Potassium channel modulators

Coghlan MJ, Carroll WA, Gopalaknshnan M (2001) Recent developments in the biology and medicinal chemistry of potassium channel modulators update from a decade of progress. JMed Chem 44 1627-1653 Pregnane X Receptor... 

Robertson, B. and Knox, R.J. (2004) A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells. Journal of Biomolecular Screening, 9, 671-677. 

Hewawasam, P. and Starrett, J. E. (Bristol-Myers Squibb) 3-Substituted-4-arylquinolin-2-one derivatives as potassium channel modulators, W00034244. 

Sodium and Potassium Channel Modulators Their Role in Neuroprotection Tihomir P. Obrenovich... 

Historically, the strategies pursued in the discovery of Kvl.5 inhibitor lead compounds have varied chemistry utilizing potassium channel modulator privileged structures as cores or scaffolds, as previously reviewed [34] rescaffolding of disclosed chemical series [41,54,56] and pharmacophore... 

This is indeed the case. In addition to gamma-aminobutyric acid (GABA), opiate and cholecystokinin receptor activities, the benzodiazepine scaffold is also found in muscle relaxants, antidepressants, neuroleptics, hypnotics, NK-1 receptor and vasopressin receptor antagonists, integrin antagonists, farnesyl transferase and phosphodiesterase inhibitors, potassium channel modulators, and others. 

Evans, J.M., Hadley, M.S. and Stemp, G. (1992) Potassium Channel Modulators Pharmacological, Molecular and Clinical Aspects (Hamilton, T.C. and Weston, A.H., eds.), 13, 341-368, Blackwell Scientific, Oxford. 

McCaully, J. (1991) Current Drugs — Potassium Channel Modulators. KCMB5-19. 

Weston AH, Hamilton TC, eds. Potassium Channel Modulators, pharmacological, molecular and clinical aspects. Oxford Blackwell, 1992. 

Hirst P, ed. Potassium Channel Modulators (from November 1991). London Current Drugs. 

While the potassium channel modulation may play an important role in the future of pain management particularly in neuropathic states, this potential has yet to be realized. The existing family representative (flupirtine) has shown limited utility and currently research and interest in this area is somewhat low... 

R.H. Poyser, T.C. Hamilton, Potassium channel modulators current situation and future expectations. Drug Future 19 (1994) 39-47. 

The conversion of the chromene 54 to epoxide 55 (a synthetic precursor for potassium channel modulators) and diol 56 (Fig. 40) may be achieved by a number of microbial catalysts, notably Mortierella rammaniana SC 13840 which gives the diol 56 in 65% yield m. 91% optical purity [62]. In an analogous conversion, the related microorganism Mortierella isabellina ATCC 42613 converted both chromenes 57 and 58 (Fig. 41) to a mixture of the corresponding cis- and tran -diols, presumably the result of regio- but nonstereo-selective acid-catalyzed hydrolysis of an intermediate epoxide, with both isomeric diols being formed in identical enantiomeric purities [34]. 

---