Discovery of MK-8970: An acetal carbonate prodrug of raltegravir with enhanced colonic absorption

ChemMedChem

Volumn 10, Issue 2, 2015, Pages 245-252

  Walji, Abbas M ^a   Sanchez, Rosa I ^a   Clas, Sophie Dorothee ^a,b   Nofsinger, Rebecca ^a   De Lera Ruiz, Manuel ^a   Li, Jing ^a   Bennet, Amrithraj ^a   John, Christopher ^a   Bennett Dr, David Jonathan ^a   Sanders, John M ^a   Di Marco, Christina N ^a   Kim, Somang Hope ^a   Balsells, Jaume ^a   Ceglia, Scott S ^a   Dang, Qun ^a   Manser, Kimberly ^a   Nissley, Becky ^a   Wai, John S ^a   Hafey, Michael ^a   Wang, Junying ^a   Chessen, Gene ^a   Templeton, Allen ^a   Higgins, John ^a   Smith, Ronald ^a   Wu, Yunhui ^a   Grobler, Jay ^a   Coleman, Paul J ^a   more..

^a MERCK RESEARCH LABORATORIES   (United States)

^b PharmaSolv Consulting   (Canada)

Author keywords

Antiviral agents; Colonic absorption; Controlled release formulation; HIV 1; Once daily dosing; Prodrugs; Raltegravir

Indexed keywords

1 [[4 [(4 FLUOROBENZYL)CARBAMOYL] 1 METHYL 2 [2 (5 METHYL 1,3,4 OXADIAZOLE 2 CARBOXAMIDO)PROPAN 2YL] 6 OXO 1,6 DIHYDROPYRIMDIN 5 YL]OXY] 2 METHYLPROPYL ISOPROPYL CARBONATE; 1 [[4 [(4 FLUOROBENZYL)CARBAMOYL] 1 METHYL 2 [2 (5 METHYL 1,3,4 OXADIAZOLE 2 CARBOXAMIDO)PROPAN 2YL] 6 OXO 1,6 DIHYDROPYRIMDIN 5 YL]OXY]ETHYL (2 METHOXYETHYL) CARBONATE; 1 [[4 [(4 FLUOROBENZYL)CARBAMOYL] 1 METHYL 2 [2 (5 METHYL 1,3,4 OXADIAZOLE 2 CARBOXAMIDO)PROPAN 2YL] 6 OXO 1,6 DIHYDROPYRIMDIN 5 YL]OXY]ETHYL ISOPROPYL CARBONATE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CARBONIC ACID DERIVATIVE; ETHYL [1 [[4 [(4 FLUOROBENZYL)CARBAMOYL] 1 METHYL 2 [2 (5 METHYL 1,3,4 OXADIAZOLE 2 CARBOXAMIDO)PROPAN 2YL] 6 OXO 1,6 DIHYDROPYRIMDIN 5 YL]OXY]ETHYL]CARBONATE; ETHYL [1 [[4 [(4 FLUOROBENZYL)CARBAMOYL] 1 METHYL 2 [2 (5 METHYL 1,3,4 OXADIAZOLE 2 CARBOXAMIDO)PROPAN 2YL] 6 OXO 1,6 DIHYDROPYRIMDIN 5 YL]OXY]PROPYL] CARBONATE; RALTEGRAVIR; UNCLASSIFIED DRUG; [[4 [(4 FLUOROBENZYL)CARBAMOYL] 1 METHYL 2 [2 (5 METHYL 1,3,4 OXADIAZOLE 2 CARBOXAMIDO)PROPAN 2YL] 6 OXO 1,6 DIHYDROPYRIMDIN 5 YL]OXY]METHYL PIVALATE; 2 PYRROLIDONE DERIVATIVE; ACETAL DERIVATIVE; ETHYL (1-((4-((4-FLUOROBENZYL)CARBAMOYL)-1-METHYL-2-(2-(5-METHYL-1,3,4-OXADIAZOLE-2-CARBOXAMIDO)PROPAN-2-YL)-6-OXO-1,6-DIHYDROPYRIMIDIN-5-YL)OXY)ETHYL)CARBONATE; INTEGRASE; INTEGRASE INHIBITOR; OXADIAZOLE DERIVATIVE; PRODRUG; PYRIMIDINONE DERIVATIVE;

ANIMAL EXPERIMENT; ANTIVIRAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; COLON ABSORPTION; CRYSTALLIZATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG SOLUBILITY; DRUG SYNTHESIS; DRUG TOLERABILITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROLYSIS; IN VITRO STUDY; IN VIVO STUDY; INTRINSIC CLEARANCE; LIMIT OF QUANTITATION; LIPOPHILICITY; LIQUID CHROMATOGRAPHY; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; STRUCTURE ACTIVITY RELATION; TANDEM MASS SPECTROMETRY; THIN LAYER CHROMATOGRAPHY; VOLUME OF DISTRIBUTION AT STEADY-STATE; ANIMAL; CHEMISTRY; DOG; DRUG SCREENING; ENZYMOLOGY; HALF LIFE TIME; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; INTESTINE; LIVER CELL; METABOLISM; RECEIVER OPERATING CHARACTERISTIC; SYNTHESIS; WISTAR RAT;

ACETALS; ANIMALS; AREA UNDER CURVE; CARBONATES; DOGS; DRUG EVALUATION, PRECLINICAL; HALF-LIFE; HEPATOCYTES; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; INTESTINES; MALE; OXADIAZOLES; PRODRUGS; PYRIMIDINONES; PYRROLIDINONES; RATS; RATS, WISTAR; ROC CURVE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84921726198     PISSN: 18607179     EISSN: 18607187     Source Type: Journal    
DOI: 10.1002/cmdc.201402393     Document Type: Article

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