31874-34-7Relevant articles and documents
Synthesis of 3,5-disubstituted isoxazolines as protein tyrosine phosphatase 1B inhibitors
Maurya, Rakesh,Gupta, Prasoon,Ahmad, Ghufran,Yadav, Dinesh Kumar,Chand, Kailash,Singh, Amar Bahadur,Tamrakar, Akhilesh K.,Srivastava, Arvind K.
, p. 123 - 136 (2008)
The protein tyrosine phosphatases (PTPase) are a group of regulatory enzymes that are critically important to a wide variety of cellular functions. PTPase 1B has recently been implicated in the pathogenesis of diabetes, neuronal disease, and autoimmune diseases. A number of these PTPase that act as negative regulators of the insulin signaling cascade have been identified as novel targets for the therapeutic enhancement of insulin action in insulin-resistant disease states like type II diabetes. Therefore, in the present work we describes a study of the synthesis and structure-activity relationship (SAR) of chromene and 2,4-dimethoxy benzaldehyde-based isoxazolines, which are structurally related to potent PTPase inhibitors. Compounds 5-7 and 10-19 were synthesized via 1,3-dipolar cycloaddition reaction and evaluated against PTPase enzyme in vitro. Compounds 10, 14, and 19 displayed significant inhibitory activity with IC50 values of 69, 88, and 62.7 μM, respectively. Active compounds 10, 11, 14-16, and 19 were also tested in the STZ-S in vivo assay model, and compounds 10, 14, and 19 were found to be active.
Synthesis and SAR study of simple aryl oximes and nitrofuranyl derivatives with potent activity against Mycobacterium tuberculosis
Calixto, Stephane Lima,Carvalho, Guilherme da Silva Louren?o,Coimbra, Elaine Soares,Granato, Juliana da Trindade,Louren?o, Maria Cristina da Silva,Wardell, James,da Costa, Cristiane Fran?a,de Souza, Marcus Vinicius Nora
, p. 12 - 20 (2020/02/06)
Background: Oximes and nitrofuranyl derivatives are particularly important compounds in medicinal chemistry. Thus, many researchers have been reported to possess antibacterial, antiparasitic, insecticidal and fungicidal activities. Methods: In this work, we report the synthesis and the biological activity against Mycobacterium tuberculosis H37RV of a series of fifty aryl oximes, ArCH=N-OH, I, and eight nitrofuranyl compounds, 2-nitrofuranyl-X, II. Results: Among the oximes, I: Ar = 2-OH-4-OH, 42, and I: Ar = 5-nitrofuranyl, 46, possessed the best activity at 3.74 and 32.0 μM, respectively. Also, 46, the nitrofuran compounds, II; X = MeO, 55, and II: X = NHCH2Ph, 58, (14.6 and 12.6 μM, respectively), exhibited excellent biological activities and were non-cytotoxic. Conclusion: The compound 55 showed a selectivity index of 9.85. Further antibacterial tests were performed with compound 55 which was inactive against Enterococcus faecalis, Klebisiella pneumonae, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhymurium and Shigel-la flexneri. This study adds important information to the rational design of new lead anti-TB drugs. Structure-activity Relationship (SAR) is reported.
A Threonine-Forming Oxazetidine Amino Acid for the Chemical Synthesis of Proteins through KAHA Ligation
Baldauf, Simon,Schauenburg, Dominik,Bode, Jeffrey W.
supporting information, p. 12599 - 12603 (2019/08/01)
α-Ketoacid-hydroxylamine (KAHA) ligation allows the coupling of unprotected peptide segments through the chemoselective formation of an amide bond. Currently, the most widely used variant employs a 5-membered cyclic hydroxylamine that forms a homoserine ester as the primary ligation product. In order to directly form amide-linked threonine residues at the ligation site, we prepared a new 4-membered cyclic hydroxylamine building block. This monomer was applied to the synthesis of wild-type ubiquitin-conjugating enzyme UbcH5a (146 residues) and Titin protein domain TI I27 (89 residues). Both the resulting UbcH5a and the variant with two homoserine residues showed identical activity to a recombinant variant in a ubiquitination assay.
