Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections

Journal of Medicinal Chemistry

Volumn 60, Issue 7, 2017, Pages 2669-2684

  Tan, Liang ^a,b   Tao, Yunliang ^c   Wang, Ting ^d   Zou, Feng ^d   Zhang, Shuhua ^d   Kou, Qunhuan ^a,b   Niu, Ao ^e   Chen, Qian ^a,b   Chu, Wenjing ^a,b   Chen, Xiaoyan ^a,b   Wang, Haidong ^c   Yang, Yushe ^a,b  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^c JIAXING UNIVERSITY   (China)

^d Sichuan Primed Bio tech Group Co Ltd   (China)

^e CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

2 [[[1 (2 AMINOTHIAZOL 4 YL) 2 [[2,2 DIMETHYL 4 OXO 1 (SULFOOXY)AZETIDIN 3 YL]AMINO] 2 OXOETHYLIDENE]AMINO]OXY] 2 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL)ACETIC ACID; 3 [ 2 (2 AMINO 5 CHLOROTHIAZOL 4 YL) 2 [[ 1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO] ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [ 2 (2 AMINO 5 CHLOROTHIAZOL 4 YL) 2 [[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO] ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [ 2 (2 AMINOTHIAZOL 4 YL) 2 [[ 1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [ 2 (2 AMINOTHIAZOL 4 YL) 2 [[(1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL)(THIOPHEN 2 YL)METHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [ 2 (5 AMINO 1,2,4 THIADIAZOL 3 YL) 2 [[ 1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDTOPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO] ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [ 2 (5 AMINO 1,2,4 THIADIAZOL 3 YL) 2 [[ 1 (1,5 DIHYDROXY 4 OXO1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO] ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [ 2 (5 AMINO 1,2,4 THIADIAZOL 3 YL) 2 [[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDRO PYRIDIN 2 YL)ETHYOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXAZETIDIN 1 YL HYDROGEN SULFATE; 3 [ 2 (5 AMINO 1,2,4 THIADIAZOL 3 YL) 2 [[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO] ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINO 5 CHLOROTHIAZOL 4 YL) 2 [[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL] 2 METHYLPROPOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[ 1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 (METHYLTHIO)ETHOXY]IMINO]ACETIMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[ 1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[(1 HYDROXY 2 OXO 1,2 DIHYDROPYRIDIN 4 YL)METHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[(1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL)(PHENYL)NETHOXY]IMINIO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIM 2 YL)ETHOXY]IMINO]ACETAMIDO]2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 Y) 2 (METHYLTHIO)ETHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 METHYLPROPOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[1 (1,5 DIHYDROXY-4-OXO 1,4 DIHYDROPYRIDIN 2 YL)PROPOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[2 ( N HYDROXYACETAMIDO) ETHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[2 (5 HYDROXY 2 METHYL 4 OXOPYRIDIN 1(4H) YL)ETHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[2 [(6 HYDROXY 2 METHYL 5 OXO 2,5 DIHYDRO 1,2,4 TRIAZIN 3 YL)THIO]ETHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[CYCLOPROPYL(1,5 DIHYDROXY 4 OXO 1,4 DIHYDRO PYRIDIN 2 YL)METHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (2 AMINOTHIAZOL 4 YL) 2 [[[1 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL)ALLYL]OXY]IMINO]ACETAMIDO 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; 3 [2 (AMINOTHIAZOL 4 YL) 2 [[(1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL) 2 [[(1,5 DIHYDROXY 4 OXO 1,4 DIHYDROPYRIDIN 2 YL)(THIAZOL 2 YL)METHOXY]IMINO]ACETAMIDO] 2,2 DIMETHYL 4 OXOAZETIDIN 1 YL HYDROGEN SULFATE; ANTIBIOTIC AGENT; MEROPENEM; METHYL 2 [[[1 (2 AMINOTHIAZOL 4 YL) 2 [[2,2 DIMETHYL 4 OXO 1 (SULFOOXY)AZETIDIN 3 YL]AMINO] 2 OXOETHYLIDENE]AMINO]OXY] 2 (1,5 DIHYDROXY 4 OXO 1,4 DIHYDTOPYRIDIN 2 YL)ACETATE; PYRIDONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ANTIINFECTIVE AGENT; BAL 30072; MONOBACTAM DERIVATIVE; THIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG DESIGN; DRUG EFFICACY; DRUG HALF LIFE; DRUG SYNTHESIS; GRAM NEGATIVE INFECTION; KLEBSIELLA PNEUMONIAE; MALE; MOUSE; NONHUMAN; PLASMA PROTEIN BINDING; RAT; STRUCTURE ACTIVITY RELATION; VOLUME OF DISTRIBUTION AT STEADY-STATE; ANIMAL; BLOOD; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; ESCHERICHIA COLI; ESCHERICHIA COLI INFECTIONS; GRAM NEGATIVE BACTERIUM; GRAM-NEGATIVE BACTERIAL INFECTIONS; HUMAN; KLEBSIELLA INFECTIONS; MICROBIAL SENSITIVITY TEST; MULTIDRUG RESISTANCE; SPRAGUE DAWLEY RAT;

ANIMALS; ANTI-BACTERIAL AGENTS; DRUG DISCOVERY; DRUG RESISTANCE, MULTIPLE, BACTERIAL; ESCHERICHIA COLI; ESCHERICHIA COLI INFECTIONS; GRAM-NEGATIVE BACTERIA; GRAM-NEGATIVE BACTERIAL INFECTIONS; HUMANS; KLEBSIELLA INFECTIONS; KLEBSIELLA PNEUMONIAE; MALE; MICE; MICROBIAL SENSITIVITY TESTS; MONOBACTAMS; PYRIDONES; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

EID: 85017525110     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b01261     Document Type: Article

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