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Literature DB >> 25815146

Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors.

Frederik J R Rombouts¹, Gary Tresadern¹, Peter Buijnsters¹, Xavier Langlois¹, Fulgencio Tovar², Thomas B Steinbrecher³, Greet Vanhoof¹, Marijke Somers¹, José-Ignacio Andrés⁴, Andrés A Trabanco⁴.

Abstract

A novel series of pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the phenyl ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations. Rat pharmacokinetic data and in vivo receptor occupancy data are given for two representative compounds 6 and 12.

Entities: Chemical Gene Species

Keywords: PDE2 inhibitor; Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazine; phosphodiesterase 2 inhibitor; selective; tricycle

Year: 2015 PMID： 25815146 PMCID： PMC4360147 DOI： 10.1021/ml500463t

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

15 in total

1. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.

Authors: Richard A Friesner; Jay L Banks; Robert B Murphy; Thomas A Halgren; Jasna J Klicic; Daniel T Mainz; Matthew P Repasky; Eric H Knoll; Mee Shelley; Jason K Perry; David E Shaw; Perry Francis; Peter S Shenkin
Journal: J Med Chem Date: 2004-03-25 Impact factor: 7.446

Review 2. Phosphodiesterase inhibitors as potential cognition enhancing agents.

Authors: Christopher J Schmidt
Journal: Curr Top Med Chem Date: 2010 Impact factor: 3.295

Review 3. Advances in targeting cyclic nucleotide phosphodiesterases.

Authors: Donald H Maurice; Hengming Ke; Faiyaz Ahmad; Yousheng Wang; Jay Chung; Vincent C Manganiello
Journal: Nat Rev Drug Discov Date: 2014-04 Impact factor: 84.694

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. Discovery of a new series of [1,2,4]triazolo[4,3-a]quinoxalines as dual phosphodiesterase 2/phosphodiesterase 10 (PDE2/PDE10) inhibitors.

Authors: José-Ignacio Andrés; Peter Buijnsters; Meri De Angelis; Xavier Langlois; Frederik Rombouts; Andrés A Trabanco; Greet Vanhoof
Journal: Bioorg Med Chem Lett Date: 2012-12-01 Impact factor: 2.823

6. Structure-Based Design of a Potent, Selective, and Brain Penetrating PDE2 Inhibitor with Demonstrated Target Engagement.

Authors: Peter Buijnsters; Meri De Angelis; Xavier Langlois; Frederik J R Rombouts; Wendy Sanderson; Gary Tresadern; Alison Ritchie; Andrés A Trabanco; Greet VanHoof; Yves Van Roosbroeck; José-Ignacio Andrés
Journal: ACS Med Chem Lett Date: 2014-07-22 Impact factor: 4.345

7. Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues.

Authors: Viktor Lakics; Eric H Karran; Frank G Boess
Journal: Neuropharmacology Date: 2010-05-21 Impact factor: 5.250

Review 8. The role of phosphodiesterases in hippocampal synaptic plasticity.

Authors: Thomas M Sanderson; Emanuele Sher
Journal: Neuropharmacology Date: 2013-01-25 Impact factor: 5.250

9. Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia.

Authors: Patrick R Verhoest; Douglas S Chapin; Michael Corman; Kari Fonseca; John F Harms; Xinjun Hou; Eric S Marr; Frank S Menniti; Frederick Nelson; Rebecca O'Connor; Jayvardhan Pandit; Caroline Proulx-Lafrance; Anne W Schmidt; Christopher J Schmidt; Judith A Suiciak; Spiros Liras
Journal: J Med Chem Date: 2009-08-27 Impact factor: 7.446

Review 10. Efficient drug lead discovery and optimization.

Authors: William L Jorgensen
Journal: Acc Chem Res Date: 2009-06-16 Impact factor: 22.384

8 in total

1. First-in-Human Assessment of the Novel PDE2A PET Radiotracer 18F-PF-05270430.

Authors: Mika Naganawa; Rikki N Waterhouse; Nabeel Nabulsi; Shu-Fei Lin; David Labaree; Jim Ropchan; Sanela Tarabar; Nicholas DeMartinis; Adam Ogden; Anindita Banerjee; Yiyun Huang; Richard E Carson
Journal: J Nucl Med Date: 2016-04-21 Impact factor: 10.057

2. 1,3,4-Oxadiazole and Heteroaromatic-Fused 1,2,4-Triazole Synthesis using Diverted Umpolung Amide Synthesis.

Authors: Kazuyuki Tokumaru; Kalisankar Bera; Jeffrey N Johnston
Journal: Synthesis (Stuttg) Date: 2017-08-07 Impact factor: 3.157

3. Large scale relative protein ligand binding affinities using non-equilibrium alchemy.

Authors: Vytautas Gapsys; Laura Pérez-Benito; Matteo Aldeghi; Daniel Seeliger; Herman van Vlijmen; Gary Tresadern; Bert L de Groot
Journal: Chem Sci Date: 2019-12-02 Impact factor: 9.825

4. KI-catalyzed oxidative cyclization of α-keto acids and 2-hydrazinopyridines: efficient one-pot synthesis of 1,2,4-triazolo[4,3-a]pyridines.

Authors: De-Suo Yang; Juan Wang; Peng Gao; Zi-Jing Bai; Dong-Zhu Duan; Ming-Jin Fan
Journal: RSC Adv Date: 2018-09-21 Impact factor: 3.361

5. 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