Kimura, Hidenori; Suda, Hitoshi; Kassai, Momoe; Endo, Mika; Deai, Yoko; Yahata, Masahiro; Miyajima, Mari; Isobe, Yoshiaki published the artcile< N-(6-phenylpyridazin-3-yl)benzenesulfonamides as highly potent, brain-permeable, and orally active kynurenine monooxygenase inhibitors>, Electric Literature of 721401-43-0, the main research area is Huntington disease pyridazinylsulfonamide kynurenine monooxygenase inhibitor neuroprotection; 3-HK; BBB; Brain permeable; Huntington’s disease; KMO; KYNA; Kynurenine monooxygenase; Kynurenine pathway; R6/2.
Huntington’s disease (HD) is one of the serious neurodegenerative diseases and no disease modifiers are available to date. The correction of unbalanced kynurenine pathway metabolites may be useful to treat disease progression and kynurenine monooxygenase (KMO) is considered an ideal drug target. A couple of KMO inhibitors have been reported, but their brain permeability was very poor. We found pyridazinylsulfonamide as a novel lead compound, and it was optimized to the brain-permeable and highly potent KMO inhibitor 12, which was equipotent with CHDI-340246 and superior to CHDI-340246 in terms of brain penetration. Compound 12 was effective in R6/2 mice (HD model mice), i.e. neuroprotective kynurenic acid was increased, whereas neurotoxic 3-hydroxykynurenine was suppressed. In addition, impaired cognitive function was improved. Therefore, the brain-permeable KMO inhibitor was considered to be a disease modifier for HD treatment.
Bioorganic & Medicinal Chemistry Letters published new progress about Ataxia. 721401-43-0 belongs to class isoquinoline, and the molecular formula is C9H8BNO2, Electric Literature of 721401-43-0.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem