendy B. ,  MORENO, David, A.

IPC: C07C311/08 ,  C07D213/75 ,  A61K31/44 ,  A61P35/00

CPC classification number: C07D213/75 ,  C07C311/48 ,  C07D213/80 ,  C07D213/82 ,  C07D213/85 ,  C07D401/04 ,  C07D401/06 ,  C07D405/04 ,  C07D417/04

Abstract: Compounds of Formula (I) are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro , in situ , and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract translation: 式（I）的化合物可用于抑制Raf激酶。 公开了使用式I化合物及其立体异构体及其药学上可接受的盐在体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理状况中的这种病症的方法。

公开(公告)号：WO2002072579A1

公开(公告)日：2002-09-19

申请号：PCT/IB2002/000424

申请日：2002-02-08

Applicant: PFIZER PRODUCTS INC. ,  DOMBROSKI, Mark, Anthony ,  DUPLANTIER, Allen, Jacob ,  LAIRD, Ellen, Ruth ,  LETAVIC, Michael, Anthony ,  MCCLURE, Kim, Francis

Inventor： DOMBROSKI, Mark, Anthony ,  DUPLANTIER, Allen, Jacob ,  LAIRD, Ellen, Ruth ,  LETAVIC, Michael, Anthony ,  MCCLURE, Kim, Francis

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: The present invention relates to novel triazolo-pyridines of the formula I wherein Het is an optionally substituted 5-membered heterocycle containing one to two heteroatoms selected from nitrogen, sulfur and oxygen wherein at least one of said heteroatoms atoms must be nitrogen; R 2 is selected from the group consisting of hydrogen, (C 1 -C 6 ) alkyl or other suitable substituents; R 3 is selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl or other suitable substituents; s is an integer from 0-5; to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the present invention are potent inhibitors of MAP kinases, preferably p38 kinase. They are useful in the treatment of inflammation, osteoarthritis, rheumatoid arthritis, cancer, repurfusion or ischemia in stroke or heart attack, autoimmune diseases and other disorders.

Abstract translation: 本发明涉及式I的新型三唑并 - 吡啶，其中Het是含有一至二个选自氮，硫和氧的杂原子的任选取代的5元杂环，其中至少一个所述杂原子必须是氮; R 2选自氢，（C 1 -C 6）烷基或其它合适的取代基; R 3选自氢，（C 1 -C 6）烷基或其它合适的取代基; s是0-5的整数; 制备中间体，含有它们的药物组合物及其药物用途。 本发明的化合物是MAP激酶的有效抑制剂，优选p38激酶。 它们可用于治疗炎症，骨关节炎，类风湿性关节炎，癌症，中风或心脏病发作中的再灌注或缺血，自身免疫性疾病和其他疾病。