Yasuda, Yorinobu et al. published their research in Bioorganic & Medicinal Chemistry in 2015 | CAS: 15953-73-8

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Category: pyrazoles-derivatives

Design, synthesis, and structure-activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors was written by Yasuda, Yorinobu;Arakawa, Takeaki;Nawata, Yumi;Shimada, Sayaka;Oishi, Shinya;Fujii, Nobutaka;Nishimura, Shinichi;Hattori, Akira;Kakeya, Hideaki. And the article was included in Bioorganic & Medicinal Chemistry in 2015.Category: pyrazoles-derivatives This article mentions the following:

Hypoxia-inducible factor (HIF)-1 is well known as a promising target for cancer chemotherapy. By screening an inhouse chem. library using a hypoxia-responsive luciferase reporter gene assay, the authors identified CLB-016 containing 1-ethylpyrazole-3-carboxamide as a HIF-1 inhibitor (IC50 = 19.1 μM). In a subsequent extensive structure-activity relationship (SAR) study, the authors developed compound 11Ae (4-[5-[(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)methyl]furan-2-carboxamido]-1-ethyl-1H-pyrazole-3-carboxamide) with an IC50 value of 8.1 μM against HIF-1-driven luciferase activity. CLB-016 and compound 11Ae were shown to significantly suppress the HIF-1-mediated hypoxia response, including carbonic anhydrase IX (CAIX) gene expression and migration of human sarcoma HT1080 cells. These results revealed 1-ethylpyrazole-3-carboxamide as a novel scaffold to develop promising anti-cancer drugs targeting the HIF-1 signaling pathway. In the experiment, the researchers used many compounds, for example, 4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8Category: pyrazoles-derivatives).

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Category: pyrazoles-derivatives

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics