319014-94-3

Upstream product

• 2746-25-0 p-Methoxybenzyl bromide 
• 138585-08-7 (4-((tert-butyldimethylsilyl)oxy)phenyl)methanol 
• 148869-66-3 4-[N-(1,2,4-triazol-4-yl)amino]benzonitrile 
• 536974-64-8 4-[(4-benzyloxybenzyl)[1,2,4]triazol-4-ylamino]benzonitrile 
• 1194-02-1 4-fluorobenzonitrile 

Relevant academic research and scientific papers

4-(((4-Iodophenyl)methyl)-4H-1,2,4-triazol-4-ylamino)-benzonitrile: A Potential Imaging Agent for Aromatase

Aromatase (CYP19) is a rate-limiting enzyme that catalyzes the biosynthesis of estrogens. Imaging agents based on aromatase inhibitors (AIs) have been developed for a PET/SPECT study. A series of compounds was synthesized based on YM511, which has previou

Dual aromatase-steroid sulfatase inhibitors

By introducting the steroid sulfatase inhibitory pharmacophore into aromatase inhibitor 1 (YM511), two series of single agent dual aromatase-sulfatase inhibitors (DASIs) were generated. The best DASIs in'vitro (JEG-3 cells) are 5, (IC50(aromatase) = 0.82 nM; IC 50(sulfatase) = 39 nM), and 14, (IC50(aromatase) = 0.77 nM; IC50(sulfatase) = 590 nM). X-ray crystallography of 5, and docking studies of selected compounds into an aromatase homology model and the steroid sulfatase crystal structure are presented. Both 5 and 14 inhibit aromatase and sulfatase in PMSG pretreated adult female Wistar rats potently 3 h after a single oral 10 mg/kg dose. Almost complete dual inhibition is observed for 5 but the levels were reduced to 85% (aromatase) and 72% (sulfatase) after 24 h. DASI 5 did not inhibit aldosterone synthesis. The development of a potent and selective DASI should allow the therapeutic potential of dual aromatase-sulfatase inhibition in hormone-dependent breast cancer to be assessed.

First dual aromatase-steroid sulfatase inhibitors

Aromatase inhibitors in clinical use block the biosynthesis of estrogens. Hydrolysis of estrone 3-sulfate by steroid sulfatase is an important additional source of tumor estrogen, and blockade of both enzymes should provide a more effective endocrine therapy. Sulfamoylated derivatives of the aromatase inhibitor YM511 inhibited sulfatase and aromatase in JEG-3 cells with respective IC50 values of 20-227 and 0.82-100 nM (cf. letrozole, 0.89 nM). One dual inhibitor was potent against both enzymes in vivo, validating the concept.

PHENYL SULFAMATE DERIVATIVES

Phenyl sulfamate derivatives represented by the following formula or salts thereof have a powerful inhibitory effect on steroid sulfatase and are hence useful for the prophylaxis or treatment of diseases associated with steroids such as estrogens, such as breast cancer, corpus uteri cancer, endometrial hyperplasia, infertility, endometriosis, adenomyosis uteri, autoimmune disease, dementia or Alzheimer's disease. wherein R1 and R2 each independently represent a hydrogen atom or a lower alkyl group; R3 represents a hydrogen atom, a halogen atom, a lower alkyl group, -OSO2NR1R2, a lower alkanoylamino group, a nitro group or a cyano group; and A represents a substituted or unsubstituted phenyl group, a group of the formula -X-NR4R5, or the like.