Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: Optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches

Huang, Boshi; Li, Cuicui; Chen, Wenmin; Liu, Tao; Yu, Mingyan; Fu, Lu; Sun, Yueyue; Liu, Huiqing; Clercq, Erik De; Pannecouque, Christophe; Balzarini, Jan; Zhan, Peng; Liu, Xinyong

doi:10.1016/j.ejmech.2015.01.042

Cited by 78 publications

(33 citation statements)

References 35 publications

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“…During the last decades, fused heterocycles bearing 1,2,4-triazolo [1,5-a]pyrimidine scaffold proved to be of pharmaceutical interest due to the diverse biological activities of these derivatives [1][2][3][4][5]. For example, a derivative functionalized with N-substituted piperidine proved a very good antiviral activity against the wild-type HIV-1 strain, being more potent than the currently used drugs [3].…”

Section: Introductionmentioning

confidence: 99%

“…For example, a derivative functionalized with N-substituted piperidine proved a very good antiviral activity against the wild-type HIV-1 strain, being more potent than the currently used drugs [3]. Polycondensed species with steroid nucleus showed potent inhibitory activity against PC-3 (human prostatic carcinoma), MCF-7 (human breast carcinoma) and EC9706 (human oesophageal carcinoma) cell lines [4].…”

Section: Introductionmentioning

confidence: 99%

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Thermal behaviour of some biologically active species based on complexes with a triazolopyrimidine pharmacophore

Olar

Calu

Badea

et al. 2016

J Therm Anal Calorim

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A series of complexes of type M(pmtp)(CH 3 COO) 2 ÁnH 2 O ((1) M: Co, n = 4.5; (2) M: Ni, n = 3.5; (3) M: Cu, n = 0.5; (4) M: Zn, n = 0; pmtp: 5-phenyl-7-methyl-1,2,4-triazolo[1,5-a]pyrimidine) were synthesised by one-pot condensation. The complexes were characterized by elemental analysis, ESI-MS, IR, UV-Vis-NIR, EPR spectra, magnetic susceptibility at room temperature as well as thermogravimetric analysis. The modifications in the IR spectra of complexes are in accordance with the condensation process and indicate the triazolopyrimidine coordination as unidentate. The electronic and EPR spectra together with magnetic moments indicate an octahedral stereochemistry for paramagnetic ions, except for Cu(II) with a square pyramidal geometry. Processes such as water elimination, acetate into carbonate transformation, as well as oxidative degradation of the triazolopyrimidine derivative were evidenced during thermal decomposition. The complexes exhibited an improved antimicrobial activity in comparison with the ligand, on both planktonic and biofilm-embedded microbial cells. The best antimicrobial activity in both susceptible and resistant strains was obtained for complex (3) followed by complex (1), which can be related to both oxidation state and stereochemical versatility. At high concentrations, the Cu(II) complex exhibits both cytotoxicity on HT 29 tumour cell line and anti-inflammatory activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thermal behaviour of some biologically active species based on complexes with a triazolopyrimidine pharmacophore

Olar

Calu

Badea

et al. 2016

J Therm Anal Calorim

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show abstract

“…The linker's length and size between piperidine NH and the terminal phenyl ring should be appropriate, to make compounds well adopted in the NNIBP of HIV-1 RT. [112] Henen et al described a series of [1,2,4]triazolo[4,3-a] quinoxaline derivatives incorporating thioamide fragment (142,143) with the aim to obtain potent antiviral agents (Figure 45). The antiviral activity of the synthesized compounds was screened against herpes simplex virus-1 (HSV-1) using aphidicolin (APD) as a positive control.…”

Section: Non-nucleoside Bridgehead 124-triazolesmentioning

confidence: 99%

Recent Advances in 1,2,4‐Triazole Scaffolds as Antiviral Agents

El‐Sebaey

2020

ChemistrySelect

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In recent years, severe viral infections have emerged, and antiviral chemotherapeutic agents are not adequately effective in curing these infections, leading to serious human diseases and loss of life. Consequently, a novel antiviral is urgently needed, which undoubtedly essential for the therapy of various fatal and debilitating viral infections. 1,2,4-Triazole derivatives occupy a pivotal position in modern medicinal chemistry and have been incorporated in numerous clinical drugs, including antiviral drugs. To my best knowledge, there are few review articles exclusively handling 1,2,4-triazole scaffold with the antiviral potential. This review aims to figure out recent perspectives and advances of 1,2,4-triazole nucleus roles in various kinds of antiviral agents over the past decade, with some examples of rational design and some structure-activity relationships. This review will hopefully provide perception into especially powerful compounds as lead structures and help in the rational design and development of novel 1,2,4-triazolebased compounds with strong anti-virus efficacy.

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“…Among resistance mutations, K103N and E188K are the most frequent for these drugs . Accordingly, new DAPY analogs having good safety and pharmacokinetic profiles that can overcome drug resistance are still needed and their development is still a hot research focus to develop the next generation of NNRTIs …”

Section: Drug Design Strategiesmentioning

confidence: 99%

Challenges and approaches in the discovery of human immunodeficiency virus type‐1 non‐nucleoside reverse transcriptase inhibitors

Battini

Bollini

2018

Medicinal Research Reviews

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The type I human immunodeficiency virus (HIV‐1) pandemic affecting over 37 million people worldwide continues, with 1.8 million people newly infected each year. Highly active antiretroviral therapy is efficient at reducing viral load and nearly one‐half of the infected population is on treatment. One of the most successful approaches for the treatment of HIV infections is the use of inhibitors for human immunodeficiency virus type‐1 reverse transcriptase (HIV‐1 RT). At present, there are six nonnucleoside reverse transcriptase inhibitors (NNRTIs) approved for clinical use: nevirapine (NVP), delavirdine (DLV), efavirenz (EFV), etravirine (ETV), rilpivirine (RPV), and elsulfavirine. In this review, we will cover the development of different classes of NNRTIs over the last two decades. We will give an overview of traditional medicinal chemistry strategies for structural modification as bioisosterism principles, scaffold hopping, substitute decoration, and molecular hybridization. Furthermore, computer‐aid design as virtual screening, de novo design and free‐energy perturbation will be described in details.

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Fused heterocycles bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 3: Optimization of [1,2,4]triazolo[1,5-a]pyrimidine core via structure-based and physicochemical property-driven approaches

Cited by 78 publications

References 35 publications

Thermal behaviour of some biologically active species based on complexes with a triazolopyrimidine pharmacophore

Thermal behaviour of some biologically active species based on complexes with a triazolopyrimidine pharmacophore

Recent Advances in 1,2,4‐Triazole Scaffolds as Antiviral Agents

Challenges and approaches in the discovery of human immunodeficiency virus type‐1 non‐nucleoside reverse transcriptase inhibitors

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