Results 81 to 90 of about 989 (99)

Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of HIV-1 allosteric integrase inhibitors

Bioorganic & Medicinal Chemistry, 2022
Allosteric integrase inhibitors (ALLINIs) of HIV-1 may hold promise as a novel mechanism for HIV therapeutics and cure. Scaffold modifications to the 4-(4,4-dimethylpiperidinyl) 2,6-dimethylpyridinyl class of ALLINIs provided a series of potent compounds with differentiated 5/6 fused ring systems.
Kyle, Parcella, Manoj, Patel, Yong, Tu, Kyle, Eastman, Kevin, Peese, Eric, Gillis, Makonen, Belema, Ira B, Dicker, Brian, McAuliffe, Bo, Ding, Paul, Falk, Jean, Simmermacher, Dawn D, Parker, Prasanna, Sivaprakasam, Javed A, Khan, Kevin, Kish, Hal, Lewis, Umesh, Hanumegowda, Susan, Jenkins, John F, Kadow, Mark, Krystal, Nicholas A, Meanwell, B Narasimhulu, Naidu   +22 more
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Discovery of tricyclic HIV-1 integrase-LEDGF/p75 allosteric inhibitors by intramolecular direct arylation reaction

Bioorganic & Medicinal Chemistry Letters, 2022
We have been conducting exploratory research to develop human immunodeficiency virus type-1 (HIV-1) integrase-LEDGF/p75 allosteric inhibitors (INLAIs). Here, we report on a newly designed compound with a tricyclic scaffold that shows promise as an inhibitor.
Yoshiyuki, Taoda, Toshiyuki, Akiyama, Kenji, Tomita, Misato, Fujiwara-Kitamura, Yoshinori, Tamura, Takashi, Kawasuji, Eriko, Matsuoka, Erika, Akihisa, Takahiro, Seki, Tomokazu, Yoshinaga   +9 more
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Structure-based amelioration of PXR transactivation in a novel series of macrocyclic allosteric inhibitors of HIV-1 integrase

Bioorganic & Medicinal Chemistry Letters, 2020
Previous studies have identified a series of imidazo[1,2-a]pyridine (IZP) derivatives as potent allosteric inhibitors of HIV-1 integrase (ALLINIs) and virus infection in cell culture. However, IZPs were also found to be relatively potent activators of the pregnane-X receptor (PXR), raising the specter of induction of CYP-mediated drug disposition ...
Prasanna Sivaprakasam, Zhongyu Wang, Nicholas A. Meanwell, Javed A. Khan, David R. Langley, Stephen R. Johnson, Guo Li, Annapurna Pendri, Timothy P. Connolly, Mian Gao, Daniel M. Camac, Cheryl Klakouski, Tatyana Zvyaga, Christopher Cianci, Brian McAuliffe, Bo Ding, Linda Discotto, Mark R. Krystal, Susan Jenkins, Kevin M. Peese, B. Narasimhulu Naidu   +20 more
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Design, synthesis and SAR study of novel C2-pyrazolopyrimidine amides and amide isosteres as allosteric integrase inhibitors

Bioorganic & Medicinal Chemistry Letters, 2020
The design, synthesis and structure-activity relationships associated with a series of C2-substituted pyrazolopyrimidines as potent allosteric inhibitors of HIV-1 integrase (ALLINIs) are described. Structural modifications to these molecules were made in order to examine the effect on potency and, for select compounds, pharmacokinetic properties.
Christopher W. Allard, Beatrice Minassian, Christopher Cianci, Linda Discotto, Susan Jenkins, Susan Jenkins, Mark Krystal, Mark Krystal, Dawn D. Parker, Dawn D. Parker, B. Narasimhulu Naidu, B. Narasimhulu Naidu, Brian McAuliffe, Brian McAuliffe, Jean Simmermacher, Jean Simmermacher, Manoj Patel, Manoj Patel, Nicholas A. Meanwell   +18 more
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Discovery of a Distinct Chemical and Mechanistic Class of Allosteric HIV-1 Integrase Inhibitors with Antiretroviral Activity

ACS Chemical Biology, 2017
Allosteric integrase inhibitors (ALLINIs) bind to the lens epithelial-derived growth factor (LEDGF) pocket on HIV-1 integrase (IN) and possess potent antiviral effects. Rather than blocking proviral integration, ALLINIs trigger IN conformational changes that have catastrophic effects on viral maturation, rendering the virions assembled in the presence ...
Christine Burlein, Cheng Wang, Min Xu, Triveni Bhatt, Mark Stahlhut, Yangsi Ou, Gregory C. Adam, Jeffrey Heath, Daniel J. Klein, John Sanders, Kartik Narayan, Pravien Abeywickrema, Mee Ra Heo, Steven S. Carroll, Jay A. Grobler, Sujata Sharma, Tracy L. Diamond, Antonella Converso, Daniel J. Krosky   +18 more
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5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors

Journal of Medicinal Chemistry, 2019
A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for activity against HIV-1 infection in cell culture.
Kevin M. Peese, Christopher W. Allard, Timothy Connolly, Barry L. Johnson, Chen Li, Manoj Patel, Margaret E. Sorensen, Michael A. Walker, Nicholas A. Meanwell, Brian McAuliffe, Beatrice Minassian, Mark Krystal, Dawn D. Parker, Hal A. Lewis, Kevin Kish, Ping Zhang, Robert T. Nolte, Jean Simmermacher, Susan Jenkins, Christopher Cianci, B. Narasimhulu Naidu   +20 more
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Design and synthesis of novel and potent allosteric HIV-1 integrase inhibitors with a spirocyclic moiety

Bioorganic & Medicinal Chemistry Letters
We report herein the design and discovery of novel allosteric HIV-1 integrase inhibitors. Our design concept utilized the spirocyclic moiety to restrain the flexibility of the conformation of the lipophilic part of the inhibitor. Compound 5 showed antiviral activity by binding to the nuclear lens epithelium-derived growth factor (LEDGF/p75) binding ...
Kaoru, Adachi, Tomoyuki, Manabe, Takayuki, Yamasaki, Akira, Suma, Takuya, Orita, Tomoko, Furuzono, Tsuyoshi, Adachi, Yoshitsugu, Ohata, Yoshiyuki, Akiyama, Susumu, Miyazaki   +9 more
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Crystal Structures of Novel Allosteric Peptide Inhibitors of HIV Integrase Identify New Interactions at the LEDGF Binding Site

ChemBioChem, 2011
AbstractAn optimised method of solution cyclisation gave us access to a series of peptides including SLKIDNLD (2). We investigated the crystallographic complexes of the HIV integrase (HIV‐IN) catalytic core domain with 13 of the peptides and identified multiple interactions at the binding site, including hydrogen bonds with residues Thr125 and Gln95 ...
Jonathan Coates, Thomas S. Peat, John Martyn, Philip Rea, Janet Newman, David Ian Rhodes, Dharshini Jeevarajah, Nicholas J. Ede, Nick Vandegraaff, John Deadman   +9 more
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Synthesis of an Allosteric HIV-1 Integrase Inhibitor

Synfacts, 2020
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The Development of HIV-1 Integrase Allosteric Inhibitors Using a Fragment Based Drug Discovery Approach

2018
HIV-1 integrase (IN) is an enzyme that is essential for viral replication. Previous work within our group identified a molecule as a hit that bound to IN and had potential to be developed as an inhibitor of HIV. This thesis describes the hit-to-lead optimisation process of developing the hit into a high-affinity lead compound using a Fragment-Based ...
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