Thiophene carboxamide inhibitors of JAK2 as potential treatments for myleoproliferative neoplasms

Autor:	Thomas S. Rush, Lin Xu, Paul Tempest, Grace Chan, Eric Bachman, Melaney Bouthillette, Craig Rosenstein, Anjili Mathur, Anna A. Zabierek, Andrew M. Haidle, Kaleen Konrad Childers, Jonathan R. Young, Jan-Rung Mo, Michael D. Altman, C. Gary Marshall
Rok vydání:	2014
Předmět:	Stereochemistry medicine.drug_class Clinical Biochemistry Substituent Pharmaceutical Science Carboxamide Antineoplastic Agents Thiophenes Biochemistry Models Biological chemistry.chemical_compound In vivo Microsomes Drug Discovery Thiophene medicine Molecule Animals Humans Molecular Biology Protein Kinase Inhibitors Molecular Structure Organic Chemistry Janus Kinase 2 Aminoimidazole Carboxamide Rats Enzyme Activation Disease Models Animal Leukemia Myeloid Acute chemistry Urea Molecular Medicine Bioisostere
Zdroj:	Bioorganicmedicinal chemistry letters. 24(8)
ISSN:	1464-3405
Popis:	A series of carboxamide-substituted thiophenes demonstrating inhibition of JAK2 is described. Development of this chemical series began with the bioisosteric replacement of a urea substituent by a pyridyl ring. Issues of chemical and metabolic stability were solved using the results of both in vitro and in vivo studies, ultimately delivering compounds such as 24 and 25 that performed well in an acute PK/PD model measuring p-STAT5 inhibition.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8479eda3c03567a3d0c98a3784b3649a https://pubmed.ncbi.nlm.nih.gov/24666646 Zobrazit plný text záznamu Full Text from ScienceDirect