Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/ 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives

Farmaco

Volumn 58, Issue 1, 2003, Pages 17-24

  Yarim, Mine ^a   Saraç, Selma ^a   Kiliç, F Sultan ^b   Erol, Kevser ^b  

^a HACETTEPE UNIVERSITY   (Turkey)

^b ESKISEHIR OSMANGAZI UNIVERSITY   (Turkey)

Author keywords

1,2,3,4,5,6,7,8 Octahydroquinazoline 2,5 diones; Calcium antagonists; Condensed dihydropyrimidines; Synthesis

Indexed keywords

5,5 DIMETHYL 1,3 CYCLOHEXANEDIONE; ALDEHYDE; CALCIUM ANTAGONIST; METHYLUREA; NICARDIPINE; QUINAZOLINE DERIVATIVE; UREA; CALCIUM CHANNEL BLOCKING AGENT;

ANALYTIC METHOD; ANIMAL TISSUE; AORTA; ARTICLE; BIGINELLI REACTION; CAROTID ARTERY; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFECT; DRUG ISOLATION; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ILEUM; IN VITRO STUDY; LAMB; NONHUMAN; POLYMERIZATION; RAT; REACTION ANALYSIS; SPECTROSCOPY; STANDARD; STRUCTURE ANALYSIS; VASODILATATION; ANIMAL; CHEMISTRY; FEMALE; MALE; METHODOLOGY; PHARMACEUTICS; PHYSIOLOGY; SHEEP; SYNTHESIS;

ANIMALS; CALCIUM CHANNEL BLOCKERS; CAROTID ARTERIES; FEMALE; ILEUM; MALE; QUINAZOLINES; RATS; SHEEP; TECHNOLOGY, PHARMACEUTICAL;

EID: 0041967088     PISSN: 0014827X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0014-827X(02)00009-5     Document Type: Article

References (28)

1. Kappe C.O. 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron. 49:1993;6937.
2. Atwal K., Rovnyak G.C., Schwartz J., Moreland S., Herdberg A., Gougoutas J.Z., Malley M.F., Floyd D.M. Dihydropyrimidine calcium channel blockers: 2-Heterosubstituted 4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines. J. Med. Chem. 33:1990;1510.
3. Atwal K.S., Rovnyak G.C., Kimball S.D., Floyd D.M., Moreland S., Swanson B.N., Gougoutas J.Z., Schwartz J., Smillie K.M., Malley M.F. Dihydropyrimidine calcium channel blockers. 2. 3-Substituted-4-aryl-1,4-dihydro-6-methyl-5- pyrimidine-carboxylic acid esters as potent mimics of dihydropyridines. J. Med. Chem. 33:1990;2629.
4. Atwal K.S., Swanson B.N., Unger S.E., Floyd D.M., Moreland S., Hedberg A., O'Reilly B.C. Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents. J. Med. Chem. 34:1991;806.
5. Grover G.J., Dzwonczyk S., McMullen D.M., Normandin D.E., Parham C.S., Sleph P.G., Moreland S. Pharmacologic profile of the dihydropyrimidine calcium channel blockers SQ 32 547 and SQ 32 946. J. Cardiovasc. Pharmacol. 26:1995;289.
6. Kappe C.O. Biologically active dihydropyrimidones of the Biginelli-type - a literature survey. Eur. J. Med. Chem. 35:2000;1043.
7. Saraç S., Yarim M., Ertan M., Erol K., Aktan Y. 4-Aryl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives: synthesis, enantiomeric separation and in vitro screening as calcium antagonists. Boll. Chim. Farm. 136:1997;657.
8. Saraç S., Yarim M., Ertan M., Boydag S., Erol K. Synthesis, chemical and pharmacological properties of some 4-aryl-1,2,3,4,5,6,7,8- octahydroquinazoline-2,5-diones. Pharmazie. 53:1998;91.
9. Saraç S., Yarim M., Ertan M., Kiliç F.S., Erol K. 4-Aryl-6,6-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones: synthesis, chromatographic resolution and pharmacological activity. Pharmazie. 56:2001;298.
10. Yarim M., Saraç S., Ertan M., Kiliç F.S., Erol K. Synthesis, enantioseparation and pharmacological activity of 4-aryl-7,7-dimethyl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones. Arzneim.-Forsch. Drug Res. 52:2002;27.
11. Biginelli P. Ueber Aldeyhduramide des Acetessigäthers. Chem. Ber. 24:1891;1317.
12. Candan M.M., Kendi E., Yarim M., Saraç S., Ertan M. Crystal structure of 1,7,7-trimethyl-4-(4-methylphenyl)-1,2,3,4,5,6,7,8- octahydroquinazoline-2,5-dione. Anal. Sci. 17:2001;681.
13. Candan M.M., Kendi E., Yarim M., Saraç S., Ertan M. Crystal structure of 4-(4-bromophenyl)-1,7,7-trimethyl-1,2,3,4,5,6,7,8- octahydroquinazoline-2,5-dione. Anal. Sci. 17:2001;1023.
14. O'Reilly B.C., Atwal K.S. Synthesis of substituted 1,2,3,4-tetrahydro-6- methyl-2-oxo-5-pyrimidinecarboxylic acid esters: the Biginelli condensation revisited. Heterocycles. 26:1987;1185.
15. Sadanandam Y.S., Shetty M.M., Diwan P.V. Synthesis and biological evaluation of new 3,4-dihydro-6-methyl-5-N-methylcarbamoyl-4-(substituted phenyl)-2(1H)-pyrimidinones and pyrimidinethiones. Eur. J. Med. Chem. 27:1992;87.
16. Pretsch E., Clerck T., Seibl J., Simon W. Tables of Spectral Data for Structure Determination of Organic Compounds. 1983;Springer, Berlin, Heidelberg; Germany. English translation of the revised 2nd German edition 1981.
17. Mayer K.K., Dove S., Pongratz H., Ertan M., Wiegrebe W. Electron impact induced fragmentation of 4-aryl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-diones. Heterocycles. 48:1998;1169.
18. Drayer D.E. Pharmacodynamic and pharmacokinetic differences between drug enantiomers in humans: an overview. Clin. Pharmacol. Ther. 40:1986;125.
19. Rovnyak G.C., Kimball S.D., Beyer B., Cucinotta G., DiMarco J.D., Gougoutas J., Hedberg A., Malley M., McCarthy J.P., Zhang R., Moreland S. Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators. J. Med. Chem. 38:1995;119.
20. M. Yarim, S. Saraç, Enantiomeric separation of 4-aryl-7,7-dimethyl/1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2, 5-diones by chiral HPLC, Chromatographia 56 (2002) 307.
21. Rose U. Kalzium-modulatoren von typ annelierter Dihydropyridine, Synthese und pharmakologische Wirkung. Arzneim.-Forsch. Drug Res. 39:1989;1393.
22. Rose U. 5-Oxo-1,4-dihydroindenopyridines. Calcium modulators with partial calcium agonistic activity. J. Heterocycl. Chem. 27:1990;237.
23. Rose U. Synthesis and pharmacological activities of calcium modulatory hexahydroquinolinones. J. Heterocycl. Chem. 28:1991;2005.
24. Kazda S., Garthoff B., Meyer H., Scloßmann K., Stoepel K., Towart R., Vater W., Wehinger E. Pharmacology of a new calcium antagonistic compound, isobutyl methyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine- dicarboxylate (Nisoldipine, Bay K 5552). Arzneim.-Forsch. Drug Res. 30:1980;2144.
25. Şafak C., Erdemli İ., Sunal R. Synthesis of some 1,4,5,6,7,8-hexahydroquinoline derivatives and their calcium antagonistic activity. Arzneim.-Forsch./Drug Res. 43:1993;1052.
26. Rose U., Dräger M. Synthesis, configuration and calcium modulatory properties of enantiomerically pure 5-oxo-1,4,5,6,7,8-hexahydroquinoline-3- carboxylates. J. Med. Chem. 35:1992;2238.
27. Şafak C., Özkanli F., Erol K., Aktan Y. 3-Acetyl-4-aryl-5- oxo-2,7,7-trimethyl-1,4,5,6,7,8-hexahydroquinoline derivatives and their calcium antagonistic activities. Arzneim.-Forsch./Drug Res. 45:1995;1154.
28. Spedding M., Cavero I. Calcium antagonists: a class of drugs with a bright future. Part II. Determination of basic pharmacological properties. Life Sci. 35:1984;575.