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Arzneimittelforschung 2008; 58(10): 521-528
DOI: 10.1055/s-0031-1296552
Antibiotics · Antimycotics · Antiparasitics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

Synthesis and Antitumor Screening of Novel 3-Phenylthiazolo [4,5-d]pyrimidin-2-thione Derivatives

Lilianna Becan
Department of Drugs Technology, Wroclaw Medical University, Wroclaw, Poland
,
Edwin Wagner
Department of Drugs Technology, Wroclaw Medical University, Wroclaw, Poland
› Author Affiliations
Further Information

Publication History

Publication Date:
19 December 2011 (online)

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Abstract

A series of new derivatives of 3-phenylthiazolo[4,5-d]pyrimidine-2-thiones were synthesized by the cyclization of 4-amino-5-alkyl(aryl) carboxamido-2,3-dihydrothiazolo-2-thione with aromatic aldehydes. Amine moieties were substituted in position 7 of the obtained bicyclic compounds. The synthesized compounds were characterized by elemental analysis, IR, 1H-NMR, and 13C-NMR spectral data. Some of the newly synthesized compounds were selected by the US National Cancer Institute for in vitro antitumor screening. The two compounds 3d 7-chloro-5-(4-fluorophenyl)-3-phenyl-4,5-di-hydro-3H-thiazolo[4,5-(flpyrimidine-2-thione and 4i 5-(2-chlorophenyl)-7-(4-fluorobenzylamino)-3-phenyl-4,5-dihydro-3H-thiazolo[4,5-d]pyrimidine-2-thione proved to be the most active in the present study and their antitumor activities against 60 human tumor cell lines were described.

Key words

Antitumor agents - Thiazolo[4,5-d]pyrimidines, in vitro studies, synthesis
 

  • References

  • 1 Rida SM, Habib NS, Badawey EAM, Fahmy HTY, Ghozlan HA. Synthesis of novel thiazolo[4,5-d]pyrimidine derivatives for antimicrobial, anti-HIV and anticancer investigation. Pharmazie. 1996; 51: 927-931
    PubMedGoogle Scholar
  • 2 Fahmy HTY, Rostom SAF, Bekhit AA. Synthesis and Antitumor Evaluation of New Polysubstituted Thiazole and Derived Thiazolo[4.5-d]pyrimidine Systems. Arch Pharm Pharm Med Chem. 2002; 5: 213-222
    PubMedGoogle Scholar
  • 3 Fahmy HTY, Rostom AAF, Saudi MN, Zjawiony JK, Robins DJ. Synthesis and in vitro evaluation of the anticancer activity of novel fluorinated thiazolo[4,5-d]pyrimidines. Arch Pharm Pharm Med Chem. 2003; 336: 216-225
    CrossrefPubMedGoogle Scholar
  • 4 Urgun H, Balkan A, Özalp M. New Thiazolo[4,5-d]pyrimi dine Derivatives as Potential Antimicrobial Agents. Arzneimittel-Forschung (Drug Research). 2000; 50: 1115-1119
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Balkan A, Urgun H, Özalp M. Synthesis and Antimicrobial Evaluation of Some New Thiazolo[4,5-d]pyrimidines. Arzneimittel-Forschung (Drug Research). 2001; 51: 839-842
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Bekhit AA, Fahmy HTY, Rostom SAF, Baraka AM. Design and synthesis of some substituted lH-pyrazolyl-thiazolo [4,5-d]pyrimidines as anti-inflammatory-antimicrobial Agents. Eur J Med Chem. 2003; 38: 27-36
    CrossrefPubMedGoogle Scholar
  • 7 Balkan A, Gören Z, Urgun H, Çali Ü, Çakar AN, Atilla P et al. Evaluation of the Analgesic and Anti-inflammatory Activities of Some Thiazolo[4,5-d]pyrimidines. Arzneimittel-Forschung (Drug Research). 2002; 52: 462-67
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Devani MB, Shishoo CJ, Pathak US, Parikh SH, Radhakrishnan AV, Padhya AC. Synthesis and Pharmacological Properties of some 4-Amino-5-substituted Thiazole-2(3H)-thiones and Thiazolo[4,5-d]pyrimidin-7(6H)-one-2(3H)-thiones. Arzneimittel-Forschung (Drug Research). 1977; 27: 1652-1655
    PubMedGoogle Scholar
  • 9 Beck JP, Curry MA, Chorvat RJ, Fitzgerald LW, Giligan PJ, Zaczek R et al. Thiazolo[4,5-d]pyrimidine thiones and -ones as corticotrophin-releasing hormone (CRH-R1) receptor antagonists. Bioorg Med Chem Lett. 1999; 9: 1185-1188
    CrossrefPubMedGoogle Scholar
  • 10 Lewis AF, Drach JC, Fennewald SM, Huffman JH, Ptak RG, Sommadossi JP et al. Inhibition of Human Cytomegalovirus in Culture by Alkenyl Guanine Analogs of the Thiazolo[4,5-d]Pyrimidine Ring System. Antimicrob Agents Chemother. 1994; 38: 2889-2895
    CrossrefPubMedGoogle Scholar
  • 11 Revankar GR, Ojwang JO, Mustain SD, Rando RF, De Clerq E, Huffman JH et al. Thiazolo[4,5-d]pyrimidines. Part II. Synthesis and anti-human cytomegalovirus activity in vitro of certain acyclonucleosides and acyclonucleosides derived from the guanine analogue 5-aminothiazolo[4,5-d]-pyrimidine-2,7(3H,6H)-dione. Antivir Chem Chemother. 1998; 9: 53-63
    PubMedGoogle Scholar
  • 12 Gewald K. Reaktion von methylenaktiven Nitrilen mit Senfölen und Schwefel. J Prakt Chem. 1966; 32: 26-30
    CrossrefPubMedGoogle Scholar
  • 13 Monks A, Scudiero DA, Skehan P, Shoemaker RH, Paull KD, Vistica DT et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst. 1991; 83: 757-766
    CrossrefPubMedGoogle Scholar
  • 14 Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL et al. Feasility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988; 48: 589-601
    PubMedGoogle Scholar
  • 15 Shoemaker RH, Monks S, Alley MC, Scudiero DA, Fine DL, McLemore TL et al. Development of human tumor cell line panels for use in disease-oriented drug screening. Prog Clin Biol Res. 1988; 276: 265-286
    PubMedGoogle Scholar
  • 16 Skehan P, Storeng R, Scudiero DA, Monks A, McMahon J, Vistica D et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst. 1990; 82: 1107-1112
    CrossrefPubMedGoogle Scholar
  • 17 Rubinstein LV, Shoemaker RH, Paull KD, Simon RM, Tosini S, Skehan P et al. Comparison of in vitro anticancer-drug-screening data generated with a tetra-zolium assay versus a protein assay against a diverse panel of human tumor cell lines. J Natl Cancer Inst. 1990; 82: 1113-1118
    CrossrefPubMedGoogle Scholar