Discovery of 7-azaindole derivatives as potent Orai inhibitors showing efficacy in a preclinical model of asthma

Autor:	Laura Vidal, Sonia Sentellas, Gema Tarrasón, Soledad Alzina, Silvia Gual, Bernat Vidal, Cristina Esteve, Irene Jover, Jacob González, Jorge De Alba, Montserrat Miralpeix, Raquel Horrillo
Rok vydání:	2015
Předmět:	Indoles Ovalbumin Pyridines Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Pharmacology medicine.disease_cause Models Biological Biochemistry Jurkat cells Jurkat Cells Structure-Activity Relationship Allergen Pharmacokinetics Microsomes Drug Discovery Hypersensitivity medicine Animals Humans Potency Pyrroles Molecular Biology Asthma Aza Compounds Chemistry Organic Chemistry respiratory system Calcium Channel Blockers medicine.disease Rats respiratory tract diseases Disease Models Animal Lipophilicity Interleukin-2 Molecular Medicine Calcium Channels Half-Life Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 25:1217-1222
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2015.01.063
Popis:	Synthesis and SAR of a series of 7-azaindoles as Orai channel inhibitors showing good potency inhibiting IL-2 production in Jurkat cells is described. Compound 14d displaying best pharmacokinetic properties was further characterized in a model of allergen induced asthma showing inhibition in the number of eosinophils in BALF. High lipophilicity remains as one of the main challenges for this class of compounds.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::825a7ee7d35a2e46075e136353eb9a3f https://doi.org/10.1016/j.bmcl.2015.01.063 Zobrazit plný text záznamu Full Text from ScienceDirect