期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 56, 期 22, 页码 9351-9355出版社
AMER CHEMICAL SOC
DOI: 10.1021/jm4013246
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资金
- NIH/MLPCN [US4 MH084659, U54 MH084512]
A functional high throughput screen and subsequent multidimensional, iterative parallel synthesis effort identified the first muscarinic acetylcholine receptor (mAChR) negative allosteric modulator (NAM) selective for the M-5 subtype. ML375 is a highly selective M-5 NAM with submicromolar potency (human M-5 IC50 = 300 nM, rat M-5 IC50 = 790 nM, M1-M4 IC50 > 30 mu M), excellent multispecies PK, high CNS penetration, and enantiospecific inhibition.
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