Design and validation of bicyclic iminopyrimidinones as beta amyloid cleaving enzyme-1 (BACE1) inhibitors: Conformational constraint to favor a bioactive conformation

Journal of Medicinal Chemistry

Volumn 55, Issue 21, 2012, Pages 9331-9345

  Mandal, Mihirbaran ^a   Zhu, Zhaoning ^a   Cumming, Jared N ^a   Liu, Xiaoxiang ^a   Strickland, Corey ^a   Mazzola, Robert D ^a   Caldwell, John P ^a   Leach, Prescott ^a   Grzelak, Michael ^a   Hyde, Lynn ^a   Zhang, Qi ^a   Terracina, Giuseppe ^a   Zhang, Lili ^a   Chen, Xia ^a   Kuvelkar, Reshma ^a   Kennedy, Matthew E ^a   Favreau, Leonard ^a   Cox, Kathleen ^a   Orth, Peter ^a   Buevich, Alexei ^a   Voigt, Johannes ^a   Wang, Hongwu ^a   Kazakevich, Irina ^a   McKittrick, Brian A ^a   Greenlee, William ^a   Parker, Eric M ^a   Stamford, Andrew W ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [5 [6 (5 FLUOROPYRIMIDIN 2 YL) 2 IMINO 3 METHYL 4 OXOOCTAHYDRO 1H PYRROLO[3,4 D]PYRIMIDIN 7A YL]THIOPHEN 3 YL]BENZONITRILE; AMYLOID BETA PROTEIN[1-40]; BETA SECRETASE 1; BETA SECRETASE INHIBITOR; NITROGEN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DOSE RESPONSE; DRUG CONFORMATION; DRUG DESIGN; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; NONHUMAN; RAT; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; VALIDATION PROCESS;

ADMINISTRATION, ORAL; AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; ASPARTIC ACID ENDOPEPTIDASES; BICYCLO COMPOUNDS, HETEROCYCLIC; CEREBRAL CORTEX; CRYSTALLOGRAPHY, X-RAY; HEK293 CELLS; HUMANS; MACACA FASCICULARIS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; NITRILES; PEPTIDE FRAGMENTS; PERMEABILITY; PYRIMIDINES; PYRIMIDINONES; QUANTUM THEORY; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THERMODYNAMICS; THIOPHENES;

EID: 84868590120     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301039c     Document Type: Article

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