Structure-activity relationship and properties optimization of a series of Quinazoline-2,4-diones as inhibitors of the canonical Wnt pathway

European Journal of Medicinal Chemistry

Volumn 95, Issue , 2015, Pages 526-545

  Nencini, Arianna ^a   Pratelli, Carmela ^a   Quinn, Joanna M ^a,b   Salerno, Massimiliano ^a   Tunici, Patrizia ^a   De Robertis, Alessandra ^a   Valensin, Silvia ^a   Mennillo, Federica ^a   Rossi, Marco ^a   Bakker, Annette ^a,c   Benicchi, Tiziana ^a,d   Cappelli, Federico ^a   Turlizzi, Elisa ^a   Nibbio, Martina ^a,e   Caradonna, Nicola P ^a   Zanelli, Ugo ^a,f   Andreini, Matteo ^a   Magnani, Matteo ^a   Varrone, Maurizio ^a,g  

^a Siena Biotech SpA   (Italy)

^b Aptuit Inc   (United States)

^c Children's Tumor Foundation   (United States)

^d TES Pharma Srl   (Italy)

^e NOVARTIS VACCINES AND DIAGNOSTICS   (Italy)

^f MERCK KGAA   (Germany)

^g GSK Neural Pathways DPU   (Singapore)

Author keywords

Glioblastoma; Small molecule; Structureeactivity relationship; Wnt pathway; catenin

Indexed keywords

1 METHYL 3 [4 (4 PHENYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 1 METHYL 3 [4 (4 PHENYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 3H QUINAZOLINE 4 ONE; 2 METHYL 3 [4 (4 PHENYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 3H QUINAZOLINE 4 ONE; 2 [4 (4 PHENYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL]ISOINDOLE 1,3 DIONE; 3 [4 (2,3,5,6 TETRAHYDRO [1,2' ]BIPYRAZINYL 4 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 ACETYL PIPERAZINE 1 CARBONYL) CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 ACETYL PIPERAZINE 1 CARBONYL) CYCLOHEXYLMETHYL]6 METHOXY 1 METHYL 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 ACETYL PIPERAZINE 1 CARBONYL)CYCLO HEXYLMETHYL] 6 METHOXY 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 BENZYL PIPERAZINE 1 CARBONYL) CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 CYCLOBUTANECARBONYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 CYCLOPROPANECARBONYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 CYCLOPROPYLMETHYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 ISOBUTYRYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 ISOBUTYRYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 6 METHOXY 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 ISOBUTYRYL PIPERAZINE 1 CARBONYL)CYCLOHEXYMETHYL] 5 METHOXY 1H QUINAZOLINE 2,4 DIONE; 3 [4 (4 PYRIMIDIN 2 YL PIPERAZINE 1 CARBONYL) CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 [4 (2 METHOXY ACETYL)PIPRAZINE 1 CARBONYL]CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 [4 (2 METHOXY PHENYL) PIPERAZINE 1 CARBONYL]CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 3 [4 [4 (ISOXAZOLE 5 CARBONYL)PIPERAZINE 1 CARBONYL]CYCLOHEXYLMETHYL]QUINAZOLINE 2,4 DIONE DIONE; 5 CHLORO 3 [4 (4 ISOBUTYRYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 5 FUORO 3 [4 (4 ISOBUTYRYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL] 1H QUINAZOLINE 2,4 DIONE; 6 METHOXY 3 [4 [4 (2 METHOXY ACETYL) PIPERAZINE 1 CARBONYL]CYCLOHEXYMETHYL] 1 METHYL 1H QUINAZOLINE 2,4 DIONE; 6 METHOXY 3 [4 [4 (2 METHOXY ACETYL) PIPERAZINE 1 CARBONYL]CYCLOHEXYMETHYL] 1H QUINAZOLINE 2,4 DIONE; 7 CHLORO 3 [4 (4 ISOBUTYRYL PIPERAZINE 1 CARBONYL)CYCLOHEXYLMETHYL]1H QUINAZOLINE 2,4 DIONE; 7,8 DIHYDRO 2 [4 (TRIFLUOROMETHYL)PHENYL] 5H THIOPYRANO[4,3 D]PYRIMIDIN 4 OL; ANTINEOPLASTIC AGENT; QUINAZOLINE DERIVATIVE; QUINAZOLINE2,4 DIONE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; WNT PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CHEMICAL ANALYSIS; CLINICAL ASSESSMENT; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG IDENTIFICATION; FEMALE; GLIOBLASTOMA; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; MEDICINAL CHEMISTRY; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; PROCESS OPTIMIZATION; SARCOMA; SINGLE DRUG DOSE; STOMACH CANCER; STRUCTURE ACTIVITY RELATION; WNT SIGNALING PATHWAY; ANIMAL; CELL PROLIFERATION; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; IC50; METABOLISM; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; FEMALE; HUMANS; INHIBITORY CONCENTRATION 50; MALE; MICE; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP; WNT SIGNALING PATHWAY; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84926377390     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2015.03.055     Document Type: Article

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