Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

Kim, Jun Won; Lee, Doohyun; Park, Changmin; So, Wonyoung; Jo, Mi-Na; Ok, Taedong; Kwon, Jeongjin; Kong, Sunju; Jo, Suyeon; Kim, Youngmi; Choi, Jihyun; Kim, Hyoung Cheul; Ko, Yoonae; Choi, Inhee; Park, Young-Sam; Yoon, Jaewan; Ju, Moon Kyeong; Kim, Junghwan; Han, Sung‐Jun; Kim, Tae-Hee; Cechetto, Jonathan; Nam, Jiyoun; Sommer, Peter; Liuzzi, Michel; Lee, Jinhwa; No, Zaesung

doi:10.1021/ml300146q

Cited by 28 publications

(23 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kim et al identified a novel class of aryl substituted pyrazole compounds as potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) for anti-human immunodeficiency virus (HIV) activity using a cell-based full replication assay. The optimization of the antiviral activity leading to the discovery of compound 411 which possessed excellent potency against wild-type HIV-1 (EC 50 = 0.2 nM) as well as viruses bearing Y181C and K103N resistance mutations in the reverse transcriptase gene [ 309 ]. Ndungu et al the synthesis and a SAR strategy that led to the discovery of novel pyrazole derivatives as potent measles virus (MeV).…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

View full text Add to dashboard Cite

Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

show abstract

Section: Pharmacological Activitiesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

View full text Add to dashboard Cite

show abstract

“… 1 Among these, S. aureus accounts for 16% of HAIs and is responsible for more deaths in the U.S. annually than HIV/AIDS. 1 − 3 The organism’s high morbidity and mortality rates are, in part, attributable to the fact that S. aureus has developed resistance to currently available antibiotics. 4 The quinolone class of antibiotics was once a predominant treatment option for S. aureus infections; 5 however, due to increasing quinolone resistance, these drugs continue to have diminishing efficacy.…”

Section: Introductionmentioning

confidence: 99%

Repurposing the Antihistamine Terfenadine for Antimicrobial Activity against Staphylococcus aureus

et al. 2014

View full text Add to dashboard Cite

Staphylococcus aureus is a rapidly growing health threat in the U.S., with resistance to several commonly prescribed treatments. A high-throughput screen identified the antihistamine terfenadine to possess, previously unreported, antimicrobial activity against S. aureus and other Gram-positive bacteria. In an effort to repurpose this drug, structure–activity relationship studies yielded 84 terfenadine-based analogues with several modifications providing increased activity versus S. aureus and other bacterial pathogens, including Mycobacterium tuberculosis. Mechanism of action studies revealed these compounds to exert their antibacterial effects, at least in part, through inhibition of the bacterial type II topoisomerases. This scaffold suffers from hERG liabilities which were not remedied through this round of optimization; however, given the overall improvement in activity of the set, terfenadine-based analogues provide a novel structural class of antimicrobial compounds with potential for further characterization as part of the continuing process to meet the current need for new antibiotics.

show abstract

“…The first one is a group of "phenylaminopyridine" derivatives that inhibit HIV-1 replication [22]. Table 2 and Fig.…”

Section: Selected Systemsmentioning

confidence: 99%

“…We show the usefulness of our new model by presenting and analyzing structure-activity relationship results for the inhibition of HIV-1 WT replication by some phenylaminopyridine (PAP) derivatives [22] and for the inhibition of cell growth by several 1-azabenzanthrone derivatives [23]. Recently a series of compounds based on a 4-phenyl-2-phenylaminopyridine scaffold that are potent and selective inhibitors of Traf2-and Nck-interacting kinase activity have been described [24].…”

Section: Introductionmentioning

confidence: 99%

Quantum-chemical Modeling of the Relationships between Molecular Structure and In Vitro Multi-Step, Multimechanistic Drug Effects. HIV-1 Replication Inhibition and Inhibition of Cell Proliferation as Examples

2013

Can Chem Trans

View full text Add to dashboard Cite

Abstract:The general hypothesis that any in vitro or in vivo biological activity can be explained only in terms of local atomic reactivity indices has been proposed and tested for the inhibition of HIV-1 WT replication by some phenylaminopyridine derivatives and the inhibition of cell growth by several 1-azabenzanthrone derivatives. In all of them good structure-activity relationships have been obtained and some requirements for potent biological activity have been suggested. For the cases tested here the common skeleton hypothesis works well. As this hypothesis has a logical conceptual basis but does not yet have a formal general mathematical background, it cannot be generalized and must be tested case by case.This methodology gives an account of the whole process and, in the case of multi-step processes, is unable to relate the different reactivity indices appearing in the SAR equations to any particular step.

show abstract

Discovery of Phenylaminopyridine Derivatives as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

Cited by 28 publications

References 23 publications

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Repurposing the Antihistamine Terfenadine for Antimicrobial Activity against Staphylococcus aureus

Quantum-chemical Modeling of the Relationships between Molecular Structure and In Vitro Multi-Step, Multimechanistic Drug Effects. HIV-1 Replication Inhibition and Inhibition of Cell Proliferation as Examples

Contact Info

Product

Resources

About