40746-64-3Relevant articles and documents
Kinetics and mechanism of 1-phenyl-5-methyltetrazole nitration in HNO3–H2SO4system
Ostrovskii,Enin,Boiko,Trifonov,Popova,Pavlyukova, Yu. N.,Dolmatov, V. Yu.
, p. 1674 - 1680 (2016)
At nitration of 1-phenyl-5-methyltetrazole with nitric acid in aqueous solutions of sulfuric acid of 84–96% concentration a mixture forms of 1-(4-nitrophenyl)- and 1-(3-nitrophenyl)-5-methyltetrazoles in a ratio 60: 40. According to kinetic data, the tetrazole ring in the substrate is present in a protonated form. The protonation constants of 1-(4-carboxyphenyl)-5-methyltetrazole at the tetrazole ring and the carboxy group were determined. The Hammet’s electronic constant of the protonated tetrazole ring was calculated.
Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency
De Lucca, George V.,Ui, Tae Kim,Vargo, Brian J.,Duncia, John V.,Santella III, Joseph B.,Gardner, Daniel S.,Zheng, Changsheng,Liauw, Ann,Wang, Zhang,Emmett, George,Wacker, Dean A.,Welch, Patricia K.,Covington, Maryanne,Stowell, Nicole C.,Wadman, Eric A.,Das, Anuk M.,Davies, Paul,Yeleswaram, Swamy,Graden, Danielle M.,Solomon, Kimberly A.,Newton, Robert C.,Trainor, George L.,Decicco, Carl P.,Ko, Soo S.
, p. 2194 - 2211 (2007/10/03)
Starting with our previously described20 class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC50 = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC50 = 41 nM) and its oral bioavailability in mice (20% F) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase I clinical trials.
