1222137-77-0Relevant academic research and scientific papers
Synthesis and Behavioral Studies of Chiral Cyclopropanes as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile. Part III
Onajole, Oluseye K.,Vallerini, Gian Paolo,Eaton, J. Brek,Lukas, Ronald J.,Brunner, Dani,Caldarone, Barbara J.,Kozikowski, Alan P.
, p. 811 - 822 (2016/07/06)
We report the synthesis and biological characterization of novel derivatives of 3-[(1-methyl-2(S)-pyrrolidinyl)methoxy]-5-cyclopropylpyridine (4a-f and 5) as potent and highly selective α4β2-nicotinic acetylcholine receptor (nAChR) full or partial agonist
NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF
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Paragraph 1202, (2013/07/25)
The invention relates to pyridinyl nicotinic acetylcholine receptor ligands, compositions comprising an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand and methods to treat or prevent a condition, such as depression and nicotine dependence, comprising administering to an animal in need thereof an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand.
Chemistry, pharmacology, and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile. part II
Zhang, Han-Kun,Yu, Li-Fang,Eaton, J. Brek,Whiteaker, Paul,Onajole, Oluseye K.,Hanania, Taleen,Brunner, Daniela,Lukas, Ronald J.,Kozikowski, Alan P.
supporting information, p. 5495 - 5504 (2013/07/26)
A 3-pyridyl ether scaffold bearing a cyclopropane-containing side chain was recently identified in our efforts to create novel antidepressants that act as partial agonists at α4β2-nicotinic acetylcholine receptors. In this study, a systematic structure-activity relationship investigation was carried out on both the azetidine moiety present in compound 3 and its right-hand side chain, thereby discovering a variety of novel nicotinic ligands that retain bioactivity and feature improved chemical stability. The most promising compounds, 24, 26, and 30, demonstrated comparable or enhanced pharmacological profiles compared to the parent compound 4, and the N-methylpyrrolidine analogue 26 also exhibited robust antidepressant-like efficacy in the mouse forced swim test. The favorable ADMET profile and chemical stability of 26 further indicate this compound to be a promising lead as a drug candidate warranting further advancement down the drug discovery pipeline.
Chemistry and behavioral studies identify chiral cyclopropanes as selective α4β2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile
Zhang, Hankun,Tückmantel, Werner,Eaton, J. Brek,Yuen, Po-Wai,Yu, Li-Fang,Bajjuri, Krishna Mohan,Fedolak, Allison,Wang, Daguang,Ghavami, Afshin,Caldarone, Barbara,Paterson, Neil E.,Lowe, David A.,Brunner, Daniela,Lukas, Ronald J.,Kozikowski, Alan P.
supporting information; experimental part, p. 717 - 724 (2012/03/27)
Despite their discovery in the early 20th century and intensive study over the last 20 years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing α4β2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity while acting as partial agonists at α4β2-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening toward other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other α4β2-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression.
NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF
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Page/Page column 202, (2010/04/30)
The invention relates to pyridinyl nicotinic acetylcholine receptor ligands, compositions comprising an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand and methods to treat or prevent a condition, such as depression and nicotine dependence, comprising administering to an animal in need thereof an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand.
