A Year In Review — Curia's Contributions to Science in 2020

1. “Optimized plant compound with potent anti-biofilm activity across gram-negative species,” Bioorganic & Medicinal Chemistry 2020, 28(5), 115229.
https://doi.org/10.1016/j.bmc.2019.115229
Julie A. Lawrence,¹ Zhongping Huang,² Sivaprakash Rathinavelu,¹ Jin-Feng Hu,¹ Eliane Garo,¹ Michael Ellis,² Vanessa L. Norman,¹ Ronald Buckle,² Russell B. Williams,¹ Courtney M. Starks¹,* and Gary R.Eldridge^1
1Sequoia Sciences, Inc., St. Louis, Missouri, USA
²Medicinal Chemistry, AMRI Albany and AMRI Buffalo

2. “CSTI-300 (SMP-100): A Novel 5-HT3 receptor partial agonist with potential to treat patients with irritable bowel syndrome or carcinoid syndrome,” Journal of Pharmacology and Experimental Therapeutics 2020, 373(1), 122- 134.
https://doi.org/10.1124/jpet.119.261008
Alexander Roberts,¹ Gillian Grafton,¹ Andrew D. Powell,⁴ Kristian Brock,³ Chunlin Chen,⁵ Dejian Xie,⁶ Jinkun Huang,⁶ Shuang Liu,⁷ Alison J. Cooper,¹ Catherine A. Brady,¹ Omar Qureshi,¹ Zania Stamataki,² David D. Manning,⁸ Nicholas A. Moore,⁸ Bruce J. Sargent,⁹ Peter R. Guzzo⁷ and Nicholas M. Barnes¹,*
¹Neuropharmacology Research Group, Institute of Clinical Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
²Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
³Diagnostics, Drugs, Devices and Biomarkers, Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
⁴Department of Life Science, School of Health Sciences, Birmingham City University, Birmingham, UK
⁵Shanghai Medicilon Inc., Shanghai, China
⁶Chengdu SciMount Pharmatech Co. Ltd., Chengdu, China
⁷ConSynance Therapeutics, Inc., Rensselaer, New York, USA
⁸AMRI Albany
⁹Sargent Consulting, Hendersonville, North Carolina, USA

3. “Readily accessible sp3-rich cyclic hydrazine frameworks exploiting nitrogen fluxionality,” Chemical Science 2020, 11(6), 1636-1642.
https://doi.org/10.1039/C9SC04849A
Conor Dean, ¹ Sundaram Rajkumar, ¹ Stefan Roesner, ¹ Nessa Carson, ² Guy J. Clarkson, ¹ Martin Wills, ¹ Matthew Jones ³ and Michael Shipman1,*
¹Department of Chemistry, University of Warwick, Coventry, UK
²AMRI UK
³Eli Lilly & Company, Erl Wood Manor, Surrey, UK

4. “Discovery of [1,2,4]triazolo[1,5-a]pyridine derivatives as potent and orally bioavailable RORyt inverse agonists,” ACS Medicinal Chemistry Letters 2020, 11(4), 528-534.
https://doi.org/10.1021/acsmedchemlett.9b00649
Ryota Nakajima,¹,* Hiroyuki Oono,¹ Sakae Sugiyama,¹ Yohei Matsueda,¹ Tomohide Ida,¹ Shinji Kakuda,¹ Jun Hirata,¹ Atsushi Baba,¹ Akito Makino,¹ Ryo Matsuyama,¹ Ryan D. White,² Ryan P. Wurz,³ Youngsook Shin,³ Xiaoshan Min,⁴ Angel Guzman-Perez,² Zhulun Wang,⁵ Antony Symons,⁶ Sanjay K. Singh,⁷ Srinivasa Reddy Mothe,⁷ Sergei Belyakov,⁷ Anjan Chakrabarti⁷ and Satoshi Shuto^8,9,*
¹Teijin Institute for Bio-medical Research, Teijin Pharma Limited, Tokyo, Japan
²Department of Medicinal Chemistry, Amgen Discovery Research, Amgen Inc., Cambridge, Massachusetts, USA
³Department of ‡Medicinal Chemistry, Amgen Discovery Research, Amgen Inc., Thousand Oaks, California, USA Departments of
⁴Biologics
⁵Inflammation & Oncology Research and
⁶Molecular Engineering, Amgen Discovery Research, Amgen Inc., South San Francisco, California, USA
⁷AMRI Singapore Research Centre
⁸Faculty of Pharmaceutical Sciences and 9Center for Research and Education on Drug Discovery, Hokkaido University, Sapporo, Japan

5. “Imaging mutant Huntingtin aggregates: Development of a potential PET ligand,” Journal of Medicinal Chemistry 2020, 63(15), 8608-8633.
https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00955
Longbin Liu,¹,* Michael E. Prime,²,* Matt R. Lee,¹ Vinod Khetarpal,¹ Christopher J. Brown,² Peter D. Johnson,² Patricia Miranda-Azpiazu,³ Xuemei Chen,⁴ Daniel Clark-Frew,² Samuel Coe,² Randall Davis,⁴ Anthony Dickie,² Andreas Ebneth,² Simone Esposito,⁵ Elise Gadouleau,² Xinjie Gai,² Sebastien Galan,² Samantha Green,² Catherine Greenaway,² Paul Giles,² Christer Halldin,³ Sarah Hayes,² Todd Herbst,¹ Frank Herrmann,⁶ Manuela Heßmann,⁶ Zhisheng Jia,³ Alexander Kiselyov,¹ Adrian Kotey,² Thomas Krulle,² John E. Mangette,⁴ Richard W. Marston,² Sergio Menta,⁵ Matthew R. Mills,² Edith Monteagudo,⁵ Sangram Nag,³ Martina Nibbio,⁵ Laura Orsatti,⁵ Sabine Schaertl,⁶ Christoph Scheich,⁶ Joanne Sproston,² Vladimir Stepanov,³ Marie Svedberg,³ Akihiro Takano,³ Malcolm Taylor,² Wayne Thomas,² Miklós Toth,³ Darshan Vaidya,² Katarina Vanräs,³ Derek Weddell,² Ian Wigginton,² John Wityak,¹ Ladislav Mrzljak,¹ Ignacio Munoz-Sanjuan,¹ Jonathan A. Bard¹ and Celia Dominguez¹,*
¹CHDI Foundation, Los Angeles, California, USA
²Evotec UK Ltd, Abingdon, UK
³Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
⁴AMRI Albany, USA
⁵IRBM, IRBM Science Park S.p.A., Pomezia, Italy
⁶Evotec AG, Hamburg, Germany

6. “Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators,” Bioorganic & Medicinal Chemistry 2020, 28(22), 115734.
https://doi.org/10.1016/j.bmc.2020.115734
Kevin D. Rynearson,¹,* Ronald N. Buckle,² R. Jason Herr,² Nicholas J. Mayhew,², Xinchao Chen,² William D. Paquette,² Samuel A. Sakwa,² Jinhai Yang,² Keith D. Barnes,² Phuong Nguyen,¹ William C. Mobley,¹ Graham Johnson,³ Juinn H. Lin,⁴ Rudolph E. Tanzi⁵ and Steven L. Wagner^1,6
1Department of Neurosciences, University of California, San Diego, La Jolla, California, USA
²Department of Medicinal Chemistry, AMRI Albany
³NuPharmAdvise, Sanbornton, New Hampshire, USA
⁴Biopharm Consulting Partners, Ambler, Pennsylvania, USA
⁵Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, USA
⁶Veterans Administrative San Diego Healthcare System, La Jolla, California, USA

7. “Design, synthesis and biological evaluation of novel Pseudomonas aeruginosa DNA gyrase B inhibitors,” Bioorganic Chemistry 2020, 100, 103905.
https://doi.org/10.1016/j.bioorg.2020.103905
Sridhar Jogula,¹ Vagolu Siva Krishna,¹ Nikhila Meda,¹ Vadla Balraju² and Dharmarajan Sriram¹,*
¹Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad, India
²Albany Molecular Research Hyderabad Research Centre

8. “Structural analysis of the catalytic domain of Artemis endonuclease/SNM1C reveals distinct structural features,” The Journal of Biological Chemistry 2020, 295(35), 12368-12377.
https://doi.org/10.1074/jbc.RA120.014136
Md Fazlul Karim,¹ Shanshan Liu,¹ Adrian R. Laciak,¹ Leah Volk,¹ Mary Koszelak-Rosenblum,¹ Michael R. Lieber,² Mousheng Wu,³ Rory Curtis,¹ Nian N. Huang,¹ Grant Carr¹,* and Guangyu Zhu¹,*
¹Discovery Biology, Albany Molecular Research Inc., Buffalo
²USC Norris Comprehensive Cancer Center, Departments of Pathology, Biochemistry & Molecular Biology, and Molecular Microbiology & Immunology, and the Molecular and Computational Biology Section of the Department of Biological Sciences, University of Southern California Keck School of Medicine, Los Angeles, California, USA
³Chemistry Department, Drug Discovery Division, Southern Research, Birmingham, Alabama, USA

9. “Towards developing discriminating dissolution methods for formulations containing nano-particulates in solution; The impact of particle drift and drug activity in solution,” Molecular Pharmaceutics 2020, 17(11), 4125-4140.
https://doi.org/10.1021/acs.molpharmaceut.0c00599
Freddy A. Arce,¹ Nico Setiawan,² Heather R. Campbell,¹ Xingyu Lu,^3,4 Matthew J. Nethercott,⁵ Paul Bummer,¹ Yongchao Su^3,6,7 and Patrick J. Marsac¹,*
¹Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA
²Albany Molecular Research Inc., West Lafayette
³Pharmaceutical Sciences, Merck & Co., Kenilworth, New Jersey, USA
⁴Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, Hangzhou, Zhejiang, China
⁵Kansas Analytical Services, LLC, Loveland, Colorado, USA
⁶Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA
⁷Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, Indiana, USA

10. “In situ XRPD study of the ambient-pressure synthesis of nonstoichiometric Ag3O from Ag-Ag2O thin films: Phase abundance, unit-cell parameters, and c/a as a function of temperature and time,” Powder Diffraction 2020, 35(4), 247-261.
https://doi.org/10.1017/S0885715620000561
Paul J. Schields,* Nicholas Dunwoody, David Field and Zachary Wilson
AMRI West Lafayette

Patents

1. Krasutsky, S.; Tweedie, S.; Ramamoorthy, G. Process for preparing 1,4-dihydro-4-oxoquinoline-2-carboxylates and 4-aminoquinoline compounds therefrom. U.S. Patent 10,875,831, December 29, 2020.
2. Smith, A.; White, H. S.; Tavares, F. X.; Krasutsky, S.; Chen, J.; Dorrow, R. L.; Zhong, H. Synthesis of n-(heteroaryl)- pyrrolo[3,2-d]pyrimidin-2-amines. U.S. Patent 10,865,210, December 15, 2020.
3. Mehta, S. V.; Teng, J.; Selbo, J. Polymorphs of cocrystals of epigallocatechin gallate and caffeine. U.S. Patent 10,813,938, October 27, 2020.
4. Petrukhin, K.; Cioffi, C.; Johnson, G.; Dobri, N.; Freeman, E.; Chen, P.; Conlon, M.; Zhu, L. Octahydropyrrolopyrroles their preparation and use. U.S. Patent 10,787,453, September 29, 2020.
5. Quinn, J. F.; Duffy, B. C.; Liu, S.; Wang, R.; Jiang, M. X.; Martin, G. S.; Wagner, G. S.; Young, P. R. Bicyclic bromodomain inhibitors. U.S. Patent 10,772,892, September 15, 2020.
6. Grisenti, P.; Argese, M.; Pengo, D.; Grilli, M. D.; Fumagalli, E.; Motta, G. Polymorphic mixture of Rifaximin and its use for the preparation of solid formulations. U.S. Patent 10,745,415, August 18, 2020.
7. DeCrescenzo, G.; Welsch, D.; Vlahova, P. I.; Boerrigter, S. X. M.; Aronov, A.; Keshavarz-Shokri, A.; Scangas, A. N.; Stavropoulos, K.; Littler, B.; Kadiyala, I. N.; Alargova, R. G. Crystalline forms of C.sub.21H.sub.22Cl.sub.2N.sub.4O- sub.2. U.S. Patent 10,738,027, August 11, 2020.
8. Jiang, X.; Walling, J. A.; Bevill, M. J.; Seadeek, C. S.; Smit, J. P. Co-crystal forms of a novobiocin analog and proline. U.S. Patent 10,717,755, July 21, 2020.
9. Jiang, M. X.; Molino, B. F.; Liu, S.; Wang, R.; Duffy, B. C.; Quinn, J. F.; Wagner, G. S. Substituted pyridinones as bromodomain inhibitors. U.S. Patent 10,710,992, July 14, 2020.
10. Greer, E.; Anderson, S.; Maloney, M.; Yu, S.; Albert, E.; Rigsbee, E. Solid state forms of (S)-2-(((S)-6,8-difluoro- 1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2- -methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)-pentanamide and uses thereof. U.S. Patent 10,710,966, July 14, 2020.
11. Surman, M.; Thottathil, J. K.; Golden, K.; Pasetto, P.; Jin, X.; Jiang, X.; Camara, F. Methods and compositions for preventing opioid abuse. U.S. Patent 10,695,342, June 30, 2020.
12. Cacatian, S.; Claremon, D. A.; Dillard, L. W.; Dong, C.; Fan, Y.; Jia, L.; Lotesta, S. D.; Marcus, A.; Morales-Ramos, A.; Singh, S. B.; Venkatraman, S.; Yuan, J.; Zheng, Y.; Zhuang, L.; Parent, S. D.; Houston, T. L. Inhibitors of the menin-MLL interaction. U.S. Patent 10,683,302, June 16, 2020.
13. Emanuele, R. M.; Shattock-Gordon, T.; Williford, T.; Andres, M.; Andres, P. Solid forms of cannabidiol and uses thereof. U.S. Patent 10,604,467, March 31, 2020.
14. Herr, R. J.; Gregg, B. T.; Geiss, W. B. Methods and intermediates for the preparation of omacetaxine and cephalotaxine derivatives thereof. U.S. Patent 10,597,401, March 24, 2020.
15. Perez Encabo, A.; Turiel Hernandez, J.; Fernandez Sainz, Y.; Lorente Bonde-Larsen, A. Process and intermediates for the preparation of benzo[b]thiophene compounds. U.S. Patent 10,597,386, March 24, 2020.
16. Greer, E.; Anderson, S.; Maloney, M.; Yu, S.; Albert, E.; Rigsbee, E. Solid state forms of (S)-2-(((S)-6,8-difluoro- 1,2,3,4-tetrahydronaphthalen-2-yl)amino)-N-(1-(2- -methyl-1-(neopentylamino)propan-2-yl)-1H-imidazol-4-yl)-pentanamide and uses thereof. U.S. Patent 10,590,087, March 17, 2020.
17. Petrukhin, K.; Cioffi, C.; Johnson, G.; Dobri, N.; Freeman, E.; Chen, P.; Conlon, M.; Zhu, L. N-alkyl-2- phenoxyethanamines, their preparation and use. U.S. Patent 10,570,148, February 25, 2020.
18. Grisenti, P.; Argese, M.; Pengo, D.; Grilli, M. D.; Fumagalli, E.; Motta, G. Polymorphic mixture of Rifaximin and its use for the preparation of solid formulations. U.S. Patent 10,556,915, February 11, 2020.
19. Statler, J. A.; Shaw, A. A.; Imbert, D. C.; Nelson, J. L.; Andres, P.; McQueen, L. L.; Boerrigter, S. X. M.; Selbo, J. G.; Andres, M. C. Glycopyrrolate salts. U.S. Patent 10,548,875, February 4, 2020.
20. Statler, J. A.; Shaw, A. A.; Imbert, D. C.; Nelson, J. L.; Andres, P.; McQueen, L. L.; Boerrigter, S. X. M.; Selbo, J. G.; Andres, M. C. Glycopyrrolate salts. U.S. Patent 10,543,192, January 28, 2020.

Compiled by R. Jason Herr, Ph.D. and Wendy Quinn, AMRI