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Fifteen novel β-lactams bearing N-ethyl tert-butyl carbamate group 5a-o and fifteen N-(2-aminoethyl) β-lactams 6a-o were synthesized by [2+2] ketene-imine cycloaddition reaction (Staudinger). The cycloaddition reaction was found to be totally diastereoselective leading exclusively to theformation of cis-β-lactam derivatives. These newly synthesized β-lactams were evaluated for their antimalarial activity against p. falciparum K14 resistant strain and showed good to excellent EC50 values. Of the thirty β-lactams tested, 5 h, 6a and 6c showed IC50 < 20 μM while 5b, 5c, 5e, 5f, 5g, 5i, 5j, 6d, 6g and 6h exhibited IC50 <50 . Compounds 5c, 5h, and 5q-t were examined for their anticancer properties against K562 Leukemia cell line and 5s showed the best activity. Compounds 3a-j, 5a-o, 6a-o, were tested against S. aureus, E. coli, C. albicans and showed no activity below 125 μg/mL. [ABSTRACT FROM AUTHOR]

A new method of the synthesis of heterocyclic derivatives of trifluoroalanine based on the cyclocondensation of methyl trifluoropyruvate tert-butoxycarbonylimine with C, N- and N, N-binucleophiles, like Nsubstituted ureas, 1-benzyl-6-aminouracil, benzamidine, and 3-aminocrotononitrile, followed by hydrolysis of the resulting Boc-derivatives to 5-amino-5-trifluoromethylimidazolidine-2,4-diones, 5-amino-5-trifluoromethyl-1-benzyl-5,7-dihydropyrrolo[2,3- d]-pyrimidine-2,4,6-3 H-trione, 4-amino-2-methyl-5-oxo-4-(trifluoromethyl)-4,5-dihydro-1 H-pyrrole-3-carbonitrile, or 5-amino-5-trifluoromethyl-2-phenyl-3,5-dihydroimidazol-4-one, respectively, was developed. [ABSTRACT FROM AUTHOR]

Simple preparation and isolation of N-(tert-butoxycarbonyl)-N'-methylthiourea on a large scale are described. [ABSTRACT FROM AUTHOR]

A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as psoriasis and inflammatory bowel diseases (IBD), by selective targeting of TYK2. Hit triage, following a high-throughput screen for TYK2 inhibitors, revealed pyridine 1 as a promising starting point for lead identification. Initial expansion of 3 separate regions of the molecule led to eventual identification of cyclopropyl amide 46, a potent lead analog with good kinase selectivity, physicochemical properties, and pharmacokinetic profile. Analysis of the binding modes of the series in TYK2 and JAK2 crystal structures revealed key interactions leading to good TYK2 potency and design options for future optimization of selectivity., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)