Cihat ŞAFAK, Elvan DOĞAN, Kevser EROL

Studies on 2-Ethyl-3-carbmethoxy-4-aryl-5-oxo-1,4,5,6,7,8-hexahydroquinoline Derivatives and Calcium Modulatory Activities

Twelve new compounds having a 2-ethyl-3-carbmethoxy-4-aryl-5-oxo-1,4,5,6,7,8-hexahydroquinoline structure were synthesized, characterized and screened for their calcium modulatory activities. The calcium antagonistic activities of the compounds were investigated by tests performed on isolated rat ileum and lamb carotid artery. Compounds 1, 4, 8 and 9 showed considerable activity.Calcium channel antagonists inhibit muscle contraction by blocking the influx of Ca2+ through calcium channels and are used as antianginal and antihypertensive drugs 1−5. Nifedipine, with 1,4-dihydropyridine (DHP) moiety in its structure, is the prototype of this group.

Anahtar Kelimeler:

Dihydropyridine, hexahydroquinoline, antihypertensive activity, calcium antagonist

Studies on 2-Ethyl-3-carbmethoxy-4-aryl-5-oxo-1,4,5,6,7,8-hexahydroquinoline Derivatives and Calcium Modulatory Activities

Keywords:

Dihydropyridine, hexahydroquinoline, antihypertensive activity, calcium antagonist,

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R. Fossheim, A. Joslyn, A.J. Solo, E. Luchowski, A. Rutledge and D.J.Triggle, J. Med. Chem. 31, 300-5 (1988).
R.A. Coburn, M. Wierzba, M.J. Suto, A.J. Solo, A.M. Triggle and D.J.Triggle, J. Med. Chem. 31, 2103-7 (1988).
R. Towart and M. Schramm, Trends Pharmacol. Sci. 111-3 (1984).
E. Wehinger and R. Gross, Ann. Rep. Med. Chem. 21, 85-95 (1986).
A. Ashimori, T. Ono, T. Uchida, Y. Ohtaki, C. Fukaya, M. Watanabe and K. Yokoyama, Chem.Pharm.Bull. (9), 2446-58 (1990).
T. Kobayashi, T. Inoue, Z. Kıta, H. Yoshiya, S. Nishino, K. Ouzumi and T.Kimura, Chem. Pharm. Bull. (5), 788-96 (1995).
R.A. Janis and D.J. Triggle, J. Med. Chem. 26, 775-85, 1983.
J. E. Arrowsmith, S. F. Campbell, P. E. Cross, R. A. Burges and D. G. Gardiner, J. Med. Chem. 32, 562-8, G.C. Rovnyak, S.D. Kimball, B. Beyer, G. Cucinotta, J.D. DiMarco, J. Gouguotas, A. Hedberg, M. Malley, J.P. McCarthy, R. Zhang and S. Moreland, J. Med. Chem. 38, 119-29 (1995).
J.J. Baldwin, D.A. Claremon, P.K. Lumma, D.E. McClure, S.A., Rosenthal, R.J. Winquist, E.P. Faison, G.J. Kaczorowski, M.J. Trumble and G.M. Smith, J. Med. Chem. 30, 690-5 (1987).
U. Rose, Pharm.Acta Helv. 65, 178-85 (1990).
U. Rose, Arch. Pharm., 323, 281-6 (1990).
C. S¸afak, F. ¨Ozkanlı, K. Erol and Y.Aktan, Arzneim. Forsch. Drug Res. 45, 1154-6 (1995).
C. S¸afak, ˙I.S. Erdemli and R. Sunal, Arzneim. Forsch. Drug Res. 43, 1052-5 (1993).
U. Rose, Arzneim. Forsch. Drug Res. 41, 199-203 (1991).
R. S¸im¸sek, C. S¸afak, K. Erol and B. Sırmag¨ul, Arzneim. Forsch. Drug Res. 51, 959-63, 2001.
R. S¸im¸sek, C. S¸afak, K. Erol and B.Sırmag¨ul, Pharmazie 56, 665-6 (2001).
R. S¸im¸sek, U.B. ˙Ismailo˘glu, C. S¸afak and I.S. Erdemli, Il Farmaco 55, 665-8 (2000).
C. S¸afak, R. S¸im¸sek,Y. Alta¸s, S. Boyda˘g and K. Erol, Boll. Chim. Farm. 136, 665-9 (1997).
R. S¸im¸sek, C. S¸afak, K. Erol, S¸. Ataman, M. ¨Ulgen and A.Linden, Arzneim. Forsch. Drug Res. 53, 159-66 (2003).
E. Kısmetli, C. S¸afak, K. Erol, B. Sırmag¨ul and A.Linden, Arzneim. Forsch. Drug Res. 54, 371-5 (2004).
U. Rose, J. Heterocycl. Chem. 27, 237-42 (1990).
Y. Alta¸s, C. S¸afak, O.S. Batu and K.Erol, Arzneim. Forsch. Drug Res. 49, 824-9 (1999).
U. Rose, Arzneim. Forsch. Drug Res. 39, 1393-8 (1989).
U. Rose and M.Dr¨ager, J. Med. Chem. 35, 2238-43 (1992).
B. Kazda, B. Garthoff, H. Meyer, K. Schlossmann, K. Stoepel, R. Towart, W. Water and E. Wehinger, Arzneim. Forsch. Drug Res. 30, 2144-62 (1980).
A. Hantzsch, Justus Liebigs Ann. Chem. 215, 1-15 (1882).
B.J.S. Wang and E.R.J. Thornton, Am. Chem. Soc. 90, 1216-21 (1968).
L. Prokai, B. Hsu, H. Farag and N. Bodor, Anal. Chem. 61, 1723-8 (1989).