Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and stargardt disease

Journal of Medicinal Chemistry

Volumn 57, Issue 18, 2014, Pages 7731-7757

  Cioffi, Christopher L ^a   Dobri, Nicoleta ^b   Freeman, Emily E ^a   Conlon, Michael P ^a   Chen, Ping ^a   Stafford, Douglas G ^a   Schwarz, Daniel M C ^a   Golden, Kathy C ^a   Zhu, Lei ^a   Kitchen, Douglas B ^a   Barnes, Keith D ^a   Racz, Boglarka ^b   Qin, Qiong ^b   Michelotti, Enrique ^f   Cywin, Charles L ^g   Martin, William H ^e   Pearson, Paul G ^d   Johnson, Graham ^c   Petrukhin, Konstantin ^b  

^a ALBANY MOLECULAR RESEARCH INC   (United States)

^b Department of Medicine   (United States)

^c NuPharmAdvise LLC   (United States)

^d Pearson Pharma Partners   (United States)

^e WHM Consulting LLC   (United States)

^f NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^g NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [4 [2 (TRIFLUOROMETHYL)PHENYL]PIPERIDINE 1 CARBONYL]PYRROLIDINE 2 CARBOXYLIC ACID; 2 (2,3 DIHYDROSPIRO[INDENE 1,4' PIPERIDIN] 1' YLCARBOXAMIDO)BENZOIC ACID; 2 (2,3,4,5 TETRAHYDRO 1H BENZO[D]AZEPINE 3 CARBOXAMIDO)BENZOIC ACID; 2 5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]BENZOIC ACID; 2 OXO 2 [4 [2 (TRIFLUOROMETHYL)PHENYL]PIPERIDIN 1 YL]ACETIC ACID; 2 [3 METHYL 3 [2 [2 (TRIFLUOROMETHYL)PHENOXY]ETHYL]UREIDO]BENZOIC ACID; 2 [3 [2 (TRIFLUOROMETHYL)PHENOXY]AZETIDINE 1 CARBOXAMIDO]BENZOIC ACID; 2 [3 [2 (TRIFLUOROMETHYL)PHENYL]AZETIDINE 1 CARBOXAMIDO]BENZOIC ACID; 2 [3 [2 [2 (TERT BUTYL) 4 CHLOROPHENOXY]ETHYL] 3 METHYLUREIDO]BENZOIC ACID; 2 [3 [2 [2 (TERT BUTYL) 4 FLUOROPHENOXY]ETHYL] 3 METHYLUREIDO]BENZOIC ACID; 2 [3 [2 [2 (TERT BUTYL)PHENOXY]ETHYL] 3 METHYLUREIDO]BENZOIC ACID; 2 [5 [2 (TRIFLUOROMETHYL)PHENYL] 1,2,3,3A,4,6A HEXAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]BENZOIC ACID; 2 [5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]NICOTINIC ACID; 2 [6 [2 (TRIFLUOROMETHYL)PHENYL] 2,6 DIAZASPIRO[3.3]HEPTANE 2 CARBOXAMIDO]BENZOIC ACID; 2 [6 [2 (TRIFLUOROMETHYL)PHENYL] 3 AZABICYCLO[3.1.0]HEXANE 3 CARBOXAMIDO]BENZOIC ACID; 3 OXO 3 [4 [2 (TRIFLUOROMETHYL)PHENYL]PIPERIDIN 1 YL]PROPANOIC ACID; 4 [5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]NICOTINIC ACID; 5 (METHYLSULFONYL) 2 [5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]BENZOIC ACID; 5 CHLORO 2 [5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]BENZOIC ACID; 5 FLUORO 2 [5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]BENZOIC ACID; 5 METHOXY 2 [5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]BENZOIC ACID; 6 METHYL 4 [5 [2 (TRIFLUOROMETHYL)PHENYL]OCTAHYDROCYCLOPENTA[C]PYRROLE 2 CARBOXAMIDO]NICOTINIC ACID; A 1120; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; N [2 [(CYCLOPROPYLSULFONYL)CARBAMOYL]PHENYL] 4 [2 (TRIFLUOROMETHYL)PHENYL]PIPERIDINE 1 CARBOXAMIDE; N [2 [(METHYLSULFONYL)CARBAMOYL]PHENYL] 4 [2 (TRIFLUOROMETHYL)PHENYL]PIPERIDINE 1 CARBOXAMIDE; OXO 4 [4 [2 (TRIFLUOROMETHYL)PHENYL]PIPERIDIN 1 YL]BUTANOIC ACID; PROTEIN INHIBITOR; RETINOL BINDING PROTEIN 4; UNCLASSIFIED DRUG; LIGAND; PIPERIDINE; PIPERIDINE DERIVATIVE; PLASMA RETINOL BINDING PROTEIN; PREALBUMIN; RBP4 PROTEIN, MOUSE;

AEROBIC METABOLISM; AGE RELATED MACULAR DEGENERATION; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONFORMATION; DRUG DESIGN; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG SOLUBILITY; DRUG SYNTHESIS; ELIMINATION HALF-LIFE; HYDROGEN BOND; HYDROPHOBICITY; IC50; IN VITRO STUDY; MAXIMUM PLASMA CONCENTRATION; MOLECULAR DOCKING; NONHUMAN; OXIDATION; RAT; STARGARDT DISEASE; STRUCTURE ACTIVITY RELATION; VOLUME OF DISTRIBUTION AT STEADY-STATE; X RAY CRYSTALLOGRAPHY; ANIMAL; ANTAGONISTS AND INHIBITORS; ATROPHY; CHEMISTRY; MACULAR DEGENERATION; MALE; METABOLISM; MOUSE; PATHOLOGY; PROTEIN CONFORMATION; SYNTHESIS;

ANIMALS; ATROPHY; CHEMISTRY TECHNIQUES, SYNTHETIC; DRUG DESIGN; LIGANDS; MACULAR DEGENERATION; MALE; MICE; MOLECULAR DOCKING SIMULATION; PIPERIDINES; PREALBUMIN; PROTEIN CONFORMATION; RATS; RETINOL-BINDING PROTEINS, PLASMA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84907465312     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5010013     Document Type: Article

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