Pfizer Corporation

Nicholas Kenneth Terrett

Andrew Simon Bell

John C Danilewicz

Ian T Barnish

Keith James

Michael T Williams

Gillian M Samuels

Martin James Wythes

David Graham Brown

Peter Ellis

Martin J Wythes

Pyrazolopyrimidinones for the treatment of impotence

Compounds are disclosed which are useful as PDE1 inhibitors. The compounds have the formula:

5-substituted pyrazolo&lsqb;4,3-D&rsqb;pyrimidin-7-ones

##STR1## Compounds of formula (I), and pharmaceutically acceptable salts thereof, wherein R.sup.1 is C.sub.1 -C.sub.4 alkyl; R.sup.2 is C.sub.2 -C.sub.4 alkyl; R.sup.3 is H or SO.sub.2 NR.sup.4 R.sup.5 ; R.sup.4 and R.sup.5 together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, morpholino or 4-N-(R.sup.6)-1-piperazinyl group; and R.sup.6 is H or C.sub.1 -C.sub.3 alkyl; are selective cGMP PDE inhibitors useful in the treatment of, inter alia, cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis.

Purinone antianginal agents

Pyridopyrimidinone antianginal agents

Quinazolinone antianginal agents

Compounds of the formula: ##STR1## wherein R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, C.sub.3 -C.sub.5 cycloalkyl or C.sub.1 -C.sub.3 perfluoroalkyl; R.sup.2 is H, C.sub.1 -C.sub.6 alkyl optionally substituted by OH, C.sub.1 -C.sub.3 alkoxy or C.sub.3 -C.sub.6 cycloalkyl, or C.sub.1 -C.sub.3 perfluoroalkyl; R.sup.3 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 alkynyl, C.sub.3 -C.sub.6 alkynyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.6 perfluoroalkyl or (C.sub.3 -C.sub.6 cycloalky)C.sub.1 -C.sub.6 alkyl; R.sup.4 taken together with the nitrogen atom to which it is attached completes a pyrrolidinyl, piperidino, morpholino, or 4-N-(R.sup.6)-piperazinyl group; R.sup.5 is H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.3 alkoxy, NR.sup.7 R.sup.8, or CONR.sup.7 R.sup.8 ; R.sup.6 is H, C.sub.1 -C.sub.6 alkyl, (C.sub.1 -C.sub.3 alkoxy) C.sub.2 -C.sub.6 alkyl, hydroxy C.sub.2 -C.sub.6 alkyl, (R.sup.7 R.sup.8 N)C.sub.2 -C.sub.6 alkyl, (R.sup.7 R.sup.8 NCO)C.sub.1 -C.sub.6 alkyl, CONR.sup.7 R.sup.8, CSNR.sup.7 R.sup.8 or C(NH)NR.sup.7 R.sup.8 ; R.sup.7 and R.sup.8 are each independently H, C.sub.1 -C.sub.4 alkyl, (C.sub.1 -C.sub.3 alkoxy)C.sub.2 -C.sub.4 alkyl or hydroxy C.sub.2 -C.sub.4 alkyl; and pharmaceutically acceptable salts thereof, are selective cGMP PDE inhibitors useful in the treatment of cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis.

Pyrazolopyrimidinone antianginal agents

A series of novel spiro-substituted glutaramide derivatives have been prepared, including the pharmaceutically acceptable salts thereof and bioprecursors therefor, wherein the spiro-substituent completes a 5- or 6- membered carbocyclic ring and is located at the carbon atom adjacent to the carbamoyl group. These particular compounds are inhibitors of the neutral endopeptidase E.C.3,4.24.11 enzyme and are therefore useful in therapy as diuretic agents for the treatment of hypertension, heart failure, renal insufficiency and other disorders. Methods for preparing these compounds from known starting materials are provided.

Glutaramide diuretic agents

A series of novel spiro-substituted glutaramide derivatives have been prepared, including the pharmaceutically acceptable salts thereof and bioprecursors therefor, wherein the spiro-substituent completes a 5- or 6-membered carbocycyclic ring and is located at the carbon atom adjacent to the carbamoyl group. These particular compounds are inhibitors of the neutral endopeptidase E.C.3.4.24.11 enzyme and are therefore useful in therapy as diuretic agents for the treatment of hypertension, heart failure, renal insufficiency and other disorders. Methods for preparing these compounds from known starting materials are provided.

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Sandwich, United Kingdom

Nicholas Kenneth Terrett