- Synthesis and evaluation of isatin analogs as caspase-3 inhibitors: Introduction of a hydrophilic group increases potency in a whole cell assay
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A series of isatin analogs containing a hydrophilic group, including a pyridine ring, ethylene glycol group, and a triazole ring, have been synthesized, and their inhibition potency for caspase-3 was measured both in vitro (i.e., recombinant enzyme) and in whole cells (HeLa cells). The analogs having a hydrophilic group, including 12, 13, 16, 38, and 40, have dramatically increased activity in vitro and in HeLa cells compared to the corresponding unsubstituted N-phenyl isatin analogs.
- Chu, Wenhua,Rothfuss, Justin,Zhou, Dong,MacH, Robert H.
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p. 2192 - 2197
(2011/05/15)
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- Synthesis of a new precursor to the nicotinic receptor tracer 5-IA-85380 precursor using trimethylsilyl iodide as deblocking agent
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We describe the synthesis of a new precursor of 5-IA-85380, specific radiotracer for α4β2 nicotinic acetylcholine receptors. (S)-5-Trimethylstannyl-3-(2-azetidinylmethoxy)pyridine (4) was prepared in six steps and 62% overall yield starting from (S)-2- azetidinecarboxylic acid. The key step of this synthesis is selective release of the amine function without removing the stannyl moiety using trimethylsilyl iodine.
- Brenner, Eric,Baldwin, Ronald M.,Tamagnan, Gilles
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p. 3607 - 3610
(2007/10/03)
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- 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling neurotransmitter release
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Novel heterocyclic ether compounds of the formula: STR1 wherein n, *, R1, R2, R3 and y are specifically defined, or pharmaceutically acceptable salts or prodrugs thereof, which are useful in selectively controlling neurotransmitter release; therapeutically-effective pharmaceutical compositions of these compounds; and use of said compositions to selectively control neurotransmitter release in mammals.
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- Novel 3-pyridyl ethers with subnanomolar affinity for central neuronal nicotinic acetylcholine receptors
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Recent evidence indicating the therapeutic potential of cholinergic channel modulators for the treatment of central nervous system (CNS) disorders as well as the diversity of brain neuronal nicotinic acetylcholine receptors (nAChRs) have suggested an opportunity to develop subtype-selective nAChR ligands for the treatment of specific CNS disorders with reduced side effect liabilities. We report a novel series of 3-pyridyl ether compounds which possess subnanomolar affinity for brain nAChRs and differentially activate subtypes of neuronal nAChRs. The synthesis and structure-activity relationships for the leading members of the series are described, including A-85380 (4a), which possesses ca. 50 pM affinity for rat brain [3H]-(- )cytisine binding sites and 163% efficacy compared to nicotine to stimulate ion flux at human α4β2 nAChR subtype, and A-84543 (2a), which exhibits 84- fold selectivity to stimulate ion flux at human α4β2 nAChR subtype compared to human ganglionic type nAChRs. Computational studies indicate that a reasonable superposition of a low energy conformer of 4a with (S)-nicotine and (-)-epibatidine can be achieved.
- Abreo, Melwyn A.,Lin, Nan-Horng,Garvey, David S.,Gunn, David E.,Hettinger, Ann-Marie,Wasicak, James T.,Pavlik, Patricia A.,Martin, Yvonne C.,Donnelly-Roberts, Diana L.,Anderson, David J.,Sullivan, James P.,Williams, Michael,Arneric, Stephen P.,Holladay, Mark W.
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p. 817 - 825
(2007/10/03)
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