A series of mono-pyrrolo[2,3-d]pyrimidines 4a-4k, unsymmetrical bis-purine isosteres 5a-5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolyl)phenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa) cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent a...

A number of new functionalized 4,5-dihydropyrazolo[1,5- a ]thieno[3,2- e ]pyrimidine derivatives were obtained by the domino reaction thienylhydrazonyl chlorides with (1,2,4-oxadiazol-5-yl)acetonitrile. In organic synthesis, much attention has been recently paid to tandem and reactions. The advantage such reactions concerns high selectivity, ease performance, reduction intermediate steps, atom ...

Dipyridamole, an inhibitor of facilitated transport systems for purines and pyrimidines, was shown to enhance the toxicity of methotrexate (MTX) against cells in culture and in mice. Under certain incubation conditions, the availability of preformed pu rines and pyrimidines in undialyzed serum appeared to render Chinese hamster ovary cells insensitive to MTX. Addition to the culture of nontoxic...

Purinergic receptors, represented by several families, are arguably the most abundant receptors in living organisms and appeared early in evolution. After slow acceptance, purinergic signalling in both peripheral and central nervous systems is a rapidly expanding field. Here, we emphasize purinergic co-transmission, mechanisms of release and breakdown of ATP, ion channel and G-protein-coupled-r...

The treatment of Human African trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important; pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp., has been identified as a candidate target, and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 fr...

We have previously reported the anti-neoplastic properties of ~-methylthio-4-amino-5-hydroxymethylpyrimidine (methioprim) and of other related pyrimidines with modification of the 2alkylthio substituent (2). These compounds were initially chosen for study following the observations of Guthrie et a/. that collateral sensitivity for methioprim was demonstrable in amethopterin-resistant strains of...

Dihydrofolate reductase (DHFR) plays a ubiquitous role in the biosynthesis of DNA, RNA and essential amino acid methionine, and exhibits potential application in the treatment and prophylaxis of AIDS-associated opportunistic microbial infections. In this study, a series of DHFR analogs of 2,4-diaminopyrido[2,3-d]pyrimidines and 2,4-diaminopyrrolo[2,3-d]pyrimidines were subjected to quantitative...

Since the first synthesis of trifluoromethyl ethers in 1935, the trifluoromethoxy (OCF3) group has made a remarkable impact in medicinal, agrochemical, and materials science research. However, our inability to facilely incorporate the OCF3 group into molecules, especially heteroaromatics, has limited its potential across a broad spectrum of technological applications. Herein, we report a scalab...

Inspired by the reported antiviral activity of pyrimidines and triazolopyrimidines, two series 2-anilinopyrimidines (5a-e) 1-aryl-[1,2,4]triazolo[4,3-a]pyrimidines (14a-k) were designed synthesized as potential agents. X-ray crystallographic study compounds (14d) (14k) confirmed structure desired isomer revealed coplanarity fused [1,2,4]triazolo[4,3-a]pyrimidine rings with aryl side group. DFT ...