Title:
肝細胞増殖因子受容体自己リン酸化を阻害するキノリン誘導体およびキナゾリン誘導体並びにそれらを含有する医薬組成物
Document Type and Number:
Japanese Patent JP4342935
Kind Code:
B2
Abstract:
4-Phenoxy or phenylthio-quinoline and quinazoline derivatives (I) are new. 4-Phenoxy or phenylthio-quinoline and quinazoline derivatives of formula (I) and their salts and solvates are new. [Image] X : CH or N; Z, L : O or S; M : C(R 1 0)R 1 1 or NR 1 2; R 1 0, R 1 1H, 1-4C alkyl or 1-4C alkoxy; R 1 2H or 1-4C alkyl; R 1-R 3H, OH, halo, NO 2, Q or A, 2-6C alkenyl, 2-6C alkynyl or O-A all optionally substituted by OH, halo, O-A, COO-A, Q or Cyc (optionally substituted by A, 1-6C hydroxyalkyl or O-A); Q : amino (optionally substituted by A, 1-6C hydroxyalkyl or O-A); A : 1-6C alkyl; Cyc : optionally unsaturated 3-8 membered carbocyclyl or heterocyclyl; R 5-R 8H, halo, A or O-A; R 9A (optionally substituted by R 1 4, T-R 1 5 or N(R 1 6)R 1 7), N(R 1 8)R 1 9 or Cyc 1; T : O, S or NH; R 1 4Cyc 1; R 1 5-R 1 7A or Cyc 1; Cyc 1Cyc (optionally substituted by A, O-A, halo, NO 2, CF 3, COO-A, CN, 1-6C cyanoalkyl, S-A, phenoxy, acetyl or 5 or 6 membered optionally unsaturated heterocyclyl or 2 alkyl substituents together form alkylene; R 1 8, R 1 9H, A (optionally substituted by O-A, S-A or Cyc 2) or Cyc 2; Cyc 2Cyc 1 or Cyc 1 fused to another Cyc 1 group; and provided that: (a) when X is CH, then Z and L is O, and M is NH, and R 1, R 4-R 8 is H; and (b) R 2 and R 3 is OMe then R 9 is not phenyl, OEt or pyridin-2-yl. ACTIVITY : Cytostatic. In tests on nude mice implanted with MKN45 cells a compound of formula (Ia) at 30 mg/kg b.i.d orally for 5 days reduced tumor growth by 81%. MECHANISM OF ACTION : HGF-Inhibitor.
Inventors:
Yasunari Fujiwara
Senda Senbun
Nishi Toba Go
Ritsushi Osawa
Atsushi Miwa
Nakamura Kazuhide
Senda Senbun
Nishi Toba Go
Ritsushi Osawa
Atsushi Miwa
Nakamura Kazuhide
Application Number:
JP2003507066A
Publication Date:
October 14, 2009
Filing Date:
June 21, 2002
Export Citation:
Assignee:
Kyowa Hakko Kirin Co., Ltd.
International Classes:
C07D215/22; A61K31/47; A61K31/4704; A61K31/4709; A61K31/496; A61K31/517; A61K31/5377; A61K31/541; A61K31/551; A61P35/00; A61P43/00; C07D215/233; C07D215/40; C07D239/88; C07D401/12; C07D405/12; C07D409/12; C07D413/12
Foreign References:
| WO1997017329A1 | ||||
| WO2000043366A1 | ||||
| WO2001047890A1 |
Attorney, Agent or Firm:
Kenji Yoshitake
Yukitaka Nakamura
Konno Akio
Noritaka Yokota
Yukitaka Nakamura
Konno Akio
Noritaka Yokota