Synthesis and characterization of methylsalicylate and acetaminophen silyl ether canditates for prodrugs

Assadi, M. G.; Golipour, N.

doi:10.1080/10241220701456032

Cited by 8 publications

(4 citation statements)

References 15 publications

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“…Si-C bonds had strong infrared absorbances at 1231-1268 cm À1 [21][22][23]. These derivatives also showed strong intensity absorptions at 1115-1118 from (Si-O-C) stretching vibrations.…”

Section: Spectroscopic Studiesmentioning

confidence: 99%

Synthesis and characterization of aryltriphenylsilyl ethers and crystal structure of 2,4,6-tri-methylphenyl triphenylsilyl ether

Begeç

Kılıç

Yüksel

et al. 2013

Journal of Coordination Chemistry

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“…Si-C bonds had strong infrared absorbances at 1231-1268 cm À1 [21][22][23]. These derivatives also showed strong intensity absorptions at 1115-1118 from (Si-O-C) stretching vibrations.…”

Section: Spectroscopic Studiesmentioning

confidence: 99%

Synthesis and characterization of aryltriphenylsilyl ethers and crystal structure of 2,4,6-tri-methylphenyl triphenylsilyl ether

Begeç

Kılıç

Yüksel

et al. 2013

Journal of Coordination Chemistry

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“…Acetaminophen has some undesirable properties, including poor compaction, low aqueous solubility and an acrid taste. To overcome such problems associated with acetaminophen several prodrugs have been reported [1][2][3][4] and are in the development stage [5][6][7][8]. In order to fulfill the prerequisite property of drugs i.e.…”

Section: Introductionmentioning

confidence: 99%

Micellar Effects upon the Alkaline Hydrolysis of Acetaminophen Prodrugs: Carboxylic and Carbonic Acid Esters

et al. 2014

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The rates of alkaline hydrolysis for four carboxylate esters (4-acetaminophenyl acetate, 4-acetaminophenyl butyrate, 4-acetaminophenyl heptanoate and 4-acetaminophenyl benzoate) and three carbonate ester (4-acetaminophenyl methylcarbonate, 4-acetaminophenyl ethylcarbonates and 4-acetaminophenyl propylcarbonates) prodrugs of acetaminophen derivatives were determined in aqueous and micellar media. The cationic micelles of cetyltrimethylammonium bromide (CTABr) and cetyltrimethylammonium sulfate [(CTA) 2 SO 4 ] catalyzed the rate of the reaction. The anionic sodium dodecyl sulphate (SDS) and non-ionic Brij-35 surfactants inhibited the rate of the reaction. Added salt did not influence the rate of the reaction in the aqueous medium but decreased the values of observed rate constant in the micellar media. The rate enhancement in cationic micelles was treated by applying the pseudophase ion exchange model while the inhibition effect on the rate of hydrolysis was described using the Poisson-Boltzman pseudophase model. The binding constant (K s ) for the acetaminophen derivatives increased with increasing hydrocarbon chain length while the values of micellar rate constant (k m ) decreased with the increase in chain length. The increase in values of K s and decrease in k m are ascribed to the hydrophobic interaction between the acetaminophen derivative and surfactant molecule and molecular orientation of the substrate in the micelles.

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“…Methylsilyl ether groups have characteristics that are sensitive to acidity, and have been used as protective bases for organic synthesis and drug release groups for nanomaterials [32,33,34]. In addition, these groups have also been used in the design of prodrugs, mainly limited to hydroxyl-conjugated drugs (e.g., acetaminophen, and docetaxel) due to the limitation of the silyl ether structure [35,36]. Although this type of linker has been tried for model ADC construction, which exhibits the characteristics of stability and acid-dependent cleavage, gemcitabine does not meet the high-efficiency requirements for ADC’s payload and it has not been evaluated for its efficacy [37].…”

Section: Introductionmentioning

confidence: 99%

Novel Silyl Ether-Based Acid-Cleavable Antibody-MMAE Conjugates with Appropriate Stability and Efficacy

Wang¹,

Fan²,

Xiao³

et al. 2019

Cancers

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Antibody-drug conjugate (ADC) is a novel efficient drug delivery system that has been successfully used in clinical practice, and it has become a research hotspot in the anti-tumor drug field. Acid-cleavable linkers were first used in clinical ADCs, but their structural variety (e.g., hydrazone and carbonate) is still limited, and their stability is usually insufficient. Designing novel acid-cleavable linkers for the conjugation of the popular cytotoxin monomethyl auristatin E (MMAE) has always been a significant topic. In this paper, we generate a novel, silyl ether-based acid-cleavable antibody-MMAE conjugate, which skillfully achieves efficient combination of amino-conjugated MMAE with the acid-triggered silyl ether group by introducing p-hydroxybenzyl alcohol (PHB). The stability, acid-dependence cleavage, effective mechanism, efficacy and safety of the resulting ADC were systematically studied; the results show that it exhibits a significant improvement in stability, while maintaining appropriate efficacy and controlled therapeutic toxicity. This strategy is expected to expand a new type of acid-cleavable linkers for the development of ADCs with highly potent payloads.

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Synthesis and characterization of methylsalicylate and acetaminophen silyl ether canditates for prodrugs

Cited by 8 publications

References 15 publications

Synthesis and characterization of aryltriphenylsilyl ethers and crystal structure of 2,4,6-tri-methylphenyl triphenylsilyl ether

Synthesis and characterization of aryltriphenylsilyl ethers and crystal structure of 2,4,6-tri-methylphenyl triphenylsilyl ether

Micellar Effects upon the Alkaline Hydrolysis of Acetaminophen Prodrugs: Carboxylic and Carbonic Acid Esters

Novel Silyl Ether-Based Acid-Cleavable Antibody-MMAE Conjugates with Appropriate Stability and Efficacy

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