Design and Synthesis of New 1,3,5‐Trisubstituted Triazines for the Treatment of Cancer and Inflammation

ChemistryOpen

Dr. Shaun D. Abbott¹  Valérie Perron¹  Jean‐Simon Duceppe¹  Dr. Lyne Gagnon¹  Lilianne Geerts¹  Dr. Brigitte Grouix¹  Dr. Boulos Zacharie¹  Dr. Christopher L. Penney¹  François Sarra‐Bournet¹  Dr. Nicole Wilb¹  Pierre Laurin¹  Liette Gervais¹ 

[1] Prometic Biosciences Inc. 500 boul. Cartier Ouest, Bureau 150 Laval Québec H7V 5B7 Canada;

关键词: autoimmune diseases;    cancer;    inflammation;    structure–activity relationships;    triazines;   

DOI  :  10.1002/open.201800136

来源: DOAJ

【 摘 要 】

Abstract Low‐molecular‐weight synthetic molecules 1 with the general 2‐(fluorophenylamino)‐4,6‐disubstituted 1,3,5‐triazine structure and showing anti‐inflammatory and anticancer activities were explored. Structure–activity relationship studies demonstrated the importance of the aminopentyl chain, the 3‐ or 4‐fluorophenylaniline component, and the presence of at least one substituent, such as a tyramine moiety, attached directly to the triazine ring as essential for good activity. These compounds, represented by leads 4‐{2‐[4‐(5‐Aminopentylamino)‐6‐(3‐fluorophenylamino)‐1,3,5‐triazin‐2‐ylamino]ethyl}phenol (6) and 4‐{2‐[4‐(5‐Aminopentylamino)‐6‐(4‐fluorophenylamino)‐1,3,5‐triazin‐2‐ylamino]ethyl}phenol (10), displayed moderate and significant in vitro and in vivo dual activities, respectively, and address the molecular link between inflammation and cancer. Compound 10 demonstrated significant antitumor efficacy upon administration by the oral and intravenous routes in several animal models. This class of triazine compounds is new, safe, and nontoxic and offers a novel approach to the treatment of inflammation and cancer.

【 授权许可】

Unknown