- CARBAMIC ACID COMPOUNDS COMPRISING A BICYCLIC HETEROARYL GROUP AS HDAC INHIBITORS
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This invention pertains to certain carbamic acid compounds of the following formula, which inhibit HDAC (histone deacetylase) activity wherein: A is independently an unsubstituted or substituted bicyclic C9-10heteroaryl group (e.g., quinolinyl; quinoxalinyl; benzoxazolyl; benzothiazolyl); Q is an acid leader group, and is independently an unsubstituted or substituted, saturated or unsaturated C1 7alkylene group having a backbone length of 4 or less; with the proviso that if A is unsubstituted benzothiazol-2-yl, then Q is an unsaturated group; and with the proviso that if A is unsubstituted quinolin-6-yl, then Q is unsubstituted at the α-position; and with the proviso that A is not benzimidazol-2-yl; 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 invitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.
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- Non-thiol farnesyltransferase inhibitors: utilization of an aryl binding site by 5-arylacryloylaminobenzophenones.
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We recently described a novel aryl binding site of farnesyltransferase. The 2-naphthylacryloyl residue was developed as an appropriate substituent for our benzophenone-based AAX-peptidomimetic capable of occupying this binding site, resulting in a non-thiol farnesyltransferase inhibitor with nanomolar activity. The activity of this inhibitor is readily explained on the basis of docking studies which show the 2-naphthyl residue fitting into the aryl binding site.
- Mitsch, Andreas,Boehm, Markus,Wissner, Pia,Sattler, Isabel,Schlitzer, Martin
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p. 2657 - 2662
(2007/10/03)
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