Structure-guided design and optimization of dipeptidyl inhibitors of norovirus 3CL protease. Structure-activity relationships and biochemical, X-ray crystallographic, cell-based, and in vivo studies

Journal of Medicinal Chemistry

Volumn 58, Issue 7, 2015, Pages 3144-3155

  Galasiti Kankanamalage, Anushka C ^a   Kim, Yunjeong ^b   Weerawarna, Pathum M ^a   Uy, Roxanne Adeline Z ^a   Damalanka, Vishnu C ^a   Mandadapu, Sivakoteswara Rao ^a   Alliston, Kevin R ^a   Mehzabeen, Nurjahan ^c   Battaile, Kevin P ^d   Lovell, Scott ^c   Chang, Kyeong Ok ^b   Groutas, William C ^a  

^a WICHITA STATE UNIVERSITY   (United States)

^b KANSAS STATE UNIVERSITY   (United States)

^c UNIVERSITY OF KANSAS   (United States)

^d ARGONNE NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(2S) 2 [(S) 2 ((((2 CHLOROBENZYL)OXY)CARBONYL)AMINO) 3 CYCLOHEXYLPROPANA MIDO) 1 HYDROXY 3 ((S) 2 OXOPYRROLIDIN 3 YL]PROPANE 1 SULFONATE; (2S) 2 [(S) 2 ((((3 BROMOBENZYL)OXY)CARBONYL)AMINO) 3 CYCLOHEXYLPROPANA MIDO) 1 HYDROXY 3 ((S) 2 OXOPYRROLIDIN 3 YL]PROPANE 1 SULFONATE; (2S) 2 [(S) 2 ((((3 CHLOROBENZYL)OXY)CARBONYL)AMINO) 3 CYCLOHEXYLPROPANA MIDO) 1 HYDROXY 3 ((S) 2 OXOPYRROLIDIN 3 YL]PROPANE 1 SULFONATE; (2S) 2 [(S) 3 CYCLOHEXYL 2 ((((3 IODOBENZYL)OXY)CARBONYL)AMINO)PROPANE MIDO) 1 HYDROXY 3 ((2) 2 OXOPYRROLIDIN 3 YL]PROPANE 1 SULFONATE; 2 CHLOROBENZYL [(2S) 3 CYCLOHEXYL 1 (((2S) 1 (DIETHOXYPHOSPHORYL) 1 HYDROXY 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO) 1 OXOPROPAN 2 YL]CARBAMATE; 2 CHLOROBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 2 FLUOROBENZYL [(2S) 3 CYCLOHEXYL 1 (((2S) 1 (DIETHOXYPHOSPHORYL) 1 HYDROXY 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO) 1 OXOPROPAN 2 YL]CARBAMATE; 2 FLUOROBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 2 METHOXYBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 BROMOBENZYL [(2S) 3 CYCLOHEXYL 1 (((2S) 1 (DIETHOXYPHOSPHORYL) 1 HYDROXY 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO) 1 OXOPROPAN 2 YL]CARBAMATE; 3 BROMOBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 CHLOROBENZYL [(2S) 3 CYCLOHEXYL 1 (((2S) 1 (DIETHOXYPHOSPHORYL) 1 HYDROXY 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO) 1 OXOPROPAN 2 YL]CARBAMATE; 3 CHLOROBENZYL [(S) 1 CYCLOHEXYL 2 OXO 2 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)ETHYL]CARBAMATE; 3 CHLOROBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 CHLOROBENZYL [(S) 4 METHYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PENTAN 2 YL]CARBAMATE; 3 CYANOBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 FLUOROBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 IODOBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 METHOXYBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 NITROBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 3 [(TERT BUTOXYCARBONYL)AMINO]BENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; 4 CHLOROBENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; ANTIVIRUS AGENT; BENZYL [(S) 3 CYCLOHEXYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PROPAN 2 YL]CARBAMATE; BENZYL [(S) 4 METHYL 1 OXO 1 (((S) 1 OXO 3 ((S) 2 OXOPYRROLIDIN 3 YL)PROPAN 2 YL)AMINO)PENTAN 2 YL]CARBAMATE; NOROVIRUS 3CL PROTEASE; PROTEINASE; PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIRUS ENZYME; 3C-LIKE PROTEASE, SARS CORONAVIRUS; CYSTEINE PROTEINASE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; PEPTIDE HYDROLASE; VIRUS PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG DOSE; DRUG SYNTHESIS; ENZYME ASSAY; HYDROGEN BOND; IC50; IN VIVO STUDY; MOUSE; NONHUMAN; NOROVIRUS INFECTION; PROTON NUCLEAR MAGNETIC RESONANCE; REPLICON; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; ENZYMOLOGY; FEMALE; MACROPHAGE; METABOLISM; NOROVIRUS; PATHOGENICITY; PROTEIN CONFORMATION; SYNTHESIS; VIROLOGY;

ANIMALS; ANTIVIRAL AGENTS; CELL LINE; CHEMISTRY TECHNIQUES, SYNTHETIC; CRYSTALLOGRAPHY, X-RAY; CYSTEINE ENDOPEPTIDASES; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; FEMALE; MACROPHAGES; MICE, INBRED BALB C; MODELS, MOLECULAR; NOROVIRUS; PEPTIDE HYDROLASES; PROTEASE INHIBITORS; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP; VIRAL PROTEINS;

EID: 84927759277     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5019934     Document Type: Article

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