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Details for Patent: 6,784,179

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Details for Patent: 6,784,179

Title: Tetracyclic derivatives, process of preparation and use
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; R.sup.1 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halo C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkylC.sub.1-3 alkyl, arylC.sub.1-3 alkyl or heteroaryl C.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 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, including the treatment of cardiovascular disorders.
Inventor(s): Daugan; Alain Claude-Marie (Les Ulis, FR)
Assignee: ICOS Corporation (Bothell, WA)
Filing Date:Feb 05, 2002
Application Number:10/068,114
Claims:1. A method of treating a vascular disease comprising administering to a human or nonhuman body the following: a) an endothelium-derived relaxing factor, an atrial natriuretic factor, a brain natriuretic peptide, a C-type natriuretic peptide, or an endothelium-dependent relaxing agent, and b) a therapeutically effective amount of a compound having a formula of ##STR20## or salts or 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, wherein aryl is phenyl or phenyl substituted with one to three substituents selected from the group consisting of halogen, C.sub.1-6 alkyl, C.sub.1-4 alkoxy, methylenedioxy, and mixtures thereof, or heteroarylC.sub.1-3 alkyl, wherein heteroaryl is thienyl, furyl or pyridyl, each optionally substituted with one to three substituents selected from the group consisting of halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, and mixtures thereof; R.sup.2 represents an optionally substituted monocyclic aromatic ring, selected from benzene, thiophene, furan, and pyridine, or an optionally substituted bicyclic ring ##STR21## 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, sulfur, and nitrogen; and R.sup.3 represents hydrogen or C.sub.1-3 alkyl, or R.sup.1 or R.sup.3 together represent a 3- or 4-membered alkyl or alkenyl chain component of a 5- or 6-membered ring.

2. The method of claim 1 wherein the endothelium-dependent relaxing agent is bradykinin, acetylcholine, or 5-HT.
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