Substituted heterocycles as angiotensin ii antagonists

C - Chemistry – Metallurgy – 07 – D

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C07D 403/12 (2006.01) A61K 31/505 (2006.01) C07D 239/94 (2006.01) C07D 405/12 (2006.01) C07D 409/12 (2006.01) C07D 487/04 (2006.01) C07D 491/048 (2006.01) C07D 495/04 (2006.01)

Patent

CA 2121816

2121816 9308170 PCTABS00021 There are disclosed compounds of general formula (I), wherein A is O, S, NR6, -CR7=CR8-; Z is O, S, NR6, -CR7=CR8-; X is H, NR9R10, OR11, CN, F, Cl, I, Br, perfluoroalkyl, alkyl, alkyl-OH, alkoxyalkyl, -(CH2)nCO2R11, -(CH2)nCONR9R10; with the proviso that when Z=-CR7=CR8- then Y is NR13, NR13CR12R14, CR12R14NR13; with the proviso that when Z=O, S, NR6 then Y is NR13CR12R14; R1 is 5-tetrazolyl, CO2R11, SO3H, NHSO2CH3, NHSO2CF3; R2,R3, R4, R7, R8 is H, alkyl, alkoxyalkyl, alkyl-OH, perfluoroalkyl, aralkyl, CN, NO2, SO2R13, -(CH2)nCO2R11, -(CH2)nCONR9R10, OR11, F, Cl, Br, I, NR9R10; with the proviso that when A=-CR7=CR8- then R5 is alkyl, alkoxyalkyl, alkyl-OH, perfluoroalkyl, aralkyl, H, -CN, NO2, SO2R13, -(CH2)nCO2R11, -(CH2)nCONR9R10, -OH, OR11, F, Cl, Br, I, NR9R10; with the proviso that when A=O, S, NR6 then R5 is alkyl, alkoxyalkyl, alkyl-OH, perfluoroalkyl, aralkyl, H, -CN, NO2, SO2R13, -(CH2)nCO2R11, -(CH2)nCONR9R10; R6 is H, alkyl, aralkyl; R9, R10 is H, alkyl, alkoxyalkyl, alkyl-OH, perfluoroalkyl, aralkyl; R11 is H, alkyl, aralkyl, alkoxyalkyl; R12, R14 is H, alkyl, alkoxy, alkoxyalkyl, alkyl-OH, perfluoroalkyl, aralkyl, CN, NO2, SO2R13, -(CH2)nCO2R11, -(CH2)nCONR9R10; R13 is H, OR11, alkyl, perfluoroalkyl, aralkyl, -(CH2)nCO2R11, -(CH2)nCONR9R10; n is 0, 1, 2 or 3; wherein alkyl is defined as 1-8 carbons, branched or straight chain; perfluoroalkyl is defined as 1-6 carbons; aralkyl is defined as 7-12 carbons or 7-12 carbons substituted with fluorine, bromine or chlorine and the pharmaceutically acceptable salts, solvates and hydrates thereof, which by virtue of their ability to antagonize angiotensin II are useful for the treatment of hypertension and congestive heart failure. The compounds are also useful for reducing lipid levels in the blood plasma and are thus useful for treating hyperlipidemia and hypercholesterolemia. Also disclosed are processes for the production of said compounds and pharmaceutical compositions containing said compounds.

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