1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives: A novel type II Raf kinase inhibitors

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

doi:10.1016/j.bmcl.2010.04.039

1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives: A novel type II Raf kinase inhibitors

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

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

37 Citations (Scopus)

Abstract

The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC₅₀ = 0.56-0.86 μM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics.

Original language	English
Pages (from-to)	3805-3808
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2010.04.039
Publication status	Published - 2010

Bibliographical note

Funding Information:
This research was supported by Korea Institute of Science and Technology 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.).

Keywords

1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives
Antiproliferative activity
Melanoma cell line
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.2010.04.039

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title = "1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives: A novel type II Raf kinase inhibitors",

abstract = "The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC50 = 0.56-0.86 μM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics.",

keywords = "1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives, Antiproliferative activity, Melanoma cell line, Selectivity",

author = "Hana Yu and Yunkyung Jung and Hwan Kim and Junghun Lee 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 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.).",

year = "2010",

doi = "10.1016/j.bmcl.2010.04.039",

language = "English",

volume = "20",

pages = "3805--3808",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - 1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives

T2 - A novel type II Raf kinase inhibitors

AU - Yu, Hana

AU - Jung, Yunkyung

AU - Kim, Hwan

AU - Lee, Junghun

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 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.).

PY - 2010

Y1 - 2010

N2 - The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC50 = 0.56-0.86 μM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics.

AB - The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC50 = 0.56-0.86 μM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics.

KW - 1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives

KW - Antiproliferative activity

KW - Melanoma cell line

KW - Selectivity

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SN - 0960-894X

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EP - 3808

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 12

ER -

1,4-Dihydropyrazolo[4,3-d]imidazole phenyl derivatives: A novel type II Raf kinase inhibitors

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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