52798-36-4

Upstream product

• 6940-50-7 4-bromo-DL-mandelic acid 
• 557-21-1 zinc(II) cyanide 
• 127709-20-0 α-hydroxy-(p-bromophenyl)-acetic acid methyl ester 
• 67-56-1 methanol 
• 121986-03-6 α-(4-cyanophenyl)-α-hydroxyacetonitrile 
• 105-07-7 4-cyanobenzaldehyde 

Relevant academic research and scientific papers

Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists

GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76percent inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1, exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model.

BIARYL UREA DERIVATIVE OR SALT THEREOF, AND MANUFACTURING AND APPLICATION OF SAME

The present invention discloses a biaryl urea RORγt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORγt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORγt-related disease.

Synthesis of dichlorophenyl-, cyanophenyl-and quinolinyl-substituted α-ethoxyacetic acids and derivatives, via α-hydroxyarylacetic acids

A synthetic approach to novel series of α-ethoxy-α-phenylacetamides and α-ethoxy-α-quinolinylacetamides was developed. Aryl aldehydes were converted to cyanohydrins, which were then hydrolyzed or alcoholyzed. Following ethylation of the α-hydroxy group, p

Process for producing α-hydroxy-carbonyl compound

The invention provides a process for producing an α-hydroxy-carbonyl compound or an α-protected hydroxy-carbonyl compound by reacting a carbonyl compound (I) with a compound (II) and a compound (III). The compounds (I), (II) and (III) are defined below. R1, R2, R3and R4are an organic group. PG is a protective group for hydroxy group. Y is R4N, S or O. The product is useful in pharmacology.