Structure-activity relationship of 6-methylidene penems bearing tricyclic heterocycles as broad-spectrum β-lactamase inhibitors: Crystallographic structures show unexpected binding of 1,4-thiazepine intermediates

Journal of Medicinal Chemistry

Volumn 47, Issue 26, 2004, Pages 6556-6568

  Venkatesan, Aranapakam M ^a   Gu, Yansong ^a   Santos, Osvaldo Dos ^a   Abe, Takao ^b   Agarwal, Atul ^a   Yang, Youjun ^a   Petersen, Peter J ^a   Weiss, William J ^a   Mansour, Tarek S ^a   Nukaga, Michiyoshi ^c   Hujer, Andrea M ^d   Bonomo, Robert A ^d   Knox, James R ^d  

^a WYETH RESEARCH   (United States)

^b Department of Pharmacokinetics   (Japan)

^c UNIVERSITY OF CONNECTICUT   (United States)

^d LOUIS STOKES CLEVELAND VA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (1 METHYL 1,2,3 TRIAZOL 4 YLMETHYLENE)PENEM 3 CARBOXYLIC ACID; 6 (5 METHYLIMIDAZO[2,1 B][1,3]BENZOTHIAZOL 2 YLMETHYLEN) 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 6 (6,7 DIHYDRO 5H CYCLOPENTA[D]IMIDAZO[2,1 B][1,3]BENZOTHIAZOL 2 YLMETHYLEN) 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 6 (7 CHLOROIMIDAZO[2,1 B][1,3]BENZOTHIAZOL 2 YLMETHYLEN) 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 6 (7 FLUOROIMIDAZO[2,1 B][1,3]BENZOTHIAZOL 2 YLMETHYLEN) 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 6 (7 METHOXYIMIDAZO[2,1 B][1,3]BENZOTHIAZOL 2 YLMETHYLEN) 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 6 (7 METHYLIMIDAZO[2,1 B][1,3]BENZOTHIAZOL 2 YLMETHYLEN) 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; 6 (IMIDAZO[2,1 B][1,3]BENZOTHIAZOL 2 YLMETHYLEN) 7 OXO 4 THIA 1 AZABICYCLO[3.2.0]HEPT 2 ENE 2 CARBOXYLIC ACID; BETA LACTAMASE; BETA LACTAMASE INHIBITOR; PENEM DERIVATIVE; PIPERACILLIN; TAZOBACTAM; THIAZEPINE DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBIOTIC RESISTANCE; ANTIMICROBIAL ACTIVITY; ARTICLE; COMPLEX FORMATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG PROTEIN BINDING; DRUG SENSITIVITY; DRUG SYNTHESIS; ENTEROBACTER CLOACAE; ENZYME ACTIVE SITE; ENZYME INHIBITION; ESCHERICHIA COLI; HYDROPHOBICITY; KLEBSIELLA PNEUMONIAE; NONHUMAN; NUCLEOTIDE SEQUENCE; PROTEIN INTERACTION; PSEUDOMONAS AERUGINOSA; SERRATIA MARCESCENS; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION;

BETA-LACTAMASES; BETA-LACTAMS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; ENTEROBACTER CLOACAE; ESCHERICHIA COLI; HETEROCYCLIC COMPOUNDS, 2-RING; HETEROCYCLIC COMPOUNDS, 3-RING; HYDROLYSIS; KLEBSIELLA PNEUMONIAE; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; PROTEIN BINDING; PSEUDOMONAS AERUGINOSA; SERRATIA MARCESCENS; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZEPINES;

EID: 10644224325     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049680x     Document Type: Article

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