22944-65-6Relevant academic research and scientific papers
Guanidine Synthesis: Use of Amidines as Guanylating Agents
Baeten, Mattijs,Maes, Bert U. W.
supporting information, p. 826 - 833 (2016/03/12)
The use of amidines for the tandem or one-pot synthesis of guanidines is reported. Guanidines are obtained by oxidative rearrangement of readily available and stable amidines into carbodiimides, followed by in situ reaction with amines. The protocol can be executed under mild reaction conditions (30°C), in a green solvent (dimethyl carbonate). The amine scope is broad, including sterically hindered, oxidation-sensitive and chiral amines. Examples for the synthesis of both acyclic and cyclic guanidines are provided. 2-Propoxyphenyl iodide (2-PrOPhI) by-product, generated from the oxidant [N-(p-toluenesulfonyl)imino](2-propoxyphenyl)iodinane (2-PrOPhINTs), can be isolated in high yields making regeneration of the hypervalent iodine reagent possible. The utility and greenness of the synthetic method versus the state-of-the-art is demonstrated by a new route towards the antihypertensive drug Pinacidil. The process mass intensity (PMI) of the new route is only 24% of the classical one.
Synthesis and evaluation of 6-methylene-bridged uracil derivatives. Part 2: Optimization of inhibitors of human thymidine phosphorylase and their selectivity with uridine phosphorylase
Yano, Shingo,Kazuno, Hideki,Sato, Tsutomu,Suzuki, Norihiko,Emura, Tomohiro,Wierzba, Konstanty,Yamashita, Jun-Ichi,Tada, Yukio,Yamada, Yuji,Fukushima, Masakazu,Asao, Tetsuji
, p. 3443 - 3450 (2007/10/03)
A series of novel 6-methylene-bridged uracil derivatives have been optimized for clinical use as the inhibitors of human thymidine phosphorylase (TP). We describe their synthesis and evaluation. Introduction of a guanidino or an amidino group enhanced the in vitro inhibitory activity of TP comparing with formerly reported inhibitor 1. Their selectivity for TP based on uridine phosphorylase inhibitory activity was also evaluated. Compound 2 (TPI) has been selected for clinical evaluation based on its strong TP inhibition and excellent modulation of 2′-deoxy-5-(trifluoromethyl)uridine (F3dThd) pharmacokinetics. As a result, TAS-102 (a combination of F3dThd and TPI) is currently in phase 1 clinical studies.
