Title:
カルボキサミジン誘導体及び血管疾患の治療におけるそれらの使用
Document Type and Number:
Japanese Patent JP2005514418
Kind Code:
A
Abstract:
Carboxamidine derivatives (I)-(III) are used for treating or preventing vascular diseases. Carboxamidine derivatives of formula (I)-(III) or their salts are used for treating or preventing vascular diseases. R 1>, R 2>1-6C alkyl (optionally substituted by phenyl), or H, or NR 1>R 2>T; T : 5-7 membered saturated heterocyclyl optionally containing further N or O heteroatoms (optionally substituted by 1 or 2 OH, oxo or benzyl); A : phenyl (optionally substituted by 1 or 2 1-4C alkyl, 1-4C haloalkyl, NO 2or CN), or 5- or 6-membered heteroaryl containing at least one N, O or S and optionally having an N-oxide structure on the N heteroatom; n : 0-2; z : 0 or 1; X : halo or NR 4>R 5>; R 3>-R 5>H or 1-6C alkyl; Y : H, OH, halo or 1-22C acyloxy, and X 1>O, provided that: (1) when R 4>and R 5>are simultaneously H, then Y is not OH; (2) when Y is not halo, then NR 1>R 2>is T, A is N-containing heteroaryl optionally having a N-oxide structure on the N heteroatom and z is 1; (3) when X is halo and Y is hydroxy or acyloxy, then NR 1>R 1>is T; (4) when R 1>and R 2>are 1-6C alkyl (optionally substituted by phenyl), H, and NR 1>R 2>is 5-7 membered saturated heterocyclyl containing N or O, then A is heteroaryl containing O, S or N-containing heteroaryl having a N-oxide structure on the N heteroatom; and (5) when A is phenyl (optionally substituted by 1 or 2 1-4C alkyl, 1-4C haloalkyl, NO 2or halo), or 5- or 6-membered N-containing heteroaryl, then NR 1>R 2>is T. N.B: The formulae (I)-(III) are not shown in the specification. Independent claims are included for the following: (1) new compounds (I), with the further proviso that when Y is H and/or X is NR 4>R 5>, then NR 1>R 2>is T or A is N-containing heteroaryl optionally having an N-oxide structure on the N heteroatom; (2) new compounds (II), with the further proviso that when Y is not halo, then NR 1>R 2>is T and A is N-containing heteroaryl optionally having a N-oxide structure on the N heteroatom, and (3) new compounds (III). ACTIVITY : Vasotropic; Cardiovascular-Gen. In a wounding migration assay in an endothelial cell culture using wounded monolayers of human umbilical vein endothelial cells (HUVEC), results showed that N-[2-chloro-3-(1-piperidinyl)propoxy]-3-nitro-benzimidoyl-chloride hydrochloride gave number of cells/mm 2>at 24 hours of 60, compared to 30 for 5,6-dihydro-5-(1-piperidinyl)-methyl-3-(3-pyridyl)-4H-1,2,4-oxadiazine used as a control. MECHANISM OF ACTION : None given.
Inventors:
Jagesnay, Charkai Jita
Marbanos, Ede
Eulogdy, Larslow
Telezone Magdorna, Batzone
Danesh, Laslaw
Marbanos, Ede
Eulogdy, Larslow
Telezone Magdorna, Batzone
Danesh, Laslaw
Application Number:
JP2003557981A
Publication Date:
May 19, 2005
Filing Date:
January 10, 2003
Export Citation:
Assignee:
Biorex Kuta To S Fayrestee Arte.
International Classes:
A61K31/4406; A61K31/45; A61K31/4545; A61K31/5375; A61K31/5395; A61P9/00; C07C259/02; C07D213/89; C07D295/088; C07D295/22; C07D295/08; C07D413/04; C07D413/14; (IPC1-7): C07D213/89; A61K31/45; A61K31/4545; A61K31/5375; A61K31/5395; A61P9/00; C07D295/08; C07D295/22; C07D413/04; C07D413/14
Attorney, Agent or Firm:
Atsushi Aoki
Takashi Ishida
Tetsuji Koga
Yoichi Watanabe
Masaya Nishiyama
Takashi Ishida
Tetsuji Koga
Yoichi Watanabe
Masaya Nishiyama