Synthesis and brain antihypoxic activity of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid

Javor Mitkov; Nikolai Danchev; Irina Nikolova; Alexander Zlatkov

doi:10.2478/v10007-007-0029-1

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Synthesis and brain antihypoxic activity of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid

Acta Pharmaceutica

Volume 57 (2007): Issue 3 (September 2007)

By: Javor Mitkov, Nikolai Danchev, Irina Nikolova and Alexander Zlatkov

Open Access

|Sep 2007

Abstract

The synthesis of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid was studied. The structures of synthesized compounds were proved by micro-analyses, IR- and ¹H NMR data. Values of acute p.o. and i.p. toxicity in mice show lower toxicity compared to caffeine. Declines in spontaneous locomotor activity support the idea of depressive CNS activity of the compounds. Two compounds exhibited brain antihypoxic activity (5a and 5b against haemic and circulatory hypoxia, respectively).

References

U. Muhl-Kufner, H. Ensinger, J. Mierau, F. J. Kuhn, E. Lehr and E. Muller, Unsymmetrisch substituierte Xanthine, DE 43 25 254 A1, Jul 28, 1993; ref. Chem. Abstr.121 (1994) 280676s.
Search in Google Scholar
M. Rother, B. Kittner, K. Rudolphi, M. Rössner and K. H. Labs, HWA 285 (propentofylline) - a new compound for the treatment of both vascular dementia and dementia of the Alzheimer type, Ann. N. Y. Acad. Sci.777 (1996) 404--409.
Search in Google Scholar
N. Danchev, Al. Zlatkov and Pl. Peikov, Synthesis, toxicological and pharmacological investigations of 8-basic substituted derivatives of caffeine, Compt. Rend. Bulg. Acad. Sci.48 (1995) 119--122.
Search in Google Scholar
AutoNom 2000 Add-in for MDL ISIS/Draw. Software for generating IUPAC chemical names. MDL Information Systems; http://www.mdli.com
Search in Google Scholar
J. Gagauzov, P. Peikov, D. Davkov and K. Sharankov, Synthesis of 8-bromomethylxanthines, Pharmacia (Sofia)37 (1987) 8--10.
Search in Google Scholar
Acute Oral Toxicity — Up-and-Down Procedure, OECD Organization for Economic Cooperation and Development (2001). Guideline for the Testing of Chemicals 425, Paris 2001; http://www.epa.gov/oppfead1/harmonization/docs/E425guideline.pdf.
Search in Google Scholar
C. Caillard, A. Menn, M. Plotkine and P. Rossignol, Do anticonvulsant drugs exert protective effect against hypoxia? Life Sci.16 (1975) 1607--1612; DOI: 10.1016/0024-3205(75)90078-8.10.1016/0024-3205(75)90078-8
Search in Google Scholar
L. Roshtina and R. Ostrovskaya, Effect of piracetam on the body resistance to hypoxia, Farmakol. Toksikol.44 (1981) 210--213.
Search in Google Scholar
E. Sumina, V. Shugaev and V. Shugaev, The mechanism of circulatory hypoxia in acute sodium fluoride poisoning, Farmakol. Toksikol.41 (1978) 480--482.
Search in Google Scholar
W. Persch and R. Beyerle, Mercury - containing xanthine compounds, Ger. Pat. 1,005,517, Apr 4, 1957; ref. Chem. Abstr.53 (1957) 18070d.
Search in Google Scholar
B. A. Prijmenko, N. I. Romanenko, I. V. Fedulova, L. P. Ostrenko, A. Chervinskij and S. N. Garmash, Synthesis and biological properties of derivatives of (3-methyl-7-alkylxanthinyl-8)-thioacetic acids, Khim. Pharm. Zh.20 (1986) 1322--1324.
Search in Google Scholar
H. Wiener and C. Gilon, An improved method for the catalytic preparation of t-butyl esters of carboxylic and fatty acids, J. Mol. Catal.37 (1986) 45--52.
Search in Google Scholar
D. F. De Tar and R. Silverstein, Reactions of carbodiimides. I. Mechanisms of the reactions of acetic acid with dicyclohexylcarbodiimide, J. Am. Chem. Soc.88 (1966) 1013--1016; DOI: 10.1021/ja00957a027.10.1021/ja00957a027
Search in Google Scholar
D. F. De Tar and R. Silverstein, Reactions of carbodiimides. II. Reactions of dicyclohexylcarbodiimide with carboxylic acids in the presence of amines and phenols, J. Am. Chem. Soc.88 (1966) 1020--1024; DOI: 10.1021/ja00957a028.10.1021/ja00957a028
Search in Google Scholar
D. L. Bowton, D. A. Stump, D. S. Prough, D. S. Lefkowitz and L. Coker, Pentoxifylline increases cerebral blood flow in patients with cerebrovascular disease, Stroke20 (1989) 1662--1666.
Search in Google Scholar
C. D. Nicholson, Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia, Psychopharmacology101 (1990) 147--159; DOI: 10.1007/BF02244119.10.1007/BF022441192190256
Search in Google Scholar
B. L. Eun, X. H. Liu and J. D. E. Barks, Pentoxifylline attenuates hypoxic-ishemic brain injury in immature rats, Ped. Res.47 (2000) 73--78.
Search in Google Scholar

Articles in this issue

DOI: https://doi.org/10.2478/v10007-007-0029-1 | Journal eISSN: 1846-9558 | Journal ISSN: 1330-0075

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Language: English

Page range: 361 - 370

Published on: Sep 18, 2007

Published by: Croatian Pharmaceutical Society

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

caffeine-8-thioglycolic acid,

aliphatic and arylaliphatic amides,

acute toxicity,

brain antihypoxic activity

Related subjects:

Pharmacy,

Pharmacy, other

© 2007 Javor Mitkov, Nikolai Danchev, Irina Nikolova, Alexander Zlatkov, published by Croatian Pharmaceutical Society
This work is licensed under the Creative Commons License.

Volume 57 (2007): Issue 3 (September 2007)