Generic placeholder image

Current Medicinal Chemistry

Author(s): Ying Li, Chen-Fu Liu and Guo-Wu Rao*

DOI: 10.2174/0929867327666200312113011

DownloadDownload PDF Flyer Cite As
A Review on Poly (ADP-ribose) Polymerase (PARP) Inhibitors and Synthetic Methodologies

Page: [1565 - 1584] Pages: 20

  • * (Excluding Mailing and Handling)

Abstract

Poly (ADP-ribose) polymerase (PARP) acts as an essential DNA repair enzyme. PARP inhibitors are novel small molecule targeted drugs based on the principle of "Synthetic Lethality", which affect DNA repair process by competitively inhibiting the activity of PARP enzyme and thereby kill cancer cells. Currently, four PARP inhibitors including olaparib, rucaparib, niraparib, and talazoparib have been approved by FDA for cancer treatment and have achieved great success in the treatment of ovarian cancer, breast cancer, and pancreatic cancer, etc. This paper provides a general overview of the research progress of PARP inhibitors including the major structure types, structure-activity relationship (SAR), and synthetic routes, with the aim of providing ideas for the discovery and synthesis of novel PARP inhibitors.

Keywords: Ovarian cancer, synthetic lethality, PARP inhibitors, olaparib, structure-activity relationship, phthalazinones, synthesis.

[1]
Davar, D.; Beumer, J.H.; Hamieh, L.; Tawbi, H. Role of PARP inhibitors in cancer biology and therapy. Curr. Med. Chem., 2012, 19(23), 3907-3921.
[http://dx.doi.org/10.2174/092986712802002464] [PMID: 22788767]
[2]
Plummer, R. Perspective on the pipeline of drugs being developed with modulation of DNA damage as a target. Clin. Cancer Res., 2010, 16(18), 4527-4531.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-0984] [PMID: 20823148]
[3]
Chambon, P.; Weill, J.D.; Mandel, P. Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem. Biophys. Res. Commun., 1963, 11, 39-43.
[http://dx.doi.org/10.1016/0006-291X(63)90024-X] [PMID: 14019961]
[4]
Liscio, P.; Camaioni, E.; Carotti, A.; Pellicciari, R.; Macchiarulo, A. From polypharmacology to target specificity: the case of PARP inhibitors. Curr. Top. Med. Chem., 2013, 13(23), 2939-2954.
[http://dx.doi.org/10.2174/15680266113136660209] [PMID: 24171773]
[5]
Kamal, A.; Riyaz, S.; Srivastava, A.K.; Rahim, A. Tankyrase inhibitors as therapeutic targets for cancer. Curr. Top. Med. Chem., 2014, 14(17), 1967-1976.
[http://dx.doi.org/10.2174/1568026614666140929115831] [PMID: 25262803]
[6]
Piskunova, T.S.; Yurova, M.N.; Ovsyannikov, A.I.; Semenchenko, A.V.; Zabezhinski, M.A.; Popovich, I.G.; Wang, Z.Q.; Anisimov, V.N. deficiency in poly(adp-ribose) polymerase-1 (parp-1) accelerates aging and spontaneous carcinogenesis in mice. Curr. Gerontol. Geriatr. Res., 2008, 2008754190
[http://dx.doi.org/10.1155/2008/754190] [PMID: 19415146]
[7]
Lord, C.J.; Ashworth, A. PARP inhibitors: synthetic lethality in the clinic. Science, 2017, 355(6330), 1152-1158.
[http://dx.doi.org/10.1126/science.aam7344] [PMID: 28302823]
[8]
Palazzo, L.; Ahel, I. PARPs in genome stability and signal transduction: implications for cancer therapy. Biochem. Soc. Trans., 2018, 46(6), 1681-1695.
[http://dx.doi.org/10.1042/BST20180418] [PMID: 30420415]
[9]
Isabelle, M.; Moreel, X.; Gagné, J.P.; Rouleau, M.; Ethier, C.; Gagné, P.; Hendzel, M.J.; Poirier, G.G. Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry. Proteome Sci., 2010, 8, 22.
[http://dx.doi.org/10.1186/1477-5956-8-22] [PMID: 20388209]
[10]
Shah, G.M.; Robu, M.; Purohit, N.K.; Rajawat, J.; Tentori, L.; Graziani, G. PARP inhibitors in cancer therapy: magic bullets but moving targets. Front. Oncol., 2013, 3, 279.
[http://dx.doi.org/10.3389/fonc.2013.00279] [PMID: 24294592]
[11]
Usmani, H.; Hussain, S.A.; Sheikh, A. PARP inhibitors: current status and implications for anticancer therapeutics. Infect. Agent. Cancer, 2013, 8(1), 46.
[http://dx.doi.org/10.1186/1750-9378-8-46] [PMID: 24289880]
[12]
Gupte, R.; Liu, Z.; Kraus, W.L. PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes. Genes Dev., 2017, 31(2), 101-126.
[http://dx.doi.org/10.1101/gad.291518.116] [PMID: 28202539]
[13]
Chen, Q.; Kassab, M.A.; Dantzer, F.; Yu, X. PARP2 mediates branched poly ADP-ribosylation in response to DNA damage. Nat. Commun., 2018, 9(1), 3233.
[http://dx.doi.org/10.1038/s41467-018-05588-5] [PMID: 30104678]
[14]
Zarkovic, G.; Belousova, E.A.; Talhaoui, I.; Saint-Pierre, C.; Kutuzov, M.M.; Matkarimov, B.T.; Biard, D.; Gasparutto, D.; Lavrik, O.I.; Ishchenko, A.A. Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new insights into DNA ADP-ribosylation. Nucleic Acids Res., 2018, 46(5), 2417-2431.
[http://dx.doi.org/10.1093/nar/gkx1318] [PMID: 29361132]
[15]
Ström, C.E.; Helleday, T. Strategies for the use of poly(adenosine diphosphate ribose) polymerase (parp) inhibitors in cancer therapy. Biomolecules, 2012, 2(4), 635-649.
[http://dx.doi.org/10.3390/biom2040635] [PMID: 24970153]
[16]
Curtin, N.J. PARP inhibitors for cancer therapy. Expert Rev. Mol. Med., 2005, 7(4), 1-20.
[http://dx.doi.org/10.1017/S146239940500904X] [PMID: 15836799]
[17]
Bryant, H.E.; Schultz, N.; Thomas, H.D.; Parker, K.M.; Flower, D.; Lopez, E.; Kyle, S.; Meuth, M.; Curtin, N.J.; Helleday, T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature, 2005, 434(7035), 913-917.
[http://dx.doi.org/10.1038/nature03443] [PMID: 15829966]
[18]
Farmer, H.; McCabe, N.; Lord, C.J.; Tutt, A.N.; Johnson, D.A.; Richardson, T.B.; Santarosa, M.; Dillon, K.J.; Hickson, I.; Knights, C.; Martin, N.M.; Jackson, S.P.; Smith, G.C.; Ashworth, A. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature, 2005, 434(7035), 917-921.
[http://dx.doi.org/10.1038/nature03445] [PMID: 15829967]
[19]
Golan, T.; Hammel, P.; Reni, M.; Van Cutsem, E.; Macarulla, T.; Hall, M.J.; Park, J.O.; Hochhauser, D.; Arnold, D.; Oh, D.Y.; Reinacher-Schick, A.; Tortora, G.; Algül, H.; O’Reilly, E.M.; McGuinness, D.; Cui, K.Y.; Schlienger, K.; Locker, G.Y.; Kindler, H.L. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N. Engl. J. Med., 2019, 381(4), 317-327.
[http://dx.doi.org/10.1056/NEJMoa1903387] [PMID: 31157963]
[20]
McCabe, N.; Turner, N.C.; Lord, C.J.; Kluzek, K.; Bialkowska, A.; Swift, S.; Giavara, S.; O’Connor, M.J.; Tutt, A.N.; Zdzienicka, M.Z.; Smith, G.C.; Ashworth, A. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res., 2006, 66(16), 8109-8115.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0140] [PMID: 16912188]
[21]
Narod, S.A.; Foulkes, W.D. BRCA1 and BRCA2: 1994 and beyond. Nat. Rev. Cancer, 2004, 4(9), 665-676.
[http://dx.doi.org/10.1038/nrc1431] [PMID: 15343273]
[22]
Curtin, N. PARP inhibitors for anticancer therapy. Biochem. Soc. Trans., 2014, 42(1), 82-88.
[http://dx.doi.org/10.1042/BST20130187] [PMID: 24450632]
[23]
Lee, J.M.; Ledermann, J.A.; Kohn, E.C. PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann. Oncol., 2014, 25(1), 32-40.
[http://dx.doi.org/10.1093/annonc/mdt384] [PMID: 24225019]
[24]
Fong, P.C.; Boss, D.S.; Yap, T.A.; Tutt, A.; Wu, P.; Mergui-Roelvink, M.; Mortimer, P.; Swaisland, H.; Lau, A.; O’Connor, M.J.; Ashworth, A.; Carmichael, J.; Kaye, S.B.; Schellens, J.H.; de Bono, J.S. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med., 2009, 361(2), 123-134.
[http://dx.doi.org/10.1056/NEJMoa0900212] [PMID: 19553641]
[25]
Wang, Y.Q.; Wang, P.Y.; Wang, Y.T.; Yang, G.F.; Zhang, A.; Miao, Z.H. An update on poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors: opportunities and challenges in cancer therapy. J. Med. Chem., 2016, 59(21), 9575-9598.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00055] [PMID: 27416328]
[26]
Murai, J.; Huang, S.Y.; Renaud, A.; Zhang, Y.; Ji, J.; Takeda, S.; Morris, J.; Teicher, B.; Doroshow, J.H.; Pommier, Y. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol. Cancer Ther., 2014, 13(2), 433-443.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0803] [PMID: 24356813]
[27]
Murai, J.; Huang, S.Y.; Das, B.B.; Renaud, A.; Zhang, Y.; Doroshow, J.H.; Ji, J.; Takeda, S.; Pommier, Y. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res., 2012, 72(21), 5588-5599.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-2753] [PMID: 23118055]
[28]
Shen, Y.; Aoyagi-Scharber, M.; Wang, B. Trapping Poly(ADP-Ribose). Polymerase. J. Pharmacol. Exp. Ther., 2015, 353(3), 446-457.
[http://dx.doi.org/10.1124/jpet.114.222448] [PMID: 25758918]
[29]
Rao, G.W.; Guo, Y.M.; Hu, W.X. Synthesis, structure analysis, and antitumor evaluation of 3,6-dimethyl-1,2,4,5-tetrazine-1,4-dicarboxamide derivatives. ChemMedChem, 2012, 7(6), 973-976.
[http://dx.doi.org/10.1002/cmdc.201200109] [PMID: 22539490]
[30]
Rao, G.W.; Xu, G.J.; Wang, J.; Jiang, X.L.; Li, H.B. Synthesis, antitumor evaluation and docking study of novel 4-anilinoquinazoline derivatives as potential epidermal growth factor receptor (EGFR) inhibitors. ChemMedChem, 2013, 8(6), 928-933.
[http://dx.doi.org/10.1002/cmdc.201300120] [PMID: 23640754]
[31]
Rao, G.W.; Wang, C.; Wang, J.; Zhao, Z.G.; Hu, W.X. Synthesis, structure analysis, antitumor evaluation and 3D-QSAR studies of 3,6-disubstituted-dihydro-1,2,4,5-tetrazine derivatives. Bioorg. Med. Chem. Lett., 2013, 23(23), 6474-6480.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.036] [PMID: 24120541]
[32]
Jin, H.; Dan, H-G.; Rao, G-W. Research progress in quinazoline derivatives as multi-target tyrosine kinase inhibitors. Heterocycl. Commun., 2018, 24, 1-10.
[http://dx.doi.org/10.1515/hc-2017-0066]
[33]
Wu, Y-C.; Ren, X-Y.; Rao, G-W. Research progress of diphenyl urea derivatives as anticancer agents and synthetic methodologies. Mini Rev. Org. Chem., 2019, 16(7), 617-630.
[http://dx.doi.org/10.2174/1570193X15666181029130418]
[34]
Curtin, N.J.; Szabo, C. Therapeutic applications of PARP inhibitors: anticancer therapy and beyond. Mol. Aspects Med., 2013, 34(6), 1217-1256.
[http://dx.doi.org/10.1016/j.mam.2013.01.006] [PMID: 23370117]
[35]
Ekblad, T.; Camaioni, E.; Schüler, H.; Macchiarulo, A. PARP inhibitors: polypharmacology versus selective inhibition. FEBS J., 2013, 280(15), 3563-3575.
[http://dx.doi.org/10.1111/febs.12298] [PMID: 23601167]
[36]
Lupo, B.; Trusolino, L. Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited. Biochim. Biophys. Acta, 2014, 1846(1), 201-215.
[http://dx.doi.org/10.1016/j.bbcan.2014.07.004] [PMID: 25026313]
[37]
Menear, K.A.; Adcock, C.; Boulter, R.; Cockcroft, X.L.; Copsey, L.; Cranston, A.; Dillon, K.J.; Drzewiecki, J.; Garman, S.; Gomez, S.; Javaid, H.; Kerrigan, F.; Knights, C.; Lau, A.; Loh, V.M. Jr.; Matthews, I.T.; Moore, S.; O’Connor, M.J.; Smith, G.C.; Martin, N.M. 4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenz-yl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J. Med. Chem., 2008, 51(20), 6581-6591.
[http://dx.doi.org/10.1021/jm8001263] [PMID: 18800822]
[38]
Canan Koch, S.S.; Thoresen, L.H.; Tikhe, J.G.; Maegley, K.A.; Almassy, R.J.; Li, J.; Yu, X.H.; Zook, S.E.; Kumpf, R.A.; Zhang, C.; Boritzki, T.J.; Mansour, R.N.; Zhang, K.E.; Ekker, A.; Calabrese, C.R.; Curtin, N.J.; Kyle, S.; Thomas, H.D.; Wang, L.Z.; Calvert, A.H.; Golding, B.T.; Griffin, R.J.; Newell, D.R.; Webber, S.E.; Hostomsky, Z. Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design, synthesis, and X-ray cocrystal structure. J. Med. Chem., 2002, 45(23), 4961-4974.
[http://dx.doi.org/10.1021/jm020259n] [PMID: 12408707]
[39]
Thomas, H.D.; Calabrese, C.R.; Batey, M.A.; Canan, S.; Hostomsky, Z.; Kyle, S.; Maegley, K.A.; Newell, D.R.; Skalitzky, D.; Wang, L.Z.; Webber, S.E.; Curtin, N.J. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol. Cancer Ther., 2007, 6(3), 945-956.
[http://dx.doi.org/10.1158/1535-7163.MCT-06-0552] [PMID: 17363489]
[40]
Jones, P.; Altamura, S.; Boueres, J.; Ferrigno, F.; Fonsi, M.; Giomini, C.; Lamartina, S.; Monteagudo, E.; Ontoria, J.M.; Orsale, M.V.; Palumbi, M.C.; Pesci, S.; Roscilli, G.; Scarpelli, R.; Schultz-Fademrecht, C.; Toniatti, C.; Rowley, M. Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J. Med. Chem., 2009, 52(22), 7170-7185.
[http://dx.doi.org/10.1021/jm901188v] [PMID: 19873981]
[41]
Jones, P.; Wilcoxen, K.; Rowley, M.; Toniatti, C. Niraparib: a poly(ADP-ribose) polymerase (PARP) inhibitor for the treatment of tumors with defective homologous recombination. J. Med. Chem., 2015, 58(8), 3302-3314.
[http://dx.doi.org/10.1021/jm5018237] [PMID: 25761096]
[42]
Shen, Y.; Rehman, F.L.; Feng, Y.; Boshuizen, J.; Bajrami, I.; Elliott, R.; Wang, B.; Lord, C.J.; Post, L.E.; Ashworth, A. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency. Clin. Cancer Res., 2013, 19(18), 5003-5015.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-1391] [PMID: 23881923]
[43]
Donawho, C.K.; Luo, Y.; Luo, Y.; Penning, T.D.; Bauch, J.L.; Bouska, J.J.; Bontcheva-Diaz, V.D.; Cox, B.F.; DeWeese, T.L.; Dillehay, L.E.; Ferguson, D.C.; Ghoreishi-Haack, N.S.; Grimm, D.R.; Guan, R.; Han, E.K.; Holley-Shanks, R.R.; Hristov, B.; Idler, K.B.; Jarvis, K.; Johnson, E.F.; Kleinberg, L.R.; Klinghofer, V.; Lasko, L.M.; Liu, X.; Marsh, K.C.; McGonigal, T.P.; Meulbroek, J.A.; Olson, A.M.; Palma, J.P.; Rodriguez, L.E.; Shi, Y.; Stavropoulos, J.A.; Tsurutani, A.C.; Zhu, G.D.; Rosenberg, S.H.; Giranda, V.L.; Frost, D.J. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin. Cancer Res., 2007, 13(9), 2728-2737.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-3039] [PMID: 17473206]
[44]
Penning, T.D.; Zhu, G.D.; Gandhi, V.B.; Gong, J.; Thomas, S.; Lubisch, W.; Grandel, R.; Wernet, W.; Park, C.H.; Fry, E.H.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E.F.; Donawho, C.K.; Frost, D.J.; Bontcheva-Diaz, V.; Bouska, J.J.; Olson, A.M.; Marsh, K.C.; Luo, Y.; Rosenberg, S.H.; Giranda, V.L. Discovery and SAR of 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide: a potent inhibitor of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer. Bioorg. Med. Chem., 2008, 16(14), 6965-6975.
[http://dx.doi.org/10.1016/j.bmc.2008.05.044] [PMID: 18541433]
[45]
Penning, T.D.; Zhu, G.D.; Gandhi, V.B.; Gong, J.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E.F.; Donawho, C.K.; Frost, D.J.; Bontcheva-Diaz, V.; Bouska, J.J.; Osterling, D.J.; Olson, A.M.; Marsh, K.C.; Luo, Y.; Giranda, V.L. Discovery of the poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J. Med. Chem., 2009, 52(2), 514-523.
[http://dx.doi.org/10.1021/jm801171j] [PMID: 19143569]
[46]
Gangloff, A.R.; Brown, J.; de Jong, R.; Dougan, D.R.; Grimshaw, C.E.; Hixon, M.; Jennings, A.; Kamran, R.; Kiryanov, A.; O’Connell, S.; Taylor, E.; Vu, P. Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(16), 4501-4505.
[http://dx.doi.org/10.1016/j.bmcl.2013.06.055] [PMID: 23850199]
[47]
Ye, N.; Chen, C.H.; Chen, T.; Song, Z.; He, J.X.; Huan, X.J.; Song, S.S.; Liu, Q.; Chen, Y.; Ding, J.; Xu, Y.; Miao, Z.H.; Zhang, A. Design, synthesis, and biological evaluation of a series of benzo[de][1,7]naphthyridin-7(8H)-ones bearing a functionalized longer chain appendage as novel PARP1 inhibitors. J. Med. Chem., 2013, 56(7), 2885-2903.
[http://dx.doi.org/10.1021/jm301825t] [PMID: 23473053]
[48]
Papeo, G.; Orsini, P.; Avanzi, N.R.; Borghi, D.; Casale, E.; Ciomei, M.; Cirla, A.; Desperati, V.; Donati, D.; Felder, E.R.; Galvani, A.; Guanci, M.; Isacchi, A.; Posteri, H.; Rainoldi, S.; Riccardi-Sirtori, F.; Scolaro, A.; Montagnoli, A. Discovery of stereospecific PARP-1 inhibitor isoindolinone NMS-P515. ACS Med. Chem. Lett., 2019, 10(4), 534-538.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00569] [PMID: 30996792]
[49]
Penning, T.D.; Zhu, G.D.; Gong, J.; Thomas, S.; Gandhi, V.B.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E.F.; Park, C.H.; Fry, E.H.; Donawho, C.K.; Frost, D.J.; Buchanan, F.G.; Bukofzer, G.T.; Rodriguez, L.E.; Bontcheva-Diaz, V.; Bouska, J.J.; Osterling, D.J.; Olson, A.M.; Marsh, K.C.; Luo, Y.; Giranda, V.L. Optimization of phenyl-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious inhibitor. J. Med. Chem., 2010, 53(8), 3142-3153.
[http://dx.doi.org/10.1021/jm901775y] [PMID: 20337371]
[50]
Yuan, B.; Ye, N.; Song, S-S.; Wang, Y-T.; Song, Z.; Chen, H-D.; Chen, C-H.; Huan, X-J.; Wang, Y-Q.; Su, Y.; Shen, Y-Y.; Sun, Y-M.; Yang, X-Y.; Chen, Y.; Guo, S-Y.; Gan, Y.; Gao, Z-W.; Chen, X-Y.; Ding, J.; Miao, Z-H. Poly(ADP-ribose)polymerase (PARP) inhibition and anticancer activity of simmiparib, a new inhibitor undergoing clinical trials. Cancer Lett., 2017, 386, 47-56.
[http://dx.doi.org/10.1016/j.canlet.2016.11.010] [PMID: 27847302]
[51]
O’Shaughnessy, J.; Schwartzberg, L.; Danso, M.; Rugo, H.; Miller, K.; Yardley, D.; Carlson, R.; Finn, S.R.; Charpentier, E.; Freese, M.; Gupta, S.; Blackwood-Chirchir, A.; Winer, P E. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). J. Clin. Oncol., 2011, 29(Suppl. 15), 1007.
[http://dx.doi.org/10.1200/jco.2011.29.15_suppl.1007]
[52]
Patel, A.G.; De Lorenzo, S.B.; Flatten, K.S.; Poirier, G.G.; Kaufmann, S.H. Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro. Clin. Cancer Res., 2012, 18(6), 1655-1662.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-2890] [PMID: 22291137]
[53]
Ledermann, J.; Harter, P.; Gourley, C.; Friedlander, M.; Vergote, I.; Rustin, G.; Scott, C.L.; Meier, W.; Shapira-Frommer, R.; Safra, T.; Matei, D.; Fielding, A.; Spencer, S.; Dougherty, B.; Orr, M.; Hodgson, D.; Barrett, J.C.; Matulonis, U. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol., 2014, 15(8), 852-861.
[http://dx.doi.org/10.1016/S1470-2045(14)70228-1] [PMID: 24882434]
[54]
Ruf, A.; de Murcia, G.; Schulz, G.E. Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal structures and homology modeling. Biochemistry, 1998, 37(11), 3893-3900.
[http://dx.doi.org/10.1021/bi972383s] [PMID: 9521710]
[55]
Singh, S.S.; Sarma, J.A.; Narasu, L.; Dayam, R.; Xu, S.; Neamati, N. A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors. Curr. Top. Med. Chem., 2014, 14(17), 2020-2030.
[http://dx.doi.org/10.2174/1568026614666140929152123] [PMID: 25262797]
[56]
Clark, J.B.; Ferris, G.M.; Pinder, S. Inhibition of nuclear NAD nucleosidase and poly ADP-ribose polymerase activity from rat liver by nicotinamide and 5′-methyl nicotinamide. Biochim. Biophys. Acta, 1971, 238(1), 82-85.
[http://dx.doi.org/10.1016/0005-2787(71)90012-8] [PMID: 4325158]
[57]
Peralta-Leal, A.; Rodríguez-Vargas, J.M.; Aguilar-Quesada, R.; Rodríguez, M.I.; Linares, J.L.; de Almodóvar, M.R.; Oliver, F.J. PARP inhibitors: new partners in the therapy of cancer and inflammatory diseases. Free Radic. Biol. Med., 2009, 47(1), 13-26.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.04.008] [PMID: 19362586]
[58]
Xie, Z.; Zhou, Y.; Zhao, W.; Jiao, H.; Chen, Y.; Yang, Y.; Li, Z. Identification of novel PARP-1 inhibitors: Drug design, synthesis and biological evaluation. Bioorg. Med. Chem. Lett., 2015, 25(20), 4557-4561.
[http://dx.doi.org/10.1016/j.bmcl.2015.08.060] [PMID: 26342868]
[59]
Ferraris, D.V. Evolution of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. From concept to clinic. J. Med. Chem., 2010, 53(12), 4561-4584.
[http://dx.doi.org/10.1021/jm100012m] [PMID: 20364863]
[60]
F.D.A. FDA approves olaparib tablets for maintenance 60 treatment in ovarian cancer. Available at: https://www.fda. gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-tablets-maintenance-treatment-ovarian-cancerAccessed date: August 17, 2017.).
[61]
Reilly, S.W.; Puentes, L.N.; Hsieh, C-J.; Makvandi, M.; Mach, R.H. Altering nitrogen heterocycles of AZD2461 affords high affinity poly(ADP-ribose) polymerase-1 inhibitors with decreased p-glycoprotein interactions. ACS Omega, 2018, 3(8), 9997-10001.
[http://dx.doi.org/10.1021/acsomega.8b00896] [PMID: 30198004]
[62]
Jaspers, J.E.; Kersbergen, A.; Boon, U.; Sol, W.; van Deemter, L.; Zander, S.A.; Drost, R.; Wientjens, E.; Ji, J.; Aly, A.; Doroshow, J.H.; Cranston, A.; Martin, N.M.; Lau, A.; O’Connor, M.J.; Ganesan, S.; Borst, P.; Jonkers, J.; Rottenberg, S. Loss of 53BP1 causes PARP inhibitor resistance in brca1-mutated mouse mammary tumors. Cancer Discov., 2013, 3(1), 68-81.
[http://dx.doi.org/10.1158/2159-8290.CD-12-0049] [PMID: 23103855]
[63]
Russo, A.L.; Kwon, H.C.; Burgan, W.E.; Carter, D.; Beam, K.; Weizheng, X.; Zhang, J.; Slusher, B.S.; Chakravarti, A.; Tofilon, P.J.; Camphausen, K. In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016. Clin. Cancer Res., 2009, 15(2), 607-612.
[http://dx.doi.org/10.1158/1078-0432.CCR-08-2079] [PMID: 19147766]
[64]
McGonigle, S.; Chen, Z.; Wu, J.; Chang, P.; Kolber-Simonds, D.; Ackermann, K.; Twine, N.C.; Shie, J.L.; Miu, J.T.; Huang, K.C.; Moniz, G.A.; Nomoto, K. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget, 2015, 6(38), 41307-41323.
[http://dx.doi.org/10.18632/oncotarget.5846] [PMID: 26513298]
[65]
Wang, B.; Chu, D.; Feng, Y.; Shen, Y.; Aoyagi-Scharber, M.; Post, L.E. Discovery and characterization of (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a novel, highly potent, and orally efficacious poly(ADP-ribose) polymerase-1/2 inhibitor, as an anticancer agent. J. Med. Chem., 2016, 59(1), 335-357.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01498] [PMID: 26652717]
[66]
Litton, J.K.; Rugo, H.S.; Ettl, J.; Hurvitz, S.A.; Gonçalves, A.; Lee, K.H.; Fehrenbacher, L.; Yerushalmi, R.; Mina, L.A.; Martin, M.; Roché, H.; Im, Y.H.; Quek, R.G.W.; Markova, D.; Tudor, I.C.; Hannah, A.L.; Eiermann, W.; Blum, J.L. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N. Engl. J. Med., 2018, 379(8), 753-763.
[http://dx.doi.org/10.1056/NEJMoa1802905] [PMID: 30110579]
[67]
F.D.A. FDA approves talazoparib for gBRCAm HER2-negative locally advanced or metastatic breast cancer. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-gbrcam-her2-negative-locally-advanced-or-metastatic-breast-cancer(Accessed date: December 14, 2018.).
[68]
Hoy, S.M. Talazoparib: First Global Approval. Drugs, 2018, 78(18), 1939-1946.
[http://dx.doi.org/10.1007/s40265-018-1026-z] [PMID: 30506138]
[69]
White, A.W.; Almassy, R.; Calvert, A.H.; Curtin, N.J.; Griffin, R.J.; Hostomsky, Z.; Maegley, K.; Newell, D.R.; Srinivasan, S.; Golding, B.T. Resistance-modifying agents. 9. Synthesis and biological properties of benzimidazole inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase. J. Med. Chem., 2000, 43(22), 4084-4097.
[http://dx.doi.org/10.1021/jm000950v] [PMID: 11063605]
[70]
Coleman, R.L.; Sill, M.W.; Bell-McGuinn, K.; Aghajanian, C.; Gray, H.J.; Tewari, K.S.; Rubin, S.C.; Rutherford, T.J.; Chan, J.K.; Chen, A.; Swisher, E.M. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation - an NRG oncology/gynecologic oncology group study. Gynecol. Oncol., 2015, 137(3), 386-391.
[http://dx.doi.org/10.1016/j.ygyno.2015.03.042] [PMID: 25818403]
[71]
Niraparib, F.D.A. Available at: https://www.fda.gov/drugs/resources-info-rmation-approved-drugs/niraparib-zejula(Accessed date: May 30, 2017.)..
[72]
Scott, L.J. Niraparib: first global approval. Drugs, 2017, 77(9), 1029-1034.
[http://dx.doi.org/10.1007/s40265-017-0752-y] [PMID: 28474297]
[73]
Kolaczkowski, L.; Barkalow, J.; Barnes, D.M.; Haight, A.; Pritts, W.; Schellinger, A. Synthesis of (R)-Boc-2-methylproline via a memory of chirality cyclization. application to the synthesis of veliparib, a poly(ADP-ribose) polymerase inhibitor. J. Org. Chem., 2019, 84(8), 4837-4845.
[http://dx.doi.org/10.1021/acs.joc.8b02866] [PMID: 30716275]
[74]
Barkalow, J.H.; Breting, J.; Gaede, B.J.; Haight, A.R.; Henry, R.; Kotecki, B.; Mei, J.; Pearl, K.B.; Tedrow, J.S.; Viswanath, S.K. Process development for ABT-472, a benzimidazole PARP inhibitor. Org. Process Res. Dev., 2007, 11(4), 693-698.
[http://dx.doi.org/10.1021/op7000194]
[75]
Kasamatsu, K.; Yoshimura, T.; Mandi, A.; Taniguchi, T.; Monde, K.; Furuta, T.; Kawabata, T. α-arylation of α-amino acid derivatives with arynes via memory of chirality: asymmetric synthesis of benzocyclobutenones with tetrasubstituted carbon. Org. Lett., 2017, 19(2), 352-355.
[http://dx.doi.org/10.1021/acs.orglett.6b03533] [PMID: 28045272]
[76]
Kawabata, T.; Moriyama, K.; Kawakami, S.; Tsubaki, K. Powdered KOH in DMSO: an efficient base for asymmetric cyclization via memory of chirality at ambient temperature. J. Am. Chem. Soc., 2008, 130(12), 4153-4157.
[http://dx.doi.org/10.1021/ja077684w] [PMID: 18303890]
[77]
Rucaparib, F.D.A. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/rucaparib (Accessed date: May 18, 2017.)..
[78]
Webber, S.E.; Canan-Koch, S.S.; Tikhe, J.; Thoresen, L.H. Tricyclic Inhibitors of Poly(ADP-Ribose) Polymerases. U.S. Patent 6,495,541B1. December 17 2002.
[79]
Hughes, D.L. Patent review of manufacturing routes to recently approved PARP inhibitors: olaparib, rucaparib, and niraparib. Org. Process Res. Dev., 2017, 21(9), 1227-1244.
[http://dx.doi.org/10.1021/acs.oprd.7b00235]
[80]
Tang, Z.; Jiang, B.; Shi, Z.; Gong, W.; Liu, Y.; Wang, X.; Gao, Y.; Yu, F.; Zhou, C.; Luo, L.; Wei, M.; Wang, L. Abstract 1651: BGB-290, a novel PARP inhibitor with unique brain penetration ability, demonstrated strong synergism with temozolomide in subcutaneous and intracranial xenograft models. Cancer Res., 2015, 75(15)(Suppl.), 1651.
[http://dx.doi.org/10.1158/1538-7445.AM2015-1651]
[81]
Tang, Z.; Liu, Y.; Zhen, Q.; Ren, B.; Wang, H.; Shi, Z.; Gong, W.; Liu, Y.; Wang, X.; Gao, Y.; Yu, F.; Wu, Y.; Jiang, B.; Sun, X.; Wei, M.; Zhou, C.; Luo, L.; Li, Z.; Yu, J.; Zhao, J.; Wang, J.; Wang, L. Abstract 1653: BGB-290: A highly potent and specific PARP1/2 inhibitor potentiates anti-tumor activity of chemotherapeutics in patient biopsy derived SCLC models. Cancer Res., 2015, 75(15)(Suppl.), 1653.
[http://dx.doi.org/10.1158/1538-7445.AM2015-1653]
[82]
Papeo, G.; Posteri, H.; Borghi, D.; Busel, A.A.; Caprera, F.; Casale, E.; Ciomei, M.; Cirla, A.; Corti, E.; D’Anello, M.; Fasolini, M.; Forte, B.; Galvani, A.; Isacchi, A.; Khvat, A.; Krasavin, M.Y.; Lupi, R.; Orsini, P.; Perego, R.; Pesenti, E.; Pezzetta, D.; Rainoldi, S.; Riccardi-Sirtori, F.; Scolaro, A.; Sola, F.; Zuccotto, F.; Felder, E.R.; Donati, D.; Montagnoli, A. Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): a potent, orally available, and highly selective PARP-1 inhibitor for cancer therapy. J. Med. Chem., 2015, 58(17), 6875-6898.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00680] [PMID: 26222319]
[83]
Jagtap, P.; Soriano, F.G.; Virág, L.; Liaudet, L.; Mabley, J.; Szabó, E.; Haskó, G.; Marton, A.; Lorigados, C.B.; Gallyas, F., Jr; Sümegi, B.; Hoyt, D.G.; Baloglu, E.; VanDuzer, J.; Salzman, A.L.; Southan, G.J.; Szabó, C. Novel phenanthridinone inhibitors of poly (adenosine 5′-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents. Crit. Care Med., 2002, 30(5), 1071-1082.
[http://dx.doi.org/10.1097/00003246-200205000-00019] [PMID: 12006805]
[84]
Jagtap, P.; Szabó, C. Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat. Rev. Drug Discov., 2005, 4(5), 421-440.
[http://dx.doi.org/10.1038/nrd1718] [PMID: 15864271]
[85]
Madison, D.L.; Stauffer, D.; Lundblad, J.R. The PARP inhibitor PJ34 causes a PARP1-independent, p21 dependent mitotic arrest. DNA Repair (Amst.), 2011, 10(10), 1003-1013.
[http://dx.doi.org/10.1016/j.dnarep.2011.07.006] [PMID: 21840268]
[86]
Visochek, L.; Castiel, A.; Mittelman, L.; Elkin, M.; Atias, D.; Golan, T.; Izraeli, S.; Peretz, T.; Cohen-Armon, M. Exclusive destruction of mitotic spindles in human cancer cells. Oncotarget, 2017, 8(13), 20813-20824.
[http://dx.doi.org/10.18632/oncotarget.15343] [PMID: 28209915]
[87]
Castiel, A.; Visochek, L.; Mittelman, L.; Dantzer, F.; Izraeli, S.; Cohen-Armon, M. A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent exclusively eradicating human cancer cells. BMC Cancer, 2011, 11(1), 412.
[http://dx.doi.org/10.1186/1471-2407-11-412] [PMID: 21943092]
[88]
Jagtap, P.G.; Baloglu, E.; Southan, G.J.; Mabley, J.G.; Li, H.; Zhou, J.; van Duzer, J.; Salzman, A.L.; Szabó, C. Discovery of potent poly(ADP-ribose) polymerase-1 inhibitors from the modification of indeno[1,2-c]isoquinolinone. J. Med. Chem., 2005, 48(16), 5100-5103.
[http://dx.doi.org/10.1021/jm0502891] [PMID: 16078828]
[89]
He, J.X.; Wang, M.; Huan, X.J.; Chen, C.H.; Song, S.S.; Wang, Y.Q.; Liao, X.M.; Tan, C.; He, Q.; Tong, L.J.; Wang, Y.T.; Li, X.H.; Su, Y.; Shen, Y.Y.; Sun, Y.M.; Yang, X.Y.; Chen, Y.; Gao, Z.W.; Chen, X.Y.; Xiong, B.; Lu, X.L.; Ding, J.; Yang, C.H.; Miao, Z.H. Novel PARP1/2 inhibitor mefuparib hydrochloride elicits potent in vitro and in vivo anticancer activity, characteristic of high tissue distribution. Oncotarget, 2017, 8(3), 4156-4168.
[http://dx.doi.org/10.18632/oncotarget.13749] [PMID: 27926532]
[90]
Mei, T.S.; Giri, R.; Maugel, N.; Yu, J.Q. Pd(II)-catalyzed monoselective ortho halogenation of C-H bonds assisted by counter cations: a complementary method to directed ortho lithiation. Angew. Chem. Int. Ed. Engl., 2008, 47(28), 5215-5219.
[http://dx.doi.org/10.1002/anie.200705613] [PMID: 18523942]
[91]
Yang, B.H.; Li, Q.; Tian, H.; Yu, J. Process development on a PARP inhibitor (PARP) of 4-{ [3-[[2-(trifluoromethyl)-5,6,7,8-tetrahydro-(1,2,4) triazolo (1,5-α) pyrazine-7-yl] carbonyl]-4-fluorophenyl] methyl } (2H) phthalazine-1-one. Jingxi Yu Zhuanyong Huaxuepin, 2015, 23(12), 27-29.
[http://dx.doi.org/10.3969/j.issn.1008-1100.2015.12.007 ]
[92]
Lu, T.X.; Wang, L.X.; Wang, X.K.; Hu, C.; Zhou, X.B. Improved synthesis of PARP antagonist veliparib. Zhongguo Yaowu Huaxue Zazhi, 2013, 23(6), 476-479.
[http://dx.doi.org/10.14142/j.cnki.cn21-1313/r.2013.06.003]