99512-72-8

Upstream product

• 50332-66-6 3-nitro-quinolin-4-ol 
• 125836-07-9 3-nitro-4-(1H)-quinolone 
• 152904-43-3 (E)-2-(2-nitrovinylamino)benzoic acid 
• 121845-92-9 2-<2-nitroethylideneamino>benzoic acid 
• 118-92-3 anthranilic acid 

Downstream Products

• 234-11-7 oxazolo[4,5-c]quinoline 
• 15260-89-6 2-Methyl-oxazolo<4.5-c>-chinolin 
• 103862-98-2 N-(4-hydroxyquinolin-3-yl)acetamide 
• 256922-53-9 2-propyl[1,3]thiazolo[4,5-c]quinolin-4-amine 
• 1421771-62-1 C₂₀H₁₉N₃O₂S₂ 
• 1421771-49-4 C₂₀H₁₇N₃OS 
• 1198154-30-1 1H-4-oxa-1,9-diaza-phenanthren-2-one 

Relevant academic research and scientific papers

Discovery of N -(2,4-Di- tert -butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, Ivacaftor), a potent and orally bioavailable CFTR potentiator

Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screening in NIH-3T3 cells expressing the F508del-CFTR mutation. Extensive medicinal chemistry and iterative structure-activity relationship (SAR) studies to evaluate potency, selectivity, and pharmacokinetic properties resulted in the identification of N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (VX-770, 48, ivacaftor), an investigational drug candidate approved by the FDA for the treatment of CF patients 6 years of age and older carrying the G551D mutation.

Toll-like receptor-8 agonistic activities in C2, C4, and C8 modified thiazolo[4,5-c]quinolines

Toll-like receptor (TLR)-8 agonists typified by the 2-alkylthiazolo[4,5-c] quinolin-4-amine (CL075) chemotype are uniquely potent in activating adaptive immune responses by inducing robust production of T helper 1-polarizing cytokines, suggesting that TLR8-active compounds could be promising candidate vaccine adjuvants, especially for neonatal vaccines. Alkylthiazoloquinolines with methyl, ethyl, propyl and butyl groups at C2 displayed comparable TLR8-agonistic potencies; activity diminished precipitously in the C2-pentyl compound, and higher homologues were inactive. The C2-butyl compound was unique in possessing substantial TLR7-agonistic activity. Analogues with branched alkyl groups at C2 displayed poor tolerance of terminal steric bulk. Virtually all modifications at C8 led to abrogation of agonistic activity. Alkylation on the C4-amine was not tolerated, whereas N-acyl analogues with short acyl groups (other than acetyl) retained TLR8 agonistic activity, but were substantially less water-soluble. Immunization in rabbits with a model subunit antigen adjuvanted with the lead C2-butyl thiazoloquinoline showed enhancements of antigen-specific antibody titers.

HETEROCYCLIC DERIVATIVES

The present invention relates to heterocyclic derivatives, and more particularly, to novel heterocyclic derivatives useful for the preparation of medicaments for treating diseases related to uric acid.