GluK1 antagonists from 6-(carboxy)phenyl decahydroisoquinoline derivatives. SAR and evaluation of a prodrug strategy for oral efficacy in pain models

Autor:	Brian M. Arnold, Miriam del Prado, Smriti Iyengar, Edward L. Mattiuz, Zhipei Wu, Mark A. Winter, David Bleakman, Ken H. Ho, Ann Marie L. Ogden, Paul L. Ornstein, Carrie K. Jones, Sandra Ann Filla, Brian Michael Mathes, Michael Gregory Bell, Douglas Richard Stack, Ana Maria Escribano, Thomas J. Bleisch, Ana I. Mateo, Kevin John Hudziak, Andrew Alt, Rosa Maria A. Simmons, Harlan E. Shannon, Robert E. Stratford, Jose A. Martinez-Perez, Esteban Dominguez, Ana M. Castaño
Rok vydání:	2013
Předmět:	Molecular Sequence Data Clinical Biochemistry Administration Oral Pain Pharmaceutical Science Pharmacology Biochemistry Structure-Activity Relationship chemistry.chemical_compound Receptors Kainic Acid Oral administration In vivo Drug Discovery Animals Prodrugs Amino Acid Sequence Molecular Biology Benzoic acid chemistry.chemical_classification Chemistry Organic Chemistry Haplorhini Prodrug Isoquinolines Amino acid Disease Models Animal Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 23:6459-6462
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2013.09.046
Popis:	The synthesis and structure-activity relationship of decahydroisoquinoline derivatives with various benzoic acid substitutions as GluK1 antagonists are described. Potent and selective antagonists were selected for a tailored prodrug approach in order to facilitate the evaluation of the new compounds in pain models after oral administration. Several diester prodrugs allowed for acceptable amino acid exposure and moderate efficacy in vivo.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::94941d0e80ddda4525e54e7a232591e5 https://doi.org/10.1016/j.bmcl.2013.09.046 Zobrazit plný text záznamu Full Text from ScienceDirect