162853-41-0

Usage

Uses

Used in Perfumery and Flavoring Industry:
METHYL 7-PHENYLCARBAMOYLHEPTANATE is used as a fragrance ingredient for its sweet, floral scent, enhancing the aroma of products such as air fresheners, soaps, and cosmetics.
Used in Food and Beverage Industry:
In the food and beverage sector, METHYL 7-PHENYLCARBAMOYLHEPTANATE is utilized as a flavoring agent to impart a pleasant taste and aroma to a variety of consumable products.
Used in Pharmaceutical Research:
METHYL 7-PHENYLCARBAMOYLHEPTANATE is also being explored for its potential in treating inflammatory and neurodegenerative diseases due to its anti-inflammatory and antioxidant properties. However, further research is needed to evaluate its safety and potential side effects in these applications.

Upstream product

• 67-56-1 methanol 
• 149648-52-2 suberanilic acid 
• 41624-92-4 methyl 8-chloro-8-oxooctanoate 
• 62-53-3 aniline 
• 3946-32-5 suberic acid monomethyl ester 
• 5454-83-1 5-bromovaleric acid methyl ester 
• 2210-24-4 N-acryloylaniline 
• 10521-06-9 oxonane-2,9-dione 
• 505-48-6 octane-1,8-dioic acid 

Downstream Products

• 149647-78-9 vorinostat 
• 149648-52-2 suberanilic acid 
• 852619-59-1 octanedioic acid phenylamide (2-tritylsulfanyl-ethyl)-amide 
• 1017261-04-9 7-(1H-indol-2-yl)-N-phenylheptanamide 
• 1227736-21-1 suberoylanilide hydroxamic acid potassium salt 

Relevant academic research and scientific papers

An Endogenous Reactive Oxygen Species (ROS)-Activated Histone Deacetylase Inhibitor Prodrug for Cancer Chemotherapy

Suberoylanilide hydroxamic acid (SAHA, vorinostat) is a potent small-molecule pan-inhibitor of histone deacetylases (HDACs) approved for treatment of cutaneous T-cell lymphoma (CTCL). However, SAHA exhibits poor selectivity for cancer cells over noncancer cells. With an aim to improving its selectivity for cancer cells, we generated a novel SAHA prodrug (SAHA-OBP) that is activated in the presence of hydrogen peroxide, a reactive oxygen species (ROS) known to be overexpressed in cancer cells. The high endogenous ROS content in cancer cells triggers rapid removal of the 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl carbonyl (OBP) cap to release active SAHA. The SAHA-OBP prodrug demonstrates selective activity against multiple cancer cell lines such as HeLa, MCF-7, MDA-MB-231, and B16-F10, while remaining benign toward noncancer cells. The downstream effects of SAHA released from SAHA-OBP in cancer cells is the induction of apoptosis. SAHA-OBP was also found to be effective on multicellular tumor spheroids (MCTS). The SAHA prodrug designed in this study undergoes rapid ROS-dependent activation and imparts much-needed selectivity to SAHA for cancer cells.

Silyl-mediated photoredox-catalyzed Giese reaction: Addition of non-activated alkyl bromides

The emergence of photoredox catalysis has enabled the discovery of mild and efficient conditions for the generation of a variety of radical reaction platforms. Herein is disclosed the development of a conjugate addition reaction of non-activated alkyl bromides to Michael acceptors under visible-light photoredox catalysis. Optimization of the reaction was achieved using high-throughput experimentation (HTE) tools to enable the identification of mild, general and practical reaction conditions. A diverse set of alkyl bromides was successfully added to cyclic or acyclic α,β-unsaturated esters and amides. The features of this transformation allowed also access to a key intermediate of Vorinostat, an HDAC inhibitor used to fight cancer and HIV.

H2O2/Peroxynitrite-Activated Hydroxamic Acid HDAC Inhibitor Prodrugs Show Antileukemic Activities against AML Cells

Occurrence of acute myeloid leukemia (AML) results in abundant endogenous reactive oxygen species (ROS)/reactive nitrogen species (RNS) in AML cells and in disease-relevant microenvironments. Histone deacetylase inhibitor (HDACi) prodrug approach was designed accordingly by masking the hydroxamic acid zinc binding group with hydrogen peroxide (H2O2)/peroxynitrite (PNT)-sensitive, self-immolative aryl boronic acid moiety. Model prodrugs 5-82 and 5-23 were activated in AML cells to release cytotoxic HDACis, evidenced by inducing acetylation markers and reducing viability of AML cells. Intracellular activation and antileukemic activities of prodrug were increased or decreased by ROS/PNT inducers and scavengers, respectively. Prodrugs 5-82 and 5-23 also enhanced the potency of chemotherapy drug cytarabine, supporting the potentials of this prodrug class in combinatorial treatment.

Pendant HDAC inhibitor SAHA derivatised polymer as a novel prodrug micellar carrier for anticancer drugs

Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACi) approved by FDA for the treatment of cutaneous T cell lymphoma, is a promising anticancer drug for various cancers with a unique mode of action. However, it demonstrates limited clinical benefits in solid tumours as a single drug. In order to achieve enhanced and synergistic co-delivery of SAHA and doxorubicin (DOX), a cleavable SAHA-based prodrug polymer (POEG-b-PSAHA), consisting of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) blocks and hydrophobic SAHA segments, has been developed. POEG-b-PSAHA prodrug polymer was able to form spherical micelles with a diameter around 60 nm and well retained the pharmacological activity of SAHA in either inhibiting the proliferation of tumour cells or inducing histone acetylation. DOX formulated in POEG-b-PSAHA-based micelles showed a sustained release profile. DOX-loaded POEG-b-PSAHA exhibited more potent cytotoxicity towards tumour cells than free DOX and DOX loaded in a pharmacologically ‘inert’ nanocarrier, POEG-b-POM. Consistently, DOX/POEG-b-PSAHA formulation resulted in an improved therapeutic effect in vivo compared to free DOX, Doxil or DOX formulated in POEG-b-POM micelles. These results suggest that SAHA-based prodrug micelles may serve as a dual functional carrier for combination strategies in epigenetic-oriented anticancer therapy.

Method for preparing anticarcinogen vorinostat

The invention discloses a method for preparing anticarcinogen vorinostat. The method includes: (1) subjecting suberic anhydride and aniline to contact reaction in water and 1,4-dioxane at the temperature of 5-10 DEG C in the presence of CuI, performing filtering after reaction is finished, regulating the pH of filtrate to 5-6, performing suction filtration, washing filter cake obtained after suction filtration, and drying to obtain 7-phenylcarbamoylheptanoic acid; (2) dissolving the 7-phenylcarbamoylheptanoic acid in methanol, adding cation exchange resin and ZnCl2, heating to 50-55 DEG C for reaction for 3 hours, concentrating, extracting with ethyl acetate, concentrating, washing with petroleum ether, and drying to obtain suberanilic acid methyl ester; (3) subjecting hydroxylamine hydrochloride and sodium methoxide to stirring reaction in absolute methanol for 0.5-1h, filtering prior to adding the suberanilic acid methyl ester into filtrate for reaction at the temperature of 40 DEG C for 3-5 hours, cooling to room temperature, regulating the pH to 7, performing suction filtration, washing filter cake, and performing recrystallization with ethyl alcohol to obtain the vorinostat. The method is high in yield, quick in reaction and simple to operate.

Novel SAHA analogues inhibit HDACs, induce apoptosis and modulate the expression of microRNAs in hepatocellular carcinoma

In eukaryotes, transcriptional regulation occurs via chromatin remodeling, mainly through post translational modifications of histones that package DNA into structural units. Histone deacetylases (HDACs) are enzymes that play important role in various biological processes by repressing gene expression. Suberoylanilide hydroxamic acid (SAHA) is a known HDAC inhibitor that showed significant anti cancer activity by relieving gene silencing against hematologic and solid tumors. We have designed and synthesized a series of SAHA analogs C1–C4 and performed biological studies to elucidate its anti-cancer effects. It is observed that SAHA analogs significantly inhibited cell proliferation and induced apoptosis in hepatocellular carcinoma (HCC) cell lines HepG2 and SK-HEP-1. These analogs also showed non-toxic activity towards primary human hepatocytes, which describes its tumor specificity. SAHA analogs exhibited strong HDAC inhibition, which is 2–3 fold higher compared to SAHA. Moreover, these molecules induced hyper acetylation of histone H3 at various positions on the lysine residue. Further, it is observed that SAHA analogs are strong inducers of apoptosis, as they regulated the expression of various proteins involved in both extrinsic and intrinsic pathways. Interestingly, SAHA analogs induced upregulation of tumor suppressor miRNAs by activating its biogenesis pathway. Further, it is confirmed by microRNA (miRNA) prediction tools that these miRNAs are capable of targeting various anti-apoptotic genes. Based on these findings we conclude that SAHA analogs could be strong HDAC inhibitors with promising apoptosis inducing nature in HCC.

Synergistic effect of the combination of novel suberoylanilide hydroxamanic acid derivatives with cisplatin on anti-proliferation of human cancer cells

A novel, green, and atom-economical boric acid catalyzed direct amidation without the use of any coupling agents for the preparation of suberoylanilide hydroxamic acid (SAHA) and SAHA-based inhibitors targeting anti-proliferation of cancer cells is provided. The new SAHA-based inhibitor B123, when used alone, exhibited higher anti-proliferative activities than SAHA or Cisplatin against a number of human cancer cells. We have examined the effect of combination of these SAHA-based inhibitors with Cisplatin. We found synergistic effects of the combination of SAHA-based inhibitors with Cisplatin over a wide range of concentrations against human liver cancer cells HepG2 and two human lung cancer cell lines H1299 and H460. This synergism leads up to 8-fold of dose reduction for Cisplatin in the combination with our synthesized inhibitor B123 against H1299.

Synthesis and biological evaluation of aziridin-1-yl oxime-based vorinostat analogs as anticancer agents

The suberoyl anilide hydroxamic acid (vorinostat) analogs with the aziridin-1-yl oxime moiety as a possible metal chelating functionality have been synthesized. Their biological activity and stability under physiological conditions have been evaluated. Although some of the synthesized compounds demonstrated high antiproliferative activity against human HT1080 fibrosarcoma (HT1080, IC50 0.3-7.7 μM) comparable to vorinostat (HT1080, IC50 2.4 μM), they showed only weak histone deacetylase inhibition activity in HeLa cell line extracts.

Synthesis and anti-tumor activities of novel phenyl substituted suberoylanilide hydroxamic acid derivatives against human cancer cells

A facile and atom-economical boric acid catalyzed direct amidation without any coupling agents for the preparation of Suberoylanilide Hydroxamic Acid (SAHA) and SAHA-based inhibitors targeting anti-proliferation of cancer cells is described. It is applicable to the preparation of SAHAbased inhibitors having an unprotected hydroxyl group in the phenyl ring without the need of the protection. The in-vitro assays data indicate that the nature and the position of the substituents (activating and/or deactivating) in the capping group (phenyl ring) of SAHA-based inhibitors synthesized in this study have a vital impact on the potency of anti-proliferative activity against cancer cells. With low toxicity toward the normal cells, a number of synthesized SAHA-based inhibitors with two substituents in the phenyl ring possess higher antiproliferative activity than SAHA and Cisplatin toward six studied cancer cell lines: A375 human skin cancer cells, A549 human lung cancer cells, MGC80-3 human gastric cancer cells, H460 human lung cancer cells, H1299 human lung cancer cells, and HepG2 human liver cancer cells. Cisplatin is a common chemotherapeutic drug with high cytotoxicity for a variety of cancer treatments. The inhibitors provided in this study might signify future therapeutic drugs for cancer treatment.

Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, induces the production of anti-inflammatory cyclodepsipeptides from Beauveria felina

The addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid to a culture of the filamentous fungus Beauveria felina significantly changed its secondary metabolite profile and led to the isolation of eight compounds, including three new cyclodepsipeptides, desmethylisaridin E (1), desmethylisaridin C2 (2), and isaridin F (3), along with five known cyclodepsipeptide compounds. Isaridin F (3) possesses a cyclodepsipeptide ring with N-methylbutyric acid, which is rare in natural peptides. Absolute configurations of the new cyclodepsipeptides were achieved by Marfey's method. The anti-inflammatory activity of the isolated compounds was investigated through evaluating their effect on superoxide anion production and elastase release by FMLP-induced human neutrophils. Among the tested compounds, desmethylisaridin E (1) inhibited superoxide anion production and desmethylisaridin C2 (2) inhibited elastase release, with IC50 values of 10.00 ± 0.80 and 10.01 ± 0.46 μM, respectively.