Synthesis of novel Hantzsch dihydropyridines and Biginelli dihydropyrimidines of biological interest: A 3D-QSAR study on their cytotoxicity

Medicinal Chemistry Research

Volumn 19, Issue 4, 2010, Pages 344-363

  Prashantha Kumar, B R ^a   Masih, Pankaj ^a   Karthikeyan, E ^a   Bansal, Ankur ^a   Suja, ^a   Vijayan, Pottekad ^a  

^a JSS COLLEGE OF PHARMACY   (India)

Author keywords

CoMFA; Cytotoxicity; Dihydropyridines; Dihydropyrimidines

Indexed keywords

4 (2 HYDROXYPHENYL) N (4 METHOXYPHENYL) 6 METHYL 2 OXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 (2 HYDROXYPHENYL) N (4 METHOXYPHENYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 (3 CHLOROPHENYL) N (4 METHOXYPHENYL) 6 METHYL 2 OXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 (3 CHLOROPHENYL) N (4 METHOXYPHENYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 (3 CHLOROPHENYL) N,N BIS(4 CHLOROPHENYL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; 4 (4 HYDROXY 3 METHOXYPHENYL) N (4 METHOXYPHENYL) 6 METHYL 2 OXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 (4 HYDROXY 3 METHOXYPHENYL) N (4 METHOXYPHENYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 (FURAN 2 YL) N (4 METHOXYPHENYL) 6 METHYL 2 OXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 (FURAN 2 YL) N (4 METHOXYPHENYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 4 [4 (DIMETHYLAMINO)PHENYL] N (4 METHOXYPHENYL) 6 METHYL 2 OXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; 6 ETHYL 1,2,3,4 TETRAHYDRO N (4 METHOXYPHENYL) 2 OXO 4 PHENYLPYRIMIDINE 5 CARBOXAMIDE; DIHYDROPYRIDINE DERIVATIVE; N (4 METHOXYPHENYL) 6 METHYL 2 OXO 4 STYRYL 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; N (4 METHOXYPHENYL) 6 METHYL 4 (3 NITROPHENYL) 2 OXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; N (4 METHOXYPHENYL) 6 METHYL 4 (3 NITROPHENYL) 2 THIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; N (4 METHOXYPHENYL) 6 METHYL 4 PHENYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; N BIS(4 METHOXYPHENYL) 6 METHYL 2 OXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; N BIS(4 METHOXYPHENYL) 6 METHYL 2 THIOXO 1,2,3,4 TETRAHYDROPYRIMIDINE 5 CARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 2,6 DIMETHYL 4 PHENYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 2,6 DIMETHYL 4 STYRYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 4 (2 HYDROXYPHENYL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 4 (3 NITROPHENYL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 4 (4 DIMETHYLAMINO)PHENYL 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 4 (4 HYDROXY 3 METHOXYPHENYL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 4 (4 METHOXYPHENYL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 4 (4 PYRIDYL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; N,N BIS(4 CHLOROPHENYL) 4 (FURAN 2 YL) 2,6 DIMETHYL 1,4 DIHYDROPYRIDINE 3,5 DICARBOXAMIDE; PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; BACILLUS SUBTILIS; BIGINELLI REACTION; COMPARATIVE MOLECULAR FIELD ANALYSIS; CONTROLLED STUDY; CYTOTOXICITY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STAPHYLOCOCCUS AUREUS; VERO CELL;

EID: 77953522443     PISSN: 10542523     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00044-009-9195-7     Document Type: Article

References (38)

1. H Andreas H Gunter B Ute R Detlef 1999 Solid-state photodimerization of 4-aryl-1,4-dihydropyridines studied by 13C CPMAS NMR spectroscopy Solid State NMR 13 231 243 10.1016/S0926-2040(98)00090-3 10.1016/S0926-2040(98)00090-3 (Pubitemid 34867526)
2. ZD Aron LE Overman 2004 The tethered Biginelli condensation in natural product synthesis Chem Commun 3 253 265 10.1039/b309910e 10.1039/b309910e
3. P Biginelli 1893 Aldehyde-urea derivatives of aceto- and oxaloacetic acids Gazz Chim Ital 23 360
4. Bruce TC, Bencovic SJ (1966) Bioorganic mechanism, vol II. W. A. Benjamin, New York, 301 pp
5. M Clark RD Cramer III N Van Opdenbosch 1989 Validation of the general-purpose Tripos 5.2 force-field J Comput Chem 10 982 1012 10.1002/jcc.540100804 10.1002/jcc.540100804 1:CAS:528:DyaK3cXhtlygsbk%3D
6. M Clark RD Cramer III DM Jones DE Patterson PE Simeroth 1990 Comparative molecular field analysis (CoMFA): toward its use with 3D structural databases Tetrahedron Comput Methodol 3 47 59 10.1016/0898-5529(90)90120-W 10.1016/0898-5529(90)90120-W 1:CAS:528:DyaK3MXhtVSmtbs%3D
7. RD Cramer III DE Patterson JD Bunce 1988 Comparative molecular field analysis (CoMFA): effect of shape on binding of steroids to carried protein J Am Chem Soc 110 5959 5967 10.1021/ja00226a005 10.1021/ja00226a005 1:CAS:528:DyaL1cXltVCqsbs%3D
8. RD Cramer III JD Bunce DE Patterson LE Frank 1988 Cross-validation, bootstrapping, and partial least squares compared with multiple regression in conventional QSAR studies Quant Struct Act Relat 7 18 25 10.1002/qsar. 19880070105 10.1002/qsar.19880070105
9. D Dallinger A Stadler CO Kappe 2004 Solid and solution phase synthesis of bioactive dihydropyrimidines Pure Appl Chem 76 1017 1024 10.1351/ pac200476051017 10.1351/pac200476051017 1:CAS:528:DC%2BD2cXlvFehtbc%3D
10. B Desai D Sureja Y Naliapara A Shah AK Saxena 2001 Synthesis and QSAR studies of 4-substituted phenyl-2,6-dimethyl-3,5-bis-n-(substituted phenyl) carbamoyl-1,4-dihydropyridines as potential antitubercular agents Bioorg Med Chem 9 1993 1998 10.1016/S0968-0896(01)00141-9 10.1016/S0968-0896(01)00141-9 1:CAS:528:DC%2BD3MXlvFWiurw%3D 11504636 (Pubitemid 32739187)
11. U Eisner J Kuthan 1972 The chemistry of dihydropyridines Chem Rev 72 1 42 10.1021/cr60275a001 10.1021/cr60275a001 1:CAS:528:DyaE38Xnt1ehsw%3D%3D
12. JJV Eynde O Watte 2003 Insoluble versus soluble polymer-assisted synthesis: a first approach for the preparation of a Biginelli compound Arkivoc 4 93 101
13. Frankel S, Reitman S, Sonnenwirth AC (1970) Gradwol's clinical laboratory methods and diagnosis, 7th edn. Mosby, Germany, 1406 pp
14. J Gasteiger M Marsili 1980 Iterative partial equalization of orbital-electronegativity: a rapid access to atomic charges Tetrahedron 36 3219 3228 10.1016/0040-4020(80)80168-2 10.1016/0040-4020(80)80168-2 1:CAS:528:DyaL3MXhslCjtbs%3D
15. A Hantzsch 1882 Uber die synthese pyridinartiger verbindungen aus acetessigather und aldehydammoniak Justus Liebigs Ann Chim 215 1 15
16. K Hattori Y Kohchi N Oikawa H Suda M Ura T Ishikawa M Miwa M Endoh H Eda H Tanimura A Kawashima I Horii H Ishitsuka N Shimma 2003 Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine Bioorg Med Chem Lett 13 867 872 10.1016/S0960-894X(02)01082-X 10.1016/S0960-894X(02)01082-X 1:CAS:528:DC%2BD3sXhs1altrc%3D 12617910 (Pubitemid 36255556)
17. L Heys CG Moore PJ Murphy 2000 The guanidine metabolites of Ptilocaulis spiculifer and related compounds; isolation and synthesis Chem Soc Rev 29 57 67 10.1039/a903712h 10.1039/a903712h 1:CAS:528:DC%2BD3cXitFartg%3D%3D
18. DC Hooper JS Wolfson GL McHugh MB Winters MN Swartz 1982 Effects of novobiocin, coumermycin A1, clorobiocin, and their analogs on Escherichia coli DNA gyrase and bacterial growth Antimicrob Agents Chemother 22 662 671 1:CAS:528:DyaL3sXhtVCisLY%3D 6295263
19. DA Horton GT Bourne ML Smythe 2003 The combinatorial synthesis of bicyclic privileged structures or privileged substructures Chem Rev 103 893 930 10.1021/cr020033s 10.1021/cr020033s 1:CAS:528:DC%2BD3sXhtlGkt7k%3D 12630855
20. Jones G (1984) Comprehensive heterocyclic chemistry. Pergamon, Oxford, 482 pp
21. CO Kappe 1993 100 years of the Biginelli dihydropyrimidine synthesis Tetrahedron 49 6937 6963 10.1016/S0040-4020(01)87971-0 10.1016/S0040-4020(01) 87971-0 1:CAS:528:DyaK2cXnslWrtA%3D%3D
22. CO Kappe 2000 Biologically active dihydropyrimidines of the Biginelli-type a literature survey Eur J Med Chem 35 1043 1052 10.1016/S0223-5234(00)01189-2 10.1016/S0223-5234(00)01189-2 1:CAS:528: DC%2BD3MXoslWkuw%3D%3D 11248403 (Pubitemid 32050011)
23. CO Kappe 2000 Recent advances in the Biginelli dihydropyrimidine synthesis. New tricks from an old dog Acc Chem Res 33 879 888 10.1021/ar000048h 10.1021/ar000048h 1:CAS:528:DC%2BD3cXmsl2js7k%3D 11123887 (Pubitemid 32056773)
24. CO Kappe 2003 The generation of dihydropyrimidine libraries utilizing Biginelli multicomponent chemistry QSAR Comb Sci 22 630 645 10.1002/qsar. 200320001 10.1002/qsar.200320001 1:CAS:528:DC%2BD3sXms1Whs7Y%3D
25. Kappe CO, Stadler A (2004) The Biginelli dihydropyrimidine synthesis in organic reaction. Wiley, New York, pp 1-116
26. M Kawase A Shah H Gaveriya N Motohashi H Sakagami A Varga J Molnar 2002 3,5-Dibenzoyl-1,4-dihydropyridines: synthesis and MDR reversal in tumor cells Bioorg Med Chem 10 4 1051 10.1016/S0968-0896(01)00363-7 10.1016/S0968-0896(01) 00363-7 1:CAS:528:DC%2BD38XhtVKhsb0%3D 11836114 (Pubitemid 34139920)
27. Kubinyi H, Wolff ME (1995) Burger's medicinal chemistry: principles and practice, 5th edn. Wiley, New York, 498 pp
28. B Loev SJ Ehrreich RE Tedeschi 1972 Dihydropyridines with potent hypotensive activity prepared by the Hantzsch reaction J Pharm Pharmacol 24 917 1008 1:CAS:528:DyaE3sXpt1eqtg%3D%3D 4405663
29. B Loev MM Goodman KM Snader R Tedeschi E Macko 1974 Hantzsch-type dihydropyridine hypotensive agents J Med Chem 17 953 965 10.1021/jm00255a010 10.1021/jm00255a010
30. PP Mager RA Coburn AJ Solo DJ Triggle H Rothe 1992 QSAR, diagnostic statistics and molecular modelling of 1,4-dihydropyridine calcium antagonists: a difficult road ahead Drug Des Discov 8 273 289 1:CAS:528:DyaK3sXntlWgtQ%3D%3D 1445993
31. H Meyer F Bossert E Wehinger K Stoepel W Vater 1981 Synthesis and comparative pharmacological studies of 1,4-dihydro-2,6-dimethyl-4-(3- nitrophenyl) pyridine-3,5-dicarbonsäuereestern with non-identical ester functions Arzneim Forsch 31 407 409 1:CAS:528:DyaL3MXktVKqu7k%3D
32. Moldeus P, Hogberg J, Orrhenius S, Fleischer S, Parker L (1978) Methods in enzymology. Academic Press, New York, pp 60-71
33. S Philip S Rista S Dominic M Anne M James 1990 New colorimetric cytotoxicity assay for anticancer drug screening J Natl Cancer Inst 82 32 1107 1112
34. BR Prashantha Kumar S Yuvaraj A Srivastava V Chaturvedi YK Manju B Suresh MJ Nanjan 2008 CoMFA study, syntheses, antitubercular and anticancer activity of some novel 1,4-dihydropyridines Lett Drug Des Discov 5 7 14 10.2174/157018008783406688 10.2174/157018008783406688 (Pubitemid 351225639)
35. R Shanumugam G Annie PT Perumal 2003 Synthesis of novel 3, 4-dihydropyrimidinones on water soluble solid support catalyzed by indium triflate J Heterocycl Chem 40 879 884 10.1002/jhet.5570400521
36. BB Snider Z Shi 1993 Biomimetic syntheses of (A)-crambines A, B, C1, and C2. Revision of the structures of crambines B and C1 J Org Chem 58 3828 3839 10.1021/jo00067a014 10.1021/jo00067a014 1:CAS:528:DyaK3sXlvVWjtL0%3D
37. DM Stout AI Meyers 1982 Recent advances in the chemistry of dihydropyridines Chem Rev 82 223 243 10.1021/cr00048a004 10.1021/cr00048a004 1:CAS:528:DyaL38XitFOmu7Y%3D
38. T Tsuji T Sawai H Yamashita H Takeshita T Nakagoe S Hidaka A Nanashima H Yamaguchi H Yasutake T Nagayasu Y Tagawa 2004 Tumor dihydropyrimidine dehydrogenase in stage II and III colorectal cancer: low level expression is a beneficial marker in oral-adjuvant chemotherapy, but is also a predictor for poor prognosis in patients treated with curative surgery alone Cancer Lett 204 97 104 10.1016/j.canlet.2003.09.030 10.1016/j.canlet.2003.09.030 1:CAS:528:DC%2BD2cXntV2jsw%3D%3D 14744539 (Pubitemid 38117198)