ChemInform Abstract: Pyridazines. Part 77. Synthetic Building Blocks Containing the 1,2‐ Diazine Moiety: N‐ and O‐Protected 3‐(4‐Pyridazinyl)isoserines.

Heinisch, G.; Langer, Thierry; Tonnel, J.; Mereiter, Kurt; Wurst, Klaus

doi:10.1002/chin.199638208

Cited by 1 publication

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Spectroscopic data are consistent with those reported in the literature. 13 (1R*,2R*,3R*)-Ethyl-2-phenyl-3-(pyridazin-4-yl)cyclopropanecarboxylate (14a') Following procedure C from 13a' (94 mg, 0.53 mmol) and 1-benzyltetrahydro-1H-thiophenium bromide (205 mg, 0.79 mmol). As the reaction was incomplete after 1 h, the reaction was cooled to -20 °C and additional amounts of sulfonium salt, 12-crown-4 and LiHMDS (0.5 eq each) were added.…”

Section: S10 (E)-ethyl-3-(pyridazin-4-yl)acrylate (13a')mentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Potent and Selective Class IIa Histone Deacetylase (HDAC) Inhibitors as a Potential Therapy for Huntington’s Disease

Bürli¹,

Luckhurst²,

Aziz³

et al. 2013

J. Med. Chem.

133

138

View full text Add to dashboard Cite

Inhibition of class IIa histone deacetylase (HDAC) enzymes have been suggested as a therapeutic strategy for a number of diseases, including Huntington's disease. Catalytic-site small molecule inhibitors of the class IIa HDAC4, -5, -7, and -9 were developed. These trisubstituted diarylcyclopropanehydroxamic acids were designed to exploit a lower pocket that is characteristic for the class IIa HDACs, not present in other HDAC classes. Selected inhibitors were cocrystallized with the catalytic domain of human HDAC4. We describe the first HDAC4 catalytic domain crystal structure in a "closed-loop" form, which in our view represents the biologically relevant conformation. We have demonstrated that these molecules can differentiate class IIa HDACs from class I and class IIb subtypes. They exhibited pharmacokinetic properties that should enable the assessment of their therapeutic benefit in both peripheral and CNS disorders. These selective inhibitors provide a means for evaluating potential efficacy in preclinical models in vivo.

show abstract

Section: S10 (E)-ethyl-3-(pyridazin-4-yl)acrylate (13a')mentioning

confidence: 99%