N

Solvay subsequently published in vitro, in vivo, computational and X-ray diffraction data relating to this series of 3,4-diarylpyrazolines [297]. In this publication, a number of compounds were evaluated, in the first instance in vitro at the human CB1 and CB2 receptors, expressed into Chinese hamster ovary (CHO) cells by radioligand binding. In addition, the CB1 functional activity was measured via an arachidonic acid release functional assay. Results for a number of the compounds are shown in Table 6.37.

For compounds (431-434), a significant improvement in binding affinity was observed when the 4-Me group in (430) was substituted with either Cl

(431), 2,4,6-trimethyl (433) or F (434). Replacement of 4-Me with 4-OMe

(432) failed to improve the affinity or functional activity. In the amidine-substituted series (435)-(447), dimethyl compounds (435) and (436) both

Table 6.37 PYRAZOLINE DERIVATIVES AND RIMONABANT (382) - IN VITRO

DATA [297]

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