Patent ID: 6495533
Filing Date: 2002-12-17
Classification: A61K,A61P,C07F

Abstract:
Phosphoric acid derivatives of the formula (I) wherein R1 is (1) C1-20 alkyl, (2) C1-20 alkyl which one carbon atom is replaced by an oxygen atom, a sulfur atom, â€”S(O)â€” or S(O)2â€” (with the proviso that, a carbon atom which attached with E is not replaced by these groups), (3) C2-20 alkenyl, (4) C2-20 alkynyl, (5) Cyc1 (wherein Cyc1 is C5-15 membered mono-, bi- or tricarbocyclic ring or 5-15 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom), (6) C1-20 alkyl, C2-20 alkenyl or C2-20 alkynyl substituted by Cyc1 (wherein all symbols are the same meaning as hereinbefore defined), Cyc1 may be substituted by one or more substituents selected from the following (a)-(r): (a) C1-8 alkyl, (b) C1-8 alkoxy, (c) nitro, (d) halogen atom, (e) trfluoromethyl, (f) trifluoromethyloxy, (g) hydroxy, (h) cyano, (i) NR10R11 (wherein R10 and R11 each, independently, is a hydrogen atom, C1-8 alkyl, C1-8 hydroxyalkyl, C2-5 acyl or C1-8 alkylsulfonyl), (j) COOR20 (wherein R20 is a hydrogen atom or C1-4 alkyl), (k) CONR30R31 (wherein R30 and R31 each, independently, is a hydrogen atom or C1-4 alkyl), (l) â€”S(O)mâ€”R32 (wherein m is 0, 1 or 2, R32 is 1-8 alkyl or C1-8 alkyl substituted by C1-8 alkoxy, COOR20 (wherein R20 is the same meaning as hereinbefore defined) or CONR30R31 (wherein R30 and R31 each, independently, is a hydrogen atom or C1-4 alkyl)), (m) â€”Oâ€”Cyc2 (wherein Cyc2 is C3-8 cycloalkyl or phenyl), (n) â€”Sâ€”Cyc2 (wherein Cyc2 is the same meaning as hereinbefore defined), (o) C1-8alkyl substituted by one substituent selected from C1-8 alkoxy, COOR20 (wherein R20  is the same meaning as hereinbefore defined), CONR30R31 (wherein R30 and R31 are the same meaning as hereinbefore defined), phenyl or hydroxy, (p) C1-8alkoxy substituted by one substituent selected from C1-8 alkoxy, COOR20 (wherein R20 is the same meaning as hereinbefore defined), CONR30R31 (wherein R30 and R31 are the same meaning as hereinbefore defined), phenyl or hydroxy. (q) C3-15 membered mono-, bi- or tricarbocyclic ring, (r) 5-15 membered mono-, bi- or tricyclic hetero ring containing 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom, E is (a) â€”NR7COâ€”, (b) â€”NR7SO2â€”, (c) â€”NR7CONR8â€”, (d) â€”NR7COOâ€”, (e) â€”CONR7â€”, (f) â€”NR7CSâ€”, (g) â€”NR7CSNR8â€”, (h) â€”NR7CSâ€”Oâ€”, (i) â€”CSNR7â€” or (j) â€”NR7â€” (wherein R7 and R8 each, independently, is a hydrogen or C1-4 alkyl), A ring is C3-15 membered mono-, bi- or tricarbocyclic ring or 5-15 membered mono-, bi- or trycyclic hetero ring containing 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom, R2 is the same meaning as hereinbefore defined substituents (a)-(r), R3 and R4 i) each, independently, is a hydrogen atom, C1-8 alkyl, C1-8 alkoxy, C1-8 hydroxyalkyl or phenyl, or ii) taken together represents C2-6 alkylene, or iii) one of R3 or R4, taken together with R2, represent C1-5 alkylene, and the other one is a hydrogen atom, C1-8alkyl or C1-8alkoxy, n is an integer of 0, 1 or more, R5 and R6 each, independently, is a hydrogen atom, C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl, C1-4 alkyl substituted by cyano or C1-4 alkyl substituted by trihalomethyl, Y and Z each, independently, is an oxygen atom or a sulfur atom. with the proviso that,(1) when n is 2 or more integer, then R2 is the same or different, (2) when R1 and R2 contains a sulfur atom, then Y is an oxygen atom, and R1 and R2 do not contains a sulfur atom at the same time or a non-toxic salt thereof.