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Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Review Article

Synthesis and Clinical Development of Palbociclib: An Overview

Author(s): Debabrata Konar, Saurabh Maru, Subhabrata Kar and Kapil Kumar*

Volume 18 , Issue 1 , 2022

Published on: 04 December, 2020

Page: [2 - 25] Pages: 24

DOI: 10.2174/1573406417666201204161243

Price: $65

Abstract

Breast cancer is the second most commonly identified cancer in women in the United States after skin cancer. The past few years have seen a substantial increase in breast cancer awareness campaigns and active research in fields of diagnosis and targeted therapy. These factors have led to a better mechanistic understanding of the disease, detection at earlier stages, and a more personalized approach to treatment, ultimately causing a crucial increase in the survival rates after detection. However, with the advances in treatment, cases of patients developing primary resistance and acquired resistance are increasing. Most of the breast cancers which develop resistance to therapy are ER+ and are typically treated with tamoxifen and fulvestrant. These drugs either lower the levels of estrogen or inhibit the receptors for estrogen and prevent the tumor from spreading. Around one-third of women treated with these drugs develop resistance to them, lowering their chances of survival. This has directed the search for newer drug therapies to target advanced breast cancer and resistance. One of these efforts has resulted in the development of Palbociclib, a first in class inhibitor of cyclin dependent kinases 4 and 6 (CDK4 and CDK6), which was granted accelerated approval from the FDA for combination therapy in postmenopausal women with ER+, HER2- metastatic breast cancer. This review is focused on the various aspects of “Palbociclib” including its synthesis, molecular modeling studies, and efficacy and safety profile with data obtained from various clinical trials.

Keywords: Palbociclib, Breast cancer, CDK4, CDK6, Clinical trial, carcinoma.

Graphical Abstract
[1]
Ferlay, J.; Steliarova-Foucher, E.; Lortet-Tieulent, J.; Rosso, S.; Coebergh, J.W.; Comber, H.; Forman, D.; Bray, F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur. J. Cancer, 2013, 49(6), 1374-1403.
[http://dx.doi.org/10.1016/j.ejca.2012.12.027] [PMID: 23485231]
[2]
Miller, K.D.; Siegel, R.L.; Lin, C.C.; Mariotto, A.B.; Kramer, J.L.; Rowland, J.H.; Stein, K.D.; Alteri, R.; Jemal, A. Cancer treatment and survivorship statistics, 2016. CA Cancer J. Clin., 2016, 66(4), 271-289.
[http://dx.doi.org/10.3322/caac.21349] [PMID: 27253694]
[3]
Bohon, C. Cancer recognition and screening for common breast disorders and malignancy. Obstet. Gynecol. Clin. North Am., 2017, 44(2), 257-270.
[http://dx.doi.org/10.1016/j.ogc.2017.02.005] [PMID: 28499535]
[4]
Fry, D.W.; Garrett, M.D. Inhibitors of cyclin-dependent kinases as therapeutic agents for the treatment of cancer. Curr. Opin. Oncol. Endocrine Metab. Invest. Drugs, 2000, 2, 40-59.
[5]
Sielecki, T.M.; Boylan, J.F.; Benfield, P.A.; Trainor, G.L. Cyclin-dependent kinase inhibitors: useful targets in cell cycle regulation. J. Med. Chem., 2000, 43(1), 1-18.
[http://dx.doi.org/10.1021/jm990256j] [PMID: 10633033]
[6]
Honma, T.; Hayashi, K.; Aoyama, T.; Hashimoto, N.; Machida, T.; Fukasawa, K.; Iwama, T.; Ikeura, C.; Ikuta, M.; Suzuki-Takahashi, I.; Iwasawa, Y.; Hayama, T.; Nishimura, S.; Morishima, H. Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. J. Med. Chem., 2001, 44(26), 4615-4627.
[http://dx.doi.org/10.1021/jm0103256] [PMID: 11741479]
[7]
Breault, G.A.; Ellston, R.P.A.; Green, S.; James, S.R.; Jewsbury, P.J.; Midgley, C.J.; Pauptit, R.A.; Minshull, C.A.; Tucker, J.A.; Pease, J.E. Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 2: identification and optimisation of substituted 2,4-bis anilino pyrimidines. Bioorg. Med. Chem. Lett., 2003, 13(18), 2961-2966.
[http://dx.doi.org/10.1016/S0960-894X(03)00203-8] [PMID: 12941312]
[8]
Abdolmohammadi, S. α-ZrP: a highly efficient catalyst for solvent-free synthesis of pyrimido[5′,4′:5,6]pyrido[2,3-d]pyrimidinetetraone and 4-arylacridinedione derivatives. Lett. Org. Chem., 2014, 11, 465-469.
[http://dx.doi.org/10.2174/1570178611666140124002242]
[9]
Abdolmohammadi, S.; Afsharpour, M. An operationally simple green procedure for the synthesis of dihydropyrimido[4,5-d]pyrimidinetriones using CuI nanoparticles as a highly efficient catalyst. Z. Naturforsch. B, 2015, 70, 171-176.
[http://dx.doi.org/10.1515/znb-2014-0207]
[10]
Kiani, M.; Abdolmohammadi, S.; Janitabar-Darzi, S. Fast and efficient synthesis of chromeno[d]pyrimidinedionescatalysed by a TiO2-SiO2 nanocomposite in aqueous media. J. Chem. Res., 2017, 41(6), 337-340.
[http://dx.doi.org/10.3184/174751917X14949407124706]
[11]
Fakheri-Vayeghan, S.; Abdolmohammadi, S.; Kia-Kojoori, R. An expedient synthesis of 6-amino-5-[(4-hydroxy-2-oxo-2H-chromen-3-yl)(aryl)methyl]-1,3-dimethyl-2,4,6 (1H,3H)-pyrimidinedione derivatives using Fe3O4@TiO2 nanocomposite as an efficient, magnetically separable, and reusable catalyst. Naturforsch. B, 2018, 73(8), 545-551.
[http://dx.doi.org/10.1515/znb-2018-0030]
[12]
Yaltaghian-Khiabani, N.; Abdolmohammadi, S.; Sadegh-Samiei, S. Aqueous media preparation of pyrido[d]pyrimidines over calcined TiO2-SiO2 nanocomposite as an efficient catalyst at ambient temperature. Lett. Org. Chem., 2019, 16(11), 915-921.
[http://dx.doi.org/10.2174/1570178616666181210102146]
[13]
Rabiei, A.; Abdolmohammadi, S.; Shafaei, F. A green approach for an efficient preparation of 2,4-diamino-6-aryl-5-pyrimidinecarbonitriles using a TiO2/SiO2 nanocomposite catalyst under solvent-free conditions. Z. Naturforsch. B, 2017, 72(4), 241-247.
[http://dx.doi.org/10.1515/znb-2016-0219]
[14]
Roberts, P.J.; Bisi, J.E.; Strum, J.C.; Combest, A.J.; Darr, D.B.; Usary, J.E.; Zamboni, W.C.; Wong, K.K.; Perou, C.M.; Sharpless, N.E. Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. J. Natl. Cancer Inst., 2012, 104(6), 476-487.
[http://dx.doi.org/10.1093/jnci/djs002] [PMID: 22302033]
[15]
Carey, L.A.; Perou, C.M. Palbociclib-taking breast-cancer cells out of gear. N. Engl. J. Med., 2015, 373(3), 273-274.
[http://dx.doi.org/10.1056/NEJMe1506680] [PMID: 26176385]
[16]
McCain, J. First-in-class CDK4/6 inhibitor palbociclib could usher in a new wave of combination therapies for HR+, HER2-. P&T, 2015, 40(8), 511-520.
[PMID: 26236140]
[17]
Garber, K. The cancer drug that almost wasn’t. Science, 2014, 345(6199), 865-867.
[http://dx.doi.org/10.1126/science.345.6199.865] [PMID: 25146265]
[18]
Morikawa, A.; Henry, N.L. Palbociclib for the treatment of estrogen receptor-positive, HER2-negative metastatic breast cancer. Clin. Cancer Res., 2015, 21(16), 3591-3596.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0390] [PMID: 26100274]
[19]
Kastan, M.B.; Bartek, J. Cell-cycle checkpoints and cancer. Nature, 2004, 432(7015), 316-323.
[http://dx.doi.org/10.1038/nature03097] [PMID: 15549093]
[20]
Alevizopoulos, K.; Vlach, J.; Hennecke, S.; Amati, B. Cyclin E and c-Myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins. EMBO J., 1997, 16(17), 5322-5333.
[http://dx.doi.org/10.1093/emboj/16.17.5322] [PMID: 9311992]
[21]
Harbour, J.W.; Dean, D.C. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev., 2000, 14(19), 2393-2409.
[http://dx.doi.org/10.1101/gad.813200] [PMID: 11018009]
[22]
Coqueret, O. New roles for p21 and p27 cell-cycle inhibitors: a function for each cell compartment? Trends Cell Biol., 2003, 13(2), 65-70.
[http://dx.doi.org/10.1016/S0962-8924(02)00043-0] [PMID: 12559756]
[23]
Dickson, M.A. Molecular pathways: CDK4 inhibitors for cancer therapy. Clin. Cancer Res., 2014, 20(13), 3379-3383.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-1551] [PMID: 24795392]
[24]
Dorée, M.; Galas, S. The cyclin-dependent protein kinases and the control of cell division. FASEB J., 1994, 8(14), 1114-1121.
[http://dx.doi.org/10.1096/fasebj.8.14.7958616] [PMID: 7958616]
[25]
Capparelli, C.; Chiavarina, B.; Whitaker-Menezes, D.; Pestell, T.G.; Pestell, R.G.; Hulit, J.; Andò, S.; Howell, A.; Martinez-Outschoorn, U.E.; Sotgia, F.; Lisanti, M.P. CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, “fueling” tumor growth via paracrine interactions, without an increase in neo-angiogenesis. Cell Cycle, 2012, 11(19), 3599-3610.
[http://dx.doi.org/10.4161/cc.21884] [PMID: 22935696]
[26]
Murphy, C.G.; Dickler, M.N. The Role of CDK4/6 inhibition in breast cancer. Oncologist, 2015, 20(5), 483-490.
[http://dx.doi.org/10.1634/theoncologist.2014-0443] [PMID: 25876993]
[27]
Feng, Y.; Spezia, M.; Huang, S.; Yuan, C.; Zeng, Z.; Zhang, L.; Ji, X.; Liu, W.; Huang, B.; Luo, W.; Liu, B.; Lei, Y.; Du, S.; Vuppalapati, A.; Luu, H.H.; Haydon, R.C.; He, T.C.; Ren, G. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis., 2018, 5(2), 77-106.
[http://dx.doi.org/10.1016/j.gendis.2018.05.001] [PMID: 30258937]
[28]
Barvian, M.U.S. Patent,7,208,489, 2007.
[29]
Erdman, D.T.U.S. Patent,7,781,583 2010.
[30]
Piers, E.; McEachern, E.J.; Romero, M.A. Copper chloride catalyzed and hydrochloric acid-mediated chemoselective protiodestannylations of alkyl (Z)- or (E)-2,3-bis(trimethylstannyl)-2-alkenoates. J. Org. Chem., 1997, 62, 6034-6040.
[http://dx.doi.org/10.1021/jo9707693]
[31]
Chekal, B.P.; Ewers, J.; Guinness, S.M.; Ide, N.D.; Leeman, K.R.; Post, R.J.; Rane, A.M.; Sutherland, K.; Wang, K.; Webster, M. Palbociclib commercial manufacturing process development Part III: deprotection followed by crystallization for API particle property control. Org. Process Res. Dev., 2016, 20, 1217-1226.
[http://dx.doi.org/10.1021/acs.oprd.6b00071]
[32]
Duan, S.; Place, D.; Perfect, H.H.; Ide, N.D.; Maloney, M.; Sutherland, K.; Price Wiglesworth, K.E.; Wang, K.; Olivier, M.; Kong, F.; Leeman, K.; Blunt, J.; Draper, J.; McAuliffe, M.; O’Sullivan, M.; Lynch, D. Palbociclib commercial manufacturing process development Part I: control of regioselectivity in a grignard-mediated SNAr coupling. Org. Process Res. Dev., 2016, 20, 1191-1202.
[http://dx.doi.org/10.1021/acs.oprd.6b00070]
[33]
Maloney, M.T.; Jones, B.P.; Olivier, M.A.; Magano, J.; Wang, K.; Ide, N.D.; Palm, A.S.; Bill, D.R.; Leeman, K.R.; Sutherland, K. Palbociclib commercial manufacturing process development Part II: regioselective heck coupling with polymorph control for processability. Org. Process Res. Dev., 2016, 20, 1203-1216.
[http://dx.doi.org/10.1021/acs.oprd.6b00069]
[34]
Poratti, M.; Marzaro, G. Third-generation CDK inhibitors: A review on the synthesis and binding modes of Palbociclib, Ribociclib and Abemaciclib. Eur. J. Med. Chem., 2019, 172, 143-153.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.064] [PMID: 30978559]
[35]
Lu, H.; Schulze-Gahmen, U. Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition. J. Med. Chem., 2006, 49(13), 3826-3831.
[http://dx.doi.org/10.1021/jm0600388] [PMID: 16789739]
[36]
Alkorta, I.; Elguero, J.A. Theoretical study of the structure and protonation of Palbociclib (PD 0332991). J. Mol. Struct., 2014, 1056, 209-215.
[http://dx.doi.org/10.1016/j.molstruc.2013.10.040]
[37]
VanderWel, S.N.; Harvey, P.J.; McNamara, D.J.; Repine, J.T.; Keller, P.R.; Quin, J., III; Booth, R.J.; Elliott, W.L.; Dobrusin, E.M.; Fry, D.W.; Toogood, P.L. Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4. J. Med. Chem., 2005, 48(7), 2371-2387.
[http://dx.doi.org/10.1021/jm049355+] [PMID: 15801830]
[38]
Rocca, A.; Farolfi, A.; Bravaccini, S.; Schirone, A.; Amadori, D. Palbociclib (PD 0332991): targeting the cell cycle machinery in breast cancer. Expert Opin. Pharmacother., 2014, 15(3), 407-420.
[http://dx.doi.org/10.1517/14656566.2014.870555] [PMID: 24369047]
[39]
Clark, A.S.; Karasic, T.B.; DeMichele, A.; Vaughn, D.J.; O’Hara, M.; Perini, R.; Zhang, P.; Lal, P.; Feldman, M.; Gallagher, M.; O’Dwyer, P.J. Palbociclib (PD0332991)-a selective and potent cyclin-dependent kinase inhibitor: A review of pharmacodynamics and clinical development. JAMA Oncol., 2016, 2(2), 253-260.
[http://dx.doi.org/10.1001/jamaoncol.2015.4701] [PMID: 26633733]
[40]
Finn, R.S.; Crown, J.P.; Lang, I.; Boer, K.; Bondarenko, I.M.; Kulyk, S.O.; Ettl, J.; Patel, R.; Pinter, T.; Schmidt, M.; Shparyk, Y.; Thummala, A.R.; Voytko, N.L.; Fowst, C.; Huang, X.; Kim, S.T.; Randolph, S.; Slamon, D.J. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol., 2015, 16(1), 25-35.
[http://dx.doi.org/10.1016/S1470-2045(14)71159-3] [PMID: 25524798]
[41]
Gutman, S.I.; Piper, M.; Grant, M.D. Progression-free survival: What does it mean for psychological well-being or quality of life? agency for healthcare research and quality (US) 2013.https://www.ncbi.nlm.nih.gov/books/NBK137763/
[42]
Finn, R.S.; Martin, M.; Rugo, H.S.; Jones, S. Im, S.A.; Gelmon, K.; Harbeck, N.; Lipatov, O.N.; Walshe, J.M.; Moulder, S.; Gauthier, E.; Lu, D.R.; Randolph, S.; Diéras, V.; Slamon, D.J. Palbociclib and Letrozole in Advanced Breast Cancer. N. Engl. J. Med., 2016, 375(20), 1925-1936.
[http://dx.doi.org/10.1056/NEJMoa1607303] [PMID: 27959613]
[43]
Eisenhauer, E.A.; Therasse, P.; Bogaerts, J.; Schwartz, L.H.; Sargent, D.; Ford, R.; Dancey, J.; Arbuck, S.; Gwyther, S.; Mooney, M.; Rubinstein, L.; Shankar, L.; Dodd, L.; Kaplan, R.; Lacombe, D.; Verweij, J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer, 2009, 45(2), 228-247.
[http://dx.doi.org/10.1016/j.ejca.2008.10.026] [PMID: 19097774]
[44]
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. PALOMA3 Study Group. Palbociclib in hormone-receptor-positive advanced breast cancer. N. Engl. J. Med., 2015, 373(3), 209-219.
[http://dx.doi.org/10.1056/NEJMoa1505270] [PMID: 26030518]
[45]
Cristofanilli, M.; Turner, N.C.; Bondarenko, I.; Ro, J.; Im, S.A.; Masuda, N.; Colleoni, M.; DeMichele, A.; Loi, S.; Verma, S.; Iwata, H.; Harbeck, N.; Zhang, K.; Theall, K.P.; Jiang, Y.; Bartlett, C.H.; Koehler, M.; Slamon, D. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol., 2016, 17(4), 425-439.
[http://dx.doi.org/10.1016/S1470-2045(15)00613-0] [PMID: 26947331]
[46]
Dhillon, S. Palbociclib: first global approval. Drugs, 2015, 75(5), 543-551.
[http://dx.doi.org/10.1007/s40265-015-0379-9] [PMID: 25792301]
[47]
Pfizer Canada Inc. IBRANCE® product monograph., 2016.
[48]
Pfizer Canada Inc. IBRANCE® product monograph. 2017.
[49]
Pfizer Inc. IBRANCE® product monograph 2016.
[51]
Beaver, J.A.; Amiri-Kordestani, L.; Charlab, R.; Chen, W.; Palmby, T.; Tilley, A.; Zirkelbach, J.F.; Yu, J.; Liu, Q.; Zhao, L.; Crich, J.; Chen, X.H.; Hughes, M.; Bloomquist, E.; Tang, S.; Sridhara, R.; Kluetz, P.G.; Kim, G.; Ibrahim, A.; Pazdur, R.; Cortazar, P. FDA approval: Palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. Clin. Cancer Res., 2015, 21(21), 4760-4766.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-1185] [PMID: 26324739]
[52]
Musgrove, E.A.; Caldon, C.E.; Barraclough, J.; Stone, A.; Sutherland, R.L. Cyclin D as a therapeutic target in cancer. Nat. Rev. Cancer, 2011, 11(8), 558-572.
[http://dx.doi.org/10.1038/nrc3090] [PMID: 21734724]
[53]
Schiff, R.; Massarweh, S.A.; Shou, J.; Bharwani, L.; Mohsin, S.K.; Osborne, C.K. Cross-talk between estrogen receptor and growth factor pathways as a molecular target for overcoming endocrine resistance. Clin. Cancer Res., 2004, 10(1 Pt 2), 331S-336S.
[http://dx.doi.org/10.1158/1078-0432.CCR-031212] [PMID: 14734488]
[54]
Miller, T.W.; Hennessy, B.T.; González-Angulo, A.M.; Fox, E.M.; Mills, G.B.; Chen, H.; Higham, C.; García-Echeverría, C.; Shyr, Y.; Arteaga, C.L. Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer. J. Clin. Invest., 2010, 120(7), 2406-2413.
[http://dx.doi.org/10.1172/JCI41680] [PMID: 20530877]
[55]
Toy, W.; Shen, Y.; Won, H.; Green, B.; Sakr, R.A.; Will, M.; Li, Z.; Gala, K.; Fanning, S.; King, T.A.; Hudis, C.; Chen, D.; Taran, T.; Hortobagyi, G.; Greene, G.; Berger, M.; Baselga, J.; Chandarlapaty, S. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat. Genet., 2013, 45(12), 1439-1445.
[http://dx.doi.org/10.1038/ng.2822] [PMID: 24185512]
[56]
Robinson, D.R.; Wu, Y.M.; Vats, P.; Su, F.; Lonigro, R.J.; Cao, X.; Kalyana-Sundaram, S.; Wang, R.; Ning, Y.; Hodges, L.; Gursky, A.; Siddiqui, J.; Tomlins, S.A.; Roychowdhury, S.; Pienta, K.J.; Kim, S.Y.; Roberts, J.S.; Rae, J.M.; Van Poznak, C.H.; Hayes, D.F.; Chugh, R.; Kunju, L.P.; Talpaz, M.; Schott, A.F.; Chinnaiyan, A.M. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat. Genet., 2013, 45(12), 1446-1451.
[http://dx.doi.org/10.1038/ng.2823] [PMID: 24185510]
[57]
Bowles, H.J.; Clarke, K.L. Palbociclib: A new option for front line treatment of metastatic, harmone receptor positive, HER2 negative breast cancer. J. Adv. Pract. Oncol., 2015, 6(6), 577-581.
[PMID: 27648347]
[58]
Bernards, R.; Weinberg, R.A. A progression puzzle. Nature, 2002, 418(6900), 823.
[http://dx.doi.org/10.1038/418823a] [PMID: 12192390]
[59]
Kaur, R.; Manjal, S.K.; Rawal, R.K.; Kumar, K. Recent synthetic and medicinal perspectives of tryptanthrin. Bioorg. Med. Chem., 2017, 25(17), 4533-4552.
[http://dx.doi.org/10.1016/j.bmc.2017.07.003] [PMID: 28720329]
[60]
Kaur Manjal, S.; Kaur, R.; Bhatia, R.; Kumar, K.; Singh, V.; Shankar, R.; Kaur, R.; Rawal, R.K. Synthetic and medicinal perspective of thiazolidinones: A review. Bioorg. Chem., 2017, 75, 406-423.
[http://dx.doi.org/10.1016/j.bioorg.2017.10.014] [PMID: 29102723]
[61]
Kaur, R.; Chaudhary, S.; Kumar, K.; Gupta, M.K.; Rawal, R.K. Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review. Eur. J. Med. Chem., 2017, 132, 108-134.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.025] [PMID: 28342939]
[62]
Kumar, B.; Singh, V.; Shankar, R.; Kumar, K.; Rawal, R.K. Synthetic and medicinal prospective of structurally modified curcumins. Curr. Top. Med. Chem., 2017, 17(2), 148-161.
[http://dx.doi.org/10.2174/1568026616666160605050052] [PMID: 27280465]
[63]
Mittal, M.; Kumar, K.; Anghore, D.; Rawal, R.K. ICP-MS: Analytical method foridentification and detection of elemental impurities. Curr. Drug Discov. Technol., 2017, 14(2), 106-120.
[http://dx.doi.org/10.2174/1570163813666161221141402] [PMID: 28003007]
[64]
Talwan, P.; Choudhary, S.; Kumar, K.; Rawal, R.K. Chemical and medicinalversatility of substituted 1, 4-dihydropyridines. Curr. Bioact. Compd., 2017, 13, 109.
[http://dx.doi.org/10.2174/1573407212666160607090202]
[65]
Kaur, R.; Kapoor, Y.; Manjal, S.K.; Rawal, R.K.; Kumar, K. Diversity-oriented synthetic approaches for furoindoline: A review. Curr. Org. Synth., 2019, 16(3), 342-368.
[http://dx.doi.org/10.2174/1570179416666190328211509] [PMID: 31984898]
[66]
Kapoor, Y.; Kumar, K. Structural and clinical impact of anti-allergy agents: An overview. Bioorg. Chem., 2020.94103351
[http://dx.doi.org/10.1016/j.bioorg.2019.103351] [PMID: 31668464]
[67]
Kumar, K.; Siddique, J.; Gangar, M.; Goyal, S.; Rawal, R.K.; Nair, V.A. ZrCl4 catalysed diastereoselective synthesis of spirocarbocyclic oxindoles via [4+2] cycloaddition. ChemistrySelect, 2016, 1, 2409.
[http://dx.doi.org/10.1002/slct.201600447]
[68]
Kumar, K.; Rawal, R.K. CuI/DBU-mediated MBH reaction of isatins: A convenient synthesis of 3-substituted-3-hydroxy-2-oxindole. ChemistrySelect, 2020, 5, 3048-3051.
[http://dx.doi.org/10.1002/slct.201903703]
[69]
Manjal, S.K.; Pathania, S.; Bhatia, R.; Kaur, R.; Kumar, K.; Rawal, R.K. Diversified synthetic strategies for pyrroloindoles: An overview. J. Heterocycl. Chem., 2019, 56, 2318-2332.
[http://dx.doi.org/10.1002/jhet.3661]
[70]
Kumar, K. TosMIC: A powerful synthon for cyclization and sulfonylation. ChemistrySelect, 2020, 5, 10298-10328.
[http://dx.doi.org/10.1002/slct.202001344]

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