L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor.
Bioorg Med Chem Lett
; 8(7): 817-22, 1998 Apr 07.
Article
em En
| MEDLINE
| ID: mdl-9871547
ABSTRACT
Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM). Compound 5 is highly selective for thrombin over trypsin, is efficacious in the rat ferric chloride model of arterial thrombosis and is orally bioavailable in dogs and cynomolgus monkeys. The structural basis for the critical importance of both methyl groups in 5 was confirmed by X-ray crystallography.
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Base de dados:
MEDLINE
Assunto principal:
Piridonas
/
Sulfonamidas
/
Trombina
/
Anticoagulantes
Limite:
Animals
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article