Asian Journal of Research in Chemistry

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Synthesis of Substituted Thienopyrimidines and Their Evaluation as Antibacterial


Affiliations
1 Department of Pharmaceutical Chemistry, Nargund College of Pharmacy, Dattatreya Nagar, II main, 100 Ft Ring Road, BSK II Stage, Bangalore- 560085, India
2 Department of Chemistry, Texas State University, San Marcos, United States
     

   Subscribe/Renew Journal


We have synthesized various substituted thieno(2,3-d)pyrimidines, first by synthesizing ethyl 2-aminothiophene-3- carboxylate (3), by treatment of diethane with ethyl cynoacetate in presence of triethylamine, acetic acid and DMF. Further, the intermediate Ethyl 2-(ethoxycarbonyl)thiophene-3-carboxylate (5) was prepared by compound (3) refluxed with ethyl chloroformate. The key intermediate 3-(3-chloro-4-fluorophenyl) thieno [2, 3-d]pyrimidine-2, 4(1H, 3H)-dione (7) was prepared by cyclisation of compound (5) with 3-chloro-4-fluoro aniline. The nucleophilic substitution of compound 3-(3-chloro-4-fluorophenyl) thieno [2, 3-d]pyrimidine-2, 4(1 H, 3 H)-dione (7) with various aromatic amines(8a-m), aminophenol(8n) gives substituted thienopyrimidines(8a-n). The synthesized new compounds were characterized by MP, TLC, IR and NMR spectra.

Keywords

Thienopyrimidine
Subscription Login to verify subscription
User
Notifications
Font Size


  • Kavitha PN, Vijayanthimala P, Saravanan J and Mohan S. Synthesis, characterization and in-vitro antimicrobial activity of some novel 3-substituted amino 2-mercapto 5,6,7,8-tetra hydro benzo(b)thieno-(2,3-d)-pyrimidine-4-(3H)-one. Research Journal of Pharmaceutical Biological Chemical Sciences, 2010, 2, 124-30.

  • Shetty NS, Lamani RS and Khazi IA. Synthesis and antimicrobial activity of some novel thienopyrimidines and triazolothienopyrimidines. Journal of Chemical Sciences, 2009, 121 (3), 301-07.

  • Salahuddin M, Kakad S and Shantakumar SM. Synthesis of some novel thieno[2, 3d] pyrimidines and their antibacterial activity. EJournal of Chemistry. 6 (3); 2009: 801-08.

  • Ei-Saghier AM, Matough FS, Farhat MF, Saleh NA, Kreddan KM, Ei-Tier SO, et al., Synthesis and biological evaluation of some new thienopyridine and thienopyrimidine derivatives. Jordan Journal of Chemistry, 2008,3 (3), 223-32.

  • Abdel-Fattah B, Kandeel MM, Abdel-Hakeem M, and Fahmy ZM. Synthesis of certain fused thienopyrimidines of biological interest. Journal of Chinese Chemical Society, 2006, 53, 403- 12.

  • Alagarsamy V, Meena S, Ramseshu KV, Soloman VR, Thirumurugan K and Dhanabal K. Synthesis, analgesic, antiinflammatory, ulcerogenic index and antibacterial activities of Novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno (2, 3-d) pyrimidine-4(3H)-ones. European Journal of Medicinal Chemistry, 2006, 41(11), 1293-1300.

  • Adrian J, Khatereh A, Wendy K, Sonia A, Stewart J, Gary B, et.al., The identification of 2-(1H-indazol-4-yl)-6-(4- methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno [3,2-d] pyrimidine as a potent, selective, orally bioavailable inhibitor of Class I PI3 Kinase for the treatment of Cancer. Journal of Medicinal Chemistry, 2008, 51, 5522–32.

  • Jennings LD, Kincaid SL, Yanong DW, Krishnamurthy G, Beyer CF. Parallel synthesis and biological evaluation of 5,6,7,8- tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one cytotoxic agents selective for p21-deficient cells. Bioorganic and Medicinal Chemistry Letters, 2005,15,4731-35.

  • Wang YD, Johnson S, Powell D, McGinnis JP, Miranda M, Rabindran SK. Inhibition of tumour cell proliferation by thieno[2,3-d]pyrimidin-4(1H)-one-based analogs. Bioorganic and Medicinal Chemistry Letters, 2005, 15, 3763-66.

  • Horiuchi T, Chiba J, Uoto K, Soga T. Discovery of novel thieno[2,3-d]pyrimidin-4-yl Bioorganic and Medicinal Chemistry Letters, 2009, 19, 305–08.

  • Ogawva K, Yamawaki I, Mtsusita YI, Nomura N, Kador PF, Kinoshita JH, et al., syntheses of substituted 2,4-dioxothienopyrimidin- 1-acetic acids and their evaluation as aldose reductase inhibitors. European Journal of Medicinal Chemistry. 1993, 28, 769-781

  • Deng J, Peng L, Zhang G and Hu W. The highly potent and selective dipeptidyl peptidase IV inhibitors bearing a thienopyrimidine scaffold effectively treat type-2 diabetes. European Journal of Medicinal Chemistry, 2010, 30, 1-6.

  • Rashad AE, Shamroukh AH, Abdel-Megeid RE, Mostafa A, El- Shesheny R, Kandeil A, et al. Synthesis and screening of some novel fused thiophene and thienopyrimidine derivatives for antiavian influenza virus (H5N1) activity. European Journal of Medicinal Chemistry. 2010, 45, 5251-257.

  • Angell A, McGuigan C, Sevillano LG, Snoeck R, Andrei G, Clercq ED, et al. , Bicyclic anti-VZV nucleosides: Thieno analogues bearing an alkyl phenyl side chain have reduced antiviral activity. Bioorganic and Medicinal Chemistry Letters. 2004, 14, 2397–99.

  • El-Gazzar AB, Hussein HA and Hafez HN. Synthesis and biological evalution of thieno[2,3-d] pyrimidine derivatives for anti-inflammatory, analgesic and ulcerogenic activity. Acta Pharmaceutica. 2007, 57, 395-411.

  • Algarsamy V, Vijaykumar S and Solomon VR. Synthesis of 2- mercapto-3-substituted-5,6-dimethylthieno[2,3-d]pyrimidine- 4(3H)-ones as new analgesic, anti-inflammatory agents. Biomedicine and Pharmacotherapy, 2007, 61, 285-91.

  • Santagati M, Modica M, Santagati A, Russo F, Spampinato S. Synthesis of aminothienopyrimidine and thienotriazolopyrimidine derivatives as potential anticonvulsant agents. Pharmazie. 1996, 51(1), 7-11.

  • Sharma C, Yerande S, Chavan R and Bhosale AV. Synthesis of thienopyrimidines and their antipsychotic activity. E-Journal of Chemistry, 2010, 7(2), 655-64.

  • Donkor IO, Hui Li and Queener SF. Synthesis and DHFR inhibitory activity of a series of 6-substituted-2, 4- diaminothieno[2,3-d]pyrimidines. European Journal of Medicinal Chemistry. 2003, 38, 605-11.

  • Michael JM, Jean SB, Jeffery MC, Beth AC, Jonathan LD. Design and SAR of thienopyrimidines inhibitors of VEGFR-2 kinase activity. Bioorganic and Medicinal Chemistry Letters, 2004, 14, 21-24.

  • Dai Y, Guo Y, Frey RR, Zhiqin J, Curtin ML, Ahmed AA, et al. Thienopyrimidine ureas as novel and potent multi targeted recept or tyrosine kinase inhibitors. Journal of Medicinal Chemistry, 2005, 48, 6066-83.

  • Prasad RM, Raghuram RA, Rao PS, Rajan KS, Meena S and Madhavi K. Synthesis and adenosine receptor binding studies of some novel triazolothienopyrimidines. European Journal of Medicinal Chemistry, 2008, 43, 614-20.

  • Hesse S, Perspicace E, Kirsch G. Microwave-assisted synthesis of 2-aminothiophene-3-carboxylic acid derivatives, 3H-thieno [2,3-d]pyrimidin-4-one and 4-chlorothieno[2,3-d]pyrimidine. Tetrahedron Letters, 2007, 48(30), 5261-5264.

  • Afolayan, A.J.; Meyer, J.J.M. The antimicrobial activity of 3,5,7- trihydroxyflavone isolated from the shoots of Helichrysum aureonitens. Journal of Ethnopharmacology 1997; 57: 177- 181


Abstract Views: 453

PDF Views: 2




  • Synthesis of Substituted Thienopyrimidines and Their Evaluation as Antibacterial

Abstract Views: 453  |  PDF Views: 2

Authors

Rahul More
Department of Pharmaceutical Chemistry, Nargund College of Pharmacy, Dattatreya Nagar, II main, 100 Ft Ring Road, BSK II Stage, Bangalore- 560085, India
J. N. Narendra Sharath Chandra
Department of Pharmaceutical Chemistry, Nargund College of Pharmacy, Dattatreya Nagar, II main, 100 Ft Ring Road, BSK II Stage, Bangalore- 560085, India
Shachindra. L. Nargund
Department of Chemistry, Texas State University, San Marcos, United States
L.V.G. Nargund
Department of Pharmaceutical Chemistry, Nargund College of Pharmacy, Dattatreya Nagar, II main, 100 Ft Ring Road, BSK II Stage, Bangalore- 560085, India

Abstract


We have synthesized various substituted thieno(2,3-d)pyrimidines, first by synthesizing ethyl 2-aminothiophene-3- carboxylate (3), by treatment of diethane with ethyl cynoacetate in presence of triethylamine, acetic acid and DMF. Further, the intermediate Ethyl 2-(ethoxycarbonyl)thiophene-3-carboxylate (5) was prepared by compound (3) refluxed with ethyl chloroformate. The key intermediate 3-(3-chloro-4-fluorophenyl) thieno [2, 3-d]pyrimidine-2, 4(1H, 3H)-dione (7) was prepared by cyclisation of compound (5) with 3-chloro-4-fluoro aniline. The nucleophilic substitution of compound 3-(3-chloro-4-fluorophenyl) thieno [2, 3-d]pyrimidine-2, 4(1 H, 3 H)-dione (7) with various aromatic amines(8a-m), aminophenol(8n) gives substituted thienopyrimidines(8a-n). The synthesized new compounds were characterized by MP, TLC, IR and NMR spectra.

Keywords


Thienopyrimidine

References