Structure-guided discovery of 1,3,5 tri-substituted benzenes as potent and selective matriptase inhibitors exhibiting in vivo antitumor efficacy

Bioorganic and Medicinal Chemistry

Volumn 22, Issue 12, 2014, Pages 3187-3203

  Goswami, Rajeev ^a   Mukherjee, Subhendu ^a   Ghadiyaram, Chakshusmathi ^a   Wohlfahrt, Gerd ^b   Sistla, Ramesh K ^a   Nagaraj, Jwala ^a   Satyam, Leena K ^a   Subbarao, Krishnaprasad ^a   Palakurthy, Rajendra K ^a   Gopinath, Sreevalsam ^a   Krishnamurthy, Narasimha R ^a   Ikonen, Tarja ^b   Moilanen, Anu ^b   Subramanya, Hosahalli S ^a   Kallio, Pekka ^b   Ramachandra, Murali ^a  

^a Aurigene Discovery Technologies Limited   (India)

^b ORION CORPORATION   (Finland)

Author keywords

Amidine; Cancer; Crystallography; In vivo activity; Matriptase; Molecular docking

Indexed keywords

1 (2 AMINOETHYL) N [3,5 BIS(4 CARBAMIMIDOYLPHENOXY)PHENYL]PIPERIDINE 4 CARBOXAMIDE; 1 (3 AMINOPROPANOYL) N [3,5 BIS(4 CARBAMIMIDOYLPHENOXY)PHENYL]PIPERIDINE 4 CARBOXAMIDE; 1 [3,5 BIS(4 CARBAMIMIDOYLPHENOXY)BENZOYL]PIPERIDINE 4 CARBOXYLIC ACID; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY) N (4 FLUOROPHENYL)BENZAMIDE; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY) N (4 HYDROXYCYCLOHEXYL)BENZAMIDE; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY) N (4 METHYLCYCLOHEXYL)BENZAMIDE; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY) N (CYCLOHEXYLMETHYL)BENZAMIDE; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY) N CYCLOHEXYLBENZAMIDE; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY) N [(4 HYDROXYCYCLOHEXYL)METHYL]BENZAMIDE; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY) N [1 (2 HYDROXYETHYL)PIPERIDIN4 YL]BENZAMIDE; 3,5 BIS(4 CARBAMIMIDOYLPHENOXY)BENZAMIDE; 4 AMINO N (3,5 BIS(4 CARBAMIMIDOYLPHENOXY)PHENYL)CYCLOHEXANECARBOXAMIDE; 4 AMINOCYCLOHEXYL 3,5 BIS(4 CARBAMIMIDOYLPHENOXY)BENZOATE; 4,4' [[5 (1,2,3,4 TETRAHYDROISOQUINOLINE 2 CARBONYL) 1,3 PHENYLENE]BIS(OXY)]DIBENZAMIDE; 4,4' [[5 (4 FLUOROPHENYLSULFONAMIDO) 1,3 PHENYLENE]BIS(OXY)]DIBENZAMIDE; 4,4' [[5 (DECAHYDROQUINOLINE 1 CARBONYL) 1,3 PHENYLENE]BIS(OXY)]DIBENZAMIDE; 4,4' [[5 [4 (2 AMINOETHYL)PIPERIDINE 1 CARBONYL] 1,3 PHENYLENE]BIS(OXY)]DIBENZAMIDE; 5 PHENYLENE 1,3 BIS(OXY)DIBENZIMIDAMIDE DERIVATIVE; ANTINEOPLASTIC AGENT; ETHYL 4 [3,5 BIS(4 CARBAMIMIDOYLPHENOXY)BENZAMIDO]PIPERIDINE 1 CARBOXYLATE; HYDROXYL GROUP; MATRIPTASE; METHYL GROUP; N (4 AMINOCYCLOHEXYL) 3,5 BIS(4 CARBAMIMIDOYLPHENOXY)BENZAMIDE; N [1 (3 AMINOPROPYL)PIPERIDIN 4 YL] 3,5 BIS(4 CARBAMIMIDOYLPHENOXY)BENZAMIDE; N [3,5 BIS(4 CARBAMIMIDOYLPHENOXY)PHENYL] 1 (2 HYDROXYETHYL)PIPERIDINE 4 CARBOXAMIDE; N [3,5 BIS(4 CARBAMIMIDOYLPHENOXY)PHENYL] 4 METHYLCYCLOHEXANECARBOXAMIDE; NITRILE; SERINE PROTEINASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; (1R,4R)-4-AMINO-N-(3,5-BIS(4-CARBAMIMIDOYLPHENOXY)PHENYL)CYCLOHEXANECARBOXAMIDE; BENZAMIDE DERIVATIVE; BENZENE; CYCLOHEXANE DERIVATIVE; N-(4-AMINOCYCLOHEXYL)-3,5-BIS(4-CARBAMIMIDOYLPHENOXY)BENZAMIDE; SERINE PROTEINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; CANCER CELL LINE; CANCER INHIBITION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BLOOD LEVEL; DRUG CONFORMATION; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG SOLUBILITY; DRUG STABILITY; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME INHIBITION; HYDROGEN BOND; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MOLECULAR DOCKING; MOLECULAR INTERACTION; MOUSE; NONHUMAN; PROSTATE CANCER; SALT BRIDGE INTERACTION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; TIME TO MAXIMUM PLASMA CONCENTRATION; TUMOR XENOGRAFT; X RAY CRYSTALLOGRAPHY; AMINO ACID SEQUENCE; ANIMAL; BINDING SITE; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DEVELOPMENT; DRUG EFFECTS; HUMAN; MOLECULAR GENETICS; PATHOLOGY; PROSTATIC NEOPLASMS; SCID MOUSE; SEQUENCE HOMOLOGY; SYNTHESIS;

AMINO ACID SEQUENCE; ANIMALS; ANTINEOPLASTIC AGENTS; BENZAMIDES; BENZENE; BINDING SITES; CELL PROLIFERATION; CRYSTALLOGRAPHY, X-RAY; CYCLOHEXANES; DRUG DISCOVERY; HUMANS; MALE; MICE; MICE, SCID; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROSTATIC NEOPLASMS; SEQUENCE HOMOLOGY, AMINO ACID; SERINE ENDOPEPTIDASES; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84901234338     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2014.04.013     Document Type: Article

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