Development of chemical probes: Toward the mode of action of a methylene-linked di(aryl acetate) E1

Smith, Mark E.; Gunn, Richard M.; Rosivatz, Evelyn; Mak, Lok Hang; Woscholski, Rüdiger; Hailes, Helen C.

doi:10.1016/j.bmc.2010.06.017

Cited by 1 publication

(2 citation statements)

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“…The ester derivatives were obtained as reported in Scheme . Chloroethyl derivative 18 was obtained from commercially available 4‐(hydroxyethyl)phenol by treatment with SOCl 2 in ethanol‐free CHCl 3 and anhydrous triethylamine by using a slightly modified version of the procedure described by Smith; 18 was then treated with 6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline hydrochloride in anhydrous acetonitrile in the presence of K 2 CO 3 , which led to phenol 19 . As in the case of the amides, esters 7 – 11 were obtained by reaction of 19 with the appropriate carboxylic acid chloride, whereas propiolic derivative 12 was obtained by reaction of 19 with 3‐(3,4,5‐trimethoxyphenyl)propiolic acid by using EDCI and DMAP.…”

Section: Resultsmentioning

confidence: 99%

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Structure–Activity Relationship Studies on 6,7‐Dimethoxy‐2‐phenethyl‐1,2,3,4‐tetrahydroisoquinoline Derivatives as Multidrug Resistance Reversers

et al. 2017

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A series of derivatives were synthesized and studied with the aim to investigate the structure–activity relationships of the two P‐glycoprotein (P‐gp) modulators elacridar and tariquidar. Then, different aryl‐substituted amides were inserted, and to explore the effects of varying the amide function, the corresponding isosteric ester derivatives and some alkylamine analogues were synthesized. The new compounds were studied to evaluate their P‐gp interaction profile and selectivity toward the two other ABC transporters, multidrug‐resistance‐associated protein‐1 (MRP‐1) and breast cancer resistance protein (BCRP). Investigation of the chemical stability of the amide and ester derivatives toward spontaneous or enzymatic hydrolysis showed that these compounds were stable in phosphate‐buffered saline and human plasma. This study allowed us to evaluate the selectivity of the three series on the three efflux pumps and to propose the structural requirements that define the P‐gp interaction profile. We identified two P‐gp substrates, a P‐gp inhibitor, and three ester derivatives that were active on BCRP, which opens a new scenario in the development of ligands active toward this pump.

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Section: Resultsmentioning

confidence: 99%

“…4‐(2‐Chloroethyl)phenol (18) : SOCl 2 (0.2 mL, 2.90 mmol) was added to a solution of 4‐(2‐hydroxyethyl)phenol (200.0 mg, 1.45 mmol) and anhydrous Et 3 N (0.5 mL 3.60 mmol) in ethanol‐free CHCl 3 (6 mL). After 24 h, the solvent was removed under reduced pressure, and the mixture was treated with CH 2 Cl 2 (10 mL).…”

Section: Methodsmentioning

confidence: 99%