Synthesis of 3-(Pyridin-2-yl)quinazolin-2,4(13)-diones Via Annulation of Anthranilic Esters with -pyridyl Ureas

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Apr 28

PMID 37108796

Authors

Svetlana O Baykova

Kirill K Geyl

Sergey V Baykov

Vadim P Boyarskiy

Affiliations

Soon will be listed here.

Abstract

A new route for the synthesis of quinazolin-2,4(13)-diones and thieno [2,3-]pyrimidine-2,4(1,3)-diones substituted by pyridyl/quinolinyl moiety in position 3 has been developed. The proposed method concluded in an annulation of substituted anthranilic esters or 2-aminothiophene-3-carboxylates with 1,1-dimethyl-3-(pyridin-2-yl) ureas. The process consists of the formation of -aryl-'-pyridyl ureas followed by their cyclocondensation into the corresponding fused heterocycles. The reaction does not require the use of metal catalysts and proceeds with moderate to good yields (up to 89%). The scope of the method is more than 30 examples, including compounds with both electron-withdrawing and electron-donating groups, as well as diverse functionalities. At the same time, strong electron-acceptor substituents in the pyridine ring of the starting ureas reduce the product yield or even prevent the cyclocondensation step. The reaction can be easily scaled to gram quantities.

References

Dong X, Ma P, Zhang T, Jalani H, Li G, Lu H . Iridium-Catalyzed C-H Amination of Weinreb Amides: A Facile Pathway toward Anilines and Quinazolin-2,4-diones. J Org Chem. 2020; 85(20):13096-13107. DOI: 10.1021/acs.joc.0c01789. View

El-Adl K, El-Helby A, Sakr H, El-Hddad S . Design, synthesis, molecular docking, and anticancer evaluations of 1-benzylquinazoline-2,4(1H,3H)-dione bearing different moieties as VEGFR-2 inhibitors. Arch Pharm (Weinheim). 2020; 353(8):e2000068. DOI: 10.1002/ardp.202000068. View

Falsini M, Squarcialupi L, Catarzi D, Varano F, Betti M, Di Cesare Mannelli L . 3-Hydroxy-1H-quinazoline-2,4-dione as a New Scaffold To Develop Potent and Selective Inhibitors of the Tumor-Associated Carbonic Anhydrases IX and XII. J Med Chem. 2017; 60(14):6428-6439. DOI: 10.1021/acs.jmedchem.7b00766. View

Lee S, Xing J, Catlett I, Adamczyk R, Griffies A, Liu A . Safety, pharmacokinetics, and pharmacodynamics of BMS-986142, a novel reversible BTK inhibitor, in healthy participants. Eur J Clin Pharmacol. 2017; 73(6):689-698. PMC: 5423977. DOI: 10.1007/s00228-017-2226-2. View

Boshta N, El-Essawy F, Alshammari M, Noreldein S, Darwesh O . Discovery of Quinazoline-2,4(1,3)-Dione Derivatives as Potential Antibacterial Agent: Design, Synthesis, and Their Antibacterial Activity. Molecules. 2022; 27(12). PMC: 9228007. DOI: 10.3390/molecules27123853. View

Ueno M, Rao S, Angiolillo D . Elinogrel: pharmacological principles, preclinical and early phase clinical testing. Future Cardiol. 2010; 6(4):445-53. DOI: 10.2217/fca.10.67. View

Geyl K, Baykov S, Kalinin S, Bunev A, Troshina M, Sharonova T . Synthesis, Structure, and Antiproliferative Action of 2-Pyridyl Urea-Based Cu(II) Complexes. Biomedicines. 2022; 10(2). PMC: 8962293. DOI: 10.3390/biomedicines10020461. View

Gao B, Voskoboynik M, Cooper A, Wilkinson K, Hoon S, Hsieh C . A phase 1 dose-escalation study of the poly(ADP-ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors. Cancer. 2023; 129(7):1041-1050. DOI: 10.1002/cncr.34662. View

Dhillon S . Carotegrast Methyl: First Approval. Drugs. 2022; 82(9):1011-1016. DOI: 10.1007/s40265-022-01732-0. View

10.

Siller-Matula J, Krumphuber J, Jilma B . Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases. Br J Pharmacol. 2010; 159(3):502-17. PMC: 2828016. DOI: 10.1111/j.1476-5381.2009.00555.x. View

11.

Tatarinov D, Garifullin B, Belenok M, Andreeva O, Strobykina I, Shepelina A . The First 5'-Phosphorylated 1,2,3-Triazolyl Nucleoside Analogues with Uracil and Quinazoline-2,4-Dione Moieties: A Synthesis and Antiviral Evaluation. Molecules. 2022; 27(19). PMC: 9573387. DOI: 10.3390/molecules27196214. View

12.

Ali E, Abdel-Maksoud M, Oh C . Thieno[2,3-d]pyrimidine as a promising scaffold in medicinal chemistry: Recent advances. Bioorg Med Chem. 2019; 27(7):1159-1194. DOI: 10.1016/j.bmc.2019.02.044. View

13.

Qin D, Lin X, Liu Z, Chen Y, Zhang Z, Wu C . Discovery of Orally Bioavailable Ligand Efficient Quinazolindiones as Potent and Selective Tankyrases Inhibitors. ACS Med Chem Lett. 2021; 12(6):1005-1010. PMC: 8201761. DOI: 10.1021/acsmedchemlett.1c00160. View

14.

Ji Q, Yang D, Wang X, Chen C, Deng Q, Ge Z . Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents. Bioorg Med Chem. 2014; 22(13):3405-13. DOI: 10.1016/j.bmc.2014.04.042. View

15.

Hu W, Zhang F, Chen C, Qi T, Shen Y, Qian G . Metal-free C8-H functionalization of quinoline -oxides with ynamides. Chem Commun (Camb). 2021; 57(57):6995-6998. DOI: 10.1039/d1cc02138a. View

16.

Shimoshige Y, Minoura K, Matsuoka N, Takakura S, Mutoh S, Kamijo M . Thirteen-month inhibition of aldose reductase by zenarestat prevents morphological abnormalities in the dorsal root ganglia of streptozotocin-induced diabetic rats. Brain Res. 2008; 1247:182-7. DOI: 10.1016/j.brainres.2008.10.018. View

17.

Zou F, Wang Y, Yu D, Liu C, Lu J, Zhao M . Discovery of the thieno[2,3-d]pyrimidine-2,4-dione derivative 21a: A potent and orally bioavailable gonadotropin-releasing hormone receptor antagonist. Eur J Med Chem. 2022; 242:114679. DOI: 10.1016/j.ejmech.2022.114679. View

18.

Dewal M, Wani A, Vidaillac C, Oupicky D, Rybak M, Firestine S . Thieno[2,3-d]pyrimidinedione derivatives as antibacterial agents. Eur J Med Chem. 2012; 51:145-53. PMC: 3340521. DOI: 10.1016/j.ejmech.2012.02.035. View

19.

Loomba R, Noureddin M, Kowdley K, Kohli A, Sheikh A, Neff G . Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH. Hepatology. 2020; 73(2):625-643. DOI: 10.1002/hep.31622. View

20.

Miwa K, Hitaka T, Imada T, Sasaki S, Yoshimatsu M, Kusaka M . Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human.... J Med Chem. 2011; 54(14):4998-5012. DOI: 10.1021/jm200216q. View