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

US6087380A · kind A · 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: Feb 18, 1998
• Grant date: Jul 11, 2000
• Expiry date: Feb 18, 2018

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 formula EQU R.sub.a --A--Het--B--Ar--E (I) Compounds of the above general formula I, wherein E denotes an R.sub.b NH--C(.dbd.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: PA1 (a) 1-Methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-phenyl-N-(2-hydroxycarbonylethyl)-amide, PA1 (b) 1-Methyl-2-[N-(4-amidinophenyl)-aminomethyl]-benzimidazol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(hydroxycarbonylmethyl)-amide, PA1 (c) 1-Methyl-2-[N-(4-amidino-2-methoxy-phenyl)-aminomethyl]-benzimidazol-5-yl- carboxylic acid-N-(2-pyridyl)-N-(hydroxycarbonylmethyl)-amide, and PA1 (d) 1-Methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]aminomethyl]-benzimid azol-5-yl-carboxylic acid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl) amide.