SYNTHESIS, STRUCTURE, AND BIOLOGICAL ACTIVITY OF NOVEL BISPIDINE DERIVATIVES
DOI:
https://doi.org/10.22159/ijap.2021.v13s1.Y1013Keywords:
Bispidine, Synthesis, Structure, Activity, Anesthetics, Acute toxicityAbstract
Objective: Derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one attract considerable attention from pharmacists for the treatment of a wide range
of diseases. According to this interest, the novel derivatives of 3-cyclopropanmethyl-7-alkoxyalkyl-3,7-diazabicyclo[3.3.1]nonan-9-one with
isopropoxypropyl and ethoxypropyl substituents in the position 7 had been synthesized to study their biological activity and toxicity. The practical
significance of the work is in the accumulation and development of scientific representations about diazabicyclic compounds, methods for their
synthesis, structure, and properties, which can subsequently be used in a targeted design and identification of even more complex systems, as well
as in the development of further research in the field of 3,7-diazabicyclo[3.3.1]nonanes. For this purpose, complexes of the synthesized compounds
with β-cyclodextrin are obtained and their biological activity is investigated at the Department of Pharmacology of S.D. Asfendiyarov Kazakh National
Medical University with the aid of the pharmacological tests.
Methods: An experimental study of local anesthetic activity on the models of infiltration, conduction anesthesia, and acute toxicity of synthesized
molecules was carried out using primary screening methods.
Results: As a result of pharmacological screening, it has been found that the compounds exhibit local anesthetic activity and low toxicity and was
recommended for in-depth study of their pharmacological properties.
Conclusion: It turned out that a nature of the N-alkoxyalkyl radical does not affect the toxicity of cyclopropanmethyl- substituted bispidines. In the
series of O-benzoyloximes of bispidinones, the isopropoxypropyl- substituted analog is 1.3 times less toxic than ethoxypropyl- one.
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References
Bispidine-amino acid conjugates act as a novel scaffold for the design
Negl Trop Dis 2013;7:e2005.
2. Kuhl U, Cambareri A, Sauber C, Sörgel F, Hartmann R, Euler H,
et al. Synthesis, X-ray analysis and spectroscopic characterization of
the hemiaminal cyclization product from 2,4-dipyridine substituted
3,7-diazabicyclo[3.3.1]nonanone 1,5-diesters. J Chem Soc
1999;2:2083-8.
3. Smith GS, Thompson MD, Berlin KD, Holt EM, Scherlag BJ,
Patterson E, et al. A study of the synthesis and antiarrhythmic properties
of selected 3,7-diheterabicyclo[3.3.1]nonanes with substituents at the
2,4-positions and at the 9-position. Eur J Med Chem 1990;25:1-8.
4. Klepikova SG, Solomin VA, Iskakova TK, Yu VK. Spatial structure of
isomers of 3,7-bis(alkoxyalkyl)-3,7-diazabicyclo[3.3.1]nonan-9-ols.
Chem Heterocycl Compd 2003;39:504-10.
5. Tran K, Berlin KD, Eastman MA, Holt EM. Synthesis, stereochemical, and
conformational studies of selected 3,7-diheterabicyclo[3.3.1]nonan-9-ols:
X-ray diffraction analyses of 7-benzyl-9-phenyl-3-oxa-7-azabicyclo[3.3.1]
nonan-9-ol and 7-benzyl-9-(4-N,N’-dimethylaminophenyl)-3-thia-7-
azabicyclo[3.3.1]nonan-9-ol, a rare stable chair-boat form with trigonal
nitrogen. Phosphorus Sulfur Silicon Relat Elem 2007;182:99-119.
6. Klepikova SG, Yu VK, Fomicheva EE, Mukhasheva RD, Praliev KD,
Berlin KD. 1H NMR spectroscopy in the study of the three-dimensional
structure of 7-alkoxyalkyl-3-thia-7-azabicyclo-[3.3.1]nonan-9-ones and
some of their derivatives. Chem Heterocycl Compd 2008;44:1398-403.
7. Berlin KD, Iskakova TK, Faskhutdinov MF, Praliyev KD, Lee CP.
Unusual conformational behavior of 3,7-dihetera(N,N-;N,O-;N,S-)
bicyclo[3.3.1]nonan-9-ols in CDCl3. Phosphorus Sulfur Silicon Relat
Elem 2014;189:864-72.
8. Pichkhadze GM, Smagulova GS, Kadyrova DM, Praliev KD, Yu VK.
Local anesthetic activity of a promising piperidine derivative (LAS-54)
in combination with epinephrine. Pharm Chem J 2016;50:600-2.
9. Malmakova AE, Praliyev KD, Welch JT, Iskakova TK, Ibraeva SS.
Synthesis of novel 3,7-diazabicyclo[3.3.1]nonane derivatives. Eur
Chem Technol J 2014;16:85-9.
10. Praliyev KD, Iskakova TK, Baktybaeva LK, Malmakova AE. Synthesis
and myelostimulatory activity of a number of 3,7-diazabicyclo[3.3.1]
nonane derivatives. Pharm Chem J 2015;49:292-5.
11. Zheng Y, Obeng S, Wang H, Jali AM, Peddibhotla B, Williams DA,
et al. Design, synthesis, and biological evaluation of the third generation
17-cyclopropanmethyl-3,14?-dihydroxy-4,5?-epoxy-6?-[(4’-pyridyl)
carboxamido]morphinan (NAP) derivatives as ?/? opioid receptor dual
selective ligands. J Med Chem 2019;62:561-74.
12. Yuan Y, Elbegdorj O, Chen J, Akubathini SK, Beletskaya IO,
Selley DE, et al. Structure selectivity relationship studies of
17-cyclopropanmethyl-3,14?-dihydroxy-4,5?-epoxy-6?-[(4’-
pyridyl)carboxamido]morphinan derivatives toward the development
of the mu opioid receptor antagonists. Bioorg Med Chem Lett
2011;21:5625-9.
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