No abstract

A first-in-class series of low molecular weight trisubstituted triazines were synthesized and evaluated for their ability to mimic protein A binding to human IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3-phenylenediamine component was essential for robust activity. Twenty-two compounds, represented by lead molecule 34, displayed significant activity compared to protein A. These compounds may prove useful for the treatment of autoimmune disease.

gem-Dimethylcyclopropanes were obtained by a cyclopropanation of allylic alcohols and ethers using a mixture of diethylzinc and 2,2-diiodopropane in 53-96% yields. Enantioenriched gem-dimethylcyclopropanes were also synthesized using a glucosederived auxiliary.

A valuable alternative to the traditional Simmons–Smith reagents is offered by the title compounds, as a result of their ease of preparation and high reactivities towards unfunctionalized olefins (see scheme).

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.