Restless leg syndrome presenting as chronic severe limb pain in a dialysis patient.

"Chronic pain" is a commonly reported symptom among hemodialysis patients. Despite its high prevalence and the poor health-related quality of life associated with it, chronic pain remains an ineffectively assessed and managed entity in dialysis patients. We report a case of a 55-year-old gentleman on maintenance hemodialysis who presented with 3 months history of "excruciating flitting and fleeting type" of pain largely involving both lower limbs and occasionally neck, shoulder, chest, and upper limbs.

Medicinal chemistry of vicinal diaryl scaffold: A mini review.

The privileged structures have been widely used as a valuable template in new drug discovery. 1,2-Diaryl or vicinal diaryl is a simple scaffold found in many drugs and naturally occurring compounds. From synthetic point of view, the vicinal diaryl derivatives are easily accessible due to their facile and expedient syntheses.

Assessment of antiplatelet activity of 2-aminopyrimidines.

A series of 4,6-diaryl-2-aminopyrimidines was developed as antiplatelet agents and their potency was evaluated by in vitro assay. Compound 14k was found to be two times more potent than aspirin. These encouraging results could be helpful for the development of new antiplatelet compounds.

Recent development of 3C and 3CL protease inhibitors for anti-coronavirus and anti-picornavirus drug discovery.

SARS-CoV (severe acute respiratory syndrome-associated coronavirus) caused infection of ~8000 people and death of ~800 patients around the world during the 2003 outbreak. In addition, picornaviruses such as enterovirus, coxsackievirus and rhinovirus also can cause life-threatening diseases. Replication of picornaviruses and coronaviruses requires 3Cpro (3C protease) and 3CLpro (3C-like protease) respectively, which are structurally analogous with chymotrypsin-fold, but the former is a monomer and the latter is dimeric due to an extra third domain for dimerization.

Synthesis and evaluation of pyrazolone compounds as SARS-coronavirus 3C-like protease inhibitors.

A series of pyrazolone compounds as possible SARS-CoV 3CL protease inhibitors were designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide in which several showed potent inhibition against the 3CL protease. Interestingly, one of the inhibitors was also active against 3C protease from coxsackievirus B3. These inhibitors could be potentially developed into anti-coronaviral and anti-picornaviral agents.

Synthesis, docking studies, and evaluation of pyrimidines as inhibitors of SARS-CoV 3CL protease.

A series of 2-(benzylthio)-6-oxo-4-phenyl-1,6-dihydropyrimidine as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Two candidates had encouraging results for the development of new anti-SARS compounds.

Synthesis and anti-HIV-1 integrase activity of cyano pyrimidinones.

A series of 2-phenethyl/benzylthio-6-oxo-4-phenyl-1,6-dihydropyrimidine-5-carbonitrile were synthesized and tested against recombinant HIV-1 integrase in an enzyme assay. 2-(Phenethylthio)-4-(4-chlorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 4m and 2-(phenethylthio)-4-(3-chlorophenyl)-6-oxo-1,6-dihydropyrimidine-5-carbonitrile 4o showed significant inhibition against integrase in the assay (strand transfer: IC(50) values of 16 and 17 microM, respectively).

The search for potent, small molecule NNRTIs: A review.

AIDS has become the leading pandemic disease, and is the cause of death worldwide. Presently, HAART treatment, a combination of reverse transcriptase (RT) and protease inhibitors is also unsuccessful due to the virus getting resistant to the drugs because of mutational changes. Two types of RT inhibitors exist namely nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Synthesis and antiproliferative activity of some diaryldiazepines and diarylpyrimidines.

Novel substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines and 4,6-diaryl-2-aminopyrimidines were synthesized and tested for their antiproliferative activity. Title compounds were obtained by cyclocondensation of a substituted flavone with ethylenediamine and guanidine respectively. The cytotoxicity in vitro against various human leukemic cancer cell lines viz.

Synthesis, antileukemic and antiplatelet activities of 2,3-diaryl-6,7-dihydro-5H-1,4-diazepines.

The synthesis, antileukemic and antiplatelet activity evaluation of 2,3-diaryl-6,7-dihydro-5H-1,4-diazepines are described. In general, it was found that compound 17o showed moderate antileukemic activity against MOLT3 human leukemic cancer cell lines. An arachidonic acid induced platelet aggregation effect on washed rat platelets was studied.

Current scenario of 1,4-diazepines as potent biomolecules--a mini review.

The aim of this review is precisely to give a comprehensive account of the large volume of work carried out on 1,4-diazepines regardless of the degree of unsaturation in the diazepine system. This review mainly emphasizes recent work on the diazepines also including earlier work.