Design, synthesis, and biological evaluation of novel 2-pyridinyl-[1,2,4] triazoles as inhibitors of transforming growth factor β1 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 β1 type 1 receptor

Dae Kee Kim, Joonseop Kim, Hyun Ju Park

Department of Pharmaceutical Sciences

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

25 Scopus citations

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 5μM that is comparable to that of SB-431542 (SBE-Luciferase, 79%; p3TP-Luciferase, 88%), but weak p38α MAP kinase inhibition (4%) at a concentration of 10μM 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.

Original language	English
Pages (from-to)	2013-2020
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	12
Issue number	9
DOIs	https://doi.org/10.1016/j.bmc.2004.03.004
State	Published - 1 May 2004

Bibliographical note

Funding Information:
This work was supported by the Ewha Womans University Research Grant of 2002 and a grant from KISTEP, Korea (M1-0310-43-0000).

Keywords

2-Pyridinyl-[1,2,4]triazoles
ALK5
Inhibitors
TGF-β1 type 1 receptor

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10.1016/j.bmc.2004.03.004

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title = "Design, synthesis, and biological evaluation of novel 2-pyridinyl-[1,2,4] triazoles as inhibitors of transforming growth factor β1 type 1 receptor",

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 5μM that is comparable to that of SB-431542 (SBE-Luciferase, 79%; p3TP-Luciferase, 88%), but weak p38α MAP kinase inhibition (4%) at a concentration of 10μM 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.",

keywords = "2-Pyridinyl-[1,2,4]triazoles, ALK5, Inhibitors, TGF-β1 type 1 receptor",

author = "Kim, {Dae Kee} and Joonseop Kim and Park, {Hyun Ju}",

note = "Funding Information: This work was supported by the Ewha Womans University Research Grant of 2002 and a grant from KISTEP, Korea (M1-0310-43-0000).",

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doi = "10.1016/j.bmc.2004.03.004",

language = "English",

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AU - Kim, Dae Kee

AU - Kim, Joonseop

AU - Park, Hyun Ju

N1 - Funding Information: This work was supported by the Ewha Womans University Research Grant of 2002 and a grant from KISTEP, Korea (M1-0310-43-0000).

PY - 2004/5/1

Y1 - 2004/5/1

N2 - 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 5μM that is comparable to that of SB-431542 (SBE-Luciferase, 79%; p3TP-Luciferase, 88%), but weak p38α MAP kinase inhibition (4%) at a concentration of 10μM 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.

AB - 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 5μM that is comparable to that of SB-431542 (SBE-Luciferase, 79%; p3TP-Luciferase, 88%), but weak p38α MAP kinase inhibition (4%) at a concentration of 10μM 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.

KW - 2-Pyridinyl-[1,2,4]triazoles

KW - ALK5

KW - Inhibitors

KW - TGF-β1 type 1 receptor

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DO - 10.1016/j.bmc.2004.03.004

M3 - Article

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AN - SCOPUS:1842636360

SN - 0968-0896

VL - 12

SP - 2013

EP - 2020

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 9

ER -

Design, synthesis, and biological evaluation of novel 2-pyridinyl-[1,2,4] triazoles as inhibitors of transforming growth factor β1 type 1 receptor

Abstract

Bibliographical note

Keywords

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