The synthesis, conformation and antimuscarinic properties of ketone analogues of tropane esters

M Tavasli; David O'Hagan; AS Batsanov; GR Foxon; RF Halliwell; JAK Howard

doi:10.1039/a907130j

The synthesis, conformation and antimuscarinic properties of ketone analogues of tropane esters

M Tavasli, David O'Hagan, AS Batsanov, GR Foxon, RF Halliwell, JAK Howard

Research output: Contribution to journal › Article › peer-review

Abstract

A synthesis of the ketone analogues of three naturally occurring tropane esters has been developed and one of the ketones has been evaluated for its efficacy as a muscarinic acetylcholine receptor (mAChR) antagonist in guinea-pig ileum. The ketone analogue of apoatropine displayed an IC50 value in the micromolar range when compared to atropine, which has antagonist activity in the nanomolar range. The conformational change in replacing the bridging oxygen of the ester moiety by CH2 has been assessed by X-ray structure analysis of one of the compounds and has been evaluated more widely in a Cambridge Crystallographic Database survey. The structural data reveals that both the tropane esters and tropane ketones adopt similar conformations.

Original language	English
Pages (from-to)	3455-3461
Number of pages	7
Journal	Journal of the Chemical Society, Perkin Transactions 1
Issue number	23
DOIs	https://doi.org/10.1039/a907130j
Publication status	Published - 1999

Keywords

PHARMACOLOGICAL ACTIVITY
RECEPTOR ANTAGONISTS
BINDING
DERIVATIVES
OXIDATION
ALCOHOLS
POTENT

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abstract = "A synthesis of the ketone analogues of three naturally occurring tropane esters has been developed and one of the ketones has been evaluated for its efficacy as a muscarinic acetylcholine receptor (mAChR) antagonist in guinea-pig ileum. The ketone analogue of apoatropine displayed an IC50 value in the micromolar range when compared to atropine, which has antagonist activity in the nanomolar range. The conformational change in replacing the bridging oxygen of the ester moiety by CH2 has been assessed by X-ray structure analysis of one of the compounds and has been evaluated more widely in a Cambridge Crystallographic Database survey. The structural data reveals that both the tropane esters and tropane ketones adopt similar conformations.",

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T1 - The synthesis, conformation and antimuscarinic properties of ketone analogues of tropane esters

AU - Tavasli, M

AU - O'Hagan, David

AU - Batsanov, AS

AU - Foxon, GR

AU - Halliwell, RF

AU - Howard, JAK

PY - 1999

Y1 - 1999

N2 - A synthesis of the ketone analogues of three naturally occurring tropane esters has been developed and one of the ketones has been evaluated for its efficacy as a muscarinic acetylcholine receptor (mAChR) antagonist in guinea-pig ileum. The ketone analogue of apoatropine displayed an IC50 value in the micromolar range when compared to atropine, which has antagonist activity in the nanomolar range. The conformational change in replacing the bridging oxygen of the ester moiety by CH2 has been assessed by X-ray structure analysis of one of the compounds and has been evaluated more widely in a Cambridge Crystallographic Database survey. The structural data reveals that both the tropane esters and tropane ketones adopt similar conformations.

AB - A synthesis of the ketone analogues of three naturally occurring tropane esters has been developed and one of the ketones has been evaluated for its efficacy as a muscarinic acetylcholine receptor (mAChR) antagonist in guinea-pig ileum. The ketone analogue of apoatropine displayed an IC50 value in the micromolar range when compared to atropine, which has antagonist activity in the nanomolar range. The conformational change in replacing the bridging oxygen of the ester moiety by CH2 has been assessed by X-ray structure analysis of one of the compounds and has been evaluated more widely in a Cambridge Crystallographic Database survey. The structural data reveals that both the tropane esters and tropane ketones adopt similar conformations.

KW - PHARMACOLOGICAL ACTIVITY

KW - RECEPTOR ANTAGONISTS

KW - BINDING

KW - DERIVATIVES

KW - OXIDATION

KW - ALCOHOLS

KW - POTENT

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DO - 10.1039/a907130j

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JO - Journal of the Chemical Society, Perkin Transactions 1

JF - Journal of the Chemical Society, Perkin Transactions 1

IS - 23

ER -

The synthesis, conformation and antimuscarinic properties of ketone analogues of tropane esters

Abstract

Keywords

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