Balancing oral exposure with Cyp3A4 inhibition in benzimidazole-based IGF-IR inhibitors

Autor:	Joan M. Carboni, David R. Langley, Upender Velaparthi, Aixin Li, Saulnier Mark G, Ann Greer, Kurt Zimmermann, Xiaopeng Sang, Zheng Yang, Mark D. Wittman, Ricardo M. Attar, Lorell Discenza, Dolatrai M. Vyas, Praveen Balimane, Marco M. Gottardis, David B. Frennesson
Rok vydání:	2008
Předmět:	Benzimidazole Nitrogen Decarboxylation Stereochemistry Chemistry Pharmaceutical medicine.medical_treatment Clinical Biochemistry Administration Oral Pharmaceutical Science Biochemistry Receptor IGF Type 1 Inhibitory Concentration 50 chemistry.chemical_compound Insulin-like growth factor Adenosine Triphosphate Somatomedins Oral administration Drug Discovery medicine Cytochrome P-450 CYP3A Humans Molecular Biology chemistry.chemical_classification Kinase Organic Chemistry Synthon Fluorine Malonate Enzyme Models Chemical chemistry Area Under Curve Drug Design Cytochrome P-450 CYP3A Inhibitors Molecular Medicine Benzimidazoles Thymidine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 18:4075-4080
ISSN:	0960-894X
Popis:	3-(Benzimidazol-2-yl)-pyridine-2-one-based ATP competitive inhibitors of Insulin-like Growth Factor 1 Kinase (IGF-IR) were optimized for reduced Cyp3A4 inhibition and improved oral exposure. The use of malonate as methyl anion synthon via S(N)Ar reaction and double decarboxylation under mild conditions is demonstrated.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfaeacbf99e265402bcdc337b405f271 https://doi.org/10.1016/j.bmcl.2008.05.104 Zobrazit plný text záznamu Full Text from ScienceDirect