202475-60-3

Usage

Uses

Used in Autoimmune Type 1 Diabetes Treatment:
JAK3 INHIBITOR I is used as a therapeutic agent for delaying or preventing the development of autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. It suppresses the proliferation of short-term cultured NOD CD4+ T cells through induction of apoptosis, while promoting the survival of a particular population of long-term cultured cells.
Used in Neurodegenerative Disease Treatment:
In a mouse ALS model, JAK3 INHIBITOR I is used as a neuroprotective agent, increasing survival rates and potentially slowing down the progression of the disease.
Used in Inflammatory Disease Treatment:
JAK3 INHIBITOR I is used as an anti-inflammatory agent in mouse models of peritonitis, colitis, cellulitis, and systemic inflammatory response syndrome. It exhibits potent anti-inflammatory activity, which may help in managing these conditions.
Used in Cardiovascular Disease Treatment:
JAK3 INHIBITOR I is used as a protective agent against myocardial ischemia and reperfusion injury in mouse models. It displays protective effects, which may help in reducing the damage caused by these conditions.
Used in Cancer Treatment:
JAK3 INHIBITOR I is used as an inhibitor of human glioblastoma cell adhesion and invasion. By inhibiting JAK3, it may help in reducing the aggressiveness and metastatic potential of glioblastoma cells.

References

1) Narla et al. (1998), Inhibition of human glioblastoma cell adhesion and invasion by 4-(4’-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) and 4-(3’-bromo-4’-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P154); Mol. Clin. Cancer Res., 4 2463 2) Trieu et al. (2000), A specific inhibitor of janus kinase-3 increases survival in a transgenic mouse model of amyotrophic lateral sclerosis; Biochem. Biophys. Res. Commun., 267 22 3) Cetkovic-Cvrlje et al. (2003), Targeting JAK3 with JANEX-1 for prevention of autoimmune type 1 diabetes in NOD mice; Clin. Immunol., 106 213 4) Uckun et al. (2008), Anti-inflammatory activity profile of JANEX-1 in preclinical animal models; Bioorg. Med. Chem., 16 1287 5) Oh et al. (2013), Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice; Exp. Mol. Med., 45 e23

Upstream product

• 123-30-8 4-amino-phenol 
• 13790-39-1 6,7-dimethoxy-4-chloroquinazoline 
• 5004-88-6 4,5-dimethoxyanthranilamide 
• 4998-07-6 4,5-dimethoxy-2-nitro-benzoic acid 
• 4959-60-8 4,5-dimethoxy-2-nitrobenzamide 
• 13794-72-4 3H-6,7-dimethoxyquinazolin-4-one 

Downstream Products

• 1348589-21-8 diethyl (4-(6,7-dimethoxyquinazolin-4-ylamino)phenoxy)methylphosphonate 

Relevant academic research and scientific papers

QUINAZOLINE DERIVATIVES AS ECTONUCLEOTIDE PYROPHOSPHATASE PHOSPHODIESTERASE 1 INHIBITORS

The present disclosure provides certain quinazoline compounds that inhibit ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzymatic activity and are therefore useful for the treatment of diseases and conditions modulated at least in part by ENPP1. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity

Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clinically approved multi-kinase inhibitors that target RET as a secondary pharmacology but additional activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clinical need for more specific RET kinase inhibitors. Herein we report our efforts towards identifying a potent and selective RET inhibitor using vandetanib 1 as the starting point for structure-based drug design. Phenolic anilinoquinazolines exemplified by 6 showed improved affinities towards RET but, unsurprisingly, suffered from high metabolic clearance. Efforts to mitigate the metabolic liability of the phenol led to the discovery that a flanking substituent not only improved the hepatocyte stability, but could also impart a significant gain in selectivity. This culminated in the identification of 36; a potent RET inhibitor with much improved selectivity against KDR.

4-(4′-hydroxyphenyl) amino-6,7-dimethoxyquinazoline to prevent development of colorectal cancer

The present invention is directed to a method of preventing the development or recurrence of colorectal cancer in a mammal comprising administering to the mammal, an effective cancer preventative amount of 4-(4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoli

Quinazoline formulations and therapeutic use thereof

Pharmaceutical compositions for parenteral administration of poorly soluble quinazoline compounds in the form of microemulsions or micellar solutions are described. The compositions are useful in treating patients suffering from cancer or having allergic

Treatment of atherosclerosis in apolipoprotein E-deficient mice with 4- (3'-bromobenzoyl)-6,7-dimethoxyquinazoline (WHI-P164), a potent inhibitor of triglyceride synthesis

We identified a novel organic compound, 4-(3'-bromobenzoyl)-6,7- dimethoxyquinazoline (compound WHI-P164), as a potent inhibitor of triglyceride (TG) synthesis. In an in vitro model of lipid synthesis, WHI- P164 (but not any one of the three structurally similar control dimethoxyquinazoline compounds) inhibited the accumulation of TG-rich intracellular lipid droplets in Caco-2 human intestinal cells in a concentration-dependent fashion. WHI-P164 caused no acute toxicity associated with morbidity or mortality in mice when administered at dose levels ranging from 0.5 to 80 mg/kg. In pharmacokinetic studies in mice, WHI-P164 was rapidly eliminated from plasma with a terminal elimination half-life of 26.1 ± 1.3 min after intraperitoneal administration and 33.3 ± 11.3 min after intravenous administration. Treatment with 40 mg/kg WHI-P164 (but not one of three structurally similar control dimethoxyquinazoline compounds) administered intraperitoneally once daily for 7 consecutive treatment days blocked the in vivo hepatic TG synthesis in both apoE-deficient and wild-type C57B1/6 mice. In apoE-deficient mice maintained on a high-fat/high- cholesterol Western diet, WHI-P164 substantially reduced the lipid accumulation in the liver after 7 days of treatment and the lipid accumulation in the aorta after 1 month of treatment. Our results in apoE- deficient mice show that lipid accumulation in hepatocytes and foam cells are related events, and inhibiting TG synthesis with WHI-P164 offers an effective means to treat atherosclerosis.