155378-73-7

Upstream product

• 140-10-3 (E)-3-phenylacrylic acid 
• 7790-94-5 chlorosulfonic acid 

Downstream Products

• 28995-22-4 4-mercapto-trans-cinnamic acid 
• 1353887-49-6 N-[[4-(2-carboxyethenyl)phenyl]sulfonyl]-L-valine 
• 1353889-07-2 C₂₈H₃₄N₂O₁₂S₂ 
• 1353887-48-5 N-[[4-(2-carboxyethenyl)phenyl]sulfonyl]valine 
• 1602487-73-9 (E)-3-(4-(N-(2-((1R,2R,4S)-2-hydroxy-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl)ethyl)sulfamoyl)phenyl)acrylic acid 
• 391229-93-9 (E)-3-(4-(N-(2-(furan-2-yl)methyl)sulfamoyl)phenyl)acrylic acid 
• 1133001-67-8 (E)-methyl 3-(4-(chlorosulfonyl)phenyl)acrylate 
• 1133001-70-3 (E)-methyl 3-(4-(N-(5-((5-tert-butyloxazol-2-yl)methylthio)thiazol-2-yl)-sulfamoyl)phenyl)acrylate 
• 1255536-44-7 C₁₂H₁₃NO₆S 
• 1255536-46-9 C₁₃H₁₅NO₆S 
• 1255536-45-8 C₁₂H₁₃NO₆S 
• 866323-90-2 (2E)-3-{4-[(phenylamino)sulfonyl]phenyl}prop-2-enoic acid 
• 501683-06-3 3-[4-(Biphenyl-4-ylsulfamoyl)-phenyl]-acrylic acid 

Relevant academic research and scientific papers

Design, synthesis and evaluation of N-hydroxypropenamides based on adamantane to overcome resistance in NSCLC

A series of novel N-hydroxypropenamides containing adamantane moiety were identified and most of them exhibited HDAC inhibitory activity and could reverse the resistance of cisplatin in NSCLC cell lines. In this process, molecular docking was employed to verify the rationality of designing, subsequently, target compounds were synthesized and conducted to enzyme- and cell-based biological evaluation. Most of synthesized compounds could inhibit HDAC activity with the IC50 values lower than 50 nM and result in the increase of Ac-H4 and p21 in A549 cells. Importantly, we assessed the reversal effect of those compounds and found several compounds display an anti-resistant effect in lung cancer cells, especially compound 8f. As compared to belinostat and cisplatin, compound 8f showed improved inhibitory activity against A549/CDDP cell lines with IC50 value of 5.76 μM, and far lower resistance index of 1.24. Moreover, the structure–activity relationships of these compounds were summarized and compound 8f could serve as a research tool for identifying the mechanism of reversing resistance and a template for designing novel compounds to reverse cisplatin resistance.

Targeting HDAC/OAZ1 axis with a novel inhibitor effectively reverses cisplatin resistance in non-small cell lung cancer

Cisplatin yields significant efficacy and is generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, acquired resistance strongly limits its application. Here, we identified that a novel histone deacetylase (HDAC) inhibitor S11, with P-glycoprotein inhibitory activity, could obviously suppress cell growth in cisplatin-resistant NSCLC cell lines. In addition, S11 could increase the expression of Ac-H4 and p21, which confirmed its HDAC inhibitory action, suppress colony formation, and block cell migration of cisplatin-resistant NSCLC cells. Notably, co-treatment with S11 and cisplatin exhibited synergistically inhibitory efficacy in cisplatin-resistant NSCLC cells. Gene microarray data showed that OAZ1 was downregulated in resistant cells but upregulated after S11 treatment. Further study indicated that knockdown of OAZ1 by siRNA resulted in the decrease of sensitivity of resistant cells to cisplatin treatment and contributed to the increase of resistant cell migration. Additionally, ChIP assay data demonstrated that HDAC inhibitor S11 could increase the accumulation of Ac-H4 in OAZ1 promoter region, suggesting the direct regulation of OAZ1 by HDAC. Importantly, the combination of S11 and cisplatin overcome resistance through inhibiting HDAC activity and subsequently increasing the OAZ1 expression in preclinical model. Moreover, we observed that positive expression of HDAC1 was associated with the downregulation of OAZ1 in NSCLC patients with platinum-based treatment, and predicted drug resistance and poor prognosis. In summary, we demonstrated a role of HDAC/OAZ1 axis in cisplatin-resistant NSCLC and identified a promising compound to overcome cisplatin resistance.

Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox

Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.

In vitro and in vivo evaluation of novel cinnamyl sulfonamide hydroxamate derivative against colon adenocarcinoma

The potential of cinnamic acid as an anti-inflammatory and anti-cancer agent has been studied previously. In our investigation, novel bio-isosters of cinnamyl sulfonamide hydroxamate were synthesized, characterized and confirmed for their structure and ev

A photoreactive crystalline quasiracemate

Rationally designed racemic and quasiracemic sulfonamidecinnamic acids assemble to give hydrogen-bonded dimers with coplanar alignment of neighboring olefins. The quasiracemate phase contains near inversion-related motifs with chemically distinct components forming supramolecular heterodimers that undergo asymmetric photodimerization.

CDK INHIBITORS CONTAINING A ZINC BINDING MOIETY

The present invention relates to CDK inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The compounds of the invention may further act as HDAC inhibitors.

One-pot synthesis of trans-4-alkylthio- And 4-arylthio-cinnamic acids from trans-4-chlorosulfonylcinnamic acid in an aqueous medium

A one-pot syntheses of trans-4-alkylthio- and 4-arylthio-cinnamic acids were achieved in high yields by reduction of trans-4-chlorosulfonylcinnamic acid with stannous chloride dihydrate followed by alkylation and arylation of the resulting trans-4-thiocinnamic acid with various kinds of alkyl and activated aryl halides in an aqueous medium.

Novel sulfonamide derivatives as inhibitors of histone deacetylase

Inhibition of the enzyme histone deacetylase (HDAC) is emerging as a novel approach to the treatment of cancer. A series of novel sulfonamide derivatives were synthesized and evaluated for their ability to inhibit human HDAC. Compounds were identified which are potent enzyme inhibitors, with IC 50 values in the low nanomolar range against enzyme obtained from HeLa cell extracts, and with antiproliferative effects in cell culture. Extensive characterization of the structure - activity relationships of this series identified key requirements for activity. These include the direction of the sulfonamide bond and substitution patterns on the central phenyl ring. The alkyl spacer between the aromatic head group and the sulfonamide functionality also influenced the HDAC inhibitory activity. One of these compounds, m11.1, also designated PXD101, has entered clinical trials for solid tumors and haematological malignancies.

Carbamic acid compounds comprising a sulfonamide linkage as hdac inhibitors

This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S (═O)2NR1— and —NR1S(═O)2—; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is —S(═O)2NR1—, then Q1 is an aryl 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.