118306-90-4

Usage

Chemical Class

Phthalazines

Mechanism of Action

Selective Estrogen Receptor Modulator (SERM)

Effects

Exhibits both antiestrogenic and estrogenic effects

Potential Applications

Treatment of hormone-dependent cancers (e.g. breast cancer), osteoporosis, osteoarthritis, and neuroprotection

抗癌特性

Inhibits the growth of cancer cells by blocking the estrogen receptor

研究结果

Shown to have promising results in anti-cancer properties

Upstream product

• 201806-33-9 4-(4-chloro-1-phthalazinyl)-1-piperazinecarboxylic acid tert-butyl ester 
• 223587-51-7 4-chloro-1-(1-piperazinyl)phthalazine 
• 205259-55-8 4-(1-phthalazinyl)-1-piperazinecarboxylic acid tert-butyl ester 
• 4752-10-7 1,4-dichlorophthalazine 

Relevant academic research and scientific papers

Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1 antagonists

A series of pyridazinylpiperazines were synthesized and evaluated for VR1 antagonist activity in order to improve upon the pharmaceutical and pharmacological properties of BCTC. A structurally biased chemical library of pyridazinylpiperazine analogs was prepared in an effort to improve the pharmaceutical and pharmacological profile of the lead compound N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H) -carboxamide (BCTC). The library was evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH 5.5-induced (pH) FLIPR assays in a human VR1-expressing HEK293 cell line. The most potent VR1 antagonists were found to have IC50 values in the range of 9-200 nM with improved pharmaceutical and pharmacological profiles versus the lead BCTC. These compounds represent possible second-generation BCTC analogs.

Potent and Selective Inhibitors of Platelet-Derived Growth Factor Receptor Phosphorylation. 3. Replacement of Quinazoline Moiety and Improvement of Metabolic Polymorphism of 4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline Derivatives

We have previously reported that a series of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives were potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation and demonstrated several biological effects such as suppression of neointima formation following balloon injury in rat carotid artery by oral administration. Here, we investigated structure-activity relationships of the 6,7-dimethoxyquinazolinyl moiety. In regard to 6,7-dimethoxy groups, ethoxy analogues showed potent activity (IC50 of 16b is 0.04 μM; IC50 of 17a is 0.01 μM) and further extension of the alkyl group reduced activity. Interestingly, methoxyethoxy (IC50 of 16j is 0.02μM; IC50 of 17h is 0.01 μM) and ethoxyethoxy (IC50 of 17j is 0.02 μM) analogues showed the most potent activity, suggesting that the inserted oxygen atom significantly interacts with β-PDGFR. Among tricyclic quinazoline derivatives, the 2-oxoimidazo[4,5-e]quinazoline derivative 21a showed potent activity (IC 50 = 0.10 μM). Regarding replacements of quinazoline by other heterocyclic rings, pyrazolo[3,4-d]pyrimidine (39a, IC50 = 0.17 μM) and quinoline (IC50 of 40a is 0.18 μM; IC50 of 40b is 0.09 μM) derivatives showed potent activity. Isoquinoline and some pyridopyrimidine derivatives were completely inactive; therefore, 1-aza has an important role. Also 7-aza and 8-aza substitution on the parent quinazoline ring has a detrimental effect on the interaction with β-PDGFR. We also demonstrated that the substituents on the quinazoline ring possess major consequences for metabolic polymorphism. Although there existed extensive metabolizers and poor metabolizers in Sprague-Dawley rats administrated 6,7-dimethoxyquinazoline derivatives (1b and 1c), 6-(2-methoxy)ethoxy-7-methoxyquinazoline analogue 16k showed no metabolic polymorphism.