Synthesis and Biological Activities of Novel 1,2,3,5-Tetrahydroimidazo[2,1-b]quinazoline Derivatives

• Autorzy: Kornicka, A. , Sączewski, F. , Petrusewicz, J. , Rejdych, A. , Tyacke, R. , Hudson, A. , Nutt, D.
• Języki publikacji: EN

Abstrakty

EN

A series of variously substituted 1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline derivatives 3-4 and 6-7 were prepared by the reactions of 2-chloro-4,5-dihydroimidazole (1) with the appropriate 2-aminophenyl ketones 2 and 5. The structures of the new compounds obtained were determined by elemental analysis as well as IR and NMR spectroscopic data. Biological activities of the compounds 3 and 6 was examined on P2 membrane preparations obtained from rat whole brains and rat tail artery. Among the compounds tested, 5-methylidene-1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline (6a) showed high and moderate binding affinities to I2 imidazoline (Ki = 5.2 nM) and alfa2-adrenergic (Ki = 149 nM) receptors, respectively.

Słowa kluczowe

EN

5-hydroxy- or 5-methylidene-1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline; I2 imidazoline and alfa2-adrenergic receptors binding affinities; synthesis; circulatory activity

• Czasopismo: Polish Journal of Chemistry
• Rocznik: 2005
• Tom: Vol. 79 / nr 1
• Strony: 89-100
• Opis fizyczny: Bibliogr. 26 poz., rys.

Twórcy

autor

Kornicka, A.

• Department of Chemical Technology of Drugs, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland

autor

Sączewski, F.

• Department of Chemical Technology of Drugs, Medical University of Gdansk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland

autor

Petrusewicz, J.

• Department of Pharmacology, Medical University of Gdańsk, Poland

autor

Rejdych, A.

• Department of Pharmacology, Medical University of Gdańsk, Poland

autor

Tyacke, R.

• Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, UK

autor

Hudson, A.

• Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, UK

autor

Nutt, D.

• Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, UK

Bibliografia

• 1. Hieble J.P., Bondinell W.E. and Ruffolo R.R., J. Med. Chem., 38, 3415 (1995).
• 2. Rutfolo Jr.R.R., Bondinell W.E. and Hieble J.P., J. Med. Chem., 38, 3681 (1995).
• 3. Munk S.A., Harcourt D.A., Arasasingham P.N., Burke J.A., Kharlamb A.B., Manlapaz C.A., Padillo E.U., Roberts D., Runde E., Williams L., WheelerL.A. and Garst M.E.,.l Med. Chem., 40, 18 (1997).
• 4. Gentili F., Bousquet P., Brasili L., Caretto M., Carrieri A., Dontenwill M., Giannella M., Manicci G., Perfumi M., Piergentili A., Quaglia W., Rescente C. and Pigini M., J. Med. Chem., 45, 32 (2002).
• 5.Farsang C. and Kapocsi J., Brain Res. BulI., 49, 317 (1999).
• 6. Coates P.A., Grundt P., Robinson E.S.J., Nutt D.J., Tyacke R., Hudson A.L., Lewis J.W. and Husbands S.M., Biaorg. Med. Chem. Lett, 10, 605 (2000).
• 7. Anastassiadou M., Danoun S., Crane L., Baziard-Mouysset G., Payard M., Caignard D.H., Rettori M.C. and Renard P., Bioorg. Med. Chem. Lett., 9, 585 (2001).
• 8. Chapleo C.B., Myers P.L., Butler R.C.M., Doxey J.C., Roach A.G. and Smith C.F.C.,.J. Med. Chem., 26, 823 (1983).
• 9. Carrieri A., Brasili L., Leonetti F., Pigini M., Giannella M., Bousquet P. and Caroti A., Bioorg. Med. Chem., 5, 843 (1997).
• 10. Hudson A.L., Husbands S., Lewis J.W. and Nutt D.J., Br: .J. PharmacoI., 112, S320 (1994).
• 11. Staehle H.., Koeppe H., Knmmer W. and Samtleben H.W. (Boehringer, C. H., Sohn), Ger. Ofien. 2, 118, 261; C.A., 78, 29773a (1973).
• 12. Jen T., Bender P., Van Hoeven H., Dienel B. and Loev B., .1. Med. Chem., 16, 407 (1973).
• 13. Jen T., DienelB., Bowman H., Petta J., Helt A. and Loev B., .1. Med. Chem., 1, 727 (1972).
• 14. Ishikawa F., Kosasayama A. and Higashi K., Chem. Pharm. BuIl., 28, 2024 (1980).
• 15. Houlihan W.J., Ahmad U.F., Koletar J., Kelly L., Brand L. and Kopajtic T.A., J. Med. Chem., 45, 4110 (2002).
• 16. Kulkami S., Hauck Newman A. and Houlihan W.J., .J. Med. Chem., 45, 4119 (2002).
• 17. Komicka A., Sqczewski F. and Gdaniec M., Molecules, 9, 86 (2004).
• 18. For other examples of carbon disulfide promoted reactions of l with N-nucleophiles see: Sączewski F., Sączewski J. and Gdaniec M., Chem. Pharm. Bull. 49, 1203 (2001).
• 19. Jackman L.M. and Jen T.,.J. Am. Chem. Soc. 97, 2811 (1975).
• 20. Trani A. and Bellasio E., .J. Heterocycl. Chem., 11, 257 (1974).
• 21. Sugasawa T., Toyoda T., Adachi M. and Sasakura K., J Am. Chem. Sac., 19, 4842 (1978).
• 22. Simpson J .C.E., Atkinson C.M., Schofield K. and Stephenson 0., .J. Chem. Soc. Part II, 646 (1945).
• 23. Ockenden D.W. and Schofield K., .J. Chem. Soc., 3440 (1953).
• 24. Keneford J.R. and Simpson J .C.E., .J. Chem. Soc. Part I, 354 (1948).
• 25. Morgenstern 0., Richter P.H. and Ahrens H., Pharmazie, 47, 25 (1992).
• 26. Nicholas T.U., .1 Pharm. PharmacoI., 21, 826 (1969).