Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: synthesis and neuropharmacology
Yogeeswari, P; Sharma, M; Samala, G; Gangadhar, M; Karthick, S; Mallipeddi, S; Semwal, A; Sriram, D
| HERO ID | 2236371 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | Discovery of novel tetrahydro-pyrazolo [4,3-c] pyridines for the treatment of neuropathic pain: synthesis and neuropharmacology |
| Authors | Yogeeswari, P; Sharma, M; Samala, G; Gangadhar, M; Karthick, S; Mallipeddi, S; Semwal, A; Sriram, D |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 66 |
| Page Numbers | 211-220 |
| 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. |
| Doi | 10.1016/j.ejmech.2013.05.022 |
| Pmid | 23807113 |
| Wosid | WOS:000323628500023 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Antihyperalgesic; Antiallodynic; Tetrahydropyrazolo-pyridine; Cannabinoid receptor; Nitric oxide; Antioxidant |