5932-32-1

Usage

Uses

Used in Pharmaceutical Industry:
1,4,5,6-Tetrahydrocyclopenta[c]pyrazole-3-carboxylic Acid is used as a key intermediate for the synthetic preparation of pyrazole derivatives. These derivatives act as partial agonists for the nicotinic acid receptor, which plays a crucial role in various physiological processes. By modulating the activity of this receptor, these pyrazole derivatives have the potential to be developed into therapeutic agents for treating conditions such as cognitive impairment, neurodegenerative diseases, and other related disorders.

InChI:InChI=1/C7H8N2O2/c10-7(11)6-4-2-1-3-5(4)8-9-6/h1-3H2,(H,8,9)(H,10,11)

Upstream product

• 120-92-3 cyclopentanone 
• 39163-39-8 oxo-(2-oxo-cyclopentyl)-acetic acid ethyl ester 
• 5932-31-0 1,2-diazabicyclo[3,3,0^4,8]octa-3,8-diene-3-carboxylic acid ethyl ester 

Downstream Products

• 1044586-75-5 N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-yl]-1,4,5,6-tetrahydrocyclopenta[a]pyrazole-3-carboxamide 
• 69631-56-7 methyl cyclopenta[c]pyrazole-3-carboxylate 
• 851776-30-2 1,4,5,6-tetrahydro-cyclopentapyrazole-3-carboxylic acid amide 
• 2214-03-1 5,6-dihydro-1H,4H-cyclopenta[c]pyrazole 

Relevant academic research and scientific papers

Development of a scaleable synthesis of a partial nicotinic acid receptor agonist

A practical and efficient synthesis of 1,4,5,6-tetrahydro-3-(1Htetrazol- 5-yl)cyclopenta[c]pyrazole, 1, is described. A new one-pot process has been developed, starting from the commercially available 1H-tetrazole-5-carboxylic acid-ethyl ester sodium salt which is reacted in a pseudo-Claisen condensation reaction with cyclopentanone, followed by the addition of hydrazine.

3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): A partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice

The discovery and profiling of 3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro- cyclopentapyrazole (5a, MK-0354), a partial agonist of GPR109a, is described. Compound 5a retained the plasma free fatty acid lowering effects in mice associated with GPR109a agonism,

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.