Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors

Minjung Kim; Junghun Lee; Kyungjin Jung; Hyangmi Kim; Waqar Aman; Jae Sang Ryu; Jung Mi Hah

doi:10.1016/j.bmcl.2014.05.030

Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors

Minjung Kim, Junghun Lee, Kyungjin Jung, Hyangmi Kim, Waqar Aman, Jae Sang Ryu, Jung Mi Hah

Department of Pharmaceutical Sciences

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

18 Scopus citations

Abstract

The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC₅₀ = 38.3 nM and 8.79 nM).

Original language	English
Pages (from-to)	3600-3604
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2014.05.030
State	Published - 1 Aug 2014

Bibliographical note

Funding Information:
This work was supported by the research fund of Hanyang University ( HY-2012-N ).

Keywords

(4-Aminobenzyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives
Antiproliferative activity
BRAF V600E
CRAF
Melanoma
Selectivity

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10.1016/j.bmcl.2014.05.030

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title = "Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors",

abstract = "The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC50 = 38.3 nM and 8.79 nM).",

keywords = "(4-Aminobenzyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives, Antiproliferative activity, BRAF V600E, CRAF, Melanoma, Selectivity",

author = "Minjung Kim and Junghun Lee and Kyungjin Jung and Hyangmi Kim and Waqar Aman and Ryu, {Jae Sang} and Hah, {Jung Mi}",

note = "Funding Information: This work was supported by the research fund of Hanyang University ( HY-2012-N ). ",

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doi = "10.1016/j.bmcl.2014.05.030",

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AU - Kim, Minjung

AU - Lee, Junghun

AU - Jung, Kyungjin

AU - Kim, Hyangmi

AU - Aman, Waqar

AU - Ryu, Jae Sang

AU - Hah, Jung Mi

N1 - Funding Information: This work was supported by the research fund of Hanyang University ( HY-2012-N ).

PY - 2014/8/1

Y1 - 2014/8/1

N2 - The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC50 = 38.3 nM and 8.79 nM).

AB - The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC50 = 38.3 nM and 8.79 nM).

KW - (4-Aminobenzyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives

KW - Antiproliferative activity

KW - BRAF V600E

KW - CRAF

KW - Melanoma

KW - Selectivity

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DO - 10.1016/j.bmcl.2014.05.030

M3 - Article

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AN - SCOPUS:84904054114

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VL - 24

SP - 3600

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors

Abstract

Bibliographical note

Keywords

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