49573-96-8Relevant academic research and scientific papers
Design and synthesis of a novel series of 4-heteroarylamino-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octanes as α7 nicotinic receptor agonists 2. Development of 4-heteroaryl SAR
Iwuagwu, Christiana,King, Dalton,McDonald, Ivar M.,Cook, James,Zusi, F. Christopher,Hill, Matthew D.,Mate, Robert A.,Fang, Haiquan,Knox, Ronald,Gallagher, Lizbeth,Post-Munson Amy Easton, Debra,Miller, Regina,Benitex, Yulia,Siuciak, Judy,Lodge, Nicholas,Zaczek, Robert,Morgan, Daniel,Bristow, Linda,Macor, John E.,Olson, Richard E.
supporting information, p. 1261 - 1266 (2017/06/19)
Quinuclidine-containing spirooxazolines, as described in the previous report in this series, were demonstrated to have utility as α7 nicotinic acetylcholine receptor (α7 nAChR) partial agonists. In this work, the SAR of this chemotype was expanded to include an array of diazine heterocyclic substitutions. Many of the heterocyclic analogs were potent partial agonists of the α7 receptor, selective against other nicotinic receptors and the serotinergic 5HT3A receptor. (1′S,3′R,4′S)-N-(6-phenylpyrimidin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine, a potent and selective α7 nAChR partial agonist, was demonstrated to improve cognition in the mouse novel object recognition (NOR) model of episodic memory.
Design, synthesis, and evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis
?ink, Roman,Sosi?, Izidor,?ivec, Matej,Fernandez-Menendez, Raquel,Turk, Samo,Pajk, Stane,Alvarez-Gomez, Daniel,Lopez-Roman, Eva Maria,Gonzales-Cortez, Carolina,Rullas-Triconado, Joaquin,Angulo-Barturen, Inigo,Barros, David,Ballell-Pages, Lluís,Young, Robert J.,Encinas, Lourdes,Gobec, Stanislav
supporting information, p. 613 - 624 (2015/01/30)
Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.
