ChemInform Abstract: Discovery of 1‐(4‐Fluorophenyl)‐(3R)‐ [3‐(4‐fluorophenyl)‐(3S)‐hydroxypropyl] ‐(4S)‐(4‐hydroxyphenyl)‐2‐azetidinone (SCH 58235): A Designed, Potent, Orally Active Inhibitor of Cholesterol Absorption.

Rosenblum, Stuart B.; Huynh, Tram; Afonso, Adriano; Davis, Harry R.; Yumibe, Nathan; Clader, John W.; Burnett, Duane A.

doi:10.1002/chin.199828132

Cited by 4 publications

(4 citation statements)

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“…The drug Ezetimibe inhibits the absorption of cholesterol from the intestine. 33 the compound and facilitates membrane penetration, thereby increasing bioavailability. 34−37 Inspired by these reports, the hydrogen atom or methoxyl in the salicylaldehyde scaffold of complexes Cu1 and Cu2 was replaced with fluorine or other halogen atoms in this study.…”

Section: ■ Introductionmentioning

confidence: 99%

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

et al. 2022

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Twelve new complexes Cu(L1)2 –Cu(L12)2 were designed and synthesized to improve their chemotherapeutic properties. They showed considerable antiproliferative activity against T24 cancer cells but lower cytotoxicity to human normal cells HL-7702 and WI-38. A mechanism study indicated that Cu(L4)2 and Cu(L10)2 were reduced to Fenton-like Cu+ by glutathione depletion, and the resulting Cu+ catalyzed the generation of highly toxic hydroxyl radicals from excess H2O2. Simultaneously, Cu(L4)2 and Cu(L10)2 could decrease the catalase activity to restrain H2O2 transfer to H2O for enhanced chemodynamic therapy (CDT). These induced mitochondrial dysfunctions and endoplasmic reticulum stress to induce T24 cell apoptosis. In addition, Cu(L4)2 and Cu(L10)2 inhibited autophagy flux to promote cell apoptosis. Cu(L4)2 and Cu(L10)2 demonstrated strong tumor inhibition ability in the T24 xenograft model. Moreover, Cu(L10)2 showed higher antitumor activity and a better safety profile than the CDT agent Cu1. Cu(L10)2 exhibited excellent pharmacokinetic properties. Collectively, Cu(L4)2 and Cu(L10)2 could be developed as potential CDT candidates for cancer treatment.

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Section: ■ Introductionmentioning

confidence: 99%

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

et al. 2022

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“…The involvement of MCRs in the synthesis of bioactive scaffolds in medicinal chemistry and drug discovery paved the way for the discovery and preparation of drugs such as lidocaine (xylocaine) [88], mandipropamid [89],nifedipine (procardia) [90], ezetimibe (zetia) [91], and prostaglandin B1 [92].…”

Section: Discussionmentioning

confidence: 99%

Multicomponent Reactions as an Efficient and Facile Alternative Route in Organic Synthesis and Applications

Mohlala¹,

Rashamuse²,

Coyanis³

2023

Preprint

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Multicomponent reactions (MCRs) have been used for more than a century; since their discovery in 1850 by Strecker. To date, MCRs route is regarded as a beneficial strategy due to its capacity to quickly produce molecular diversity and structural complexity of interest for a variety of applications. Despite having famous MRCs such as the Ugi, Passerini, Biginelli, and Hantzsch, this re-view portrays the importance of MCRs in the synthesis of desired products towards applications such as medicinal purposes, sustainable chemistry, and polymerisation. MCRs provide ad-vantages such as reducing the number of sequential multiple reactions to one step, atom economy, recyclable catalysts, mild conditions, preventing waste and reduce solvent use.

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“…The incorporation of at least one fluorine atom or a trifluoromethyl group into bioactive compounds could improve metabolic stability, membrane permeability, bioavailability, and the binding affinity of the compound to a target protein, 1 which results in profound pharmacological activities. 2–8 In recent years, fluorinated compounds have been used for a broad range of therapeutic purposes, 9 such as anti-cancer agents, 10 antimicrobial agents, anti-inflammatory agents, 11 anesthetics, and central nervous system drugs. 12 For example, celecoxib ( 1 ), a selective cyclooxygenase-2 inhibitor, has been known as a nonsteroidal anti-inflammatory drug for the treatment of rheumatoid arthritis and osteoarthritis (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Cytotoxic Evaluation of Fluoro and Trifluoromethyl Substituents Containing Novel Naphthoquinone-Fused Podophyllotoxins

Thành

Phương

Anh

et al. 2022

Natural Product Communications

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A series of novel naphthoquinone-fused podophyllotoxins containing fluoro and trifluoromethyl substituents were synthesized in a medium with good yields using two different synthetic approaches: microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, tetronic acid, fluorinated arylaldehydes, and ammonium acetate, and microwave-assisted three-component reactions of 2-amino-1,4-naphthoquinone, tetronic acid, and fluorinated arylaldehydes. The structures of all products were confirmed by spectral analysis. Together, cytotoxicity assessment of the products against four human cancer cell lines (human carcinoma [KB], human hepatocellular carcinoma [HepG2], lung cancer [A549], breast carcinoma [MCF7], and human embryonic kidney [Hek-293]) was performed by MTT assay. Among the obtained compounds, compound 7f turned out to be the most potent anticancer agent with significant cytotoxic activity against KB, HepG2, and MCF cancer cell lines.

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ChemInform Abstract: Discovery of 1‐(4‐Fluorophenyl)‐(3R)‐ [3‐(4‐fluorophenyl)‐(3S)‐hydroxypropyl] ‐(4S)‐(4‐hydroxyphenyl)‐2‐azetidinone (SCH 58235): A Designed, Potent, Orally Active Inhibitor of Cholesterol Absorption.

Cited by 4 publications

References 1 publication

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

Copper(II) Complexes of Halogenated Quinoline Schiff Base Derivatives Enabled Cancer Therapy through Glutathione-Assisted Chemodynamic Therapy and Inhibition of Autophagy Flux

Multicomponent Reactions as an Efficient and Facile Alternative Route in Organic Synthesis and Applications

Synthesis and Cytotoxic Evaluation of Fluoro and Trifluoromethyl Substituents Containing Novel Naphthoquinone-Fused Podophyllotoxins

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