Structure- and property-based design of factor Xa inhibitors: pyrrolidin-2-ones with acyclic alanyl amides as P4 motifs

Autor:	Matthew Campbell, Ping Zhou, Robert J. Young, Weston Helen Elisabeth, Savvas Kleanthous, David W. Brown, Champa Patel, Satish Dayal, Shah Gita Punjabhai, Alan D. Borthwick, N. Paul King, Cynthia L. Burns-Kurtis, Stefan Senger, Hawa Diallo, Máire A. Convery, Nigel S. Watson, Paul W. Smith, Henry Anderson Kelly, Miriam Crowe, Chuen Chan, Anthony J. Pateman, Jackie E. Mordaunt, Andrew M. Mason
Rok vydání:	2006
Předmět:	Models Molecular medicine.drug_mechanism_of_action Molecular model Stereochemistry Clinical Biochemistry Factor Xa Inhibitor Antithrombin III Substituent Pharmaceutical Science Crystallography X-Ray Biochemistry Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Amide Drug Discovery Hydrolase medicine Pyrroles Molecular Biology chemistry.chemical_classification Alanine Binding Sites Molecular Structure Organic Chemistry Anticoagulants Amides Sulfonamide chemistry Drug Design Lipophilicity Factor Xa Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 16(23)
ISSN:	0960-894X
Popis:	Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de3b9901e5afa05ffed0024b5adc2fb9 https://pubmed.ncbi.nlm.nih.gov/16982190 Zobrazit plný text záznamu Full Text from ScienceDirect