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ACS Med Chem Lett
2018 Oct 11;911:1144-1148. doi: 10.1021/acsmedchemlett.8b00407.
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B-973, a Novel α7 nAChR Ago-PAM: Racemic and Asymmetric Synthesis, Electrophysiological Studies, and in Vivo Evaluation.
Garai S
,
Raja KS
,
Papke RL
,
Deschamps JR
,
Damaj MI
,
Thakur GA
.
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We report here the total synthesis of B-973 (five steps), a recently identified α7 nAChR ago-PAM, its enantiomeric resolution, and its electrophysiological characterization in Xenopus oocytes to identify (-)-B-973B as the bioactive enantiomer. The asymmetric synthesis of B-973B was accomplished in 99% ee, and X-ray crystallography studies revealed its absolute "S" stereochemistry. B-973B was effective in attenuating pain behavior and decreasing paw edema (formalin test), and its analgesic effects were mediated through α7 nAChR.
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