Discovery of novel, highly potent, and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without a zinc binding group using a structure-based design approach

Journal of Medicinal Chemistry

Volumn 57, Issue 21, 2014, Pages 8886-8902

  Nara, Hiroshi ^a   Sato, Kenjiro ^a   Naito, Takako ^a   Mototani, Hideyuki ^a   Oki, Hideyuki ^a   Yamamoto, Yoshio ^a   Kuno, Haruhiko ^a   Santou, Takashi ^a   Kanzaki, Naoyuki ^a   Terauchi, Jun ^a   Uchikawa, Osamu ^a   Kori, Masakuni ^a  

^a TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 [[6 FLUORO 2 [[[[3 (METHYLOXY)PHENYL]METHYL]AMINO]CARBONYL] 4 OXO 3,4 DIHYDROQUINAZOLIN 5 YL]OXY]ETHYL]BENZOIC ACID; 4 [[[4 (4 CHLOROPHENOXY)PHENYL]SULFONYL]METHYL]TETRAHYDRO 2H PYRAN 4 CARBOHYDROXAMIC ACID; 5 (METHYLOXY) N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 5 FLUORO N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 5 METHYL N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 5 [(2 CYCLOHEXYLETHYL)OXY] N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 5 [[2 (4 AMINOPHENYL)ETHYL]OXY] 6 FLUORO N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 6 (ETHYLOXY) N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 6 (METHYLOXY) N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 6 CYANO N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 6 FLUORO 5 [[2 (4 FLUOROPHENYL)ETHYL]OXY] N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 IDHYDROQUINAZOLINE 2 CARBOXAMIDE; 6 FLUORO N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 6 FLUORO N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 5 [(2 PHENYLETHYL)OXY] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 6 METHYL N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 7 (METHYLOXY) N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; 8 (METHYLOXY) N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; MATRIX METALLOPROTEINASE INHIBITOR; N [[3 (METHYLOXY) PHENYL]METHYL] 4 OXO 5 [(PHENYLMETHYL)OXY] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 5 [(2 PHENYLETHYL)THIO] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 5 [(3 PHENYLPROPYL)OXY] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 5 [[2 [(PHENYLMETHYL)OXY]ETHYL]OXY] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 6 (TRIFLUOROMETHYL) 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 6 PHENYL 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 6 [(PHENYLMETHYL)OXY] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 4 OXO 6 [(TRIFLUOROMETHYL)OXY] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 6 (METHYLSULFONYL) 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL] 6 (METHYLTHIO) 4 OXO 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; N [[3 (METHYLOXY)PHENYL]METHYL]4 OXO 5 [(2 PHENYLETHYL)OXY] 3,4 DIHYDROQUINAZOLINE 2 CARBOXAMIDE; SODIUM 4 [2 [[6 FLUORO 2 [[[[3 (METHYLOXY)PHENYL]METHYL]AMINO]CARBONYL] 4 OXO 3,4 DIHYDROQUINAZOLIN 5 YL]OXY]ETHYL]BENZOATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; 4-(2-((6-FLUORO-2-((((3-(METHYLOXY)PHENYL)METHYL)AMINO)CARBONYL)-4-OXO-3,4-DIHYDROQUINAZOLIN-5-YL)OXY)ETHYL)BENZOIC ACID; BENZOIC ACID DERIVATIVE; COLLAGENASE 3; QUINAZOLINE DERIVATIVE;

ACIDITY; ACYLATION; AEROBIC METABOLISM; ALKYLATION; AMINOLYSIS; ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; ARTICULAR CARTILAGE; BROMINATION; COLLAGEN DEGRADATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; CYCLIZATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DESIGN; DRUG HYDROLYSIS; DRUG POTENCY; DRUG SAFETY; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; ELIMINATION HALF-LIFE; ENZYME INHIBITION; EXPERIMENTAL DOG; EXPERIMENTAL GUINEA PIG; EXPERIMENTAL MONKEY; EXPERIMENTAL RABBIT; FEMALE; HIGH THROUGHPUT SCREENING; HUMAN; HUMIDITY; HYDROGEN BOND; HYDROGENATION; IC50; IN VITRO STUDY; IN VIVO STUDY; JOINT CAVITY; LITHIATION; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; NUCLEOPHILICITY; OSTEOARTHRITIS; PROTEIN CLEAVAGE; RAT; REPEATED DRUG DOSE; SINGLE DRUG DOSE; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; TIME TO MAXIMUM PLASMA CONCENTRATION; VOLUME OF DISTRIBUTION; WETTABILITY; X RAY CRYSTALLOGRAPHY; ANIMAL; BINDING SITE; DRUG EFFECTS; SYNTHESIS;

ANIMALS; BENZOATES; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; HUMANS; INHIBITORY CONCENTRATION 50; MATRIX METALLOPROTEINASE 13; MATRIX METALLOPROTEINASE INHIBITORS; OSTEOARTHRITIS; QUINAZOLINES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84923244141     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500981k     Document Type: Article

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