Design and synthesis of a novel class EGFR/HER2 dual inhibitors containing tricyclic oxazine fused quinazolines scaffold期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

按检索

Design and synthesis of a novel class EGFR/HER2 dual inhibitors containing tricyclic oxazine fused quinazolines scaffold

Institution:	1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt;2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt;3. Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, 20139, Milan, Italy;4. Department of Biosciences, University of Milan, Milan, 20100, Italy;1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA;2. Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave., SGM 628, Boston, MA 02115, USA;3. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Misr International University, Km 28 Cairo-Ismailia Road (Ahmed Orabi District) Cairo, Egypt;4. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA;5. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, 11566 Cairo, Egypt;1. Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt;2. Institute of Biotechnology for Postgraduate Studies and Research, Suez Canal University, Ismailia, Egypt;3. Chemistry Department, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo P.O. Box, 11562, Egypt;2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, New Giza University, Newgiza, km 22 Cairo–Alexandria Desert Road, Cairo, Egypt;3. Head of Confirmatory Diagnostic Unit, VACSERA, Cairo, Egypt;1. Department of Drug Radiation Research, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo 113701, Egypt;2. Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia

Abstract:	Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed, synthesized and evaluated for their inhibitory activity against EGFR and HER2. Structure-activity relationship (SAR) of these compounds was discussed. From the SAR studies, we found that intramolecular cyclization which possessed a functional Michael acceptor group can enhance the antitumor activities. Compounds 1e and 1h were identified as lead compounds which displayed almost 3–4 times more potent inhibition of EGFR and HER2 than the approved drug lapatinib. The satisfactory physicochemical properties of these compounds were also supported by ACD labs. The results presented here will promote the development of newer dual inhibitors of EGFR and HER2.

Keywords:	Tricyclic fused quinazolines Antitumor activity EGFR HER2 SAR
本文献已被 ScienceDirect 等数据库收录！

设为首页 | 免责声明 | 关于勤云 | 加入收藏