| 摘要 |
This invention is directed to benzamidine derivatives which are useful as anticoagulants. 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. Accordingly, in one aspect, this invention provides compounds selected from the group consisting of formulae (I), (II), (III), (IV), (V), (VI), (VII), and (VIII), wherein: A is -C(R11)= or -N=; Z1 and Z2 are independently -O-, -N(R8)-, -S-, or -OCH2-; R1 and R3 are independently hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro, -N(R8)R9, -C(O)OR8, -C(O)N(R8)CH2C(O)N(R8)R9, N(R8)C(O)N(R8)R9, -N(R8)C(O)R8, -N(R8)S(O)2R12, or N(R8)C(O)N(R8)CH2C(O)N(R8)R9; R2 is hydrogen; halo; alkyl; haloalkoxy; -OR8; C(O)OR8; -C(O)N(R8)R9; -N(R8)R9; -C(O)N(R8)(CH2)mC(O)OR8 (where m is 0 to 3); N(R8)(CH2)nC(O)OR8 (where n is 1 to 3); -N((CH2)nN(R8)R9)(CH2)nC(O)OR8 (where each n is 1 to 3); -O(CH2)nC(O)N(R8)R9 (where n is 1 to 3); -O(CH2)pC(O)OR8 (where p is 1 to 6); -N(R8)(CH2)nC(O)N(R8)(CH2)nC(O)OR8 (where each n is independently 1 to 3); morpholin-4-yl; 3-tetrahydrofuranoxyl; etc.; R4 and R7 are independently hydrogen, halo, alkyl, nitro, -OR8, -C(O)OR8, -C(O)N(R8)R9, N(R8)R9, -N(H)C(O)R8, or -N(H)S(O)2R12; R5 is -C(NH)NH2, -C(NH)N(H)OR8, C(NH)N(H)C(O)OR12, -C(NH)N(H)S(O)2R12, -C(NH)N(H)C(O)N(R8)R9, or C(NH)N(H)C(O)R8; R6 is halo, alkyl, haloalkyl, haloalkoxy, nitro, amino, ureido, guanidino, -OR8, -C(NH)NH2, -C(NH)NHOH, -C(O)R10, -(CH2)mC(O)N(R8)R9 (where m is 0 to 3), -CH(OH)C(O)N(R8)R9, -(CH2)mN(R8)R9 (where m is 0 to 3), (CH2)mC(O)OR8 (where m is 0 to 3), -N(H)C(O)R8, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl); each R8 and R9 is independently hydrogen alkyl, aryl, or aralkyl; R10 is hydrogen, alkyl, aryl, aralkyl, 1-pyrrolidinyl, 4-morpolinyl, 4-piperazinyl, 4-(N-methyl)piperazinyl, or piperidin-1-yl; R11 is hydrogen, alkyl or halo; and R12 is alkyl, aryl or aralkyl; or a pharmaceutically acceptable salt thereof.
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