Synthesis and activity of (R)-(−)-m-trimethylacetoxy-α-[(methylamino)methyl]benzyl alcohol hydrochloride: A prodrug form of (R)-(−)-phenylephrine

Yuan, Sun-Shine; Bodor, Nicolae

doi:10.1002/jps.2600650637

Cited by 20 publications

(4 citation statements)

References 5 publications

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“…The structures of the two isomers were assigned based on the similarity of 1 H NMR spectra of an analogue for which a single crystal X‐ray structure has been obtained (unpublished results). Compound 12 has been reported previously, although the diastereomers have never been isolated.…”

Section: Resultsmentioning

confidence: 88%

Scoping Studies into the Structure‐Activity Relationship (SAR) of Phenylephrine‐Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense

et al. 2016

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Human African Trypanosomiasis (HAT) is a disease caused by the parasite Trypanosoma brucei and is classified as a neglected tropical disease of concern in sub‐Saharan Africa. A scoping study has been undertaken to develop a preliminary structure activity relationship of a tetrahydroisoquinoline scaffold. Fourteen compounds based around this core scaffold were synthesised and evaluated for their activity against Trypanosoma brucei rhodesiense in vitro. Initial results are promising with a number of analogues showing low micromolar inhibition of T.b.rhodesiense with acceptable selectivity over mammalian cells. The most promising is a secondary amine analogue showing the most potent inhibition of T.b.rhodesiense, with an IC50 value of 0.25 ± 0.02 μM, while also showing low cytotoxicity to mammalian cells.

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Section: Resultsmentioning

confidence: 88%

Scoping Studies into the Structure‐Activity Relationship (SAR) of Phenylephrine‐Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense

et al. 2016

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“…Lipophilic chemical modification has been widely used for various hydrophilic drugs to improve their ocular bioavailability 4–8. The lipophilic prodrug modification may release GCV continuously in the eye, depending on the rate of hydrolysis and elimination of the pro moiety.…”

Section: Introductionmentioning

confidence: 99%

Effect of Mono‐ and Di‐acylation on the Ocular Disposition of Ganciclovir: Physicochemical Properties, Ocular Bioreversion, and Antiviral Activity of Short Chain Ester Prodrugs

Dias

Anand

Mitra

2002

Journal of Pharmaceutical Sciences

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“…The two isomers were separated by column chromatography and represent the two diastereoisomers of the para‐ substituted product. This derivative has been reported previously, however the separation of the diastereoisomers has not been reported.…”

Section: Resultsmentioning

confidence: 57%

Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline

et al. 2017

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Condensation of phenylephrine with different aldehydes, under Pictet‐Spengler cyclisation conditions, afforded a series of tetrahydroisoquinoline derivatives as mixtures of cis/trans isomers. Single crystal X‐ray analysis of the dibenzoate derivative of one of the 4‐nitrophenyl isomers confirmed it to be the trans isomer. The conformation of the cis isomer was determined through computational experiments and comparison of the predicted and observed 1H NMR spectra, particularly the magnitude of the coupling constants. Fourteen tetrahydroisoquinoline derivatives were then evaluated for their activity towards T. b. rhodesiense, two strains of P. falciparum, and mammalian cells. The most promising derivative, the undecyl derivative, showed good activity towards T. b. rhodesiense with an IC50 value in the sub‐micromolar range and good selectivity over mammalian cells. The same derivative also showed activity against both strains of P. falciparum with IC50 values in the low micromolar range.

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Synthesis and activity of (R)-(−)-m-trimethylacetoxy-α-[(methylamino)methyl]benzyl alcohol hydrochloride: A prodrug form of (R)-(−)-phenylephrine

Cited by 20 publications

References 5 publications

Scoping Studies into the Structure‐Activity Relationship (SAR) of Phenylephrine‐Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense

Scoping Studies into the Structure‐Activity Relationship (SAR) of Phenylephrine‐Derived Analogues as Inhibitors of Trypanosoma brucei rhodesiense

Effect of Mono‐ and Di‐acylation on the Ocular Disposition of Ganciclovir: Physicochemical Properties, Ocular Bioreversion, and Antiviral Activity of Short Chain Ester Prodrugs

Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline

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