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Discovery of potent furan piperazine sodium channel blockers for treatment of neuropathic pain.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2008 Jun 15; Vol. 16 (12), pp. 6379-86. Date of Electronic Publication: 2008 May 06. - Publication Year :
- 2008
-
Abstract
- The synthesis and pharmacological characterization of a novel furan-based class of voltage-gated sodium channel blockers is reported. Compounds were evaluated for their ability to block the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3) as well as the Na(v)1.2 and Na(v)1.5 subtypes. Benchmark compounds from this series possessed enhanced potency, oral bioavailability, and robust efficacy in a rodent model of neuropathic pain, together with improved CNS and cardiovascular safety profiles compared to the clinically used sodium channel blockers mexiletine and lamotrigine.
- Subjects :
- Analgesics, Non-Narcotic chemical synthesis
Animals
Ether-A-Go-Go Potassium Channels antagonists & inhibitors
Furans chemical synthesis
Humans
Male
Mice
Piperazines chemical synthesis
Rats
Rats, Sprague-Dawley
Sodium Channel Blockers chemical synthesis
Structure-Activity Relationship
Analgesics, Non-Narcotic chemistry
Analgesics, Non-Narcotic pharmacology
Furans chemistry
Furans pharmacology
Neuralgia drug therapy
Piperazines chemistry
Piperazines pharmacology
Sodium Channel Blockers chemistry
Sodium Channel Blockers pharmacology
Sodium Channels drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 16
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18501613
- Full Text :
- https://doi.org/10.1016/j.bmc.2008.05.003