Literature DB >> 31413793

Quick Building Blocks (QBB): An Innovative and Efficient Business Model To Speed Medicinal Chemistry Analog Synthesis.

Christopher J Helal1, Mark Bundesmann1, Susan Hammond1, Melissa Holmstrom2, Jacquelyn Klug-McLeod1, Bruce A Lefker3, Dale McLeod1, Chakrapani Subramanyam1, Oleg Zakaryants4, Sylvie Sakata2.   

Abstract

Many pharmaceutical companies have invested millions of dollars in establishing internal chemical stores to provide reliable access to large numbers of building blocks (BB) for the synthesis of new molecules, especially for the timely design and execution of parallel (library) synthesis. Recognizing budget and logistical limitations, we required a more economically scalable process to provide diverse BB. We disclose a novel business partnership that achieves the goals of just-in-time, economical access to commercial BB that increases chemical space coverage and accelerates the synthesis of new drug candidates. We believe that this model can be of benefit to companies of all sizes that are engaged in drug discovery by reducing cost, increasing diversity of analog molecules in a time-conscious manner, and reducing BB inventory. More efficient use of BB by customers may allow commercial vendors to devote a greater portion of their resources to preparing novel BB that increase chemical diversity as opposed to resynthesizing out-of-stock compounds that are inaccessible within company compound collections.

Entities:  

Year:  2019        PMID: 31413793      PMCID: PMC6691476          DOI: 10.1021/acsmedchemlett.9b00205

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN: 1948-5875            Impact factor:   4.345


  20 in total

Review 1.  Factors determining the selection of organic reactions by medicinal chemists and the use of these reactions in arrays (small focused libraries).

Authors:  Tony W J Cooper; Ian B Campbell; Simon J F Macdonald
Journal:  Angew Chem Int Ed Engl       Date:  2010-10-25       Impact factor: 15.336

2.  Identification of a brain penetrant PDE9A inhibitor utilizing prospective design and chemical enablement as a rapid lead optimization strategy.

Authors:  Patrick R Verhoest; Caroline Proulx-Lafrance; Michael Corman; Lois Chenard; Christopher J Helal; Xinjun Hou; Robin Kleiman; Shenping Liu; Eric Marr; Frank S Menniti; Christopher J Schmidt; Michelle Vanase-Frawley; Anne W Schmidt; Robert D Williams; Frederick R Nelson; Kari R Fonseca; Spiros Liras
Journal:  J Med Chem       Date:  2009-12-24       Impact factor: 7.446

3.  Organic chemistry. Nanomole-scale high-throughput chemistry for the synthesis of complex molecules.

Authors:  Alexander Buitrago Santanilla; Erik L Regalado; Tony Pereira; Michael Shevlin; Kevin Bateman; Louis-Charles Campeau; Jonathan Schneeweis; Simon Berritt; Zhi-Cai Shi; Philippe Nantermet; Yong Liu; Roy Helmy; Christopher J Welch; Petr Vachal; Ian W Davies; Tim Cernak; Spencer D Dreher
Journal:  Science       Date:  2014-11-20       Impact factor: 47.728

Review 4.  DNA-encoded chemistry: enabling the deeper sampling of chemical space.

Authors:  Robert A Goodnow; Christoph E Dumelin; Anthony D Keefe
Journal:  Nat Rev Drug Discov       Date:  2016-12-09       Impact factor: 84.694

Review 5.  Designing novel building blocks is an overlooked strategy to improve compound quality.

Authors:  Frederick W Goldberg; Jason G Kettle; Thierry Kogej; Matthew W D Perry; Nick P Tomkinson
Journal:  Drug Discov Today       Date:  2014-10-02       Impact factor: 7.851

6.  Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors.

Authors:  Michelle M Claffey; Christopher J Helal; Patrick R Verhoest; Zhijun Kang; Kristina S Fors; Stanley Jung; Jiaying Zhong; Mark W Bundesmann; Xinjun Hou; Shenping Lui; Robin J Kleiman; Michelle Vanase-Frawley; Anne W Schmidt; Frank Menniti; Christopher J Schmidt; William E Hoffman; Mihaly Hajos; Laura McDowell; Rebecca E O'Connor; Mary Macdougall-Murphy; Kari R Fonseca; Stacey L Becker; Frederick R Nelson; Spiros Liras
Journal:  J Med Chem       Date:  2012-10-12       Impact factor: 7.446

7.  Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design.

Authors:  Katherine L Lee; Catherine M Ambler; David R Anderson; Brian P Boscoe; Andrea G Bree; Joanne I Brodfuehrer; Jeanne S Chang; Chulho Choi; Seungwon Chung; Kevin J Curran; Jacqueline E Day; Christoph M Dehnhardt; Ken Dower; Susan E Drozda; Richard K Frisbie; Lori K Gavrin; Joel A Goldberg; Seungil Han; Martin Hegen; David Hepworth; Heidi R Hope; Satwik Kamtekar; Iain C Kilty; Arthur Lee; Lih-Ling Lin; Frank E Lovering; Michael D Lowe; John P Mathias; Heidi M Morgan; Elizabeth A Murphy; Nikolaos Papaioannou; Akshay Patny; Betsy S Pierce; Vikram R Rao; Eddine Saiah; Ivan J Samardjiev; Brian M Samas; Marina W H Shen; Julia H Shin; Holly H Soutter; Joseph W Strohbach; Peter T Symanowicz; Jennifer R Thomason; John D Trzupek; Richard Vargas; Fabien Vincent; Jiangli Yan; Christoph W Zapf; Stephen W Wright
Journal:  J Med Chem       Date:  2017-06-14       Impact factor: 7.446

8.  Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor.

Authors:  Christopher J Helal; Eric P Arnold; Tracey L Boyden; Cheng Chang; Thomas A Chappie; Kimberly F Fennell; Michael D Forman; Mihaly Hajos; John F Harms; William E Hoffman; John M Humphrey; Zhijun Kang; Robin J Kleiman; Bethany L Kormos; Che-Wah Lee; Jiemin Lu; Noha Maklad; Laura McDowell; Scot Mente; Rebecca E O'Connor; Jayvardhan Pandit; Mary Piotrowski; Anne W Schmidt; Christopher J Schmidt; Hirokazu Ueno; Patrick R Verhoest; Edward X Yang
Journal:  J Med Chem       Date:  2017-06-16       Impact factor: 7.446

9.  Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK).

Authors:  Kim Huard; Kay Ahn; Paul Amor; David A Beebe; Kris A Borzilleri; Boris A Chrunyk; Steven B Coffey; Yang Cong; Edward L Conn; Jeffrey S Culp; Matthew S Dowling; Matthew F Gorgoglione; Jemy A Gutierrez; John D Knafels; Erik A Lachapelle; Jayvardhan Pandit; Kevin D Parris; Sylvie Perez; Jeffrey A Pfefferkorn; David A Price; Brian Raymer; Trenton T Ross; Andre Shavnya; Aaron C Smith; Timothy A Subashi; Gregory J Tesz; Benjamin A Thuma; Meihua Tu; John D Weaver; Yan Weng; Jane M Withka; Gang Xing; Thomas V Magee
Journal:  J Med Chem       Date:  2017-09-11       Impact factor: 7.446

10.  Academia-industry symbiosis in organic chemistry.

Authors:  Quentin Michaudel; Yoshihiro Ishihara; Phil S Baran
Journal:  Acc Chem Res       Date:  2015-02-23       Impact factor: 22.384

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  3 in total

1.  Decarbonylative Pd-Catalyzed Suzuki Cross-Coupling for the Synthesis of Structurally Diverse Heterobiaryls.

Authors:  Alejandro Cervantes-Reyes; Aaron C Smith; Gary M Chinigo; David C Blakemore; Michal Szostak
Journal:  Org Lett       Date:  2022-02-24       Impact factor: 6.072

Review 2.  DNA-Encoded Chemistry: Drug Discovery from a Few Good Reactions.

Authors:  Patrick R Fitzgerald; Brian M Paegel
Journal:  Chem Rev       Date:  2020-10-12       Impact factor: 72.087

Review 3.  Fragment-based drug discovery: opportunities for organic synthesis.

Authors:  Jeffrey D St Denis; Richard J Hall; Christopher W Murray; Tom D Heightman; David C Rees
Journal:  RSC Med Chem       Date:  2020-12-24
  3 in total

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