- Design and synthesis of dihydrobenzofuran amides as orally bioavailable, centrally active γ-secretase modulators
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We report the discovery and optimization of a novel series of dihydrobenzofuran amides as γ-secretase modulators (GSMs). Strategies for aligning in vitro potency with drug-like physicochemical properties and good microsomal stability while avoiding P-gp mediated efflux are discussed. Lead compounds such as 35 and 43 have moderate to good in vitro potency and excellent selectivity against Notch. Good oral bioavailability was achieved as well as robust brain Aβ42 lowering activity at 100 mg/kg po dose.
- Pettersson, Martin,Johnson, Douglas S.,Subramanyam, Chakrapani,Bales, Kelly R.,Am Ende, Christopher W.,Fish, Benjamin A.,Green, Michael E.,Kauffman, Gregory W.,Lira, Ricardo,Mullins, Patrick B.,Navaratnam, Thayalan,Sakya, Subas M.,Stiff, Cory M.,Tran, Tuan P.,Vetelino, Beth C.,Xie, Longfei,Zhang, Liming,Pustilnik, Leslie R.,Wood, Kathleen M.,O'Donnell, Christopher J.
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scheme or table
p. 2906 - 2911
(2012/06/04)
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- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Compounds of formula (I): wherein R4, R6 and R7 are defined herein, are useful as inhibitors of HIV replication.
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Page/Page column 81
(2009/06/27)
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- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Compounds of formula (I): wherein c, X, Y, R2, R4 and R5 are defined herein, are useful as inhibitors of HIV replication.
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Page/Page column 91
(2009/06/27)
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- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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The present invention relates to compounds of formula (I) wherein c, X, Y, R2, R3, R4 and R6 are as defined herein, compositions and uses thereof for treating human immunodeficiency virus (HIV) infection. In particular, the present invention provides novel inhibitors of HIV integrase, pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HIV infection
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Page/Page column 88
(2009/06/27)
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- INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Compounds of formula I : wherein c, R2, R3, R4, R5, R6, R7 and R8 are defined herein, are useful as inhibitors of HIV replication.
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Page/Page column 94
(2009/06/27)
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