Optimization of pyrrolamide topoisomerase II inhibitors toward identification of an antibacterial clinical candidate (AZD5099)

Journal of Medicinal Chemistry

Volumn 57, Issue 14, 2014, Pages 6060-6082

  Basarab, Gregory S ^a   Hill, Pamela J ^a   Garner, C Edwin ^a,b   Hull, Ken ^a,c   Green, Oluyinka ^a   Sherer, Brian A ^a,d   Dangel, P Brian ^a,e   Manchester, John I ^a   Bist, Shanta ^a   Hauck, Sheila ^a   Zhou, Fei ^a   Uria Nickelsen, Maria ^a,f   Illingworth, Ruth ^a   Alm, Richard ^a   Rooney, Mike ^a   Eakin, Ann E ^a,g  

^a ASTRAZENECA   (United Kingdom)

^b Oso Corredor Scientific Consulting   (United States)

^c TEXAS A AND M UNIVERSITY   (United States)

^d EMD Serono Research Institute   (United States)

^e LEAP PAL Parts   (United States)

^f PFIZER INC   (United States)

^g NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [ REL 11 [[(3,4 DICHLORO 5 METHYL 1H PYRROL 2 YL)CARBONYL]AMINO] 3 METHOXY 1,5 DIOXA 8 AZASPIRO[5.5]UNDEC 8 YL] 5 THIAZOLECARBOXYLIC ACID; 2 [11 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 5,12 DIOXA 8 AZADISPIRO[2.2.56.23]TRIDECAN 8 YL]THIAZOLE 5 CARBOXYLIX ACID; 2 [4 [(3,4 DICHLORO 5 METHYL 1 PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL]THIAZOLE 5 CARBOXYLIC ACID; 2 [4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 (2 METHYL 1,2,4 TRIAZOLE 3 YL)THIAZOLE 5 CARBOXYLIC ACID; 2 [4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 (METHYLCARBAMOYL)THIAZOLE 5 CARBOXYLIC ACID; 2 [4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 PYRAZIN 2 YL THIAZOLE 5 CARBOXYLIC ACID; 2 [4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 PYRIMIDIN 2 YL THIAZOLE 5 CARBOXYLIC ACID; 2 [4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 [[2 METHOXY 1 (METHYLMETHYL)ETHYL]CARBOMOYL]THIAZOLE 5 CARBOXYLIC ACID; 2 [4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 [[2 METHOXY 1 METHYL ETHYL]CARBOMOYL]THIAZOLE 5 CARBOXYLIC ACID; ADENOSINE TRIPHOSPHATE; ANTIINFECTIVE AGENT; AZD 5099; CARBOXYLIC ACID; ETHYL 2 [4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMNO] 3 METHOXY 1 PIPERIDYL] 4 (METHYLCARBAMOYL)THIAZOLE 5 CARBOXYLATE; ETHYL 2 [4[(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 [[2 METHOXY 1 METHYL ETHYL]CARBAMOYL]THIAZOLE 5 CARBOXYLATE; ETHYL 2 [REL 4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 (MORPHOLINE 4 CARBONYL)THIAZOLE 5 CARBOXYLATE; ETHYL 4 [(3,4 DICHLORO 5 METHYL 1 PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 PYRAZIN 2 YL THIAZOLE 5 CARBOXYLIC ACID; ETHYL 4 [(3,4 DICHLORO 5 METHYL 1 PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 PYRIMIDIN 2 YL THIAZOLE 5 CARBOXYLATE; ETHYL 4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 [[2 METHOXY 1(METHOXYMETHYL)ETHYL]CARBAMOYL]THIAZOLE 5 CARBOXYLATE; GYRASE INHIBITOR; METHYL 2 [4 [(3,4 DICHLORO 5 METHYL 1 PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL]THIAZOLE 5 CARBOXYLATE; METHYL 4 [(3,4 DICHLORO 5 METHYL 1H PYRROLE 2 CARBONYL)AMINO] 3 METHOXY 1 PIPERIDYL] 4 (2 METHYL 1,2,4 TRIAZOLE 3 YL)THIAZOLE 5 CARBOXATE; METHYL 5 (2 AMINOTHIAZOL 4 YL) 2 [4 [(3,4 DICHLORO 5 METHYL IH PYRROLE 2 CARBONYL)AMINO] 3 MEHTOXY 1 PIPERIDYL]THIAZOLE 4 CARBOXYLATE; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 2; PIPERIDINE DERIVATIVE; THIAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL CLEARANCE; CHEMICAL REACTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG EFFICACY; DRUG EXPOSURE; DRUG IDENTIFICATION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HYDROGEN BOND; IN VIVO STUDY; MOUSE; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PROCESS OPTIMIZATION; STAPHYLOCOCCUS INFECTION;

ADENOSINE TRIPHOSPHATASES; AMIDES; ANIMALS; ANTI-BACTERIAL AGENTS; CRYSTALLOGRAPHY, X-RAY; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MICE; MICE, KNOCKOUT; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRROLES; RATS; RATS, WISTAR; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; TOPOISOMERASE II INHIBITORS;

EID: 84905015435     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500462x     Document Type: Article

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