1,3-Dipolar cycloaddition of nitrile oxides to (R)-1-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: synthesis and antimycobacterial evaluation of novel enantiomerically pure di- and trispiroheterocycles

Enantiomerically pure (R)-(1-phenylethyl)-3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones were synthesized for the first time, and their 1,3-dipolar cycloaddition with nitrile oxides affording di- and trispiroheterocycles regio- and stereoselectively in moderate yields was investigated. These compounds were evaluated against Mycobacterium tuberculosis H37Rv (MTB) and multi-drug-resistant M. tuberculosis (MDR-TB). Among the compounds screened, the dispiroheterocycle, namely, (5R,6R,10S)-3,9-bis(4-chlorophenyl)-10-(2,4-dichlorophenyl)-14-[(E)-(2,4-dichlorophenyl)methylidene]-12-[(R)-1-phenylethyl]-1,4,7-trioxa-2,8,12-tri-azadispiro[4.0.4.4]tetradeca-2,8-diene 5m was found to possess the maximum activity with MIC of 0.49 μM against MTB, being 9.6 and 15.6 times more potent than ciprofloxacin and ethambutol, respectively. Against MDR-TB, 5m displayed maximum activity with an MIC of 0.49 μM, with it thus being more active than rifampicin, isoniazid, ciprofloxacin and ethambutol by 7.8, 23, 77 and 124 times, respectively.     

Arc Hyperbolic sine creep theory applied to torsion-tension member of circular cross section

A multiaxial creep theory is presented in this paper which will predict the total deformations of a load-carrying member at any specified time after load. Load-deformation relations are derived based on the assumption that the isochronous stress-strain diagram of the material can be represented by an arc hyperbolic sine function [see, eq (2)]. A closed solution was obtained for the torsion-tension member considered in this investigation. Experimental data were obtainsed for nylon and high-density polyethylene members in a controlled-environment room and for 17-7PH stainless-steel members at 972° F. Good agreement was found between theory and experiment.Formerly with Department of Theoretical and Applied Mechaaics, University of Illinois, Urbana, Ill.Paper was presented at 1963 SESA Spring Meeting held in Seatle, Wash., on May 8–10.     

Facile three-component domino reactions in the regioselective synthesis and antimycobacterial evaluation of novel indolizines and pyrrolo[2,1-a]isoquinolines

The domino reactions of pyridine/isoquinoline, bromoacetonitrile/ethyl bromoacetate and a series of β-nitrostyrenes in the presence of triethylamine afforded novel tri-/disubstituted indolizines and pyrrolo[2,1-a]isoquinolines regioselectively, presumably via substitution-dipole generation-1,3-dipolar cycloaddition-elimination and/or aromatisation sequence. In vitro screening of all the seventeen compounds synthesized against Mycobacterium tuberculosis H37Rv discloses that ethyl 2-(4-fluorophenyl)pyrrolo[2,1-a]isoquinoline-3-carboxylate displays maximum potency with minimum inhibitory concentration (MIC) of 1.0 μM, being 7.6 and 4.7 times more potent than the standard first line TB drugs, ethambutol and ciprofloxacin, respectively.     

Epibatidine and its analogues as nicotinic acetylcholine receptor agonist: an update

Epibatidine (EPB) (1), an alkaloid isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor has attracted attention because of its exceptionally powerful analgesic properties: several hundred times greater than those of morphine, and the fact that it acts at nicotine rather than opiate receptors. Although the substance is toxic, it does serve as a lead compound in the development of drugs for pain relief as well as treatment of disorders whose pathogenesis involves nicotinic receptors. In this article, isolation, synthetic methods, effect on neuronal and neuromuscular nicotinic receptors, therapeutic potential, toxicity, nicotinic pharmacophore structural modifications related issues of 1 are discussed.     

Progress in the research of artemisinin and its analogues as antimalarials: an update

Malaria is the number one infectious disease in the world today. Worldwide, over two million people die each year from malaria. This shocking reality is largely due to the emergence of drug resistant strains of Plasmodium falciparum. Artemisinin, a sesquiterpene lactone endoperoxide isolated from Artemesia annua has been shown to be a fast acting, safe and effective drug against multidrug-resistant and sensitive strains of P. falciparum. This article reports a survey of the literature dealing with artemisinin related antimalarial issues that have appeared from 1980s to the beginning of 2003. A broad range of medical and pharmaceutical disciplines is covered, including a brief introduction about discovery, phytochemical aspects, antimalarial mechanism of action, pharmacokinetics, and major drawbacks and various structural modifications made to overcome them.     

Bis-spirochromanones as potent inhibitors of Mycobacterium tuberculosis: synthesis and biological evaluation

Molecular Diversity - On the basis of reported antimycobacterial property of chroman-4-one pharmacophore, a series of chemically modified bis-spirochromanones were synthesized starting from...     

Synthesis and antimicrobial activities of some novel substituted 2-imidazolyl-N-(4-oxo-quinazolin-3(4H)-yl)-acetamides

Several substituted-quinazolin-3(4H)-ones 8-11ad were synthesized by condensation of 2-chloro-N-(4-oxo-substituted-quinazolin-3(4H)-yl)-acetamides with various substituted imidazoles through one pot reaction. Elemental analysis, IR, (1)H-NMR and mass spectral data confirmed the structure of the newly synthesized compounds. Synthesized quinazolin-4-one derivatives were investigated for their antitubercular, antibacterial and antifungal activities. Some of the tested compounds showed good antitubercular activity. None of the synthesized compounds showed significant antibacterial and antifungal activity.