Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Maddeboina Krishnaiah; Cheng Hua Jin; Domalapally Sreenu; Vura Bala Subrahmanyam; Kota Sudhakar Rao; Do Hyun Son; Hyun Ju Park; Seung Won Kim; Yhun Yhong Sheen; Dae Kee Kim

doi:10.1016/j.ejmech.2012.09.011

Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Maddeboina Krishnaiah
, Cheng Hua Jin
, Domalapally Sreenu
, Vura Bala Subrahmanyam
, Kota Sudhakar Rao
, Do Hyun Son
, Hyun Ju Park
, Seung Won Kim
, Yhun Yhong Sheen
, Dae Kee Kim

Department of Pharmaceutical Sciences

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

25 Scopus citations

Abstract

A series of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4] triazolo[1,5-a]pyridin-6-yl)thiazoles 12a-ab, 13a, 13b, and 18a-d has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The N-(3-fluorobenzyl)-4-(6- methylpyridin-2-yl)-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazol-2-amine (12b) inhibited ALK5 phosphorylation with an IC₅₀ value of 7.01 nM and showed 61% inhibition at 30 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.

Original language	English
Pages (from-to)	74-84
Number of pages	11
Journal	European Journal of Medicinal Chemistry
Volume	57
DOIs	https://doi.org/10.1016/j.ejmech.2012.09.011
State	Published - Nov 2012

Bibliographical note

Funding Information:
This work was supported by a grant from Ministry of Education, Science and Technology, Korea ( 20100029596 ).

Keywords

ALK5 inhibitor
Cancer
Cell-based luciferase reporter assay
Docking
Fibrosis
Kinase assay
TGF-β

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10.1016/j.ejmech.2012.09.011

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Krishnaiah, M., Jin, C. H., Sreenu, D., Subrahmanyam, V. B., Rao, K. S., Son, D. H., Park, H. J., Kim, S. W., Sheen, Y. Y., & Kim, D. K. (2012). Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors. European Journal of Medicinal Chemistry, 57, 74-84. https://doi.org/10.1016/j.ejmech.2012.09.011

@article{747d52a26a8c4d8e845b9c2d30ace4d1,

title = "Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors",

abstract = "A series of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4] triazolo[1,5-a]pyridin-6-yl)thiazoles 12a-ab, 13a, 13b, and 18a-d has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The N-(3-fluorobenzyl)-4-(6- methylpyridin-2-yl)-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazol-2-amine (12b) inhibited ALK5 phosphorylation with an IC50 value of 7.01 nM and showed 61\% inhibition at 30 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.",

keywords = "ALK5 inhibitor, Cancer, Cell-based luciferase reporter assay, Docking, Fibrosis, Kinase assay, TGF-β",

author = "Maddeboina Krishnaiah and Jin, \{Cheng Hua\} and Domalapally Sreenu and Subrahmanyam, \{Vura Bala\} and Rao, \{Kota Sudhakar\} and Son, \{Do Hyun\} and Park, \{Hyun Ju\} and Kim, \{Seung Won\} and Sheen, \{Yhun Yhong\} and Kim, \{Dae Kee\}",

note = "Funding Information: This work was supported by a grant from Ministry of Education, Science and Technology, Korea ( 20100029596 ). ",

year = "2012",

month = nov,

doi = "10.1016/j.ejmech.2012.09.011",

language = "English",

volume = "57",

pages = "74--84",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

Krishnaiah, M, Jin, CH, Sreenu, D, Subrahmanyam, VB, Rao, KS, Son, DH, Park, HJ, Kim, SW, Sheen, YY & Kim, DK 2012, 'Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors', European Journal of Medicinal Chemistry, vol. 57, pp. 74-84. https://doi.org/10.1016/j.ejmech.2012.09.011

Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors. / Krishnaiah, Maddeboina; Jin, Cheng Hua; Sreenu, Domalapally et al.
In: European Journal of Medicinal Chemistry, Vol. 57, 11.2012, p. 74-84.

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

TY - JOUR

T1 - Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors

AU - Krishnaiah, Maddeboina

AU - Jin, Cheng Hua

AU - Sreenu, Domalapally

AU - Subrahmanyam, Vura Bala

AU - Rao, Kota Sudhakar

AU - Son, Do Hyun

AU - Park, Hyun Ju

AU - Kim, Seung Won

AU - Sheen, Yhun Yhong

AU - Kim, Dae Kee

N1 - Funding Information: This work was supported by a grant from Ministry of Education, Science and Technology, Korea ( 20100029596 ).

PY - 2012/11

Y1 - 2012/11

N2 - A series of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4] triazolo[1,5-a]pyridin-6-yl)thiazoles 12a-ab, 13a, 13b, and 18a-d has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The N-(3-fluorobenzyl)-4-(6- methylpyridin-2-yl)-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazol-2-amine (12b) inhibited ALK5 phosphorylation with an IC50 value of 7.01 nM and showed 61% inhibition at 30 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.

AB - A series of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4] triazolo[1,5-a]pyridin-6-yl)thiazoles 12a-ab, 13a, 13b, and 18a-d has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The N-(3-fluorobenzyl)-4-(6- methylpyridin-2-yl)-5-([1,2,4]triazolo[1,5-a]pyridin-6-yl)thiazol-2-amine (12b) inhibited ALK5 phosphorylation with an IC50 value of 7.01 nM and showed 61% inhibition at 30 nM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.

KW - ALK5 inhibitor

KW - Cancer

KW - Cell-based luciferase reporter assay

KW - Docking

KW - Fibrosis

KW - Kinase assay

KW - TGF-β

UR - https://www.scopus.com/pages/publications/84867021810

U2 - 10.1016/j.ejmech.2012.09.011

DO - 10.1016/j.ejmech.2012.09.011

M3 - Article

C2 - 23047226

AN - SCOPUS:84867021810

SN - 0223-5234

VL - 57

SP - 74

EP - 84

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin- 2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Abstract

Bibliographical note

Keywords

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