Novel Quinolinylaminoisoquinoline Bioisosteres of Sorafenib as Selective RAFI Kinase Inhibitors: Design, Synthesis, and Antiproliferative Activity against Melanoma Cell Line

  • Cho, Hye Jung
  • El-Gamal, Mohammed Ibrahim
  • Oh, Chang-Hyun
  • Lee, So Ha
  • Sim, Taebo
  • 외 4명
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초록

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, id, 1g, and 1j showed the highest potency against A375P cell line with IC50 values in sub-micromolar scale. In addition, compound id exerted high selectivity towards RAF1 serine/threonine kinase with 96.47% inhibition at 101 mu m, and IC50 of 0.961 mu m. This compound can possess antiproliferative activity against melanoma cells through inhibition of RAF1 kinase.

키워드

bioisosteremelanomaquinolinylaminoisoquinolineSorafenibantiproliferative activityTHERAPEUTIC TARGETDERIVATIVESDIARYLAMIDESDIARYLUREAS
제목
Novel Quinolinylaminoisoquinoline Bioisosteres of Sorafenib as Selective RAFI Kinase Inhibitors: Design, Synthesis, and Antiproliferative Activity against Melanoma Cell Line
저자
Cho, Hye JungEl-Gamal, Mohammed IbrahimOh, Chang-HyunLee, So HaSim, TaeboKim, GaramChoi, Hong SeokChoi, Jung HoonYoo, Kyung Ho
DOI
10.1248/cpb.c13-00283
발행일
2013-07
유형
Article
저널명
Chemical and Pharmaceutical Bulletin
61
7
페이지
747 ~ 756