COA of Formula: C7H8N2O. Recently I am researching about BIOLOGICAL EVALUATION; RECOGNITION; DERIVATIVES; ANTAGONISTS; ACTIVATION; DISCOVERY, Saw an article supported by the Slovenian Research AgencySlovenian Research Agency – Slovenia [P1-0208, BI-US/18-20-087]. Published in ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER in ISSY-LES-MOULINEAUX ,Authors: Dolsak, A; Svajger, U; Lesnik, S; Konc, J; Gobec, S; Sova, M. The CAS is 88-68-6. Through research, I have a further understanding and discovery of 2-Aminobenzamide
Toll-like receptors (TLRs) are promising targets for treatment of viral infections, autoimmune diseases, and cancers. Here, two new series of selective small-molecule TLR7 agonists with novel scaffolds and good selectivity over TLR8 are described, some with potencies in the low micromolar range. 8-Hydroxy-1-isobutylchromeno[3,4-d]imidazol-4(1H)-one (26) from the first series was designed and synthesized on the basis of previously described TLR7 antagonist 2, and is shown to be a selective TLR7 agonist (EC50, 1.8 mu M). The second series was based on 2-(trifluoromethyl)quinolin-4-amine and 2-(trifluoromethyl) quinazolin-4-amine scaffolds, which were defined according to our in-house ligand-based virtual screening protocol. Further synthesis of a focused library of analogs, biological evaluation, and docking studies provided systematic exploration of the structure-activity relationships, which indicate that a secondary or tertiary amine with smaller flexible alkyl substituents up to three carbon atoms in length, or bulkier rigid aliphatic rings is required at position 4 on 2-(trifluoromethyl)quinoline/quinazoline scaffold for potent TLR7 agonist activity. The influence of selected TLR7 agonists on cytokine production is also reported showing that N-cyclopropyl-2-(trifluoromethyl)quinazolin-4-amine (46) is able to induce increased levels of IL-6 and IL-8. These data demonstrate successful in-silico definition of novel TLR7 versus TLR8-selective compounds as promising chemical probes for further development of potent small-molecule immunomodulators. (C) 2019 Elsevier Masson SAS. All rights reserved.
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Reference:
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