Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious gamma-secretase inhibitors (Part II)

Xiaocong M Ye; Andrei W Konradi; Jenifer Smith; Danielle L Aubele; Albert W Garofalo; Jennifer Marugg; Marty L Neitzel; Chris M Semko; Hing L Sham; Minghua Sun; Anh P Truong; Jing Wu; Hongbin Zhang; Erich Goldbach; John-Michael Sauer; Elizabeth F Brigham; Michael Bova; Guriqbal S Basi

doi:10.1016/j.bmcl.2010.04.148

Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious gamma-secretase inhibitors (Part II)

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3502-6. doi: 10.1016/j.bmcl.2010.04.148. Epub 2010 May 6.

Authors

Xiaocong M Ye¹, Andrei W Konradi, Jenifer Smith, Danielle L Aubele, Albert W Garofalo, Jennifer Marugg, Marty L Neitzel, Chris M Semko, Hing L Sham, Minghua Sun, Anh P Truong, Jing Wu, Hongbin Zhang, Erich Goldbach, John-Michael Sauer, Elizabeth F Brigham, Michael Bova, Guriqbal S Basi

Affiliation

¹ Department of Medicinal Chemistry, Elan Pharmaceuticals, South San Francisco, CA 94080, USA. michael.ye@elan.com

PMID: 20529683
DOI: 10.1016/j.bmcl.2010.04.148

Abstract

Significant improvement in metabolic stability on the pyrazolopiperidine scaffold over the original series were achieved and this stability improvement translated in an improved in vivo efficacy.

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Animals
Drug Discovery
Drug Stability
Microsomes, Liver / metabolism
Piperidines / chemical synthesis
Piperidines / chemistry*
Piperidines / pharmacology
Protease Inhibitors / chemical synthesis
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacology

Substances

Piperidines
Protease Inhibitors
Sulfonamides
Amyloid Precursor Protein Secretases