Benzamidine derivatives substituted by cyclic amino acid or...

C - Chemistry – Metallurgy – 07 – D

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C07D 401/12 (2006.01) A61K 31/415 (2006.01) A61K 31/44 (2006.01) C07D 401/14 (2006.01) C07D 417/14 (2006.01)

Patent

CA 2264521

This invention is directed to benzamidine derivatives substituted by cyclic amico acid and cyclic hydroxy acid derivatives which are useful as anti- coagulants as represented by formulae (I), (II), (III), (IV), (V), (VI), (VII) wherein: A is -C(R8)= or -N=; Z1 and Z2 are independently -O-, -N(R9)-, -S-, - S(O)-, -S(O)2-, or -OCH2-; R2 is -C(NH)NH2, -C(NH)N(H)OR9, -C(NH)N(H)C(O)OR12, -C(NH)N(H)C(O)R9, -C(NH)N(H)S(O)2R12, or -C(NH)N(H)C(O)N(H)R9; R7 is -N(R9)- (C(R9)(R10))n-R13 (where n is 0 to 4), -O-(C(R9)(R10))n-R13 (where n is 0 to 4), or -N(R14)R15; R1 and R3 - R6 are as defined in the description. This invention is also directed to pharmaceutical compositions containing the compounds of the invention, and methods of using the compounds to treat disease-states characterized by thrombotic activity.

Cette invention porte sur des dérivés benzamidine, substitués par des dérivés d'acides aminés cycliques et d'hydroxyacides cycliques, utiles en tant qu'anticoagulants et répondant aux formules (I) à (VII) dans lesquelles A représente -C(R?8¿)= ou -N=, Z?1¿ et Z?2¿ représentent indépendamment -O-, -N(R?9¿)-, -S-, -S(O)-, -S(O)¿2?-, ou -OCH¿2?-, R?2¿ représente -C(NH)NH¿2?, -C(NH)N(H)OR?9¿, -C(NH)N(H)C(O)OR?12¿, -C(NH)N(H)C(O)R?9¿, -C(NH)N(H)S(O)¿2?R?12¿, ou -C(NH)N(H)C(O)N(H)R?9¿, R?7¿ représente -N(R?9¿)-(C(R?9¿)(R?10¿))¿n?-R?13¿ (où n vaut 0 à 4), -O-(C(R?9¿)(R?10¿))¿n?-R?13¿ (où n vaut 0 à 4), ou -N(R?14¿)R?15¿, R?1¿ et R?3¿ à R?6¿ possédant les notations données dans la description. Cette invention porte étalement sur des compositions pharmaceutiques contenant ces composés, ainsi que sur des procédés d'utilisation de ceux-ci pour traiter des états pathologiques caractérisés par une activité thrombotique.

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