20698-04-8Relevant articles and documents
TAU-PROTEIN TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
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Paragraph 0973; 0974, (2021/02/12)
The present disclosure relates to bifunctional compounds, which find utility as modulators of tan protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tan protein, such that tan protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tan. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tan protein. Diseases or disorders that result from aggregation or accumulation of tan protein are treated or prevented with compounds and compositions of the present disclosure.
Bulk Inclusions of Double Pyridazine Molecular Rotors in Hexagonal Tris(o-phenylene)cyclotriphosphazene
Kaleta, Ji?í,Bastien, Guillaume,Wen, Jin,Dra?ínsky, Martin,Tortorici, Edward,Císa?ová, Ivana,Beale, Paul D.,Rogers, Charles T.,Michl, Josef
, p. 8449 - 8467 (2019/07/03)
A new generation of double pyridazine molecular rotors differing in intramolecular dipole-dipole spacing was synthesized. All rotor molecules formed bulk inclusions in a tris(o-phenylenedioxy)cyclotriphosphazene (TPP) host. Results of dielectric spectroscopy were fitted to a pair of nine-state models that accounted for interactions of neighboring dipoles at either an aligned or opposed possible orientation of the local threefold dipole rotation potentials within a channel of the TPP host. The results indicate dipole-dipole interaction strengths at the 100 to 200 K scale that lead dipoles to preferentially populate a subset of low-energy configurations. They also reveal that pyridazines with ethynyl substituents in 3- and 6-positions have slightly higher rotational barriers (3.2-3.5 kcal/mol) than those carrying one ethynyl and one tert-butyl group (1.9-3.0 kcal/mol). Upon cooling, these barriers reduce the rate of thermal transitions between the potential wells so much that the inclusions cannot achieve ordered dipolar ground states.
First synthesis of novel 3,3′-bipyridazine derivatives as new potent antihepatocellular carcinoma agents
Yue, Qiming,Zhao, Yi,Hai, Li,Zhang, Tao,Guo, Li,Wu, Yong
, p. 7670 - 7675 (2015/09/07)
Hepatocellular carcinoma is one of the most common kind of cancers in clinical, and its clinical treatment is quite difficult. The latest research suggests that pyridazinone with a novel molecular skeleton shows excellent activity against hepatocellular c
