scholarly journals Nature Inspired Molecular Design: Stereoselective Synthesis of Bicyclic and Polycyclic Ethers for Potent HIV-1 Protease Inhibitors

2018 ◽  
Vol 7 (8) ◽  
pp. 1448-1466 ◽  
Author(s):  
Arun K. Ghosh ◽  
Margherita Brindisi
Keyword(s):  
Protease Inhibitors ◽  
Stereoselective Synthesis ◽  
Molecular Design ◽  
Polycyclic Ethers ◽  
Hiv 1

ChemInform Abstract: Potent HIV-1 Protease Inhibitors: Stereoselective Synthesis of a Dipeptide Mimic.

ChemInform ◽  
2010 ◽  
Vol 24 (22) ◽  
pp. no-no
Author(s):  
A. K. GHOSH ◽  
S. P. MCKEE ◽  
W. J. THOMPSON ◽  
P. L. DARKE ◽  
J. C. ZUGAY
Keyword(s):  
Protease Inhibitors ◽  
Stereoselective Synthesis ◽  
Hiv 1

Stereoselective Synthesis of 3-Aminoindan-1-ones and Subsequent Incorporation into HIV-1 Protease Inhibitors

2006 ◽  
Vol 71 (3) ◽  
pp. 1265-1268 ◽  
Author(s):  
Anna Arefalk ◽  
Johan Wannberg ◽  
Mats Larhed ◽  
Anders Hallberg
Keyword(s):  
Protease Inhibitors ◽  
Stereoselective Synthesis ◽  
Hiv 1 ◽  
Subsequent Incorporation

scholarly journals Potent HIV-1 protease inhibitors: stereoselective synthesis of a dipeptide mimic

1993 ◽  
Vol 58 (5) ◽  
pp. 1025-1029 ◽  
Author(s):  
Arun K. Ghosh ◽  
Sean P. McKee ◽  
Wayne J. Thompson ◽  
Paul L. Darke ◽  
Joan C. Zugay
Keyword(s):  
Protease Inhibitors ◽  
Stereoselective Synthesis ◽  
Hiv 1

scholarly journals Novel Protease Inhibitors (PIs) Containing Macrocyclic Components and 3(R),3a(S),6a(R)-bis-Tetrahydrofuranylurethane That Are Potent against Multi-PI-Resistant HIV-1 Variants In Vitro

2010 ◽  
Vol 54 (8) ◽  
pp. 3460-3470 ◽  
Author(s):  
Yasushi Tojo ◽  
Yasuhiro Koh ◽  
Masayuki Amano ◽  
Manabu Aoki ◽  
Debananda Das ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Molecular Design ◽  
Antiviral Agent ◽  
Structural Features ◽  
Biological Properties ◽  
Van Der Waals Interactions ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Hiv 1

ABSTRACT Natural products with macrocyclic structural features often display intriguing biological properties. Molecular design incorporating macrocycles may lead to molecules with unique protein-ligand interactions. We generated novel human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a macrocycle and bis-tetrahydrofuranylurethane. Four such compounds exerted potent activity against HIV-1LAI and had 50% effective concentrations (EC50s) of as low as 0.002 μM with minimal cytotoxicity. GRL-216 and GRL-286 blocked the replication of HIV-1NL4-3 variants selected by up to 5 μM saquinavir, ritonavir, nelfinavir, lopinavir, or atazanavir; they had EC50s of 0.020 to 0.046 μM and potent activities against six multi-PI-resistant clinical HIV-1 (HIVmPIr ) variants with EC50s of 0.027 to 0.089 μM. GRL-216 and -286 also blocked HIV-1 protease dimerization as efficiently as darunavir. When HIV-1NL4-3 was selected by GRL-216, it replicated progressively more poorly and failed to replicate in the presence of >0.26 μM GRL-216, suggesting that the emergence of GRL-216-resistant HIV-1 variants is substantially delayed. At passage 50 with GRL-216 (the HIV isolate selected with GRL-216 at up to 0.16 μM [HIV216-0.16 μM]), HIV-1NL4-3 containing the L10I, L24I, M46L, V82I, and I84V mutations remained relatively sensitive to PIs, including darunavir, with the EC50s being 3- to 8-fold-greater than the EC50 of each drug for HIV-1NL4-3. Interestingly, HIV216-0.16 μM had 10-fold increased sensitivity to tipranavir. Analysis of the protein-ligand X-ray structures of GRL-216 revealed that the macrocycle occupied a greater volume of the binding cavity of protease and formed greater van der Waals interactions with V82 and I84 than darunavir. The present data warrant the further development of GRL-216 as a potential antiviral agent for treating individuals harboring wild-type and/or HIVmPIr .

ChemInform Abstract: Stereoselective Synthesis of Xaaψ(CH2CH(OH))Yaa Dipeptidomimetics and Their Inclusion in HIV-1 Protease Inhibitors.

ChemInform ◽  
2010 ◽  
Vol 26 (27) ◽  
pp. no-no
Author(s):  
H. G. CHEN ◽  
J. M. TUSTIN ◽  
P. G. M. WUTS ◽  
T. K. SAWYER ◽  
C. W. SMITH
Keyword(s):  
Protease Inhibitors ◽  
Stereoselective Synthesis ◽  
Hiv 1

Stereoselective synthesis of Xaaψ[CH2CH(OH)]Yaa dipeptidomimetics and their inclusion in HIV-1 protease inhibitors

2009 ◽  
Vol 45 (1) ◽  
pp. 1-10 ◽  
Author(s):  
HUAI G. CHEN ◽  
JAMES M. TUSTIN ◽  
P.G.M. WUTS ◽  
TOMI K. SAWYER ◽  
CLARK W. SMITH
Keyword(s):  
Protease Inhibitors ◽  
Stereoselective Synthesis ◽  
Hiv 1

An oral high dose of cholecalciferol restores vitamin D status in deficient postmenopausal HIV-1 infected women independently of protease inhibitors therapy

2015 ◽  
Author(s):  
Jessica Pepe ◽  
Ivano Mezzaroma ◽  
Alessandra Fantauzzi ◽  
Mario Falciano ◽  
Alessandra Salotti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Protease Inhibitors ◽  
High Dose ◽  
Vitamin D Status ◽  
Hiv 1

A convergent synthesis of the spiroketal moiety of the HIV-1 protease inhibitors didemnaketals

Tetrahedron ◽  
2002 ◽  
Vol 58 (9) ◽  
pp. 1697-1708 ◽  
Author(s):  
Yan Xing Jia ◽  
Xin Li ◽  
Bin Wu ◽  
Xue Zhi Zhao ◽  
Yong Qiang Tu
Keyword(s):  
Protease Inhibitors ◽  
Convergent Synthesis ◽  
Hiv 1

scholarly journals Substrate Envelope-Designed Potent HIV-1 Protease Inhibitors to Avoid Drug Resistance

2013 ◽  
Vol 20 (9) ◽  
pp. 1116-1124 ◽  
Author(s):  
Madhavi N.L. Nalam ◽  
Akbar Ali ◽  
G.S. Kiran Kumar Reddy ◽  
Hong Cao ◽  
Saima G. Anjum ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Protease Inhibitors ◽  
Hiv 1 ◽  
Substrate Envelope
Sign in / Sign up

Export Citation Format

Share Document