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Usage

Uses

Used in Pharmaceutical Industry:
5-Butyl-1H-pyrazole-3-carboxylic acid is used as a drug candidate for the treatment of dyslipidemic disorders. It functions as a partial agonist of HCA2 (GPR109A), a G protein-coupled receptor, which plays a crucial role in lipid metabolism. By activating this receptor, 5-Butyl-1H-pyrazole-3-carboxylic acid can achieve a beneficial lipid-lowering effect similar to niacin, making it a promising candidate for the development of new therapeutic agents to treat dyslipidemia.
Used in Drug Discovery and Development:
5-Butyl-1H-pyrazole-3-carboxylic acid can be used as a starting point for the design and synthesis of new drugs targeting HCA2 receptors. Its unique structure and functional groups can be modified to create a series of analogs with improved potency, selectivity, and pharmacokinetic properties. 5-Butyl-1H-pyrazole-3-carboxylic acid can serve as a valuable tool in the discovery and development of novel therapeutic agents for the treatment of dyslipidemia and related metabolic disorders.

Upstream product

• 60415-21-6 2,4-dioxo-octanoic acid 
• 72894-00-9 5-butyl-1H-pyrazole-3-carboxylic acid ethyl ester 
• 102540-71-6 ethyl 2,4-dioxooctanoate 
• 591-78-6 n-hexan-2-one 

Relevant academic research and scientific papers

Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a

A series of 5-alkyl pyrazole-3-carboxylic acids were prepared and found to act as potent and selective agonists of the human GPCR, GPR109a, the high affinity nicotinic acid receptor. No activity was observed at the highly homologous low affinity niacin receptor, GPR109b. A further series of 4-fluoro-5-alkyl pyrazole-3-carboxylic acids were shown to display similar potency. One example from the series was shown to have improved properties in vivo compared to niacin.

Pyrazole derivatives as partial agonists for the nicotinic acid receptor

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,O 4,8]octa-3,8-diene-3-carboxylic acid (4c) and 5-propylpyrazole-3-carboxylic acid (4f) proved active with Ki values of approximately 0.15 μM and EC50 values of approximately 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 competive mechanism of action.