Acrylic Acid Moiety Research Articles

Design, synthesis, and biological evaluation of (E)-3-(4-methanesulfonylphenyl)-2-(aryl)acrylic acids as dual inhibitors of cyclooxygenases and lipoxygenases

A group of (E)-3-(4-methanesulfonylphenyl)acrylic acids possessing a substituted-phenyl ring (4-H, 4-Br, 3-Br, 4-F, 4-OH, 4-OMe, 4-OAc, and 4-NHAc) attached to the acrylic acid C-2 position were prepared using a stereospecific Perkin condensation reaction. A related group of compounds having 4- and 3-(4-isopropyloxyphenyl)phenyl, 4- and 3-(2,4-difluorophenyl)phenyl and 4- and 3-(4-methanesulfonylphenyl)phenyl substituents attached to the acrylic acid C-2 position were also synthesized, using a palladium-catalyzed Suzuki cross-coupling reaction, for evaluation as dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors. (E)-2-(3-Bromophenyl)-3-(4-methanesulfonylphenyl)acrylic acid (9h), and compounds having 4-(4-isopropyloxyphenyl-, 2,4-difluorophenyl-, or 4-methylsulfonylphenyl)phenyl moieties at the acrylic acid C-2 position (11a,b,d), were particularly potent COX-2 inhibitors with a high COX-2 selectivity index (COX-2 IC50≈0.32μM, SI>316) similar to the reference drug rofecoxib (COX-2 IC50=0.5μM, SI>200). Acrylic acid analogs with a C-2 4-hydoxyphenyl (9d, IC50=0.56μM), or 4-acetamidophenyl (9g, IC50=0.11μM), substituent were particularly potent 5-LOX inhibitors that may participate in an additional specific hydrogen-bonding interaction. A number of compounds possessing a C-2 substituted-phenyl moiety (4-Br, 4-F, and 4-OH), or a 4- or 3-(2,4-difluorophenyl)phenyl moiety, showed potent 15-LOX inhibitory activity (IC50 values in the 0.31–0.49μM range) relative to the reference drug luteolin (IC50=3.2μM). Compounds having a C-2 4-acetylaminophenyl, or 4-(2,4-difluorophenyl)phenyl, moiety exhibited anti-inflammatory activities that were equipotent to aspirin, but less than that of celecoxib. The structure–activity data acquired indicate the acrylic acid moiety constitutes a suitable scaffold (template) to design novel acyclic dual inhibitors of the COX and LOX isozymes.

Synthesis and characterization of UV-curable dual hybrid oligomers based on epoxy acrylate containing pendant alkoxysilane groups

This work involves the synthesis of novel hybrid oligomers based on a UV-curable epoxy acrylate resin (EA). The EA resin was modified with various amount of 3-isocyanatopropyl trimethoxysilane (IPTMS) coupling agent. The modification percentage of the hybrid oligomer was varied from 0 to 50 wt.%. UV-curable, hard and transparent organic–inorganic hybrid coatings were prepared on Plexiglas substrates and their characterization was performed by the analyses of various properties such as hardness, gloss, tape adhesion test and stress–strain test. Results from the mechanical measurements show that the properties of hybrid coatings improve with the increase in modification ratio. The thermal behavior of coatings was also evaluated. It is observed that the thermal stability of epoxy acrylate coatings is enhanced with incorporation of siloxane. Gas chromatography/mass spectrometry analyses showed that the initial weight loss obtained in thermogravimetric analysis is due to the degradation products of the photoinitator and the acrylic acid moiety of acrylic monomers.

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 4: Addressing the problem of poor stability due to photoisomerization of an acrylic acid moiety

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 4: Addressing the problem of poor stability due to photoisomerization of an acrylic acid moiety

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 4: Addressing the problem of poor stability due to photoisomerization of an acrylic acid moiety

Exchange of the ethylene tether in a series of pyridopyrimidine-based MexAB-OprM specific efflux pump inhibitors to an amide bond stabilized the olefin of the acrylic acid moiety, preventing facile photoisomerization to the Z-isomer. Furthermore, the activity was drastically improved in the amide tether variants, providing extremely potent acrylic acid and vinyl tetrazole analogues.

Conjugate Addition of Trimethylsilylmethyl Cuprates to Artemisinic Acid: Homologation and Subsequent Conversion to 9β-Modified Artemisinin Analogs

Conjugate addition to the acrylic acid moiety of artemisinic acid 2 was made possible by in situ protection as a silyl ester followed by treatment with a trimethylsilylmethyl cuprate such as (TMSCH2)C4H9CuLi•LiX, where X = CN or I. After deprotective workup, the homologated carboxylic acid 9 was obtained in excellent yields. Photoxygenation and acid treatment of 9 then led to the facile preparation of potent 9β-modified analogs of the naturally occurring antimalarial agent, artemisinin.

Optical Properties and Photopolymerization of Liquid Crystalline (Acetyl) (Ethyl) Cellulose/Acrylic Acid System

The structure and properties of a chiral nematic phase, which reflects one hand of circularly polarized light in a narrow region of wavelength, of fully acetylated (ethyl) cellulose [(acetyl) (ethyl) cellulose, AEC] in acrylic acid (AA) were studied in comparison with (ethyl) cellulose (EC). AEC mesophase formed right-handed chiral nematic structure while EC formed left-handed one. AEC mesophase showed higher birefringence and reflection intensity. The relationship between the reflection wavelength and the polymer concentration was negatively correlated for both AEC and EC mesophases. The relationship between the reflection wavelength and the molecular weight was also negative for AEC mesophase whereas positive for EC mesophase. AEC mesophase was solidified by photopolymerization of AA moiety. It was revealed that the optical properties of AEC mesophase could be preserved by photopolymerization, since the resulting solid material reflects selectively one hand of circularly polarized light.

Conjugate Addition of a Cyano-Gilman Cuprate to an Acrylic Acid: Homologation of Artemisinic Acid and Subsequent Conversion to 16-Butylartemisinin

Conjugate addition to the acrylic acid moiety of artemisinic acid 2 was made possible by in situ protection as a silyl ester, treatment with a cyano-Gilman cuprate [Bu2CuLi·LiCN] to facilitate 1,4-addition, and deprotective workup affording the homologated carboxylic acid 9. Photoxygenation and acid treatment of 9 then led to the facile preparation of potent antimalarial 9-modified analogs of artemisinin.

A general method for the synthesis of bridged indole alkaloids

Abstract

ChemInform Abstract: The Biosynthesis of Sparsomycin (I). Further Investigations of the Biosynthesis of the Uracil Acrylic Acid Moiety.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The biosynthesis of sparsomycin. Further investigations of the biosynthesis of the uracil acrylic acid moiety

Precursor incorporation experiments have ruled out the involvement of N′-formylkynurenine in the biosynthesis of the uracil acrylic acid moiety of sparsomycin. An enzyme has been partially purified from the sparsomycin-producer that catalyzes the synthesis of the uracil acrylic acid from a pyrimidine acrylic acid previously shown to be a sparsomycin precursor. The enzymatic synthesis of the uracil acrylic acid requires NAD +, a result which indicates that the mechanism of the uracil acrylic acid synthase is similar to that of inosine-5′-monophosphate dehydrogenase. Analog studies demonstrate that the enzyme lacks rigid substrate specificity.

Synthesis of a dibenz[b,e]oxepin-bovine serum albumin conjugate for radioimmunoassay of KW-4679 ((Z)-11-[3-(dimethylamino)propylidene]-6,11- dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride).

(Z)-11-[3-(Dimethylamino)propylidene]-2-(methoxycarbonyl)methyl-6, 11- dihydrodibenz[b,e]oxepin-9-acrylic acid (5) was prepared for application to the radioimmunoassay of KW-4679 (1, (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e ] oxepin-2-acetic acid hydrochloride). The acrylic acid moiety in the 9-position of 5 was employed for coupling with an amino group of bovine serum albumin (BSA) to provide 17. Subsequently, the conjugate 17 was treated with aqueous NaOH to hydrolyze the terminal methoxycarbonyl group in the 2-position of the BSA conjugated 5. Antiserum raised against the antigenic BSA-conjugate 4 finally obtained was specific for 1.

Studies on quinoline and isoquinoline derivatives. IX. Synthesis of pyrrolo(1,2-b)isoquinolines from 3-bromoisoquinoline derivatives.

The reaction of 3-bromo-1-methoxyisoquinoline with propargyl alcohol in the presence of dichlorobis (triphenylphosphine) palladium and cuprous iodide gave 3-(1-methoxy-3-isoquinolyl) propargyl alcohol in good yield. Cyclization of 3-(1-methoxy-3-isoquinolyl) propanol obtained by the catalytic reduction of the propargyl alcohol, afforded a 1, 2, 3, 5-tetrahydropyrrolo [1, 2-b] isoquinoline derivative. The synthesis of a pyrrolo [3, 2, 1-de] phenanthridine derivative was accomplished by the introduction of an acrylic acid moiety into the pyrrolo [1, 2-b] isoquinoline and subsequent reduction and cyclization of the resulting ethyl pyrrolo [1, 2-b] isoquinoline-10-acrylate.