De novo design and synthesis of HIV-1 integrase inhibitors

Makhija, Mahindra T.; Kasliwal, Rajesh T; Kulkarni, Vithal M.; Neamati, Nouri

doi:10.1016/j.bmc.2004.02.005

Cited by 52 publications

(29 citation statements)

References 42 publications

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“…The yield was decreased when the reaction was conducted using increased power input for 4.0 min (Entry 3, Table 1) perhaps due to the partial decomposition of the product formed. In order to compare the present method with the conventional one 21 the reaction of 1a with 2a was carried out in methanol under refluxing condition for 10h when 3a was isolated in 88% yield (Entry 4, Table 1). It is therefore clear that the present method, although does not offer any significant advantages over the conventional method in terms of product nature and yield, can however, reduce the reaction time remarkably avoiding the use of solvent and prolonged heating conditions.…”

Section: Resultsmentioning

confidence: 99%

“…19,20 These methods are diverse, but frequently involve the condensation of a b-keto ester or b-keto aldehyde with substituted or unsubstituted hydrazines. 21,22 These methodologies, although utilized for the preparation of a variety of pyrazolones, often require the use of refluxing conditions and lengthy reaction time, ideally 3-10 h. Moreover, the use of excess solvent and its recovery can pose a major environmental problem especially in the large-scale synthesis. Due to the increased environmental consciousness throughout the world extensive efforts have been devoted to develop an alternate synthetic approach for biologically and synthetically important compounds.…”

Section: Introductionmentioning

confidence: 99%

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High speed synthesis of pyrazolones using microwave-assisted neat reaction technology

Pal¹,

Mareddy²,

Devi³

2008

J. Braz. Chem. Soc.

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Descrevemos uma síntese rápida e pratica de pirazolonas, na ausência de solvente, sob irradiação de microondas. Esta metodologia sintética envolve a reação de b-cetoésteres com hidrazinas substituídas e não-substituídas e oferece uma preparação simples e direta de diferentes pirazolonas com alta regioseletividade. Essas pirazolonas podem existir em diferentes formas tautoméricas em solução e o anel 2-aril-pirazol-3-ona permanece torcido em relação ao plano da pirazolona no estado cristalino. O mecanismo da reação é proposto levando em conta a regiosseletividade. Uma das pirazolonas obtidas nesse processo foi usada na preparação de um derivado espirociclohexanona de significativo potencial biológico.A high speed, solvent-free, and practical synthesis of pyrazolones under microwave irradiation is described. This greener synthetic methodology involves the reaction of b-keto ester with substituted or unsubstituted hydrazine and provides a simple and straightforward one-pot approach for the synthesis of a variety of pyrazolone derivatives with high regioselectivity. These pyrazolones can exist in different tautomeric forms in solution and the aryl ring of 2-aryl pyrazol-3-ones remain twisted with respect to the pyrazole plane in the crystal state. Mechanism of the reaction accounting the regioselectivity has been proposed. One of the pyrazolones obtained via this process was utilized to prepare a spirocyclohexanone derivative of potential biological significance.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High speed synthesis of pyrazolones using microwave-assisted neat reaction technology

Pal¹,

Mareddy²,

Devi³

2008

J. Braz. Chem. Soc.

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“…The preparation of pyrazolone derivatives involve the condensation of a β-keto ester with substituted or unsubstituted hydrazines. The compounds were synthesized via a similar method described elsewhere (Khalil et al, 2005;Makhija et al, 2004;Song and Zhu, 2001;Abood and Al-Shlhai, 2012). The synthesis of 3-propyl -5 -pyrazolone and the structures of the compounds in this investigation are shown…”

Section: Methodsmentioning

confidence: 99%

<i>In vitro</i> antimicrobial evaluation of pyrazolone derivatives

Ahar

Sadr

Zare

et al. 2015

Bangladesh J Pharmacol

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“…69 All these newly designed compounds were synthesized and evaluated for their IN inhibitory activity. Unfortunately, none of these compounds exhibited potent IN inhibitory activity.…”

Section: Miscellaneous Compoundsmentioning

confidence: 99%

HIV‐1 integrase inhibitors: 2003–2004 update

Dayam

Deng

Neamati

2006

Medicinal Research Reviews

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The integration of viral cDNA into the host genome is an essential step in the HIV-1-life cycle and is mediated by the virally encoded enzyme, integrase (IN). Inhibition of this process provides an attractive strategy for antiviral drug design. The discovery of beta-diketo acid inhibitors played a major role in validating IN as a legitimate antiretroviral drug target. Over a decade of research, a plethora of IN inhibitors have been discovered and some showed antiviral activity consistent with their effect on IN. To date, at least two compounds have been tested in human but none are close to the FDA approval. In this review, we provide a comprehensive report of all small-molecule IN inhibitors discovered during the years 2003 and 2004. Compilation of such data will prove beneficial in developing QSAR, virtual screening, pharmacophore hypothesis generation, and validation.

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De novo design and synthesis of HIV-1 integrase inhibitors

Cited by 52 publications

References 42 publications

High speed synthesis of pyrazolones using microwave-assisted neat reaction technology

High speed synthesis of pyrazolones using microwave-assisted neat reaction technology

<i>In vitro</i> antimicrobial evaluation of pyrazolone derivatives

HIV‐1 integrase inhibitors: 2003–2004 update

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