The multidirectional profile of pharmacological activity of methylxanthines and their biochemical mechanism of action is the reason for the development of the research in this group. Tricyclic theophylline derivatives, annelated six or seven membered heterocyclic ring at 7,8-position of theophylline generally demonstrated a different profile of its central nervous system activity, in comparison to the reference compound (theophylline). The pharmacological evaluation of a series of tricyclic theophylline derivatives with a pyrimido- or diazepino-moiety demonstrated sedative, hypothermizing and neuroleptic-like effects on the CNS [1, 2]. Derivatives of imidazo- and pyrimido[2,1-f]theophylline with various LCAPs moiety showed high or very high 5-HT_1A receptor affinity and diversified pharmacological profile. Preclinical studies indicated that 8-[3-(N4-phenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl-(1H,8H)-imidazo[2,1-f]purine-2,4-dione exerts anxiolytic-like activity in the four-plate test in mice; however its effect was weaker, than that produced by Diazepam. This compound and 8-[3-(N4-20- metoxyphenyl)-piperazin-N1-yl-propyl]-1,3-dimethyl- (1H,8H)-imida- zo-[2,1-f]purine-2,4-dione behaved like antidepressants in the forced swimming test in mice; and their activity in that model was comparable with the effect of Imipramine [3]. Derivatives of oxazolo- and oxazino-purinediones as bioisosteric analogs of 8-styryl xanthines, showed mainly affinity for adenosine A_2A and some of them showed anticonvulsant activity in MES and scMet tests [4].

    As a continuation of our studies, in this course we decided to designed, synthesized and preliminary evaluated on pharmacological studies, derivatives of oxazolo- and oxazino[2,3-f]theophyllines with various arylpiperazinyl moiety. These compounds were synthesized by cyclization of 8-bromotheophylline with various oxiranes, in presence of a catalytic amount of pirydine.

References:

[1] E. Chojnacka-Wójcik, A.Kłodzińska, A. Drabczyńska, M. Pawłowski, S. Charakchieva-Minol, G. Chłoń , M. Gorczyca, Eur. J. Med. Chem. 30 (1995) 587–592.

[2] M. Pawłowski, J. Katlabi, A. Drabczyńska, B. Duszyńska, S. Charakchieva-Minol, A. Dereń-Wesołek, E. Tatarczyńska, E. Chojnacka-Wójcik, M.J. Mokrosz, A.J. Bojarski, Eur. J. Med. Chem. 34 (1999) 167–175.

[3] A. Zagórska, S.Jurczyk , M. Pawłowski , M. Dybała, G. Nowak, E. Tatarczyńska, A. Nikiforuk, E. Chojnacka-Wójcik, Eur. J. Med. Chem. 44 (2009) 4288–4296.

[4] A. Drabczyńska, C.E. Müller, B. Schumacher, S. Hinz, J. Karolak-Wojciechowska, B. Michalak, E. Pękala, K. Kieć-Kononowicz, Bioorg. Med. Chem. 12 (2004) 4895-4908.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/23117 must be provided.

1. The highly versatile handle for synthesis of secondary amine derivatives with potential CNS activity: The Pipecolic Linker
2. The multiobjective based design, synthesis and evaluation of the arylsulfonamide/amide derivatives of arylxyethyl- and arylthioethyl- piperidines and pyrrolidines as a novel class of potent 5-HT₇ receptor antagonists
3. Induced Fit Homology Model of the 5-HT₆ Serotonin Receptor - Application for Virtual Screening
4. A novel handle for chemistry on solid support: the Pipecolic linker
5. Quinolinesulfonamides as potential 5-HT₇ and 5-HT_1A receptor ligands
6. Synthesis of long-chain arylpiperazine theophylline derivatives as potential 5-HT₇ and 5-HT₆ receptors ligands
7. Mannich bases, 5-arylimidazolidine-2,4-dione derivatives with arylpiperazine moiety, as 5-HT_1A receptor ligands with serotonin transporter affinity
8. Homology modeling of the 5-HT_1A and 5-HT_2A serotonin receptors on the novel ß₂-adrenergic receptor template
9. Solid-phase synthesis and preliminary biological investigation of arylpiperazine library as 5-HT_1A and 5-HT_2A receptor ligands
10. Tricyclic theophylline derivatives with arylalkylpiperazinyl moiety as CNS agents
11. New serotonin receptors ligands in the group of 8-acylamide derivatives of 1,3-dimethyl-7-[(4-phenyl- piperazin-1-yl)-alkyl]-1H-purine-2,6-(3H,7H)-dione
12. Synthesis and serotonin receptors activity of new purine-2,6-dione derivatives with arylpiperazinylalkoxy moieties
13. ARYLPIPERAZINYLBUTYL DERIVATIVES OF SOME IMIDAZO[2,1-f]THEOPHYLLINE AS CNS RECEPTOR LIGANDS.
14. THE BIOLOGICAL TARGET DERIVED PHARMACOPHORIC MODEL FOR 5-HT₇ SEROTONIN RECEPTOR ANTAGONISM
15. THE STRUCTURE OF AZO-ANALOGS OF 8-STYRYLXANTHINES - X-RAY AND MOLECULAR MODELLING STUDIES
16. SYNTHESIS AND ANTICONVULSANT ACTIVITY OF 4-ARYLPIPERAZINYL METHYL DERIVATIVES OF 5-CYCLOPROPYL-5-PHENYL HYDANTOINS
17. SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF NEW 5,5-DISUBSTITUTED HYDANTOINS
18. SYNTHESIS, IN VITRO AND IN VIVO ACTIVITY OF THE ARYLPIPERAZINYLPROPYL DERIVATIVES OF THE IMIDAZO[2,1-f]THEO- PHYLLINE
19. 8-ALKOXY-PURINE-2,6-DIONES WITH 7-PHENYLPIPERAZINYLALKYL AND 7-TETRAHYDRO-ISOQUINOLINYLALKYL MOIETIES AS 5-HT_1A, 5-HT_2A, 5-HT₇ RECEPTOR LIGANDS
20. DESIGN AND SYNTHESIS OF NEW 7-PHENYLPIPERAZINYLALKYL AND 7-TETRAHYDROISOQUINOLINYLALKYL DERIVATIVES OF PURINE-2,6,8-TRIONE AS POTENTIAL SEROTONIN RECEPTOR AGENTS