The beta-diketo acids (DKAs) represent a major advance for anti-HIV-1 integrase drug development. We compared the inhibition of HIV-1 integrase by six DKA derivatives using the wild-type enzyme or the double-mutant F185K/C280S, which has been previously used for crystal structure determinations. With the wild-type enzyme, we found that DKAs could be classified into two groups: those similarly p...

The synthesis and characterization of new 4-[(2-alkyl)-2H-tetrazol-5-yl]phenyl 4-alkyloxybenzoates (5a–i) and 5-{4-[(4-substituted)benzyloxy]phenyl}-2-alkyl-2H-tetrazoles (7a–e) are reported. The reported tetrazoles contain two alkyl chains (six to ten carbon atoms) except for 5h and 7e which have a chiral citronellyl group linked at the N-2 nitrogen atom of the tetrazole ring and 5i having a b...

In this work, 5-mercapto-1-methyltetrazole was studied by low temperature matrix-isolation and solid-state infrared spectroscopy, DFT(B3LYP)/6-311CCG(d,p) calculations and photochemical methods. In the low temperature neat solid phase and isolated in an argon matrix, the compound was found to exist in the 1-methyl-1,4-dihydro-5H-tetrazole-5-thione tautomeric form. The infrared spectra of the co...

A series of 5-(4-alkoxyphenylalkyl)-1H-tetrazole derivatives, containing an oxazole-based group at the alkoxy moiety, was prepared and their antidiabetic effects were evaluated in two genetically obese and diabetic animal models, KKAy mice and Wistar fatty rats. Syntheses were performed by cyclization of the corresponding nitrites reacting with azide compounds. A large number of the 5-(4-alkoxy...

During the process development for multigram-scale synthesis of olmesartan medoxomil (OM), two principal regioisomeric process-related impurities were observed along with the final active pharmaceutical ingredient (API). The impurities were identified as N-1- and N-2-(5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl derivatives of OM. Both compounds, of which N-2 isomer of olmesartan dimedoxomil is a no...

The synthesis of 5-nitro-2-nitratomethyl-1,2,3,4-tetrazole (4) and its full characterization are given here. Compound 4 was synthesized through the nitration of 5-nitro-2-hydroxymethyl-tetrazole (3) with fuming nitric acid and acetic anhydride and its structure was characterized by MS, FT-IR, ¹H-NMR and ¹³C-NMR techniques. The crystal structure of 4 was determined by X-ray single crystal diffra...

INTRODUCTION We report the synthesis of novel 1,4-dihydropyridine derivatives containing biphenyl-2'-tetrazole moieties. We hypothesized that merging the key structural elements present in an AT1 receptor antagonist with key structural elements in 1,4-dihydropyridine calcium channel blockers would yield novel analogs with potential dual activity for both receptors. This strategy led to the desi...

A variety of novel tetrazole derivatives attached to the β-lactam ring was made utilizing heptanitrile in a reaction with generated azide-β-lactam derivatives, and these compounds were then studied using IR NMR spectroscopy. Biological testing showed that most final good antibacterial antifungal activity, particularly derivative (b3), which shown efficacy on par or even superior reference drugs...

Tetrazoles are an important class of heterocycles in a wide range of applications, such as, organocatalysis and transition metal catalysis, propellants, explosives, and perhaps most commonly, as nonclassical isosteres of carboxylic acids in medicinal chemistry. This broad utility has prompted significant effort toward tetrazole synthesis, and notable among these is that of Sharpless, in which a...