Studies on the synthesis and biological activitiy of 6-ethyl-4-aryl-5- methoxycarbonyl-3,4,-dihydropyrimidin-2(1H)-ones

Arzneimittel-Forschung/Drug Research

Volumn 57, Issue 3, 2007, Pages 137-142

  Saraç, Selma ^a   Çiftçi, Murat ^b   Zorkun, Inci Selin ^a   Tunç, Özgül ^c   Erol, Kevser ^c  

^a HACETTEPE UNIVERSITY   (Turkey)

^b Damla Pharmacy   (Turkey)

^c ESKISEHIR OSMANGAZI UNIVERSITY   (Turkey)

Author keywords

4 Aryl 3,4 dihydropyrimidin 2(1H) ones, calcium channel blocker activity, synthesis; Calcium channel blocker

Indexed keywords

6 ETHYL 4 ARYL 5 METHOXYCARBONYL 3,4 DIHYDROPYRIMIDIN 2(1H) ONE DERIVATIVE; CALCIUM CHANNEL BLOCKING AGENT; CHLORIDE; NICARDIPINE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CAROTID ARTERY; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; ILEUM; MALE; MASS SPECTROMETRY; NONHUMAN; RAT;

EID: 34147220137     PISSN: 00044172     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-0031-1296596     Document Type: Article

References (47)

1. Armstrong RW, Combs AP, Tempest PA, Brown SD, Keating TA. Multiple-component condensation strategies for combinatorial library synthesis. Acc Chem Res. 1996;29:123-131.
2. Tietze LF, Lieb ME. Domino reactions for library synthesis of small molecules in combinatorial chemistry. Curr Opin Chem Biol. 1998;2:363-371.
3. Kappe CO. A reexamination of the mechanism of the Biginelli dihydropyrimidine synthesis. Support for an N-acyliminium ion intermediate. J Org Chem. 1997;62:7201-7204.
4. Kappe CO. 4-Aryldihydropyrimidines via the Biginelli condensation: Aza-analogs of nifedipine-type calcium channel modulators. Molecules. 1998;3:1-9.
5. Kappe CO. Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog. Acc Chem Res. 2000;33:879-888.
6. Barrow JC, Nantermet PG, Selnick HG, Glass KL, Rittle KE, Gilbert KF, et al. In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective α1a receptor antagonists for the treatment of benign prostatic hyperplasia. J Med Chem. 2000;43:2703-2718.
7. Biginelli P. Aldehyde-urea derivatives of aceto- and oxaloacetic acids. Gazz Chim Ital. 1893;23:360-416.
8. Atwal KS, Swanson BN, Unger SE, Floyd DM, Moreland S, Hedberg A, et al. Dihydropyrimidine calcium channel blockers. 3-Carbamoyl-4-aryl-1,2,3,4- tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents. J Med Chem. 1991;34:806-811.
9. Rovynak GC, Atwal KS, Hedberg A, Kimball SD, Moreland S, Gougoutas JZ, et al. Dihydropyrimidine calcium channel blockers. 3-Substituted-4-aryl- 1,4-dihydropyrimidine-5-carboxylic acid esters. Potent antihypertensive agents. J Med Chem. 1992;35:3254-3263.
10. Grover GJ, Dzwonczyk S, McMullen DM, Normandin DE, Parham CS, Sleph PG, et al. Pharmacologic profile of the dihydropyrimidine calcium channel blockers SQ 32,547 and SQ 32,926. J Cardiovasc Pharmacol. 1995;26:289-294.
11. 1a adrenoceptor-selective antagonists. Structure-activity relationship in dihydropyrimidinones. J Med Chem. 1999;42:4764-4777.
12. 1a adrenoceptor-selective antagonists. 2. Approaches to eliminate opioid agonist metabolites via modification of linker and 4-methoxycarbonyl-4-phenylpiperidine moiety. J Med Chem. 1999;42:4778-4793.
13. Bruce MA, Pointdexter GS, Johnson G. Preparation of dihydropyrimidones as NPY antagonists. PCT Int. Appl. WO 98 33,791 (Ref: Chem Abstr. 1999;129:148989g).
14. Patil AD, Kumar NV, Kokke WC, Bean MF, Freyer AJ, De Brosse C, et al. Novel alkaloids from the sponge Batzella sp.: Inhibitors of HIV gp120-human CD4 binding. J Org Chem. 1995;60:1182-1188.
15. Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science. 1999;286:971-974.
16. Haggarty SJ, Mayer TU, Miyamoto DT, Fathi R, King RW, Mitchison TJ, et al. Dissecting cellular processes using small molecules: Identification of colchicine-like, taxol-like and other small molecules that perturb mitosis. Chem Biol. 2000;7:275-286.
17. Ertan M, Balkan A, Saraç S, Uma S, Renaud JF, Rolland Y. Synthesis and calcium antagonistic activity of some new 2-thioxo-1,2,3,4- tetrahydropyrimidine derivatives. Arch Pharm (Weinheim). 1991;324:135-139.
18. Ertan M, Balkan A, Saraç S, Uma S, Rübseman K, Renaud JF. Synthesis and biological evaluations of some 2-thioxo-1,2,3,4- tetrahydropyrimidine derivatives. Arzneimittel-Forschung (Drug Research). 1991;41:725-727.
19. Tozkoparan B, Yarim M, Sarac S, Ertan M, Kelicen P, Altinok G, et al. Studies on synthesis, chromatographic resolution and antiinflammatory activities of some 2-thioxo-1,2,3,4-tetrahydropyrimidines and their condensed derivatives. Arch Pharm Pharm Med Chem. 2000;333:415-420.
20. Zorkun İS, Saraç S, Çelebi S, Erol K. Synthesis of 4-aryl-3,4-dihydropyrimidin-2(1H)-thione derivatives as potential calcium channel blockers. Bioorg Med Chem. 2006; 14: 8582-8589.
21. Yarim M, Sarac S, Ertan M, Kiliç FS, 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. Arzneimittel-Forschung (Drug Research). 2002; 52:27-33.
22. Yarim M, Saraç S, Kiliç FS, Erol K. 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. Il Farmaco. 2003;58:17-24.
23. Hu EH, Sidler DR, Dolling U-H. Unprecedented catalytic three component one-pot condensation reaction; An efficient synthesis of 5-alkoxycarbonyl-4- aryl-3,4-dihydropyrimidin-2(1H)-ones. J Org Chem. 1998;63:3454-3457.
24. Ranu CB, Hajra A, Jana U. Indium(III) chloride-catalyzed one-pot synthesis of dihydropyrimidinones by a three-component coupling of 1,3-dicarbonyl compounds, aldehydes, and urea: An improved procedure for the Biginelli reaction. J Org Chem. 2000;65:6270-6272.
25. Kappe CO. 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron. 1993;49:6937-6963.
26. Lu J, Bai Y, Wang Z, Yang B, Ma H. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using lanthanum chloride as a catalyst. Tetrahedron Lett. 2000;41:9075-9078.
27. Lu J, Ma H. Iron(III)-catalyzed synthesis of dihydropyrimidinones. Synlett. 2000;63-64.
28. Ma Y, Qian C, Wang L, Yang M. Lanthanide triflate catalyzed Biginelli reaction. One-pot synthesis of dihydropyrimidinones under solvent-free conditions. J Org Chem. 2000;65:3864-3868.
29. Ramalinga K, Vijayalakshmi P, Kaimal TNB. Bismuth(III)-catalyzed synthesis of dihydropyrimidinones: Improved protocol conditions for the Biginelli reaction. Synlett. 2001;863-865.
30. 2O-mediated three-component, one-pot condensation reaction: An efficient synthesis of 4-aryl-substituted 3,4-dihydropyrimidin-2-ones. Tetrahedron Lett. 2001;42: 7873-7875.
31. Fan X, Zhang X, Zhang Y. Samarium chloride catalysed Biginelli reaction: One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones. J Chem Research (S). 2002;436-438.
32. Reddy CV, Mahesh M, Raju PVK, Babu TR, Reddy WN. Zirconium(IV) chloride catalyzed one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Tetrahedron Lett. 2002;43: 2657-2659.
33. Fu N-Y, Yuan Y-F, Cao Z, Wang S-W, Wang J-T, Peppe C. Indium(III) bromide-catalyzed preparation of dihydropyrimidinones: Improved protocol conditions for the Biginelli reaction. Tetrahedron. 2002;58:4801-1807.
34. Lu J, Bai Y. Catalysis of the Biginelli reaction by ferric and nickel chloride hexahydrates. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones. Synthesis 2002;466-470.
35. Tu S, Fang F, Miao C, Jiang H, Feng Y, Shi D, et al. One-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones using boric asid as catalyst. Tetrahedron Lett. 2003;44: 6153-6155.
36. Cappe CO, Stadler A. The Biginelli dihydropyrimidine synthesis. In: Overman, LE, ed. Organic Reactions. New York: John Wiley&Sons; 2004. p. 1-116.
37. Kappe CO, Falsone SF. Polyphosphate ester-mediated synthesis of dihydropyrimidines. Improved conditions for the Biginelli reaction. Synlett. 1998;718-720.
38. Falsone FS, Kappe CO. The Biginelli dihydropyrimidone synthesis using polyphosphate ester as a mild and efficient cyclocondensation/dehydration reagent. ARKIVOC. 2001 (Part 2);122-134.
39. Kappe CO, Kumar D, Varma RS. Microwave-assisted high-speed parallel synthesis of 4-aryl-3,4-dihydropyrimidin-2(1H)-ones using a solventless Biginelli condensation protocol. Synthesis. 1999;1799-1803.
40. Stadler A, Kappe CO. Microwave-mediated Biginelli reactions revisited. On the nature of rate and yield enhancements. J Chem Soc Perkin Trans. 2000;2:1363-1368.
41. O'Reilly BC, Atwal KS. Synthesis of substituted 1,2,3,4-tetrahydro-6- methyl-2-oxo-5-pyrimidinecarboxylic acid esters: The Biginelli condensation revisited. Heterocycles. 1987;26:1185-1188.
42. Atwal KS, Rovnyak GC, O'Reilly BC, Schwartz J. Substituted 1,4-dihydropyrimidines. Synthesis of selectively functionalized 2-hetero-1,4-dihydropyrimidines. J Org Chem. 1989; 54:5898-5907.
43. Barluenga J, Tomás M, Ballesteros A, López LA. 1,4-Cycloaddition of 1,3-diazabutadienes with enamines: An efficient route to the pyrimidine ring. Tetrahedron Lett. 1989;30:4573-4576.
44. Kappe CO, Fabian WMF, Semones MA. Conformational analysis of 4-aryl-dihydropyrimidine calcium channel modulators. A comparison of ab initio, semiempirical and X-ray crystallographic studies. Tetrahedron. 1997;53:2803-2816.
45. Wipf P, Cunningham A. A solid-phase protocol of the Biginelli dihydropyrimidine synthesis suitable for combinatorial chemistry. Tetrahedron Lett. 1995;36:7819-7822.
46. Studer A, Jeger R Wipf P, Curan DP. Fluorous synthesis: Fluorous protocols for the Ugi and Biginelli multicomponent condensations. J Org Chem. 1997;62:2917-2924.
47. Studer A, Hadida S, Ferrito R, Kim S-Y, Jeger P, Wipf P et al. Fluorous synthesis: A fluorous-phase strategy for improving separation efficiency in organic synthesis. Science. 1997;275:823-826.