Display options
Cite
Garner P, Cox PB, Rathnayake U, et al. Design and Synthesis of Pyrrolidine-based Fragments That Sample Three-dimensional Molecular Space. ACS Med Chem Lett. 2019;10(5):811-815doi: 10.1021/acsmedchemlett.9b00070.
Garner, P., Cox, P. B., Rathnayake, U., Holloran, N., & Erdman, P. (2019). Design and Synthesis of Pyrrolidine-based Fragments That Sample Three-dimensional Molecular Space. ACS medicinal chemistry letters, 10(5), 811-815. https://doi.org/10.1021/acsmedchemlett.9b00070
Garner, Philip, et al. "Design and Synthesis of Pyrrolidine-based Fragments That Sample Three-dimensional Molecular Space." ACS medicinal chemistry letters vol. 10,5 (2019): 811-815. doi: https://doi.org/10.1021/acsmedchemlett.9b00070
Garner P, Cox PB, Rathnayake U, Holloran N, Erdman P. Design and Synthesis of Pyrrolidine-based Fragments That Sample Three-dimensional Molecular Space. ACS Med Chem Lett. 2019 Apr 12;10(5):811-815. doi: 10.1021/acsmedchemlett.9b00070. eCollection 2019 May 09. PMID: 31098004; PMCID: PMC6511948.
Copy Download .nbib Format: NLM
Share it on

ACS Med Chem Lett. 2019 Apr 12;10(5):811-815. doi: 10.1021/acsmedchemlett.9b00070. eCollection 2019 May 09.

Design and Synthesis of Pyrrolidine-based Fragments That Sample Three-dimensional Molecular Space.

ACS medicinal chemistry letters

Philip Garner, Philip B Cox, Upendra Rathnayake, Nicholas Holloran, Paul Erdman

Affiliations

  1. Department of Chemistry, Washington State University, Pullman, Washington 99164-4630, United States.
  2. Discovery Chemistry and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, Illinois 60064-6217, United States.

PMID: 31098004 PMCID: PMC6511948 DOI: 10.1021/acsmedchemlett.9b00070

Abstract

Fragment-based drug discovery (FBDD) is a well-established technology for lead compound generation in drug discovery. As this technology has evolved, the design of fragments for screening has also evolved to engender not just an understanding of the role of modulating the physicochemical properties of fragments (Rule of Three, Ro3) but also the importance and implications of incorporating shape and, in particular, 3D characteristics into fragments. Herein, we describe the design and synthesis of pyrrolidine-based fragments with good fragment-like (Ro3) physicochemical properties that effectively sample three-dimensional molecular space.

Conflict of interest statement

The authors declare the following competing financial interest(s): P.C. and P.E. are employees of AbbVie, and U.R. was an employee during the time of this study. The design, study content, and financi

References

  1. J Am Chem Soc. 2002 Nov 13;124(45):13400-1 - PubMed
  2. Org Lett. 2005 Oct 27;7(22):5055-8 - PubMed
  3. Org Lett. 2006 Aug 17;8(17):3647-50 - PubMed
  4. J Org Chem. 2008 Apr 18;73(8):3094-102 - PubMed
  5. J Chem Inf Model. 2008 May;48(5):941-8 - PubMed
  6. J Am Chem Soc. 2008 Dec 24;130(51):17250-1 - PubMed
  7. J Med Chem. 2009 Nov 12;52(21):6752-6 - PubMed
  8. Org Lett. 2010 Dec 17;12(24):5608-11 - PubMed
  9. Angew Chem Int Ed Engl. 2011 May 16;50(21):4893-6 - PubMed
  10. J Chem Inf Model. 2012 Oct 22;52(10):2516-25 - PubMed
  11. J Org Chem. 2013 Sep 20;78(18):9471-6 - PubMed
  12. Chem Commun (Camb). 2014 Oct 25;50(83):12434-46 - PubMed
  13. J Med Chem. 2014 Dec 26;57(24):10257-74 - PubMed
  14. Prog Biophys Mol Biol. 2014 Nov-Dec;116(2-3):82-91 - PubMed
  15. Chem Rev. 2015 Jun 10;115(11):5366-412 - PubMed
  16. Essays Biochem. 2017 Nov 8;61(5):453-464 - PubMed
  17. J Am Chem Soc. 2019 Jan 16;141(2):961-971 - PubMed

Publication Types