Literature DB >> 25698055

Structural requirements for TLR7-selective signaling by 9-(4-piperidinylalkyl)-8-oxoadenine derivatives.

Hélène G Bazin1, Yufeng Li1, Juhienah K Khalaf1, Sandra Mwakwari1, Mark T Livesay1, Jay T Evans1, David A Johnson1.   

Abstract

We report the synthesis and biological evaluation of a new series of 8-oxoadenines substituted at the 9-position with a 4-piperidinylalkyl moiety. In vitro evaluation of the piperidinyl-substituted oxoadenines 3a-g in human TLR7- or TLR8-transfected HEK293 cells and in human PBMCs indicated that TLR7/8 selectivity/potency and cytokine induction can be modulated by varying the length of the alkyl linker. Oxoadenine 3f containing a 5-carbon linker was found to be the most potent TLR7 agonist and IFNα inducer in the series whereas 3b possessing a 1-carbon linker was the most potent TLR8 agonist.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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Keywords:  Immunostimulants; Oxoadenine; TLR7/8 agonist

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Year:  2015        PMID： 25698055      PMCID： PMC4357173          DOI： 10.1016/j.bmcl.2015.01.037

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  21 in total

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2.  Synthesis and biological evaluation of novel 9-substituted-8-hydroxyadenine derivatives as potent interferon inducers.

Authors:  Yoshiaki Isobe; Ayumu Kurimoto; Masanori Tobe; Kazuki Hashimoto; Tomoaki Nakamura; Kei Norimura; Haruhisa Ogita; Haruo Takaku
Journal:  J Med Chem       Date:  2006-03-23       Impact factor: 7.446

3.  Synthesis and immunostimulatory activity of 8-substituted amino 9-benzyladenines as potent Toll-like receptor 7 agonists.

Authors:  Guangyi Jin; Christina C N Wu; Rommel I Tawatao; Michael Chan; Dennis A Carson; Howard B Cottam
Journal:  Bioorg Med Chem Lett       Date:  2006-06-19       Impact factor: 2.823

4.  Synthesis and structure-activity-relationships of 1H-imidazo[4,5-c]quinolines that induce interferon production.

Authors:  John F Gerster; Kyle J Lindstrom; Richard L Miller; Mark A Tomai; Woubalem Birmachu; Shannon N Bomersine; Shiela J Gibson; Linda M Imbertson; Joel R Jacobson; Roy T Knafla; Peter V Maye; Nickolas Nikolaides; Folakemi Y Oneyemi; Gwen J Parkhurst; Sharon E Pecore; Michael J Reiter; Lisa S Scribner; Tracy L Testerman; Natalie J Thompson; Tammy L Wagner; Charles E Weeks; Jean-Denis Andre; Daniel Lagain; Yvon Bastard; Michel Lupu
Journal:  J Med Chem       Date:  2005-05-19       Impact factor: 7.446

5.  Synthesis and biological evaluation of 8-oxoadenine derivatives as toll-like receptor 7 agonists introducing the antedrug concept.

Authors:  Ayumu Kurimoto; Kazuki Hashimoto; Tomoaki Nakamura; Kei Norimura; Haruhisa Ogita; Haruo Takaku; Roger Bonnert; Tom McInally; Hiroki Wada; Yoshiaki Isobe
Journal:  J Med Chem       Date:  2010-04-08       Impact factor: 7.446

6.  2-Azidoalkoxy-7-hydro-8-oxoadenine derivatives as TLR7 agonists inducing dendritic cell maturation.

Authors:  Jimmy J Weterings; Selina Khan; Gerbrand J van der Heden van Noort; Cornelis J M Melief; Herman S Overkleeft; Sjoerd H van der Burg; Ferry Ossendorp; Gijsbert A van der Marel; Dmitri V Filippov
Journal:  Bioorg Med Chem Lett       Date:  2009-02-27       Impact factor: 2.823

7.  Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands.

Authors:  Hiromi Tanji; Umeharu Ohto; Takuma Shibata; Kensuke Miyake; Toshiyuki Shimizu
Journal:  Science       Date:  2013-03-22       Impact factor: 47.728

8.  Structure-activity relationships of adenine and deazaadenine derivatives as ligands for adenine receptors, a new purinergic receptor family.

Authors:  Thomas Borrmann; Aliaa Abdelrahman; Rosaria Volpini; Catia Lambertucci; Edgars Alksnis; Simone Gorzalka; Melanie Knospe; Anke C Schiedel; Gloria Cristalli; Christa E Müller
Journal:  J Med Chem       Date:  2009-10-08       Impact factor: 7.446

9.  Synthesis and evaluation of 8-oxoadenine derivatives as potent Toll-like receptor 7 agonists with high water solubility.

Authors:  Tomoaki Nakamura; Hiroki Wada; Hirotaka Kurebayashi; Tom McInally; Roger Bonnert; Yoshiaki Isobe
Journal:  Bioorg Med Chem Lett       Date:  2012-12-05       Impact factor: 2.823

10.  Synthesis and immunological characterization of toll-like receptor 7 agonistic conjugates.

Authors:  Michael Chan; Tomoko Hayashi; Crystal S Kuy; Christine S Gray; Christina C N Wu; Maripat Corr; Wolfgang Wrasidlo; Howard B Cottam; Dennis A Carson
Journal:  Bioconjug Chem       Date:  2009-06       Impact factor: 4.774
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  9 in total

1.  Evaluation of novel synthetic TLR7/8 agonists as vaccine adjuvants.

Authors:  Alyson J Smith; Yufeng Li; Hélène G Bazin; Julien R St-Jean; Daniel Larocque; Jay T Evans; Jory R Baldridge
Journal:  Vaccine       Date:  2016-07-09       Impact factor: 3.641

2.  Optimization of 8-oxoadenines with toll-like-receptor 7 and 8 activity.

Authors:  Hélène G Bazin; Laura S Bess; Mark T Livesay; Yufeng Li; Van Cybulski; Shannon M Miller; David A Johnson; Jay T Evans
Journal:  Bioorg Med Chem Lett       Date:  2020-01-22       Impact factor: 2.823

3.  Development of a TLR7/8 agonist adjuvant formulation to overcome early life hyporesponsiveness to DTaP vaccination.

Authors:  David J Dowling; Soumik Barman; Alyson J Smith; Francesco Borriello; Danielle Chaney; Spencer E Brightman; Gandolina Melhem; Byron Brook; Manisha Menon; Dheeraj Soni; Simone Schüller; Karthik Siram; Etsuro Nanishi; Hélène G Bazin; David J Burkhart; Ofer Levy; Jay T Evans
Journal:  Sci Rep       Date:  2022-10-18       Impact factor: 4.996

4.  Co-encapsulation of synthetic lipidated TLR4 and TLR7/8 agonists in the liposomal bilayer results in a rapid, synergistic enhancement of vaccine-mediated humoral immunity.

Authors:  Kristopher K Short; Shannon M Miller; Lois Walsh; Van Cybulski; Hélène Bazin; Jay T Evans; David Burkhart
Journal:  J Control Release       Date:  2019-10-22       Impact factor: 9.776

5.  Identification of Adjuvantic Activity of Amphotericin B in a Novel, Multiplexed, Poly-TLR/NLR High-Throughput Screen.

Authors:  Alex C D Salyer; Giuseppe Caruso; Karishma K Khetani; Lauren M Fox; Subbalakshmi S Malladi; Sunil A David
Journal:  PLoS One       Date:  2016-02-26       Impact factor: 3.240

6.  Species-Specific Structural Requirements of Alpha-Branched Trehalose Diester Mincle Agonists.

Authors:  Alyson J Smith; Shannon M Miller; Cassandra Buhl; Robert Child; Margaret Whitacre; Roman Schoener; George Ettenger; David Burkhart; Kendal Ryter; Jay T Evans
Journal:  Front Immunol       Date:  2019-02-28       Impact factor: 7.561

7.  Synthetic Toll-like Receptors 7 and 8 Agonists: Structure-Activity Relationship in the Oxoadenine Series.

Authors:  Jay T Evans; Laura S Bess; Sandra C Mwakwari; Mark T Livesay; Yufeng Li; Van Cybulski; David A Johnson; Hélène G Bazin
Journal:  ACS Omega       Date:  2019-09-10

Review 8.  Structural evolution of toll-like receptor 7/8 agonists from imidazoquinolines to imidazoles.

Authors:  Deepender Kaushik; Arshpreet Kaur; Nikolai Petrovsky; Deepak B Salunke
Journal:  RSC Med Chem       Date:  2021-05-14

Review 9.  Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.

Authors:  Sachin Bhagchandani; Jeremiah A Johnson; Darrell J Irvine
Journal:  Adv Drug Deliv Rev       Date:  2021-05-29       Impact factor: 15.470
  9 in total

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