Beta 3 agonists. Part 1: evolution from inception to BMS-194449

Autor:	Kenneth E.J. Dickinson, Michael Cap, Peter T. W. Cheng, A.V. Gavai, Arvind Mathur, Belay Tesfamariam, G.T. Allen, T.W. Harper, D.E. Hillyer, Tamara Dejneka, Dorothy Slusarchyk, S. Skwish, P.J. McCann, Chongqing Sun, Richard E. Gregg, D.A. Young, Carl P. Ciosek, Tammy C. Wang, Ravindar N. Girotra, Philip M. Sher, B.E. Abboa-Offei, A A Seymour, William N. Washburn, C.M. Arbeeny, Amarendra B. Mikkilineni, Poss Kathleen M, T.L. Waldron, R.J. George, B.H. Frohlich, Anita D. Russell, Denis E. Ryono
Rok vydání:	2001
Předmět:	Agonist Stereochemistry medicine.drug_class Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Administration Oral Biological Availability Adrenergic beta-3 Receptor Agonists Biochemistry Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Ethanolamine Drug Discovery Chlorocebus aethiops medicine Structure–activity relationship Animals Humans Anilides Beta (finance) Molecular Biology Aryl Organic Chemistry Adrenergic beta-Agonists Rats chemistry Ethanolamines Benzyl group Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 11(23)
ISSN:	0960-894X
Popis:	Screening of the BMS collection identified 4-hydroxy-3-methylsulfonanilidoethanolamines as full beta 3 agonists. Substitution of the ethanolamine nitrogen with a benzyl group bearing a para hydrogen bond acceptor promoted beta(3) selectivity. SAR elucidation established that highly selective beta(3) agonists were generated upon substitution of C(alpha) with either benzyl to form (R)-1,2-diarylethylamines or with aryl to generate 1,1-diarylmethylamines. This latter subset yielded a clinical candidate, BMS-194449 (35).(1)
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a03ede478701d49831f880574ab7cfb https://pubmed.ncbi.nlm.nih.gov/11714605 Zobrazit plný text záznamu Full Text from ScienceDirect