Identification of pyrazolopyrimidine arylsulfonamides as CC-chemokine receptor 4 (CCR4) antagonists

Add time:07/11/2019    Source:sciencedirect.com

A novel 4-aminoindazole sulfonamide hit (13) was identified as a human CCR4 antagonists from testing a focussed library of compounds in the primary GTPγS assay. Replacing the indazole core with a pyrazolopyrimidine, and introduction of a methoxy group adjacent to the sulfonamide substituent, resulted in the identification of pyrazolopyrimidine 37a, which exhibited good binding affinity in the GTPγS assay (pIC50 = 7.2), low lipophilicity (c log P = 2.2, chromlog D7.4 = 2.4), high LE (0.41), high solubility (CLND solubility ≥581 µM), and an excellent PK profile in both the rat (F = 62%) and the dog (F = 100%). Further SAR investigation of the pyrazolopyrimidine suggested that substitution at N1 is tolerated, providing a suitable vector to modulate the properties, and increase the potency in a lead optimisation campaign.

We also recommend Trading Suppliers and Manufacturers of 4-bromo-N,N-dichlorobenzenesulfonamide (cas 1836-19-7). Pls Click Website Link as below: cas 1836-19-7 suppliers

Prev:Tunable blue-emitting fluorophores—benzo[1,2-b:4,3-b′]dithiophene and trithia[5]helicene end-capped with electron-rich or electron-deficient aryl substituents
Next:Structure, conformation and hydrogen bonding of 4-(N-methylpiperidinium)-butyric acid bromide)