A possible structural determinant of selectivity of boldine and derivatives for the α_1A‐adrenoceptor subtype

Abstract

1 The selectivity of action of boldine and the related aporphine alkaloids, predicentrine (9-0-methylboldine) and glaucine (2,9-0-dimethylboldine) on 5 These results suggest that whereas the aporphine structure shared by these alkaloids is responsible for their selectivity of action for the aIA-adrenoceptor subtype in rat cerebral cortex, defined functional groups, namely the 2-hydroxy function, induces a significant increase in aCIA-subtype selectivity and affinity.

Role of α-Adrenergic Receptors in the Effect of the β-Adrenergic Receptor Ligands, CGP 12177, Bupranolol, and SR 59230A, on the Contraction of Rat Intrapulmonary Artery

“…After decapitation, the brain was rapidly removed from female Wistar rats (180 -200 g, 12 weeks old, obtained from Harlan Interfauna Ibérica, Barcelona, Spain). Cerebral cortex membranes were prepared as previously described (Madrero et al, 1996). Protein concentration was determined according to the method of Bradford (1976) .…”

N-Substitution AND Á1-Adrenergic RECEPTOR AFFINITY OF LAUDANOSINE ANALOGUES

“…6 On the other hand, the aporphine glaucine (6) also binds to these receptors with slightly greater affinity, and the inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components attributed to α 1A -and α 1B -receptor binding (K i = 0.07 and 1.20 µM, respectively). 12 The rather small differences in the affinities of tetrahydropalmatine and glaucine, on one hand, and of the N-unsubstituted and N-substituted BTHIQs, on the other, suggest that both the extended and the semifolded conformations can be accommodated by the ligand site of the α 1 -adrenergic receptor.…”

Evaluation and synthesis of 7-arylhydroxymethyltriazolopyridines as potential cardiovascular agents

“…In the context of our work on synthesis and reactivity of [1,2,3]triazolo[1,5-a]pyridines 1 and 2, 5 we have studied lithiation reactions that are regioselective at the 7 position. The 7-lithio derivatives are formed at -40ºC and can be trapped by electrophiles.…”

“…Some aporphine alkaloids have been also reported to have a relaxant effect on vascular smooth muscle that is also related to their capacity to inhibit Ca +2 influx through voltage-operated Ca +2 channels or to block α 1 -adrenoceptors. [1][2][3][4] The search for new compounds with activity in vascular pathologies is an interesting challenge, considering that these conditions are the major cause of death in the European Community. The idea that 7-arylhydroxymethyltriazolopyridines might be considered as structural analogues of the above mentioned compounds led us to synthesize a series of these triazolopyridine derivatives and to carry out a preliminary evaluation of them as cardiovascular agents.…”

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Abstract 7-Arylhydroxymethyltriazolopyridines 3a-c and 4a-d were synthesized by regioselective lithiation of [1,2,3]triazolo[1,5-a]pyridines 1 and 2 and subsequent trapping of the 7-lithioderivatives formed using aryl aldehydes as electrophiles. The structural relationship between compounds 3a-c and 4a-d and arylethanolamines suggested their consideration as potential cardiovascular agents.

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