117390-07-5

Upstream product

• 619-42-1 4-methoxycarbonylphenyl bromide 
• 79-10-7 acrylic acid 
• 619-44-3 methyl 4-iodobenzoate 
• 110-89-4 piperidine 
• 1571-08-0 methyl 4-formylbenzoate 
• 108-31-6 maleic anhydride 
• 619-66-9 4-Carboxybenzaldehyde 
• 141-82-2 malonic acid 

Downstream Products

• 179621-04-6 8-[2,6-Dichloro-3-[N-[4-(methoxycarbonyl)cinnamoylglycyl]-N-methylamino]benzyloxy]-2-methylquinoline 
• 145241-74-3 methyl (E)‐4‐(3‐chloro‐3‐oxoprop‐1‐en‐1‐yl)benzoate 
• 115665-79-7 (E)-4-(β-bromovinyl)benzoic acid methyl ester 
• 117389-63-6 (E)-methyl 4-(3-bromoprop-1-en-1-yl)benzoate 
• 117389-82-9 2-(4-methoxycinnamylthio)-4-methoxycarbonyl-Δ²-1,3-thiazoline 
• 117432-91-4 3-(4-methoxycarbonylcinnamyl)-4-methoxycarbonyl-1,3-thiazolidine-2-thione 
• 1041867-88-2 C₁₇H₁₃N₃O₃ 
• 1012036-96-2 methyl (E)-4-(3-phenylprop-1-en-1-yl)benzoate 
• 1143460-71-2 methyl (E)-4-(3-oxo-3-(((tetrahydro-2H-pyran-2-yl)oxy)amino)propan-1-en-1-yl)benzoate 

Relevant academic research and scientific papers

8-substituted styryl xanthine derivative and application thereof

The invention discloses an 8-substituted styryl xanthine derivative and application thereof, and particularly relates to a novel 8-substituted styryl xanthine derivative and a pharmaceutical composition containing the 8-substituted styryl xanthine derivat

Histone deacetylase and proteasome double-target inhibitor, and preparation method and application thereof

The invention relates to a protein deacetylase and proteasome double-target inhibitor, and a pharmaceutically acceptable salt, a stereoisomer, a preparation method and an application thereof. The compound is represented by general formula I, the compound has good histone deacetylase resisting activity, proteasome resisting activity and tumor cell proliferation resisting activity, and can be used for preparing medicines for preventing or treating related mammalian diseases caused by abnormal histone deacetylase expression or proteasome abnormality. The invention also relates to a pharmaceuticalapplication of a composition containing the compound with the structure of general formula I.

Discovery of peptide boronate derivatives as histone deacetylase and proteasome dual inhibitors for overcoming bortezomib resistance of multiple myeloma

While proteasome inhibitors such as bortezomib showed satisfactory clinical benefits in the initial treatment of multiple myeloma (MM), drug resistance and relapse are unavoidable. Recent studies suggested inhibition of histone deacetylases (HDACs) restored sensitivity of bortezomib-resistant MM. Hence, we designed dual inhibitors targeting both HDACs and proteasomes to address the resistance of bortezomib. The most potent inhibitors, ZY-2 and ZY-13 showed excellent inhibition against proteasome and good selectivity against HDACs. In particular, ZY-2 not only exhibited good antiproliferative activities on the MM cell lines RPMI-8226, U266, and KM3 (IC50 values of 6.66, 4.31, and 10.1 nM, respectively) but also showed more potent antiproliferative activities against the bortezomib-resistant MM cell line KM3/BTZ compared with bortezomib (IC50 values of 8.98 vs. 226 nM, P 50 values of 8.98 vs. 98.0 nM, P 0.01).

Bioassay of ferulic acid derivatives as influenza neuraminidase inhibitors

Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC50 values of 12.77 ± 0.47 and 12.96 ± 1.34 μg/ml, respectively. On the basis of the biological results, a preliminary structure–activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.

HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF

Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low expression of specific genes, the presence of one or more cytogenetic or molecular risk factors such as intermediate cytogenetic risk, Normal Karyotype (A/K), mutated NPM1, mutated CEBPA, mutated FLT3, mutated DNMT3A, mutated TET2, mutated IDH1, mutated IDH2, mutated RUNX1, mutated WT1, mutated SRSF2, intermediate cytogenetic risk with abnormal karyotype (intern(abnK)), trisomy 8 (+8) and/or abnormal chromosome (5/7), and/or a high leukemic stem cell (LSC) frequency.

Discovery and anti-inflammatory evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β)

Glycogen synthase kinase-3β (GSK-3β) has been identified to promote inflammation and its inhibitors have also been proven to treat some inflammatory mediated diseases in animal models. Non-ATP competitive inhibitors inherently have better therapeutical value due to their higher specificity than ATP competitive ones. In this paper, we designed and synthesized a series of new BTZ derivatives as non-ATP competitive GSK-3β inhibitors. Kinetic analysis revealed two typical compounds 6j and 3j showed the different non-ATP competitive mechanism of substrate competition or allosteric modulation to GSK-3β, respectively. As expected, the two compounds showed good specificity in a panel test of 16 protein kinases, even to the closest enzymes, like CDK-1/cyclin B and CK-II. The in vivo results proved that both compounds can greatly attenuate the LPS-induced acute lung injury (ALI) and diminish inflammation response in mice by inhibiting the mRNA expression of IL-1β and IL-6. Western blot analysis demonstrated that they negatively regulated GSK-3β, and the mechanism of the observed beneficial effects of the inhibitors may involve both the increased phosphorylation of the Ser9 residue on GSK-3β and protein expression of Sirtuin 1 (SIRT1). The results support that such novel BTZ compounds have a protective role in LPS-induced ALI, and might be attractive candidates for further development of inflammation pharmacotherapy, which greatly thanks to their inherently high selectivities by the non-ATP competitive mode of action. Finally, we proposed suggesting binding modes by Docking study to well explain the impacts of compounds on the target site.

Transition-metal-free C-P bond formation via decarboxylative phosphorylation of cinnamic acids with P(O)H compounds

A novel, transition-metal-free phosphorylation of cinnamic acids with P(O)H compounds has been developed via radical-promoted decarboxylation under mild conditions. This method provides simple, efficient, and versatile access to valuable (E)-alkenylphosphine oxides in satisfactory yields with a wide variety of substrates.

Polystyrene supported palladium nanoparticles catalyzed cinnamic acid synthesis using maleic anhydride as a substitute for acrylic acid

Maleic anhydride was explored as a substitute for acrylic acid to synthesize cinnamic acids from aryl halides under heterogeneous palladium catalyzed conditions. The combined role of surface and impregnated catalyst together performed an upright engineering to hold in situ generated molecules on the surface and subsequently facilitate their interaction for the desired product synthesis. Overall, a surface mediated approach for cinnamic acid synthesis from maleic anhydride following a major unexplored pathway through catalyst promoted decarboxylation was critically investigated.

4-Biphenylalanine- and 3-Phenyltyrosine-Derived Hydroxamic Acids as Inhibitors of the JumonjiC-Domain-Containing Histone Demethylase KDM4A

Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate-based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC50value of 25.4 μm. Herein we report the synthesis and biochemical evaluations, with two orthogonal in vitro assays, of a series of derivatives of this lead structure. With extensive chemical modifications on the lead structure, also by exploiting the versatility of the radical arylation with aryldiazonium salts, we were able to increase the potency of the derivatives against KDM4A to the low-micromolar range and, more importantly, to obtain demethylase selectivity with respect to HDACs. Cell-permeable derivatives clearly showed a demethylase-inhibition-dependent antiproliferative effect against HL-60 human promyelocytic leukemia cells.

CINNAMIC ACID AMIDE DERIVATIVE

The present invention provides a cinnamic acid amide derivative having an excellent analgesic action. The cinnamic acid amide derivative of the present invention is a compound showing excellent analgesic actions to not only a nociceptive pain model animal but also a neuropathic pain model animal, which is very useful as an agent for treating various pain diseases showing acute or chronic pains or neuropathic pains.