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：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。