39755-33-4Relevant academic research and scientific papers
Differential analgesic activity of the enantiomers of atropine derivatives does not correlate with their muscarinic subtype selectivity
Dei,Bartolini,Bellucci,Ghelardini,Gualtieri,Manetti,Romanelli,Scapecchi,Teodori
, p. 595 - 605 (2007/10/03)
The enantiomers of several tropic and p-substituted tropic acid esters related to atropine obtained by esterification under non-racemizing conditions after resolution of the corresponding racemic acids [(+)- and (-)-18, (+)- and (-)-19] are reported. They were tested in vitro on muscarinic subtype receptors and in vivo for their analgesic activity on mice. As in the case of the lead compound, R-(+)-hyoscyamine, these substances show enantioselectivity in analgesic tests, the eutomers being the R-(+) or R-(+)-p-substituted tropic acid derivatives. However, this property, which is a consequence of increased central release of ACh, seems unrelated to muscarinic subtype selectivity insofar as the compounds are unable to discriminate muscarinic subtype receptors. A possible explanation of these results which does not involve subtype selectivity is proposed, based on the recently developed concept of inverse agonism.
Molecular Modification of Anticholinergics as Probes for Muscarinic Receptors. Amino Esters of α-Substituted Phenylacetic Acid and Related Analogues
Lu, Mattias C.,Wung, Walley E.,Shih, Lisa B.,Callejas, Soledad,Gearien, James E.,Thompson, Emmanuel B.
, p. 273 - 278 (2007/10/02)
Two series of compounds having the general structure of C6H5CRR'COOCH2CH2NEt2 were synthesized and examined for their antispasmodic activities.These compounds were selected as structural probes for exploring the nature of muscarinic cholinergic receptor binding sites that interact with atropine-like anticholinergics.These studies indicate a rather strict size limitation for the hydrophobic region of the receptor and suggest intramolecular hydrogen bonding as a possible means to explain the observed stereoselectivity.
