Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes

Bioorganic and Medicinal Chemistry

Volumn 20, Issue 14, 2012, Pages 4377-4389

  Sandgren, Veronica ^a   Agback, Tatiana ^b   Johansson, Per Ola ^b   Lindberg, Jimmy ^b   Kvarnström, Ingemar ^a   Samuelsson, Bertil ^b   Belda, Oscar ^b   Dahlgren, Anders ^a  

^a LINKÖPING UNIVERSITY   (Sweden)

^b MEDIVIR AB   (Sweden)

Author keywords

Alzheimer's disease; BACE 1 inhibition; Hydroxyethylamine (HEA) isostere; Macrocycles

Indexed keywords

(1 AZIBUT 3 YN 1 YL)BENZENE; 1 PHENYLBUT 3 YN 1 AMINE; 1 PHENYLBUT 3 YN 1 OL; 2 (ALLYLOXY) 1 (2,2 DIMETHYL 1,3 DIOXOLAN 4 YL) ETHANAMINE; 4 (2 (ALLYLOXY) 1 AZIDOETHYL) 2,2 DIMETHYL 1,3 DIOXOLANE; [2 ALLOXY 1 ( 2,2 DIMETHYL 1,3 DIOXOLAN 4 YL) ETHYL] N BUT 3 ENYL 5 (METHANESULFONYL METHYL AMINO) ISOPHTHALAMIDE; BACE1 INHIBITOR; ENZYME INHIBITOR; METHYL 3 (BUT 3 EN 1 YLCARBAMOYL) 5 (N METHYLMETHYLSULFONAMIDE)BENZOIC ACID; METHYL 3 (N METHYLMETHYLSULFONAMIDO) 5 [(1 PHENYLBUT 3 EN 1 YL)CARBOMYL]BENZOIC ACID; METHYL 3 (N METHYLMETHYLSULFONAMIDO) 5 [(1 PHENYLBUT 3 EN YL)CARBOMYL]BENZOIC ACID; METHYL 3 (N METHYLMETHYLSULFONAMIDO) 5 [(1 PHENYLBUT 3 YN 1 YL)CARBOMYL]BENZOIC ACID; METHYL 3 [BUT 3 EN 1 YL(METHYL)CARBOMYL] 5 (N METHYLMETHYL SULFONAMIDO)BENZOIC ACID; METHYL 3 METHYL 5 [(1 PHENYLBUT 3 EN 1 YL)CARBAMOYL]BENZOIC ACID; METHYL 3 METHYL 5 [(1 PHENYLBUT 3 YN 1 YL)CARBAMOYL]BENZOIC ACID; N [ 4 (1,2 DIHYDROXY ETHYL) 2,13 DIOXO 6 OXA 3,12 DIAZA BICYCLO[12.3.1] OCTADECA 1,18,14,16 TETRAEN 16 YL] N METHYL METHANESULFONAMIDE; N [1 (ALLYLOXY) 3,4 DIHYDROXYBUTAN 2 YL] N (BUT 3 EN 1YL) 5 (N METHYLMETHYLSULFONAMIDO)ISOPHTHALAMIDE; N [4 ( 2 BENZYLAMINO 1 HYDROXY ETHYL) 2,13 DIOXO 6 OXA 3,12 DIAZA BICYCLO[12.3.1]OCTADECA 1(17),8,14(18),15 TETRAEN 16 YL] N METHYL METHANESULFONAMIDE; N [4 (1,2 DIHYDROXY ETHYL) 2,14 DIOXO 6 OXA 3,13 DIAZA BICYCLO[12.3.1]OCTADECA 1(18),14,16 TRIEN 16 YL] N METHYL METHANESULFONAMIDE; N [4 (1,2 DIHYDROXY ETHYL) 2,14 DIOXO 6 OXA 3,13 DIAZA BICYCLO[13.3.1]NONADECA 1(19),15,17 TETRAEN 17 YL] N METHYL METHANESULFONAMIDE; N [4 (1,2 DIHYDROXY ETHYL) 2,14 DIOXO 6 OXA 3,13 DIAZA BICYCLO[13.3.1]NONADECA 1(19),8,15,17 TETRAEN 17 YL] N METHYL METHANESULFONAMIDE; N [4 (2 BENZYLAMINO 1 HYDROXY ETHYL) 2,13 DIOXO 6 OXA 3,12 DIAZA BICYCLO[12.3.1]OCTADECA 1(18),14,16 TRIEN 16 YL] N METHYL METHANE SULFONAMIDE; N [4 (2 BENZYLAMINO 1 HYDROXY ETHYL) 2,13 DIOXO 6 OXA 3,12 DIAZA BICYCLO[12.3.1]OCTADECA 1(18),14,16 TRIEN 6 YL] N METHYL METHANESULFONAMIDE; N [4 [1 HYDROXY 2 (3 ISOPROPYL BENZYLAMINO) ETHYL] 2,13 DIOXO 6 OXA 3,13 DIAZA BICYCLO[12.3.1]OCTADECA 1 (18),14,16 TRIEN 16 YL]; N [4 [1 HYDROXY 2 (3 ISOPROPYL BENZYLAMINO)ETHYL] 2,14 DIOXO 6 OXA 3,13 DIAZA BICYCLO[13.3.1]NONADECA 1 (19),15,17 TRIEN 17 YL] N METHYL METHANESULFONAMIDE; N [4 [1 HYDROXY 2 (3 ISOPROPYL BENZYLAMINO)ETHYL] 2,14 DIOXO 6 OXA 3,13 DIAZABICYCLO[13.3.1]NONADECA 1(18),8,15(19),16 TETRAEN 17 YL] N METHYL METHANESULFONAMIDE; N [4 [1 HYDROXY 2 (3 ISOPROPYLBENZYLAMINO) ETHYL] 2,13 DIOXO 6 OXA 3,12 DIAZABICYCLO [12.3.1]OCTADECA 1(18),8,14,16 TETRAEN 16 YL] N METHYLMETHANESULFONAMIDE; N [4 [2 (3 TERT BENZYLAMINO) 1 HYDROXY ETHYL] 2,13 DIOXO 6 OXA 3,12 DIAZA BICYCLO[12.3.1]OCTADECA 1(17),8,14(18),15 TETRAEN 16 YL] N METHYL METHANESULFONAMIDE; TOLUENE 4 SULFONIC ACID 2 HYDROXY 2 [ 16 (METHANESULFONYL METHYL AMINO) 2,13 DIOXO 6 OXA 3,12 DIAZA BICYCLO[12.3.1]OCTADECA 1(18),8,14,16 TETRAEN YL] ETHYL ESTER; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CELL ACTIVITY; CONCENTRATION RESPONSE; CRYSTAL STRUCTURE; CYCLIZATION; DRUG DESIGN; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ACTIVITY; IC 50; STRUCTURE ACTIVITY RELATION;

AMYLOID PRECURSOR PROTEIN SECRETASES; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; ENZYME INHIBITORS; ETHYLAMINES; PROTEIN STRUCTURE, TERTIARY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84863201045     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.05.039     Document Type: Article

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