Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Cheng Hua Jin; Maddeboina Krishnaiah; Domalapally Sreenu; Kota Sudhakar Rao; Vura Bala Subrahmanyam; Chul Yong Park; Jee Yeon Son; Yhun Yhong Sheen; Dae Kee Kim

doi:10.1016/j.bmc.2011.03.008

Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Cheng Hua Jin, Maddeboina Krishnaiah, Domalapally Sreenu, Kota Sudhakar Rao, Vura Bala Subrahmanyam, Chul Yong Park, Jee Yeon Son, Yhun Yhong Sheen, Dae Kee Kim

Department of Pharmaceutical Sciences

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34 Scopus citations

Abstract

A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinolin-6-yl) pyrazoles 14a-e, 15a-e, 17a-c, and 18a-d have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 6-quinolinyl pyrazole analogue 14b inhibited ALK5 phosphorylation with IC₅₀ value of 0.022 μM and showed 84% inhibition at 0.1 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.

Original language	English
Pages (from-to)	2633-2640
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	19
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2011.03.008
State	Published - 15 Apr 2011

Bibliographical note

Funding Information:
This work was supported by RP-Grant 2009 of Ewha Womans University.

Keywords

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

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10.1016/j.bmc.2011.03.008

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Jin, C. H., Krishnaiah, M., Sreenu, D., Rao, K. S., Subrahmanyam, V. B., Park, C. Y., Son, J. Y., Sheen, Y. Y., & Kim, D. K. (2011). Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors. Bioorganic and Medicinal Chemistry, 19(8), 2633-2640. https://doi.org/10.1016/j.bmc.2011.03.008

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title = "Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors",

abstract = "A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinolin-6-yl) pyrazoles 14a-e, 15a-e, 17a-c, and 18a-d have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 6-quinolinyl pyrazole analogue 14b inhibited ALK5 phosphorylation with IC50 value of 0.022 μM and showed 84\% inhibition at 0.1 μM in a luciferase reporter assay using HaCaT cells permanently transfected with p3TP-luc reporter construct.",

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

author = "Jin, \{Cheng Hua\} and Maddeboina Krishnaiah and Domalapally Sreenu and Rao, \{Kota Sudhakar\} and Subrahmanyam, \{Vura Bala\} and Park, \{Chul Yong\} and Son, \{Jee Yeon\} and Sheen, \{Yhun Yhong\} and Kim, \{Dae Kee\}",

note = "Funding Information: This work was supported by RP-Grant 2009 of Ewha Womans University. ",

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doi = "10.1016/j.bmc.2011.03.008",

language = "English",

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Jin, CH, Krishnaiah, M, Sreenu, D, Rao, KS, Subrahmanyam, VB, Park, CY, Son, JY, Sheen, YY & Kim, DK 2011, 'Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors', Bioorganic and Medicinal Chemistry, vol. 19, no. 8, pp. 2633-2640. https://doi.org/10.1016/j.bmc.2011.03.008

Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors. / Jin, Cheng Hua; Krishnaiah, Maddeboina; Sreenu, Domalapally et al.
In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 8, 15.04.2011, p. 2633-2640.

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

TY - JOUR

T1 - Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

AU - Jin, Cheng Hua

AU - Krishnaiah, Maddeboina

AU - Sreenu, Domalapally

AU - Rao, Kota Sudhakar

AU - Subrahmanyam, Vura Bala

AU - Park, Chul Yong

AU - Son, Jee Yeon

AU - Sheen, Yhun Yhong

AU - Kim, Dae Kee

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KW - Cell-based luciferase reporter assay

KW - Fibrosis

KW - Kinase assay

KW - TGF-β

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Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Abstract

Bibliographical note

Keywords

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