Vishnu Ji Ram

Oxygenated chalcones and bischalcones as potential antimalarial agents.

Oxygenated chalcones (3a,b) and bischalcones (4a-j) have been synthesized and evaluated for antimalarial activity against chloroquine sensitive and resistant strains of Plasmodium berghei in mice. Some of the screened compounds, 3a, 4c, 4e, 4f and 4i, have shown significant activity at 100 mg/kg dose against sensitive strain.

Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones

A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycemic activity but only 4a,b,d,j,o displayed significant reduction in blood glucose level in streptozotocin and sucrose loaded rat models.

Chloropyrimidines as a new class of antimicrobial agents.

In the course of our investigations of pyrimidines as antimycotic agents, we have identified a sub-class, with significant in vitro activity against mycobacteria. The salient feature of these pyrimidine derivatives (3a-o and 7a,b) is their appended aryl, heteroaryl and alkylthio substituent at position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of Mycobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 microg/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 microg/mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 microg/mL. All the synthesized compounds were also evaluated for their antimycotic activity against five pathogenic fungi but only some of them 3j-n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes.

Suitably functionalised pyrimidines as potential antimycotic agents

Various suitably functionalized pyrimidine derivatives have been synthesized to explore their potential as antimycotic agents. Some of the synthesized compounds 4c, 4d, 8a-e have shown highly significant in vitro antifungal activity against five human pathogenic fungi.

A Convenient Synthesis and Hepatoprotective Activity of Imidazo(1,2-c)pyrimido(5,4-e)pyrimidine, Tetraazaacenaphthene and Tetraazaphenalene from Cyclic Ketene Aminals Through Tandem Addition-Cyclization Reactions {

A novel one-pot synthesis of imidazo[1,2-c]pyrimido[5,4-e]pyrimidinones (2), tetraazaacenaphthene-3,6-diones (4), tetarazaphenalene-1,7-dione (4d) is delineated from the reaction of cyclic ketene aminal (1) and alkyl or aryl isothiocyanate through tandem addition-cyclization reactions. However, reaction of ketene aminal (1a) with alkyl isothiocyanate only yielded angularly cyclized product 5 which did not react further to yield 6. The structure of 2c and 4d was ascertained by single crystal X-ray diffraction analysis which demonstrated a network of various inter- and intramolecular interactions, responsible for the stability and packing of the molecules in the crystalline state. Some of the compounds (2a--h) were screened for hepatoprotective activity but only 2a was found most effective.

Synthesis of thiophenes and thieno[3,2-c]pyran-4-ones as antileishmanial and antifungal agents

Abstract A series of highly functionalized thiophene ( 2 ) and thieno[3,2-c]pyran-4-one( 4 ) derivatives have been synthesized and evaluated for their antileishmanial and antifungal activities.

Synthesis of bridgedhead azolo[3,2-a]pyrimidines and imidazo[2,1-b]thiazines through ring transformation of 2H-pyran-2-ones

Suitably functionalized 3-carbomethoxy/cyano-2H-pyran-2-ones are excellent synthons for the synthesis of arenes and heteroarenes of therapeutic importance. The compounds 6-aryl-3-cyano-4-methylsulfanyl-2H-pyran-2-ones have been transformed into bridgedhead azolopyrimidines and imidazothiazines through thermal and base-induced ring transformation reactions with aminoazoles and imidazolidin-2-thiones, respectively.

Therapeutic role of peroxisome proliferator-activated receptors in obesity, diabetes and inflammation

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family and play a significant role in regulation of lipid metabolism, hepatic peroxisomal enzyme expression, insulin sensitivity and glucose homeostasis. PPARs have been classified into three subtypes encoded by different genes: PPARalpha (NR1C1), PPARdelta (NR1C2), and PPARgamma (NR1C3). Each subtype of PPARs appears to be differently expressed in a tissue-specific manner because of their binding to specific consensus DNA sequences, known as PPREs (peroxisome proliferator response elements). Thus, PPARs have emerged as potential molecular targets for the design and synthesis of a different class of compounds, considering the conformation of receptors for the treatment of human metabolic disorders. This review covers the rapid progress made in functional analysis of PPARs and progress made towards the identification of ligands for each subtype receptor.

Ring transformation reactions part IV: 6-Aryl-3-methoxy-carbonyl-4-methylthio-2H-pyran-2-one, a novel synthon for the synthesis of 1,3-terphenyls from aryl ketones

Abstract 4′-Methoxycarbonyl-5′-methylthio-1′,3′-terphenyls ( 3 ) and methyl (4,6-diarylpyran-2-ylidene)acetate ( 4 ) are synthesized from 6-aryl-3-methoxy-carbonyl-4-methylthio-2H-pyran-2-ones ( 1 ). The salient feature of this procedure is to provide symmetrical, unsymmetrical and heteroaryl terphenyls in single step.

Carbanion-induced base-catalyzed synthesis of unsymmetrical biaryls from suitably functionalized 2H-pyran-2-ones through ring-transformation reactions

Abstract A synthesis of unsymmetrical highly functionalized biaryls with an amino substituent juxtaposed with two nitrile groups in one of the phenyl rings is delineated and illustrated by the carbanion-induced ring-transformation of 6-aryl-4-methylsulfanyl-2 H -pyran-2-one-3-carbonitrile ( 1 ) and 4- sec -amino-6-aryl-2 H -pyran-2-one-3-carbonitrile ( 2 ) to 2-amino-4-aryl-6-methylsulfanyl-1,3-benzodinitrile ( 3 ) and 2-amino-6- sec -amino-4-aryl-1,3-benzodinitrile ( 4 ) using malononitrile as a source of the carbanion, in moderate yield.