Discovery of tetrahydropyrido[4,3-d]pyrimidine derivatives for the treatment of neuropathic pain.

A series of tetrahydropyridopyrimidine derivatives were synthesized and evaluated for neurotoxicity and peripheral analgesic activity followed by assessment of antiallodynic and antihyperalgesic potential in two peripheral neuropathic pain models, the chronic constriction injury (CCI) and partial sciatic nerve ligation (PSNL). Compounds (4b and 4d) exhibiting promising efficacies in four behavioral assays of allodynia and hyperalgesia (spontaneous pain, tactile allodynia, cold allodynia and mechanical hyperalgesia) were quantified for their ED50 values (15.12-65.

Influence of charge on encapsulation and release behavior of small molecules in self-assembled layer-by-layer microcapsules.

The objective of this study is to investigate the influence of charge of model small molecules on their encapsulation and release behavior in layer-by-layer microcapsules (LbL-MC). Poly(styrene sulfonate) and poly(ethylene imine) were sequentially adsorbed on calcium carbonate sacrificial templates to prepare LbL-MC. Model molecules with varying charge, anionic - ascorbic acid, cationic - imatinib mesylate (IM) and neutral - 5-fluorouracil were encapsulated in LbL-MC.

Discovery of Fused Triazolo-thiadiazoles as Inhibitors of TNF-alpha: Pharmacophore Hybridization for Treatment of Neuropathic Pain.

Introduction: Neuropathic pain is a complex, chronic pain state that is usually accompanied by tissue injury. With neuropathic pain, the nerve fibers themselves may be damaged, dysfunctional, or injured.

Methods: A series of pharmacophoric hybrids of substituted aryl semicarbazides incorporated into a fused triazolo-thiadiazole nucleus were synthesized and evaluated for neuropathic pain activity.

Discovery of novel 1,2,4-triazol-5-ones as tumor necrosis factor-alpha inhibitors for the treatment of neuropathic pain.

In this work, synthetic integration of substituted semicarbazides and various aliphatic, aryl and heteroaryl acids into 1,2,4-triazol-5-ones was accomplished. Following the assessment of neurotoxicity and peripheral analgesic activity, the compounds were evaluated in two peripheral models of neuropathic pain, the chronic constriction injury and partial sciatic nerve ligation to assess their antihyperalgesic and antiallodynic potential. ED(50) studies undertaken for selected compounds exhibiting promising efficacies (1c, 3c and 4a) revealed values ranging from 13.

Novel piperazinyl derivatives with anti-hyperalgesic, anti-allodynic and anti-inflammatory activities useful for the treatment of Neuropathic Pain.

A series of structurally novel compounds possessing 2-phenylpiperazin-1-yl nicotinamide template was synthesized and evaluated for neuropathic pain activity. After the assessment of neurotoxicity and peripheral analgesic activity, the compounds were evaluated in a peripheral neuropathic pain model, the chronic constriction injury (CCI) to assess their antiallodynic and antihyperalgesic potential. Studies carried out to assess the underlying mechanism revealed that the compounds (5 and 6) suppressed the inflammatory component of the neuropathic pain and inhibited oxidative and nitrosative stress.