Discovery of a cyclic boronic acid β-lactamase inhibitor (RPX7009) with utility vs class A serine carbapenemases

Journal of Medicinal Chemistry

Volumn 58, Issue 9, 2015, Pages 3682-3692

  Hecker, Scott J ^a   Reddy, K Raja ^a   Totrov, Maxim ^b   Hirst, Gavin C ^a   Lomovskaya, Olga ^a   Griffith, David C ^a   King, Paula ^a   Tsivkovski, Ruslan ^a   Sun, Dongxu ^a   Sabet, Mojgan ^a   Tarazi, Ziad ^a   Clifton, Matthew C ^c   Atkins, Kateri ^c   Raymond, Amy ^c   Potts, Kristy T ^c   Abendroth, Jan ^c   Boyer, Serge H ^a   Loutit, Jeffrey S ^a   Morgan, Elizabeth E ^a   Durso, Stephanie ^a   Dudley, Michael N ^a   more..

^a Medicines Company   (United States)

^b Molsoft LLC   (United States)

^c Beryllium   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(2 HYDROXY 3 (2 THIOPHEN 2 YLACETYLAMINO) [1,2]OXABORINAN 6 YL)ACETIC ACID; 2 HYDROXY 3 (2 THIENYLACETAMIDO) 1,5,2 DIOXABOREPANE 7 ACETIC ACID; BIAPENEM; CARBAPENEM DERIVATIVE; CEFEPIME; CLAVULANIC ACID; ERTAPENEM; IMIPENEM; MEROPENEM; TAZOBACTAM; TERT BUTYL 3 (TERT BUTYDIMETHYLSILYLOXY) 6 (2 THIO PEHN 2 YL ACETYLAMINO) 6 ( 2,9,9 TRIMETHYL 3,5 DIOXA 4 BORATRICYCLO [6.1.1.0 2.6]DECAN 4 YL)HEXANOATE; TERT BUTYL 3 (TERT BUTYDIMETHYLSILYLOXY) 6 CHLORO 6 ( 2,9,9 TRIMETHYL 3,5 DIOXA 4 BORATRICYCLO [6.1.1.0 2.6] DECAN 4 YL)HEXANOATE; TERT BUTYL 3 (TERT BUTYLDIMETHYLSILYLOXY) 5 ( 2,9,9 TRIMETHYL 3,5 DIOXA 4 BORATRICYCLO [6.1.10 2.6]DECAN 4 YL) PENTANOATE; TERT BUTYL 3 (TERT BUTYLDIMETHYLSILYLOXY) 5 (4,4,5,5 TETRAMETHYL[1,3,2]DIOXABOROLAN 2 YL)PENTANOATE; TERT BUTYL 3 (TERT BUTYLDIMETHYLSILYLOXY) PENT 4 ENOATE; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; BETA LACTAMASE; BETA LACTAMASE INHIBITOR; BORONIC ACID DERIVATIVE; CARBAPENEMASE; SINGLE HETEROCYCLIC RINGS;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIBACTERIAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BIOCHEMICAL ANALYSIS; CONTINUOUS INFUSION; CRYSTALLIZATION; DEVELOPMENTAL TOXICITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TOLERABILITY; ENZYME ACTIVE SITE; ENZYME CONFORMATION; GENOTOXICITY; GRAM NEGATIVE INFECTION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYDROGEN BOND; IC50; IN VITRO STUDY; IN VIVO STUDY; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; RAT; REPRODUCTIVE TOXICITY; STEREOCHEMISTRY; SWISS WEBSTER MOUSE; TIME TO MAXIMUM PLASMA CONCENTRATION; VOLUME OF DISTRIBUTION; X RAY CRYSTALLOGRAPHY; ANIMAL; ANTAGONISTS AND INHIBITORS; ANTIBIOTIC RESISTANCE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; DRUG POTENTIATION; ENZYMOLOGY; GRAM NEGATIVE BACTERIUM; ISOLATION AND PURIFICATION; MICROBIAL SENSITIVITY TEST; STEREOISOMERISM; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; BETA-LACTAMASE INHIBITORS; BETA-LACTAMASES; BORONIC ACIDS; CARBAPENEMS; CRYSTALLOGRAPHY, X-RAY; DRUG RESISTANCE, BACTERIAL; DRUG SYNERGISM; GRAM-NEGATIVE BACTERIA; HETEROCYCLIC COMPOUNDS, 1-RING; MICE; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84929340109     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00127     Document Type: Article

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