The structural modification of a series of [3.3.1] bicyclic sulfonamide based gamma-secretase inhibitors is described. Appropriate substitution on the bicyclic scaffold provides a significant increase in the metabolic stability of the compounds resulting in an improved in vivo metabolic profile.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.bmcl.2009.10.060 | DOI Listing |
Chem Commun (Camb)
April 2018
State Key Laboratory of Physical Chemistry of Solid Surfaces and Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
Despite the excellent chemical properties of N-heterocycles, pyrido[1,2-α]azepine remains elusive due to its potential antiaromaticity and lability. Herein, we demonstrate the synthesis and characterization of the first bicyclic pyrido[1,2-α]azepine that leverages the coordination to the ruthenium center to promote the stability of N-bridged bicycle.
View Article and Find Full Text PDFEur J Med Chem
June 2015
Neuroscience Medicinal Chemistry, Janssen Research & Development, Janssen-Cilag S.A., C/Jarama 75, 45007 Toledo, Spain. Electronic address:
The search for novel heterobicyclic compounds within the drug-like chemical space continues to be an area of interest in medicinal chemistry. Unsaturated N-bridgehead heterocycles are well represented in marketed drugs for a variety of therapeutic areas, and continue to play an important role in central nervous system (CNS) drug discovery programs. Examples of medicinal chemistry strategies that make use of N-bridged 5,6-bicyclic pyridines are discussed here in this Minireview, which covers the literature from 2010 up to 2014.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2009
Department of Medicinal Chemistry, Elan Pharmaceuticals, 800 Gateway Boulevard, South San Francisco, CA 94080, USA.
The structural modification of a series of [3.3.1] bicyclic sulfonamide based gamma-secretase inhibitors is described.
View Article and Find Full Text PDFDalton Trans
October 2008
Department of Chemistry, Loughborough University, Loughborough, UK LE11 3TU.
Reaction of the mixed thioether/ether crowns [9]aneO2S , [12]aneO3S and [18]aneO4S2 with one mol. equivalent of the aminating agent MSH (o-mesitylsulfonylhydroxylamine) in Et2O results in the formation of the mono-sulfimidated systems {[9]aneO2(S=NH2)}+, {[12]aneO3(S=NH2)}+ and {[18]aneO4S(S=NH2)}+, while using two mol. equivalents of MSH with gives the disulfimidium cation {[18]aneO4(S=NH2)2}2+.
View Article and Find Full Text PDFJ Org Chem
December 2002
Chemistry Department, Bar-Ilan University, Ramat-Gan 52900, Israel.
The hitherto unsolved problem of the origin of the unusually high nitrogen inversion-rotation (NIR) barriers in 7-azabicyclo[2.2.1]heptanes (the bicyclic effect) was examined using the natural bond orbital (NBO) approach.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!