118468-19-2Relevant academic research and scientific papers
6-SUBSTITUTED PHENOXYCHROMAN CARBOXYLIC ACID DERIVATIVES
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Page/Page column 152, (2010/01/30)
Compounds of Formula (I): in which A1, A2, W, L, G, R7a, R7b, R8, R9 and R10 have the meanings given in the specification, are DP2 receptor modulators useful in the treatment of immunologic diseases.
Substituted 1-(aminomethyl)-2-(arylacetyl)-1,2,3,4- tetrahydroisoquinolines: A novel class of very potent antinociceptive agents with varying degrees of selectivity for κ and μ opioid receptors
Vecchietti,Clarke,Colle,Dondio,Giardina,Petrone,Sbacchi
, p. 2970 - 2978 (2007/10/02)
This study describes the synthesis of a series of novel substituted 1- (aminomethyl)-2-(arylacetyl)-1,2,3,4-tetrahydroisoquinolines, and discusses their structure-activity relationships (SARs) using binding affinity for opioid receptors and antinociceptive potency as the indices of biological activity. The introduction of a hydroxy substituent in position 5 of the isoquinoline nucleus generated a compound, 40, which is 2 times more potent than the previously disclosed unsubstituted analogue 39 in mouse models of antinociception. A QSAR analysis of the 5-substitution clearly demonstrates that antinociceptive activity is inversely associated with the lipophilicity of the substituents. The substituted compounds described herein are less selective for the κ opioid receptors than the unsubstituted isoquinoline 39. For example, the 5-hydroxy-substituted compound 59 shows high affinity for κ opioid receptors (K(i) κ = 0.09 nM) and a (K(i) μ/K(i) κ ratio of only 5. However, a multiple linear regression analysis demonstrates a lack of correlation between antinociceptive activity and affinity for the μ opioid receptor. On the other hand, the correlation between binding affinity to κ opioid receptor and antinociceptive activity was statistically significant.
