Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5- (quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Fei Li; Yunjeong Park; Jung Mi Hah; Jae Sang Ryu

doi:10.1016/j.bmcl.2012.12.008

Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5- (quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Fei Li, Yunjeong Park, Jung Mi Hah, Jae Sang Ryu

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

A series of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles has been synthesized and evaluated for their ALK5 inhibitory activity. The 1-(6-methylpyridin-2-yl)-1,2,3-triazoles were assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Following this, quinoxaline was introduced through Pd-catalyzed direct arylation. The synthesized 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles revealed significant selectivity differences with respect to p38α MAP kinase. In particular, 12k showed 80.8% ALK5 inhibitory activity at a concentration of 10 μM and IC₅₀ value of 4.69 μM, but did not show p38α MAP kinase inhibitory activity (-1.94% inhibition at a concentration of 10 μM).

Original language	English
Pages (from-to)	1083-1086
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	4
DOIs	https://doi.org/10.1016/j.bmcl.2012.12.008
State	Published - 15 Feb 2013

Bibliographical note

Funding Information:
This work was supported by a grant from Basic Science Research Program ( 2009-0075425 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology .

Keywords

1,2,3-Triazole
ALK5
Anticancer
Click chemistry
TGF-β type 1 receptor kinase

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10.1016/j.bmcl.2012.12.008

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title = "Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5- (quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors",

abstract = "A series of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles has been synthesized and evaluated for their ALK5 inhibitory activity. The 1-(6-methylpyridin-2-yl)-1,2,3-triazoles were assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Following this, quinoxaline was introduced through Pd-catalyzed direct arylation. The synthesized 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles revealed significant selectivity differences with respect to p38α MAP kinase. In particular, 12k showed 80.8% ALK5 inhibitory activity at a concentration of 10 μM and IC50 value of 4.69 μM, but did not show p38α MAP kinase inhibitory activity (-1.94% inhibition at a concentration of 10 μM).",

keywords = "1,2,3-Triazole, ALK5, Anticancer, Click chemistry, TGF-β type 1 receptor kinase",

author = "Fei Li and Yunjeong Park and Hah, {Jung Mi} and Ryu, {Jae Sang}",

note = "Funding Information: This work was supported by a grant from Basic Science Research Program ( 2009-0075425 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology . ",

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Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5- (quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors. / Li, Fei; Park, Yunjeong; Hah, Jung Mi et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 4, 15.02.2013, p. 1083-1086.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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AU - Park, Yunjeong

AU - Hah, Jung Mi

AU - Ryu, Jae Sang

N1 - Funding Information: This work was supported by a grant from Basic Science Research Program ( 2009-0075425 ) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology .

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Y1 - 2013/2/15

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AB - A series of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles has been synthesized and evaluated for their ALK5 inhibitory activity. The 1-(6-methylpyridin-2-yl)-1,2,3-triazoles were assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Following this, quinoxaline was introduced through Pd-catalyzed direct arylation. The synthesized 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles revealed significant selectivity differences with respect to p38α MAP kinase. In particular, 12k showed 80.8% ALK5 inhibitory activity at a concentration of 10 μM and IC50 value of 4.69 μM, but did not show p38α MAP kinase inhibitory activity (-1.94% inhibition at a concentration of 10 μM).

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Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5- (quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Abstract

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Keywords

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