Synthesis of novel 1,4-Dihydropyridine derivative labeled with Carbon-14

Ahmadi Faghih, M.A; Mosslemin, M.H; Shirvani, G; Javaheri, M

doi:10.24200/nst.2019.1031

Synthesis of novel 1,4-Dihydropyridine derivative labeled with Carbon-14

Document Type : Research Paper

Authors

M.A Ahmadi Faghih

M.H Mosslemin

G Shirvani

M Javaheri

https://doi.org/10.24200/nst.2019.1031

Abstract

Synthesis of ¹⁴C-labeled organic compounds is being required by the medical, pharmaceutical, agricultural, industrial, and research centers. The Carbon-14 is essential for the tracking and recognizing the mechanism and performance of the synthesized chemical compounds. The Dihydropyridine is synthetically labeled with Carbon-14 in this work to pursue a further study about the mechanism of its action and to support the current metabolism. Therefore, to clarify further the mechanism of its operation and to support the current research on its metabolism, there is a need for the analogs of these compounds that are Carbon-14 labeled in a biologically stable site. The 1,4-Dihydropyridine channel blockers are clinically significant antihypertensive drugs and have been immensely valuable as molecular tools to probe into the structural and functional aspects of the channel function. In this study, N-Phenyl-3,5-Dicarboxylate-2,4,6-Triphenyl-1,4[¹⁴C]-Dihydropyridine, which is a new compound of the Dihydropyridine derivative and had labeled with the Carbon-14, was synthesized. This novel synthetic compound having an N-Phenyl derivative is one of the new drug metabolites that have anti-cancer properties. Using a multicomponent reaction with the shortest stage in the preparation, separation, and purification, as well as, suitable conditions with an encellent radiochemical yield was developed.

Highlights

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A. Velena, et al. 1,4-Dihydropyridine derivatives: dihydronicotinamide analogues—model compounds targeting oxidative stress, J. Oxidative Medicine and Cellular Longevity, 35, 1892412, (2016), doi: 10.1155/2016/1892412.
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J. Zhu, and H. Bienayme, Multicomponent Reactions (Eds.) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim (2005).
A. Moshtaghi Zenouz, M. Raisossadat Oskuie, and S. Mollazadeh, Synthesis of Novel Asymmetrical 1,4‐Dihydropyridine Derivatives, Synthetic Communications, 35, 2895 (2005).
A. Mai et al. Study of 1,4-dihydropyridine structural scaffold: discovery of novel sirtuin activators and Inhibitors, J. Med. Chem. 52, 5496 (2009).
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U. Pleiss, 1,4-Dihydropyridines (DHPs) – a class of very potent drugs: syntheses of isotopically labeled DHP derivatives during the last four decades, J. Label Compd Radiopharm, 50, 818 (2007).

10. J. Yanga et al. A clean procedure for the synthesis of 1,4-dihydropyridines via Hantzsch reaction in water, Green Chemistry Letters and Reviews, 6 (3), 262 (2013).

11. M. Nasr Esfahani, B. Karimi, and M. Behzadi, A simple, Efficient, One-Pot Three-Component Domino Synthesis of Hantzsch Pyridines under Solvent-free Condition, Journal Heterocyclic Chemistry, 46, 931 (2009).

12. C.W. Perry, W. Burger, and C.M. Delaney, Synthesis of ¹⁴C-labeled 4-hydroxy indole as an intermediate for the preparation of (S)-2-[4-[2-[3-(indole-2-[¹⁴C]-4-yloxy0-2-hydroxy propylamine]-2-methylpropyl]-phenoxy] pyridine-5-carboxamide-glycolate, J. Labeled Cpd. Radiopharm, 45, 1146 (2002).

13. C.W. Perry, W. Burger, and C.M. Delaney, An improved method of preparation of potassium cyanide-¹⁴C, J. Labelled Comp Radiopharm, 16, 645 (1978).

14. N. Saadatjoo et al. Synthesis of the olanzapine labeled by carbon-14, Journal of Labelled Compounds and Radiopharmaceuticals, 59 (8), 325 (2016).

15. F. Lentz et al. Discovery of novel N-phenyl 1,4-dihydropyridines with a dual mode of antimycobacterial activity, Bioorganic & Medicinal Chemistry Letters, 26, 5896 (2016).

Keywords

Dihydropyridine (DHP)

Labeling

Carbon-14

Multicomponent Reaction

20.1001.1.17351871.1398.40.3.12.8

M. Nami et al. Preparation of fentanyl labeled with carbon-14, Radiochemistry, 60 (1), 42 (2018).
A. Velena, et al. 1,4-Dihydropyridine derivatives: dihydronicotinamide analogues—model compounds targeting oxidative stress, J. Oxidative Medicine and Cellular Longevity, 35, 1892412, (2016), doi: 10.1155/2016/1892412.
O. Arjomandi et al. Strategy for ¹⁴C-labeling of a series of bis (heteroaryl) piperazines, J. Label Compd Radiopharm, 54 (7), 363 (2011).
M. Basooti, et al. Synthesis of two carbon-14 analogue of Thioflavanones, J. Label Compd Radiopharm, 60 (11), 550 (2017).
J. Zhu, and H. Bienayme, Multicomponent Reactions (Eds.) WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim (2005).
A. Moshtaghi Zenouz, M. Raisossadat Oskuie, and S. Mollazadeh, Synthesis of Novel Asymmetrical 1,4‐Dihydropyridine Derivatives, Synthetic Communications, 35, 2895 (2005).
A. Mai et al. Study of 1,4-dihydropyridine structural scaffold: discovery of novel sirtuin activators and Inhibitors, J. Med. Chem. 52, 5496 (2009).
R. Smits, B. Vigante, and G.W. Buchanan, Synthesis of novel cationic 1,4-dihydropyridine and 3,4-dihydropyridone based fluorous amphiphiles for possible transmembrane delivery applications, J. University of latvia faculty of chemistry dissertation, (2012) dspace.lu.lv/dspace/bitstream/handle/7/4832/33548-Rufs_Smits.
U. Pleiss, 1,4-Dihydropyridines (DHPs) – a class of very potent drugs: syntheses of isotopically labeled DHP derivatives during the last four decades, J. Label Compd Radiopharm, 50, 818 (2007).

10. J. Yanga et al. A clean procedure for the synthesis of 1,4-dihydropyridines via Hantzsch reaction in water, Green Chemistry Letters and Reviews, 6 (3), 262 (2013).

13. C.W. Perry, W. Burger, and C.M. Delaney, An improved method of preparation of potassium cyanide-¹⁴C, J. Labelled Comp Radiopharm, 16, 645 (1978).

14. N. Saadatjoo et al. Synthesis of the olanzapine labeled by carbon-14, Journal of Labelled Compounds and Radiopharmaceuticals, 59 (8), 325 (2016).

15. F. Lentz et al. Discovery of novel N-phenyl 1,4-dihydropyridines with a dual mode of antimycobacterial activity, Bioorganic & Medicinal Chemistry Letters, 26, 5896 (2016).