2-Phenyl-substituited Imidazotriazinones as Phoshodiesterase Inhibitors

• Main Authors: DEMBOWSKY KLAUS DR, ES-SAYED MAZEN DR, PERZBORN ELISABETH DR, NOWAKOWSKI MARC DR, HANING HELMUT DR, SCHENKE THOMAS DR, SERNO PETER DR, KELDENICH JORG DR, SCHLEMMER KARL-HEINZ DR, BISCHOFF ERWIN DR, NIEWOHNER ULRICH DR
• Format: Patent
• Language: English; Slovenian
• Published: 28.09.2012
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

2-(Sulfamoyl-substituted phenyl)-3H-imidazo (5,1-f) (1,2,4) triazin-4-ones (I) are new. Imidazotriazinones of formula (I) and their salts, N-oxides and isomeric forms are new: [Image] R 1H or 1-4C alkyl; R 21-4C straight chain alkyl; R 3, R 4H, 2-8C alkenyl, 1-8C alkoxy or 1-10C alkyl (optionally interrupted by O and/or substituted by a very wide range of specific groups); or R 3 or R 4NR 2 0R 2 1, adamantyl, 2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl, sulfolanyl, hydroxy-sulfolanyl, 2-oxo-tetrahydrofuran-3-yl; or 3-8C cycloalkyl, 6-10C aryl or 5-7 membered heterocycle, all optionally substituted by specific groups; or NR 3R 4(a) optionally benzo-fused, saturated, partially unsaturated or unsaturated 5-7 membered heterocycle, optionally containing 1-3 of S, N, O and NR 3 7 and optionally substituted by a very wide range of specific groups; or (b) a group of formula (i)-(iv); R 2 0,R 2 1H or 1-6C alkyl; R 3 7H, OH, CHO, CF 3, up to 4C acyl, up to 4C alkoxycarbonyl, 1-4C alkoxy, 1-6C alkyl (optionally substituted by specific groups) or -(CO) iE; i : 0 or 1; E : 3-7C cycloalkyl or benzyl; 6-10C aryl or 5- or 6-membered heteroaryl, both optionally substituted by specific groups ; or 5-methyl-1-oxo-2,1,3-oxadiazol-4-yl, N-methylpiperazino or morpholino; R 5,R 6H, 1-6C alkyl, OH or 1-6C alkoxy. [Image] The full definitions are given in the DEFINITIONS (Full Definitions) field. An independent claim is included for the preparation of (I). ACTIVITY : Cardiovascular; urogenital; antihypertensive; antiarrhythmic; smooth muscle relaxant. MECHANISM OF ACTION : Phosphodiesterase (PDE) inhibitor. (I) are especially potent and selective inhibitors of PDE's which metabolize cyclic guanosine monophosphate (c-GMP) (rather than cyclic adenosine monophosphate (c-AMP)), i.e. the isoenzymes PDE-I, PDE-II and/or PDE-V. 2-(2-Ethoxy-5-(4-hydroxy-piperidine-1-sulfonyl)-phenyl)-5-methyl-7-propyl-3H-imidazo (5,1-f) (1,2,4) triazin-4-one (Ia) had an IC 5 0 value of 1 nM for the inhibition of PDE-V.