Tetracyclic derivatives; process of preparation and use

US5859006A · kind A · utility

Assignee

• ICOS CORPORATION · US

Inventor

• Alain Claude-Marie Daugan · Les Ulis, FR

Key dates

• Filing date: Jul 16, 1996
• Grant date: Jan 12, 1999
• Expiry date: Jul 16, 2016

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P43/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A compound of formula (I) ##STR1## and salts and solvates thereof, in which: R.sup.0 represents hydrogen, halogen or C.sub.1-6 alkyl; PA1 R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, haloC.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkylC.sub.1-3 alkyl, arylC.sub.1-3 alkyl or heteroarylC.sub.1-3 alkyl; R.sup.2 represents an optionally substituted monocyclic aromatic ring selected from benzene, thiophene, furan and pyridine or an optionally substituted bicyclic ring ##STR2## attached to the rest of the molecule via one of the benzene ring carbon atoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxygen, sulphur and nitrogen; and PA1 R.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 and R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain. PA1 A compound of formula (I) is a potent and selective inhibitor of cyclic guanosine 3', 5'-monophosphate specific phosphodiesterase (cGMP specific PDE) having a utility in a variety of therapeutic areas where such inhibition is be…