230293-43-3Relevant academic research and scientific papers
Further structure-activity relationships in the series of tropanyl esters endowed with potent antinociceptive activity
Scapecchi, Serena,Giorgi, Antonella,Bellucci, Cristina,Dei, Silvia,Ghelardini, Carla,Manetti, Dina,Romanelli, M. Novella,Teodori, Elisabetta
, p. 764 - 772 (2007/10/03)
Several analogs of the α-tropanyl esters of 2-(4-chlorophenoxy)butyric acid (SM21) and 2-phenylthiobutyric acid (SM32), endowed with potent antinociceptive and cognition enhancing activity, were synthesized, aimed at obtaining more potent and safe drug candidates. Variation of the acyl moiety, as well as the conformational restriction of atropine to give the α-tropanyl ester of 2,3-dihydrobenzofurane-3-carboxylic acid (18), practically abolished activity. In the case of 18, the antimuscarinic activity was also severely affected by the conformation restrain. On the contrary, conformational restriction of phenoxybutyric and phenylthiobutyric acid derivatives to give the α-tropanyl ester of 2,3-dihydro-benzofurane-2-carboxylic acid and 2,3-dihydro-benzothiophene-2-carboxylic acid, afforded potent analgesic drugs that unfortunately were too toxic to be reliable drug candidates. A series of related esters of benzofurane-3-carboxylic acid and benzothiophene-3-carboxylic acid were also studied and found to be potent but toxic analgesics.
α-Adrenoreceptor Reagents. 2. Effects of Modification of the 1,4-Benzodioxan Ring System on α-Adrenoreceptor Activity
Chapleo, Christopher B.,Myers, Peter L.,Butler, Richard C. M.,Davis, John A.,Doxey, John C.,et al.
, p. 570 - 576 (2007/10/02)
Modification of the 1,4-benzodioxan ring present in RX 781094 (1) has not previously been considered.This paper describes a number of analogues of this ring system, including compounds in which one of the oxygen atoms has been replaced by a methylene group and also those in which the ring size has been changed to give, for example, furan and thiophene derivatives.The dihydroxybenzofuranylimidazoline compound 7 is the only analogue possesing presynaptic antagonist potency and selectivity comparable to that of 1.In view of this result, a number of derivatives was prepared to determine the structure-activity relationships within this series.Many derivatives, as well as the parent compound 7, were found to possess presynaptic α2-adrenoreceptor antagonist and postsynaptic α1-adrenoreceptor partial agonist properties.Two of the selective presynaptic antagonists,13 and 14, possess greater potency and selectivity than that possessed by 1.The 5-chloro derivative 25 is twice as potent as 1 after oral administration but only about half as potent when given intravenously.
