title: Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity.
abstract: A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.
authors.affiliation: Nerviano Medical Sciences-Oncology, via Pasteur 10, 20014 Nerviano, Milan, Italy. simona.bindi@nervianoms.com
authors.forename: Simona
authors.initials: S
authors.lastname: Bindi
authors.forename: Daniele
authors.initials: D
authors.lastname: Fancelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Alli
authors.forename: Daniela
authors.initials: D
authors.lastname: Berta
authors.forename: Jay A
authors.initials: JA
authors.lastname: Bertrand
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cameron
authors.forename: Paolo
authors.initials: P
authors.lastname: Cappella
authors.forename: Patrizia
authors.initials: P
authors.lastname: Carpinelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cervi
authors.forename: Valter
authors.initials: V
authors.lastname: Croci
authors.forename: Matteo
authors.initials: M
authors.lastname: D'Anello
authors.forename: Barbara
authors.initials: B
authors.lastname: Forte
authors.forename: M Laura
authors.initials: ML
authors.lastname: Giorgini
authors.forename: Aurelio
authors.initials: A
authors.lastname: Marsiglio
authors.forename: Juergen
authors.initials: J
authors.lastname: Moll
authors.forename: Enrico
authors.initials: E
authors.lastname: Pesenti
authors.forename: Valeria
authors.initials: V
authors.lastname: Pittalà
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pulici
authors.forename: Federico
authors.initials: F
authors.lastname: Riccardi-Sirtori
authors.forename: Fulvia
authors.initials: F
authors.lastname: Roletto
authors.forename: Chiara
authors.initials: C
authors.lastname: Soncini
authors.forename: Paola
authors.initials: P
authors.lastname: Storici
authors.forename: Mario
authors.initials: M
authors.lastname: Varasi
authors.forename: Daniele
authors.initials: D
authors.lastname: Volpi
authors.forename: Paola
authors.initials: P
authors.lastname: Zugnoni
authors.forename: Paola
authors.initials: P
authors.lastname: Vianello
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D064127:Aurora Kinases; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: C554997:3-(4-morpholin-4-yl-benzoylamino)-1H-thieno(3,2-c)pyrazole-5-carboxylic acid ((S)-1-phenyl-2-pyrrolidin-1-yl-ethyl)-amide; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D013876:Thiophenes; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases