Literature DB >> 23937980

Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility.

Mariela Bollini1, José A Cisneros, Krasimir A Spasov, Karen S Anderson, William L Jorgensen.   

Abstract

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are reported that have ca. 100-fold greater solubility than the structurally related drugs etravirine and rilpivirine, while retaining high anti-viral activity. The solubility enhancements come from strategic placement of a morpholinylalkoxy substituent in the entrance channel of the NNRTI binding site. Compound 4d shows low-nanomolar activity similar to etravirine towards wild-type HIV-1 and key viral variants.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Anti-HIV agent; Drug solubility; NNRTI

Mesh：

Substances：

Year:  2013        PMID： 23937980      PMCID： PMC3759246          DOI： 10.1016/j.bmcl.2013.06.091

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


  24 in total

Review 1.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.

Authors:  C A Lipinski; F Lombardo; B W Dominy; P J Feeney
Journal:  Adv Drug Deliv Rev       Date:  2001-03-01       Impact factor: 15.470

Review 2.  Prediction of drug solubility from structure.

Authors:  William L Jorgensen; Erin M Duffy
Journal:  Adv Drug Deliv Rev       Date:  2002-03-31       Impact factor: 15.470

3.  Potential energy functions for atomic-level simulations of water and organic and biomolecular systems.

Authors:  William L Jorgensen; Julian Tirado-Rives
Journal:  Proc Natl Acad Sci U S A       Date:  2005-05-03       Impact factor: 11.205

Review 4.  Molecular modeling of organic and biomolecular systems using BOSS and MCPRO.

Authors:  William L Jorgensen; Julian Tirado-Rives
Journal:  J Comput Chem       Date:  2005-12       Impact factor: 3.376

5.  Estimation and correlation of drug water solubility with pharmacological parameters required for biological activity.

Authors:  M M Morelock; L L Choi; G L Bell; J L Wright
Journal:  J Pharm Sci       Date:  1994-07       Impact factor: 3.534

Review 6.  In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine).

Authors:  Paul A J Janssen; Paul J Lewi; Eddy Arnold; Frits Daeyaert; Marc de Jonge; Jan Heeres; Luc Koymans; Maarten Vinkers; Jérôme Guillemont; Elisabeth Pasquier; Mike Kukla; Don Ludovici; Koen Andries; Marie-Pierre de Béthune; Rudi Pauwels; Kalyan Das; Art D Clark; Yulia Volovik Frenkel; Stephen H Hughes; Bart Medaer; Fons De Knaep; Hilde Bohets; Fred De Clerck; Ann Lampo; Peter Williams; Paul Stoffels
Journal:  J Med Chem       Date:  2005-03-24       Impact factor: 7.446

7.  Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1.

Authors:  Jerome Guillemont; Elisabeth Pasquier; Patrice Palandjian; Daniel Vernier; Sandrine Gaurrand; Paul J Lewi; Jan Heeres; Marc R de Jonge; Lucien M H Koymans; Frits F D Daeyaert; Maarten H Vinkers; Eddy Arnold; Kalyan Das; Rudi Pauwels; Koen Andries; Marie-Pierre de Béthune; Eva Bettens; Kurt Hertogs; Piet Wigerinck; Philip Timmerman; Paul A J Janssen
Journal:  J Med Chem       Date:  2005-03-24       Impact factor: 7.446

8.  Concentration and pH dependent aggregation of hydrophobic drug molecules and relevance to oral bioavailability.

Authors:  Yulia Volovik Frenkel; Arthur D Clark; Kalyan Das; Yuh-Hwa Wang; Paul J Lewi; Paul A J Janssen; Eddy Arnold
Journal:  J Med Chem       Date:  2005-03-24       Impact factor: 7.446

9.  Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants.

Authors:  Kalyan Das; Arthur D Clark; Paul J Lewi; Jan Heeres; Marc R De Jonge; Lucien M H Koymans; H Maarten Vinkers; Frederik Daeyaert; Donald W Ludovici; Michael J Kukla; Bart De Corte; Robert W Kavash; Chih Y Ho; Hong Ye; Mark A Lichtenstein; Koen Andries; Rudi Pauwels; Marie-Pierre De Béthune; Paul L Boyer; Patrick Clark; Stephen H Hughes; Paul A J Janssen; Eddy Arnold
Journal:  J Med Chem       Date:  2004-05-06       Impact factor: 7.446

10.  Extension into the entrance channel of HIV-1 reverse transcriptase--crystallography and enhanced solubility.

Authors:  Mariela Bollini; Kathleen M Frey; José A Cisneros; Krasimir A Spasov; Kalyan Das; Joseph D Bauman; Eddy Arnold; Karen S Anderson; William L Jorgensen
Journal:  Bioorg Med Chem Lett       Date:  2013-07-08       Impact factor: 2.823
View more
  12 in total

1.  Computer-aided discovery of anti-HIV agents.

Authors:  William L Jorgensen
Journal:  Bioorg Med Chem       Date:  2016-07-21       Impact factor: 3.641

2.  Picomolar Inhibitors of HIV-1 Reverse Transcriptase: Design and Crystallography of Naphthyl Phenyl Ethers.

Authors:  Won-Gil Lee; Kathleen M Frey; Ricardo Gallardo-Macias; Krasimir A Spasov; Mariela Bollini; Karen S Anderson; William L Jorgensen
Journal:  ACS Med Chem Lett       Date:  2014-10-13       Impact factor: 4.345

3.  Structural and pharmacological evaluation of a novel non-nucleoside reverse transcriptase inhibitor as a promising long acting nanoformulation for treating HIV.

Authors:  Shalley N Kudalkar; Irfan Ullah; Nicole Bertoletti; Hanna K Mandl; José A Cisneros; Jagadish Beloor; Albert H Chan; Elias Quijano; W Mark Saltzman; William L Jorgensen; Priti Kumar; Karen S Anderson
Journal:  Antiviral Res       Date:  2019-04-26       Impact factor: 5.970

4.  Systematic Study of Effects of Structural Modifications on the Aqueous Solubility of Drug-like Molecules.

Authors:  José A Cisneros; Michael J Robertson; Brandon Q Mercado; William L Jorgensen
Journal:  ACS Med Chem Lett       Date:  2016-12-01       Impact factor: 4.345

5.  Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group.

Authors:  Won-Gil Lee; Ricardo Gallardo-Macias; Kathleen M Frey; Krasimir A Spasov; Mariela Bollini; Karen S Anderson; William L Jorgensen
Journal:  J Am Chem Soc       Date:  2013-10-24       Impact factor: 15.419

6.  Design, synthesis, and protein crystallography of biaryltriazoles as potent tautomerase inhibitors of macrophage migration inhibitory factor.

Authors:  Pawel Dziedzic; José A Cisneros; Michael J Robertson; Alissa A Hare; Nadia E Danford; Richard H G Baxter; William L Jorgensen
Journal:  J Am Chem Soc       Date:  2015-02-20       Impact factor: 15.419

7.  Structural and Preclinical Studies of Computationally Designed Non-Nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection.

Authors:  Shalley N Kudalkar; Jagadish Beloor; Albert H Chan; Won-Gil Lee; William L Jorgensen; Priti Kumar; Karen S Anderson
Journal:  Mol Pharmacol       Date:  2017-02-06       Impact factor: 4.436

8.  Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase.

Authors:  Won-Gil Lee; Kathleen M Frey; Ricardo Gallardo-Macias; Krasimir A Spasov; Albert H Chan; Karen S Anderson; William L Jorgensen
Journal:  Bioorg Med Chem Lett       Date:  2015-07-09       Impact factor: 2.823

9.  A mechanistic and structural investigation of modified derivatives of the diaryltriazine class of NNRTIs targeting HIV-1 reverse transcriptase.

Authors:  Andrea C Mislak; Kathleen M Frey; Mariela Bollini; William L Jorgensen; Karen S Anderson
Journal:  Biochim Biophys Acta       Date:  2014-04-12

10.  Diaryl ethers with carboxymethoxyphenacyl motif as potent HIV-1 reverse transcriptase inhibitors with improved solubility.

Authors:  Tomasz Frączek; Rafał Kamiński; Agnieszka Krakowiak; Evelien Naessens; Bruno Verhasselt; Piotr Paneth
Journal:  J Enzyme Inhib Med Chem       Date:  2018-12       Impact factor: 5.051
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.