Synthesis of desformylflustrabromine and its evaluation as an alpha4beta2 and alpha7 nACh receptor modulator.
Desformylflustrabromine (dFBr; 1) and desformylflustrabromine-B (dFBr-B; 2) have been previously isolated from natural sources, and the former has been demonstrated to be a novel and selective positive allosteric modulator of alpha4beta2 nicotinic acetylcholine (nACh) receptors. The present study describes the synthesis of water-soluble salts of 1 and 2, and confirms and further investigates the actions of 1 and 2 using two-electrode voltage clamp recordings.
Kim
Jin-Sung
JS
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Padnya
Anshul
A
Weltzin
Maegan
M
Edmonds
Brian W
BW
Schulte
Marvin K
MK
Glennon
Richard A
RA
D000495:Allosteric Site; D000818:Animals; D001966:Bromine / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis* / Q000494:pharmacology; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D018733:Nicotinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014867:Water / Q000737:chemistry; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D006842:Hydrocarbons, Brominated; D026121:Indole Alkaloids; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C524215:desformylflustrabromine; C403531:nicotinic receptor alpha4beta2; D014867:Water; D001966:Bromine