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Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: Synthesis and neuropharmacology.

By June 29, 2013No Comments
 pm1[Epub ahead of print]

Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: Synthesis and neuropharmacology.

Source

Neuropathic Pain Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science – Pilani, Hyderabad Campus, R.R. District, 500078 Andhra Pradesh, India. Electronic address: pyogee@hyderabad.bits-pilani.ac.in.

Abstract

We disclose the discovery of a novel series of tetrahydropyrido-pyrazoles that are potent inhibitors of tumour necrosis factor-alpha (TNF-α), nitric oxide and cannabinoid receptor subtype 1 (CB1). We report herein the synthesis and neuropharmacological screening results of the titled compounds in two acute pain and two neuropathic pain models in rodents. Particularly the analogue N-(4-bromophenyl)-3-tert-butyl-5-ethyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide (8a) exhibited pronounced acute antinociceptive efficacy, also being effective in chronic constriction injury (ED50 = 23.8 mg/kg) and partial sciatic nerve injury (ED50 = 29.0 mg/kg) models with CB1 receptor activity (IC50 = 49.6 nM) and inhibitory effect on TNF-α (86.4% inhibition at 100 mg/kg). These results suggest the importance of the development of this lead as multi-targeted treatment strategy for neuropathic pain.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
PMID:

 

23807113

 

[PubMed – as supplied by publisher]
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