Engers, Darren W. published the artcileDiscovery and characterization of N-(1,3-dialkyl-1H-indazol-6-yl)-1H-pyrazolo[4,3-b]pyridin-3-amine scaffold as mGlu4 positive allosteric modulators that mitigate CYP1A2 induction liability, Computed Properties of 108281-78-3, the main research area is preparation dialkylindazolyl pyrazolopyridin amine derivative Parkinson’s; CYP induction; Parkinson’s disease; Positive allosteric modulator; Structure-activity relationship; mGlu4 PAM.
Previous reports from our laboratory disclosed the structure and activity of a novel 1H-pyrazolo[4,3-b]pyridine-3-amine scaffold (VU8506) which showed excellent potency, selectivity and in vivo efficacy in preclin. rodent models of Parkinson’s disease. Unfortunately, this compound suffered from significant CYP1A2 induction as measured through upstream AhR activation (125-fold) and thus was precluded from further advancement in chronic studies. Herein, we report a new scaffold developed recently which was systematically studied in order to mitigate the CYP1A2 liabilities presented in the earlier scaffolds. We have identified a novel structure that maintains the potency and selectivity of other mGlu4 PAMs, leading to 9i (hmGlu4 EC50 = 43 nM; AhR activation = 2.3-fold).
Bioorganic & Medicinal Chemistry Letters published new progress about Antiparkinsonian agents. 108281-78-3 belongs to class triazoles, name is 6-Bromo-3-methyl-[1,2,4]triazolo[4,3-a]pyridine, and the molecular formula is C7H6BrN3, Computed Properties of 108281-78-3.
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics