46413-67-6Relevant articles and documents
Intramolecular Cyclization of Vinyldiazoacetates as a Versatile Route to Substituted Pyrazoles
Drikermann, Denis,G?rls, Helmar,Kerndl, Valerie,Vilotijevic, Ivan
, p. 1158 - 1162 (2020/07/20)
Vinyldiazo compounds undergo a thermal electrocyclization to form pyrazoles in yields of up to 95percent. The reactions are operationally simple, use readily available starting materials, require no intervention of a catalyst, and enable the synthesis of mono-, di- A nd tri-substituted pyrazoles. With the ability to produce highly substituted pyrazoles and the flexibility in installing various types of substituents, this method constitutes a new entry to this valuable heterocyclic scaffold and may be of interest to all branches of the chemical industry.
Synthesis and anticancer activity of heteroaromatic linked 4β-amido podophyllotoxins as apoptotic inducing agents
Kamal, Ahmed,Tamboli, Jaki R.,Vishnuvardhan,Adil,Nayak, V. Lakshma,Ramakrishna
, p. 273 - 280 (2013/02/25)
A series of different heteroaromatic linked 4β-amidopodophyllotoxin conjugates (16a-i, 17a-i and 18a-d) were synthesized and evaluated for anticancer activity against five human cancer cell lines. Among the series, one of the compound 17g showed significant antiproliferative activity in A549 (lung cancer) cell line. Flow cytometric analysis showed that 17g arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggests that 17g induces cell death by apoptosis.
Pyrazole derivatives as partial agonists for the nicotinic acid receptor
Van Herk,Brussee,Van den Nieuwendijk,Van der Klein,IJzerman,Stannek,Burmeister,Lorenzen
, p. 3945 - 3951 (2007/10/03)
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.