A series of novel pyranochromene-containing tetrazoles fused with pyrimidinethiones, pyrimidines, and diazepines 3a–f, 4a–f, and 5a–f were synthesized by condensation of the corresponding tetrazoles 2a–f with carbon disulfide, benzaldehyde, and 4-methoxy phenacyl bromide, respectively. The compound 2a–f was obtained by reaction of pyrano[3,2-c]chromenes 1a–f with sodium azide. The structures of the newly synthesized compounds 2a–f to 5a–f were established on the basis of their elemental analyses, IR, 1H NMR, 13C NMR, and mass spectral data. All of the title compounds were subjected to in vitro antibacterial testing against four pathogenic strains and antifungal screening against two fungi. Preliminary results indicate that some of them exhibited promising activities and that they deserve more consideration as potential antimicrobials. 1. Introduction Pyrano[3,2-c]chromene derivatives are a class of important heterocycles with a wide range of biological properties [1] such as spasmolytic, diuretic, anticoagulant, anticancer, and antianaphylactic activities [2–5]. Tetrazoles represent an important class of heterocyclic compounds with wide ranging applications [6]. The synthesis of novel tetrazole derivatives and the investigation of their chemical and biological behavior has gained more importance in the recent decades for biological and pharmaceutical reasons. They have found use in pharmaceuticals as lipophilic spacers and carboxylic acid surrogates, which improves oral absorption [7]. Their derivatives were reported to possess broad spectrum of biological activity in both medicinal and pharmaceutical areas such as antinociceptive [8], antibacterial [9], antifungal [10], anti-HIV, anticancer, immunosuppressive [11], anti-inflammatory [12] and antiulcer [13], antiproliferative [14], antiallergic [15], and analgesic [16] activities. On the other hand, pyrimidine scaffold was the base of many bioactive molecules such as antitubercular, antimicrobial [17], antiviral [18], antitumor [19, 20], anti-inflammatory, analgesic [21], antioxidant [22], antiproliferative [23], and antileishmanial agents [24]. Consequently, synthetic methodologies for synthesis of novel pyrimidines or pyrimidine fused compounds are of particular interests to organic and medicinal chemists. The diazepine family represents one of the most prominent classes of privileged scaffolds in the field of drugs and pharmaceuticals. These compounds are widely used as anticonvulsant, antianxiety, analgesic, sedative, antidepressive, and hypnotic agents [25–27]. In view of the abovementioned facts,
References
[1]
G. R. Green, J. M. Evans, A. K. Vong, A. R. Katritzky, C. W. Rees, and E. F. Scriven, Comprehensive Heterocyclic Chemistry, vol. 5, Pergamon Press, Oxford, UK, 1995.
[2]
W. O. Foye, Principi Di Chemico Frmaceutica, Piccin, Padova, Italy, 1991.
[3]
L. Bonsignore, G. Loy, D. Secci, and A. Calignano, “Synthesis and pharmacological activity of 2-oxo-(2H) 1-benzopyran-3-carboxamide derivatives,” European Journal of Medicinal Chemistry, vol. 28, no. 6, pp. 517–520, 1993.
[4]
L. L. Andreani and E. Lapi, “On some new esters of coumarin-3-carboxylic acid wit balsamic and bronchodilator action,” Bollettino Chimico Farmaceutico, vol. 99, pp. 583–586, 1960.
[5]
E. C. Witte, P. Neubert, and A. Roesch, “7-(piperazinyl propoxy)-2H-1-benzopyran-2-ones,” Ger. Offen DE, 3427985, Chemical Abstracts 104, 224915f, 1986.
[6]
R. N. Butler, A. R. Katritzky, C. W. Rees, and E. F. V. Scriven, Comprehensive Heterocyclic Chemistry, vol. 4, Pergamon Press, Oxford, UK, 1996.
[7]
R. J. Herr, “5-Substituted-1H-tetrazoles as carboxylic acid isosteres: medicinal chemistry and synthetic methods,” Bioorganic and Medicinal Chemistry, vol. 10, no. 11, pp. 3379–3393, 2002.
[8]
A. Rajasekaran and P. P. Thampi, “Synthesis and antinociceptive activity of some substituted-{5-[2-(1,2,3,4- tetrahydrocarbazol-9-yl)ethyl]tetrazol-1-yl}alkanones,” European Journal of Medicinal Chemistry, vol. 40, no. 12, pp. 1359–1364, 2005.
[9]
R. M. Demarinis, J. R. E. Hoover, and G. L. Dunn, “A new parenteral cephalosporin. SK&F 59962: 7 trifluoromethylthioacetamido 3 (1 methyl 1H tetrazol 5 ylthiomethyl) 3 cephem 4 carboxylic acid. Chemistry and structure activity relationships,” Journal of Antibiotics, vol. 28, no. 6, pp. 463–470, 1975.
[10]
R. S. Upadhayaya, S. Jain, N. Sinha, N. Kishore, R. Chandra, and S. K. Arora, “Synthesis of novel substituted tetrazoles having antifungal activity,” European Journal of Medicinal Chemistry, vol. 39, no. 7, pp. 579–592, 2004.
[11]
A. Dlugosz, “Synthesis and biological activity of pyrimidobenzodiazepine derivatives. New ring systems: triazolo- and tetrazolo-pyrimidobenzodiazepines,” Pharmazie, vol. 50, no. 3, pp. 180–182, 1995.
[12]
E. E. Knaus and P. Kumar, “Synthesis and antiinflammatory activity of 5-(1,2-dihydropyridyl)-tetrazol-2-acetic acids, esters and amides,” European Journal of Medicinal Chemistry, vol. 28, no. 11, pp. 881–885, 1993.
[13]
K. Terashima, T. Tanimura, H. Shimamura et al., “Studies on antiulcer agents. II. Antiulcer properties of N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides inhibiting release of histamine from passively sensitized rat peritoneal mast cells,” Chemical and Pharmaceutical Bulletin, vol. 43, no. 6, pp. 1042–1044, 1995.
[14]
A. S. Gundugola, K. L. Chandra, E. M. Perchellet, A. M. Waters, J.-P. H. Perchellet, and S. Rayat, “Synthesis and antiproliferative evaluation of 5-oxo and 5-thio derivatives of 1,4-diaryl tetrazoles,” Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 13, pp. 3920–3924, 2010.
[15]
A. Nohara, H. Kuriki, T. Saijo, H. Sugihara, M. Kanno, and Y. Sanno, “Studies on antianaphylactic agents. 5. Synthesis of 3-(1H-tetrazol-5-yl)chromones, a new series of antiallergic substances,” Journal of Medicinal Chemistry, vol. 20, no. 1, pp. 141–145, 1977.
[16]
A. Rajasekaran and P. P. Thampi, “Synthesis and analgesic evaluation of some 5-[β-(10-phenothiazinyl) ethyl]-1-(acyl)-1,2,3,4-tetrazoles,” European Journal of Medicinal Chemistry, vol. 39, no. 3, pp. 273–279, 2004.
[17]
N. R. Kamdar, D. D. Haveliwala, P. T. Mistry, and S. K. Patel, “Design, synthesis and in vitro evaluation of antitubercular and antimicrobial activity of some novel pyranopyrimidines,” European Journal of Medicinal Chemistry, vol. 45, no. 11, pp. 5056–5063, 2010.
[18]
D. Hocková, A. Holy, M. Masojídková et al., “Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2- (phosphonomethoxy)ethoxy]pyrimidine and related compounds,” Bioorganic and Medicinal Chemistry, vol. 12, no. 12, pp. 3197–3202, 2004.
[19]
R. Lin, S. G. Johnson, P. J. Connolly et al., “Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d] pyrimidine analogues as anti-tumor epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors,” Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 8, pp. 2333–2337, 2009.
[20]
A. A. Aly, M. Ramadan, A. M. Mohamed, and E. A. Ishak, “Thieno[2, 3-d]pyrimidines in the synthesis of new fused heterocyclic compounds of prospective antitumor and antioxidant agents,” Journal of Heterocyclic Chemistry, vol. 49, no. 5, pp. 1009–1018, 2012.
[21]
M. T. Chhabria, H. G. Bhatt, H. G. Raval, and P. M. Oza, “Synthesis and biological evaluation of some 5-ethoxycarbonyl-6-isopropylamino-4-(substitutedphenyl)aminopyrimidines as potent analgesic and anti-inflammatory agents,” Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 4, pp. 1022–1024, 2007.
[22]
Y. Kotaiah, N. Harikrishna, K. Nagaraju, and C. V. Rao, “Synthesis and antioxidant activity of 1, 3, 4-oxadiazole tagged thieno[2, 3-d]pyrimidine derivatives,” European Journal of Medicinal Chemistry, vol. 58, pp. 340–345, 2012.
[23]
A. M. Marini, F. da Settimo, S. Salerno et al., “Synthesis and in vitro antiproliferative activity of new substituted benzo[3′,2′:5,6]thiopyrano[4,3-d]pyrimidines,” Journal of Heterocyclic Chemistry, vol. 45, no. 3, pp. 745–749, 2008.
[24]
A. Agarwal, R. Ramesh, A. Ashutosh, N. Goyal, P. M. S. Chauhan, and S. Gupta, “Dihydropyrido[2,3-d]pyrimidines as a new class of antileishmanial agents,” Bioorganic and Medicinal Chemistry, vol. 13, no. 24, pp. 6678–6684, 2005.
[25]
J. K. Landquist, A. R. Katritzky, and C. W. Rees, Comprehensive Heterocyclic Chemistry, vol. 1, Pergamon Press, Oxford, UK, 1984.
[26]
U. Rudolph and H. M？hler, “GABA-based therapeutic approaches: GABAA receptor subtype functions,” Current Opinion in Pharmacology, vol. 6, no. 1, pp. 18–23, 2006.
[27]
L. Costantino and D. Barlocco, “Privileged structures as leads in medicinal chemistry,” Current Medicinal Chemistry, vol. 13, no. 1, pp. 65–85, 2006.
[28]
S. Kanakaraju, B. Prasanna, S. Basavoju, and G. V. P. Chandramouli, “Ionic liquid catalyzed one-pot multi-component synthesis, characterization and antibacterial activity of novel chromeno[2, 3-d]pyrimidine-8-amine derivatives,” Journal of Molecular Structure, vol. 1017, pp. 60–64, 2012.
[29]
S. Kanakaraju, B. Prasanna, and G. V. P. Chandramouli, “An efficient one-pot three-component synthesis of novel sulfanyl tetrazoles using ionic liquids,” Journal of Chemistry, vol. 2013, Article ID 104690, 6 pages, 2013.
[30]
S. Abdolmohammadi and S. Balalaie, “Novel and efficient catalysts for the one-pot synthesis of 3,4-dihydropyrano[c]chromene derivatives in aqueous media,” Tetrahedron Letters, vol. 48, no. 18, pp. 3299–3303, 2007.
[31]
P. R. Murray, E. J. Baron, M. A. Pfaller et al., Manual of Clinical Microbiology, American Society of Microbiology, Washington, DC, USA, 1995.
