1006657-20-0Relevant articles and documents
Ferrocenyl, Alkyl, and Aryl-Pyrido[2,3-d]Pyrimidines as Vasorelaxant of Smooth Muscle of Rat Aorta via cAMP Conservation Through Phosphodiesterase Inhibition
Arellano, Ivonne,Rodríguez-Ramos, Fernando,González-Andrade, Martín,Navarrete, Andrés,Sharma, Manju,Rosas, Noé,Sharma, Pankaj
, p. 1147 - 1154 (2016)
New pyrido[2,3-d]pyrimidines 11, 12, 13, and 21 have been synthesized. The vasorelaxant effect on smooth muscle isolated from rat aorta, via PDEs inhibition, of these compounds along with other pyrido[2,3-d]pyrimidines 14, 15, 16, 17, 18, 19, 20 reported earlier by our group, has also been determined. These pyrido[2,3-d]pyrimidines 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 were synthesized by the reaction of ferrocenyl-ethynyl ketones (1, 2, 3, 4) or α-alkynyl ketones (5, 6, 7, 8, 9, 10) with 6-amino-1,3-dimethyluracil using [Ni(CN)4]?4as an active catalytic species, formed in situ in a Ni(CN)2/NaOH/H2O/CO/KCN aqueous system. Evaluation of the vasorelaxant effect of compounds 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 demonstrated that all compounds relax the tissue in a concentration-dependent manner. The structural changes do not alter the effectiveness; however, there are differences related to potency expressed as EC50. Compounds 12 (7-ferrocenyl-1,3-dimethyl-5-(m-tolyl)-pyrido[2,3-d]pyrimidine) and 13 (7-ferrocenyl-1,3-dipropyl-5-(4-metoxyphenyl)-pyrido[2,3-d]pyrimidine) were the most potent compounds, even more than rolipram, reference drug; the EC50was 0.41 ± 0.02 μM and 0.81 ± 0.11 μM for 12 and 13, correspondingly. The EC50of compounds 15 (7-ferrocenyl-1,3-dimethyl-5-phenyl-pyrido[2,3-d]pyrimidine), 14 (7-ferrocenyl-5-(3,5-dimethoxyphenyl)-1,3-dimethylpyrido[2,3-d]pyrimidine), and 19 (5-n-butyl-7-ethyl-1,3-dimethylpyrido[2,3-d]pyrimidine) was similar to EC50of rolipram. Compounds 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 significantly induce concentration-dependent vasorelaxation in endothelium-intact aortic rings. In addition, the relaxation responses to each compound in either endothelium-intact or endothelium denuded aortic rings were comparable, suggesting that removal of the functional endothelium has no significant influence on its intrinsic vasorelaxant activity. In vitro capability of conserving cyclic-AMP or cyclic-GMP (adenosine and guanosine 3′, 5′-cyclic monophosphate) via PDE inhibition for compounds 12, 13, 14, 15 and 19 was evaluated. Compounds 15 and 19 show the highest percent inhibition effect (94.83% and 83.98%, respectively) for the decomposition of c-AMP. Docking studies showed that the compound 15 was selective for the inhibition of PDE-4.
First catalytic synthesis of 7-ferrocenyl-2,4-dioxopyrido [2,3-d]pyrimidines derivatives in water
Arellano, Ivonne,Sharma, Pankaj,Arias, José Luis,Toscano, Alfredo,Cabrera, Armando,Rosas, Noé
, p. 294 - 299 (2008/10/09)
The reaction of 6-amino-1,3-dimethyluracil with substituted ferrocenyl-ketoalkynes using nickel cyanide as homogeneous catalyst precursor in aqueous alkaline medium, affords 5-substituted-7-ferrocenyl-dioxopyrido[2,3-d]pyrimidines derivatives, in moderate
