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Bioorg Med Chem Lett. 2017 Mar 1;27(5):1261-1266. doi: 10.1016/j.bmcl.2017.01.058. Epub 2017 Jan 20.

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.

Author information

1
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-7660, USA. Electronic address: christiana.iwuagwu@bms.com.
2
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-7660, USA.

Abstract

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.

KEYWORDS:

5HT(3A) receptor; Schizophrenia; Spirooxazolines; α7 nicotinic acetylcholine receptor

PMID:
28169167
DOI:
10.1016/j.bmcl.2017.01.058
[Indexed for MEDLINE]

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