412270-29-2Relevant academic research and scientific papers
Novel sulfonamide derivatives as inhibitors of histone deacetylase
Finn, Paul W.,Bandara, Morwena,Butcher, Chris,Finn, Angela,Hollinshead, Ruth,Khan, Nagma,Law, Norman,Murthy, Sreenivasa,Romero, Rosario,Watkins, Clare,Andrianov, Victor,Bokaldere, Rasma M.,Dikovska, Klara,Gailite, Vija,Loza, Einars,Piskunova, Irina,Starchenkov, Igor,Vorona, Maxim,Kalvinsh, Ivars
, p. 1630 - 1657 (2007/10/03)
Inhibition of the enzyme histone deacetylase (HDAC) is emerging as a novel approach to the treatment of cancer. A series of novel sulfonamide derivatives were synthesized and evaluated for their ability to inhibit human HDAC. Compounds were identified which are potent enzyme inhibitors, with IC 50 values in the low nanomolar range against enzyme obtained from HeLa cell extracts, and with antiproliferative effects in cell culture. Extensive characterization of the structure - activity relationships of this series identified key requirements for activity. These include the direction of the sulfonamide bond and substitution patterns on the central phenyl ring. The alkyl spacer between the aromatic head group and the sulfonamide functionality also influenced the HDAC inhibitory activity. One of these compounds, m11.1, also designated PXD101, has entered clinical trials for solid tumors and haematological malignancies.
Carbamic acid compounds comprising a sulfonamide linkage as hdac inhibitors
-
, (2008/06/13)
This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S (═O)2NR1— and —NR1S(═O)2—; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is —S(═O)2NR1—, then Q1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.
