2. Academic Validation
  3. Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors

Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors

  • Bioorg Med Chem Lett. 2013 Feb 1;23(3):844-9. doi: 10.1016/j.bmcl.2012.11.047.
Wen-Lian Wu 1,  Theodros Asberom,  Thomas Bara,  Chad Bennett,  Duane A Burnett,  John Clader,  Martin Domalski,  William J Greenlee,  Hubert Josien,  Mark McBriar,  Murali Rajagopalan,  Monica Vicarel,  Ruo Xu,  Lynn A Hyde,  Robert A Del Vecchio,  Mary E Cohen-Williams,  Lixin Song,  Julie Lee,  Giuseppe Terracina,  Qi Zhang,  Amin Nomeir,  Eric M Parker,  Lili Zhang
Affiliations

Affiliation

  • 1 Merck Research Laboratories, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA. wen-lian.wu@merck.com
PMID: 23265892 DOI: 10.1016/j.bmcl.2012.11.047
Abstract

An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (SCH 900229), a potent, PS1-selective γ-secretase Inhibitor and clinical candidate for the treatment of Alzheimer's disease. Specifically, 4-CF(3) and 4-Br substituted arylsulfone analogs, (-)-1b and (-)-1c, are equipotent to compound (-)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated.

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