Application of fragment-based lead generation to the discovery of novel, cyclic amidine β-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency

Journal of Medicinal Chemistry

Volumn 50, Issue 24, 2007, Pages 5912-5925

  Edwards, Philip D ^a   Albert, Jeffrey S ^a   Sylvester, Mark ^a   Aharony, David ^a   Andisik, Donald ^a   Callaghan, Owen ^c   Campbell, James B ^a   Carr, Robin A ^c   Chessari, Gianni ^c   Congreve, Miles ^c   Frederickson, Martyn ^c   Folmer, Rutger H A ^b   Geschwindner, Stefan ^b   Koether, Gerard ^a   Kolmodin, Karin ^b   Krumrine, Jennifer ^a   Mauger, Russell C ^a   Murray, Christopher W ^c   Olsson, Lise Lotte ^b   Patel, Sahil ^c   Spear, Nate ^a   Tian, Gaochao ^a   more..

^a ASTRAZENECA   (United Kingdom)

^b ASTRAZENECA R AND D   (Sweden)

^c ASTEX PHARMACEUTICALS   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 6 [2 (3' METHOXYBIPHENYL 3 YL)ETHYL] 3,6 DIMETHYL 5,6 DIHYDRO 3H PYRIMIDIN 4 ONE; 4 PYRIMIDINONE DERIVATIVE; AMIDINE; BETA SECRETASE INHIBITOR; CYTOSINE; DIHYDROISOCYTOSINE; LIGAND; UNCLASSIFIED DRUG;

ARTICLE; CRYSTAL STRUCTURE; DRUG POTENCY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; NUCLEAR MAGNETIC RESONANCE; PROCESS OPTIMIZATION; STRUCTURE ACTIVITY RELATION; SURFACE PLASMON RESONANCE; X RAY CRYSTALLOGRAPHY;

AMIDINES; AMYLOID PRECURSOR PROTEIN SECRETASES; ASPARTIC ENDOPEPTIDASES; CELL LINE; CRYSTALLOGRAPHY, X-RAY; CYTOSINE; FLUORESCENCE RESONANCE ENERGY TRANSFER; HUMANS; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; PYRIMIDINES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 37849043411     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm070829p     Document Type: Article

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