64991-61-3Relevant academic research and scientific papers
Modified 5'-Trityl Nucleosides as Inhibitors of Plasmodium falciparum dUTPase
Ruda, Gian Filippo,Nguyen, Corinne,Ziemkowski, Przemyslaw,Felczak, Krzysztof,Kasinathan, Ganasan,Musso-Buendia, Alexander,Sund, Christian,Zhou, Xiao Xiong,Kaiser, Marcel,Ruiz-Perez, Luis M.,Brun, Reto,Kulikowski, Tadeusz,Johansson, Nils Gunnar,Gonzalez-Pacanowska, Dolores,Gilbert, Ian H.
, p. 309 - 320 (2012/01/12)
2'-Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for the treatment of malaria. We previously reported the discovery of 5'-tritylated analogues of deoxyuridine as selective inhibitors of this Plasmodium falciparum enzyme. Herein we report further structure-activity studies; in particular, variations of the 5'-trityl group, the introduction of various substituents at the 3'-position of deoxyuridine, and modifications of the base. Compounds were tested against both the enzyme and the parasite. Variations of the 5'-trityl group and of the 3'-substituent were well tolerated and yielded active compounds. However, there is a clear requirement for the uracil base for activity, because modifications of the uracil ring result in loss of enzyme inhibition and significant decreases in antiplasmodial action. Fewer trips to the dUMP: dUTPase is a potential drug target for the treatment of malaria. We previously reported the discovery of 5'-tritylated analogues of deoxyuridine as selective inhibitors of this P.falciparum enzyme. Herein we report further structure-activity studies of the 5'-trityl group, the introduction of various substituents at the 3'-position of deoxyuridine, and modifications of the base.
Diphenylpyridylmethyl radicals. Part 1. Synthesis, dimerization and ENDOR spectroscopy of diphenyl(2-, 3- or 4-pyridyl)methyl radicals; bond dissociation enthalpies of their dimers
Tzerpos, Nikolaos I.,Zarkadis, Antonios K.,Kreher, Richard P.,Repas, Liesel,Lehnig, Manfred
, p. 755 - 762 (2007/10/02)
ortho-ortho hydrogen van der Waals repulsions are the origin of the propeller shape of the triphenylmethyl radical and the main reason for the low bond dissociation enthalpy (BDH) of its dimer 1 (44.8 J mol-1).In order to reduce these steric repulsions (eliminating some aromatic hydrogens), diphenyl(2-, 3- or 4-pyridyl)methyl radicals 2-4 were prepared through reductive dehalogenation of the corresponding triarylchloromethanes 2-4a with silver in benzene.They form α,p-dimers 2-4e exclusively through the pyridine ring.ENDOR spectroscopy shows that the structure of the radicals, does not deviate substantially from that of the parent radical, PH3C-radical.In contrast, the BDH values of the dimers (measured using EPR spectroscopy) show strengthening of the central C-C bond in 2e (88.7 kJ mol-1) and 3e (90.0 kJ mol-2) and a silimar value for 4e (46.4 kJ mol-1) with respect to the trityl dimer 1.This is a consequence of the ground state stabilization of the dimers 2-4e due to relief of strain (elimination of ring hydrogens), whereas in the case of 4e, this stabilization is probably compensated by the formation of a weaker C-N bond with respect to the C-C bond.The above dimers undergo easy 1,5-H-rearrangement, autocatalysed by the basic pyridyl groups themselves.
AZO ANIONS IN SYNTHESIS. USE OF TRITYL- AND DIPHENYL-4-PYRIDYLMETHYLHYDRAZONES FOR REDUCTIVE C-C BOND FORMATION.
Baldwin, Jack E.,Adlington, Robert M.,Bottaro, Jeffrey C.,Kolhe, Jayant N.,Newington, Ian M.,Perry, Matthew W. D.
, p. 4235 - 4246 (2007/10/02)
The lithium salts of trityl- and diphenyl-4-pyridylmethyl-hydrazones of both aldehydes and ketones react with electrophiles (alkyl halides, aldehydes, ketones, crotonates) at low temperature to form C-trapped azo compounds; these intermediates decompose homolytically with loss of nitrogen below room temperature and can be diverted in a synthetically useful way to alkanes, alkenes, alcohols or saturated esters.
Amino-acids and Peptides. Part 45. The Protection of the Thiol Function of Cysteine and the Imidazole-N of Histidine by the Diphenyl-4-pyridylmethyl Group
Coyle, Susan,Hallett, Allan,Munns, Michael S.,Young, Geoffrey T.
, p. 522 - 528 (2007/10/02)
S-(Diphenyl-4-pyridylmethyl)-L-cysteine (1) and its derivatives (2)-(7) have been prepared and used in peptide synthesis.In contrast to the analogous S-trityl group, this protection is stable in acid but it is cleaved readily by zinc-acetic acid, by mercury(II) acetate, by iodine, and by electrolytic reduction.N(Im)-Diphenyl-4-pyridylmethyl-L-histidine derivatives (9)-(13) are also reported; the protecting group is again stable to acid but cleaved by hydrogenolysis, by zinc-acetic acid, and by electrolytic reduction, and it has been used in the synthesis of L-histidyl-L-leucine, -L-phenylalanine, and -glycine.
