Making Sense of Structures by Utilizing Mother Nature's Chemical Libraries as Leads to Potential Drugs

Newman, David J.; Cragg, Gordon M.

doi:10.1002/9781118794623.ch21

Cited by 3 publications

(2 citation statements)

References 63 publications

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“…Privileged structures are defined as molecular frameworks that are able to provide useful ligands for multiple types of receptors or enzymes through proper structural modifications. In combination with their favorable drug-like properties, privileged structures or scaffolds are widely used in rational drug design to find new lead compounds or drug candidates [1,2,3]. Pyrazole derivatives represent one of the most active classes of compounds that possess a wide spectrum of biological activities, including antibacterial and antifungal [4,5], antitumor [6,7], anti-inflammatory and analgesic [8,9], antitubercular [10], antiviral [11,12], anti-Alzheimer’s [13,14], α-glucosidase inhibitory [15], anti-diabetic [16], antileishmanial [17,18], anti-malarial [19], radioimaging [20], acaricidal and insecticidal [21,22] activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

et al. 2019

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To find novel antitumor agents, a series of 1H-benzofuro[3,2-c]pyrazole derivatives 4a-e were designed and synthesized. The treatment of 6-methoxybenzofuran-3(2H)-one 3 with LiHMDS in anhydrous tetrahydrofuran (THF) followed by reaction with 3-substitued phenyl isothiocyanate gave the thioamide intermediates, which underwent condensation with hydrazine monohydrate in dioxane/EtOH (1:1) to provide the benzofuropyrazole derivatives 4a–e as well as the unexpected pyrazole derivatives 5a–e. In tumor cell growth inhibitory assay, all the benzofuropyrazole derivatives were not active against the breast tumor MCF-7 cell, only 4a was highly active and more potent than ABT-751 against the leukemia K562 (GI50 = 0.26 μM) and lung tumor A549 cells (GI50 = 0.19 μM), while other benzofuropyrazoles showed very weak inhibitory activity. In contrast, the pyrazoles 5a-e were in general more potent than the benzofuropyrazoles 4a–e. Compound 5a exhibited a similar tendency to that of 4a with high potency against K562 and A549 cells but weak effects on MCF-7 cell. Both pyrazoles 5b and 5e exhibited high inhibitory activities against K562, MCF-7 and A549 cells. The most active compound 5b was much more potent than ABT-751 against K562 and A549 cells with GI50 values of 0.021 and 0.69 μM, respectively. Moreover, 5b was identified as a novel tubulin polymerization inhibitor with an IC50 of 7.30 μM.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

et al. 2019

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“…Nitrogen-containing molecules are an important class of compounds, as they are ubiquitous components of biologically active molecules . Among them, N -methyl secondary amines are found in many important drugs, such as fluoxetine (Prozac), duloxetine, desipramine, betahistine, and l -epinephrine (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides

Mathieu

Patel

Lebel

2020

Org. Process Res. Dev.

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The first continuous flow process was developed to synthesize N-methyl secondary amines from alkyl mesylates and epoxides via a nucleophilic substitution using aqueous methylamine. A variety of N-methyl secondary amines were produced in good to excellent yields, including a number of bioactive compounds or their precursors. Up to 10.6 g (88% yield) of an N-methyl secondary amine was produced in 140 min process time. The amination procedure included an in-line workup, and the starting mesylate material was also produced in continuous flow from the corresponding alcohol. Finally, an in-line process combining the mesylate synthesis and nucleophilic substitution was developed.

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Natural Products as Sources of Anticancer Agents: Current Approaches and Perspectives

Cragg¹,

Newman²

2018

Natural Products as Source of Molecules With Therapeutic Potential

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Making Sense of Structures by Utilizing Mother Nature's Chemical Libraries as Leads to Potential Drugs

Cited by 3 publications

References 63 publications

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides

Natural Products as Sources of Anticancer Agents: Current Approaches and Perspectives

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