1172617-18-3

Basic information

• Product Name: 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(2-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine
• CAS NO: 1172617-18-3
• Molecular Weight: 436.535
• Mol File: 1172617-18-3.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(2-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(2-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine(1172617-18-3)
• EPA Substance Registry System: 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(2-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine(1172617-18-3)

Safety Data

• Hazardous Substances Data: 1172617-18-3(Hazardous Substances Data)

Upstream product

• 141184-47-6 1-methoxy-2-cyclopentyloxy-4-(1-hydroxyethyl)benzene 
• 141184-48-7 1-[3-(cyclopentyloxy)-4-methoxyphenyl]-ethanone 
• 67387-76-2 3-cyclopentyloxy-4-methoxybenzylaldehyde 
• 579-75-9 2-Methoxybenzoic acid 
• 7466-54-8 2-methoxybenzoylhydrazine 
• 61019-31-6 potassium [N'-(2-methoxybenzoyl)]hydrazine carbodithioate 
• 621-59-0 isovanillin 
• 61019-26-9 4-amino-5-(2-methoxyphenyl)-2,3-dihydro-4H-1,2,4-triazole-3-thione 
• 141333-65-5 2-bromo-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone 

Relevant articles and documents

Safety and Efficacy of New 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine Analogs as Potential Phosphodiesterase-4 Inhibitors in NIH-3T3 Mouse Fibroblastic Cells

A novel series of potential phosphodiesterase-4 (PDE-4) inhibitors, 6-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, were developed. Different concentrations of the synthesized compounds were tested on cultured NIH-3T3 cells to determine their safety and efficacy in NIH-3T3 mouse fibroblastic cells in comparison with rolipram, a selective PDE-4 inhibitor. The viability of cells was determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-di-phenyltetrazoliumbromide (MTT) assay. The PDE inhibition rate was measured indirectly by determination of concentrations of extracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) using enzyme-linked immunoassay technique. The results showed that all tested compounds caused a marked increase in the concentration of cAMP, whereas the concentration of cGMP stayed approximately unchanged. The cytotoxic IC50 of all synthesized compounds was approximately twofold greater than their required concentration for inhibition of PDE-4 (in terms of elevation of cAMP), and thus, these structures could be used to develop potent and safe inhibitors of PDE-4 enzyme.

Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors

An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively.