Sagar, Satish’s team published research in European Journal of Medicinal Chemistry in 2021 | CAS: 930-36-9

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Synthetic Route of C4H6N2

Synthetic Route of C4H6N2On October 15, 2021 ,《Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy》 was published in European Journal of Medicinal Chemistry. The article was written by Sagar, Satish; Singh, Sarbjit; Mallareddy, Jayapal Reddy; Sonawane, Yogesh A.; Napoleon, John V.; Rana, Sandeep; Contreras, Jacob I.; Rajesh, Christabelle; Ezell, Edward L.; Kizhake, Smitha; Garrison, Jered C.; Radhakrishnan, Prakash; Natarajan, Amarnath. The article contains the following contents:

Genetic models validated Inhibitor of nuclear factor (NF) kappa B kinase beta (IKKβ) as a therapeutic target for KRAS mutation associated pancreatic cancer. Phosphorylation of the activation loop serine residues (S177, S181) in IKKβ is a key event that drives tumor necrosis factor (TNF) α induced NF-κB mediated gene expression. Here we conducted structure activity relationship (SAR) study to improve potency and oral bioavailability of a quinoxaline analog 13-197 that was previously reported as a NFκB inhibitor for pancreatic cancer therapy. The SAR led to the identification of a novel quinoxaline urea analog 84 that reduced the levels of p-IKKβ in dose- and time-dependent studies. When compared to 13-197, analog 84 was ∼2.5-fold more potent in TNFα-induced NFκB inhibition and ∼4-fold more potent in inhibiting pancreatic cancer cell growth. Analog 84 exhibited ∼4.3-fold greater exposure (AUC0-∞) resulting in ∼5.7-fold increase in oral bioavailability (%F) when compared to 13-197. Importantly, oral administration of 84 by itself and in combination of gemcitabine reduced p-IKKβ levels and inhibited pancreatic tumor growth in a xenograft model. After reading the article, we found that the author used 1-Methylpyrazole(cas: 930-36-9Synthetic Route of C4H6N2)

1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Synthetic Route of C4H6N2

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