Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use

US6143746A · kind A · utility

Assignee

• ICOS CORPORATION · US

Inventors

• Alain Claude-Marie Daugan · Les Ulis, FR
• Francoise Gellibert · Cachan, FR

Key dates

• Filing date: Sep 16, 1998
• Grant date: Nov 7, 2000
• Expiry date: Sep 16, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D471/14
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A compound of formula (I) and salts and solvates thereof, in which: R.sup.0 represents hydrogen, halogen, or C.sub.1-6 alkyl; 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 (a) 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 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. 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 beneficial, includin…