Benzodiazinone-pyridazinone and hydroxy-pyrazolyl compounds, cardiotonic compositions including the same, and their uses

摘要

PCT No. PCT/US86/02497 Sec. 371 Date Jul. 21, 1987 Sec. 102(e) Date Jul. 21, 1987 PCT Filed Nov. 20, 1986 PCT Pub. No. WO87/03201 PCT Pub. Date Jun. 4, 1987.Compounds of the formula <IMAGE> wherein: z is O or I; X is <IMAGE> a and b are 0, 1, or 2 and a+b=0, 1 or 2; R, R1, R3, R4, R5 and R6 are each independently hydrogen, alkyl or aralkyl; Rn is hydrogen, alkyl, aralkyl, acyl, carbalkoxy, carbamyl, carbalkoxyalkyl, hydroxyalkyl, alkoxyalkyl or amidino; R5 groups on vicinal carbon atoms may together form a carbon-carbon double bond when a or b=2; R groups on vicinal carbon atoms may together form a carbon-carbon double bond when Rn is hydrogen and z=1; R4 and R5 geminal groups may together form a spiro substituent, -(CH2)d-, where d is 2 to 5; R5 and R6 groups may together form a carbon-nitrogen double bond when R3 is hydrogen and a+b=1; R2 is hydrogen or -(CH2)y-Y where y is 1-3; Y is hydrogen, -O-R alpha , -S-R alpha or <IMAGE> R alpha is hydrogen, alkyl, cycloalkyl or acyl; R beta is hydrogen or alkyl; and R alpha and R beta together may form a 3-7 membered ring which may also contain 0-2 additional hetero atoms selected from N, O and S; provided that when a+b=0 and z is 1, then at least one of Rn, R, R1, R2, R3, R4, R5 and R6 is other than hydrogen; and pharmaceutically acceptable salts thereof, and methods for increasing cardiac contractility using said compounds.