Disubstituted bicyclic heterocycles, the preparation and the use thereof as pharmaceutical compositions

US6469039B1 · kind B1 · utility

Assignee

• BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG · DE

Inventors

• Norbert Hauel · Schemmerhofen, DE
• Henning Priepke · Warthausen, DE
• Uwe Ries · Biberach an der Riß, DE
• Jean-Marie Stassen · Bad Buchau, DE
• Wolfgang Wienen · Äpfingen, DE

Key dates

• Filing date: Apr 6, 2000
• Grant date: Oct 22, 2002
• Expiry date: Apr 6, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D513/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

New disubstituted bicyclic heterocycles of general formulaRa—A—Het—B—Ar—E  (I)Compounds of the above general formula I, wherein E denotes an RbNH—C(═NH)— group, have valuable pharmacological properties, particularly a thrombin-inhibiting effect and the effect of prolonging thrombin time, and those wherein E denotes a cyano group, are valuable intermediates for preparing the other compounds of general formula I. Exemplary compounds of formula I are:(a) 1-Methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-hydroxycarbonylethyl)-amide,(b) 1-Methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(hydroxycarbonylmethyl)-amide,(c) 1-Methyl-2-[N-(4-amidino-2-methoxy-phenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(hydroxycarbonylmethyl)-amide, and(d) 1-Methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl) amide.