193550-99-1

Upstream product

• 619-84-1 p-N,N-dimethylaminobenzoic acid 
• 1926-80-3 methyl 6-aminocaproate hydrochloride 
• 251304-83-3 methyl 6-{[4-(dimethylamino)benzoyl]amino}hexanoate 

Downstream Products

• 251304-84-4 6-N-(4-dimethylaminophenylcarbamoyl)hexanoic acid N'-benzoyloxyamide 

Relevant academic research and scientific papers

Analogues of trichostatin A and trapoxin B as histone deacetylase inhibitors

Inhibitors of histone deacetylase are potent inducers of differentiation and bear considerable potential as drugs for chemoprevention and treatment of cancer. So far only complex natural products and a few synthetic congeners have been identified as specific inhibitors. We have prepared a set of simple analogues in as little as four synthetic steps that have inhibitory potencies in the range of known cyclotetrapeptide inhibitors. These compounds are interesting leads for the design of potent inhibitors of histone deacetylase.

Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR

Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (nM) range against enzyme activity in HeLa cell extracts and sub-μM for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained).

Carbamic acid compounds comprising an amide linkage as hdac inhibitors

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.

Inhibitors of human histone deacetylase: Synthesis and enzyme and cellular activity of straight chain hydroxamates

Inhibitors of histone deacetylase (HDAC) have been shown to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo. We have prepared analogues of suberoylanilide hydroxamic acid (SAHA) and trichostatin A and have evaluated them in a human HDAC enzyme inhibition assay, a p21waf1 (p21) promoter assay, and in monolayer growth inhibition assays. One compound, 4-(dimethylamino)-N-[7-(hydroxyamino)-7-oxoheptyl]-benzamide, was found to affect the growth of a panel of eight human tumor cell lines differentially.

Inhibitors of histone deacetylase suppress the growth of MCF-7 breast cancer cells

Inhibitors of histone deacetylase are attracting increasing interest due to their influence on transcription, differentiation, and apoptosis. We have investigated two synthetic inhibitors 3 and 4 of histone deacetylase and the natural product inhibitor tr

Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation

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.