PROCEDIMIENTO DE PREPARACION DE ACETILAMIDINIOFENILALANIL-CICLOHEXILGLICIL-PIRIDILALANINAMIDAS

• Main Authors: HOLLA, WOLFGANG, BECK, GERHARD, JENDRALLA, HEINER, BREIPOHL.GERHARD
• Format: Patent
• Language: Spanish
• Published: 01.12.2006
• Edition: 4
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; APPARATUS THEREFOR; CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOIDCHEMISTRY; CHEMISTRY; GENERAL METHODS OF ORGANIC CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PERFORMING OPERATIONS; PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; THEIR RELEVANT APPARATUS; TRANSPORTING

Un procedimiento para la preparación de compuestos de fórmula I, que comprende convertir el compuesto de fórmula II por hidrogenación catalítica y conversión del grupo ciano en el grupo amidino, en el compuesto de fórmula III o su sal con el ácido HX, seguido de la reacción con un compuesto de fórmula IV o su sal con el ácido HX para proporcionar un compuesto de fórmula I, en donde los aniones X son aniones fisiológicamente aceptables. The present invention relates to a process for the preparation of acetyl-amidiniophenylalanyl-cyclohexylglycyl-pyridinioalaninamides of the formula I, in which the anions X are physiologically acceptable anions, and their analogs, which are effective inhibitors of the blood coagulation factor Xa and which can be used, for example, for preventing thromboses. The process according to the invention comprises the coupling of 2-[2-acetylamino-3-(4-amidinophenyl)propionylamino]-2-cyclohexylacetic acid, which is obtained from 2-[2-acetylamino-3-(4-cyanophenyl)acryloylamino]-2-cyclohexylacetic acid by asymmetric hydrogenation and conversion of the cyano group into the amidine, or a salt thereof, with a 3-(2-amino-2-carbamoylethyl)-1-methylpyridinium salt or a salt thereof. The invention furthermore provides starting materials and intermediates for this process, processes for their preparation and acetyl-(S)-4-amidiniophenylalanyl-(S)-cyclohexylglycyl-(S)-(1-methyl-3-pyridinio)alaninamide as ditosylate salt.