Benzofused hydroxamic acids: useful fragments for the preparation of histone deacetylase inhibitors. Part 2: 7-fluorobenzothiophenes and benzofurans.
In the search for a new class of histone deacetylase inhibitors, we prepared a series of very simple benzofused hydroxamic acids to find an anchoring fragment of minimal molecular weight: they showed very good ligand efficiencies. Following these findings, classical fragment growing work was performed to increase binding energy and selective cytotoxicity. In the second phase of the work, information from the SARs of the benzothiophene series and data available in literature, we explored the in vitro pharmacological properties of the 6-substituted-7-fluoro-benzothiophene hydroxamates and the 5-susbtituted-benzofuran hydroxamates.
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Elena
E
Marastoni
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Sandra
S
Bartoli
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Marco
M
Berettoni
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Amalia
A
Cipollone
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Alessandro
A
Ettorre
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Christopher I
CI
Fincham
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Sandro
S
Mauro
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Marielle
M
Paris
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Marina
M
Porcelloni
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Mario
M
Bigioni
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Monica
M
Binaschi
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Federica
F
Nardelli
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy.
Massimo
M
Parlani
Menarini Ricerche, Via Rismondo12A, 50131 Florence, Italy.
Carlo A
CA
Maggi
Dip. di Ingegneria Industriale, Università degli Studi di Firenze, Via Santa Marta 3, 50139 Florence, Italy.
Paola
P
Paoli
Dip. di Ingegneria Industriale, Università degli Studi di Firenze, Via Santa Marta 3, 50139 Florence, Italy.
Patrizia
P
Rossi
Menarini Ricerche, Via Tito Speri 10, 00040 Pomezia (Rome), Italy. Electronic address: dfattori@menarini-ricerche.it.
Daniela
D
Fattori
D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D001572:Benzofurans; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013876:Thiophenes; D006655:Histone Deacetylases
Fragment approach; HDAC; Hydroxamic acids