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 TumorsClick to copy article linkArticle link copied!
- Philip Jones
- Sergio Altamura
- Julia Boueres
- Federica Ferrigno
- Massimiliano Fonsi
- Claudia Giomini
- Stefania Lamartina
- Edith Monteagudo
- Jesus M. Ontoria
- Maria Vittoria Orsale
- Maria Cecilia Palumbi
- Silvia Pesci
- Giuseppe Roscilli
- Rita Scarpelli
- Carsten Schultz-Fademrecht
- Carlo Toniatti
- Michael Rowley
Abstract
We disclose the development of a novel series of 2-phenyl-2H-indazole-7-carboxamides as poly(ADP-ribose)polymerase (PARP) 1 and 2 inhibitors. This series was optimized to improve enzyme and cellular activity, and the resulting PARP inhibitors display antiproliferation activities against BRCA-1 and BRCA-2 deficient cancer cells, with high selectivity over BRCA proficient cells. Extrahepatic oxidation by CYP450 1A1 and 1A2 was identified as a metabolic concern, and strategies to improve pharmacokinetic properties are reported. These efforts culminated in the identification of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide 56 (MK-4827), which displays good pharmacokinetic properties and is currently in phase I clinical trials. This compound displays excellent PARP 1 and 2 inhibition with IC50 = 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10−100 nM range. Compound 56 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.
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(9)
, 2799-2819. https://doi.org/10.1021/acsptsci.4c00251
- Qianna Wang, Junhong Feng, Yuhao Jiang, Hang Zhou, Qing Ruan, Guangxing Yin, Junbo Zhang. Preparation and Evaluation of a Novel 99mTc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent. Molecular Pharmaceutics 2024, 21
(7)
, 3321-3329. https://doi.org/10.1021/acs.molpharmaceut.4c00067
- Yiting Zhang, Xiangqian Li, Fang Liu, Xiaoyi Bai, Xiaochun Liu, Hao Sun, Chenxia Gao, Yuxi Lin, Pan Xing, Jiqiang Zhu, Ruihua Liu, Zemin Wang, Jiajia Dai, Dayong Shi. Design of Selective PARP-1 Inhibitors and Antitumor Studies. Journal of Medicinal Chemistry 2024, 67
(11)
, 8877-8901. https://doi.org/10.1021/acs.jmedchem.3c02460
- Yunfei Tian, Luping Zheng, Dongyu Guo, Yuyan Miao, Lijun Li, Weijun Fu, Zejiang Li. Photopromoted Free Radical Silylation of 2-Aryl-2H-indazoles with Silanes. The Journal of Organic Chemistry 2023, 88
(23)
, 16671-16678. https://doi.org/10.1021/acs.joc.3c02232
- Mattias F. Lindberg, Emmanuel Deau, Jonas Arfwedson, Nicolas George, Pascal George, Patricia Alfonso, Ana Corrionero, Laurent Meijer. Comparative Efficacy and Selectivity of Pharmacological Inhibitors of DYRK and CLK Protein Kinases. Journal of Medicinal Chemistry 2023, 66
(6)
, 4106-4130. https://doi.org/10.1021/acs.jmedchem.2c02068
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(9)
, 6803-6825. https://doi.org/10.1021/acs.jmedchem.2c00135
- Margarida L. F. Martins, Nancy H. C. Loos, Sümeyra Mucuk, Danielle de Jong, Maria C. Lebre, Hilde Rosing, Matthijs Tibben, Jos H. Beijnen, Alfred H. Schinkel. P-Glycoprotein (ABCB1/MDR1) Controls Brain Penetration and Intestinal Disposition of the PARP1/2 Inhibitor Niraparib. Molecular Pharmaceutics 2021, 18
(12)
, 4371-4384. https://doi.org/10.1021/acs.molpharmaceut.1c00553
- Lufeng Zheng, Ren Ren, Xiaolian Sun, Yunting Zou, Yiru Shi, Bin Di, Miao-Miao Niu. Discovery of a Dual Tubulin and Poly(ADP-Ribose) Polymerase-1 Inhibitor by Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, and Biological Evaluation. Journal of Medicinal Chemistry 2021, 64
(21)
, 15702-15715. https://doi.org/10.1021/acs.jmedchem.1c00932
- Jeffrey W. Johannes, Amber Balazs, Derek Barratt, Michal Bista, Matthew D. Chuba, Sabina Cosulich, Susan E. Critchlow, Sébastien L. Degorce, Paolo Di Fruscia, Scott D. Edmondson, Kevin Embrey, Stephen Fawell, Avipsa Ghosh, Sonja J. Gill, Anders Gunnarsson, Sudhir M. Hande, Tom D. Heightman, Paul Hemsley, Giuditta Illuzzi, Jordan Lane, Carrie Larner, Elisabetta Leo, Lina Liu, Andrew Madin, Scott Martin, Lisa McWilliams, Mark J. O’Connor, Jonathan P. Orme, Fiona Pachl, Martin J. Packer, Xiaohui Pei, Andrew Pike, Marianne Schimpl, Hongyao She, Anna D. Staniszewska, Verity Talbot, Elizabeth Underwood, Jeffrey G. Varnes, Lin Xue, Tieguang Yao, Ke Zhang, Andrew X. Zhang, Xiaolan Zheng. Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD5305): A PARP1–DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs. Journal of Medicinal Chemistry 2021, 64
(19)
, 14498-14512. https://doi.org/10.1021/acs.jmedchem.1c01012
- Nayyef Aljaar, Mousa Al-Noaimi, Jürgen Conrad, Uwe Beifuss. Direct Formation of 2-Substituted 2H-Indazoles by a Pd-Catalyzed Reaction between 2-Halobenzyl Halides and Arylhydrazines. The Journal of Organic Chemistry 2021, 86
(2)
, 1408-1418. https://doi.org/10.1021/acs.joc.0c01923
- Hexiang Wang, Bo Ren, Ye Liu, Beibei Jiang, Yin Guo, Min Wei, Lusong Luo, Xianzhao Kuang, Ming Qiu, Lei Lv, Hong Xu, Ruipeng Qi, Huibin Yan, Dexu Xu, Zhiwei Wang, Chang-Xin Huo, Yutong Zhu, Yuan Zhao, Yiyuan Wu, Zhen Qin, Dan Su, Tristin Tang, Fan Wang, Xuebing Sun, Yingcai Feng, Hao Peng, Xing Wang, Yajuan Gao, Yong Liu, Wenfeng Gong, Fenglong Yu, Xuesong Liu, Lai Wang, Changyou Zhou. Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development. Journal of Medicinal Chemistry 2020, 63
(24)
, 15541-15563. https://doi.org/10.1021/acs.jmedchem.0c01346
- Raghunath Reddy Anugu, Sailu Munnuri, John R. Falck. Picolinate-Directed Arene meta-C–H Amination via FeCl3 Catalysis. Journal of the American Chemical Society 2020, 142
(11)
, 5266-5271. https://doi.org/10.1021/jacs.9b13753
- Junwei Wang, Hui Li, Guangchao He, Zhaoxing Chu, Kewen Peng, Yiran Ge, Qihua Zhu, Yungen Xu. Discovery of Novel Dual Poly(ADP-ribose)polymerase and Phosphoinositide 3-Kinase Inhibitors as a Promising Strategy for Cancer Therapy. Journal of Medicinal Chemistry 2020, 63
(1)
, 122-139. https://doi.org/10.1021/acs.jmedchem.9b00622
- Diego Alemán-Ponce de León, Anahí C. Sánchez-Chávez, Luis A. Polindara-García. Pd-Mediated γ-C(sp3)–H Bond Activation in Ammonia–Ugi 4-CR Adducts by Using Picolinamide as Directing Group. The Journal of Organic Chemistry 2019, 84
(20)
, 12809-12834. https://doi.org/10.1021/acs.joc.9b01436
- Andrew
C. Flick, Carolyn A. Leverett, Hong X. Ding, Emma McInturff, Sarah J. Fink, Christopher J. Helal, Christopher J. O’Donnell. Synthetic Approaches to the New Drugs Approved During 2017. Journal of Medicinal Chemistry 2019, 62
(16)
, 7340-7382. https://doi.org/10.1021/acs.jmedchem.9b00196
- Jie S. Zhu, Makhluf J. Haddadin, Mark J. Kurth. Davis–Beirut Reaction: Diverse Chemistries of Highly Reactive Nitroso Intermediates in Heterocycle Synthesis. Accounts of Chemical Research 2019, 52
(8)
, 2256-2265. https://doi.org/10.1021/acs.accounts.9b00220
- Uday Kiran Velagapudi, Marie-France Langelier, Cristina Delgado-Martin, Morgan E. Diolaiti, Sietske Bakker, Alan Ashworth, Bhargav A. Patel, Xuwei Shao, John M. Pascal, Tanaji T. Talele. Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity. Journal of Medicinal Chemistry 2019, 62
(11)
, 5330-5357. https://doi.org/10.1021/acs.jmedchem.8b01709
- Jie S. Zhu, Clarabella J. Li, Ka Yi Tsui, Niklas Kraemer, Jung-Ho Son, Makhluf J. Haddadin, Dean J. Tantillo, Mark J. Kurth. Accessing Multiple Classes of 2H-Indazoles: Mechanistic Implications for the Cadogan and Davis–Beirut Reactions. Journal of the American Chemical Society 2019, 141
(15)
, 6247-6253. https://doi.org/10.1021/jacs.8b13481
- Cheng Zhang, Sailan Chang, Shanliang Dong, Lihua Qiu, Xinfang Xu. Acid-Promoted Bicyclization of Diaryl Alkynes: Synthesis of 2H-Indazoles with in Situ Generated Diazonium Salt as Nitrogen Source. The Journal of Organic Chemistry 2018, 83
(16)
, 9125-9136. https://doi.org/10.1021/acs.joc.8b01199
- Tz-Yi Wu, Sandip Dhole, Manikandan Selvaraju, Chung-Ming Sun. Regioselective Synthesis of Pyranone-Fused Indazoles via Reductive Cyclization and Alkyne Insertion. ACS Combinatorial Science 2018, 20
(3)
, 156-163. https://doi.org/10.1021/acscombsci.7b00170
- Yuanli Zhen and Yonghao Yu . Proteomic Analysis of the Downstream Signaling Network of PARP1. Biochemistry 2018, 57
(4)
, 429-440. https://doi.org/10.1021/acs.biochem.7b01022
- Jacob M. Ganley and Charles S. Yeung . Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study on Catalytic C–S Couplings in the Presence of Strong Base. The Journal of Organic Chemistry 2017, 82
(24)
, 13557-13562. https://doi.org/10.1021/acs.joc.7b02712
- David L. Hughes . Patent Review of Manufacturing Routes to Recently Approved PARP Inhibitors: Olaparib, Rucaparib, and Niraparib. Organic Process Research & Development 2017, 21
(9)
, 1227-1244. https://doi.org/10.1021/acs.oprd.7b00235
- Zhen Long, Yudong Yang, and Jingsong You . Rh(III)-Catalyzed [4 + 1]-Annulation of Azoxy Compounds with Alkynes: A Regioselective Approach to 2H-Indazoles. Organic Letters 2017, 19
(11)
, 2781-2784. https://doi.org/10.1021/acs.orglett.7b00982
- Jiarong Shi, Hai Xu, Dachuan Qiu, Jia He, and Yang Li . Selective Aryne Formation via Grob Fragmentation from the [2+2] Cycloadducts of 3-Triflyloxyarynes. Journal of the American Chemical Society 2017, 139
(2)
, 623-626. https://doi.org/10.1021/jacs.6b12161
- Safnas F. AbdulSalam, Fathima Shazna Thowfeik, and Edward J. Merino . Excessive Reactive Oxygen Species and Exotic DNA Lesions as an Exploitable Liability. Biochemistry 2016, 55
(38)
, 5341-5352. https://doi.org/10.1021/acs.biochem.6b00703
- Bing Wang, Daniel Chu, Ying Feng, Yuqiao Shen, Mika Aoyagi-Scharber, and Leonard E. Post . 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. Journal of Medicinal Chemistry 2016, 59
(1)
, 335-357. https://doi.org/10.1021/acs.jmedchem.5b01498
- Gianluca Papeo, Helena Posteri, Daniela Borghi, Alina A. Busel, Francesco Caprera, Elena Casale, Marina Ciomei, Alessandra Cirla, Emiliana Corti, Matteo D’Anello, Marina Fasolini, Barbara Forte, Arturo Galvani, Antonella Isacchi, Alexander Khvat, Mikhail Y. Krasavin, Rosita Lupi, Paolo Orsini, Rita Perego, Enrico Pesenti, Daniele Pezzetta, Sonia Rainoldi, Federico Riccardi-Sirtori, Alessandra Scolaro, Francesco Sola, Fabio Zuccotto, Eduard R. Felder, Daniele Donati, and Alessia Montagnoli . 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. Journal of Medicinal Chemistry 2015, 58
(17)
, 6875-6898. https://doi.org/10.1021/acs.jmedchem.5b00680
- Philip Jones, Keith Wilcoxen, Michael Rowley, and Carlo Toniatti . Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. Journal of Medicinal Chemistry 2015, 58
(8)
, 3302-3314. https://doi.org/10.1021/jm5018237
- Kelli M. Farber, Makhluf J. Haddadin, and Mark J. Kurth . Davis–Beirut Reaction: Route to Thiazolo-, Thiazino-, and Thiazepino-2H-indazoles. The Journal of Organic Chemistry 2014, 79
(15)
, 6939-6945. https://doi.org/10.1021/jo501014e
- Maulik R. Patel, Aaditya Bhatt, Jamin D. Steffen, Adel Chergui, Junko Murai, Yves Pommier, John M. Pascal, Louis D. Trombetta, Frank R. Fronczek, and Tanaji T. Talele . Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors. Journal of Medicinal Chemistry 2014, 57
(13)
, 5579-5601. https://doi.org/10.1021/jm5002502
- Nathan E. Genung, Liuqing Wei, and Gary E. Aspnes . Regioselective Synthesis of 2H-Indazoles Using a Mild, One-Pot Condensation–Cadogan Reductive Cyclization. Organic Letters 2014, 16
(11)
, 3114-3117. https://doi.org/10.1021/ol5012423
- Cheol K. Chung, Paul G. Bulger, Birgit Kosjek, Kevin M. Belyk, Nelo Rivera, Mark E. Scott, Guy R. Humphrey, John Limanto, Donald C. Bachert, and Khateeta M. Emerson . Process Development of C–N Cross-Coupling and Enantioselective Biocatalytic Reactions for the Asymmetric Synthesis of Niraparib. Organic Process Research & Development 2014, 18
(1)
, 215-227. https://doi.org/10.1021/op400233z
- Na Ye, Chuan-Huizi Chen, TianTian Chen, Zilan Song, Jin-Xue He, Xia-Juan Huan, Shan-Shan Song, Qiufeng Liu, Yi Chen, Jian Ding, Yechun Xu, Ze-Hong Miao, and Ao Zhang . 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. Journal of Medicinal Chemistry 2013, 56
(7)
, 2885-2903. https://doi.org/10.1021/jm301825t
- Nicolas Charrier, Zhibo Liu, and Samir Z. Zard . Desulfonylative Radical Ring Closure onto Aromatics. A Modular Route to Benzazepin-2-ones and 5-Arylpiperidin-2-ones. Organic Letters 2012, 14
(8)
, 2018-2021. https://doi.org/10.1021/ol3005276
- Debra J. Wallace, Carl A. Baxter, Karel J. M. Brands, Nadine Bremeyer, Sarah E. Brewer, Richard Desmond, Khateeta M. Emerson, Jennifer Foley, Paul Fernandez, Weifeng Hu, Stephen P. Keen, Peter Mullens, Daniel Muzzio, Peter Sajonz, Lushi Tan, Robert D. Wilson, George Zhou, and Guoyue Zhou . Development of a Fit-for-Purpose Large-Scale Synthesis of an Oral PARP Inhibitor. Organic Process Research & Development 2011, 15
(4)
, 831-840. https://doi.org/10.1021/op2000783
- Peter T. Sunderland, Esther C. Y. Woon, Archana Dhami, Aoife B. Bergin, Mary F. Mahon, Pauline J. Wood, Louise A. Jones, Sophie R. Tully, Matthew D. Lloyd, Andrew S. Thompson, Hashim Javaid, Niall M. B. Martin, and Michael D. Threadgill . 5-Benzamidoisoquinolin-1-ones and 5-(ω-Carboxyalkyl)isoquinolin-1-ones as Isoform-Selective Inhibitors of Poly(ADP-ribose) Polymerase 2 (PARP-2). Journal of Medicinal Chemistry 2011, 54
(7)
, 2049-2059. https://doi.org/10.1021/jm1010918
- Dana V. Ferraris. Evolution of Poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors. From Concept to Clinic. Journal of Medicinal Chemistry 2010, 53
(12)
, 4561-4584. https://doi.org/10.1021/jm100012m
- Thomas D. Penning, Gui-Dong Zhu, Jianchun Gong, Sheela Thomas, Viraj B. Gandhi, Xuesong Liu, Yan Shi, Vered Klinghofer, Eric F. Johnson, Chang H. Park, Elizabeth H. Fry, Cherrie K. Donawho, David J. Frost, Fritz G. Buchanan, Gail T. Bukofzer, Luis E. Rodriguez, Velitchka Bontcheva-Diaz, Jennifer J. Bouska, Donald J. Osterling, Amanda M. Olson, Kennan C. Marsh, Yan Luo and Vincent L. Giranda . 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. Journal of Medicinal Chemistry 2010, 53
(8)
, 3142-3153. https://doi.org/10.1021/jm901775y
- Yu Xia, Qingqing Chen, He-Nan Liu, Yuan Chi, Ying Zhu, Li-Shen Shan, Bing Dai, Lin Wu, Xiaobao Shi. Synthetic routes and clinical application of new drugs approved by EMA during 2023. European Journal of Medicinal Chemistry 2024, 277 , 116762. https://doi.org/10.1016/j.ejmech.2024.116762
- Hyeong In Ha, Hyung Joon Yoon, Changho Song, Eun Taeg Kim, Dong-Soo Suh, Ki Hyung Kim, Yong Jin Na, Yong Jung Song. Clinical Outcomes of Poly(ADP–Ribose) Polymerase Inhibitors as Maintenance Therapy in Patients with Ovarian Cancer in the Southeastern Region of Korea. Current Oncology 2024, 31
(11)
, 6711-6722. https://doi.org/10.3390/curroncol31110495
- Jia Xie, Maria V. Barbolina. Dual Targeting of CX3CR1 and PARP in Models of High-Grade Serous Ovarian Carcinoma. Cancers 2024, 16
(22)
, 3728. https://doi.org/10.3390/cancers16223728
- Hong‐Ren Chen, Indrajeet J. Barve, Hung‐Sheng Hsieh, Kuan‐Miao Liu, Ganesh P. Pawar, Chung‐Ming Sun. Microwave‐Assisted Rhodium (III)‐Catalyzed [3+3] Annulation of 2‐Benzyl‐2H‐Indazole‐6‐carboxylic Acids with Iodonium Ylides: A Regioselective Synthesis of Indazole‐Fused Chromenes. Advanced Synthesis & Catalysis 2024, 27 https://doi.org/10.1002/adsc.202400756
- Xinluo Song, Lingfeng Yin, Subin Hao, Yu Wang, Yanqi Chen, Cheng Ma, Ming-De Li, Li Dang. Direct deoxygenative C–N coupling to construct indazole under visible light. Green Chemistry 2024, 26
(20)
, 10473-10478. https://doi.org/10.1039/D4GC02807D
- Jie Wu, Xiaoqian Wang, Yaning Yao, Nan Du, Liancheng Duan, Ping Gong. Design, synthesis and antitumor activities of phthalazinone derivatives as PARP-1 inhibitors and PARP-1/HDAC-1 inhibitors. Bioorganic Chemistry 2024, 151 , 107556. https://doi.org/10.1016/j.bioorg.2024.107556
- Anna Rutkowska, H. Christian Eberl, Thilo Werner, Marco L. Hennrich, Daniel C. Sévin, Massimo Petretich, James P. Reddington, Shirin Pocha, Stephan Gade, Amalia Martinez-Segura, Dmytro Dvornikov, Joel Karpiak, Gavain M.A. Sweetman, Christian Fufezan, Birgit Duempelfeld, Florian Braun, Christopher Schofield, Hakan Keles, David Alvarado, Zhuo Wang, Keith H. Jansson, Maria Faelth-Savitski, Edward Curry, Katja Remlinger, Euan A. Stronach, Bin Feng, Geeta Sharma, Kevin Coleman, Paola Grandi, Marcus Bantscheff, Giovanna Bergamini. Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation. Cancer Research Communications 2024, 4
(9)
, 2427-2443. https://doi.org/10.1158/2767-9764.CRC-23-0549
- Yi‐Ru Bai, Wei‐Guang Yang, Rui Jia, Ju‐Shan Sun, Dan‐Dan Shen, Hong‐Min Liu, Shuo Yuan. The recent advance and prospect of poly(ADP‐ribose) polymerase inhibitors for the treatment of cancer. Medicinal Research Reviews 2024, 368 https://doi.org/10.1002/med.22069
- Laimujam Sidartha Singh, Kamal Kant, Sourav Banerjee, Ragini Sengupta, Abeer A. AlObaid, Maynak Pal, Saikat Dutta, Nayyef Aljaar, Chandi C. Malakar. The
γ
-Valerolactone (GVL) as Innoxious Reaction Media for the Synthesis of 2-Aryl-2
H
-Indazoles
via
C-N and N-N Bond Formation under Cu(I)-Catalyzed Ligand and Base Free Conditions. Polycyclic Aromatic Compounds 2024, 44
(7)
, 4832-4843. https://doi.org/10.1080/10406638.2023.2257846
- William Knight, Tigran Margaryan, Nader Sanai, Artak Tovmasyan. A validated LC-MS/MS method for determination of neuro-pharmacokinetic behavior of niraparib in brain tumor patients. Journal of Pharmaceutical and Biomedical Analysis 2024, 245 , 116150. https://doi.org/10.1016/j.jpba.2024.116150
- Chao Lin, Chang Liu, Panpan Hu, Zui Zou, Geng Sun. Design, synthesis, biological evaluation of novel piperidine-based derivatives as potent poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. Bioorganic Chemistry 2024, 148 , 107455. https://doi.org/10.1016/j.bioorg.2024.107455
- Bradley J. Monk, Ignacio Romero, Whitney Graybill, Cristina Churruca, David M. O'Malley, Anja Ør Knudsen, Oi Wah Stephanie Yap, Jean-François Baurain, Peter G. Rose, Hannelore Denys, Sharad Ghamande, Carmela Pisano, Michel Fabbro, Elena Ioana Braicu, Paula M. Calvert, Amnon Amit, Emily Prendergast, Adekemi Taylor, Leila Kheibarshekan, Zhi-Yi Zhang, Stefan Zajic, Roxanne C. Jewell, Divya Gupta, Antonio González-Martín. Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer. Clinical Therapeutics 2024, 52 https://doi.org/10.1016/j.clinthera.2024.06.001
- Vamshi Krishna Atikala, Siddique Akber Ansari, Irfan Aamer Ansari, Ravikumar Kapavarapu, Hari Babu Bollikolla. Synthesis of 2‐Aryl Indazole: Synthesis, Biological Evaluationand
In
‐
Silico
Studies. Chemistry & Biodiversity 2024, 21
(7)
https://doi.org/10.1002/cbdv.202302085
- Tamer M. Sakr, Mohammed F. Elsabagh, Hend Fayez, Mona O. Sarhan, Yasmin M. Syam, Manal M. Anwar, Mohammed A. Motaleb, Wafaa A. Zaghary. Multi-functionalization of reduced graphene oxide nanosheets for tumor theragnosis: Synthesis, characterization, enzyme assay, in-silico study, radiolabeling and in vivo targeting evaluation. DARU Journal of Pharmaceutical Sciences 2024, 32
(1)
, 77-95. https://doi.org/10.1007/s40199-023-00487-7
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- Inês M. Bastos, Sandra Rebelo, Vera L.M. Silva. A review of poly(ADP-ribose)polymerase-1 (PARP1) role and its inhibitors bearing pyrazole or indazole core for cancer therapy. Biochemical Pharmacology 2024, 221 , 116045. https://doi.org/10.1016/j.bcp.2024.116045
- Yiquan Wu, Mingfei Wu, Xiaoli Zheng, Hengyuan Yu, Xinfei Mao, Yuyuan Jin, Yanhong Wang, Ao Pang, Jingyu Zhang, Shenxin Zeng, Tengfei Xu, Yong Chen, Bo Zhang, Nengming Lin, Haibin Dai, Yuwei Wang, Xiaojun Yao, Xiaowu Dong, Wenhai Huang, Jinxin Che. Discovery of a potent and selective PARP1 degrader promoting cell cycle arrest via intercepting CDC25C-CDK1 axis for treating triple-negative breast cancer. Bioorganic Chemistry 2024, 142 , 106952. https://doi.org/10.1016/j.bioorg.2023.106952
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(2)
, 464. https://doi.org/10.3390/molecules29020464
- Lauro Figueroa-Valverde, Rosas-Nexticapa Marcela, Magdalena Alvarez-Ramirez, Maria Lopez-Ramos, Virginia Mateu-Armand, Hernandez-Vazquez Patricia. Interaction of Thiophene and Their Derivatives with BRCA-1 Using a Theoretical Model. Clinical Cancer Investigation Journal 2024, 13
(2)
, 40-44. https://doi.org/10.51847/4AnibsrLIW
- Qin Xue, Wang Enyang, Gong Tingting, Ma Xiaolin, Ma Qipeng, Gao Song. Anti-tumour and radiosensitising effects of PARP inhibitor on cervical cancer xenografts. Journal of Obstetrics and Gynaecology 2023, 43
(1)
https://doi.org/10.1080/01443615.2023.2171783
- Jing-Yi Zhang, Li-Jie Zhao, Ya-Tao Wang. Synthesis and clinical application of small-molecule drugs approved to treat prostatic cancer. European Journal of Medicinal Chemistry 2023, 262 , 115925. https://doi.org/10.1016/j.ejmech.2023.115925
- Amandeep Thakur, Mandeep Rana, Ritika, Jacob Mathew, Sanya Nepali, Chun-Hsu Pan, Jing Ping Liou, Kunal Nepali. Small molecule tractable PARP inhibitors: Scaffold construction approaches, mechanistic insights and structure activity relationship. Bioorganic Chemistry 2023, 141 , 106893. https://doi.org/10.1016/j.bioorg.2023.106893
- Bente Vilming, Jørgen Fallås Dahl, Anne Gry Bentzen, Vibeke Anett Ingebrigtsen, Elisabeth Berge Nilsen, Ingvild Vistad, Anne Dørum, Olesya Solheim, Line Bjørge, Manuela Zucknick, Guro Aune, Kristina Lindemann. Real-world data on niraparib maintenance treatment in patients with non-gBRCA mutated platinum-sensitive recurrent ovarian cancer. International Journal of Gynecologic Cancer 2023, 33
(12)
, 1898-1905. https://doi.org/10.1136/ijgc-2023-004484
- Soundarya Ramesh, Shannon D Almeida, Sameerana Hammigi, Govardan Katta Radhakrishna, Golla Sireesha, Theivendren Panneerselvam, Shangavi Vellingiri, Selvaraj Kunjiappan, Damodar Nayak Ammunje, Parasuraman Pavadai. A Review of PARP-1 Inhibitors: Assessing Emerging Prospects and
Tailoring Therapeutic Strategies. Drug Research 2023, 73
(09)
, 491-505. https://doi.org/10.1055/a-2181-0813
- Minmin Zhao, Shanhu Qiu, Xin Wu, Pengcheng Miao, Zhi Jiang, Tao Zhu, Xizhong Xu, Yanling Zhu, Bei Zhang, Donglan Yuan, Yang Zhang, Wei Sun, Aiqin He, Min Zhao, Wenjie Hou, Yingli Zhang, Zhuyan Shao, Meiqun Jia, Mei Li, Jun Chen, Jingcheng Xu, Bingwei Chen, Ying Zhou, Yang Shen. Efficacy and Safety of Niraparib as First-Line Maintenance Treatment for Patients with Advanced Ovarian Cancer: Real-World Data from a Multicenter Study in China. Targeted Oncology 2023, 18
(6)
, 869-883. https://doi.org/10.1007/s11523-023-00999-x
- Lan Zhang, Yongqi Zhen, Lu Feng, Zhijia Li, Yingying Lu, Guan Wang, Liang Ouyang. Discovery of a novel dual-target inhibitor of CDK12 and PARP1 that induces synthetic lethality for treatment of triple-negative breast cancer. European Journal of Medicinal Chemistry 2023, 259 , 115648. https://doi.org/10.1016/j.ejmech.2023.115648
- Cheng Wang, Heng Luo, Xinye Chen, Yonglei Zhang, Dehua Lu, Xingchen Liu, Fucheng Yin, Shang Li, Lingyi Kong, Xiaobing Wang. Discovery of dual PARP and CDK6 inhibitors for triple-negative breast cancer with wild-type BRCA. Bioorganic Chemistry 2023, 139 , 106683. https://doi.org/10.1016/j.bioorg.2023.106683
- Haya Khan, Souvik Guha, Mousumi Baruah, Shalini Yadav, Sanjana Maheshwari, Sara Sainani, Debajit Maiti, Subhabrata Sen. Blue LED Induced Three Component Reactions for the Generation of 4,6‐Dioxo‐hexahydro‐1H‐furo[3, 4‐c] pyrrole: Their Evaluation as Anticancer Agents through PARP‐1 Inhibition. Chemistry – An Asian Journal 2023, 18
(15)
https://doi.org/10.1002/asia.202300420
- Luke R. Odell, Bobo Skillinghaug, Christof Matt, Peng Wu, Tobias Koolmeister, Matthieu Desroses, Sabin Llona‐Minguez, Olov Wallner, Thomas Helleday, Martin Scobie. Synthesis of Substituted Indazole Acetic Acids by N−N Bond Forming Reactions. European Journal of Organic Chemistry 2023, 26
(29)
https://doi.org/10.1002/ejoc.202300291
- Xiaojuan Yang, Lu Xu, Li Yang. Recent advances in EZH2-based dual inhibitors in the treatment of cancers. European Journal of Medicinal Chemistry 2023, 256 , 115461. https://doi.org/10.1016/j.ejmech.2023.115461
- Maneesh Guleria, Pradeep Kumar, Suresh Thareja. Synthetic PARP-1 Inhibitors Reported During the Last Decade. Letters in Drug Design & Discovery 2023, 20
(7)
, 793-807. https://doi.org/10.2174/1570180819666220615090709
- Wen-Hao Li, Fei Wang, Gui-Yuan Song, Qing-Hua Yu, Rui-Peng Du, Ping Xu. PARP-1: a critical regulator in radioprotection and radiotherapy-mechanisms, challenges, and therapeutic opportunities. Frontiers in Pharmacology 2023, 14 https://doi.org/10.3389/fphar.2023.1198948
- Anzai Shi, Panjie Xiang, Yanxuan Wu, Chang Ge, Yan Liu, Kai Sun, Bing Yu. Visible-Light-Promoted Metal-Free 3-Arylation of 2-Aryl-2H-indazoles with Triarylsulfonium Salts. Synlett 2023, 34
(05)
, 457-464. https://doi.org/10.1055/a-1938-9550
- Zachary Quinn, Benjamin Leiby, Guru Sonpavde, Atish D. Choudhury, Christopher Sweeney, David Einstein, Russell Szmulewitz, Oliver Sartor, Karen Knudsen, Eddy Shih-Hsin Yang, Wm. Kevin Kelly. Phase I Study of Niraparib in Combination with Radium-223 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer. Clinical Cancer Research 2023, 29
(1)
, 50-59. https://doi.org/10.1158/1078-0432.CCR-22-2526
- Shannon N. Westin, Anil K. Sood, Robert L. Coleman. Targeted therapy and molecular genetics. 2023, 464-488.e11. https://doi.org/10.1016/B978-0-323-77684-4.00024-6
- Kamyar Hadian, Brent R. Stockwell. . Nature Reviews Drug Discovery 2023, 723. https://doi.org/10.1038/s41573-023-00749-8
- Maria Ornella Nicoletto, Alessandra Baldoni, Francesco Cavallin, Andrea Grego, Cristina Falci, Margherita Nardin, Enzo Mammano, Eleonora Lai, Valter Torri. Oxaliplatin prior to PARP inhibitor in BRCA-mutated ovarian cancer. Therapeutic Advances in Medical Oncology 2023, 15 https://doi.org/10.1177/17588359231173181
- Anna D. Staniszewska, Joshua Armenia, Matthew King, Chrysiis Michaloglou, Avinash Reddy, Maneesh Singh, Maryann San Martin, Laura Prickett, Zena Wilson, Theresa Proia, Deanna Russell, Morgan Thomas, Oona Delpuech, Mark J. O’Connor, Elisabetta Leo, Helen Angell, Viia Valge-Archer. PARP inhibition is a modulator of anti-tumor immune response in BRCA-deficient tumors. OncoImmunology 2022, 11
(1)
https://doi.org/10.1080/2162402X.2022.2083755
- Shengneng Ying, Xingru Liu, Tao Guo, Xuan Li, Min Zhou, Xia Wang, Mengxue Zhu, Hongmei Jiang, Qing-Wen Gui. Ultrasound-assisted bromination of indazoles at the C3 position with dibromohydantoin. RSC Advances 2022, 13
(1)
, 581-585. https://doi.org/10.1039/D2RA06867B
- Maninder Singh, Jyotika Rajawat, Jitendra Kuldeep, Nidhi Shukla, Durga Prasad Mishra, Mohammad Imran Siddiqi. Integrated support vector machine and pharmacophore based virtual screening driven identification of thiophene carboxamide scaffold containing compound as potential PARP1 inhibitor. Journal of Biomolecular Structure and Dynamics 2022, 40
(18)
, 8494-8507. https://doi.org/10.1080/07391102.2021.1913229
- Qing Wu, Wei Qian, Xiaoli Sun, Shaojie Jiang. Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021. Journal of Hematology & Oncology 2022, 15
(1)
https://doi.org/10.1186/s13045-022-01362-9
- Menglin Guo, Yamin Shu, Guosong Chen, Juan Li, Feie Li. A real-world pharmacovigilance study of FDA adverse event reporting system (FAERS) events for niraparib. Scientific Reports 2022, 12
(1)
https://doi.org/10.1038/s41598-022-23726-4
- Maaike A. C. Bruin, Gabe S. Sonke, Jos H. Beijnen, Alwin D. R. Huitema. Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology. Clinical Pharmacokinetics 2022, 61
(12)
, 1649-1675. https://doi.org/10.1007/s40262-022-01167-6
- Junkang Ren, Xu Quan, Ying Liu, Jiani Li, Xiaoyu Zhang, Zhiyu Li, Xiaomeng Zhang. Synthesis and in vitro biological evaluation of 3-ethyl-1,5-naphthyridin-2(1H)-one derivatives as potent PARP-1 selective inhibitors and PARP-1 DNA trappers. Bioorganic & Medicinal Chemistry Letters 2022, 78 , 129046. https://doi.org/10.1016/j.bmcl.2022.129046
- Chunhua Ma, Linchun Shang, Hanying Zhao, Xing He, Qiyan Lv, Dandan Zhang, Yuqin Jiang. Visible light-promoted transition metal-free direct C3-carbamoylation of 2H-Indazoles. Frontiers in Chemistry 2022, 10 https://doi.org/10.3389/fchem.2022.1087834
- Serhan Unlu, Joseph W. Kim. Emerging Role of PARP Inhibitors in Metastatic Prostate Cancer. Current Oncology Reports 2022, 24
(11)
, 1619-1631. https://doi.org/10.1007/s11912-022-01305-0
- Raymond Ng. Niraparib (Zejula), A Small Molecule, PARP1/2 Inhibitor for Treating Breast, Ovarian, and Pancreatic Cancers. 2022, 231-251. https://doi.org/10.1002/9781119847281.ch12
- Muzaffar Kayumov, Li Jia, Azizbek Pardaev, Shan-Shan Song, Sharafitdin Mirzaakhmedov, Chunyong Ding, Yong-Jun Cheng, Ruihan (Isabella) Zhang, Xubin Bao, Ze-Hong Miao, Jin-Xue He, Ao Zhang. Design, synthesis and pharmacological evaluation of new PARP1 inhibitors by merging pharmacophores of olaparib and the natural product alantolactone. European Journal of Medicinal Chemistry 2022, 240 , 114574. https://doi.org/10.1016/j.ejmech.2022.114574
- Jin Wang, Qingyuan Song, Xing He, Chunhua Ma, Yuqin Jiang, Jing Fan. Visible light-promoted, photocatalyst-free decarboxylative alkylation of 2
H
-indazoles
via
electron donor–acceptor complex activation. New Journal of Chemistry 2022, 46
(34)
, 16436-16439. https://doi.org/10.1039/D2NJ02766F
- Ling Yu, Zhi-wei Yan, You-de Wang, Hao Miao, Jing-yi Zhao, Chong Pang, Shuai Li. Recent advances in structural types and medicinal chemistry of PARP-1 inhibitors. Medicinal Chemistry Research 2022, 31
(8)
, 1265-1276. https://doi.org/10.1007/s00044-022-02919-6
- Linda A. Snyder, Rajendra Damle, Shefali Patel, Jared Bohrer, Anna Fiorella, Jenny Driscoll, Rebecca Hawkins, Christopher F. Stratton, Carol D. Manning, Kanaka Tatikola, Volha Tryputsen, Kathryn Packman, Rao N.V.S. Mamidi. Niraparib Shows Superior Tissue Distribution and Efficacy in a Prostate Cancer Bone Metastasis Model Compared with Other PARP Inhibitors. Molecular Cancer Therapeutics 2022, 21
(7)
, 1115-1124. https://doi.org/10.1158/1535-7163.MCT-21-0798
- Yizhu Xu, Huanhuan Wu, Lei Huang, Bingxin Zhai, Xiaofei Li, Shuaiqi Xu, Xingxin Wu, Qihua Zhu, Qiang Xu. Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy. European Journal of Medicinal Chemistry 2022, 237 , 114417. https://doi.org/10.1016/j.ejmech.2022.114417
- Yan Teng, Chenglu Gu, Zhuhui Chen, Hui Jiang, Yue Xiong, Dong Liu, Deli Xiao. Advances and applications of chiral resolution in pharmaceutical field. Chirality 2022, 2 https://doi.org/10.1002/chir.23453
- Xianhai Huang, David Yu‐Kai Chen. Combination Therapy Case Studies in Anticancer and Anti‐Infectious Disease Drug Discovery and Development. 2022, 341-384. https://doi.org/10.1002/9781119627784.ch14
- Ke Shen, Li Yang, Fei-Yan Li, Feng Zhang, Lei-Lei Ding, Jing Yang, Jie Lu, Nan-Nan Wang, Yan Wang. Research Progress of PARP Inhibitor Monotherapy and Combination
Therapy for Endometrial Cancer. Current Drug Targets 2022, 23
(2)
, 145-155. https://doi.org/10.2174/1389450122666210617111304
- Diana Aguilar-Morante, Daniel Gómez-Cabello, Hazel Quek, Tianqing Liu, Petra Hamerlik, Yi Chieh Lim. Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma. Biomedicines 2022, 10
(2)
, 332. https://doi.org/10.3390/biomedicines10020332
- Danfeng Wang, Jin Wang, Chunhua Ma, Yuqin Jiang, Bing Yu. C-3 Functionalization of 2-Aryl-2
H
-indazoles under Photo/Electrocatalysis. Chinese Journal of Organic Chemistry 2022, 42
(12)
, 4024. https://doi.org/10.6023/cjoc202208039
- Jiang Yu, Lingling Luo, Tong Hu, Yating Cui, Xiao Sun, Wenfeng Gou, Wenbin Hou, Yiliang Li, Tiemin Sun. Structure-based design, synthesis, and evaluation of inhibitors with high selectivity for PARP-1 over PARP-2. European Journal of Medicinal Chemistry 2022, 227 , 113898. https://doi.org/10.1016/j.ejmech.2021.113898
- Melek Akay, Ionut-Gabriel Funingana, Grisma Patel, Rami Mustapha, Ernese Gjafa, Tony Ng, Kenrick Ng, Michael J. Flynn. An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions. Oncology and Therapy 2021, 9
(2)
, 347-364. https://doi.org/10.1007/s40487-021-00167-z
- Clifford M. Csizmar, Antoine N. Saliba, Elizabeth M. Swisher, Scott H. Kaufmann. PARP Inhibitors and Myeloid Neoplasms: A Double-Edged Sword. Cancers 2021, 13
(24)
, 6385. https://doi.org/10.3390/cancers13246385
- Nicholas C. Turner, Judith Balmaña, Coralie Poncet, Theodora Goulioti, Konstantinos Tryfonidis, Aafke H. Honkoop, Gabriele Zoppoli, Evangelia Razis, Oskar T. Johannsson, Marco Colleoni, Andrew N. Tutt, William Audeh, Michail Ignatiadis, Audrey Mailliez, Olivier Trédan, Antonino Musolino, Peter Vuylsteke, Maria Jose Juan-Fita, Iain R.J. Macpherson, Bella Kaufman, Luis Manso, Lori J. Goldstein, Susan L. Ellard, István Láng, Kai Yu Jen, Virginie Adam, Saskia Litière, John Erban, David A. Cameron. Niraparib for Advanced Breast Cancer with Germline
BRCA1
and
BRCA2
Mutations: the EORTC 1307-BCG/BIG5–13/TESARO PR-30–50–10-C BRAVO Study. Clinical Cancer Research 2021, 27
(20)
, 5482-5491. https://doi.org/10.1158/1078-0432.CCR-21-0310
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