171012-65-0Relevant academic research and scientific papers
Short, enantiospecific synthesese of indolizidines 209B and 209D, and piclavine A from diethyl-L-glutamate
Jefford,Sienkiewicz,Thornton
, p. 1511 - 1524 (1995)
The 1H-pyrrole derivative obtained from diethyl L-glutamate hydrochloride and tetrahydro-2,5-dimethoxyfuran was cyclized with BBr3 to ethyl (5S)-5,6,7,8-tetrahydro-8-oxoindolizine-5-carboxylate (18). Catalytic hydrogenation of 18 over Pd/C in AcOH gave ethyl (5S,8aR)-octahydroindolizine-5-carboxylate (21), whereas hydrogenation over Rh/Al2O3 in EtOH/AcOH 99:1 afforded mainly ethyl (5S,8S,8aS)-octahydro-8-hydroxyindolizine-5-carboxylate (22). By functional-group interconversions, 21 was transformed into piclavine A (1) and indolizidine 209D (2). Similarly, (5R,8R,8aS)-octahydro-5-pentylindolizine-8-methanol (37), the final relay for indolizidine 209B (3), was obtained from 22.
Indolizidine (-)-235B′ and related structural analogs: Discovery of nicotinic receptor antagonists that inhibit nicotine-evoked [ 3H]dopamine release
Pivavarchyk, Marharyta,Smith, Andrew M.,Zhang, Zhenfa,Zhou, Dejun,Wang, Xu,Toyooka, Naoki,Tsuneki, Hiroshi,Sasaoka, Toshiyasu,McIntosh, J. Michael,Crooks, Peter A.,Dwoskin, Linda P.
, p. 132 - 139 (2011)
Although several therapeutic agents are available to aid in tobacco smoking cessation, relapse rates continue to be high, warranting the development of alternative pharmacotherapies. Nicotine-evoked dopamine release from its presynaptic terminals in the central nervous system leads to reward which maintains continued tobacco use. The ability of indolizidine (-)-235B′ and a sub-library of structurally related analogs to inhibit nicotine-evoked [ 3H]dopamine release from rat striatal slices was determined in the current study. Indolizidine (-)-235B′ inhibited nicotine-evoked [ 3H]dopamine release in a concentration-dependent manner (IC 50 = 42 nM, Imax = 55%). Compound (-)-237D, the double bond-reduced analog, afforded the greatest inhibitory potency (IC50 = 0.18 nM, Imax = 76%), and was 233-fold more potent than indolizidine (-)-235B′. The des-8-methyl aza-analog of indolizidine (-)-235B′, ZZ-272, also inhibited nicotine-evoked [3H]dopamine release (IC 50 = 413 nM, Imax = 59%). Concomitant exposure to maximally effective concentrations of indolizidine (-)-235B′, ZZ-272 or (-)-237D with a maximally effective concentration of α-conotoxin MII, a selective antagonist for α6β2-containing nicotinic receptors, resulted in inhibition of nicotine-evoked [3H]dopamine release no greater than that produced by each compound alone. The latter results suggest that indolizidine (-)-235B′, (-)-237D, ZZ-272 and α-conotoxin MII inhibit the same α-conotoxin MII-sensitive nicotinic receptor subtypes. Thus, indolizidine (-)-235B′ and its analogs act as antagonists of α6β2-nicotinic receptors and constitute a novel structural scaffold for the discovery of pharmacotherapies for smoking cessation.
