Synthesis and biological evaluation of 5-(pyridin-2-yl)thiazoles as transforming growth factor-β type1 receptor kinase inhibitors

Dae Kee Kim; Joon Hun Choi; Young Jae An; Ho Soon Lee

doi:10.1016/j.bmcl.2008.01.084

Synthesis and biological evaluation of 5-(pyridin-2-yl)thiazoles as transforming growth factor-β type1 receptor kinase inhibitors

Dae Kee Kim, Joon Hun Choi, Young Jae An, Ho Soon Lee

Department of Pharmaceutical Sciences

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

24 Scopus citations

Abstract

A series of 5-(pyridin-2-yl)thiazoles (14a-l and 15a-l) has been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 3-[[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl ]benzamide (15i) and 3-[[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl] benzamide (15k) showed more than 95% inhibition at 0.1 μM in luciferase reporter assays using HaCaT cells transiently transfected with p3TP-luc reporter construct and ARE-luciferase reporter construct.

Original language	English
Pages (from-to)	2122-2127
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2008.01.084
State	Published - 15 Mar 2008

Bibliographical note

Funding Information:
This work was supported in part by the grants from Ministry of Commerce, Industry and Energy, Korea (M1-0310-43-0001 and M1-0310-43-0002).

Keywords

ALK5 inhibitors
Fibrosis
Transforming growth factor-β (TGF-β)

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@article{105c53380af04cf89dc2f68746270993,

title = "Synthesis and biological evaluation of 5-(pyridin-2-yl)thiazoles as transforming growth factor-β type1 receptor kinase inhibitors",

abstract = "A series of 5-(pyridin-2-yl)thiazoles (14a-l and 15a-l) has been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 3-[[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl ]benzamide (15i) and 3-[[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl] benzamide (15k) showed more than 95% inhibition at 0.1 μM in luciferase reporter assays using HaCaT cells transiently transfected with p3TP-luc reporter construct and ARE-luciferase reporter construct.",

keywords = "ALK5 inhibitors, Fibrosis, Transforming growth factor-β (TGF-β)",

author = "Kim, {Dae Kee} and Choi, {Joon Hun} and An, {Young Jae} and Lee, {Ho Soon}",

note = "Funding Information: This work was supported in part by the grants from Ministry of Commerce, Industry and Energy, Korea (M1-0310-43-0001 and M1-0310-43-0002).",

year = "2008",

month = mar,

day = "15",

doi = "10.1016/j.bmcl.2008.01.084",

language = "English",

volume = "18",

pages = "2122--2127",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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T1 - Synthesis and biological evaluation of 5-(pyridin-2-yl)thiazoles as transforming growth factor-β type1 receptor kinase inhibitors

AU - Kim, Dae Kee

AU - Choi, Joon Hun

AU - An, Young Jae

AU - Lee, Ho Soon

N1 - Funding Information: This work was supported in part by the grants from Ministry of Commerce, Industry and Energy, Korea (M1-0310-43-0001 and M1-0310-43-0002).

PY - 2008/3/15

Y1 - 2008/3/15

N2 - A series of 5-(pyridin-2-yl)thiazoles (14a-l and 15a-l) has been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 3-[[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl ]benzamide (15i) and 3-[[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl] benzamide (15k) showed more than 95% inhibition at 0.1 μM in luciferase reporter assays using HaCaT cells transiently transfected with p3TP-luc reporter construct and ARE-luciferase reporter construct.

AB - A series of 5-(pyridin-2-yl)thiazoles (14a-l and 15a-l) has been synthesized and evaluated for their ALK5 inhibitory activity in cell-based luciferase reporter assays. Among them, 3-[[5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl ]benzamide (15i) and 3-[[5-(6-ethylpyridin-2-yl)-4-(quinoxalin-6-yl)thiazol-2-ylamino]methyl] benzamide (15k) showed more than 95% inhibition at 0.1 μM in luciferase reporter assays using HaCaT cells transiently transfected with p3TP-luc reporter construct and ARE-luciferase reporter construct.

KW - ALK5 inhibitors

KW - Fibrosis

KW - Transforming growth factor-β (TGF-β)

UR - http://www.scopus.com/inward/record.url?scp=40849097867&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2008.01.084

DO - 10.1016/j.bmcl.2008.01.084

M3 - Article

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AN - SCOPUS:40849097867

SN - 0960-894X

VL - 18

SP - 2122

EP - 2127

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 6

ER -

Synthesis and biological evaluation of 5-(pyridin-2-yl)thiazoles as transforming growth factor-β type1 receptor kinase inhibitors

Abstract

Bibliographical note

Keywords

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