BENZODIAZINONE-PYRIDAZINONE AND HYDROXY-PYRAZOLYL COMPOUNDS, CARDIOTONIC COMPOSITIONS INCLUDING THE SAME, AND THEIR USES

摘要

A method for increasing cardiotonic contractility in humans or other animals using a class of benzodiazinonepyridazinone and hydroxy-pyrazolyl compounds and pharmaceutical compositions including the same. The compounds of the present invention include: <IMG> where x is 0 or 1; X is <IMG> where a and b are 0, 1 or 2 and a + b = 1 or 2; R, R1, R3, R4, R5, and R6 are each independently hydrogen, C1 to C7 alkyl aralkyl group selected from the group consisting of benzyl and phenetyl; Rn is hydrogen C1 to C7 alkyl aralkyl group selected from the group consisting of benzyl and phenetyl, acyl group selected from the group consisting of acetyl, propionyl and benzoyl, 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 x = 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; and R2 is hydrogen or -(CH2)y ? Y where y is 1-3 and Y is hydrogen, -O-R .alpha., -S-R .alpha. or <IMG>where where R.alpha. is hydrogen, C1 to C7 alkyl cycloalkyl or acyl group selected from the group consisting of acetyl, propionyl and benzoyl, R.beta. is hydrogen or C1 to C7 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; or a pharmaceutically acceptable salt thereof.