Study of ALM-802 orto-alkoxi analogues cardiotropic activity
G. V. Mokrov,
A. M. Likhosherstov,
V. V. Barchukov,
V. N. Stolyaruk,
I. B. Tsorin,
M. B. Vititnova,
S. A. Kryzhanovskiy,
T. A. Gudasheva https://doi.org/10.37489/2587-7836-2019-4-18-23
Abstract
New ortho-alkoxy analogs of the compound ALM-802 1a (N1-(2-methoxybenzyl)-N2-[2-((2-methoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride) and 1b (N1-(2-ethoxybenzyl)-N2-[2-((2-ethoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride), which differ from it by the presence of alkoxy groups in the phenyl rings only in the ortho positions. It was established that these structural changes lead to the disappearance of anti-ischemic activity. At the same time, antiarrhythmic activity was revealed in compound 1b on the models of aconitine and calcium chloride arrhythmias in rats (1 mg / kg, intravenously), which was absent in 1a.
About the Authors
G. V. Mokrov
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Mokrov Grigory, SPIN code: 8755-7666, Candidate of Chemical Sciences, Leading Researcher of the fine organic synthesis laboratory at the medicinal chemistry department, Moscow
Russian Federation
Mokrov Grigory, SPIN code: 8755-7666, Candidate of Chemical Sciences, Leading Researcher of the fine organic synthesis laboratory at the medicinal chemistry department, Moscow
A. M. Likhosherstov
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
Likhosherstov Arkady, SPIN code: 1980-7331, Candidate of Chemical Sciences, Consultant of drug chemistry department, Moscow
V. V. Barchukov
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
Barchukov Vladimir, SPIN code: 6743-4280, Research Scientist of laboratory of pharmacological screening, Moscow
V. N. Stolyaruk
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
Stolyaruk Valeriy, SPIN code: 3405-8229, PhD, Senior Researcher Scientist of laboratory of pharmacological screening, Moscow
I. B. Tsorin
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
Tsorin Iosif, SPIN code: 4015-3025, Doctor of Biological Sciences, Leading researcher of laboratory of pharmacological screening, Moscow
M. B. Vititnova
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
Vititnova Marina, SPIN code: 1901-8919, Candidate of Biologicall Sciences, Senior researcher scientist of laboratory of pharmacological screening, Moscow
S. A. Kryzhanovskiy
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
Kryzhanovskii Sergey, SPIN code: 6596-4865, Doctor of Medical Sciences, Head of laboratory of pharmacological screening, Moscow
T. A. Gudasheva
FSBI «Zakusov Institute of Pharmacology»
Russian Federation
Russian Federation
Gudasheva Tatiana, SPIN code: 4970-0006, Doctor of Biological Sciences, professor, RAS corresponding member, Head of medicinal chemistry department, Moscow
References
1. Mokrov GV, Likhosherstov AM, Barchukov VV, et al. Synthesis and cardiotropic activity of linear methoxyphenyltriazalkanes. Khim.-Pharm. Journal. 2019;53(6): 16–23. (In Russ). DOI: 10.30906/0023-1134-2019-53-6-16-23
2. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86(5):580–588. DOI: 10.1161/01.RES.86.5.580
3. Aldakkak M, Camara AK, Heisner JS, et al. Ranolazine reduces Ca2+ overload and oxidative stress and improves mitochondrial integrity to protect against ischemia reperfusion injury in isolated hearts. Pharmacol Res. 2011;64(4):381–392. DOI: 10.1016/j.phrs.2011.06.018
4. Fragasso G, Salerno A, Spoladore R, et al. Effects of metabolic approach in diabetic patients with coronary artery disease. Curr. Pharm. Des. 2009;15(8):857–862. DOI: 10.2174/138161209787582093
5. Hu B, Li W, Xu T, et al. Evaluation of trimetazidine in angina pectoris by echocardiography and radionuclide angiography: a meta-analysis of randomized, controlled trials. Clin. Cardiol. 2011;34(6):395–400. DOI: 10.1002/clc.20888
6. Zhang L, Lu Y, Jiang H, et al. Additional use of trimetazidine in patients with chronic heart failure: a meta-analysis. J. Am. Coll. Cardiol. 2012;59(10):913–922. DOI: 10.1016/j.jacc.2011.11.027
7. Vizzardi E, D’Aloia A, Quinzani F, et al. A focus on antiarrhythmic properties of ranolazine. J. Cardiovasc. Pharmacol. Ther. 2012;17(4):353–356. DOI: 10.1177/1074248412442000
8. Yamamoto S, Matsui K, Sasabe M, Ohashi N. Effect of an orally active Na+/H+ exchange inhibitor, SMP-300, on experimental angina and myocardial infarction models in rats. J. Cardiovasc. Pharmacol. 2002;39(2):234–241. DOI: 10.1097/00005344-200202000-00010
9. Mironov AN. Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv, part 1. Grif i K. Moscow: 2013. (In Russ).
10. Ilushkina IA, Berchatova AN, Dyachenko IA, et al. Model evaluation of new antiarrhithmic drugs. Biomedicina. 2012:(2); 6–13. (In Russ).
Review
For citations:
Mokrov G.V., Likhosherstov A.M., Barchukov V.V., Stolyaruk V.N., Tsorin I.B., Vititnova M.B., Kryzhanovskiy S.A., Gudasheva T.A. Study of ALM-802 orto-alkoxi analogues cardiotropic activity. Pharmacokinetics and Pharmacodynamics. 2019;(4):18-23. (In Russ.) https://doi.org/10.37489/2587-7836-2019-4-18-23
Views:
677
Email this article 