3D QSAR studies on new piperazine derivatives with antihistamine and antibradykinin effects

Choo, Hea-Young Park; Chung, Bum-Jun

doi:10.1007/bf02975441

Cited by 2 publications

(1 citation statement)

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“…Piperazine and its derivatives have played a significant role in medicinal chemistry. Piperazine is a small molecule with a rigid backbone with numerous biological activities such as anticancer, 18,19 calcium channel blockers, 20,21 antimalarial, 22 antihistamine, 23,24 antimicrobial, 25 antidepressant, 26 antioxidant, 27 antiallergic, 28 antiviral, 29 antipsychotic, 30 and antiparasitic 31,32 activity. The various biological activities of piperazine nuclei are due to easy modification, proper alkalinity, water solubility, capacity for formation of hydrogen bonds, and adjustment of molecular physicochemical properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of a disubstituted piperazine derivative with T-type channel blocking action and analgesic properties

et al. 2016

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BackgroundT-type calcium channels are important contributors to signaling in the primary afferent pain pathway and are thus important targets for the development of analgesics. It has been previously reported that certain piperazine-based compounds such as flunarizine are able to inhibit T-type calcium channels. Thus, we hypothesized that novel piperazine compounds could potentially act as analgesics.ResultsHere, we have created a series of 14 compound derivatives around a diphenyl methyl-piperazine core pharmacophore. Testing their effects on transiently expressed Cav3.2 calcium channels revealed one derivative (3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(2-methoxyphenyl)-1,2,5-oxadiazole 2-oxide, compound 10e) as a potent blocker. 10e mediate tonic block of these channels with an IC50 of around 4 micromolar. 10e also blocked Cav3.1 and Cav3.3 channels, but only weakly affected high-voltage-activated Cav1.2 and Cav2.2 channels. Intrathecal delivery of 10e mediated relief from formalin and complete Freund’s adjuvant induced inflammatory pain that was ablated by genetic knockout of Cav3.2 channels.ConclusionsAltogether, our data identify a novel T-type calcium channel blocker with tight structure activity relationship (SAR) and relevant in vivo efficacy in inflammatory pain conditions.

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