title: Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides.
abstract: A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1 microM (0.0153 microM in SR leukemia) causing a block in G0-G1 phase of cell cycle. Analysis of pRb expression showed that these two compounds increased the ratio between underphosphorylated pRb and total pRb. The X-ray structure of 10w, confirmed the 3-amino-N-phenyl-1H-indazole-1-carboxamide structure of compounds 10.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi, 32, 90123 Palermo, Italy. demraffa@unipa.it
authors.forename: Demetrio
authors.initials: D
authors.lastname: Raffa
authors.forename: Benedetta
authors.initials: B
authors.lastname: Maggio
authors.forename: Stella
authors.initials: S
authors.lastname: Cascioferro
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Raimondi
authors.forename: Domenico
authors.initials: D
authors.lastname: Schillaci
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gallo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daidone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Plescia
authors.forename: Fiorella
authors.initials: F
authors.lastname: Meneghetti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Bombieri
authors.forename: Antonietta
authors.initials: A
authors.lastname: Di Cristina
authors.forename: Rosaria M
authors.initials: RM
authors.lastname: Pipitone
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D016160:Retinoblastoma Protein / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D007191:Indazoles; D016160:Retinoblastoma Protein