Design and synthesis of hydroxyethylene-based BACE-1 inhibitors incorporating extended P1 substituents

Open Medicinal Chemistry Journal

Volumn 7, Issue 1, 2013, Pages 1-15

  Sandgren, Veronica ^a   Bäck, Marcus ^a   Kvarnström, Ingemar ^a   Dahlgren, Anders ^a  

^a LINKÖPING UNIVERSITY   (Sweden)

Author keywords

Alzheimer's disease; BACE 1 inhibitors; Extended P1 substituents; Hydroxyethylene isosteres; Modifications; P1 ; S1 S3 pocket

Indexed keywords

5 AMINO 2 BENZYL N (1 (4 CHLOROBENZYLAMINO) 3 METHYL 1 OXOPENTAN 2 YL) 6 (4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY) 4 HYDROXY 2 ISOPROPYLHEXANAMIDE; 5 AMINO 2 BENZYL N (1 (4 CHLOROBENZYLAMINO) 3 METHYL 1 OXOPENTAN 2 YL) 6 (4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY) 4 HYDROXYHEXANAMIDE; 5 AMINO 2 BENZYL N (1 (4 CHLOROPHENYLAMINO) 3 METHYLPENTAN 2 YL) 6 (4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY) 4 HYDROXY 2 ISOPROPYLHEXANAMIDE; 5 AMINO 2 BENZYL N (1 (4 CHLOROPHENYLAMINO) 3 METHYLPENTAN 2 YL) 6 (4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY) 4 HYDROXYHEXANAMIDE; 5 AMINO 4 HYDROXY 2 METHOXY 6 [2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY]HEXANOIC ACID [1 (4 CHLOROBENZYLCARBAMOYL) 2 METHYLBUTYL]AMIDE; 5 AMINO 4 HYDROXY 2 METHOXY 6 [3 (3 METHOXYPROPOXY)PHENOXY]HEXANOIC ACID [1 (4 CHLOROBENZYLCARBAMOYL) 2 METHYLBUTYL]AMIDE; 5 AMINO 6 (3 BENZYLOXYPHENOXY) 4 HYDROXY 2 METHOXYHEXANOIC ACID (1 BENZYLCARBAMOYL 2 METHYLPROPYL)AMIDE; 5 AMINO 6 (4' FLUOROBIPHENYL 4 YLOXY) 4 HYDROXY 2 METHOXYHEXANOIC ACID [1 (4 CHLOROBENZYLCARBAMOYL) 2 METHYLBUTYL]AMIDE; 5 AMINO 6 [4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY] 4 HYDROXY 2 METHOXY HEXANOIC ACID [1 (4 CHLOROBENZYLCARBAMOYL) 2 METHYLBUTYL]AMIDE; 5 AMINO 6 [4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY] 4 HYDROXY 2 METHOXYHEXANOIC ACID[1 (4 CHLOROBENZYLCARBAMOYL) 2 METHYLPROPYL]AMIDE; 5 AMINO N (1 (4 CHLOROBENZYLAMINO) 3 METHYL 1 OXOPENTAN 2 YL) 2 ETHYL 6 (4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY) 4 HYDROXYHEXANAMIDE; ASPARTIC PROTEINASE INHIBITOR; BACE 1 INHIBITOR; N (6 (1 (4 CHLOROBENZYLAMINO) 3 METHYL 1 OXOPENTAN 2 YLAMINO) 1 (4' FLUORO 2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXY) 3 HYDROXY 5 METHOXY 6 OXOHEXAN 2 YL) 3 (N METHYLMETHYLSULFONAMIDO)BENZAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 1 (3 BENZYLOXYPHENOXYMETHYL) 2 HYDROXY 4 METHOXYBUTYL] 3 (METHANESULFONYLMETHYLAMINO)BENZAMIDE; N [4 (1 BENZYLCARBAMOYL 2 METHYLPROPYLCARBAMOYL) 1 (4 BENZYLOXYPHENOXYMETHYL) 2 HYDROXY 4 METHOXYBUTYL] 3 (METHANESULFONYLMETHYLAMINO)BENZAMIDE; N [4 [1 (4 CHLOROBENZYLCARBAMOYL) 2 METHYLBUTYLCARBAMOYL] 2 HYDROXY 4 METHOXY 1 [2 (3 METHOXYPROPOXY)BIPHENYL 4 YLOXYMETHYL]BUTYL] 3 (METHANESULFONYLMETHYLAMINO)BENZAMIDE; N [4 [1 (4 CHLOROBENZYLCARBAMOYL) 2 METHYLBUTYLCARBAMOYL] 2 HYDROXY 4 METHOXY 1 [2(3 METHOXYPROPOXY)BIPHENYL 4 YLOXYMETHYL]BUTYL] 5 (METHANESULFONYLMETHYLAMINO) N' (1 PHENYLETHYL)ISOPHTHALAMIDE; UNCLASSIFIED DRUG;

ARTICLE; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; CRYSTALLIZATION; DRUG DESIGN; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME BINDING; ENZYME INHIBITION; ENZYME SUBSTRATE COMPLEX; HUMAN; HUMAN CELL; IC 50; MICROWAVE IRRADIATION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 84876105470     PISSN: None     EISSN: 18741045     Source Type: Journal    
DOI: 10.2174/1874104501307010001     Document Type: Article

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