Can We Make Small Molecules Lean? Optimization of a Highly Lipophilic TarO Inhibitor

Journal of Medicinal Chemistry

Volumn 60, Issue 9, 2017, Pages 3851-3865

  Mandal, Mihirbaran ^a   Tan, Zheng ^a   Madsen Duggan, Christina ^a   Buevich, Alexei V ^a   Caldwell, John P ^a   Dejesus, Reynalda ^a   Flattery, Amy ^a   Garlisi, Charles G ^a   Gill, Charles ^a   Ha, Sookhee Nicole ^a   Ho, Ginny ^a   Koseoglu, Sandra ^a   Labroli, Marc ^a   Basu, Kallol ^a   Lee, Sang Ho ^a   Liang, Lianzhu ^a   Liu, Jenny ^a   Mayhood, Todd ^a   McGuinness, Debra ^a   McLaren, David G ^a   Wen, Xiujuan ^a   Parmee, Emma ^a   Rindgen, Diane ^a   Roemer, Terry ^a   Sheth, Payal ^a   Tawa, Paul ^a   Tata, James ^a   Yang, Christine ^a   Yang, Shu Wei ^a   Xiao, Li ^a   Wang, Hao ^a   Tan, Christopher ^a   Tang, Haifeng ^a   Walsh, Paul ^a   Walsh, Erika ^a   Wu, Jin ^a   Su, Jing ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [(ISOQUINOLIN 4 YLMETHYL)CARBAMOYL] 2 OXO 5 [3(TRIFLUOROMETHYL)PHENYL]OXAZOLIDINE 4 CARBOXYLIC ACID; 4 (HYDROXYMETHYL) N(ISOQUINOLIN 4 YLMETHYL) 2 OXO 5 [3 (TRIFLUOROMETHYL)PHENYL]OXAZOLIDINE 3 CARBOXAMIDE; 4 METHYL 5 [3 (TRIFLUOROMETHYL)PHENYL]OXAZOLIDIN 2 ONE; 4 METHYL 5 [4 (TRIFLUOROMETHYL)PYRIDIN 2 YL]OXAZOLIDIN 2 ONE; 5 (3 FLUORO 5 (TRIFLUOROMETHYL)PHENYL] 4 (2 HYDROXYETHYL) N(ISOQUINOLIN 4 YLMETHYL) 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; 5 [3 FLUORO 5 (TRIFLUOROMETHYL)PHENYL] 3 [(ISOQUINOLIN 4 YLMETHYL)CARBAMOYL]; 5 [3 FLUORO 5 (TRIFLUOROMETHYL)PHENYL] 4 (HYDROXYMETHYL) N(ISOQUINOLIN 4 YLMETHYL) 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; 5 [3 FLUORO 5 (TRIFLUOROMETHYL)PHENYL] 4 METHYLOXAZOLIDIN 2 ONE; 5 [3 FLUORO 5 (TRIFLUOROMETHYL)PHENYL] N (ISOQUINOLIN 4 YLMETHYL) 4 METHYL 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; 5 [3,5 BIS (TRIFLUOROMETHYL)PHENYL] 4 METHYL 3 [2 NAPHTHALEN 1 YL) ACETYL] OXAZOLIDIN 2 ONE; 5 [3,5 BIS(TRIFLUOROMETHYL)PHENYL) 3 [3 (ISOQUINOLIN 4 YL)PROPANOYL] 4 METHYLOXAZOLIDIN 2 ONE; 5 [3,5 BIS(TRIFLUOROMETHYL)PHENYL] 3 [2 (ISOQUINOLIN 4 YL)ACETYL] 4 METHYLOXAZOLIDIN 2 ONE; 5 [3,5 BIS(TRIFLUOROMETHYL)PHENYL] 4 (HYDROXYMETHYL) N(ISOQUINOLIN 4 YLMETHYL) 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; 5 [3,5 BIS(TRIFLUOROMETHYL)PHENYL] 4 METHYL 3 [3 (NAPHTHALEN 1 YL)PROPANOYL]OXAZOLIDIN 2 ONE; 5 [3,5 BIS(TRIFLUOROMETHYL)PHENYL] N(ISOQUINOLIN 4 YLMETHYL) 4 METHYL 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; ANTIINFECTIVE AGENT; IMIPENEM; N [(1,6 NAPHTHYRIDIN 8 YL)METHYL] 4 METHYL 2 OXO5 [3 (TRIFLUOROMETHYL)PHENY]OXAZOLIDINE 3 CARBOXAMIDE; N [(1,6 NAPHTHYRIDIN 8 YL)METHYL] 5 [3,5 BIS(4 TRIFLUOROMETHYL)PHENYL] 4 (HYDROXYMETHYL) 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; N [(1,6 NAPHTHYRIDIN 8 YL)METHYL] 5 [3,5 BIS(4 TRIFLUOROMETHYL)PHENYL] 4 METHYL 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; N [(1,6 NAPHTHYRIDIN 8 YL)METHYL] 5 [6 METHOXY 4(TRIFLUOROMETHYL)PYRIDIN 2 YL] 4 METHYL 2 OXOOXAZOLIDINE 3 CARBOXAMIDE; N(ISOQUINOLIN 4 YLMETHYL) 4 METHYL 2 OXO 5 [3(4 TRIFLUOROMETHYL)PHENYL]OXAZOLIDINE 3 CARBOXAMIDE; TEICHOIC ACID; UNCLASSIFIED DRUG; LIPID; MOLECULAR LIBRARY;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AQUEOUS SOLUTION; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG SOLUBILITY; ENZYME ASSAY; FEMALE; HYDROGEN BOND; IC50; IN VIVO STUDY; LIPOPHILICITY; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; RAT; REDUCTION (CHEMISTRY); SOLUBILITY; STAPHYLOCOCCUS; STAPHYLOCOCCUS INFECTION; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; BAGG ALBINO MOUSE; CHEMISTRY; DRUG EFFECTS; GROWTH, DEVELOPMENT AND AGING; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MICROBIAL SENSITIVITY TEST; MOLECULAR LIBRARY;

ANIMALS; FEMALE; LIPIDS; METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS; MICE; MICE, INBRED BALB C; MICROBIAL SENSITIVITY TESTS; SMALL MOLECULE LIBRARIES; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 85019267199     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.7b00113     Document Type: Article

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