Improving the oral efficacy of CNS drug candidates: discovery of highly orally efficacious piperidinyl piperidine M2 muscarinic receptor antagonists

Autor:	Samuel Chackalamannil, Ruth A. Duffy, Yuguang Wang, Herbert Binch, Zhiyong Hu, William Billard, Mary Cohen-Williams, Kathleen Cox, William J. Greenlee, Diane E. Grotz, Vilma Ruperto, Gordon Crosby, Craig D. Boyle, Vicki L. Coffin, John W. Clader, James J. Kaminski, Jean E. Lachowicz
Rok vydání:	2002
Předmět:	Drug media_common.quotation_subject Microdialysis Molecular Conformation Administration Oral Muscarinic Antagonists Pharmacology In Vitro Techniques chemistry.chemical_compound Structure-Activity Relationship Pharmacokinetics Piperidines In vivo Oral administration Drug Discovery Muscarinic acetylcholine receptor Avoidance Learning Animals Humans media_common Acetylcholine receptor Autoreceptors Receptor Muscarinic M2 Chemistry Antagonist Receptors Muscarinic Acetylcholine Corpus Striatum Rats Molecular Medicine Piperidine Central Nervous System Agents
Zdroj:	Journal of medicinal chemistry. 45(25)
ISSN:	0022-2623
Popis:	In search of a backup M(2) muscarinic receptor antagonist to the previously reported compound 1, we discovered compound (+)-14, which showed superior oral efficacy in animal models. The improvement of oral efficacy was achieved by modulating both the molecular weight and lipophilicity of the lead compounds.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8f01b5159480e9fea3765195aa02e5d https://pubmed.ncbi.nlm.nih.gov/12459007 Zobrazit plný text záznamu