730949-85-6Relevant articles and documents
Fluorine-containing 6,7-dialkoxybiaryl-based inhibitors for phosphodiesterase 10 A: Synthesis and in vitro evaluation of inhibitory potency, selectivity, and metabolism
Schwan, Gregor,Barbar Asskar, Ghadir,Hoefgen, Norbert,Kubicova, Lenka,Funke, Uta,Egerland, Ute,Zahn, Michael,Nieber, Karen,Scheunemann, Matthias,Straeter, Norbert,Brust, Peter,Briel, Detlef
supporting information, p. 1476 - 1487 (2014/07/21)
Based on the potent phosphodiesterase 10 A (PDE10A) inhibitor PQ-10, we synthesized 32 derivatives to determine relationships between their molecular structure and binding properties. Their roles as potential positron emission tomography (PET) ligands were evaluated, as well as their inhibitory potency toward PDE10A and other PDEs, and their metabolic stability was determined in vitro. According to our findings, halo-alkyl substituents at position 2 of the quinazoline moiety and/or halo-alkyloxy substituents at positions 6 or 7 affect not only the compounds′ affinity, but also their selectivity toward PDE10A. As a result of substituting the methoxy group for a monofluoroethoxy or difluoroethoxy group at position 6 of the quinazoline ring, the selectivity for PDE10A over PDE3A increased. The same result was obtained by 6,7-difluoride substitution on the quinoxaline moiety. Finally, fluorinated compounds (R)-7-(fluoromethoxy)-6-methoxy-4-(3-(quinoxaline-2-yloxy)pyrrolidine-1-yl) quinazoline (16 a), 19 a-d, (R)-tert-butyl-3-(6-fluoroquinoxalin-2-yloxy) pyrrolidine-1-carboxylate (29), and 35 (IC50 PDE10A 11-65 nM) showed the highest inhibitory potential. Further, fluoroethoxy substitution at position 7 of the quinazoline ring improved metabolic stability over that of the lead structure PQ-10. Fluor your health: Phosphodiesterase 10 A (PDE10A) has emerged as an attractive target for the development of 18F-labelled brain imaging agents for positron emission tomography. A series of fluorinated dialkoxybiaryl compounds were synthesized and evaluated as PDE10A inhibitors, assisted by QSAR docking studies. The 7-fluoromethoxy derivative appears to be a promising candidate for further development.
Cytotoxic potential of novel 6,7-dimethoxyquinazolines
Yadav, Mange R.,Grande, Fedora,Chouhan, Bishram S.,Naik, Prashant P.,Giridhar, Rajani,Garofalo, Antonio,Neamati, Nouri
experimental part, p. 231 - 243 (2012/03/26)
Herein, we report the synthesis and cytotoxicity of a series of substituted 6,7-dimethoxyquinazoline derivatives. The cytotoxic activity of all synthesized compounds has been evaluated against HCT116p53+/+ and HCT116p53 -/- colon cancer cells and a HEY ovarian cancer cell line naturally resistant to cisplatin. Nine of the tested compounds showed significant cytotoxicity in all cell lines at 10 μM. The most promising derivative (7c) showed IC50values of 0.7 and 1.7 μM in the two colon cancer cell lines.
A novel microwave-assisted green synthesis of condensed 2-substituted-pyrimidin-4(3H)-ones under solvent-free conditions
Jain, Kishor S.,Bariwal, Jitender B.,Phoujdar, Manisha S.,Nagras, Madhuri A.,Amrutkar, Rakesh D.,Munde, Manoj K.,Tamboli, Riyaj S.,Khedkar, Samrat A.,Khiste, Rahul H.,Vidyasagar, Nikhil C.,Dabholkar, Vinit V.,Kathiravan
body text, p. 178 - 185 (2009/07/19)
A rapid microwave-assisted green chemical synthesis of condensed 2-substituted-pyrimidin-4(3H)-ones 3, 4, and 5 involving the condensation of a variety of nitriles with o-aminoesters of thiophene 2a-e, benzene 2f, dimethoxybenzene 2g and quinazolinone 2h in the presence of catalytic amount of HCl alone or with the Lewis acid AlCl3 under solvent-free conditions, is described for the first time. This novel and clean one-pot methodology, which is characterized by very short reaction times and easy workup procedures, can be exploited to generate a diverse library of condensed pyrimidine heterocycles.
