Novel BACE1 inhibitors with a non-acidic heterocycle at the P 1′ position

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 21, 2013, Pages 6665-6673

  Suzuki, Kenji ^a   Hamada, Yoshio ^b   Nguyen, Jeffrey Tri ^a   Kiso, Yoshiaki ^c  

^a KYOTO PHARMACEUTICAL UNIVERSITY   (Japan)

^b KOBE GAKUIN UNIVERSITY   (Japan)

^c NAGAHAMA INSTITUTE OF BIO SCIENCE AND TECHNOLOGY   (Japan)

Author keywords

Secretase; Alzheimer's disease; Hydroxymethylcarbonyl isostere; Non acidic inhibitor; Quantitative structure activity relationship

Indexed keywords

ARGININE; BETA SECRETASE 1; BETA SECRETASE INHIBITOR; HETEROCYCLIC COMPOUND; KMI 1764; METHYL 2 [2 HYDROXY 3 [3 (N METHYLMETHANESULFONAMIDO) 5 (1 PHENYLETHYLCARBAMOYL)BENZAMIDO] 4 PHENYLBUTANAMIDO]THIAZOLE 4 CARBOXYLATE; METHYL 2 [2 HYDROXY 3 [3 (N METHYLMETHANESULFONAMIDO) 5 (1 PHENYLETHYLCARBAMOYL)BENZAMIDO] 4 PHENYLBUTANAMIDO]THIAZOLE 5 CARBOXYLATE; N1 [3 HYDROXY 4 (5 METHYL 1,3,4 THIADIAZOL 2 YLAMINO) 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [3 HYDROXY 4 (5 NITROTHIAZOL 2 YLAMINO) 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [3 HYDROXY 4 [5 (METHYLTHIO) 1,3,4 THIADIAZOL 2 YLAMINO] 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [3 HYDROXY 4 OXO 1 PHENYL 4 (5 PHENYL 1,3,4 THIADIAZOL 2 YLAMINO)BUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [3 HYDROXY 4 OXO 1 PHENYL 4 (THIAZOL 2 YLAMINO)BUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [3 HYDROXY 4 OXO 1 PHENYL 4 [5 (PYRIDIN 4 YL) 1,3,4 THIADIAZOL 2 YLAMINO]BUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [3 HYDROXY 4 OXO 1 PHENYL 4 [5 (TRIFLUOROMETHYL) 1,3,4 THIADIAZOL 2 YLAMINO]BUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [4 (1,3,4 THIADIAZOL 2 YLAMINO) 3 HYDROXY 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [4 (5 BROMO 1,3,4 THIADIAZOL 2 YLAMINO) 3 HYDROXY 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [4 (5 BROMOTHIAZOL 2 YLAMINO) 3 HYDROXY 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [4 (5 ETHYL 1,3,4 THIADIAZOL 2 YLAMINO) 3 HYDROXY 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [4 (5 TERT BUTYL 1,3,4 THIADIAZOL 2 YLAMINO) 3 HYDROXY 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [4 (BENZO[D]THIAZOL 2 YLAMINO) 3 HYDROXY 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; N1 [4 [5 (ETHYLTHIO) 1,3,4 THIADIAZOL 2 YLAMINO] 3 HYDROXY 4 OXO 1 PHENYLBUTAN 2 YL] 5 (N METHYLMETHANESULFONAMIDO) N3 (1 PHENYLETHYL)ISOPHTHALAMIDE; UNCLASSIFIED DRUG;

ACIDITY; ARTICLE; CHEMICAL BINDING; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; MOLECULAR INTERACTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION;

ALZHEIMER'S DISEASE; HYDROXYMETHYLCARBONYL ISOSTERE; NON-ACIDIC INHIBITOR; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; Β-SECRETASE;

AMYLOID PRECURSOR PROTEIN SECRETASES; ASPARTIC ACID ENDOPEPTIDASES; BENZAMIDES; HETEROCYCLIC COMPOUNDS; HUMANS; HYDROGEN BONDING; PROTEASE INHIBITORS; PROTEIN BINDING; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RECOMBINANT PROTEINS; THIADIAZOLES;

EID: 84885184601     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2013.08.016     Document Type: Article

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