Phenyl bioisosteres in medicinal chemistry: discovery of novel γ-secretase modulators as a potential treatment for Alzheimer's diseaseElectronic supplementary information (ESI) available: Full protocols for the following in vitroassays: cellular Aβ secretion assay, lipophilicity (log D) and solubility (Lysa). Synthetic routes and procedures, characterisation of the compounds described (1H NMR and MS). 1H NMR spectra of newly prepared compounds 7, 8, 11, 12, 15, 16, 19, 20, 21, 24and 25. See DOI: 10.1039/d1md00043h

Autor:	Ratni, H., Baumann, K., Bellotti, P., Cook, X. A., Green, L. G., Luebbers, T., Reutlinger, M., Stepan, A. F., Vifian, W.
Zdroj:	MedChemComm; 2021, Vol. 12 Issue: 5 p758-766, 9p
Abstrakt:	Phenyl rings are one of the most prevalent structural moieties in active pharmaceutical ingredients, even if they often contribute to poor physico-chemical properties. Herein, we propose the use of a bridged piperidine (BP) moiety as a phenyl bioisostere, which could also be seen as a superior phenyl alternative as it led to strongly improved drug like properties, in terms of solubility and lipophilicity. Additionally, this BP moiety compares favorably to the recently reported saturated phenyl bioisosteres. We applied this concept to our γ-secretase modulator (GSM) project for the potential treatment of Alzheimer's disease delivering clinical candidates.
Databáze:	Supplemental Index
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