Synthesis and biological evaluation of novel 2-pyridinyl-[1,2,3]triazoles as inhibitors of transforming growth factor beta 1 type 1 receptor.
A series of 2-pyridinyl-[1,2,3]triazoles have been synthesized and evaluated for their ALK5 inhibitory activity in the luciferase reporter assays. Compound 8d showed significant ALK5 inhibition (SBE-luciferase activity, 25%; p3TP-luciferase activity, 17%) at a concentration of 5 microM that is comparable to that of SB-431542 (SBE-luciferase activity, 21%; p3TP-luciferase activity, 12%), but weak p38 alpha MAP kinase inhibition (13%) at a concentration of 10 microM that is much lower than that of SB-431542 (54%).
Kim
Dae-Kee
DK
College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, South Korea. dkkim@ewha.ac.kr
Kim
Joonseop
J
Park
Hyun-Ju
HJ
D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors* / Q000235:genetics; D001665:Binding Sites; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000188:drug therapy / Q000517:prevention & control; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D014230:Triazoles; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human