2019: A Year in Review — AMRI's Contributions to Science

AMRI Research Publications

The following research articles appeared in peer-reviewed scientific journals that described innovations conceived by AMRI scientists. In most of these cases, these manuscripts were written by AMRI lead authors to communicate independent research, or were co-authored with customers to communicate research in collaboration with AMRI. Below are the bibliographies for these publications, including the abstracts, as they appeared with the original documents. The lead author name(s) are indicated.

1. “Comparison of Neisseria gonorrhoeae minimum inhibitory concentrations obtained using agar dilution versus microbroth dilution methods,” Journal of Journal of Microbiological Methods 2019, 157, 93-99.
Link: https://doi.org/10.1016/j.mimet.2019.01.001
Rachael K. Jacobson, Marysa J. Notaro and Grant J. Carr
Lead Discovery, AMRI Buffalo

2. “Practical enantioselective synthesis of (3S,4R)-3-hydroxypiperidine-4-carboxylic acid,” Tetrahedron Letters 2019, 60(20), 1357-1358.
Link: https://doi.org/10.1016/j.tetlet.2019.04.023
Nathan J. Line
AMRI Indianapolis

3. “Mogroside Via1, new isomer of Mogroside VI isolated from Luo Han Guo,” IOSR Journal of Applied Chemistry 2019, 12(5), 1-7.
Link: http://iosrjournals.org/iosr-jac/papers/vol12-issue5/Series-1/A1205010107.pdf
Romila Charan,¹ Krishna P. Devkota,¹ Mayank Bhanti,² Naresh C. Vadla,sup>2 Gil Ma,³ Alexandra Walsh,³ George Harrigan³ and Indra Prakash³,*
¹Analytical Development, AMRI Albany
²Analytical Development, AMRI Hyderabad
³The Coca-Cola Company, Atlanta, Georgia, USA

4. “Design and synthesis of selective Phosphodiesterase 4D (PDE4D) allosteric inhibitors for the treatment of Fragile X Syndrome and other brain disorders,” Journal of Medicinal Chemistry 2019, 62(10), 4884-4901.
Link: http://doi.org/10.1021/acs.jmedchem.9b00193
Mark E. Gurney*,¹ Richard A. Nugent,¹ Xuesheng Mo,¹ Janice A. Sindac,¹ Timothy J. Hagen,² David Fox, III,³ James M. O’Donnell,⁴ Chong Zhang,⁴ Ying Xu,⁴ Han-Ting Zhang,⁵ Vincent E. Groppi,⁶ Marc Bailie,⁷ Ronald E. White,⁸ Donna L. Romero,⁹ A. Samuel Vellekoop,¹⁰ Joel R. Walker,¹⁰ Matthew D. Surman,¹⁰ Lei Zhu¹⁰ and Robert F. Campbell^10
1Tetra Discovery Partners, Inc., Grand Rapids, Michigan, USA
²Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, Illinois, USA
³Beryllium Discovery Corp., Bainbridge Island, Washington, USA
⁴Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, New York, USA
⁵Departments of Behavioral Medicine & Psychiatry and Physiology, Pharmacology & Neuroscience, Rockefeller Neurosciences Institute, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA
⁶Michigan Drug Discovery, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA
⁷INDS Inc., Ann Arbor, Michigan, USA
⁸White Global Pharma Consultants, South Cranbury, New Jersey, USA
⁹Pharma-Vation Consulting, LLC, Chesterfield, Missouri, USA 10Medicinal Chemistry and CADD Departments, AMRI Albany

5. “The PO13 crystal structure of ROY,” CrystEngComm 2019, 21, 1363-1368.
Link: https://doi.org/10.1039/C8CE01930D
Karen S. Gushurst,¹ Jonas Nyman^2,3 and Stephan X. M. Boerrigter*,^1
1AMRI West Lafayette
²Small Molecule Design & Development, Eli Lilly and Company, Indianapolis, Indiana, USA
³School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA

6. “Design, synthesis, and preclinical efficacy of novel nonretinoid antagonists of Retinol-Binding Protein 4 in the mouse model of hepatic steatosis,” Journal of Medicinal Chemistry 2019, 62(11), 5470-5500.
Link: http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b01234
Christopher L. Cioffi,*,¹ Boglarka Racz,² Andras Varadi,² Emily E. Freeman,³ Michael P. Conlon,³ Ping Chen,³ Lei Zhu,⁴ Douglas B. Kitchen,⁴ Keith D. Barnes,³ William H. Martin,⁵ Paul G. Pearson,⁶ Graham Johnson,⁷ William S. Blaner⁸ and Konstantin Petrukhin*,^2
1Departments of Basic and Clinical Sciences and Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, USA
²Department of Ophthalmology, Columbia University Medical Center, New York, New York, USA Departments of
³Medicinal Chemistry and
⁴Computer Assisted Drug Discovery, AMRI Albany
⁵WHM Consulting LLC, Lyme, Connecticut, USA
⁶Pearson Pharma Partners, Westlake Village, California, USA
⁷NuPharmAdvise LLC, Sanbornton, New Hampshire, USA
⁸Department of Medicine, Columbia University Medical Center, New York, New York, USA

7. “Five new ent-atisene glycosides from Stevia rebaudiana,” Natural Product Communications 2019, 14(7), 1-9.
Link: https://journals.sagepub.com/doi/pdf/10.1177/1934578X19862651
Krishna P. Devkota,¹ Romila D. Charan,¹ Christopher Priedemann,¹ Ryan Donovan,¹ Tara M. Snyder,¹ Catherine Ramirez,¹ George Harrigan,² Gil Ma*,² and Indra Prakash^2
1Analytical Development, AMRI Albany
²The Coca-Cola Company, Atlanta, Georgia, USA

8. “Synthesis and pharmacological characterization of 2-(2,6-dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3- (hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a potent, subtype selective, and orally available positive allosteric modulator of the human Dopamine D1 receptor,” Journal of Medicinal Chemistry 2019, 62(19), 8711-8732.
Link: https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b00352
Junliang Hao,*,¹ James P. Beck,¹ John M. Schaus,¹ Joseph H. Krushinski,¹ Qi Chen,¹ Christopher D. Beadle,¹ Paloma Vidal,¹ Matthew R. Reinhard,¹ Bruce A. Dressman,¹ Steven M. Massey,¹ Serge L. Boulet,¹ Michael P. Cohen,¹ Brian M. Watson,¹ David Tupper,¹ Kevin M. Gardinier,¹ Jason Myers,¹ Anette M. Johansson,¹ Jeffery Richardson,¹ Daniel S. Richards,⁶ Erik J. Hembre,¹ David M. Remick,² David A. Coates,² Rajni M. Bhardwaj,² Benjamin A. Diseroad,² David Bender,² Greg Stephenson,² Craig D. Wolfangel,² Nuria Diaz,² Brian G. Getman,³ Xu-shan Wang,³ Beverly A. Heinz,³ Jeff W. Cramer,⁴ Xin Zhou,⁴ Deanna L. Maren,⁵ Julie F. Falcone,⁵ Rebecca A. Wright,⁵ Stephen N. Mitchell^,5 Guy Carter,⁵ Charles R. Yang,⁵ Robert F. Bruns¹ and Kjell A. Svensson^5
1Discovery Chemistry Research and Technologies
²Small Molecule Drug Developmen
³Quantitative Biology
⁴Drug Disposition
⁵Neuroscience Discovery, Lilly Research Laboratories, Eli Lilly & Co, Indianapolis, Indiana, USA
⁶AMRI UK Ltd, Erl Wood Manor, United Kingdom

9. “Structural and functional contributions of lipids to the stability and activity of the photosynthetic cytochrome b6f lipoprotein complex,” Journal of Biological Chemistry 2019, 294, 17758-17767.
Link: https://www.jbc.org/content/294/47/17758
Satarupa Bhaduri,¹ Huamin Zhang,² Satchal Erramilli³ and William A. Cramer*,^1
1Department of Biological Sciences, Purdue University, West Lafayette, Indiana, USA
²AMRI West Lafayette
³Department of Biochemistry and Molecular Biophysics, University of Chicago, Chicago, Illinois, USA

10. “Discovery of small-molecule antibiotics against a unique tRNA-mediated rRegulation of transcription in gram-positive bacteria,” ChemMedChem 2019, 14(7), 758-769.
Link: https://onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201800744
Kyla M. Frohlich,¹ Spencer F. Weintraub,¹ Janeen T. Bell,¹ Gabrielle C. Todd,¹ Ville Y. P. Väre,¹ Ryan Schneider,² Zachary A. Kloos,^1,3 Ebot S. Tabe,³ William A. Cantara,¹ Caren J. Stark,¹ Urenna J. Onwuanaibe,¹ Bryan C. Duffy,⁴ Maria Basanta-Sanchez,¹ Douglas B. Kitchen,⁴ Kathleen A. McDonough² and Paul F. Agris*,¹

AMRI Research Presented (Oral Papers and Posters)

AMRI scientists also delivered the following presentation during 2019, as a talk given at scientific meeting.

1. “Development of gamma-secretase modulators for the treatment of Alzheimer’s Disease,” 14th Annual Drug Discovery Chemistry Conference, San Diego, California, April 9, 2019.
   R. Jason Herr
   Medicinal Chemistry Department, AMRI Albany

AMRI Patents

1. Andres, P.; Diaz, K. M.; Smolenskaya, V. N. Solid forms of a toll-like receptor modulator. U.S. Patent 10,508,117, December 17, 2019.
2. Matsuo, Y.; Hisada, S.; Nakamura, Y.; Chakrabarti, A.; Rawat, M.; (Rai, S.; Satyanarayana, A. V.; Duan, Z.; Talukdar, A.; Ravula, S.; Decornez, H. Bicyclic compound and use thereof for inhibiting SUV39H2. U.S. Patent 10,508,109, December 17, 2019.
3. Wagner, S. L.; Mobley, W. C.; Tanzi, R. E.; Johnson, G.; Buckle, R.; Mayhew, N.; Herr; R. J.; Rynearson, K. D. Potent gamma-secretase modulators. U.S. Patent 10,472,346, November 12, 2019.
4. Han, Y.; Tummanapalli, S.; Siliphaivanh, P.; Spencer, K. Aryl sulfonamides as BLT1 antagonists. U.S. Patent 10,450,309, October 22, 2019.
5. Reichenbacher, K.; Duguid, R. J.; Ware, J. A.; Phillipson, D. Forms of R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3- fluorophenyl)-5- -hydroxymethyl oxazolidin-2-one dihydrogen phosphate. U.S. Patent 10,442,829, October 15, 2019.
6. Lippa, B. S.; Wu, X.; Li, Q.; Wrona, I.; Jackson, A. J.; Chenard, B. L.; Liu, C. M.; Liang, G.; Baevsky, M. F.; Earl,R. A.; Mcqueen, L.; Smit, J.; Cowans, B. A. Inhibiting the transient receptor potential A1 ion channel. U.S. Patent 10,428,072, October 1, 2019.
7. Petrukhin, K.; Cioffi, C.; Johnson, G.; Dobri, N.; Freeman, E.; Chen, P.; Conlon, M.; Zhu, L. Octahydrocyclopentapyrroles, their preparation and use. U.S. Patent 10,421,720, September 24, 2019.
8. Petrukhin, K.; Cioffi, C.; Johnson, G.; Allikmets, R.; Freeman, E.; Chen, P.; Conlon, M.; Zhu, L. Substituted 4-phenylpiperidines, their preparation and use. U.S. Patent 10,407,433, September 10, 2019.
9. Han, Y.; Tummanapalli, S.; Siliphaivanh, P.; Spencer, K. Aryl acylsulfonamides as BLT1 antagonists. U.S. Patent 10,370,368, August 6, 2019.
10. Gurney, M. E.; Hagen, T. J.; Mo, X.; Vellekoop, A. S.; Romero, D. L.; Campbell, R. F.; Walker, J. R.; Zhu, L. Heteroaryl inhibitors of PDE4. U.S. Patent 10,364,258, July 30, 2019.
11. 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 10,363,257, July 30, 2019.
12. Han, Y.; Lim, J.; Tummanapalli, S.; Siliphaivanh, P.; Spencer, K. Aryl acylsulfonamides as BLT1 antagonists. U.S. Patent 10,336,733, July 2, 2019.
13. Petrukhin, K.; Cioffi, C.; Johnson, G.; Dobri, N.; Freeman, E.; Chen, P.; Conlon, M.; Zhu, L. 4-phenylpiperidines, their preparation and use. U.S. Patent 10,273,243, April 30, 2019.
14. Tweedie, S.; Venkatraman, S.; Zeller, J. Continuous flow carboxylation reaction. U.S. Patent 10,273,212, April 30, 2019.
15. Speerschneider, A. C.; Yamashita, D. S.; Pitis, P. M.; Hawkins, M. J.; Liu, G.; Miskowski Daubert, T. A.; Yuan, C. C. K.; Borbo Kargbo, R.; Herr, R. J.; Romero, D.; Pacofsky, G. J. 6-membered aza-heterocyclic containing delta-opioid receptor modulating compounds, methods of using and making the same. U.S. Patent 10,246,436, April 2, 2019.
16. Kharenko, O.; Young, P. R.; Brown, S. D.; Duffy, B. C.; Liu, S. Guzzo, P. Inhibitors of bromodomains. U.S. Patent 10,231,953, March 19, 2019.
17. Liu, S.; Quinn, J. F.; Duffy, B. C.; Wang, R.; Jiang, M. X.; Martin, G. S.; Zhao, H.; Ellis, M.; Wagner, G. S.; Young, P. R. Substituted bicyclic compounds as bromodomain inhibitors. U.S. Patent 10,226,451, March 12, 2019.
18. Zeller, J. R.; Venkatraman, S.; Brot, E. C. A.; Iyer, S.; Hall, M. LFA-1 inhibitor and methods of preparation and polymorph thereof. U.S. Patent 10,214,517, February 26, 2019.
19. Scott, I. L.; Kuksa, V. A.; Gall, A.; Orme, M. W.; Gage, J.; Little, Jr., T. L.; Jiang, Q.; Rossiter, L. M.; McGee, Jr., K. F.; Kubota, R. Styrenyl derivative compounds for treating ophthalmic diseases and disorders. U.S. Patent 10,201,545, February 12, 2019.
20. Nonnenmacher, M,; Busch, T. Process for the preparation of aminoaryl- and aminoheteroaryl boronic acids and esters.U.S. Patent 10,196,406, February 5, 2019.
21. Jiang, M. X.; Molino, B. F.; Liu, S.; Wang, R.; Duffy, B. C.; Quinn, J. F.; Wagner, G. S. Substituted pyridines as bromodomain inhibitors. U.S. Patent 10,179,125, January 15, 2019.
22. Liu, S.; Quinn, J. F.; Duffy, B. C.; Wang, R.; Jiang, M. X.; Martin, G.S.; Zhao, H.; Ellis, M.; Wagner, G. S.; Young, P. R. Substituted bicyclic compounds as bromodomain inhibitors. U.S. Patent 10,166,215, January 1, 2019.

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