van Herk, T. published the artcilePyrazole Derivatives as Partial Agonists for the Nicotinic Acid Receptor, Formula: C7H10N2O2, the publication is Journal of Medicinal Chemistry (2003), 46(18), 3945-3951, database is CAplus and MEDLINE.
Nicotinic acid as a hypolipidemic agent appears unique due to its potential to increase HDL cholesterol levels to a greater extent than other drugs. However, it has some side effects, among which severe skin flushing is the most frequent and often limits patients’ compliance. In a search for novel agonists for the recently identified and cloned G protein-coupled nicotinic acid receptor, we synthesized a series of substituted pyrazole-3-carboxylic acids that proved to have substantial affinity for this receptor. The affinities were measured by inhibition of [3H]nicotinic acid binding to rat spleen membranes. Potencies and intrinsic activities relative to nicotinic acid were determined by their effects on [35S]GTPγS binding to rat adipocyte and spleen membranes. Interestingly, most compounds were partial agonists. In particular, 2-diazabicyclo[3,3,04,8]octa-3,8-diene-3-carboxylic acid (4c) and 5-propylpyrazole-3-carboxylic acid (4f) proved active with Ki values of approx. 0.15 μM and EC50 values of approx. 6 μM, while their intrinsic activity was only ∼50% when compared to nicotinic acid. Even slightly more active was 5-butylpyrazole-3-carboxylic acid (4g) with a Ki value of 0.072 μM, an EC50 value of 4.12 μM, and a relative intrinsic activity of 75%. Of the aralkyl derivatives, 4q (5-(3-chlorobenzyl)pyrazole-3-carboxylic acid) was the most active with a relatively low intrinsic activity of 39%. Partial agonism of the pyrazole derivatives was confirmed by inhibition of G protein activation in response to nicotinic acid by these compounds The pyrazoles both inhibited the maximum effect elicited by 100 μM nicotinic acid and concentration dependently shifted nicotinic acid concentration-response curves to the right, pointing to a competitive mechanism of action.
Journal of Medicinal Chemistry published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C11H10O, Formula: C7H10N2O2.
Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics