Discovery of potent BACE-1 inhibitors containing a new hydroxyethylene (HE) Scaffold: Exploration of P1′ alkoxy residues and an aminoethylene (AE) central core

Bioorganic and Medicinal Chemistry

Volumn 18, Issue 4, 2010, Pages 1711-1723

  Björklund, Catarina ^a   Adolfsson, Hans ^a   Jansson, Katarina ^b   Lindberg, Jimmy ^b   Vrang, Lotta ^b   Hallberg, Anders ^c   Rosenquist, Åsa ^b   Samuelsson, Bertil ^a,b  

^a STOCKHOLM UNIVERSITY   (Sweden)

^b MEDIVIR AB   (Sweden)

^c UPPSALA UNIVERSITY   (Sweden)

Author keywords

Alzhemier's disease; Aminoethylene (AE) isostere; BACE 1 inhibitors; Hydroxyethylene (HE) isostere; P1 modifications; Peptidomimetics

Indexed keywords

AMINO ACID DERIVATIVE; BETA SITE AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME 1 INHIBITOR; CATHEPSIN D; ETHYLENE DERIVATIVE; HYDROXYL GROUP; N [1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 4 BENZYL 1 (3,5 DIFLUOROPHENOXYMETHYL) 2 HYDROXYBUTYL] 5 (METHANESULFONYL AMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 1 (3,5 DIFLUOROPHENOXYMETHYL) 2 HYDROXY 4 (2 METHOXYETHOXY)BUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 1 (3,5 DIFLUOROPHENOXYMETHYL) 2 HYDROXY 4 METHOXYBUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 1 (3,5 DIFLUOROPHENOXYMETHYL) 4 ETHYL 2 HYDROXYBUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 1 (3,5 DIFLUOROPHENOXYMETHYL) 4 METHOXYBUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 2 AMINO 1 (3,5 DIFLUOROPHENOXYMETHYL) 4 METHOXYBUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 4 CYCLOPROPYLMETHOXY 1 (3,5 DIFLUOROPHENOXYMETHYL) 2 HYDROXYBUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 4 OXY 1 (3,5 DIFLUOROPHENOXYMETHYL) 2 HYDROXYBUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 4 PROPYLOXYBUTYL] 5 (METHANESULFONYLMETHYLAMINO) N (1 PHENYLETHYL)ISOPHTHALAMIDE; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; DEOXYGENATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; PROTEIN FOLDING; PROTEIN MOTIF; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

AMYLOID PRECURSOR PROTEIN SECRETASES; ASPARTIC ACID ENDOPEPTIDASES; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; ETHYLENES; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR STRUCTURE; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SPECTROPHOTOMETRY, ULTRAVIOLET; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 75849154226     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2009.12.051     Document Type: Article

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