Pyrazolo[4,3-H]quinazolines as Cyclin-dependent Kinase Inhibitors for Treating Cancer


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Abstract

The application describes the synthesis of 1H-pyrazolo[4,3-H]quinazoline compounds for treating cell proliferation dysfunction and is a broad-spectrum and strongly- active inhibitor for a cell cyclin-dependent kinase (CDK).

About the authors

Surya De

, Conju-Probe

Author for correspondence.
Email: info@benthamscience.net

References

  1. Malumbres, M.; Barbacid, M. Cell cycle, CDKs and cancer: A changing paradigm. Nat. Rev. Cancer, 2009, 9(3), 153-166. doi: 10.1038/nrc2602 PMID: 19238148
  2. Thiel, J.T.; Daigeler, A.; Kolbenschlag, J.; Rachunek, K.; Hoffmann, S. The role of CDK pathway dysregulation and its therapeutic potential in soft tissue sarcoma. Cancers, 2022, 14(14), 3380. doi: 10.3390/cancers14143380 PMID: 35884441
  3. Said, M.A.; Abdelrahman, M.A.; Abourehab, M.A.S.; Fares, M.; Eldehna, W.M. A patent review of anticancer CDK2 inhibitors (2017-present). Expert Opin. Ther. Pat., 2017, 32(8), 885-898. doi: 10.1080/13543776.2022.2078193
  4. Rossi, A.G.; Sawatzky, D.A.; Walker, A.; Ward, C.; Sheldrake, T.A.; Riley, N.A.; Caldicott, A.; Martinez-Losa, M.; Walker, T.R.; Duffin, R.; Gray, M.; Crescenzi, E.; Martin, M.C.; Brady, H.J.; Savill, J.S.; Dransfield, I.; Haslett, C. Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat. Med., 2006, 12(9), 1056-1064. doi: 10.1038/nm1468 PMID: 16951685
  5. Shi, Z.; Tian, L.; Qiang, T.; Li, J.; Xing, Y.; Ren, X.; Liu, C.; Liang, C. From structure modification to drug launch: A systematic review of the ongoing development of cyclin-dependent kinase inhibitors for multiple cancer therapy. J. Med. Chem., 2022, 65(9), 6390-6418. doi: 10.1021/acs.jmedchem.1c02064 PMID: 35485642
  6. Adon, T.; Shanmugarajan, D.; Kumar, H.Y. CDK4/6 inhibitors: A brief overview and prospective research directions. RSC Advances, 2021, 11(47), 29227-29246. doi: 10.1039/D1RA03820F PMID: 35479560
  7. Xie, Z.; Hou, S.; Yang, X.; Duan, Y.; Han, J.; Wang, Q.; Liao, C. Lessons learned from past cyclin-dependent kinase drug discovery efforts. J. Med. Chem., 2022, 65(9), 6356-6389. doi: 10.1021/acs.jmedchem.1c02190 PMID: 35235745
  8. Cetin, B.; Wabl, C.A.; Gumusay, O. CDK4/6 inhibitors: Mechanisms of resistance and potential biomarkers of responsiveness in breast cancer. Future Oncol., 2022, 18(9), 1143-1157. doi: 10.2217/fon-2021-0842 PMID: 35137602
  9. Elfgen, C.; Bjelic-Radisic, V. Targeted therapy in HR+ HER2- metastatic breast cancer: Current clinical trials and their implications for CDK4/6 inhibitor therapy and beyond treatment options. Cancers, 2021, 13(23), 5994. doi: 10.3390/cancers13235994 PMID: 34885105
  10. Shaikh, J.; Patel, K.; Khan, T. Advances in pyrazole based scaffold as cyclin-dependent kinase 2 inhibitors for the treatment of cancer. Mini Rev. Med. Chem., 2022, 22(8), 1197-1215. doi: 10.2174/1389557521666211027104957 PMID: 34711160
  11. Dhakal, A.; Falkson, C.; O’Regan, R.M. Adjuvant cyclin-dependent kinase 4/6 inhibition in hormone receptor–positive breast cancer: One Monarch to rule them all? Cancer, 2021, 127(18), 3302-3309. doi: 10.1002/cncr.33650 PMID: 34047359
  12. Mor, S.; Khatri, M. punia, R.; Sindhu, S. Recent progress in anticancer agents incorporating pyrazole scaffold. Mini Rev. Med. Chem., 2022, 22(1), 115-163. doi: 10.2174/1389557521666210325115218 PMID: 33823764
  13. Turner, N.C.; Ro, J.; André, F.; Loi, S.; Verma, S.; Iwata, H.; Harbeck, N.; Loibl, S.; Huang Bartlett, C.; Zhang, K.; Giorgetti, C.; Randolph, S.; Koehler, M.; Cristofanilli, M. Palbociclib in hormone-receptor–positive advanced breast cancer. N. Engl. J. Med., 2015, 373(3), 209-219. doi: 10.1056/NEJMoa1505270 PMID: 26030518
  14. Burstein, H.J. Systemic therapy for estrogen receptor–positive, HER2-negative breast cancer. N. Engl. J. Med., 2020, 383(26), 2557-2570. doi: 10.1056/NEJMra1307118 PMID: 33369357
  15. Hortobagyi, G.N.; Stemmer, S.M.; Burris, H.A.; Yap, Y.S.; Sonke, G.S.; Hart, L.; Campone, M.; Petrakova, K.; Winer, E.P.; Janni, W.; Conte, P.; Cameron, D.A.; André, F.; Arteaga, C.L.; Zarate, J.P.; Chakravartty, A.; Taran, T.; Le Gac, F.; Serra, P.; O’Shaughnessy, J. Overall survival with ribociclib plus letrozole in advanced breast cancer. N. Engl. J. Med., 2022, 386(10), 942-950. doi: 10.1056/NEJMoa2114663 PMID: 35263519

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