Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines

Junghun Lee; Hwan Kim; Hana Yu; Jae Yoon Chung; Chang Hyun Oh; Kyung Ho Yoo; Taebo Sim; Jung Mi Hah

doi:10.1016/j.bmcl.2010.01.064

Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines

Junghun Lee, Hwan Kim, Hana Yu, Jae Yoon Chung, Chang Hyun Oh, Kyung Ho Yoo, Taebo Sim, Jung Mi Hah

KU-KIST Graduate School of Converging Science and Technology

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

30 Citations (Scopus)

Abstract

The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC₅₀ = 0.62 and 4.49 μM, respectively) and turned out to be a selective and potent CRAF inhibitor.

Original language	English
Pages (from-to)	1573-1577
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2010.01.064
Publication status	Published - 2010 Mar 1

Keywords

Antiproliferative activity
BRAF
CRAF
Melanoma cell line
Pyrimidin-4-yl-1H-imidazol-2-yl derivatives
Selectivity

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2010.01.064

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@article{076459977f2e4c1a84fa030498c19407,

title = "Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines",

abstract = "The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC50 = 0.62 and 4.49 μM, respectively) and turned out to be a selective and potent CRAF inhibitor.",

keywords = "Antiproliferative activity, BRAF, CRAF, Melanoma cell line, Pyrimidin-4-yl-1H-imidazol-2-yl derivatives, Selectivity",

author = "Junghun Lee and Hwan Kim and Hana Yu and Chung, {Jae Yoon} and Oh, {Chang Hyun} and Yoo, {Kyung Ho} and Taebo Sim and Hah, {Jung Mi}",

note = "Funding Information: This research was supported by Korea Institute of Science and Technology (KIST) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0087992 ; J.M.H.). We also thank Dr. Merlyn lab at Wistar Institute for the kind supply of WM3629 cell line.",

year = "2010",

month = mar,

day = "1",

doi = "10.1016/j.bmcl.2010.01.064",

language = "English",

volume = "20",

pages = "1573--1577",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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TY - JOUR

T1 - Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines

AU - Lee, Junghun

AU - Kim, Hwan

AU - Yu, Hana

AU - Chung, Jae Yoon

AU - Oh, Chang Hyun

AU - Yoo, Kyung Ho

AU - Sim, Taebo

AU - Hah, Jung Mi

N1 - Funding Information: This research was supported by Korea Institute of Science and Technology (KIST) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0087992 ; J.M.H.). We also thank Dr. Merlyn lab at Wistar Institute for the kind supply of WM3629 cell line.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC50 = 0.62 and 4.49 μM, respectively) and turned out to be a selective and potent CRAF inhibitor.

AB - The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC50 = 0.62 and 4.49 μM, respectively) and turned out to be a selective and potent CRAF inhibitor.

KW - Antiproliferative activity

KW - BRAF

KW - CRAF

KW - Melanoma cell line

KW - Pyrimidin-4-yl-1H-imidazol-2-yl derivatives

KW - Selectivity

UR - http://www.scopus.com/inward/record.url?scp=76649090272&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2010.01.064

DO - 10.1016/j.bmcl.2010.01.064

M3 - Article

C2 - 20149658

AN - SCOPUS:76649090272

VL - 20

SP - 1573

EP - 1577

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 5

ER -

Discovery and initial SAR of pyrimidin-4-yl-1H-imidazole derivatives with antiproliferative activity against melanoma cell lines

Abstract

Keywords

ASJC Scopus subject areas

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