Design of Potent mRNA Decapping Scavenger Enzyme (DcpS) Inhibitors with Improved Physicochemical Properties To Investigate the Mechanism of Therapeutic Benefit in Spinal Muscular Atrophy (SMA)

Journal of Medicinal Chemistry

Volumn 60, Issue 7, 2017, Pages 3094-3108

  Gopalsamy, Ariamala ^a   Narayanan, Arjun ^a   Liu, Shenping ^a   Parikh, Mihir D ^a   Kyne, Robert E ^a   Fadeyi, Olugbeminiyi ^a   Tones, Michael A ^a   Cherry, Jonathan J ^a   Nabhan, Joseph F ^a   LaRosa, Gregory ^a   Petersen, Donna N ^a   Menard, Carol ^a   Foley, Timothy L ^a   Noell, Stephen ^a   Ren, Yong ^a   Loria, Paula M ^a   Maglich Goodwin, Jodi ^a   Rong, Haojing ^a   Jones, Lyn H ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 (BROMOMETHYL) 6 FLUORO 4 METHYLBENZONITRILE; 2 (BROMOMETHYL) 6 FLUOROBENZONITRILE; 2 BROMO 6 FLUORO 4 METHYLANILINE; 2 FLUORO 6 (HYDROXYMETHYL) 4 METHYLBENZONITRILE; 2 FLUORO 6 FORMYL 4 METHYLBENZONITRILE; 2 FLUORO 6 [(1 METHOXYPROPAN 2 YL)OXY]BENZONITRILE; 2 FLUORO 6 [[(2 METHYLPYRIDIN 3 YL)OXY]METHYL]BENZONITRILE; 2 [(3 CYANO 5 FLUOROPHENOXY)METHYL] 6 FLUORO 4 METHYLBENZONITRILE; 2,6 DIFLUORO 4 METHYLBENZONITRILE; 3 [(2,4 DIAMINO 7 METHYLQUINAZOLIN 5 YL)METHOXY] 5 FLUOROBENZONITRILE; 3 [(2,4 DIAMINOQUINAZOLIN 5 YL)METHOXY] 5 FLUOROBENZONITRILE; 4 [(2 CYANO 3 FLUORO 5 METHYLPHENOXY)METHYL]PIPERIDINE 1 CARBOXYLATE; 4 [[(2,4 DIAMINO 7 METHYLQUINAZOLIN 5 YL)OXY]METHYL]PIPERIDINE 1 CARBOXY; 5 [(1 METHOXYPROPAN 2 YL)OXY]QUINAZOLINE 2,4 DIAMINE; 5 [[(2 METHYLPYRIDIN 3 YL)OXY]METHYL)QUINAZOLINE 2,4 DIAMINE DIHYDROCHLORIDE; 5 [[(TETRAHYDRO 2H PYRAN 4 YL)OXY]METHYL]QUINAZOLINE 2,4 DIAMINE; 5 [[1 (2 FLUOROBENZYL)PIPERIDIN 4 YL]METHOXY] 7 METHYLQUINAZOLINE 2,4 DIAMINE; 5 [[1 (2,6 DICHLOROBENZYL)PIPERIDIN 4 YL]METHOXY] 7 METHYLQUINAZOLINE 2,4 DIAMINE; 7 METHYL 5 (PIPERIDIN 4 YLMETHOXY)QUINAZOLINE 2,4 DIAMINE; 7 METHYL 5 [(TETRAHYDRO 2H PYRAN 4 YL)METHOXY]QUINAZOLINE 2,4 DIAMINE; DECAPPING SCAVENGER ENZYME INHIBITOR; ENZYME INHIBITOR; UNCLASSIFIED DRUG; 2,4-DIAMINOQUINAZOLINE; DCPS PROTEIN, HUMAN; DCPS PROTEIN, MOUSE; MESSENGER RNA; QUINAZOLINE DERIVATIVE; RIBONUCLEASE; SURVIVAL MOTOR NEURON PROTEIN 2;

ACCUMULATION ASSAY; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG ACCUMULATION; DRUG DESIGN; DRUG PENETRATION; DRUG SOLUBILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INTRINSIC CLEARANCE; MALE; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; SPINAL MUSCULAR ATROPHY; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DISEASE MODEL; GENETICS; HEK293 CELL LINE; METABOLISM; MOLECULAR DOCKING; MUSCULAR ATROPHY, SPINAL;

ANIMALS; DISEASE MODELS, ANIMAL; DRUG DESIGN; ENDORIBONUCLEASES; ENZYME INHIBITORS; HEK293 CELLS; HUMANS; MICE; MOLECULAR DOCKING SIMULATION; MUSCULAR ATROPHY, SPINAL; QUINAZOLINES; RNA, MESSENGER; SURVIVAL OF MOTOR NEURON 2 PROTEIN;

EID: 85017558628     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.7b00124     Document Type: Article

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