1,657
Views
4
CrossRef citations to date
0
Altmetric
Research Paper

Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors

, , , , , , , , , , , & show all
Article: 2155638 | Received 21 Sep 2022, Accepted 01 Dec 2022, Published online: 17 Jan 2023

References

  • Corrie PG. Cytotoxic chemotherapy: clinical aspects. Medicine. 2008;36(1):24–28.
  • Zugazagoitia J, Guedes C, Ponce S, Ferrer I, Molina-Pinelo S, Paz-Ares L. Current challenges in cancer treatment. Clin Ther. 2016;38(7):1551–1566.
  • Katso R, Okkenhaug K, Ahmadi K, White S, Timms J, Waterfield MD. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 2001;17:615–675.
  • Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7(8):606–619.
  • Carrera AC, Anderson R. The cell biology behind the oncogenic PIP3 lipids. J Cell Sci. 2019;132:jcs228395.
  • Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005;4(12):988–1004.
  • Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017;170(4):605–635.
  • Wong KK, Engelman JA, Cantley LC. Targeting the PI3K signaling pathway in cancer. Curr Opin Genet Dev. 2010;20(1):87–90.
  • Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13(5):283–296.
  • Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 2015;15(1):7–24.
  • Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13(2):140–156.
  • Wu P, Nielsen TE, Clausen MH. FDA-approved small-molecule kinase inhibitors. Trends Pharmacol Sci. 2015;36(7):422–439.
  • Markham A. Copanlisib: first global approval. Drugs. 2017;77(18):2057–2062.
  • Scott WJ, Hentemann MF, Rowley RB, Bull CO, Jenkins S, Bullion AM, Johnson J, Redman A, Robbins AH, Esler W, et al. Discovery and SAR of Novel 2,3-DihydroImidazo[1,2-c]quinazoline PI3K Inhibitors: identification of Copanlisib (BAY 80-6946). ChemMedChem. 2016;11(14):1517–1530.
  • Burger MT, Pecchi S, Wagman A, Ni Z-J, Knapp M, Hendrickson T, Atallah G, Pfister K, Zhang Y, Bartulis S, et al. Identification of NVP-BKM120 as a potent, selective, orally bioavailable class I PI3 kinase inhibitor for treating cancer. ACS Med Chem Lett. 2011;2(10):774–779.
  • Folkes AJ, Ahmadi K, Alderton WK, Alix S, Baker SJ, Box G, Chuckowree IS, Clarke PA, Depledge P, Eccles SA, et al. The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. 2008;51(18):5522–5532.
  • André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929–1940.
  • Furet P, Guagnano V, Fairhurst RA, Imbach-Weese P, Bruce I, Knapp M, Fritsch C, Blasco F, Blanz J, Aichholz R, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 2013;23(13):3741–3748.
  • Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–1018.
  • Kendall JD, O’Connor PD, Marshall AJ, Frédérick R, Marshall ES, Lill CL, Lee W-J, Kolekar S, Chao M, Malik A, et al. Discovery of pyrazolo[1,5-a]pyridines as p110a-selective PI3 kinase inhibitors. Bioorg Med Chem. 2012;20(1):69–85.
  • Gao GR, Liu JL, Mei DS, et al. Design, synthesis and biological evaluation of acylhydrazone derivatives as PI3K inhibitors. Chin Chem Lett. 2015; 26:562–570.
  • Liao W, Wang Z, Han Y, Qi Y, Liu J, Xie J, Tian Y, Lei Q, Chen R, Sun M, et al. Design, synthesis and biological activity of novel 2,3,4,5-tetra-substituted thiophene derivatives as PI3Kα inhibitors with potent antitumor activity. Eur J Med Chem. 2020; 197:112309.
  • Tanaka H, Yoshida M, Tanimura H, Fujii T, Sakata K, Tachibana Y, Ohwada J, Ebiike H, Kuramoto S, Morita K, et al. The selective Class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011;17(10):3272–3281.
  • Knight SD, Adams ND, Burgess JL, Chaudhari AM, Darcy MG, Donatelli CA, Luengo JI, Newlander KA, Parrish CA, Ridgers LH, et al. Discovery of GSK2126458, a highly potent inhibitor of PI3K and the Mammalian target of Rapamycin. ACS Med Chem Lett. 2010;1(1):39–43.
  • Lin S, Wang C, Ji M, Wu D, Lv Y, Zhang K, Dong Y, Jin J, Chen J, Zhang J, et al. Discovery and optimization of 2‑Amino-4-methylquinazoline derivatives as highly potent phosphatidylinositol 3‑kinase inhibitors for cancer treatment. J Med Chem. 2018;61(14):6087–6109.