87236-19-9

Upstream product

• 1309366-42-4 methyl 5-(2-hydroxyphenyl)-1-isopropyl-1H-imidazole-4-carboxylate 
• 90-02-8 salicylaldehyde 

Relevant academic research and scientific papers

Selective Toll-like receptor 7 agonists with novel chromeno[3,4-d]imidazol-4(1H)-one and 2-(trifluoromethyl)quinoline/ quinazoline-4-amine scaffolds

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 μM). 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.

Simple and efficient copper(I)-catalyzed access to three versatile aminocoumarin-based scaffolds using isocyanoacetate

An efficient method has been developed for the one-pot copper(I)-catalyzed synthesis of 3-aminocoumarin and its derivatives, such as 3-substituted methylideneaminocoumarins and chromeno[3,4-d]imidazol-4(1H)-ones. Significantly, the strategy presents a straightforward and efficient approach to constructing biologically useful molecular scaffolds.

IMIDAZOLE DERIVATIVES AS PHOSPHODIESTERASE VII INHIBITORS

The invention relates to imidazole derivatives of formula (I), wherein R means H, A, benzyl, indane-5-yl, 1,2,3,4-tetrahydro-naphthaline-5-yl, dibenzothiophene-2-yl or phenyl that is unsubstituted or substituted once, twice or three times by means of Hal, A, A-CO-NH, benzyloxy, alkoxy, COOH or COOA, R means H or A, X means O or S, Hal means F, Cl, Br or I and A means alkyl with 1 to 6 C-atoms. The invention also relates to the physiologically acceptable salts and/or solvates thereof acting as phosphodiesterase VII inhibitors. The invention further relates to the use thereof for producing a medicament.