Synthesis of P-Stereogenic Diarylphosphinamides as Novel Inhibitors of Melanoma

doi:10.1007/s40242-019-9103-8

Abstract

Abstract: In this paper, the evaluation on the biological activity of an array of P-stereogenic diaryphosphinamides as novel inhibitors of malignant melanoma was presented. Among 20 derivatives being screened, several of them displayed high inhibition rate up to 90% against the B16 melanoma cells at 100 μg/mL. Moreover, one of them displayed high inhibition activity with IC₅₀ value of 5.8 μg/mL. In contrast, a comparative assay showed that all the compounds were almost inactive or showed only very weak inhibition ability against an array of cell lines including HL7702, Bel7402, HT1080, A549 and McF7 cells. The results suggested that the P-stereogenic diarylphosphinamides may serve as a class of novel lead molecules for further development of new inhibitors for selective inhibition of melanoma.

Key words: Phosphinamide, Melanoma, Cytotoxicity, Anticancer activity, Phosphorus compound

TANG Xu, DU Zhijun, WU Guojie, HAN Fushe. Synthesis of P-Stereogenic Diarylphosphinamides as Novel Inhibitors of Melanoma[J]. Chemical Research in Chinese Universities, 2019, 35(5): 812-816.

References

[1] Gladfelter P., Darwish N. H. E., Mousa S. A., Melanoma Res., 2017, 27(5), 403
[2] Siegel R. L., Miller K. D., Jemal A., CA Cancer J. Clin., 2016, 66(1), 7
[3] Tronnier M., Mitteldorf C., Cancer Manag. Res., 2014, 6, 349
[4] McArthur G. A., Chapman P. B., Robert C., Larkin J., Haanen J. B., Dummer R., Ribas A., Hogg D., Hamid O., Ascierto P. A., Lancet Oncol., 2014, 15(3), 323
[5] Trinh V. A., Davis J. E., Anderson J. E., Kim K. B., Ann. Pharmacother., 2014, 48(4), 519
[6] Lugowska I., Kosela-Paterczyk H., Kozak K., Rutkowski P., Onco. Targets Ther., 2015, 8, 2251
[7] Shahabi V., Whitney G., Hamid O., Schmidt H., Chasalow S. D., Alaparthy S., Jackson J. R., Cancer Immunol. Immuother., 2012, 61(5), 733
[8] Ugurel S., Röhmel J., Ascierto P. A., Flaherty K. T., Grob J. J., Hauschild A., Larkin J., Long G. V., Lorigan P., McArthur G. A., Ribas A., Robert C., Schadendorf D., Garbe C., Eur. J. Cancer, 2016, 53, 125
[9] van Leeuwen P. W. N. M., Kamer P. C. J., Claver C., Pàmies O., Diéguez M., Chem. Rev., 2011, 111(3), 2077
[10] Wang D., Chen Q., Lu S., Zhou Y., Chem. Rev., 2012, 112(4), 2557
[11] Xie J. H., Zhu S. F., Zhou Q. L., Chem. Soc. Rev., 2012, 41(11), 4126
[12] Chen Q., Ye Z., Duan Y., Zhou Y., Chem. Soc. Rev., 2013, 42(2), 497
[13] Dutartre M., Bayardon J., Juge S., Chem. Soc. Rev., 2016, 45(20), 5771
[14] Yang H., Yang X., Tang W., Tetrahedron, 2016, 72(41), 6143
[15] You S., Cai Q., Zeng M. Chem. Soc. Rev., 2009, 38(8), 2190
[16] Wei Y., Shi M., Acc. Chem. Res., 2010, 43(7), 1005
[17] Mahlau M., List B., Angew. Chem. Int. Ed., 2013, 52(2), 518
[18] Brak K., Jacobsen E. N., Angew. Chem. Int. Ed., 2013, 52(2), 534
[19] Phipps R. J., Hamilton G. L., Toste F. D., Nat. Chem., 2012, 4(8), 603
[20] Remond E., Juge S., Chim. Oggi., 2014, 32(4), 49
[21] Parmar D., Sugiono E., Raja S., Rueping M., Chem. Rev., 2014, 114(18), 9047
[22] Dang Q., Liu Y., Cashion D. K., Kasibhatla S. R., Jiang T., Taplin F., Jacintho J. D., Li H., Sun Z., Fan Y., DaRe J., Tian F., Li W., Gibson T., Lemus R., van Poelje P. D., Potter S. C., Erion M. D., J. Med. Chem., 2011, 54(1), 153
[23] Lassaux P., Hamel M., Gulea M., Delbrück H., Mercuri P. S., Horsfall L., Dehareng D., Kupper M., Frère J. M., Hoffmann K., Galleni M., Bebrone C., J. Med. Chem., 2010, 53(13), 4862
[24] Zhao Y. L., Wu G. J., Han F. S., Chem. Commun., 2012, 48(47), 5868
[25] Zhao Y. L., Wu G. J., Li Y., Gao L. X., Han F. S., Chem. Eur. J., 2012, 18(31), 9622
[26] Guan J., Wu G. J., Han F. S., Chem. Eur. J., 2014, 20(12), 3301
[27] Du Z. J., Guan J., Wu G. J., Xu P., Gao L. X., Han F. S., J. Am. Chem. Soc., 2015, 137(2), 632
[28] Chen Y. H., Qin X. L., Guan J., Du Z. J., Han F. S., Tetrahedron:Asymmetry, 2017, 28(4), 522
[29] Chen Y. H., Qin X. L., Han F. S., Chem. Commun., 2017, 53(43), 5826
[30] Müller K., Faeh C., Diederich F., Science, 2007, 317(5846), 1881
[31] Sheldrick G. M., Acta Crystallogr A, 2008, 64, 112
[32] Sheldrick G. M., Acta Crystallogr A, 2015, 71, 3
[33] Sheldrick G. M., Acta Crystallogr C, 2015, 71, 3
[34] Carpino L. A., Xia J., Zhang, C., El-Faham A., J. Org. Chem., 2004, 69(1), 62
[35] McPake C. B., Murray C. B., Sandford G., Aust. J. Chem., 2013, 66(2), 145
[36] Yan X., Tang X. X., Chen L., Yi Z. W., Fang M. J., Wu Z., Qiu Y. K., Mar. Drugs, 2014, 12(4), 2156