7661-21-4

Upstream product

• 22809-37-6 6-bromohexanoyl chloride 
• 62-53-3 aniline 
• 4224-70-8 6-bromohexanoic acid 
• 606092-23-3 5-hydroxy-N-phenylpentanamide 
• 502-44-3 hexahydro-2H-oxepin-2-one 

Downstream Products

• 606092-26-6 methyl-(5-phenylcarbamoyl-pentyl)-phosphinic acid ethyl ester 
• 329966-76-9 Thioacetic Acid S-(5-Phenylcarbamoyl-pentyl)ester 
• 63330-01-8 6-phthalimido-hexanoic acid anilide 
• 1225038-91-4 bis(5-phenylcarbamoylpentyl) diselenide 
• 1225038-92-5 5-phenylcarbamoylpentyl selenocyanate 

Relevant academic research and scientific papers

Boronic Acid: A Bio-Inspired Strategy to Increase the Sensitivity and Selectivity of Fluorescent NADH Probe

Fluorescent probes have emerged as an essential tool in the molecular recognition events in biological systems; however, due to the complex structures of certain biomolecules, it remains a challenge to design small-molecule fluorescent probes with high sensitivity and selectivity. Inspired by the enzyme-catalyzed reaction between biomolecule and probe, we present a novel combination-reaction two-step sensing strategy to improve sensitivity and selectivity. Based on this strategy, we successfully prepared a turn-on fluorescent reduced nicotinamide adenine dinucleotide (NADH) probe, in which boronic acid was introduced to bind with NADH and subsequently accelerate the sensing process. This probe shows remarkably improved sensitivity (detection limit: 0.084 μM) and selectivity to NADH in the absence of any enzymes. In order to improve the practicality, the boronic acid was further modified to change the measurement conditions from alkalescent (pH 9.5) to physiological environment (pH 7.4). Utilizing these probes, we not only accurately quantified the NADH weight in a health care product but also evaluated intracellular NADH levels in live cell imaging. Thus, these bio-inspired fluorescent probes offer excellent tools for elucidating the roles of NADH in biological systems as well as a practical strategy to develop future sensitive and selective probes for complicated biomolecules.

Nucleophilic substitution reactions of unbranched alkyl amines using triazine reagents

Since amines are present in many organic, biological, and drug molecules, a strategy of synthesizing desired compounds by nucleophilic substitution reactions of these amines is very attractive. By using triazine reagents, we have found that nucleophilic substitution reactions of unbranched alkyl amines via morpholine derivatives are feasible. This method can be performed under milder reaction conditions than those in previously reported methods.

A selenium-containing selective histone deacetylase 6 inhibitor for targeted: In vivo breast tumor imaging and therapy

Early detection and effective treatment are essential for the management of breast cancer, especially for triple-negative breast cancer (TNBC). However, current imaging methods and treatment strategies are ineffective because of the lack of efficient biomarkers and molecular targets. Thus, identifying novel biomarkers and their corresponding ligands is critical for controlling breast cancer. Histone deacetylase 6 (HDAC6) has emerged as a valid target for cancer therapy owing to its selective tumor inhibition and fewer side effects compared to pan-HDAC- and HDAC1-3 isoform-selective inhibitors. Here, a HDAC6-selective inhibitor, SelSA, was developed by utilizing a selenocyanide moiety instead of the conventional hydroxamic acid core, which showed 112-fold and 128-fold selective binding affinity for HDAC6 relative to HDAC1 and HDAC8. In vitro studies demonstrated that FITC-SelSA was specifically uptaken by both ERα(+) MCF-7 and TNBC MDA-MB-231 cells, with primarily cytoplasmic localization. SelSA reactivated ERα expression and sensitized TNBC cell responses to the antagonist tamoxifen, and displayed potent antitumor effects against both MCF-7 and MDA-MB-231 cells in vitro and tumor xenografts in vivo with no obvious side effects. Moreover, in in vivo near-infrared fluorescence imaging to assess SelSA biodistribution, the IRDye800CW-SelSA probe exhibited specific tumor targeting ability with high tumor-to-normal tissue contrast. The in vivo tumor treatment study revealed that SelSA possessed improved treatment efficacy and fewer side effects in both ERα(+) and TNBC tumors, compared to pan-HDAC inhibitors. Overall, our study indicated that the HDAC6 inhibitor SelSA is a highly promising candidate for targeted breast cancer imaging and therapy with clinical translational potential.

Metal-Free Synthesis of N-Aryl Amides using Organocatalytic Ring-Opening Aminolysis of Lactones

Catalytic ring-opening of bio-sourced non-strained lactones with aromatic amines can offer a straightforward, 100 % atom-economical, and sustainable pathway towards relevant N-aryl amide scaffolds. Herein, the first general, metal-free, and highly efficient N-aryl amide formation is reported from poorly reactive aromatic amines and non-strained lactones under mild operating conditions using an organic bicyclic guanidine catalyst. This protocol has high application potential as exemplified by the formal syntheses of drug-relevant molecules.

Anti-tumor drug comprising histone deacetylase inhibitors (HDACs) derivative

The invention discloses an anti-tumor drug comprising an HDACs derivative. The anti-tumor drug comprises effective quantity of HDACs derivative, a medical carrier and an excipient, and the excipient comprises one or more of PBS, normal saline and butyl-beta-cyclodextrin; the HDACs derivative is 5-benzoyl aminopentyl selenocyanate (TC1). The test shows the novel compound TC1 is a very effective antitumor drug and has the functions of resisting growth of various human tumor cell lines and inducing tumor cell apoptosis; compared the TC1 with the SAHA, the anti-tumor effect is good, the tolerance is good, the therapeutic dose is low, and the side effects produced in the therapeutic process can be reduced. The TC1 can be taken as a pro-grug of the anti-tumor drug, preferably taken as a pro-drug of an anti-solid-tumor drug; the TC1 has a great potential to be developed into a novel broad spectrum anti-tumor drug which has a great development prospect.

COMPOUNDS AND METHODS

The present invention relates to compounds that inhibit histone deacetylase (HDAC) enzymes, the preparation of these compounds or salts of said compound, the use of these compounds in the treatment of neurodegenerative diseases or conditions ameliorated by inhibition of HDAC activity and pharmaceutical compositions that are comprised of these compounds.

SelSA, selenium analogs of SAHA as potent histone deacetylase inhibitors

Cancer treatment and therapy has moved from conventional chemotherapeutics to more mechanism-based targeted approach. Disturbances in the balance of histone acetyltransferase (HAT) and deacetylase (HDAC) leads to a change in cell morphology, cell cycle, differentiation, and carcinogenesis. In particular, HDAC plays an important role in carcinogenesis and therefore it has been a target for cancer therapy. Structurally diverse group of HDAC inhibitors are known. The broadest class of HDAC inhibitor belongs to hydroxamic acid derivatives that have been shown to inhibit both class I and II HDACs. Suberoylanilide hydroxamic acid (SAHA) and Trichostatin A (TSA), which chelate the zinc ions, fall into this group. In particular, SAHA, second generation HDAC inhibitor, is in several cancer clinical trials including solid tumors and hematological malignancy, advanced refractory leukemia, metastatic head and neck cancers, and advanced cancers. To our knowledge, selenium-containing HDAC inhibitors are not reported in the literature. In order to find novel HDAC inhibitors, two selenium based-compounds modeled after SAHA were synthesized. We have compared two selenium-containing compounds; namely, SelSA-1 and SelSA-2 for their inhibitory HDAC activities against SAHA. Both, SelSA-1 and SelSA-2 were potent HDAC inhibitors; SelSA-2 having IC50 values of 8.9 nM whereas SAHA showed HDAC IC50 values of 196 nM. These results provided novel selenium-containing potent HDAC inhibitors.

Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors

Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which the mercaptoacetamide group was replaced by (mercaptomethyl)fluoroalkene, and their HDAC inhibitory activity was evaluated. Subnanomolar inhibition was observed for all synthetic compounds.

Mercaptoamides as histone deacetylase inhibitors

Mercaptoamide compounds, represented by Formulas (IA), (IB), (IIA), and (IIB): or a pharmaceutically acceptable salt thereof, inhibit histone deacetylase enzyme and are useful for the treatment and/or prevention of various infections, cancerous diseases, and conditions.

Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates

To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong activity, and its potency was comparable to that of SAHA. The cancer cell growth inhibitory activity was verified to be the result of histone hyperacetylation and subsequent induction of p21WAF1/CIP1 by Western blot analysis. Kinetical enzyme assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis within the cell interacts with the zinc ion in the active site of HDACs.