83477-74-1Relevant articles and documents
Synthesis and structure reassignment of malylglutamate, a recently discovered earthworm metabolite
Griffith, Corey M.,Feceu, Abigail,Larive, Cynthia K.,Martin, David B. C.
, p. 417 - 421 (2019)
Malylglutamate, a newly identified metabolite in earthworms, was synthesized using a traditional peptide coupling approach for assembling the amide from protected malate and glutamate precursors. The proposed structure (1) and a diastereomer were synthesized, but their NMR spectra did not match the natural sample. Further analysis of the natural sample using HMBC spectroscopy suggested an alternative attachment of the malyl moiety, and β-malylglutamate (2) diastereomers were synthesized, L,L-2 and D,D-2. NMR spectra were an excellent match with the natural sample, and chiral-phase chromatography was employed to identify (a)-β-l-malyl-l-glutamate (2) as the isomer native to Eisenia fetida.
PYRAZOLYL-SUBSTITUTED HETEROARYLS AND THEIR USE AS MEDICAMENTS
-
Page/Page column 41, (2017/03/28)
The invention relates to new substituted heteroaryls of formula 1 or of formula 1' wherein A is either N or CH, wherein R2 is selected from the group consisting of -C1-3-alkyl, -C1-3-haloalkyl, F, Br, CI, wherein Y is selected from -O- or -CH2-, and wherein R3 is defined as in claim 1, and the pharmaceutically acceptable salts thereof, and the use of these aforementioned compounds for the treatment of diseases such as asthma, COPD, allergic rhinitis, allergic dermatitis, lupus erythematodes, lupus nephritis and rheumatoid arthritis.
Design and synthesis of sulfur based inhibitors of matrix metalloproteinase-1.
Fujisawa, Tetsunori,Odake, Shinjiro,Ogawa, Yuji,Yasuda, Junko,Morita, Yasuo,Morikawa, Tadanori
, p. 239 - 252 (2007/10/03)
Fibroblast collagenase (MMP-1), a member of the matrix metalloproteinases family, is believed to be a pathogenesis of arthritis, by cleaving triple-helical type II collagen in cartilage. From the similarity of the active site zinc binding mode with hydroxamate, we designed and synthesized alpha-mercaptocarbonyl possessing compounds (3-5), which incorporated various peptide sequences as enzyme recognition sites. The P4-P1 peptide incorporating compound (3) exhibited as potent inhibition as the hydroxamate (1) and the carboxylate (2) type inhibitors, with an IC50 of 10(-6) M order against MMP-1. But the inhibitor (3) related compounds (6-8) displayed decreased or no inhibitory potencies. These results suggest that the existence of both the carbonyl and thiol groups might be critical for the inhibition, and the distance between the two functional groups is important for inhibitory potency. For Pn' peptide incorporating compounds (4a-k), except for 4h and 4k, all compounds showed IC50 values under sub-nanomolar. Among them, for potent inhibition, Leu was better than Phe and Val as the P1' amino acid, and the P2' position amino acid was necessary, and preferentially Phe. Insertion of the Pn peptide into 4d or 4k, giving compounds 5a-c, did not increase the activities of 4d and 4k. Substitution of the mercapto group with other functional groups lost the activity of compound 4a. The stereochemical preference at the thiol-attached position was also determined by preparation of both isomers of 4a. It was found that the S configuration compound (36b) is approximately 100 times more potent than the corresponding R-isomer (36a).
