Advances in the Chemistry of 6-6 Bicyclic Systems: Chemistry of Pyrido[3,4- d]pyrimidines

Author(s): Mohamed Monier, Doaa Abdel-Latif, Ahmed El-Mekabaty, Başak D. Mert, Khaled M. Elattar*

Journal Name: Current Organic Synthesis

Volume 16 , Issue 6 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

The aim of this work is to discuss the chemistry of pyrido[3,4-d]pyrimidines as one of the most important heterocyclic compounds with remarkable synthetic, biological and medical applications. In this overview, the chemistry of heterocyclic compounds incorporated the pyrido[3,4-d]pyrimidine scaffold as demonstrated by chemical reactions and different preparation processes. The anticipated compounds were synthesized from pyridine or pyrimidine compounds and a description of the reactivity of substituents attached to ring carbon and nitrogen atoms is discussed. On the other hand, the synthesis and reactions of fused heterocycles incorporated pyrido[3,4-d]pyrimidine scaffold is described. The diamine analogs included pyrido[3,4-d]pyrimidine core were reported as tyrosine kinase inhibitors. The chemical reactions of certain unexpected and chemically substantial compounds have been discussed.

Keywords: Pyrido[3, 4-d]pyrimidines, substituents’ reactivity, synthetic routes, biological applications, heterocyclic compounds, tyrosine kinase inhibitors.

[1]
Doherty, A. M.; Hallak, H. O.; Hamby, J. M. N-oxides of amino containing pyrido[2,3-d]pyrimidines US 5945422A, 1997.
[2]
Cockerill, G.S.; Guntrip, S.B.; Mckeown, S.C.; Page, M.J.; Smith, K.J.; Vile, S.; Hudson, A.T.; Barraclough, P.; Franzmann, K.W. Preparation of 4- anilinopyrido[3,4-d]pyrimidines and analogs as protein tyrosine kinase inhibitors. PCT Int. Appl. WO 9713771 A1, 4/1997.
[3]
Rewcastle, G.W.; Palmer, B.D.; Thompson, A.M.; Bridges, A.J.; Cody, D.R.; Zhou, H.; Fry, D.W.; McMichael, A.; Denny, W.A. Tyrosine kinase inhibitors. 10. Isomeric 4-[(3-bromophenyl)amino]pyrido[d]-pyrimidines are potent ATP binding site inhibitors of the tyrosine kinase function of the epidermal growth factor receptor. J. Med. Chem., 1996, 39(9), 1823-1835.
[http://dx.doi.org/10.1021/jm9508651] [PMID: 8627606]
[4]
Bridges, A. J.; Denny, W. A.; Fry, D.; Kraker, A.; Meyer, R. F.; Rewcastle, G. W.; Thompson, A. M. 2001.
[5]
Smaill, J.B.; Palmer, B.D.; Rewcastle, G.W.; Denny, W.A.; McNamara, D.J.; Dobrusin, E.M.; Bridges, A.J.; Zhou, H.; Showalter, H.D.H.; Winters, R.T.; Leopold, W.R.; Fry, D.W.; Nelson, J.M.; Slintak, V.; Elliot, W.L.; Roberts, B.J.; Vincent, P.W.; Patmore, S.J. Tyrosine kinase inhibitors. 15. 4-(Phenylamino)quinazoline and 4-(phenylamino)pyrido[d]pyrimidine acrylamides as irreversible inhibitors of the ATP binding site of the epidermal growth factor receptor. J. Med. Chem., 1999, 42(10), 1803-1815.
[http://dx.doi.org/10.1021/jm9806603] [PMID: 10346932]
[6]
Cockerill, G.S.; Lackey, K.E. Preparation of quinazolinylamines and analogs as protein tyrosine kinase inhibitors. WO 9935132, 1999. Chem. Abstr., 1999, 131102287
[7]
Carter, M.C.; Cockerill, G.S.; Guntrip, S.B.; Lackey, K.E.; Smith, K.J. Bicyclic heteroaromatic compounds [quinazolina-mines, pyridopyrimidines, and analogs] useful as protein tyrosine kinase inhibitors. PCT Int. Appl. WO 9935146, 1999. Chem. Abstr., 1999, 131102288
[8]
Carter, M.C.; Cockerill, G.S.; Guntrip, S.B.; Lackey, K.E.; Smith, K.J. Preparation of 6-(thiomorpholinomethylfuranyl)-4-quinazolinamines as protein tyrosine kinase inhibitors Brit. UK Pat. Appl. GB 2345486, 2000. Chem. Abstr 2000. 133, 362769
[9]
Cockerill, G.S.; Lackey, K.E. Preparation of Anilinoquinazolines as protein tyrosine kinase inhibitors. PCT appl. WO 2001004111, 2001. Chem. Abstr., 2001, 134100886
[10]
Smaill, J.B.; Showalter, H.D.H.; Zhou, H.; Bridges, A.J.; McNamara, D.J.; Fry, D.W.; Nelson, J.M.; Sherwood, V.; Vincent, P.W.; Roberts, B.J.; Elliott, W.L.; Denny, W.A. Tyrosine kinase inhibitors. 18. 6-Substituted 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as soluble, irreversible inhibitors of the epidermal growth factor receptor. J. Med. Chem., 2001, 44(3), 429-440.
[http://dx.doi.org/10.1021/jm000372i] [PMID: 11462982]
[11]
Cockerill, G.S.; Carter, M.C.; Guntrip, S.B.; Smith, K.J. Preparation of bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors. PCT appl. WO9802437, 1998. Chem. Abstr., 1998, 128140717
[12]
Cockerill, G.S.; Carter, M.C.; Guntrip, S.B.; Smith, K.J. Preparation of bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors. PCT Int. Appl. WO9802438, 1998. Chem. Abstr., 1998, 128140718
[13]
Rewcastle, G.W.; Murray, D.K.; Elliott, W.L.; Fry, D.W.; Howard, C.T.; Nelson, J.M.; Roberts, B.J.; Vincent, P.W.; Showalter, H.D.H.; Winters, R.T.; Denny, W.A. Tyrosine kinase inhibitors. 14. Structure-activity relationships for methylamino-substituted derivatives of 4-[(3-bromophenyl)amino]-6-(methylamino)-pyrido[3,4-d]pyrimidine (PD 158780), a potent and specific inhibitor of the tyrosine kinase activity of receptors for the EGF family of growth factors. J. Med. Chem., 1998, 41(5), 742-751.
[http://dx.doi.org/10.1021/jm970641d] [PMID: 9513602]
[14]
Fry, D.W.; Nelson, J.M.; Slintak, V.; Keller, P.R.; Rewcastle, G.W.; Denny, W.A.; Zhou, H.; Bridges, A.J. Biochemical and antiproliferative properties of 4-[ar(alk)ylamino]pyridopyrimidines, a new chemical class of potent and specific epidermal growth factor receptor tyrosine kinase inhibitor. Biochem. Pharmacol., 1997, 54(8), 877-887.
[http://dx.doi.org/10.1016/S0006-2952(97)00242-6] [PMID: 9354588]
[15]
Showalter, H.D.H.; Bridges, A.J.; Zhou, H.; Sercel, A.D.; McMichael, A.; Fry, D.W. Tyrosine kinase inhibitors. 16. 6,5,6-tricyclic benzothieno[3, 2-d]pyrimidines and pyrimido[5,4-b-] and -[4,5-b]ĭndoles as potent inhibitors of the epidermal growth factor receptor tyrosine kinase. J. Med. Chem., 1999, 42(26), 5464-5474.
[http://dx.doi.org/10.1021/jm9903949] [PMID: 10639288]
[16]
Bridges, A.J. Chemical inhibitors of protein kinases. Chem. Rev., 2001, 101(8), 2541-2572.
[http://dx.doi.org/10.1021/cr000250y] [PMID: 11749388]
[17]
Daub, H.; Specht, K.; Ullrich, A. Strategies to overcome resistance to targeted protein kinase inhibitors. Nat. Rev. Drug Discov., 2004, 3(12), 1001-1010.
[http://dx.doi.org/10.1038/nrd1579] [PMID: 15573099]
[18]
Rewcastle, G.W.; Denny, W.A.; Showalter, H.D.H. Synthesis of 4-(phenylamino)pyrimidine derivatives as ATP-competitive protein kinase inhibitors with potential for cancer chemotherapy. Curr. Org. Chem., 2000, 4(7), 679-706.
[http://dx.doi.org/10.2174/1385272003376094]
[19]
Connolly, T.J.; Matchett, M.; Sarma, K. Process development and scale-up of a selective α1-adrenoceptor antagonist. Org. Process Res. Dev., 2005, 9(1), 80-87.
[http://dx.doi.org/10.1021/op0498114]
[20]
Wollein, G.; Troschutz, R. Synthesis of 7-aza-5,8,10-trideazafolic acid and its 4-amino-derivative as potential antifolates. J. Heterocycl. Chem., 2002, 39(6), 1195-1200.
[http://dx.doi.org/10.1002/jhet.5570390613]
[21]
Arnold, L.D.; Moyer, M.P.; Sobolov-Jaynes, S.B. Preparation of heterocyclic ring-fused pyrimidines for treatment of hyperproliferative diseases. PCT Int. Appl. WO 9640142, 1996, 62 pp. Chem. Abstr., 1997, 126144288
[22]
Fox, D.N.A. (Pfizer Ltd.;Pfizer Inc.) Quinoline and quinazoline compounds useful in therapy, particularly in the treatment of benign prostatic hyperplasia. PCT Int. Appl. WO 9830560, 1998. Chem. Abstr., 1998, 129136176
[23]
Collis, A.J.; Fox, D.N.A.; Newman, J. Quinoline and quinazoline compounds useful in therapy. PCT Int. Appl. WO 9723462, 1997. Chem. Abstr., 1997, 127121749
[24]
Himmelsbach, F.; Dahmann, G.; Von Ruden, T.; Metz, T. Preparation of 4-aminopyrimidine derivatives as antitumor agents. WO 9732881, 1997. Chem. Abstr., 1997, 127278207
[25]
Bhattacharya, S.K.; Chen, J.; Connell, R.D.; Kath, J.C.; Kauffman, G.S.; Lippa, B.S.; Morris, J. Substituted heterocylces for the treatment of abnormal cell growth. US7585869B2. Appl. No. US, 2003, 10/849, 707.
[26]
Arnold, L.D.; Moyer, M.P.; Sobolov-Jaynes, S.B. Fused bicyclic pyrimidine derivatives useful as antihyperproliferative agents. PCT Int. Appl., 45 pp. WO 9823613 A1, 1998. Chem. Abstr., 1998, 129, 41143.
[27]
Piazza, G.A.; Pamukcu, R. Method of treating a patient having precancerous lesions with phenyl cycloamino pyrimidinone derivatives. US 6060477, 2000. Chem. Abstr., 2000, 132321870
[28]
Meyer, M.D.; Altenbach, R.J.; Carroll, W.A.; Drizin, I.; Lebold, S.A.; Lee, E.L.; Sippy, K.B.; Tietje, K.R.; Yamamoto, D.M.; Kerwin, J.F. Jr Bicyclic substituted hexahydrobenz[e]isoindole α-1 adrenergic antagonists. US5521181A, 1996. Chem. Abstr., 1996, 125114680
[29]
Meyer, M.D.; Altenbach, R.J.; Basha, F.Z.; Carroll, W.A.; Drizin, I.; Kerwin, J.F., Jr; Lebold, S.A.; Lee, E.L.; Pratt, J.K.; Sippy, K.B.; Tietje, K.R.; Yamamoto, D.M. Bicyclic substituted hexahydrobenze isoindole alpha-1 adrenergic antagonists. US 5792767A, 1998. Chem. Abstr., 1998, 129161567
[30]
Dumaître, B.; Dodic, N. Synthesis and cyclic GMP phosphodiesterase inhibitory activity of a series of 6-phenylpyrazolo[3,4-d]pyrimidones. J. Med. Chem., 1996, 39(8), 1635-1644.
[http://dx.doi.org/10.1021/jm950812j] [PMID: 8648603]
[31]
Bradbury, N.A.; Dormer, R.L.; McPherson, M.A. Introduction of cyclic AMP phosphodiesterase into rat submandibular acini prevents isoproterenol-stimulated cyclic AMP rise without affecting mucin secretion. Biochem. Biophys. Res. Commun., 1989, 161(2), 661-671.
[http://dx.doi.org/10.1016/0006-291X(89)92650-8] [PMID: 2544168]
[32]
Chenard, B.L.; Gallaschun, R.J. Pyrido[3,4-d]pyrimidine-2,4(1H,3H)-dione derivatives. US9440973B2 Appl. No. US14/822,232 2016.
[33]
Bunker, A.; Picard, J.; Lodaya, R.; Waldo, M.; Marlatt, M. 2005.
[34]
Chu-Moyer, M.Y.; Murry, J.A.; Mylari, B.L.; Zembrowski, W.J. Aminopyrimidines as sorbitol dehydrogenase inhibitors. WO 0059510, 2000. Chem. Abstr., 2000, 133281794
[35]
Chandrika, P.M.; Yakaiah, T.; Rao, A.R.R.; Narsaiah, B.; Reddy, N.C.; Sridhar, V.; Rao, J.V. Synthesis of novel 4,6-disubstituted quinazoline derivatives, their anti-inflammatory and anti-cancer activity (cytotoxic) against U937 leukemia cell lines. Eur. J. Med. Chem., 2008, 43(4), 846-852.
[http://dx.doi.org/10.1016/j.ejmech.2007.06.010] [PMID: 17689837]
[36]
Stefek, M.; Tsantili-Kakoulidou, A.; Milackova, I.; Juskova, M.; Snirc, V.; Triantos, N. (2-Benzyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-8-yl)-acetic acid: an aldose reductase inhibitor and antioxidant of zwitterionic nature. Bioorg. Med. Chem., 2011, 19(23), 7181-7185.
[http://dx.doi.org/10.1016/j.bmc.2011.09.053] [PMID: 22037047]
[37]
Arnaiz, D.O.; Baldwin, J.J.; Davey, D.D.; Devlin, J.J.; Dolle, R.E., III; Erickson, S.D.; McMillan, K.; Morrissey, M.M.; Ohlmeyer, H.H.J.; Pan, G.; Paradkar, V.M.; Parkinson, J.P.; Gary, B.; Ye, B.; Zhao, Z. New nitric oxide synthase inhibiting N-heterocyclic compounds. WO 9837079, 1998. Chem. Abstr., 1998, 129231019
[38]
Matsuno, K.; Nomoto, Y.; Ichimura, M.; Ide, S.; Oda, S. Nitrogenous heterocyclic compounds. WO 9951582, 1999. Chem. Abstr., 1999, 131271888
[39]
Darcy, K.M.; Wohlhueter, A.L.; Zangani, D.; Vaughan, M.M.; Russell, J.A.; Masso-Welch, P.A.; Varela, L.M.; Shoemaker, S.F.; Horn, E.; Lee, P-P.H.; Huang, R-Y.; Ip, M.M. Selective changes in EGF receptor expression and function during the proliferation, differentiation and apoptosis of mammary epithelial cells. Eur. J. Cell Biol., 1999, 78(7), 511-523.
[http://dx.doi.org/10.1016/S0171-9335(99)80077-6] [PMID: 10472803]
[40]
Edwards, P.D.; Andisik, D.W.; Strimpler, A.M.; Gomes, B.; Tuthill, P.A. Nonpeptidic inhibitors of human neutrophil elastase. 7. Design, synthesis, and in vitro activity of a series of pyridopyrimidine trifluoromethyl ketones. J. Med. Chem., 1996, 39(5), 1112-1124.
[http://dx.doi.org/10.1021/jm950684z] [PMID: 8676347]
[41]
Erion, M.D.; Reddy, M.R. Calculation of relative hydration free energy differences for heteroaromatic compounds: Use in the design of adenosine deaminase and cytidine deaminase inhibitors. J. Am. Chem. Soc., 1998, 120(14), 3295-3304.
[http://dx.doi.org/10.1021/ja972906j]
[42]
Armarego, W.L.F. Triazanaphthalenes. Part I. Covalent hydration in 1,3,5-, 1,3,6-, 1,3,7-, and 1,3,8-triazanaphthalene. J. Chem. Soc., 1962, 4094-4103.
[http://dx.doi.org/10.1039/jr9620004094]
[43]
Audoux, J.; Plé, N.; Turck, A.; Quéguiner, G. First functionalization by metallation of the pyridine moiety of pyridopyrimidin-4(3H)-ones. Diazines. Part 36. Tetrahedron, 2004, 60(18), 4107-4123.
[44]
Irwin, W.J.; Wibberley, D.G. Pyridopyrimidines: 1,3,5-, 1,3,6-, 1,3,7-, and 1,3,8-triazanaphthalenes. Edited by Katritzky, A.R.; Boulton,A.J. Adv. Heterocycl. Chem; , 1969. 10, 149-198.
[45]
Lunt, E.; Newton, C.G. 1984 Pyridodiazines and Their Benzo Derivatives. In: Comprehensive Heterocyclic Chemistry; Katritzky, A.R.; Rees, C.W., Eds.; Pergamon: Oxford, 1984; Vol. 3, pp. 199-262.
[46]
Maguire, J.H.; McKee, R.L. Condensation of benzoylcyanamide with aromatic amino esters, acids, and amides. J. Org. Chem., 1974, 39(23), 3434-3435.
[http://dx.doi.org/10.1021/jo00937a036]
[47]
Reiter, J.; Rivó, E. On triazoles. XVII. The reaction of 5-amino-1,2,4-triazoles with N-heterocyclic β-oxo-esters. J. Heterocycl. Chem., 1988, 25(5), 1497-1502.
[http://dx.doi.org/10.1002/jhet.5570250546]
[48]
Sako, M. Product Class 19: Pyridopyrimidines, 2004. Vol. 16, pp. 1155- 1267, XP001538840.
[49]
Elattar, K.M.; Mert, B.D. Recent developments in the chemistry of bicyclic 6-6 systems: Chemistry of pyrido[4,3-d]pyrimidines. RSC Advances, 2016, 6, 71827-71851.
[http://dx.doi.org/10.1039/C6RA12364C]
[50]
Aparna, E.P.; Devaky, K.S. Advances in the solid-phase synthesis of pyrimidine derivatives. ACS Comb. Sci., 2019, 21(2), 35-68.
[http://dx.doi.org/10.1021/acscombsci.8b00172] [PMID: 30607935]
[51]
(a)Elattar, K.M.; Mert, B.D.; Abozeid, M.A.; El-Mekabaty, A. Advances in 1,3,5-triazepines chemistry. RSC Advances, 2016, 6, 37286-37307.
(b)Fadda, A.A.; Elattar, K.M. Reactivity of dehydroacetic acid in organic synthesis. Synth. Commun., 2016, 46, 1-30.
[52]
Elattar, K.M.; Fadda, A.A. Chemistry of antipyrine. Synth. Commun., 2016, 46, 1567-1594.
[http://dx.doi.org/10.1080/00397911.2016.1211703]
[53]
Fadda, A.A.; Elattar, K.M. Utility of enaminonitriles in heterocyclic synthesis: Synthesis of some new azepine, azocine, and pyrroldione derivatives. J. Heterocycl. Chem., 2014, 51(6), 1697-1704.
[http://dx.doi.org/10.1002/jhet.1829]
[54]
Fadda, A.A.; El-Hadidy, S.A.; Elattar, K.M. Advances in 1,8-naphthyridines chemistry. Synth. Commun., 2015, 45(24), 2765-2801.
[http://dx.doi.org/10.1080/00397911.2015.1089577]
[55]
Fadda, A.A.; El-Mekabaty, A.; Elattar, K.M. Chemistry of enaminonitriles of pyrano[2,3-c]pyrazole and related compounds. Synth. Commun., 2013, 43(20), 2685-2719.
[http://dx.doi.org/10.1080/00397911.2012.744842]
[56]
Elattar, K.M.; Youssef, I.; Fadda, A.A. Reactivity of indolizines in organic synthesis. Synth. Commun., 2016, 46, 719-744.
[http://dx.doi.org/10.1080/00397911.2016.1166252]
[57]
Elattar, K.M.; Rabie, R.; Hammouda, M.M. Recent developments in the chemistry of bicyclic 6-6 systems: Chemistry of pyrido[1,2-c]pyrimidines. Synth. Commun., 2016, 46, 1477-1498.
[http://dx.doi.org/10.1080/00397911.2016.1211702]
[58]
Monier, M.; Abdel-Latif, D.; El-Mekabaty, A.; Elattar, K.M. Bicyclic 6 + 6 systems: the chemistry of pyrimido[4,5-d]pyrimidines and pyrimido[5,4-d]pyrimidines. RSC Advances, 2019, 9, 30835-30867.
[http://dx.doi.org/10.1039/C9RA05687D]
[59]
Elattar, K.M.; Rabie, R.; Hammouda, M.M. Recent progress in the chemistry of bicyclic 6-6 systems: Chemistry of pyrido[1,2-a]pyrimidines. Monatsh. Chem., 2017, 148, 601-627.
[http://dx.doi.org/10.1007/s00706-016-1852-1]
[60]
Showalter, H. D. H.; Winter, R. T.; Rewcastle, G. W.; Denny, W. A.; Denny, W. A. Improved process for preparing 4,6-disubstituted pyrido[3,4- d]pyrimidines. PCT Int. Appl, 1997, WO9726259 A1 19970724.
[61]
Ezaki, K.; Kobayashi, K. A novel synthesis of quinazolines by cyclization of 1-(2-isocyanophenyl)-alkylideneamines generated by the treatment of 2-(1-azidoalkyl)phenyl isocyanides with NaH. Helv. Chim. Acta, 2014, 97(6), 822-829.
[http://dx.doi.org/10.1002/hlca.201300431]
[62]
Debeljak-Sustar, M.; Stanovnik, B.; Tisler, M.; Zrimsek, Z. Neighboring group interaction in ortho-substituted aminopyridines. Pyridopyrimidines and related systems. J. Org. Chem., 1978, 43(3), 393-397.
[http://dx.doi.org/10.1021/jo00397a003]
[63]
Nishikawa, S.; Nishikimi, Y.; Maki, S.; Kumazawa, Z.; Kashimura, N. Preparation and structure-activity relationships of 4-substituted amino-2-methylpyrido[3,4-d]pyrimidines as cytokinin analogs. J. Agric. Food Chem., 1995, 43(4), 1034-1038.
[http://dx.doi.org/10.1021/jf00052a035]
[64]
Holmes, J.L.; Almeida, L.; Barlaam, B.; Croft, R.A.; Dishington, A.P.; Gingipalli, L.; Hassall, L.A.; Hawkins, J.L.; Ioannidis, S.; Johannes, J.W. Synthesis of novel hydroxymethyl-substituted fused heterocycles. Synthesis, 2016, 48(8), 1226-1234.
[http://dx.doi.org/10.1055/s-0035-1561355]
[65]
Zhang, Y.; Huang, Y.; Huang, C.C. Syntheses of [14C] and [2H4]PD0205520, an inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor. J. Labelled Comp. Radiopharm., 2005, 48(7), 485-496.
[http://dx.doi.org/10.1002/jlcr.944]
[66]
Gabriel, S.; Colman, J. Abkömmlinge der Cinchomeronsäure. II. “Derivatives of cinchomeronic acid. Chem. Ber., 1902, 35(3), 2831-2852.
[http://dx.doi.org/10.1002/cber.19020350363]
[67]
Gelling, I.R.; Wibberley, D.G. Pyridopyrimidines. Part V. Syntheses and properties of pyrido[3,4-d]pyrimidin-4(3H)-ones and -pyrimidine-2,4-(1H,3H)-diones. J. Chem. Soc. C, 1969, 1969, 931-934.
[http://dx.doi.org/10.1039/j39690000931]
[68]
Hummersone, M. G.; Gomez, S.; Menear, K. A.; Cockcroft, X. F.; Smith, G. C. M. Preparation of methylene-hydrazinotriazine-diamine derivatives and related analogs as inhibitors of mTOR PCT Int. Appl 2006. WO2006090167.
[69]
Zhang, H.; Wang, J.; Zhao, H-Y.; Yang, X-Y.; Lei, H.; Xin, M.; Cao, Y-X.; Zhang, S-Q. Synthesis and biological evaluation of irreversible EGFR tyrosine kinase inhibitors containing pyrido[3,4-d]pyrimidine scaffold. Bioorg. Med. Chem., 2018, 26(12), 3619-3633.
[http://dx.doi.org/10.1016/j.bmc.2018.05.039] [PMID: 29853340]
[70]
Westaway, S.M.; Preston, A.G.S.; Barker, M.D.; Brown, F.; Brown, J.A.; Campbell, M.; Chung, C.W.; Drewes, G.; Eagle, R.; Garton, N.; Gordon, L.; Haslam, C.; Hayhow, T.G.; Humphreys, P.G.; Joberty, G.; Katso, R.; Kruidenier, L.; Leveridge, M.; Pemberton, M.; Rioja, I.; Seal, G.A.; Shipley, T.; Singh, O.; Suckling, C.J.; Taylor, J.; Thomas, P.; Wilson, D.M.; Lee, K.; Prinjha, R.K. Cell penetrant inhibitors of the KDM4 and KDM5 families of histone lysine demethylases. 2. Pyrido[3,4-d]pyrimidin-4(3H)-one derivatives. J. Med. Chem., 2016, 59(4), 1370-1387.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01538] [PMID: 26771203]
[71]
Cox, C.D.; Raheem, I.T.; Flores, B.A.; Whitman, D.B. 7-Azaquinazolines as PDE10 inhibitors. U.S Pat. Appl. Publ US 20110319409, 2011.
[72]
Deau, E.; Hedou, D.; Chosson, E.; Levacher, V.; Besson, T. Convenient one-pot synthesis of N3-substituted pyrido[2,3-d]-, pyrido[3,4-d]-, pyrido[4,3-d]-pyrimidin-4(3H)-ones, and quinazolin-4(3H)-ones analogs. Tetrahedron Lett., 2013, 54(27), 3518-3521.
[http://dx.doi.org/10.1016/j.tetlet.2013.04.096]
[73]
Rewcastle, G.W.; Denny, W.A.; Winters, R.T.; Colbry, N.L.; Showalter, H.D.H. Synthesis of 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones via directed lithiation of 2-substituted 5-aminopyridine derivatives. J. Chem. Soc., Perkin Trans. 1, 1996, 1996(18), 2221-2226.
[http://dx.doi.org/10.1039/P19960002221]
[74]
Hayakawa, M.; Kaizawa, H.; Moritomo, H.; Koizumi, T.; Ohishi, T.; Okada, M.; Ohta, M.; Tsukamoto, S.; Parker, P.; Workman, P.; Waterfield, M. Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110α inhibitors. Bioorg. Med. Chem., 2006, 14(20), 6847-6858.
[http://dx.doi.org/10.1016/j.bmc.2006.06.046] [PMID: 16837202]
[75]
Bavetsias, V.; Lanigan, R.M.; Ruda, G.F.; Atrash, B.; McLaughlin, M.G.; Tumber, A.; Mok, N.Y.; Le Bihan, Y-V.; Dempster, S.; Boxall, K.J.; Jeganathan, F.; Hatch, S.B.; Savitsky, P.; Velupillai, S.; Krojer, T.; England, K.S.; Sejberg, J.; Thai, C.; Donovan, A.; Pal, A.; Scozzafava, G.; Bennett, J.M.; Kawamura, A.; Johansson, C.; Szykowska, A.; Gileadi, C.; Burgess-Brown, N.A.; von Delft, F.; Oppermann, U.; Walters, Z.; Shipley, J.; Raynaud, F.I.; Westaway, S.M.; Prinjha, R.K.; Fedorov, O.; Burke, R.; Schofield, C.J.; Westwood, I.M.; Bountra, C.; Müller, S.; van Montfort, R.L.; Brennan, P.E.; Blagg, J. 8-Substituted pyrido[3,4-d]pyrimidin-4(3H)-one derivatives as potent, cell permeable, KDM4 (JMJD2) and KDM5 (JARID1) histone lysine demethylase inhibitors. J. Med. Chem., 2016, 59(4), 1388-1409.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01635] [PMID: 26741168]
[76]
Wei, L.; Malhotra, S.V. Synthesis and cytotoxicity evaluation of novel pyrido[3,4-d]pyrimidine derivatives as potential anticancer agents. MedChemComm, 2012, 3(10), 1250-1257.
[http://dx.doi.org/10.1039/c2md20097j] [PMID: 25429348]
[77]
Dishington, A.P.; Johnson, P.D.; Kettle, J.G. Synthesis of a 5-alkoxypyrido[3,4-d]pyrimidin-4(3H)-one derivative via directed ortho-metalation of a pyridine analogue. Tetrahedron Lett., 2004, 45(19), 3733-3735.
[http://dx.doi.org/10.1016/j.tetlet.2004.03.087]
[78]
Maguire, J.H.; McKee, R.L. The synthesis of a pyrido[3,4-d]pyrimidine analog of pteroic acid. J. Heterocycl. Chem., 1979, 16(1), 133-136.
[http://dx.doi.org/10.1002/jhet.5570160125]
[79]
Kobayashi, K.; Inouchi, H.; Konishi, M. A simple synthesis of 4-hydroxy-3,4-dihydropyrido[3,4-d]pyrimidine-2(1H)-thione derivatives by the reaction of 3-isothiocyanato-pyridin-4-yl ketones with primary amines. Heterocycles, 2014, 89(9), 2168-2176.
[http://dx.doi.org/10.3987/COM-14-13058]
[80]
Bardhan, J.C. CCLXXXV.-The chemistry of 1,3-dicarbonyl compounds. Part I. The mechanism of the cyanoacetamide and cyanoacetic ester condensations. J. Chem. Soc., 1929, 1929, 2223-2232.
[http://dx.doi.org/10.1039/JR9290002223]
[81]
Reider, M.J.; Elderfield, R.C. Studies in the pyridine series. V. Reactions involving the ortho effect in certain β,γ substituted pyridines. J. Org. Chem., 1942, 07(3), 286-296.
[http://dx.doi.org/10.1021/jo01197a010]
[82]
Kuznetsov, A.Y.; Chapyshev, S.V. Synthesis of 7-(arylmethyl)-substituted derivatives of 4-amino-2-pyrrolidin-1-yl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine. Chem. Heterocycl. Compd., 2007, 43(9), 1167-1173.
[http://dx.doi.org/10.1007/s10593-007-0179-6]
[83]
Kuznetsov, A.Y.; Nam, N.L.; Chapyshev, S.V. Synthesis of pyrido[3,4-d]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine. Chem. Heterocycl. Compd., 2007, 43(5), 640-645.
[http://dx.doi.org/10.1007/s10593-007-0100-3]
[84]
Kuznetsov, A.Y.; Chapyshev, S.V. Synthesis of 2-pyridyl-substituted derivatives of 7-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine. Chem. Heterocycl. Compd., 2007, 43(10), 1320-1324.
[http://dx.doi.org/10.1007/s10593-007-0200-0]
[85]
Meredith, E.L.; Mainolfi, N.; Poor, S.; Qiu, Y.; Miranda, K.; Powers, J.; Liu, D.; Ma, F.; Solovay, C.; Rao, C.; Johnson, L.; Ji, N.; Artman, G.; Hardegger, L.; Hanks, S.; Shen, S.; Woolfenden, A.; Fassbender, E.; Sivak, J.M.; Zhang, Y.; Long, D.; Cepeda, R.; Liu, F.; Hosagrahara, V.P.; Lee, W.; Tarsa, P.; Anderson, K.; Elliott, J.; Jaffee, B. Discovery of oral VEGFR-2 inhibitors with prolonged ocular retention that are efficacious in models of wet age-related macular degeneration. J. Med. Chem., 2015, 58(23), 9273-9286.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01227] [PMID: 26568411]
[86]
Hirota, K.; Kuki, H.; Maki, Y. Novel synthesis of pyrido[3,4-d]pyrimidines, pyrido[2,3-d]pyrimidines, and quinazolines via palladium catalyzed oxidative coupling. Heterocycles, 1994, 37(1), 563-570.
[http://dx.doi.org/10.3987/COM-93-S99]
[87]
Noguchi, M.; Sakamoto, K.; Nagata, S.; Kajigaeshi, S. Studies on pyridopyrimidines. III. A one-step preparation of pyrido[3,4-d]pyrimidine ring system by reaction of 5-formyl-1,3,6-trimethylpyrimidine-2,4(1H,3H)-dione with primary amines. J. Heterocycl. Chem., 1988, 25(1), 205-208.
[http://dx.doi.org/10.1002/jhet.5570250131]
[88]
Sakamoto, T.; Kondo, Y.; Yamanaka, H. Studies on pyrimidine derivatives. XXVIII. Synthesis of pyridopyrimidine derivatives by cross-coupling of halopyrimidines with olefins and acetylenes. Chem. Pharm. Bull. (Tokyo), 1982, 30(7), 2410-2416.
[http://dx.doi.org/10.1248/cpb.30.2410]
[89]
Innocenti, P.; Woodward, H.; O’Fee, L.; Hoelder, S. Expanding the scope of fused pyrimidines as kinase inhibitor scaffolds: synthesis and modification of pyrido[3,4-d]pyrimidines. Org. Biomol. Chem., 2015, 13(3), 893-904.
[http://dx.doi.org/10.1039/C4OB02238F] [PMID: 25407826]
[90]
Herrmann, W.A.; Brossmer, C.; Ofele, K.; Reisinger, C.P.; Priermeier, T.; Beller, M.; Fischer, H. Palladacycles as structurally defined catalysts for the Heck olefination of chloro‐ and bromoarenes. Angew. Chem. Int. Ed. Engl., 1995, 34, 1844-1848.
[http://dx.doi.org/10.1002/anie.199518441]
[91]
Honold, K.; Paul, J.; Roeschlaub, C.; Schaefer, W.; Scheiblich, S.; Von Thomas, H.; Whittle, A. Preparation of 7H-pyrido[3,4-d]pyrimidin-8-ones WO 2007088014A1, 2007.
[92]
Nishikawa, S.; Kumazawa, Z.; Kashimura, N.; Maki, S.; Nishikimi, Y. Synthesis and cytokinin activity of 4- and 2,4-substituted-pyrido[3,4-d]pyrimidine. Agric. Biol. Chem., 1986, 50, 495-497.
[http://dx.doi.org/10.1271/bbb1961.50.495]
[93]
Nishikawa, S.; Kumazawa, Z.; Kashimura, N.; Nishikimi, Y.; Uemura, S. Alternating dependency of cytokinin activity on the number of methylene units in ω-phenylalkyl derivatives of some purine cytokinins and 4-substituted pyrido[3,4-d]pyrimidines. Agric. Biol. Chem., 1986, 50, 2243-2249.
[http://dx.doi.org/10.1080/00021369.1986.10867724]
[94]
Harbottle, G.W.; Feeder, N.; Gibson, K.R.; Glossop, M.; Maw, G.N.; Million, W.A.; Morel, F.F.; Osborne, S.; Poinsard, C. Microwave-assisted synthesis of mGluR1 ligands: Carbon, nitrogen, and oxygen linked derivatives of pyrido[3,4-d]pyrimidin-4-ylamines. Tetrahedron Lett., 2007, 48(24), 4293-4296.
[http://dx.doi.org/10.1016/j.tetlet.2007.04.035]
[95]
Odingo, J.; O’Malley, T.; Kesicki, E.A.; Alling, T.; Bailey, M.A.; Early, J.; Ollinger, J.; Dalai, S.; Kumar, N.; Singh, R.V.; Hipskind, P.A.; Cramer, J.W.; Ioerger, T.; Sacchettini, J.; Vickers, R.; Parish, T. Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents. Bioorg. Med. Chem., 2014, 22(24), 6965-6979.
[http://dx.doi.org/10.1016/j.bmc.2014.10.007] [PMID: 25456390]
[96]
Lippa, B.; Kauffman, G.S.; Arcari, J.; Kwan, T.; Chen, J.; Hungerford, W.; Bhattacharya, S.; Zhao, X.; Williams, C.; Xiao, J.; Pustilnik, L.; Su, C.; Moyer, J.D.; Ma, L.; Campbell, M.; Steyn, S. The discovery of highly selective erbB2 (Her2) inhibitors for the treatment of cancer. Bioorg. Med. Chem. Lett., 2007, 17(11), 3081-3086.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.046] [PMID: 17398092]
[97]
Innocenti, P.; Woodward, H.L.; Solanki, S.; Naud, S.; Westwood, I.M.; Cronin, N.; Hayes, A.; Roberts, J.; Henley, A.T.; Baker, R.; Faisal, A.; Mak, G.W.; Box, G.; Valenti, M.; De Haven Brandon, A.; O’Fee, L.; Saville, H.; Schmitt, J.; Matijssen, B.; Burke, R.; van Montfort, R.L.; Raynaud, F.I.; Eccles, S.A.; Linardopoulos, S.; Blagg, J.; Hoelder, S. Rapid discovery of pyrido[3,4-d]pyrimidine inhibitors of monopolar spindle kinase 1 (MPS1) using a structure-based hybridization approach. J. Med. Chem., 2016, 59(8), 3671-3688.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01811] [PMID: 27055065]
[98]
Woodward, H.L.; Innocenti, P.; Cheung, K.J.; Hayes, A.; Roberts, J.; Henley, A.T.; Faisal, A.; Mak, G.W-Y.; Box, G.; Westwood, I.M.; Cronin, N.; Carter, M.; Valenti, M.; De Haven Brandon, A.; O’Fee, L.; Saville, H.; Schmitt, J.; Burke, R.; Broccatelli, F.; van Montfort, R.L.M.; Raynaud, F.I.; Eccles, S.A.; Linardopoulos, S.; Blagg, J.; Hoelder, S. Introduction of a methyl group curbs metabolism of pyrido[3,4-d]pyrimidine Monopolar Spindle 1 (MPS1) inhibitors and enables the discovery of the phase 1 clinical candidate N2-(2-ethoxy-4-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methyl-N8-neopentylpyrido-[3,4-d]-pyrimidine-2,8-diamine (BOS172722). J. Med. Chem., 2018, 61(18), 8226-8240.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00690] [PMID: 30199249]
[99]
Kimura, H.; Okuda, H.; Ishiguro, M.; Arimitsu, K.; Makino, A.; Nishii, R.; Miyazaki, A.; Yagi, Y.; Watanabe, H.; Kawasaki, I.; Ono, M.; Saji, H. 18F-Labeled pyrido[3,4-d]pyrimidine as an effective probe for imaging of L858R-mutant epidermal growth factor receptor. ACS Med. Chem. Lett., 2017, 8(4), 418-422.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00520] [PMID: 28435529]
[100]
Taylor, E.C.; Patel, H.H.; Sabitha, G.; Chaudhari, R. Synthesis of thieno[2,3-d]pyrimidine analogues of the potent antitumor agent N-4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl-L-glutamic acid (LY231514). Heterocycles, 1996, 43(2), 349-365.
[http://dx.doi.org/10.3987/COM-95-7269]
[101]
Klutchko, S.R.; Zhou, H.; Winters, R.T.; Tran, T.P.; Bridges, A.J.; Althaus, I.W.; Amato, D.M.; Elliott, W.L.; Ellis, P.A.; Meade, M.A.; Roberts, B.J.; Fry, D.W.; Gonzales, A.J.; Harvey, P.J.; Nelson, J.M.; Sherwood, V.; Han, H.K.; Pace, G.; Smaill, J.B.; Denny, W.A.; Showalter, H.D. Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB family of tyrosine kinase receptors. J. Med. Chem., 2006, 49(4), 1475-1485.
[http://dx.doi.org/10.1021/jm050936o] [PMID: 16480284]
[102]
Edwards, P.J.; Gibson, K.R.; Mantell, S.J.; Maw, G.N.; Poinsard, C. Azaquinazoline derivatives. Pfizer Inc. U.S. Patent, 2003, WO2005016925A1,
[103]
Vaca, M.J.A.; Gil, J.I.A.; Letavic, M.A.; Rudolph, D.A.; Shireman, B.T.; Stenne, B.M.; Ziff, J.M. Preparation of pyrido[3,4-d]pyrimidines as P2X7 modulators for therapy. U.S. Pat. Appl. Publ. 2014, US 20140275120 A1, 20140918.
[104]
Schenkel, L.B.; Olivieri, P.R.; Boezio, A.A.; Deak, H.L.; Emkey, R.; Graceffa, R.F.; Gunaydin, H.; Guzman-Perez, A.; Lee, J.H.; Teffera, Y.; Wang, W.; Youngblood, B.D.; Yu, V.L.; Zhang, M.; Gavva, N.R.; Lehto, S.G.; Geuns-Meyer, S. Optimization of a novel quinazolinone-based series of transient receptor potential A1 (TRPA1) antagonists demonstrating potent in vivo activity. J. Med. Chem., 2016, 59(6), 2794-2809.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00039] [PMID: 26942860]
[105]
Li, J.J.; Nahra, J.; Johnson, A.R.; Bunker, A.; O’Brien, P.; Yue, W-S.; Ortwine, D.F.; Man, C-F.; Baragi, V.; Kilgore, K.; Dyer, R.D.; Han, H.K. Quinazolinones and pyrido[3,4-d]pyrimidin-4-ones as orally active and specific matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. J. Med. Chem., 2008, 51(4), 835-841.
[http://dx.doi.org/10.1021/jm701274v] [PMID: 18251495]
[106]
Basha, A.; Lipton, M.; Weinreb, S.W. A mild, general method for conversion of esters to amides. Tetrahedron Lett., 1977, 48, 4171-4174.
[http://dx.doi.org/10.1016/S0040-4039(01)83457-2]
[107]
Levin, J.I.; Turos, E.; Weinreb, S.W. An alternative procedure for the aluminum-mediated conversion of esters to amides. Synth. Commun., 1982, 12, 989-993.
[http://dx.doi.org/10.1080/00397918208061938]
[108]
Montalbettis, C.A.G.N.; Falque, V. Amide bond formation and peptide coupling. Tetrahedron, 2005, 61, 10827-10852.
[http://dx.doi.org/10.1016/j.tet.2005.08.031]
[109]
Petric, A.; Tisler, M.; Stanovnik, B. Ring-opening reactions of triazolo- and tetrazolopyridopyrimidines or -quinazolines with carbon nucleophiles. Monatsh. Chem., 1985, 116(11), 1309-1319.
[http://dx.doi.org/10.1007/BF00811102]
[110]
Wibberley, D.G.; Gelling, I.R.; Pyridopyrimidines, V.I.I.; Pyridopyrimidines, V.I.I. Reductive ring cleavage of pyrido[3,4-d]pyrimidin-4(3H)-ones with lithium aluminum hydride. J. Chem. Soc. Sect. C: Org, 1971, 1971, 780-784.
[111]
Gelling, I.R.; Irwin, W.J. Reductive ring cleavage of fused pyrimidin-4(3H)-ones. J. Chem. Soc., Sect. D: Chem. Commun, 1969, 1969(19), 1138-1139.
[112]
Dyachenko, I.V.; Vas’kevich, R.I.; Vovk, M.V. Fused pyrimidine systems: XIII. Synthesis and some transformations of 1,3-thiazolo(thiazino)-fused pyrido[3,4-d]pyrimidines. Russ. J. Org. Chem., 2014, 50(2), 263-270.
[http://dx.doi.org/10.1134/S1070428014020201]
[113]
Khim, D.G.; Shmygarev, V.I. Iodocyclization of 2-allythio-4(3H)-pyrimidinones. Chem. Heterocycl. Compd., 1995, 31(2), 183-185.
[http://dx.doi.org/10.1007/BF01169677]
[114]
Vas’kevich, R.I.; Khripak, S.M.; Zborovskii, Yu.L.; Staninets, V.I.; Nesterenko, A.M.; Pyrozhenko, V.V. Synthesis of thiazinothienopyrimidine derivatives and their rearrangement into thiazolothienopyrimidines. Ukr. Khim. Zh., 2000, 66, 47-52.
[115]
Rewcastle, G.W.; Bridges, A.J.; Fry, D.W.; Rubin, J.R.; Denny, W.A. Tyrosine kinase inhibitors. 12. Synthesis and structure-activity relationships for 6-substituted 4-(phenylamino)pyrimido[5,4-d]pyrimidines designed as inhibitors of the epidermal growth factor receptor. J. Med. Chem., 1997, 40(12), 1820-1826.
[http://dx.doi.org/10.1021/jm960879m] [PMID: 9191958]
[116]
Pick, A.; Wiese, M. Tyrosine kinase inhibitors influence ABCG2 expression in EGFR-positive MDCK BCRP cells via the PI3K/Akt signaling pathway. ChemMedChem, 2012, 7(4), 650-662.
[http://dx.doi.org/10.1002/cmdc.201100543] [PMID: 22354538]
[117]
Rusnak, D.W.; Affleck, K.; Cockerill, S.G.; Stubberfield, C.; Harris, R.; Page, M.; Smith, K.J.; Guntrip, S.B.; Carter, M.C.; Shaw, R.J.; Jowett, A.; Stables, J.; Topley, P.; Wood, E.R.; Brignola, P.S.; Kadwell, S.H.; Reep, B.R.; Mullin, R.J.; Alligood, K.J.; Keith, B.R.; Crosby, R.M.; Murray, D.M.; Knight, W.B.; Gilmer, T.M.; Lackey, K. The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: potential therapy for cancer. Cancer Res., 2001, 61(19), 7196-7203.
[PMID: 11585755]
[118]
Panarese, J.D.; Cho, H.P.; Adams, J.J.; Nance, K.D.; Garcia-Barrantes, P.M.; Chang, S.; Morrison, R.D.; Blobaum, A.L.; Niswender, C.M.; Stauffer, S.R.; Conn, P.J.; Lindsley, C.W. Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration. Bioorg. Med. Chem. Lett., 2016, 26(15), 3822-3825.
[http://dx.doi.org/10.1016/j.bmcl.2016.04.083] [PMID: 27173801]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 6
Year: 2019
Page: [812 - 854]
Pages: 43
DOI: 10.2174/1570179416666190704113647
Price: $65

Article Metrics

PDF: 29
HTML: 5