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Structure-Based Macrocycle Design in Small-Molecule Drug Discovery and Simple Metrics To Identify Opportunities for Macrocyclization of Small-Molecule Ligands

Cite this: J. Med. Chem. 2019, 62, 15, 6843–6853
Publication Date (Web):March 12, 2019
https://doi.org/10.1021/acs.jmedchem.8b01985
Copyright © 2019 American Chemical Society
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    Abstract

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    Interest is growing in the use of macrocycles in pharmaceutical discovery. Macrocylization may provide a gateway to an expanded chemical space for small-molecule drug discovery, and this could be beneficial in prosecuting difficult targets, e.g., protein–protein interactions. Most, but not all, macrocycle drugs are derived from natural products. Studies on synthetic drug-like small-molecule macrocycles are limited, and our current understanding of macrocycle drugs is similarly limited. Following some background discussion, we review several examples of the structure-based design of synthetic macrocycles. Our opinion is that in conformationally suitable systems macrocycles are an analog class worthy of consideration. We then summarize an approach for the initial evaluation of molecules as candidates for macrocyclization.

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    29. Jack M. Wootton, Jerry K. F. Tam, William P. Unsworth. Cascade ring expansion reactions for the synthesis of medium-sized rings and macrocycles. Chemical Communications 2024, 38 https://doi.org/10.1039/D4CC01303D
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    35. Isabela Ramirez-Velez, Brian Belardi. Storming the gate: New approaches for targeting the dynamic tight junction for improved drug delivery. Advanced Drug Delivery Reviews 2023, 199 , 114905. https://doi.org/10.1016/j.addr.2023.114905
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    39. Bichao Song, Xueying Guo, Li Yang, Haiyue Yu, Xinlei Zong, Xiujuan Liu, Hao Wang, Zhongliang Xu, Zhenyang Lin, Weibo Yang. Rhodium(III)‐Catalyzed C‐H/O 2 Dual Activation and Macrocyclization: Synthesis and Evaluation of Pyrido[2,1‐a]isoindole Grafted Macrocyclic Inhibitors for Influenza H1N1. Angewandte Chemie International Edition 2023, 62 (15) https://doi.org/10.1002/anie.202218886
    40. Siddharth Yadav, Shahzaib Ahamad, Dinesh Gupta, Puniti Mathur. Lead optimization, pharmacophore development and scaffold design of protein kinase CK2 inhibitors as potential COVID-19 therapeutics. Journal of Biomolecular Structure and Dynamics 2023, 41 (5) , 1811-1827. https://doi.org/10.1080/07391102.2021.2024449
    41. Zhongzhen Yang, Illya Zalessky, Ryan G. Epton, Adrian C. Whitwood, Jason M. Lynam, William P. Unsworth. Ring Expansion Strategies for the Synthesis of Medium Sized Ring and Macrocyclic Sulfonamides. Angewandte Chemie 2023, 135 (13) https://doi.org/10.1002/ange.202217178
    42. Zhongzhen Yang, Illya Zalessky, Ryan G. Epton, Adrian C. Whitwood, Jason M. Lynam, William P. Unsworth. Ring Expansion Strategies for the Synthesis of Medium Sized Ring and Macrocyclic Sulfonamides. Angewandte Chemie International Edition 2023, 62 (13) https://doi.org/10.1002/anie.202217178
    43. Antonio Greco, Claudio Laudani, Marco Spagnolo, Federica Agnello, Denise Cristiana Faro, Simone Finocchiaro, Marco Legnazzi, Maria Sara Mauro, Placido Maria Mazzone, Giovanni Occhipinti, Carla Rochira, Lorenzo Scalia, Davide Capodanno. Pharmacology and Clinical Development of Factor XI Inhibitors. Circulation 2023, 147 (11) , 897-913. https://doi.org/10.1161/CIRCULATIONAHA.122.062353
    44. Hao Wang, Zhongyu Li, Xiangyang Chen, Jonathan J. Wong, Tongyu Bi, Xiankun Tong, Zhongliang Xu, Mingyue Zhen, Yunhui Wan, Li Tang, Bo Liu, Xinlei Zong, Dandan Xu, Jianping Zuo, Li Yang, Wei Huang, Kendall N. Houk, Weibo Yang. Multicomponent coupling and macrocyclization enabled by Rh(III)-catalyzed dual C–H activation: Macrocyclic oxime inhibitor of influenza H1N1. Chem 2023, 9 (3) , 607-623. https://doi.org/10.1016/j.chempr.2022.10.019
    45. Mounir Cherfi, Tarik Harit, Fouad Malek. New macrocycles based on pyrazole-tetrazole subunit: synthesis, characterization and their complexing properties toward heavy metal cations. Journal of Inclusion Phenomena and Macrocyclic Chemistry 2023, 103 (1-2) , 63-70. https://doi.org/10.1007/s10847-023-01177-2
    46. Geshuyi Chen, Zhe Chang, Pei Yuan, Si Wang, Yongxiu Yang, Xiaolei Liang, Depeng Zhao. Late-stage functionalization of 5-nitrofurans derivatives and their antibacterial activities. RSC Advances 2023, 13 (5) , 3204-3209. https://doi.org/10.1039/D2RA07676D
    47. Ziquan Zhao, Ruitian Dong, Keni Cui, Qidong You, Zhengyu Jiang. An updated patent review of Nrf2 activators (2020-present). Expert Opinion on Therapeutic Patents 2023, 33 (1) , 29-49. https://doi.org/10.1080/13543776.2023.2178299
    48. Yanyan Diao, Feng Hu, Zihao Shen, Honglin Li, . MacFrag: segmenting large-scale molecules to obtain diverse fragments with high qualities. Bioinformatics 2023, 39 (1) https://doi.org/10.1093/bioinformatics/btad012
    49. Durgesh Kumar, Kamlesh Kumari, Ramesh Chandra, Pallavi Jain, Lata Vodwal, Geetu Gambhir, Prashant Singh. A review targeting the infection by CHIKV using computational and experimental approaches. Journal of Biomolecular Structure and Dynamics 2022, 40 (17) , 8127-8141. https://doi.org/10.1080/07391102.2021.1904004
    50. Alessio Ciulli, Oliver Hsia. PROTAC Degraders. 2022, 317-356. https://doi.org/10.1002/9781119774198.ch9
    51. Xiang Qi, Songwei Jiang, Zi Hui, Yuan Gao, Yang Ye, Frédéric Lirussi, Carmen Garrido, Li Xu, Xingrui He, Renren Bai, Xiang-Yang Ye, Tian Xie. Design, synthesis and antitumor efficacy evaluation of a series of novel β-elemene-based macrocycles. Bioorganic & Medicinal Chemistry 2022, 74 , 117049. https://doi.org/10.1016/j.bmc.2022.117049
    52. Vinduja Puthanveedu, Karuvanthodi Muraleedharan. Phytochemicals as potential inhibitors for COVID-19 revealed by molecular docking, molecular dynamic simulation and DFT studies. Structural Chemistry 2022, 33 (5) , 1423-1443. https://doi.org/10.1007/s11224-022-01982-4
    53. Keisuke Baba, Yasushi Goto. Lorlatinib as a treatment for ALK-positive lung cancer. Future Oncology 2022, 18 (24) , 2745-2766. https://doi.org/10.2217/fon-2022-0184
    54. Marcus Baumann. Synthesis of Bioactive Heterocycles Exploiting Modern Continuous Flow Chemistry. 2022, 411-447. https://doi.org/10.1002/9781119757153.ch12
    55. Melanie Trobe, Martin Vareka, Till Schreiner, Patrick Dobrounig, Carina Doler, Ella B. Holzinger, Andreas Steinegger, Rolf Breinbauer. A Modular Synthesis of Teraryl‐Based α‐Helix Mimetics, Part 3: Iodophenyltriflate Core Fragments Featuring Side Chains of Proteinogenic Amino Acids. European Journal of Organic Chemistry 2022, 2022 (17) https://doi.org/10.1002/ejoc.202101278
    56. Chen Chen, Jun Ge, Ling He. Selective synthesis and reactivity expansion of α,β-unsaturated geminal diazides. Organic Chemistry Frontiers 2022, 9 (8) , 2116-2120. https://doi.org/10.1039/D2QO00008C
    57. Kleopas Y. Palate, Zhongzhen Yang, Adrian C. Whitwood, William P. Unsworth. Synthesis of medium-ring lactams and macrocyclic peptide mimetics via conjugate addition/ring expansion cascade reactions. RSC Chemical Biology 2022, 3 (3) , 334-340. https://doi.org/10.1039/D1CB00245G
    58. Samantha Stone, David J. Newman, Steven L. Colletti, Derek S. Tan. Cheminformatic analysis of natural product-based drugs and chemical probes. Natural Product Reports 2022, 39 (1) , 20-32. https://doi.org/10.1039/D1NP00039J
    59. Hao Wang, Zhongyu Li, Xiangyang Chen, Jonathan Wong, Tongyu Bi, Xiankun Tong, Zhongliang Xu, Mingyue Zheng, Yunhui Wan, Li Tang, Bo Liu, Xinlei Zong, Jianping Zuo, Li Yang, Wei Huang, Kendall N. Houk, Weibo Yang. Nitrene-Mediated Multicomponent Couplings and Macrocyclization by CH-Functionalization. SSRN Electronic Journal 2022, 7 https://doi.org/10.2139/ssrn.4138710
    60. Jiping Hao, Xueying Guo, Shijun He, Zhongliang Xu, Lu Chen, Zhongyu Li, Bichao Song, Jianping Zuo, Zhenyang Lin, Weibo Yang. Marine furanocembranoids-inspired macrocycles enabled by Pd-catalyzed unactivated C(sp3)-H olefination mediated by donor/donor carbenes. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-21484-x
    61. Wenting Li, Lun Tan, Zhixiong Zhang, Qiuqi Xia, Dongsheng Lei, Yuyan Li, Ting Zhang, Shaoxue Zeng, Xiutian Sima, Yanyan Wang. The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues. Biochemical and Biophysical Research Communications 2021, 565 , 29-35. https://doi.org/10.1016/j.bbrc.2021.05.086
    62. Piotr Raubo, Rodrigo J. Carbajo, William McCoull, Joanna Raubo, Morgan Thomas. Diversity-orientated synthesis of macrocyclic heterocycles using a double S N Ar approach. Organic & Biomolecular Chemistry 2021, 19 (28) , 6274-6290. https://doi.org/10.1039/D1OB00612F
    63. Tao Sun, Shijun He, Zhongliang Xu, Jianping Zuo, Yang Yu, Weibo Yang. Rh-Catalyzed C–H alkylation enabling modular synthesis of CF 3 -substituted benzannulated macrocyclic inhibitors of B cell responses. Organic & Biomolecular Chemistry 2021, 19 (16) , 3589-3594. https://doi.org/10.1039/D1OB00296A
    64. Rosa M. Álvarez, Ana Belén García, Concepción Riesco-Fagundo, José I. Martín, Carmen Varela, Antonio Rodríguez Hergueta, Esther González Cantalapiedra, Julen Oyarzabal, Bruno Di Geronimo, Milagros Lorenzo, M Isabel Albarrán, Antonio Cebriá, David Cebrián, Sonia Martínez-González, Carmen Blanco-Aparicio, Joaquín Pastor. Omipalisib inspired macrocycles as dual PI3K/mTOR inhibitors. European Journal of Medicinal Chemistry 2021, 211 , 113109. https://doi.org/10.1016/j.ejmech.2020.113109
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    66. Lu Chen, Haitian Quan, Zhongliang Xu, Hao Wang, Yuanzhi Xia, Liguang Lou, Weibo Yang. A modular biomimetic strategy for the synthesis of macrolide P-glycoprotein inhibitors via Rh-catalyzed C-H activation. Nature Communications 2020, 11 (1) https://doi.org/10.1038/s41467-020-16084-0
    67. Maximilian J. Hochmair, Hannah Fabikan, Oliver Illini, Christoph Weinlinger, Ulrike Setinek, Dagmar Krenbek, Helmut Prosch, Markus Rauter, Michael Schumacher, Ewald Wöll, Romana Wass, Elmar Brehm, Gudrun Absenger, Tatjana Bundalo, Peter Errhalt, Matthias Urban, Arschang Valipour. Later-Line Treatment with Lorlatinib in ALK- and ROS1-Rearrangement-Positive NSCLC: A Retrospective, Multicenter Analysis. Pharmaceuticals 2020, 13 (11) , 371. https://doi.org/10.3390/ph13110371
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    69. Ruixiang Cheng, Wenfang Xiong, Chaorong Qi, Lu Wang, Yanwei Ren, Huanfeng Jiang. Macrocyclization of 3-triflyloxybenzynes with tetrahydrofuran via an anionic thia-Fries rearrangement. Chemical Communications 2020, 56 (48) , 6495-6498. https://doi.org/10.1039/D0CC00135J
    70. Xiao Ding, Feng Ren. Leucine-rich repeat kinase 2 inhibitors: a patent review (2014-present). Expert Opinion on Therapeutic Patents 2020, 30 (4) , 275-286. https://doi.org/10.1080/13543776.2020.1729354
    71. Aimee K. Clarke, William P. Unsworth. A happy medium: the synthesis of medicinally important medium-sized rings via ring expansion. Chemical Science 2020, 11 (11) , 2876-2881. https://doi.org/10.1039/D0SC00568A
    72. Saumitra Sengupta, Goverdhan Mehta. Macrocyclization via C–H functionalization: a new paradigm in macrocycle synthesis. Organic & Biomolecular Chemistry 2020, 18 (10) , 1851-1876. https://doi.org/10.1039/C9OB02765C
    73. Rami A. Al-Horani. Factor XI(a) inhibitors for thrombosis: an updated patent review (2016-present). Expert Opinion on Therapeutic Patents 2020, 30 (1) , 39-55. https://doi.org/10.1080/13543776.2020.1705783
    74. Daniel Madsen, Carlos Azevedo, Iolanda Micco, Lars Kolster Petersen, Nils Jakob Vest Hansen. An overview of DNA-encoded libraries: A versatile tool for drug discovery. 2020, 181-249. https://doi.org/10.1016/bs.pmch.2020.03.001
    75. Sarah J. Martin, I-Jen Chen, A.W. Edith Chan, Nicolas Foloppe. Modelling the binding mode of macrocycles: Docking and conformational sampling. Bioorganic & Medicinal Chemistry 2020, 28 (1) , 115143. https://doi.org/10.1016/j.bmc.2019.115143
    76. Yanling Wang, Huan Ge, Disha Wang, Huan He, Lu Li, Yanyan Diao, Zihao Shen, Lili Zhu, Shiliang Li, Zhenjiang Zhao, Honglin Li. Design and Synthesis of a Series of Novel Macrocycle Janus Kinase 2 Inhibitors. Chinese Journal of Chemistry 2019, 37 (12) , 1259-1263. https://doi.org/10.1002/cjoc.201900316
    77. Anna V. Vologzhanina. Intermolecular Interactions in Functional Crystalline Materials: From Data to Knowledge. Crystals 2019, 9 (9) , 478. https://doi.org/10.3390/cryst9090478
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