Quinolone derivatives containing strained spirocycle as orally active glycogen synthase kinase 3β (GSK-3β) inhibitors for type 2 diabetics

Bioorganic and Medicinal Chemistry

Volumn 20, Issue 3, 2012, Pages 1188-1200

  Seto, Shigeki ^a   Yumoto, Kazuhiko ^a   Okada, Kyoko ^a   Asahina, Yoshikazu ^a   Iwane, Aya ^a   Iwago, Maki ^a   Terasawa, Reiko ^a   Shreder, Kevin R ^b   Murakami, Koji ^a   Kohno, Yasushi ^a  

^a KYORIN PHARMACEUTICAL CO LTD   (Japan)

^b ACTIVX BIOSCIENCES INC   (United States)

Author keywords

GSK 3 inhibitor; Spirocycle; Tricyclic quinolones

Indexed keywords

9' AMINO 10' FLUORO 2',3' DIHYDRO 3' METHYL 8' OXO 11' [2 (2 PYRIDYLAMINO)ETHYLAMINO]SPIRO(CYLOBUTANE 1,4' [8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYIC ACID; 9' AMINO 10' FLUORO 2',3' DIHYDRO 8' OXO 11' [2 (2 PYRIDYLAMINO)ETHYLAMINO]SPIRO(CYLOPENTATE 1,4' [8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYIC ACID; 9' AMINO 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLIC ACID; 9' AMINO 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOPROPANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLIC ACID; ETHYL 1' (TERT BUTOXYCARBONYL) 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 1,4 DIHYDRO 1[1 (2 HYDROXYETHYL)CYCLOPROPYL] 4 OXO 6,7,8 TRIFLUORO 3 QUINOLINECARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 2' METHYL 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 2' METHYL 9' NITRO 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 3' METHYL 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 3' METHYL 9' NITRO 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOPENTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOPROPANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 9' NITRO 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 10',11' DIFLUORO 2',3' DIHYDRO 9' NITRO 8' OXO SPIRO(CYCLOPENTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 3 [[1 (1 HYDROXYPROPANE 2 YL)CYCLOBUTYL]AMINO] 2 (2,3,4,5 TETRAFLUOROBENZOYL)ACRYLATE; ETHYL 3 [[1 (2 HYDROXPROPANE 1 YL)CYCLOBUTYL]AMINO] 2 (2,3,4,5 TETRAFLUOROBENZOYL)ACRYLATE; ETHYL 3 [[1 (2 HYDROXYETHYL)CYCLOBUTYL]AMINO] 2 (2,3,4,5 TETRAFLUOROBENZOYL)ACRYLATE; ETHYL 3 [[1 (2 HYDROXYETHYL)CYCLOPENTYL]AMINO] 2 (2,3,4,5 TETRAFLUOROBENZOYL)ACRYLATE; ETHYL 3 [[1 (2 HYDROXYETHYL)CYCLOPROPYL]AMINO] 2 (2,3,4,5 TETRAFLUOROBENZOYL)ACRYLATE; ETHYL 3 [[1 [2 (TERT BUTOXYCARBONYLAMINO)ETHYL]CYCLOBUTYL]AMINO] 2 (2,3,4,5 TETRAFLUOROBENZOYL)ACRYLATE; ETHYL 9' AMINO 10',11' DIFLUORO 2',3' DIHYDRO 2' METHYL 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 9' AMINO 10',11' DIFLUORO 2',3' DIHYDRO 3' METHYL 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 9' AMINO 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOBUTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 9' AMINO 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOPENTANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; ETHYL 9' AMINO 10',11' DIFLUORO 2',3' DIHYDRO 8' OXO SPIRO(CYCLOPROPANE 1,4' [4H,8H]PYRIDO[1,2,3 EF][1,4]BENZOXAZEPINE) 7' CARBOXYLATE; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; GLYCOGEN SYNTHASE KINASE 3BETA; QUINOLONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG DESIGN; DRUG SYNTHESIS; ENZYME INHIBITION; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN CELL; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST;

ANIMALS; DIABETES MELLITUS, TYPE 2; DRUG DESIGN; GLUCOSE TOLERANCE TEST; GLYCOGEN SYNTHASE KINASE 3; HEP G2 CELLS; HUMANS; MALE; MICE; MODELS, MOLECULAR; QUINOLONES; SPIRO COMPOUNDS;

MUS;

EID: 84856228492     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2011.12.046     Document Type: Article

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