公开(公告)号：WO2009111279A1

公开(公告)日：2009-09-11

申请号：PCT/US2009/035381

申请日：2009-02-27

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

IPC: C07D471/04 ,  C07C311/08 ,  A61K31/437 ,  A61P13/12 ,  A61P35/00

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：WO2009111277A9

公开(公告)日：2009-09-11

申请号：PCT/US2009/035379

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, M. ,  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, M. ,  FENG, Bainian ,  MALESKY, Kim ,  MATHIEU, Simon ,  RUDOLPH, Joachim ,  WEN, Zhaoyang ,  YOUNG, Wendy, B. ,  MORENO, David, A.

IPC: C07D471/04 ,  C07C311/08 ,  A61K31/437 ,  A61P35/00 ,  A61P13/12

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.

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：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：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：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：WO2009111278A3

公开(公告)日：2009-09-11

申请号：PCT/US2009/035380

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: C07D471/04 ,  C07C311/08 ,  A61P35/00 ,  A61K31/437

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.

公开(公告)号：WO2005058808A1

公开(公告)日：2005-06-30

申请号：PCT/US2004/041851

申请日：2004-12-14

Applicant: JAPAN TOBACCO INC. ,  FRYER, Andrew, M. ,  SHIOZAKI, Makoto ,  LITTMANN, Nicole, M. ,  INABA, Takashi ,  ANDREWS, Steven, W. ,  YASUE, Katsutaka ,  LAIRD, Ellen, R. ,  YOKOTA, Masahiro ,  HAAS, Julia ,  IMAI, Hiroto ,  MAEDA, Katsuya ,  SHINOZAKI, Yuichi ,  HORI, Yoshikazu

Inventor： FRYER, Andrew, M. ,  SHIOZAKI, Makoto ,  LITTMANN, Nicole, M. ,  INABA, Takashi ,  ANDREWS, Steven, W. ,  YASUE, Katsutaka ,  LAIRD, Ellen, R. ,  YOKOTA, Masahiro ,  HAAS, Julia ,  IMAI, Hiroto ,  MAEDA, Katsuya ,  SHINOZAKI, Yuichi ,  HORI, Yoshikazu

IPC: C07C311/20

CPC classification number: C07C311/20 ,  C07C311/51 ,  C07C381/06 ,  C07C381/08 ,  C07C2601/02 ,  C07C2601/14 ,  C07D207/34 ,  C07D209/52 ,  C07D211/46 ,  C07D211/60 ,  C07D213/42 ,  C07D213/65 ,  C07D213/74 ,  C07D213/79 ,  C07D213/80 ,  C07D231/14 ,  C07D231/20 ,  C07D233/90 ,  C07D235/14 ,  C07D249/10 ,  C07D257/04 ,  C07D257/06 ,  C07D261/18 ,  C07D271/07 ,  C07D277/56 ,  C07D285/06 ,  C07D285/08 ,  C07D295/088 ,  C07D295/13 ,  C07D295/15 ,  C07D295/185 ,  C07D307/68 ,  C07D333/18 ,  C07D333/34 ,  C07D409/12 ,  C07D413/04 ,  C07D413/12

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 N-substituted-N-sulfonylaminocyclopropane compound of formula (1) : wherein R 1 is -W-A 1 -W 1 -A 2 , W is (CH 2 ) m -X-(CH 2 )n-, wherein W 1 is -(CH 2 ) m1 -X 1 -(CH 2 ) n1 -, m, m1, n and n1 are the same or different and each is 0 to 6, X and X1 are the same or different and each is a single bond, etc., A1 is an optionally substituted C 3-14 hydrocarbon ring group, etc. and A 2 is a substituted C 3-14 hydrocarbon ring group etc.; R 2 is -(CH 2 ) r -CO-R 8 , etc., wherein r is 0 to 6 and R 8 is a C 1-6 alkoxy group, etc.; R 3 and R 4 are the same or different and each is a hydrogen atom, a C 1-6 alkyl group, etc.; and R 5 is -CO 2 R 21 , etc.; R 30 and R 31 are the same or different and each 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，更具体而言，可以使用式（1）所示的N-取代-N-磺酰氨基环丙烷化合物： 其中R 1是-WA 1 -W 1 -A 2，W是（CH 2）m X-（CH 2）n - ，其中W 1是 - （CH 2）m1-X 1 - （CH 2）n - ，m ，m1，n和n1相同或不同，分别为0〜6，X和X1相同或不同，均为单键等，A1为任选取代的C3-14烃环基等。 A 2是取代的C 3-14烃环基等。 R 2为 - （CH 2）r -CO-R 8等，其中r为0至6，R 8为C 1-6烷氧基等; R 3和R 4相同或不同，各自为氢原子，C 1-6烷基等; R 5为-CO 2 R 21等; R 30和R 31相同或不同，各自为氢原子等; 或其前药或其药学上可接受的盐。

公开(公告)号：WO2009111277A1

公开(公告)日：2009-09-11

申请号：PCT/US2009035379

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 M ,  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 M ,  FENG BAINIAN ,  MALESKY KIM ,  MATHIEU SIMON ,  RUDOLPH JOACHIM ,  WEN ZHAOYANG ,  YOUNG WENDY B ,  MORENO DAVID A

IPC: C07D471/04 ,  A61K31/437 ,  A61P13/12 ,  A61P35/00 ,  C07C311/08

CPC classification number: C07D471/04 ,  C07C311/48

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。