Literature DB >> 30128073

Structure-Guided Design and Procognitive Assessment of a Potent and Selective Phosphodiesterase 2A Inhibitor.

Shawn J Stachel1, Richard Berger1, Ashley B Nomland1, Anthony T Ginnetti1, Daniel V Paone1, Deping Wang1, Vanita Puri1, Henry Lange1, Jason Drott1, Jun Lu1, Jacob Marcus1, Michael P Dwyer1, Sokreine Suon1, Jason M Uslaner1, Sean M Smith1.   

Abstract

Herein we describe the development of a series of pyrazolopyrimidinone phosphodiesterase 2A (PDE2) inhibitors using structure-guided lead identification and design. The series was derived from informed chemotype replacement based on previously identified internal leads. The initially designed compound 3, while potent on PDE2, displayed unsatisfactory selectivity against the other PDE2 isoforms. Compound 3 was subsequently optimized for improved PDE2 activity and isoform selectivity. Insights into the origins of PDE2 selectivity are described and verified using cocrystallography. An optimized lead, 4, demonstrated improved performance in both a rodent and a nonhuman primate cognition model.

Entities:  

Year:  2018        PMID： 30128073      PMCID： PMC6088355          DOI： 10.1021/acsmedchemlett.8b00214

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


  17 in total

1.  Characterization of human phosphodiesterase 12 and identification of a novel 2'-5' oligoadenylate nuclease - The ectonucleotide pyrophosphatase/phosphodiesterase 1.

Authors:  Jesper B Poulsen; Kasper R Andersen; Karina H Kjær; Anna L Vestergaard; Just Justesen; Pia M Martensen
Journal:  Biochimie       Date:  2012-01-24       Impact factor: 4.079

2.  Predicting the severity of everyday functional disability in people with schizophrenia: cognitive deficits, functional capacity, symptoms, and health status.

Authors:  Philip D Harvey; Martin Strassnig
Journal:  World Psychiatry       Date:  2012-06       Impact factor: 49.548

3.  The inverted "u-shaped" dose-effect relationships in learning and memory: modulation of arousal and consolidation.

Authors:  Elisabetta Baldi; Corrado Bucherelli
Journal:  Nonlinearity Biol Toxicol Med       Date:  2005-01

Review 4.  PDE2 inhibition: potential for the treatment of cognitive disorders.

Authors:  Laurent Gomez; J Guy Breitenbucher
Journal:  Bioorg Med Chem Lett       Date:  2013-10-24       Impact factor: 2.823

5.  Importance of R-CF3···O Tetrel Bonding Interactions in Biological Systems.

Authors:  Xavier García-LLinás; Antonio Bauzá; Saikat K Seth; Antonio Frontera
Journal:  J Phys Chem A       Date:  2017-07-11       Impact factor: 2.781

Review 6.  Novel Phosphodiesterase Inhibitors for Cognitive Improvement in Alzheimer's Disease.

Authors:  Yinuo Wu; Zhe Li; Yi-You Huang; Deyan Wu; Hai-Bin Luo
Journal:  J Med Chem       Date:  2018-02-05       Impact factor: 7.446

7.  The relationship between glycine transporter 1 occupancy and the effects of the glycine transporter 1 inhibitor RG1678 or ORG25935 on object retrieval performance in scopolamine impaired rhesus monkey.

Authors:  Donnie Eddins; Terence G Hamill; Vanita Puri; Christopher E Cannon; Jeffrey A Vivian; Sandra M Sanabria-Bohórquez; Jacquelynn J Cook; John A Morrow; Fiona Thomson; Jason M Uslaner
Journal:  Psychopharmacology (Berl)       Date:  2013-09-20       Impact factor: 4.530

8.  Indole acids as a novel PDE2 inhibitor chemotype that demonstrate pro-cognitive activity in multiple species.

Authors:  Shawn J Stachel; Melissa S Egbertson; Jenny Wai; Michelle Machacek; Dawn M Toolan; John Swestock; Donnie M Eddins; Vanita Puri; Georgia McGaughey; Hua-Poo Su; Debbie Perlow; Deping Wang; Lei Ma; Gopal Parthasarathy; John C Reid; Pravien D Abeywickrema; Sean M Smith; Jason M Uslaner
Journal:  Bioorg Med Chem Lett       Date:  2018-02-10       Impact factor: 2.823

9.  The identification of a novel lead class for phosphodiesterase 2 inhibition by fragment-based drug design.

Authors:  Ashley B Forster; Pravien Abeywickrema; Jaime Bunda; Christopher D Cox; Tamara D Cabalu; Melissa Egbertson; John Fay; Krista Getty; Dawn Hall; Maria Kornienko; Jun Lu; Gopal Parthasarathy; John Reid; Sujata Sharma; William D Shipe; Sean M Smith; Stephen Soisson; Shawn J Stachel; Hua-Poo Su; Deping Wang; Richard Berger
Journal:  Bioorg Med Chem Lett       Date:  2017-10-23       Impact factor: 2.823

10.  Discovery of Clinical Candidate N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915): A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders.

Authors:  Satoshi Mikami; Shinji Nakamura; Tomoko Ashizawa; Izumi Nomura; Masanori Kawasaki; Shigekazu Sasaki; Hideyuki Oki; Hironori Kokubo; Isaac D Hoffman; Hua Zou; Noriko Uchiyama; Kosuke Nakashima; Naomi Kamiguchi; Haruka Imada; Noriko Suzuki; Hiroki Iwashita; Takahiko Taniguchi
Journal:  J Med Chem       Date:  2017-09-05       Impact factor: 7.446
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  2 in total

1.  Long-Timescale Simulations Revealed Critical Non-Conserved Residues of Phosphodiesterases Affecting Selectivity of BAY60-7550.

Authors:  Qing Liu; Menghua Song; Yue Qiu; Elaine Lai-Han Leung; Qiang Huang; Xiaojun Yao
Journal:  Comput Struct Biotechnol J       Date:  2022-09-13       Impact factor: 6.155

2.  Chemical Space Exploration with Active Learning and Alchemical Free Energies.

Authors:  Yuriy Khalak; Gary Tresadern; David F Hahn; Bert L de Groot; Vytautas Gapsys
Journal:  J Chem Theory Comput       Date:  2022-09-23       Impact factor: 6.578
  2 in total

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