Literature DB >> 26191361

Pyrazolo-Piperidines Exhibit Dual Inhibition of CCR5/CXCR4 HIV Entry and Reverse Transcriptase.

Bryan D Cox1, Anthony R Prosser1, Yongnian Sun2, Zhufang Li2, Sangil Lee2, Ming B Huang3, Vincent C Bond3, James P Snyder1, Mark Krystal2, Lawrence J Wilson1, Dennis C Liotta1.   

Abstract

We report novel anti-HIV-1 agents with combined dual host-pathogen pharmacology. Lead compound 3, composed of a pyrazole-piperidine core, exhibits three concurrent mechanisms of action: (1) non-nucleoside reverse transcriptase inhibition, (2) CCR5-mediated M-tropic viral entry inhibition, and (3) CXCR4-based T-tropic viral entry inhibition that maintains native chemokine ligand binding. This discovery identifies important tool compounds for studying viral infectivity and prototype agents that block HIV-1 entry through dual chemokine receptor ligation.

Entities:  

Keywords:  HIV-1; chemokine receptors; multitarget drug discovery; non-nucleoside reverse transcriptase inhibitors; viral entry inhibitors

Year:  2015        PMID： 26191361      PMCID： PMC4499816          DOI： 10.1021/acsmedchemlett.5b00036

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


  20 in total

1.  Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists.

Authors:  Beili Wu; Ellen Y T Chien; Clifford D Mol; Gustavo Fenalti; Wei Liu; Vsevolod Katritch; Ruben Abagyan; Alexei Brooun; Peter Wells; F Christopher Bi; Damon J Hamel; Peter Kuhn; Tracy M Handel; Vadim Cherezov; Raymond C Stevens
Journal:  Science       Date:  2010-10-07       Impact factor: 47.728

2.  Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses.

Authors:  Denis J Kertesz; Christine Brotherton-Pleiss; Minmin Yang; Zhanguo Wang; Xianfeng Lin; Zongxing Qiu; Donald R Hirschfeld; Shelley Gleason; Taraneh Mirzadegan; Pete W Dunten; Seth F Harris; Armando G Villaseñor; Julie Qi Hang; Gabrielle M Heilek; Klaus Klumpp
Journal:  Bioorg Med Chem Lett       Date:  2010-05-16       Impact factor: 2.823

Review 3.  Novel paradigms for drug discovery: computational multitarget screening.

Authors:  Ekachai Jenwitheesuk; Jeremy A Horst; Kasey L Rivas; Wesley C Van Voorhis; Ram Samudrala
Journal:  Trends Pharmacol Sci       Date:  2008-01-10       Impact factor: 14.819

Review 4.  The future of HIV microbicides: challenges and opportunities.

Authors:  Anita B Garg; Jeremy Nuttall; Joseph Romano
Journal:  Antivir Chem Chemother       Date:  2009

5.  Activity of the HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068, against CD4-independent viruses and HIV-1 envelopes resistant to other entry inhibitors.

Authors:  Zhufang Li; Nannan Zhou; Yongnian Sun; Neelanjana Ray; Max Lataillade; George J Hanna; Mark Krystal
Journal:  Antimicrob Agents Chemother       Date:  2013-06-17       Impact factor: 5.191

6.  Development of dual-acting pyrimidinediones as novel and highly potent topical anti-HIV microbicides.

Authors:  Karen Watson Buckheit; Lu Yang; Robert W Buckheit
Journal:  Antimicrob Agents Chemother       Date:  2011-09-06       Impact factor: 5.191

7.  Anti-HIV small-molecule binding in the peptide subpocket of the CXCR4:CVX15 crystal structure.

Authors:  Bryan D Cox; Anthony R Prosser; Brooke M Katzman; Ana A Alcaraz; Dennis C Liotta; Lawrence J Wilson; James P Snyder
Journal:  Chembiochem       Date:  2014-07-02       Impact factor: 3.164

8.  Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis.

Authors:  Myriam Witvrouw; Christophe Pannecouque; William M Switzer; Thomas M Folks; Erik De Clercq; Walid Heneine
Journal:  Antivir Ther       Date:  2004-02

9.  Automated design of ligands to polypharmacological profiles.

Authors:  Jérémy Besnard; Gian Filippo Ruda; Vincent Setola; Keren Abecassis; Ramona M Rodriguiz; Xi-Ping Huang; Suzanne Norval; Maria F Sassano; Antony I Shin; Lauren A Webster; Frederick R C Simeons; Laste Stojanovski; Annik Prat; Nabil G Seidah; Daniel B Constam; G Richard Bickerton; Kevin D Read; William C Wetsel; Ian H Gilbert; Bryan L Roth; Andrew L Hopkins
Journal:  Nature       Date:  2012-12-13       Impact factor: 49.962

10.  A broad HIV-1 inhibitor blocks envelope glycoprotein transitions critical for entry.

Authors:  Alon Herschhorn; Christopher Gu; Nicole Espy; Jonathan Richard; Andrés Finzi; Joseph G Sodroski
Journal:  Nat Chem Biol       Date:  2014-08-31       Impact factor: 15.040
View more
  12 in total

Review 1.  CCR5 receptor antagonists in preclinical to phase II clinical development for treatment of HIV.

Authors:  Michelle B Kim; Kyle E Giesler; Yesim A Tahirovic; Valarie M Truax; Dennis C Liotta; Lawrence J Wilson
Journal:  Expert Opin Investig Drugs       Date:  2016-12       Impact factor: 6.206

Review 2.  Discoveries and developments of CXCR4-targeted HIV-1 entry inhibitors.

Authors:  Chaozai Zhang; Ruohan Zhu; Qizhi Cao; Xiaohong Yang; Ziwei Huang; Jing An
Journal:  Exp Biol Med (Maywood)       Date:  2020-02-04

Review 3.  Structural Analysis of Chemokine Receptor-Ligand Interactions.

Authors:  Marta Arimont; Shan-Liang Sun; Rob Leurs; Martine Smit; Iwan J P de Esch; Chris de Graaf
Journal:  J Med Chem       Date:  2017-03-10       Impact factor: 7.446

4.  Design, synthesis and antiviral evaluation of novel heteroarylcarbothioamide derivatives as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and RDDP functions.

Authors:  Angela Corona; Valentina Onnis; Alessandro Deplano; Giulia Bianco; Monica Demurtas; Simona Distinto; Yung-Chi Cheng; Stefano Alcaro; Francesca Esposito; Enzo Tramontano
Journal:  Pathog Dis       Date:  2017-08-31       Impact factor: 3.166

5.  Structure-Based Design of a Small Molecule CD4-Antagonist with Broad Spectrum Anti-HIV-1 Activity.

Authors:  Francesca Curreli; Young Do Kwon; Hongtao Zhang; Daniel Scacalossi; Dmitry S Belov; Artur A Tikhonov; Ivan A Andreev; Andrea Altieri; Alexander V Kurkin; Peter D Kwong; Asim K Debnath
Journal:  J Med Chem       Date:  2015-08-28       Impact factor: 7.446

6.  Design and synthesis of novel (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)-3-((1-substituted phenyl-1H-1,2,3-triazol-4-yl)methyl)thiazolidine-2,4-diones: a potential cytotoxic scaffolds and their molecular modeling studies.

Authors:  N J P Subhashini; Kolluri Prashanth Kumar; Edigi Praveen Kumar; Putta Shravani; Surya Sathyanarayana Singh; Tamalapakula Vani; Manga Vijjulatha
Journal:  Mol Divers       Date:  2020-05-02       Impact factor: 2.943

7.  Small molecule CXCR4 antagonists block the HIV-1 Nef/CXCR4 axis and selectively initiate the apoptotic program in breast cancer cells.

Authors:  Ming-Bo Huang; Kyle E Giesler; Brooke M Katzman; Anthony R Prosser; Valarie Truax; Dennis C Liotta; Lawrence J Wilson; Vincent C Bond
Journal:  Oncotarget       Date:  2018-02-26

Review 8.  CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy.

Authors:  Fedora Grande; Maria Antonietta Occhiuzzi; Bruno Rizzuti; Giuseppina Ioele; Michele De Luca; Paola Tucci; Valentina Svicher; Stefano Aquaro; Antonio Garofalo
Journal:  Molecules       Date:  2019-02-02       Impact factor: 4.411

Review 9.  Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

Authors:  Antoinette G Nelson; Xiaoping Zhang; Usha Ganapathi; Zoltan Szekely; Charles W Flexner; Andrew Owen; Patrick J Sinko
Journal:  J Control Release       Date:  2015-08-24       Impact factor: 9.776

10.  Pyrrolone Derivatives as Intracellular Allosteric Modulators for Chemokine Receptors: Selective and Dual-Targeting Inhibitors of CC Chemokine Receptors 1 and 2.

Authors:  Natalia V Ortiz Zacarías; Jacobus P D van Veldhoven; Laura Portner; Eric van Spronsen; Salviana Ullo; Margo Veenhuizen; Wijnand J C van der Velden; Annelien J M Zweemer; Roy M Kreekel; Kenny Oenema; Eelke B Lenselink; Laura H Heitman; Adriaan P IJzerman
Journal:  J Med Chem       Date:  2018-10-11       Impact factor: 7.446
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.