Novel 4-[5-(Substituted-1,2,4-oxadiazol-3-yl)phenylamine] Derivatives of 6,7-Dimethoxy-quinazolines as Potent Inhibitors of VEGF Receptors I and II

Abhishek Ashok1; Kannan Thanukrishnan1; Halehatty S. Bhojya Naik2; Soma Ghosh1

doi:10.14233/ajchem.2016.19884

Issue

Vol. 28 No. 10 (2016): Vol 28 Issue 10

Issue Published : June 30, 2016

This work is licensed under a Creative Commons Attribution 4.0 International License.

Novel 4-[5-(Substituted-1,2,4-oxadiazol-3-yl)phenylamine] Derivatives of 6,7-Dimethoxy-quinazolines as Potent Inhibitors of VEGF Receptors I and II

https://doi.org/10.14233/ajchem.2016.19884

Abhishek Ashok1

1Anthem Biosciences Pvt. Ltd., 49 Bommasandra Industrial Area, Bommasandra, Bangalore-560 099, India 2Department of PG Studies and Research in Industrial Chemistry, School of Chemical Sciences, Kuvempu University, Shankaraghatta-577 451, India *Corresponding author: Fax: +91 80 66724020; Tel: +91 80 66724213; E-mail: abhickm@gmail.com; abhishek.a@anthembio.com

Kannan Thanukrishnan1

Halehatty S. Bhojya Naik2

Soma Ghosh1

Asian Journal of Chemistry, Vol. 28 No. 10 (2016): Vol 28 Issue 10
Article Published : June 30, 2016

Abstract

A series of novel 4-[5-(substituted-1,2,4-oxadiazol-3-yl)phenylamine] derivatives at C-4 position of 6,7-dimethoxy-quinazolines were synthesized through multistep synthesis. The new compounds were tested for inhibition of vascular endothelial growth factor receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity with an IC₅₀ as low as 0.017 μM in an HTRF enzymatic assay. Compound 8j exhibited good antibacterial activity by inhibiting the growth of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and ATCC 35218 Escherichia coli (MIC: 0.25-16.00 μg/mL).

Keywords

Quinazolines Carboxamidamide Angiogenesis VEGFR-2 VEGFR-1.

Ashok1, A., Thanukrishnan1, K., S. Bhojya Naik2, H., & Ghosh1, S. (2016). Novel 4-[5-(Substituted-1,2,4-oxadiazol-3-yl)phenylamine] Derivatives of 6,7-Dimethoxy-quinazolines as Potent Inhibitors of VEGF Receptors I and II. Asian Journal of Chemistry, 28(10), 2122–2130. https://doi.org/10.14233/ajchem.2016.19884

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References

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References

J.A. Varner and D.A. Cheresh, in eds.: V.T. De Vita, S. Hellman and S.A. Rosenberg, Tumor Angiogenesis and the Role of Vascular Cell Integrin avb3, in Important Advances, in: Oncology, Lippincott-Raven Publishers, Philadelphia, PA, USA, pp. 69-87 (1996).

V.W.M. Van Hinsbergh, A. Collen and P. Koolwijk, Ann. Oncol., 10(Suppl. 4), 60 (1999); doi:10.1023/A:1008340820288.

J. Folkman, J. Natl. Cancer Inst., 82, 4 (1990); doi:10.1093/jnci/82.1.4.

C. Culy, Drugs Today, 41, 23 (2005); doi:10.1358/dot.2005.41.1.875776.

S.L. Fine, D.F. Martin and P. Kirkpatrick, Nat. Rev. Drug Discov., 4, 187 (2005); doi:10.1038/nrd1677.

J. Folkman, Sci. Am., 275, 150 (1996); doi:10.1038/scientificamerican0996-150.

M. Salmivirta, K. Lidholt and U. Lindahl, FASEB J., 10, 1270 (1996).

T. Mustonen and K.J. Alitalo, Cell Biol., 129, 895 (1995); doi:10.1083/jcb.129.4.895.

M. Klagsbrun and M.A. Moses, Chem. Biol., 6, R217 (1999); doi:10.1016/S1074-5521(99)80081-7.

T.P. Selvam and P.V. Kumar, Res. Pharmacy, 1, 1 (2001).

P.-P. Kung, M.D. Casper, K.L. Cook, L. Wilson-Lingardo, L.M. Risen, T.A. Vickers, R. Ranken, L.B. Blyn, J.R. Wyatt, P.D. Cook and D.J. Ecker, J. Med. Chem., 42, 4705 (1999); doi:10.1021/jm9903500.

R.A.W. Neves and R.M. Srivastava, Molecules, 11, 318 (2006); doi:10.3390/11050318.

K. Hemming, J. Chem. Res., 209 (2001); doi:10.3184/030823401103169603.

(a) K.E. Andersen, A.S. Jorgensen and C. Braestrup, Eur. J. Med. Chem., 29, 393 (1994); doi:10.1016/0223-5234(94)90065-5; (b) G.D. Diana, D.L. Volkots, T.J. Nitz, T.R. Bailey, M.A. Long, N. Vescio, S. Aldous, D.C. Pevear and F.J. Dutko, J. Med. Chem., 37, 2421 (1994); doi:10.1021/jm00041a022; (c) J. Saunders, M. Cassidy, S.B. Freedman, E.A. Harley, L.L. Iversen, C. Kneen, A.M. MacLeod, K.J. Merchant, R.J. Snow and R. Baker, J. Med. Chem., 33, 1128 (1990); doi:10.1021/jm00166a008; (d) J.C. Jochims, in eds.: A.R. Katritzky, C.W. Rees and E.F.V. Scriven, Comprehensive Heterocyclic Chemistry II, Pergamon Press: New York, vol. 4, p. 179 (1996).

(a) G.A. Showell, T.L. Gibbons, C.O. Kneen, A.M. MacLeod, K. Merchant, J. Saunders, S.B. Freedman, S. Patel and R. Baker, J. Med. Chem., 34, 1086 (1991); doi:10.1021/jm00107a032; (b) W.S. Messer, Y.F. Abuh, Y. Liu, S. Periyasamy, D.O. Ngur, M.A.N. Edgar, A.A. El-Assadi, Sbeih, P.G. Dunbar, S. Roknich, T. Rho, Z. Fang, B. Ojo, H. Zhang, J.J. Huzl and P.I. Nagy, J. Med. Chem., 40, 1230 (1997); doi:10.1021/jm960467d; (c) B.S. Orlek, F.E. Blaney, F. Brown, M.S.G. Clark, M.S. Hadley, J. Hatcher, G.J. Riley, H.E. Rosenberg, H.J. Wadsworth and P. Wyman, J. Med. Chem., 34, 2726 (1991); doi:10.1021/jm00113a009; (d) J.E. Macor, T. Ordway, R.L. Smith, P.R. Verhoest and R.A. Mack, J. Org. Chem., 61, 3228 (1996); doi:10.1021/jo9603340.

(a) F. Watjen, R. Baker, M. Engelstoff, R. Herbert, A. MacLeod, A. Knight, K. Merchant, J. Moseley and J. Saunders, J. Med. Chem., 32, 2282 (1989); doi:10.1021/jm00130a010; (b) W.R. Tully, C.R. Gardner, R.J. Gillespie and R. Westwood, J. Med. Chem., 34, 2060 (1991); doi:10.1021/jm00111a021.

C.-Y. Chen, C.H. Senanayake, T.J. Bill, R.D. Larsen, T.R. Verhoeven and P.J. Reider, J. Org. Chem., 59, 3738 (1994); doi:10.1021/jo00092a046.

C.J. Swain, R. Baker, C. Kneen, J. Moseley, J. Saunders, E.M. Seward, G. Stevenson, M. Beer, J. Stanton and K. Watling, J. Med. Chem., 34, 140 (1991); doi:10.1021/jm00105a021.

J.W. Clitherow, P. Beswick, W.J. Irving, D.I.C. Scopes, J.C. Barnes, J. Clapham, J.D. Brown, D.J. Evans and A.G. Hayes, Bioorg. Med. Chem. Lett., 6, 833 (1996);

doi:10.1016/0960-894X(96)00122-9.

H.-Z. Zhang, S. Kasibhatla, J. Kuemmerle, W. Kemnitzer, K. Ollis-Mason, L. Qiu, C. Crogan-Grundy, B. Tseng, J. Drewe and S.X. Cai, J. Med. Chem., 48, 5215 (2005); doi:10.1021/jm050292k.

(a) K.A. Jessen, N.M. English, J.Y. Wang, S. Maliartchouk, S.P. Archer, L. Qiu, R. Brand, J. Kuemmerle, H.Z. Zhang, K. Gehlsen, J. Drewe, B. Tseng, S. Xiong-Cai and S. Kasibhatla, Mol. Cancer Ther., 4, 761 (2005); doi:10.1158/1535-7163.MCT-04-0333; (b) D. Kumar, G. Patel, E.O. Johnson and K. Shah, Bioorg. Med. Chem. Lett., 19, 2739 (2009); doi:10.1016/j.bmcl.2009.03.158.

M.B. Andrus, S.N. Mettath and C. Song, J. Org. Chem., 67, 8284 (2002); doi:10.1021/jo026217o.

J.W. Jin, L. Zhang, G.-R. Meng, J.-H. Zhu and Q. Zhang, Synth. Commun., 44, 346 (2014); doi:10.1080/00397911.2013.805230.

D.P. Konakanchi, B. Gongalla, K.B. Sikha, C. Kandaswamy, K.S.B.R. Adibhatla and V.C. Nannapaneni, Anhydrous lenalidomide form-I, US Patent 20150353525 (2015).

S.H. Yang, D.B. Khadka, S.H. Cho, H.-K. Ju, K.Y. Lee, H.J. Han, K.-T. Lee and W.-J. Cho, Bioorg. Med. Chem., 19, 968 (2011); doi:10.1016/j.bmc.2010.11.057.

Issue

Vol. 28 No. 10 (2016): Vol 28 Issue 10

Novel 4-[5-(Substituted-1,2,4-oxadiazol-3-yl)phenylamine] Derivatives of 6,7-Dimethoxy-quinazolines as Potent Inhibitors of VEGF Receptors I and II

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