595610-34-7

Basic information

• Product Name: 5-(4-chlorophenyl)-2,4-dioxopentanoic acid ethyl ester
• Synonyms: 5-(4-chlorophenyl)-2,4-dioxopentanoic acid ethyl ester
• CAS NO: 595610-34-7
• Molecular Weight: 268.697
• Mol File: 595610-34-7.mol
• Article Data: 4

Chemical Properties

• CAS DataBase Reference: 5-(4-chlorophenyl)-2,4-dioxopentanoic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4-chlorophenyl)-2,4-dioxopentanoic acid ethyl ester(595610-34-7)
• EPA Substance Registry System: 5-(4-chlorophenyl)-2,4-dioxopentanoic acid ethyl ester(595610-34-7)

Safety Data

• Hazardous Substances Data: 595610-34-7(Hazardous Substances Data)

Upstream product

• 95-92-1 oxalic acid diethyl ester 
• 5586-88-9 1-(4-chlorophenyl)propan-2-one 

Relevant articles and documents

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.

PYRROLO-PYRIDAZINE DERIVATIVES AS MUSCARINIC M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS

The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers or pharmaceutically acceptable salt (s) thereof as muscarinic M1 receptor positive allosteric modulators (M1 PAMs). The present invention describes the preparation, pharmaceutical composition and the use of such compounds. (I)