| 摘要 |
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. |
