Pyrido[2,3-d]pyrimidin-7-ones: synthesis and biological properties

Authors

  • H. M. Zinchenko V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Ukraine
  • L. V. Muzychka V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Ukraine
  • O. B. Smolii V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.19.182845

Keywords:

pyrido[2, 3-d]pyrimidin-7-ones, functionalized pyrimidines and pyridines, cyclization, intramolecular cyclocondensation, kinase inhibitors

Abstract

The review summarizes and systematizes data of the last twenty years on the synthetic methods and biological properties of pyrido[2,3-d]pyrimidin-7-ones, promising objects of organic and pharmaceutical chemistry. Two main approaches to the formation of the pyrido[2,3-d]pyrimidine system are considered. The first of them involves the cyclization of substituted pyridines containing functional groups in positions 2 and 3 of the heterocyclic ring. The second approach is based on the formation of a bicyclic system by adding a pyridone moiety to the pyrimidine ring. The methods developed allow to introduce various functional groups and aromatic substituents into the pyrido[2,3-d]pyrimidine system, as well as to obtain most of the target products with high yields. The effective three-component one-pot synthetic approaches to the formation of pyridine ring with the participation of functionalized pyrimidines and compounds with an active methylene group have been proposed. The analysis of the literature has shown that functionalized pyrimidines are the most common starting reagents, which structural modification is useful for the further annelation of the pyridine cycle. Much attention is paid to the biological properties of pyrido[2,3-d]pyrimidin-7-ones. The prospect of using pyrido[2,3-d]pyrimidin-7-one derivatives as tyrosine kinase inhibitors has been shown. Data on the biological effects of pyrido[2,3-d]pyrimidin-7-one derivatives indicate the possibility of detecting new biologically active compounds among pyridopyrimidines.

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References

  1. Kraus, G. A., Gupta, V., Mokhtarian, M., Mehanovic, S., Nilsen-Hamilton, M. (2010). New effective inhibitors of the Abelson kinase. Bioorganic and Medicinal Chemistry, 18 (17), 6316–6321. https://doi:10.1016/ j.bmc.2010.07.021
  2. Antczak, C., Veach, D. R., Ramirez, C. N., Minchenko, M. A., Shuma, D., Calder, P. A., Frattini, M. G., Clarkson, B., Djaballah, H. (2009). Structure–activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorganic and Medicinal Chemistry Letters, 19 (24), 6872–6876. https://doi.org/10.1016/j.bmcl.2009.10.085
  3. Zhang, X., Huang, Y., Navarro, M. T., Hisoire, G., Caulfield, J. P. (2010). A Proof-of-concept and drug-drug Interaction study of Pamapimod, a novel p38 MAP kinase inhibitor, with methotrexate in patients with rheumatoid arthritis. Journal of Clinical Pharmacology, 50 (9), 1031–1038. https://doi.org/10.1177/0091270009357433
  4. Zhao, X., Ning, L., Xie, Z., Jie, Zh., Li, X., Wan, X., Sun, X., Huang, B., Tang, P., Shen, S., Qin, A., Ma, Y., Song, L., Fan, S., Wan, S. (2019). The novel p38 inhibitor, Pamapimod, inhibits osteoclastogenesis and counteracts estrogen-dependent bone loss in mice. Journal of Bone and Mineral Research, 34 (5), 911–922. https://doi.org/10.1002/jbmr.3655
  5. Cadoo, K. A., Gucalp, A., Traina, T. A. (2014). Palbociclib: an evidence-based review of its potential in the treatment of breast cancer. Breast Cancer: Targets and Therapy, 6, 123–133. http://dx.doi.org/10.2147/BCTT.S46725
  6. Lu, J. (2015). Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. Journal of Hematology and Oncology, 8 (98), 1–3. https://doi.org/10.1186/s13045-015-0194-5
  7. Kim, E. S., Scott, L. J. (2017). Palbociclib: a review in HR-positive, HER2-negative, advanced or metastatic breast cancer. Targeted Oncology, 12 (3), 373–383. https://doi.org/10.1007/s11523-017-0492-7
  8. Buron, F., Merour, J. Y., Akssira, M., Guillaumet, G., Routier, S. (2015). Recent advances in the chemistry and biology of pyridopyrimidines. European Journal of Medicinal Chemistry, 95, 76–95. http://dx.doi.org/10.1016/j.ejmech.2015.03.029
  9. Shamroukh, A. H., Rashad, A. E., Abdelmegeid, F. M. E. (2016). The chemistry of pyrido[2,3-d]pyrimidines and their applications. Journal of Chemical and Pharmaceutical Research, 8 (3), 734–772.
  10. Khatri, T. T., Shah, V. H. (2014). One pot synthesis of novel cyanopyridones as an intermediate of bioactive pyrido[2,3-d]pyrimidines. Journal of the Korean Chemical Society, 58 (4), 366–376. http://dx.doi.org/10.5012/jkcs.2014.58.4.366
  11. Zhao, Y., Zhu, L., Provencal, D. P., Miller, T. A., O’Bryan, C., Langston, M., Shen, M., Bailey, D., Sha, D., Palmer, T., Ho, T., Li, M. (2012). Process research and kilogram synthesis of an investigational, potent MEK inhibitor. Organic Process Research and Development, 16 (10), 1652−1659. https://doi.org/10.1021/op300198a
  12. Ammar, Y. A., El-Sharief, A. M. S., Mohamed, Y. A., Salem, M. A., Al-Sehemib, A. G., El-Gabyc, M. S. A. (2004). Cyanoacetanilides intermediates in heterocyclic synthesis. Part 1: A facile synthesis of polysubstituted and condensed pyridones. Journal of the Chinese Chemical Society, 51 (5A), 975–981. https://doi.org/10.1002/jccs.200400145
  13. Ammar, Y. A., Ismail, M. M. F., El-Sehrawi, H. M., Noaman, E., Bayomi, A. H., Shawer, T. Z. (2006). Novel Pirfenidone analogues: synthesis of pyridin-2-ones for the treatment of pulmonary fibrosis. Archiv Der Pharmazie, 339 (8), 429–436. https://doi.org/10.1002/ardp.200600017
  14. El-Adasy, A.-B. A. A. M., Khames, A. A., Gad-Elkareem, M. A. M. (2013). Synthesis of some new [1,8]naphthyridine, pyrido[2,3-d]pyrimidine, and other annulated pyridine derivatives. Journal of Heterocyclic Chemistry, 50 (1), 42–48. https://doi.org/10.1002/jhet.990
  15. Al-Afaleq, E. I. (2001). A facile method for the synthesis of novel pyridinone derivatives via ketene N,S-acetals. Synthetic Communications, 31 (22), 3557–3567. http://dx.doi.org/10.1081/scc-100106218
  16. Allam, Y. A., Swellem, R. H., Nawwar, G. A. M. (2001). Cyanoacetylurea in heterocyclic synthesis: A simple synthesis of heterocyclic condensed uracils. Journal of Chemical Research, 8, 346–348. https://doi.org/10.3184/030823401103170034
  17. Camarasa, M., Puig de la Bellacasa, R., González, À. L., Ondoño, R., Estrada, R., Franco, S., Badia, R., Esté, J., Martínez, M. Á., Teixidó, J., Clotet, B., Borrell, J. I. (2016). Design, synthesis and biological evaluation of pyrido[2,3-d]pyrimidin-7-(8H)-ones as HCV inhibitors. European Journal of Medicinal Chemistry, 115, 463–483. https://doi.org/10.1016/j.ejmech.2016.03.055
  18. Lavecchia, M. J., Puig de la Bellacasa, R., Borrell, J. I., Cavasotto, C. N. (2016). Investigating molecular dynamics-guided lead optimization of EGFR inhibitors. Bioorganic and Medicinal Chemistry, 24 (4), 768–778. http://dx.doi.org/10.1016/j.bmc.2015.12.046
  20. Borrell, J. I., Teixido, J., Martinez-Teipel, B., Serra, B., Matallana, J. L., Costa, M., Batllori, X. (2010). Unequivocal synthesis of 4-amino-1,5,6,8-tetrahydropyrido[2,3-d]pyrimidine-2,7-diones and 2-amino-3,5,6,8-tetrahydropyrido[2,3-d]pyrimidine-4,7-diones. ChemInform, 27 (39). https://doi.org/10.1002/chin.199639178
  21. Mont, N., Teixidó, J., Borrell, J. I., Kappe, C. O. (2003). A three-component synthesis of pyrido[2,3-d]pyrimidines. Tetrahedron Letters, 44 (29), 5385–5387. https://doi.org/10.1016/s0040-4039(03)01306-6
  22. Ahadi, S., Kamranifard, T., Armaghan, M., Khavasi, H. R., Bazgir, A. (2014). Domino Knoevenagel condensation–Michael addition–cyclization for the diastereoselective synthesis of dihydrofuropyrido[2,3-d]pyrimidines via pyridinium ylides in water. RSC Advances, 4 (14), 7296–7300. https://doi.org/10.1039/c3ra45795h
  23. Khattab, A. F., Kappe, T. (1996). Pyrido[2,3-d]pyrimidines, II. One step synthesis of pyrido[2,3-d]pyrimidines and pyrimido[4,5-b]quinolines from 6-amino uracils. Monatshefte Fur Chemie Chemical Monthly, 127 (8–9), 917–925. https://doi.org/10.1007/bf00807031
  24. Dong, Q., Dougan, D. R., Gong, X., Halkowycz, P., Jin, B., Kanouni, T., O’Connell, S. M., Scorah, N., Shi, L., Wallace, M. B., Zhou, F. (2011). Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer. Bioorganic and Medicinal Chemistry Letters, 21 (5), 1315–1319. https://doi.org/10.1016/j.bmcl.2011.01.071
  25. Castillo, J.-C., Quiroga, J., Rodriguez, J., Coquerel, Y. (2016). Time-efficient synthesis of pyrido[2,3-d]pyrimidinones via α-oxoketenes. European Journal of Organic Chemistry, 2016 (11), 1994–1999. http://dx.doi.org/10.1002/ejoc.201600171
  26. Vasudevan, A., Mavandadi, F., Chen, L., Gangjee, A. (1999). Reactions of 6-aminopyrimidines with biselectrophiles: manipulation of product composition with solvent and pyrimidine substitution variation. The Journal of Organic Chemistry, 64 (2), 634–638. https://doi.org/10.1021/jo9713870
  27. Takahashi, M., Nagaoka, H., Inoue, K. (2004). Synthesis of trifluoromethylated pyrido[2,3-d]pyrimidine-2,4-diones from 6-aminouracils and trifluoromethylated pyrazolo[3,4-b]pyridines from 5-aminopyrazoles. Journal of Heterocyclic Chemistry, 41 (4), 525–530. https://doi.org/10.1002/jhet.5570410408
  28. Bulicz, J., Bertarelli, D. C. G., Baumert, D., Fülle, F., Müller, C. E., Heber, D. (2006). Synthesis and pharmacology of pyrido[2,3-d]pyrimidinediones bearing polar substituents as adenosine receptor antagonists. Bioorganic and Medicinal Chemistry, 14 (8), 2837–2849. https://doi.org/10.1016/j.bmc.2005.12.008
  29. Baharfar, R., Azimi, R. (2011). A clean and efficient cyclocondensation to pyrido[2,3-d]pyrimidine derivatives in aqueous media. Chinese Chemical Letters, 22 (10), 1183–1186. https://doi.org/10.1016/j.cclet.2011.04.020
  30. Gineinah, M. M., Nasr, M. N. A., Badr, S. M. I., El-Husseiny, W. M. (2012). Synthesis and antitumor activity of new pyrido[2,3-d]pyrimidine derivatives. Medicinal Chemistry Research, 22 (8), 3943–3952. https://doi.org/10.1007/s00044-012-0396-0
  31. Dulla, B., Wan, B., Franzblau, S. G., Kapavarapu, R., Reiser, O., Iqbal, J., Pal, M. (2012). Construction and functionalization of fused pyridine ring leading to novel compounds as potential antitubercular agents. Bioorganic and Medicinal Chemistry Letters, 22 (14), 4629–4635. http://dx.doi.org/10.1016/j.bmcl.2012.05.096
  32. Reddy, M. V. R., Akula, B., Cosenza, S. C., Athuluridivakar, S., Mallireddigari, M. R., Pallela, V. R., … Reddy, E. P. (2014). Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5). Journal of Medicinal Chemistry, 57 (3), 578–599. https://doi.org/10.1021/jm401073p
  33. Goldstein, D. M., Soth, M., Gabriel, T., Dewdney, N., Kuglstatter, A., Arzeno, H., … Zecic, H. (2011). Discovery of 6-(2,4-Difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl)propylamino]-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one (Pamapimod) and 6-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (R1487) as Orally Bioavailable and Highly Selective Inhibitors of p38α Mitogen-Activated Protein Kinase. Journal of Medicinal Chemistry, 54 (7), 2255–2265. https://doi.org/10.1021/jm101423y
  34. Ren L., Ahrendt K.A., Grina J., Laird E.R., Buckmelter A.J., Hansen J.D., Newhouse B., Moreno D., Wenglowsky S., Dinkel V., Gloor S.L., Hastings G., Rana S., Rasor K., Risom T., Sturgis H.L., Voegtli W.C., Mathieu S. (2012). The discovery of potent and selective pyridopyrimidin-7-one based inhibitors of B-RafV600E kinase. Bioorganic and Medicinal Chemistry Letters, 22 (10), 3387–3391. http://dx.doi.org/10.1016/j.bmcl.2012.04.015
  35. Rudolph, J., Murray, L. J., Ndubaku, C. O., O’Brien, T., Blackwood, E., Wang, W., … Zhong, Y. (2016). Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window. Journal of Medicinal Chemistry, 59 (11), 5520–5541. https://doi.org/10.1021/acs.jmedchem.6b00638
  36. Koval, A. B., & Wuest, W. M. (2016). An optimized synthesis of the potent and selective Pak1 inhibitor FRAX-1036. Tetrahedron Letters, 57 (3), 449–451. http://dx.doi.org/10.1016/j.tetlet.2015.12.059
  38. Blass, B. E., Coburn, K., Fairweather, N., Sabat, M., & West, L. (2006). A facile, KF/Al2O3 mediated method for the preparation of functionalized pyrido[2,3-d]pyrimidin-7(8H)-ones. Tetrahedron Letters, 47 (18), 3177–3180. https://doi.org/10.1016/j.tetlet.2006.02.155
  39. Angiolini, M., Bassini, D. F., Gude, M., & Menichincheri, M. (2005). Solid-phase synthesis of pyrido[2,3-d]pyrimidin-7-ones. Tetrahedron Letters, 46 (50), 8749–8752. https://doi.org/10.1016/j.tetlet.2005.10.030
  40. Barvian, M., Boschelli, D. H., Cossrow, J., Dobrusin, E., Fattaey, A., Fritsch, A., … Zhang, E. (2000). Pyrido[2,3-d]pyrimidin-7-one Inhibitors of Cyclin-Dependent Kinases. Journal of Medicinal Chemistry, 43 (24), 4606–4616. https://doi.org/10.1021/jm000271k
  41. Yan, H., Boehm, J. C., Jin, Q., Kasparec, J., Li, H., Zhu, C., … Wan, Z. (2007). An improved and highly convergent synthesis of 4-substituted-pyrido[2,3-d]pyrimidin-7-ones. Tetrahedron Letters, 48 (7), 1205–1207. https://doi.org/10.1016/j.tetlet.2006.12.064
  42. Sakamoto, T., Koga, Y., Hikota, M., Matsuki, K., Mochida, H., Kikkawa, K., … Yamada, K. (2015). 8-(3-Chloro-4-methoxybenzyl)-8H-pyrido[2,3-d]pyrimidin-7-one derivatives as potent and selective phosphodiesterase 5 inhibitors. Bioorganic & Medicinal Chemistry Letters, 25 (7), 1431–1435. http://dx.doi.org/10.1016/j.bmcl.2015.02.041
  43. VanderWel, S. N., Harvey, P. J., McNamara, D. J., Repine, J. T., Keller, P. R., Quin, J., Booth, R. J., Elliott, W. L., Dobrusin, E. M., Fry, D. W., Toogood, P. L. (2005). Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of Cyclin-dependent kinase 4. Journal of Medicinal Chemistry, 48 (7), 2371–2387. https://doi.org/10.1021/jm049355
  44. Apsunde, T., & Wurz, R. P. (2014). Pyridin-2-one Synthesis Using Ester Enolates and Aryl Aminoaldehydes and Ketones. The Journal of Organic Chemistry, 79 (7), 3260–3266. https://doi.org/10.1021/jo500284n
  45. Wurz, R. P., Pettus, L. H., Ashton, K., Brown, J., Chen, J. J., Herberich, B., … Tasker, A. S. (2015). Oxopyrido[2,3-d]pyrimidines as Covalent L858R/T790M Mutant Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors. ACS Medicinal Chemistry Letters, 6 (9), 987–992. https://doi.org/10.1021/acsmedchemlett.5b00193
  46. Wan, Z., Yan, H., Hall, R. F., Lin, X., Livia, S., Respondek, T., … Callahan, J. F. (2009). Design and development of arrayable syntheses to accelerate SAR studies of pyridopyrimidinone and pyrimidopyrimidinone. Tetrahedron Letters, 50 (3), 370–372. https://doi.org/10.1016/j.tetlet.2008.11.014
  47. Klutchko, S. R., Hamby, J. M., Boschelli, D. H., Wu, Z., Kraker, A. J., Amar, A. M., … Doherty, A. M. (1998). 2-Substituted Aminopyrido[2,3-d]pyrimidin-7(8H)-ones. Structure−Activity Relationships Against Selected Tyrosine Kinases and in Vitro and in Vivo Anticancer Activity. Journal of Medicinal Chemistry, 41 (17), 3276–3292. https://doi.org/10.1021/jm9802259
  48. Zhang, J., Lu, D., Wei, H.-X., Gu, Y., Selkoe, D. J., Wolfe, M. S., & Augelli-Szafran, C. E. (2016). Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones. Bioorganic & Medicinal Chemistry Letters, 26 (9), 2138–2141. http://dx.doi.org/10.1016/j.bmcl.2016.03.077
  49. Zinchenko, A. N., Muzychka, L. V., Biletskii, I. I., & Smolii, O. B. (2017). Synthesis of new 4-amino-substituted 7-iminopyrido[2,3-d]pyrimidines. Chemistry of Heterocyclic Compounds, 53 (5), 589–596. https://doi.org/10.1007/s10593-017-2096-7
  50. Deb, M. L., & Bhuyan, P. J. (2006). Synthesis of Novel Classes of Pyrido[2,3-d]-pyrimidines, Pyrano[2,3-d]pyrimidines, and Pteridines. Synthetic Communications, 36 (20), 3085–3090. http://dx.doi.org/10.1080/00397910600775622
  51. Murphy-Benenato, K. E., Gingipalli, L., Boriack-Sjodin, P. A., Martinez-Botella, G., Carcanague, D., Eyermann, C. J., … Patel, S. J. (2015). Negishi cross-coupling enabled synthesis of novel NAD+-dependent DNA ligase inhibitors and SAR development. Bioorganic & Medicinal Chemistry Letters, 25 (22), 5172–5177. http://dx.doi.org/10.1016/j.bmcl.2015.09.075
  53. Spalluto, G., & Cacciari, B. (2006). Facile and Versatile Route to the Synthesis of Fused 2-Pyridones : Useful Intermediates for Polycyclic Sytems. Synthetic Communications, 36 (9), 1173–1183. http://dx.doi.org/10.1080/00397910500514063
  54. Shanmugasundaram, P., Mohanarangan, J., Raj, R. K., Aanandhi, M. V. (2009). Synthesis and biological evaluation of pyrido[2,3-d]pyrimidinecarboxylate derivatives. Rasayan Journal of Chemistry, 2 (2), 345–349.
  55. Ellingboe, J. W., Antane, M., Nguyen, T. T., Collini, M. D., Antane, S., Bender, R., … McCallum, J. (1994). Pyrido[2,3-d]pyrimidine Angiotensin II Antagonists. Journal of Medicinal Chemistry, 37 (4), 542–550. https://doi.org/10.1021/jm00030a013
  56. Harutyunyan, A. A., Panosyan, G. A., Chishmarityan, S. G., Paronikyan, R. V., & Stepanyan, H. M. (2015). Synthesis and properties of derivatives of pyrimidin-5-ylpropanoic acids and 8-aryl-4-methyl- and 4,6-dimethyl-2-phenyl-5,6,7,8-tetrahydropyrido-[2,3-d]pyrimidin-7-ones. Russian Journal of Organic Chemistry, 51 (5), 705–710. https://doi.org/10.1134/S1070428015050218
  57. Adcock, J., Gibson, C. L., Huggan, J. K., & Suckling, C. J. (2011). Diversity oriented synthesis: substitution at C5 in unreactive pyrimidines by Claisen rearrangement and reactivity in nucleophilic substitution at C2 and C4 in pteridines and pyrido[2,3-d]pyrimidines. Tetrahedron, 67 (18), 3226–3237. https://doi.org/10.1016/j.tet.2011.03.011
  58. Le, P. T., Cheng, H., Ninkovic, S., Plewe, M., Huang, X., Wang, H., … Zhang, E. (2012). Design and synthesis of a novel pyrrolidinyl pyrido pyrimidinone derivative as a potent inhibitor of PI3Kα and mTOR. Bioorganic & Medicinal Chemistry Letters, 22 (15), 5098–5103. http://dx.doi.org/10.1016/j.bmcl.2012.05.100
  59. Cheng, H., Hoffman, J. E., Le, P. T., Pairish, M., Kania, R., Farrell, W., … Rahavendran, S. V. (2013). Structure-based design, SAR analysis and antitumor activity of PI3K/mTOR dual inhibitors from 4-methylpyridopyrimidinone series. Bioorganic & Medicinal Chemistry Letters, 23 (9), 2787–2792. http://dx.doi.org/10.1016/j.bmcl.2013.02.020
  60. Elokdah, H. M., Friedrichs, G. S., Chai, S.-Y., Harrison, B. L., Primeau, J., Chlenov, M., & Crandall, D. L. (2002). Novel human metabolites of the angiotensin-II antagonist tasosartan and their pharmacological effects. Bioorganic & Medicinal Chemistry Letters, 12 (15), 1967–1971. https://doi.org/10.1016/s0960-894x(02)00303-7
  61. Blades, K., & Glossop, S. (2016). A Three-Step Protocol towards N-8-(2,2-Dimethoxyethyl)-2-methylsulfanylpyrido[2,3-d]pyrimidin-7-one. Synthesis, 49 (03), 554–556. https://doi.org/10.1055/s-0036-1588364
  62. Choi, H.-S., Wang, Z., Richmond, W., He, X., Yang, K., Jiang, T., … He, Y. (2006). Design and synthesis of 7H-pyrrolo[2,3-d]pyrimidines as focal adhesion kinase inhibitors. Part 1. Bioorganic & Medicinal Chemistry Letters, 16 (8), 2173–2176. https://doi.org/10.1016/j.bmcl.2006.01.053
  63. Boros, E. E., Thompson, J. B., Wood, E. R., McDonald, O. B., Spitzer, T. D., Sefler, A. M., & Reep, B. R. (2004). Tandem Michael-addition/cyclization synthesis and EGFR kinase inhibition activity of pyrido[2,3-d]pyrimidin-7(8H)-ones. Journal of Heterocyclic Chemistry, 41 (3), 355–358. https://doi.org/10.1002/jhet.5570410308
  64. Wang, X., Zeng, Z., Shi, D., Tu, S., Wei, X., & Zong, Z. (2005). Three-Component, One-Pot Synthesis of Pyrido[2,3‐d]pyrimidine Derivatives Catalyzed by KF‐alumina. Synthetic Communications, 35 (14), 1921–1927. http://dx.doi.org/10.1081/SCC-200064984
  65. Abdolmohammadi, S., & Afsharpour, M. (2012). Facile one-pot synthesis of pyrido[2,3-d]pyrimidine derivatives over ZrO2 nanoparticles catalyst. Chinese Chemical Letters, 23 (3), 257–260. https://doi.org/10.1016/j.cclet.2012.01.001
  66. Nasr, M. N., Gineinah, M. M. (2002). Pyrido[2,3-d]pyrimidines and pyrimido[5’,4’:5,6]pyrido[2,3-d]pyrimidines as new antiviral agents: synthesis and biological activity. Archiv der Pharmazie, 335 (6), 289–295. https://doi.org/10.1002/1521-4184(200208)335:6<289::AIDARDP289>3.0.CO;2-Z
  67. Shi, D., Ji, S., Niu, L., Shi, J., & Wang, X. (2007). One-pot synthesis of pyrido[2,3-d]pyrimidines via efficient three-component reaction in aqueous media. Journal of Heterocyclic Chemistry, 44 (5), 1083–1090. https://doi.org/10.1002/jhet.5570440517
  68. Nia, R. H., Mamaghani, M., Tabatabaeian, K., (2013). A rapid one-pot synthesis of pyrido[2,3-d]pyrimidine derivatives using brønsted-acidic ionic liquid as catalyst. Acta Chimica Slovenica, 60 (4), 889–895.
  69. Walters, I., Austin, C., Austin, R., Bonnert, R., Cage, P., Christie, M., … Robinson, D. (2008). Evaluation of a series of bicyclic CXCR2 antagonists. Bioorganic & Medicinal Chemistry Letters, 18 (2), 798–803. https://doi.org/10.1016/j.bmcl.2007.11.039
  71. Tu, S., Zhang, J., Zhu, X., Xu, J., Zhang, Y., Wang, Q., … Zhang, J. (2006). New potential inhibitors of cyclin-dependent kinase 4 : Design and synthesis of pyrido[2,3-d]pyrimidine derivatives under microwave irradiation. Bioorganic & Medicinal Chemistry Letters, 16 (13), 3578–3581. https://doi.org/10.1016/j.bmcl.2006.03.084
  72. Heravi, M. M., Saeedi, M., Beheshtiha, Y. S., & Oskooie, H. A. (2011). One-pot chemoselective synthesis of novel fused pyrimidine derivatives. Chemistry of Heterocyclic Compounds, 47 (6), 737–744. https://doi.org/10.1007/s10593-011-0828-7
  73. Zinchenko, A. M., Muzychka, L. V., Kucher, O. V., Sadkova, I. V., Mykhailiuk, P. K., & Smolii, O. B. (2018). One-Pot Synthesis of 6-Aminopyrido[2,3-d]pyrimidin-7-ones. European Journal of Organic Chemistry, 2018 (46), 6519–6523. http://dx.doi.org/10.1002/ejoc.201801204
  74. Zinchenko, A. N., Muzychka, L. V., Smolii, O. B., Bdzhola, V. G., Protopopov, M. V., & Yarmoluk, S. M. (2017). Synthesis and biological evaluation of novel amino-substituted derivatives of pyrido[2,3-d]pyrimidine as inhibitors of protein kinase CK2. Biopolymers and Cell, 33 (5), 367–378. http://dx.doi.org/10.7124/bc.000960
  75. Xu, T., Peng, T., Ren, X., Zhang, L., Yu, L., Luo, J., … Ding, K. (2015). C5-substituted pyrido[2,3-d]pyrimidin-7-ones as highly specific kinase inhibitors targeting the clinical resistance-related EGFRT790M mutant. MedChemComm, 6 (9), 1693–1697. https://doi.org/10.1039/C5MD00208G
  76. Yu, L., Huang, M., Xu, T., Tong, L., Yan, X., Zhang, Z., … Lu, X. (2017). A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFRL858R/T790M mutant with improved pharmacokinetic properties. European Journal of Medicinal Chemistry, 126, 1107–1117. https://doi.org/10.1016/j.ejmech.2016.12.006
  77. Brameld, K. A., Owens, T. D., Verner, E., Venetsanakos, E., Bradshaw, J. M., Phan, V. T., … Funk, J. O. (2017). Discovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors. Journal of Medicinal Chemistry, 60 (15), 6516–6527. https://doi.org/10.1021/acs.jmedchem.7b00360
  78. Ndubaku, C. O., Crawford, J. J., Drobnick, J., Aliagas, I., Campbell, D., Dong, P., … Rudolph, J. (2015). Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pKa Polar Moiety. ACS Medicinal Chemistry Letters, 6 (12), 1241–1246. https://doi.org/10.1021/acsmedchemlett.5b00398
  79. Khokhani, K., Khatri, T., Ram, V., Patel, P. (2013). Microwave assisted synthesis and biological investigations of novel derivatives of pyrido[2,3-d]pyrimidines. Chemistry and Biology Interface, 3 (3), 192–200.
  80. Cheng, H., Hoffman, J. E., Le, P. T., Pairish, M., Kania, R., Farrell, W., … Rahavendran, S. V. (2013). Structure-based design, SAR analysis and antitumor activity of PI3K/mTOR dual inhibitors from 4-methylpyridopyrimidinone series. Bioorganic & Medicinal Chemistry Letters, 23 (9), 2787–2792. http://dx.doi.org/10.1016/j.bmcl.2013.02.020
  81. Le, P. T., Cheng, H., Ninkovic, S., Plewe, M., Huang, X., Wang, H., … Zhang, E. (2012). Design and synthesis of a novel pyrrolidinyl pyrido pyrimidinone derivative as a potent inhibitor of PI3Kα and mTOR. Bioorganic & Medicinal Chemistry Letters, 22 (15), 5098–5103. http://dx.doi.org/10.1016/j.bmcl.2012.05.100
  82. Palmer, B. D., Smaill, J. B., Rewcastle, G. W., Dobrusin, E. M., Kraker, A., Moore, C. W., … Denny, W. A. (2005). Structure-activity relationships for 2-anilino-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-ones as inhibitors of the cellular checkpoint kinase Wee1. Bioorganic & Medicinal Chemistry Letters, 15 (7), 1931–1935. https://doi.org/10.1016/j.bmcl.2005.01.079
  83. Anderson, K., Chen, Y., Chen, Z., Dominique, R., Glenn, K., He, Y., … Zhang, X. (2013). Pyrido[2,3-d]pyrimidines: Discovery and preliminary SAR of a novel series of DYRK1B and DYRK1A inhibitors. Bioorganic & Medicinal Chemistry Letters, 23 (24), 6610–6615. http://dx.doi.org/10.1016/j.bmcl.2013.10.055

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2019-11-12

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(1)
Zinchenko, H. M.; Muzychka, L. V.; Smolii, O. B. Pyrido[2,3-d]pyrimidin-7-Ones: Synthesis and Biological Properties. J. Org. Pharm. Chem. 2019, 17, 5-17.

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Vol. 17 No. 4(68) (2019)

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Original Researches

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