Design, synthesis, and biological evaluation of novel 2-pyridinyl-[1,2,4]triazoles as inhibitors of transforming growth factor beta1 type 1 receptor

Dae-Kee Kim; Joonseop Kim; Hyun-Ju Park

doi:10.1016/j.bmc.2004.03.004

Design, synthesis, and biological evaluation of novel 2-pyridinyl-[1,2,4]triazoles as inhibitors of transforming growth factor beta1 type 1 receptor

Bioorg Med Chem. 2004 May 1;12(9):2013-20. doi: 10.1016/j.bmc.2004.03.004.

Authors

Dae-Kee Kim¹, Joonseop Kim, Hyun-Ju Park

Affiliation

¹ College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, South Korea. [email protected]

PMID: 15080905
DOI: 10.1016/j.bmc.2004.03.004

Abstract

A series of 2-pyridinyl-[1,2,4]triazoles have been synthesized and evaluated for their ALK5 inhibitory activity in the luciferase reporter assays. Compound 12b showed significant ALK5 inhibition (SBE-Luciferase, 73%; p3TP-Luciferase, 85%) at a concentration of 5 microM that is comparable to that of SB-431542 (SBE-Luciferase, 79%; p3TP-Luciferase, 88%), but weak p38 alpha MAP kinase inhibition (4%) at a concentration of 10 microM that is much lower than that of SB-431542 (54%). The binding mode of 12b generated by flexible docking studies revealed that the structure of 12b is a good fit into the (NPC-30345)-binding cavity of ALK5.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Magnetic Resonance Spectroscopy
Models, Molecular
Receptors, Transforming Growth Factor beta / antagonists & inhibitors*
Spectrometry, Mass, Electrospray Ionization
Triazoles / chemical synthesis*
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Receptors, Transforming Growth Factor beta
Triazoles