109718-56-1Relevant articles and documents
High analgesic and anti-inflammatory in vivo activities of six new hybrids NSAIAs tetrahydropyran derivatives
Capim, Saulo L.,Goncalves, Gabriela M.,Dos Santos, Gabriela C.M.,Marinho, Bruno G.,Vasconcellos, Mario L.A.A.
, p. 6003 - 6010 (2013)
We present in this article syntheses of six new hybrids compounds (4-9) that were efficiently prepared in one or two steps (70-84.6%) from our previous prototype (±)-cis-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl) methanol (3) and the NSAIAs: acetyl salicylic acid, indomethacin, ibuprofen, ketoprofen, naproxen and diclofenac. The acetic acid-induced writhing method is able to determine that all investigated new hybrids showed stronger antinociceptive properties (2- to 10-fold less ED50 values) than their precursors. The highest antinociceptive effect was observed for compound 9 showing more than 10-fold less ED50 values than diclofenac and ninefold less ED50 value than compound 2. All compounds presented greater activity than the control group in the tail-flick test confirming the central antinociceptive effect. New hybrids did not alter the motor performance of mice by rota-rod performance and open-field tests. Investigated compounds 4-9 were not toxic after oral administration (LD50 >2000 mg/kg).
(R)- and (S)-3-Hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone, New Chiral Auxiliaries for the Asymmetric Synthesis of α-Arylpropanoic Acids.
Camps, Pelayo,Gimenez, Silvia
, p. 991 - 1000 (1995)
Reaction of rac-α-arylpropanoyl chlorides with (R)- and (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone (R)- and (S)-1, in the presence of triethylamine, under standard esterification conditions, gave (R,R)- and (S,S)-3, respectively, with high diastereoselectivity.Controlled acidic hydrolysis afforded the corresponding (R)- or (S)-α-arylpropanoic acids with high enantioselectivity, the chiral auxiliary being recovered efficiently.
Novel penicillin analogues as potential antimicrobial agents; Design, synthesis and docking studies
Ashraf, Zaman,Bais, Abdul,Manir, Md. Maniruzzaman,Niazi, Umar
, (2015)
A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 ?. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.
The Effects of Prodrug Size and a Carbonyl Linker on l-Type Amino Acid Transporter 1-Targeted Cellular and Brain Uptake
Venteicher, Brooklynn,Merklin, Kasey,Ngo, Huy X.,Chien, Huan-Chieh,Hutchinson, Keino,Campbell, Jerome,Way, Hannah,Griffith, Joseph,Alvarado, Cesar,Chandra, Surabhi,Hill, Evan,Schlessinger, Avner,Thomas, Allen A.
, p. 869 - 880 (2020/12/15)
The l-type amino acid transporter 1 (LAT1, SLC7A5) imports dietary amino acids and amino acid drugs (e. g., l-DOPA) into the brain, and plays a role in cancer metabolism. Though there have been numerous reports of LAT1-targeted amino acid-drug conjugates (prodrugs), identifying the structural determinants to enhance substrate activity has been challenging. In this work, we investigated the position and orientation of a carbonyl group in linking hydrophobic moieties including the anti-inflammatory drug ketoprofen to l-tyrosine and l-phenylalanine. We found that esters of meta-carboxyl l-phenylalanine had better LAT1 transport rates than the corresponding acylated l-tyrosine analogues. However, as the size of the hydrophobic moiety increased, we observed a decrease in LAT1 transport rate with a concomitant increase in potency of inhibition. Our results have important implications for designing amino acid prodrugs that target LAT1 at the blood-brain barrier or on cancer cells.
Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source
Kariofillis, Stavros K.,Shields, Benjamin J.,Tekle-Smith, Makeda A.,Zacuto, Michael J.,Doyle, Abigail G.
supporting information, p. 7683 - 7689 (2020/04/22)
Methylation of organohalides represents a valuable transformation, but typically requires harsh reaction conditions or reagents. We report a radical approach for the methylation of (hetero)aryl chlorides using nickel/photoredox catalysis wherein trimethyl orthoformate, a common laboratory solvent, serves as a methyl source. This method permits methylation of (hetero)aryl chlorides and acyl chlorides at an early and late stage with broad functional group compatibility. Mechanistic investigations indicate that trimethyl orthoformate serves as a source of methyl radical via β-scission from a tertiary radical generated upon chlorine-mediated hydrogen atom transfer.
