AN ALKALOID WITH HIGH ANTIMALARIAL ACTIVITY FROM DICHROA FEBRIFUGA1

Koepfli, J. B.; Mead, James F.; Brockman, John A.

doi:10.1021/ja01199a513

Cited by 193 publications

(92 citation statements)

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“…The interest in the medicinal chemistry of quinazolinones derivatives was stimulated in the early 1950s with the elucidation of the structure of Febrifugina [16], an alkaloid, which was effective against malaria. The methaqualone [17] was first synthesized in 1951 and is the best known quinazolinone derivative, famous for its hypnotic-sedative effects [18].…”

Section: Quinazolinesmentioning

confidence: 99%

In Silico Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

Fernandes¹,

Pereira²,

Marinho³

et al. 2015

OJMC

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In silico pharmacokinetics studies can aid the search for molecules with potential ability to be drug candidates. In this paper, a number of quinazoline candidates for epidermal growth factor receptor inhibitors-EGFR, important targets for the treatment of cancer, are computationally analyzed. The literature described that 69 quinazoline molecules were synthesized and the respective half maximum inhibitory concentrations (IC50) were obtained. A bilinear parabolic model was built to investigate the druglikeness by correlating the corresponding lipophilicities, which can be represented by the ideal Log P, with the optimal biological activity in terms of pIC50 values. Structural characteristics leading to improved pharmacokinetics parameters were then analyzed. Compound 56 exhibited the lowest IC50 and, therefore, it had the highest ability to inhibit the EGFR. In the present work, the most potent inhibitor 56 is not calculated to be the most promising drug candidate, since it's out of the parabolic model obtained due to a Log P above 5, which is not within the expected optimum range. Finally, this work is an example of computational prediction that an experimentally, highly active EGFR inhibitor can be unsuccessful as drug candidate because of pitfalls in pharmacokinetics parameters.

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Section: Quinazolinesmentioning

confidence: 99%

In Silico Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

Fernandes¹,

Pereira²,

Marinho³

et al. 2015

OJMC

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“…1 Particularly, systems with the piperidin-2-ol skeleton having substituents at 2-position 2 and 6-position 3 are of great pharmacological interest. For instance, (+)-febrifugine (1) is a natural product isolated from Dichroa febrifuga, 4 a plant used in traditional Chinese medicine to treat malaria ( Figure 1). A synthetic propanoic acid derivative 2, with a 3-hydroxyl-2-piperidinyl unit, showed a potent in vitro activity as a GABA receptor binder, similar to that displayed by baclofen.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Aza-Henry Reaction of Chiral tert-Butanesulfinyl Imines with Methyl or Ethyl 4-Nitrobutanoate: Easy Access to Enantioenriched 6-Substituted Piperidine-2,5-diones

Muñoz¹,

Foubelo²,

Yus³

2015

HETEROCYCLES

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-The base-catalyzed addition of 4-nitrobutanoates 6 to N-tert-butanesulfinyl imines 8 under solvent-free reaction conditions proceeded with high face diastereoselectivity. The resulting β-nitroamine derivatives 9 were easily transformed into 6-substituted piperidine-2,5-diones 11 upon removal of the sulfinyl group with concomitant δ-lactam formation and functional group transformation under Nef reaction conditions.

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“…[8] Amongst numerous polyhydroxypiperidines, 3-hydroxypiperidine derivatives attracted our attention. Especially, the two naturally occurring compounds (-)-sedacryptine 2 [9] and (+)-isofebrifugine 3 [10] ( Figure 1) possess a fused fivemembered hemiketal motif, and a subgroup of these iminosugars having a bicyclic skeleton and N-alkyl-3-hydroxypiperidine substitution pattern frequently found in nature.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis of a Series of New N‐Alkyl‐3‐hydroxypiperidine Derivatives Containing a Hemiketal

Wang

Luo

et al. 2011

Eur J Org Chem

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A series of new N‐alkyl‐3‐hydroxypiperidine derivatives containing a five‐membered hemiketal were synthesized from 1‐C‐acetylmethyl sugars. Based on the stereochemistry of the products obtained, a plausible mechanism is illustrated. A new approach to the hemiketal, which has undergone hydrogenation in the presence of Pd/C and β‐elimination and intramolecular cycloaddition with 1 % NaOMe in methanol, is reported.

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AN ALKALOID WITH HIGH ANTIMALARIAL ACTIVITY FROM DICHROA FEBRIFUGA¹

Cited by 193 publications

References 0 publications

In <i>Silico</i> Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

In <i>Silico</i> Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

Stereoselective Aza-Henry Reaction of Chiral tert-Butanesulfinyl Imines with Methyl or Ethyl 4-Nitrobutanoate: Easy Access to Enantioenriched 6-Substituted Piperidine-2,5-diones

Stereoselective Synthesis of a Series of New N‐Alkyl‐3‐hydroxypiperidine Derivatives Containing a Hemiketal

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AN ALKALOID WITH HIGH ANTIMALARIAL ACTIVITY FROM DICHROA FEBRIFUGA1

Cited by 193 publications

References 0 publications

In &lt;i&gt;Silico&lt;/i&gt; Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

In &lt;i&gt;Silico&lt;/i&gt; Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

Stereoselective Aza-Henry Reaction of Chiral tert-Butanesulfinyl Imines with Methyl or Ethyl 4-Nitrobutanoate: Easy Access to Enantioenriched 6-Substituted Piperidine-2,5-diones

Stereoselective Synthesis of a Series of New N‐Alkyl‐3‐hydroxypiperidine Derivatives Containing a Hemiketal

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AN ALKALOID WITH HIGH ANTIMALARIAL ACTIVITY FROM DICHROA FEBRIFUGA¹

In <i>Silico</i> Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors

In <i>Silico</i> Pharmacokinetics Studies for Quinazolines Proposed as EGFR Inhibitors