14034-90-3

Upstream product

• 1077-58-3 2-tert-butylbenzoic acid 
• 873056-28-1 2-(tert-butyl)-5-nitrobenzonitrile 
• 1074-92-6 1-tert-butyl-2-methyl-benzene 
• 3282-56-2 4-tert-butylnitrobenzene 
• 6310-17-4 2-bromo-1-tert-butyl-4-nitrobenzene 

Downstream Products

• 14034-93-6 5-Dimethylamino-2-tert.-butyl-benzoesaeure 
• 14034-91-4 5-Amino-2-tert.-butyl-benzoesaeure 
• 873056-33-8 methyl 2-tert-butyl-5-nitrobenzoate 
• 873056-38-3 (2-tert-butyl-5-aminophenyl)methanol 
• 873056-34-9 methyl 2-tert-butyl-5-aminobenzoate 
• 873050-23-8 N-(4-tert-butyl-3-(hydroxymethyl)phenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide 
• 873054-55-8 5-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-2-tert-butyl-benzoic acid methyl ester 
• 14034-92-5 5-Brom-2-tert.-butyl-benzoesaeure 
• 14034-94-7 5-Chlor-2-tert.-butyl-benzoesaeure 

Relevant academic research and scientific papers

Structural optimization and structure–activity relationship of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase

Human dihydroorotate dehydrogenase (hDHODH), one of the attractive targets for the development of immunosuppressive drugs, is also a potential target of anticancer drugs and anti-leukemic drugs. The development of promising hDHODH inhibitors is in high demand. Based on the unique binding mode of our previous reported 4-thiazolidinone derivatives, via molecular docking method, three new series 4-thiazolidinone derivatives were designed and synthesized as hDHODH inhibitors. The preliminary structure–activity relationship was investigated. Compound 9 of biphenyl series and compound 37 of amide series displayed IC50 values of 1.32 μM and 1.45 μM, respectively. This research will provide valuable reference for the research of new structures of hDHODH inhibitors.

Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases

The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.

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.

MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS

The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES

The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.