European Journal of Chemistry 2011, 2(2), 251-259 | doi: https://doi.org/10.5155/eurjchem.2.2.251-259.380 | Get rights and content






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Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton


Hatem Moustafa Gaber (1,*) , Tarek Abdel-Mawgoud Moussa (2)

(1) National Organization for Drug Control and Research (NODCAR), Cairo-12553, Egypt
(2) Botany Department, Faculty of Science, Cairo University, Giza 12613, Egypt
(*) Corresponding Author

Received: 01 Jan 2011 | Revised: 15 Mar 2011 | Accepted: 04 Feb 2011 | Published: 30 Jun 2011 | Issue Date: June 2011

Abstract


Versatile 2-(alkylthio)pyrimidine-type and 2-(phenacylamino)thiophene building blocks (4a-d) and 16 were obtained based on an ortho functionalized thiophene derivative 1. A novel series of thieno[2,3-d]pyrimidin-4-one derivatives with annelated bridgehead nitrogen heterocycles was synthesized starting from precursors 4 and 16 through convenient methods. Cyclocondensation of 2-(phenacylthio)pyrimidinone derivative (4b) with sulfuric acid led to the tricyclic thiazole derivative 5. Initial hydrazinolysis of 3-(carbethoxymethyl)pyrimidinone derivative (4d) followed by nitrous acid deamination of the formed N-aminolactam (7) to obtain a N-protodeamino analogue 8a, which on further treatment with formaldehyde and piperidine yielded the respective Mannich-type base 8b. On the other hand, initial hydrazinolysis of 3-unsubstituted pyrimidinone derivative 4a and subsequent acetylation gave the condensed 3-methyltriazole derivative 12, whereas the condensed pyrrole derivative 19 was obtained by heterocyclization of 2-phenacylamine derivative 16 with malononitrile. All newly-obtained thienopyrimidinones with annelated bridgehead nitrogen were screened for their antimicrobial activity against strains of a representative panel of Gram-positive and Gram-negative bacteria as well as fungi together with reference drugs. The compounds under investigation displayed generally good in vitro antibacterial and antifungal activities, with compound 8b that has a N-piperidinylmethyl moiety showing essentially the highest inhibition in both assays. Despite promising antimicrobial activity of N-1-substituted imidazole derivative 8b, the corresponding N-1-unsubstituted analogue 8a displayed poor activity. The heteroannelation of a N-(piperidinylmethyl)imidazole or 3-methyltriazole moiety to the thienopyrimidinone scaffold could be considered as a potential strategy for the development of new therapeutic antimicrobial agents.2_2_251_259_800

Keywords


Thienopyrimidinone; Alkylation; Cyclodehydration; Hydrazinolysis; Acetylation; Antimicrobial activity

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DOI: 10.5155/eurjchem.2.2.251-259.380

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[1]. Sergei A. Shipilovskikh, Aleksandr E. Rubtsov
One-Pot Synthesis of Thieno[3,2-e]pyrrolo[1,2-a]pyrimidine Derivative Scaffold: A Valuable Source of PARP-1 Inhibitors
The Journal of Organic Chemistry  84(24), 15788, 2019
DOI: 10.1021/acs.joc.9b00711
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How to cite


Gaber, H.; Moussa, T. Eur. J. Chem. 2011, 2(2), 251-259. doi:10.5155/eurjchem.2.2.251-259.380
Gaber, H.; Moussa, T. Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton. Eur. J. Chem. 2011, 2(2), 251-259. doi:10.5155/eurjchem.2.2.251-259.380
Gaber, H., & Moussa, T. (2011). Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton. European Journal of Chemistry, 2(2), 251-259. doi:10.5155/eurjchem.2.2.251-259.380
Gaber, Hatem, & Tarek Abdel-Mawgoud Moussa. "Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton." European Journal of Chemistry [Online], 2.2 (2011): 251-259. Web. 11 Aug. 2020
Gaber, Hatem, AND Moussa, Tarek. "Regioselective synthesis and antimicrobial studies of novel bridgehead nitrogen heterocycles containing the thienopyrimidinone skeleton" European Journal of Chemistry [Online], Volume 2 Number 2 (30 June 2011)

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