- Carbamic acid compounds comprising an amide linkage as hdac inhibitors
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This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(═O)—and —C(═O)NR1—; R1 is an amido substituent; and, Q2 is an acid 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.
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- Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation
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Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. We have described previously analogues of the complex natural HD inhibitors trapoxin B and trichostatin A with activities in the submicromolar range. Here we report structure-activity relationship analyses of further analogues of trichostatin A with respect to in vitro inhibition of maize HD-2 and their ability to induce terminal cell differentiation in Friend leukemic cells. This is the first report that shows the correlation between HD inhibitory activity and action on cancer cells on a larger series of similar compounds. Only the compounds that inhibit HD induce differentiation and/or exert antiproliferative activities in cell culture. Our studies support the use of in vitro systems as screening tools and provide structure-activity relationships that merit further investigation of this interesting target.
- Jung, Manfred,Brosch, Gerald,K?lle, Doris,Scherf, Hans,Gerh?user, Clarissa,Loidl, Peter
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p. 4669 - 4679
(2007/10/03)
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- Composition containing a penem or carbapenem antibiotic and the use of the same
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Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially.
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- SYNTHESIS OF ALIPHATIC AMINES RELATED TO MONODANSYLCADAVERINE VIA THE OXIDATIVE REARRANGEMENT OF ALIPHATIC AMIDES WITH PHENYL IODOSYL BIS(TRIFLUOROACETATE)
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A series of aliphatic primary amides have been oxidatively rearranged to primary amines with phenyl iodosyl(trifluoroacetate).Sulfonamide groups on the substrates have not been affected.
- Pavlidis, V. H.,Chan, E. D.,Pennington, L.,McParland, M.,Whitehead, M.
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p. 1615 - 1624
(2007/10/02)
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- Composition containing a penem or carbapenem antibiotic
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Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially. The composition may be prepared by simple mixing.
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