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Small conformationally restricted piperidine N-arylsulfonamides as orally active gamma-secretase inhibitors |
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| Authors: | Josien Hubert Bara Thomas Rajagopalan Murali Asberom Theodros Clader John W Favreau Leonard Greenlee William J Hyde Lynn A Nomeir Amin A Parker Eric M Pissarnitski Dmitri A Song Lixin Wong Gwendolyn T Zhang Lili Zhang Qi Zhao Zhiqiang |
| Affiliation: | Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07302, USA. hubert.josien@spcorp.com |
| Abstract: | The design and development of a new class of small 2,6-disubstituted piperidine N-arylsulfonamide gamma-secretase inhibitors is reported. Lowering molecular weight including the use of conformational constraint led to compounds with less CYP 3A4 liability compared to early leads. Compounds active orally in lowering Abeta levels in Tg CRND8 mice were identified as potential treatments for Alzheimer's disease. |
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