Synthesis and biological evaluation of a new class of triazin–triazoles as potential inhibitors of human farnesyltransferase

Abstract

A new synthesis of ethynyldimethoxytriazine 1, an important platformcompound for developing new chemical entities for anticancer research and for other biological applications, is described. Compound 1 was further reacted with azides 5a-i to provide triazin-triazoles 2a-i, which were tested on human farnesyltransferase and on the NCI-60 human tumor cell lines. Synthesis of other dimethoxytriazine derivatives 15 and 16, linked to a sp 2 or a sp 3 carbon atom were also studied. Electronic supplementary material The online version of this article (2a-i target compounds CO 2 H 2c: IC 50 (human FTase) = 38.6 µM

Self-assembled Triazole AIE-Active Nanofibers: Synthesis, Morphology, and Photophysical Properties

“…The 2-(prop-2-yl-1-ylthio)­pyridine- N -oxide 2 has been synthesized by the reaction of propargyl bromide with sodium 2-sulfido­pyridine- N -oxide in acetonitrile. The α-azido­ketones 4a – g − were synthesized using a new biphasic (CHCl 3 –H 2 O) condition with tetrabutylammonium bromide as phase transfer catalyst . The new triazoles 5a – g were obtained by catalytic cycloaddition reaction between the propargyl derivative 2 and the α-azidoketones 4a – g .…”

Exploring isoxazoles and pyrrolidinones decorated with the 4,6‐dimethoxy‐1,3,5‐triazine unit as human farnesyltransferase inhibitors

“…Of particular interest is that starting from propionyl chloride, 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine 1 was obtained in 55% yield, whose condensation with azides furnished dimethoxytriazinyl‐triazoles 2 . These new compounds have the potential to complex the zinc atom of FTase, but presented only a modest activity as FTase inhibitors and as anticancer agents . It is known that 3,5‐diarylisoxazoles display pharmaceutical properties as interleukin‐8 receptor antagonists or hypolipidemic agents, and weak anticancer activity .…”

“…These new compounds have the potential to complex the zinc atom of FTase, but presented only a modest activity as FTase inhibitors and as anticancer agents. [15] It is known that 3,5diarylisoxazoles display pharmaceutical properties as interleukin-8 receptor antagonists [16] or hypolipidemic agents, [17] and weak anticancer activity. [18] We are now interested in the synthesis of arylisoxazoles substituted by a dimethoxytriazine group, with the general structure 3.…”

Discovery of indolizines containing triazine moiety as new leads for the development of antitumoral agents targeting mitotic events

“…The chemical strategy started with the synthesis of the key dipolarophile 3 dimethylimidodicarbonimidate salt, 23 furnished acetylenic derivative 3 (Scheme 1), used further for all the cycloaddition reactions. Target indolizines containing triazine 27-45 were next obtained by [3+2] cycloaddition reaction of the corresponding ylide 25a-r, generated in situ by triethylamine treatment of pyridinium salts 6-24, with 2-ethynyl-4,6-dimethoxy-1,3,5-triazine 3, followed by spontaneous aromatization of intermediates 26a-r (Scheme 2).…”