769968-22-1

Upstream product

• 95262-00-3 N-m-tolyl-malonamic acid 
• 100-52-7 benzaldehyde 
• 102-92-1 cinnamoyl chloride 
• 108-44-1 1-amino-3-methylbenzene 
• 99-08-1 1-methyl-3-nitrobenzene 
• 4192-77-2 ethyl cinnamate 
• 140-10-3 (E)-3-phenylacrylic acid 
• 102-92-1 Cinnamoyl chloride 
• 100-42-5 styrene 
• 13939-06-5 molybdenum hexacarbonyl 
• 766-82-5 1-ethynyl-3-methyl-benzene 
• 883972-65-4 C₁₆H₁₄O 
• 621-82-9 Cinnamic acid 

Relevant academic research and scientific papers

PRMT5 INHIBITOR COMPOUNDS

A series of PRMT5 inhibitor compounds are described. The compounds are useful as PRMT5 inhibitor compounds and in the treatment of PRMT5 mediated diseases, disorders, and symptoms thereof.

Investigation of anti-inflammatory potential of N-arylcinnamamide derivatives

A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)-3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-κB at the concentration of 2 μM and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-α. Nevertheless, subsequent tests showed that the investigated compounds affect neither IκBα level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C(2,5)0 or C(2,6)0 positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.

Synthesis and spectrum of biological activities of novel N-arylcinnamamides

A series of sixteen ring-substituted N-arylcinnamamides was prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra, Fusarium avenaceum, and Bipolaris sorokiniana. Several of the tested compounds showed antistaphylococcal, antitubercular, and antifungal activities comparable with or higher than those of ampicillin, isoniazid, and benomyl. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-phenylprop-2-enamide and (2E)-3-phenyl-N-[3-(trifluoromethyl)phenyl]prop-2-enamide showed the highest activities (MICs = 22.27 and 27.47 μM, respectively) against all four staphylococcal strains and against M. tuberculosis. These compounds showed an activity against biofilm formation of S. aureus ATCC 29213 in concentrations close to MICs and an ability to increase the activity of clinically used antibiotics with different mechanisms of action (vancomycin, ciprofloxacin, and tetracycline). In time-kill studies, a decrease of CFU/mL of >99% after 8 h from the beginning of incubation was observed. (2E)-N-(3,5-Dichlorophenyl)-and (2E)-N-(3,4-dichlorophenyl)-3-phenylprop-2-enamide had a MIC = 27.38 μM against M. tuberculosis, while a significant decrease (22.65%) of mycobacterial cell metabolism determined by the MTT assay was observed for the 3,5-dichlorophenyl derivative. (2E)-N-(3-Fluorophenyl)-and (2E)-N-(3-methylphenyl)-3-phenylprop-2-enamide exhibited MICs = 16.58 and 33.71 μM, respectively, against B. sorokiniana. The screening of the cytotoxicity of the most effective antimicrobial compounds was performed using THP-1 cells, and these chosen compounds did not shown any significant lethal effect. The compounds were also evaluated for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. (2E)-N-(3,5-dichlorophenyl)-3-phenylprop-2-enamide (IC50 = 5.1 μM) was the most active PET inhibitor. Compounds with fungicide potency did not show any in vivo toxicity against Nicotiana tabacum var. Samsun. The structure–activity relationships are discussed.

Palladium-Catalyzed Carbonylative Synthesis of α,β-Unsaturated Amides from Styrenes and Nitroarenes

A procedure on palladium-catalyzed selective aminocarbonylation of styrenes with nitroarenes for the synthesis of α,β-unsaturated amides has been developed. A range of substituted α,β-unsaturated amides were synthesized in moderate to good yields. Interestingly, nitroarenes act as both a nitrogen source and oxidant, and Mo(CO)6 acts as a solid CO source and reductant in this catalytic system.

Lewis Acid Mediated Tandem Reaction of Propargylic Alcohols with Hydroxylamine Hydrochloride to Give α,β-Unsaturated Amides and Alkenyl Nitriles

We have developed a highly selective method for the synthesis of α,β-unsaturated amides and alkenyl nitriles from readily available propargylic alcohols. The reaction proceeded smoothly under the neutral conditions with hydroxylamine hydrochloride (NH2OH·HCl) as the nitrogen source. The development of these new strategies has significantly extended the application of hydroxylamine hydrochloride to the chemistry of propargylic alcohols. Moreover, both secondary and tertiary alcohols have been highly regioselectively transformed to the desired products with good functional group compatibility.

TMSCl-mediated synthesis of α,β-unsaturated amides via C-C bond cleavage and C-N bond formation of propargyl alcohols with trimethylsilyl azide

A new method with high efficiency for the synthesis of α,β- unsaturated amides from the easily prepared propargyl alcohols and TMSN 3 using TMSCl as an acid promoter is developed. A wide variety of α,β-unsaturated amides were produced in moderate to excellent yields. Mechanistic studies indicate that this transformation involves TMSCl-mediated allenylazide intermediate formation, C-C bond cleavage, and C-N bond formation. Significantly, this reaction shows good functional group compatibility and high regioselectivity, with a relatively short reaction time and inexpensive reagents.

Synthesis, structure, and biological assay of cinnamic amides as potential EGFR kinase inhibitors

A series of derivatives of cinnamic amide (compounds 2a-2v) were synthesized and evaluated for antiproliferative activities against the human breast cancer cell line MCF-7- and EGFR-inhibitory activities. The structures of compounds 2b and 2i were determined by single-crystal X-ray diffraction analysis. Compounds 2f and 2j showed moderate EGFR inhibitory activity with IC50 values of 5.16 and 7.37 μM, respectively. Docking simulation of compound 2f was carried out to illustrate the binding mode of the molecule into the EGFR active site. Structure-activity relationship analysis found that the N-phenyl rings are required for enhancing the activities.

Synthesis and structure-activity relationship analysis of caffeic acid amides as selective matrix metalloproteinase inhibitors

Four series of acid amides were synthesized, and through measurement using a fluorogenic substrate assay with human recombinant MMP-1, MMP-2 and MMP-9, compound 3f showed considerable inhibitory activities against MMP-2, MMP-9 and the best selectivity over MMP-1. Preliminary structure-activity relationship analysis indicated that caffeic acid amides with electron-donating groups at para-position of amino phenyl group showed better inhibitory activities and selectivity than those with electron-withdrawing groups, and the presence of adjacent dihydroxy in the caffeoyl group was very important for the MMP-2 and MMP-9 inhibitory activities.

Monoamine oxidase inhibition by selected anilide derivatives

A series of anilide derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The most potent inhibitors among the derivatives that were initially evaluated were (2E)-N-(3-chlorophenyl)-3-phenylprop-2-enamide (2c) and (2E)-N-(3-bromophenyl)- 3-phenylprop-2-enamide (2d) with IC50 values of 0.53 μM and 0.45 μM, respectively. These derivatives exhibited reversible and selective inhibition of MAO-B with binding affinities 37 fold higher for MAO-B than for MAO-A. Analysis of the possible binding interactions of these inhibitors with active site models of human MAO-A and -B led to the design of phenolic and benzonitrile derivatives of 2c and 2d. Among these were (2E)-N-(3-chlorophenyl)- 3-(4-hydroxyphenyl)prop-2-enamide (7c) and (2E)-N-(3-bromophenyl)-3-(4- hydroxyphenyl)prop-2-enamide (7d) which inhibited MAO-B selectively and reversibly with IC50 values of 0.032 μM and 0.026 μM, respectively. These inhibitors were at least 14 fold more potent than 2c and 2d. This study concludes that N,3-diphenylprop-2-enamide is a suitable scaffold for the design of selective MAO-B inhibitors and structural modifications to enhance the binding affinities of the inhibitors for the MAO-B active site include substitution with halogens on the N-phenyl ring and substitution with hydroxyl and nitrile functional groups on the para and meta positions, respectively, of the C3 phenyl ring. Possible binding modes of these structures within the MAO-B active site are proposed with the emphasis on the interactions of the inhibitor halogens and the hydroxyl and nitrile functional groups with active site residues and water molecules.

DIHYDRONAPHTHYRIDINYL AND RELATED COMPOUNDS FOR USE IN TREATING OPHTHALMOLOGICAL DISORDERS

The invention provides methods of using dihydronaphthyridinyl and related compounds to treat ophthalmological disorders, such as, wet age-related macular degeneration, diabetic retinopathy, and high myopia. Pharmaceutical compositions and methods of synthesizing the dihydronaphthyridinyl and related compounds are provided