148869-66-3

Upstream product

• 584-13-4 4-amino-1,2,4-triazole 
• 1194-02-1 4-fluorobenzonitrile 

Downstream Products

• 537674-63-8 4-[(3-benzyloxybenzyl)[1,2,4]triazol-4-ylamino]benzonitrile 
• 537676-41-8 4-[(4-benzyloxy-3-chlorobenzyl)[1,2,4]triazol-4-ylamino]benzonitrile 
• 537677-52-4 4-[(4-benzyloxy-3-fluorobenzyl)[1,2,4]triazol-4-ylamino]benzonitrile 
• 536974-78-4 benzoic acid 2-bromo-4-{[(4-cyanophenyl)[1,2,4]triazol-4-ylamino]methyl}phenyl ester 
• 536974-64-8 4-[(4-benzyloxybenzyl)[1,2,4]triazol-4-ylamino]benzonitrile 
• 536974-79-5 4-[(2-bromo-ethyl)-[1,2,4]triazol-4-yl-amino]-benzonitrile 
• 537675-72-2 4-[(3-Bromo-propyl)-[1,2,4]triazol-4-yl-amino]-benzonitrile 
• 536974-81-9 4-[(5-Bromo-pentyl)-[1,2,4]triazol-4-yl-amino]-benzonitrile 
• 536974-65-9 4-{[2-(4-Benzyloxyphenyl)ethyl]-[1,2,4]triazol-4-yl-amino} benzonitrile 
• 536974-70-6 4-{[2-(4-benzyloxy-3-bromophenoxy)ethyl]-[1,2,4]triazol-4-ylamino}benzonitrile 
• 536974-73-9 4-({[6-(benzyloxy)naphthalen-2-yl]methyl}(4H-1,2,4-triazol-4-yl)amino)benzonitrile 
• 537674-68-3 4-[(3,4-Bis(benzyloxy)benzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole 
• 536974-98-8 4-({[6-(benzyloxy)benzoxazol-2-yl]methyl}(4H-1,2,4-triazol-4-yl)amino)benzonitrile 
• 536975-01-6 4-[(6-Benzyloxy-benzothiazol-2-ylmethyl)-[1,2,4]triazol-4-yl-amino]-benzonitrile 

Relevant academic research and scientific papers

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.

A series of transition metal coordination polymers based on a rigid bi-functional carboxylate-triazolate tecton

By utilizing the pre-designed bi-functional ligand 4-{bis(4-benzoic)amino}-4H-1,2,4-triazole (H2L), five new transition-metal-based coordination polymers, namely, {[Zn(L)]·H2O·DMA}n (1), {[Zn2(L)2]·DMF}n (2),{[Mn(L)]·DMF}n (3), {[Cd(L)]·DMA}n (4) and [Cu3(OH)2(L)2]n (5) have been constructed and structurally characterized. In 1, the tetrahedral zinc ion was incorporated in the final structure. However, complexes 2, 3 and 4 bear 1D Zn-, Mn- and Cd-chains composed of metal ions, triazole and carboxyl groups, respectively. Differently, 1D [Cu4(μ3-OH)2] chains had been stabilized in the 3D structure of 5. In addition, the luminescence or magnetic properties of 1-5 had been correspondingly investigated with the consideration of their crystal structure. The whole research results manifest that utilizing a bi-functional ligand containing carboxyl and triazole groups is an efficient building method in constructing functional CPs.

LABELING COMPOUND FOR PET

A labeling compound of the present invention includes a structure represented by formula (1) wherein X1 is 11CH3, CH218F, CF218F, 18F, 76Br or 124/sup

Synthesis of a new carbon-11-labeled sulfamate derivative as a potential PET tracer for imaging of breast cancer aromatase and steroid sulfatase expression

A carbon-11-labeled sulfamate derivative was designed and synthesized as a new potential positron-emission-tomography dual aromatase-steroid sulfatase inhibitor radiotracer for imaging of aromatase and steroid sulfatase expression in breast cancer. The ta

Bicyclic derivatives of the potent dual aromatase-steroid sulfatase inhibitor 2-bromo-4-{[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl} phenylsulfamate: Synthesis, SAR, crystal structure, and in vitro and in vivo activities

The design and synthesis of a series of bicyclic ring containing dual aromatase-sulfatase inhibitors (DASIs) based on the aromatase inhibitor (AI) 4-[(4-bromobenzyl)(4H-1,2,4-triazol-4-yl)amino] benzonitrile are reported. Biological evaluation with JEG-3 cells revealed structure-activity relationships. The X-ray crystal structure of sulfamate 23 was determined, and selected compounds were docked into the aromatase and steroid sulfatase (STS) crystal structures. In the sulfamate-containing series, compounds containing a naphthalene ring are both the most potent AI (39, IC50AROM=0.25 nm) and the best STS inhibitor (31, IC50STS=26 nm). The most promising DASI is 39 (IC50AROM= 0.25 nm, IC50STS=205 nm), and this was evaluated orally in vivo at 10 mgkg-1, showing potent inhibition of aromatase (93%) and STS (93%) after 3 h. Potent aromatase and STS inhibition can thus be achieved with a DASI containing a bicyclic ring system; development of such a DASI could provide an attractive new option for the treatment of hormone-dependent breast cancer.

Design and synthesis of carbon-11-labeled dual aromatase-steroid sulfatase inhibitors as new potential PET agents for imaging of aromatase and steroid sulfatase expression in breast cancer

Aromatase and steroid sulfatase (STS) are particularly attractive targets in the treatment of estrogen-receptor-positive breast cancer and the development of enzyme-based cancer imaging agents for the biomedical imaging technique positron emission tomography (PET). New carbon-11-labeled sulfamate derivatives were first designed and synthesized as potential PET dual aromatase-steroid sulfatase inhibitor (DASSI) radiotracers for imaging of aromatase and STS expression in breast cancer. The target tracers 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[11C]methoxyphenyl sulfamate ([11C]8a) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-[11C]methoxyphenyl sulfamate ([11C]8b) were prepared from their corresponding precursors 5-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (16) and 4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)-2-hydroxyphenyl sulfamate (21) with [11C]CH3OTf under basic conditions through the O-[11C]methylation and isolated by the reversed-phase high pressure liquid chromatography (HPLC) method in 30-45% radiochemical yields based on [11C]CO2 and decay corrected to end of bombardment (EOB). The specific activity at end of synthesis (EOS) was 111-185 GBq/μmol.

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.

Triazolylated teritiary amine compound or salt thereof

A triazolylated tertiary amine compound represented by general formula (I) or a salt thereof, having an aromatase inhibitory activity and being useful for preventing and treating breast cancer, mastopathy, endometriosis, prostatomergaly, etc., wherein A represents a single bond, lower alkylene or carbonyl; B represents lower alkyl, aryl, a 5- or 6-membered heterocyclic group, or a bicyclic fused heterocyclic group; D represents aryl, a 5- or 6-membered heterocyclic group, or a bicyclic fused heterocyclic group; and E represents 4H-1,2,4-triazolyl, 1H-1,2,4-triazolyl or 1H-1,2,3-triazolyl.

Studies on aromatase inhibitors. I. Synthesis and biological evaluation of 4-amino-4H-1,2,4-triazole derivatives

Various 4-N-substituted amino-4H-1,2,4-triazole derivatives were synthesized and evaluated for aromatase-inhibitory activity (in vitro) and for pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis- inhibitory activity (in vivo). The 4-(4-cya