Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: Design, synthesis, and antiproliferative activity against melanoma cell line

Hye Jung Cho; Mohammed Ibrahim El-Gamal; Chang Hyun Oh; So Ha Lee; Taebo Sim; Garam Kim; Hong Seok Choi; Jung Hoon Choi; Kyung Ho Yoo

doi:10.1248/cpb.c13-00283

Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: Design, synthesis, and antiproliferative activity against melanoma cell line

Hye Jung Cho, Mohammed Ibrahim El-Gamal, Chang Hyun Oh, So Ha Lee, Taebo Sim, Garam Kim, Hong Seok Choi, Jung Hoon Choi, Kyung Ho Yoo

KU-KIST Graduate School of Converging Science and Technology

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

8 Citations (Scopus)

Abstract

Design and synthesis of a new series of quinolinylaminoisoquinoline derivatives as conformationally restricted bioisosteres of Sorafenib are described. Their in vitro antiproliferative activity against A375P melanoma cell line was tested. Compounds 1b, 1d, 1g, and 1j showed the highest potency against A375P cell line with IC₅₀ values in sub-micromolar scale. In addition, compound 1d exerted high selectivity towards RAF1 serine/threonine kinase with 96.47% inhibition at 10 μM, and IC₅₀ of 0.96 μM. This compound can possess antiproliferative activity against melanoma cells through inhibition of RAF1 kinase.

Original language	English
Pages (from-to)	747-756
Number of pages	10
Journal	Chemical and Pharmaceutical Bulletin
Volume	61
Issue number	7
DOIs	https://doi.org/10.1248/cpb.c13-00283
Publication status	Published - 2013 Jul

Keywords

Antiproliferative activity
Bioisostere
Melanoma
Quinolinylaminoisoquinoline
Sorafenib

ASJC Scopus subject areas

Chemistry(all)
Drug Discovery

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10.1248/cpb.c13-00283

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Cho, H. J., El-Gamal, M. I., Oh, C. H., Lee, S. H., Sim, T., Kim, G., Choi, H. S., Choi, J. H., & Yoo, K. H. (2013). Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: Design, synthesis, and antiproliferative activity against melanoma cell line. Chemical and Pharmaceutical Bulletin, 61(7), 747-756. https://doi.org/10.1248/cpb.c13-00283

Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: Design, synthesis, and antiproliferative activity against melanoma cell line. / Cho, Hye Jung; El-Gamal, Mohammed Ibrahim; Oh, Chang Hyun et al.
In: Chemical and Pharmaceutical Bulletin, Vol. 61, No. 7, 07.2013, p. 747-756.

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

Cho, HJ, El-Gamal, MI, Oh, CH, Lee, SH, Sim, T, Kim, G, Choi, HS, Choi, JH & Yoo, KH 2013, 'Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: Design, synthesis, and antiproliferative activity against melanoma cell line', Chemical and Pharmaceutical Bulletin, vol. 61, no. 7, pp. 747-756. https://doi.org/10.1248/cpb.c13-00283

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abstract = "Design and synthesis of a new series of quinolinylaminoisoquinoline derivatives as conformationally restricted bioisosteres of Sorafenib are described. Their in vitro antiproliferative activity against A375P melanoma cell line was tested. Compounds 1b, 1d, 1g, and 1j showed the highest potency against A375P cell line with IC50 values in sub-micromolar scale. In addition, compound 1d exerted high selectivity towards RAF1 serine/threonine kinase with 96.47% inhibition at 10 μM, and IC50 of 0.96 μM. This compound can possess antiproliferative activity against melanoma cells through inhibition of RAF1 kinase.",

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Novel quinolinylaminoisoquinoline bioisosteres of sorafenib as selective RAF1 kinase inhibitors: Design, synthesis, and antiproliferative activity against melanoma cell line

Abstract

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