203569-23-7Relevant articles and documents
GALNAC-TGFBR1 INHIBITOR CONJUGATES FOR THE TREATMENT OF LIVER DISEASES
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Page/Page column 303-304, (2021/04/17)
Conjugates comprising GalNAc moiety and a TGFβR1 inhibitor are provided. In some embodiments, the conjugates are useful for the treatment of viral infections, cancer, and fibrosis.
Outstanding blue delayed fluorescence and significant processing stability of cuprous complexes with functional pyridine-pyrazolate diimine ligands
Zhang, Qing,Chen, Jun,Wu, Xiao-Yuan,Chen, Xu-Lin,Yu, Rongmin,Lu, Can-Zhong
, p. 6706 - 6710 (2015/04/14)
Thermally activated delayed fluorescence (TADF) of five novel cuprous complexes, with quantum yields near 1 in the solid state, has been realized. Meanwhile, these complexes are significantly stable upon processing with small emission spectral variations
Discovery and in vitro and in vivo profiles of N-ethyl-N-[2-[3-(5-fluoro-2-pyridinyl)-1H-pyrazol-1-yl]ethyl]-2-(2H-1,2,3-triazol-2-yl)-benzamide as a novel class of dual orexin receptor antagonist
Suzuki, Ryo,Nozawa, Dai,Futamura, Aya,Nishikawa-Shimono, Rie,Abe, Masahito,Hattori, Nobutaka,Ohta, Hiroshi,Araki, Yuko,Kambe, Daiji,Ohmichi, Mari,Tokura, Seiken,Aoki, Takeshi,Ohtake, Norikazu,Kawamoto, Hiroshi
, p. 1260 - 1275 (2015/03/04)
Orexins play an important role in sleep/wake regulation, and orexin receptor antagonists are a focus of novel therapy for the treatment of insomnia. We identified 27e (TASP0428980) as a potent dual orexin receptor antagonist through the systematic modification of our original designed lead A. We demonstrated the potent sleep-promoting effects of 27e at ip dose of 3 mg/kg in a rat polysomnogram study. 27e exhibited relatively short half-life profiles in rats and dogs. Furthermore, accumulating evidence regarding ADME profiles indicates that the predicted human half-life of 27e should be 1.2-1.4 h. These data indicated that 27e has a short-acting hypnotic property, suggesting that 27e might be useful for treating primary insomnia while exhibiting a low risk of next-day residual somnolence. Thus, 27e and its related compounds should be further evaluated to enable advancement to clinical trials.
Lanthanide complexes of a new sterically hindered potentially hexadentate podand ligand based on a tris(pyrazolyl)borate core; crystal structures, solution structures and luminescence properties
Reeves, Zoe R.,Mann, Karen L. V.,Jeffery, John C.,McCleverty, Jon A.,Ward, Michael D.,Barigelletti, Francesco,Armaroli, Nicola
, p. 349 - 355 (2007/10/03)
The new podand ligand hydrotris[3-(6-methyl)pyridin-2-ylpyrazol-1-yl]borate [L1]- was prepared which contains three bidentate pyrazolyl/pyridine arms attached to a {BH}- head-group. This ligand differs from an earlier ligand hydrotris[3-(2-pyridyl)pyrazol-1-yl]borate [L2]- by the presence of methyl groups attached to the C6 positions of the pyridyl rings, which would interfere with each other sterically if the ligand co-ordinated in a fully hexadentate manner. Instead, crystallographic analysis of the complexes [M(L1)(NO3)2(H2O)] (M = Eu, Tb or Gd) showed that partial dissociation of the podand occurs to relieve this potential steric problem: either one or two of the pyridyl groups are not co-ordinated, such that [L1]- is penta- or tetra-dentate, but instead are involved in intramolecular N...H-O hydrogen-bonding interactions with the co-ordinated water molecule. The presence of both structural forms in single crystals of the gadolinium and europium complexes shows that interconversion between them in solution must be facile. Variable-temperature 1H NMR spectra of the diamagnetic lanthanum(III) analogue shows that, whereas all three ligand arms are equivalent on the NMR timescale at high temperatures, at -80°C there is mirror symmetry in the complex such that two arms are equivalent and the third is different from the other two; this is consistent with the crystalline form in which [L1]- is tetradentate with two pendant pyridyl arms, which has pseudo-mirror symmetry. Luminescence studies showed that whereas the ligand-based luminescence is retained in the gadolinium(III) complex, in the europium(III) and terbium(III) complexes the ligand-centred emission is quenched by ligand-to-metal energy transfer, resulting in the usual metal-centred emission spectra. The intensity of the emission from the europium(III) and terbium(III) complexes of [L1]- is substantially reduced compared to the emission from the analogous complexes [M(L2)(NO3)2] (M = Eu or Tb) which we ascribe to the sterically induced poorer co-ordination of the podand ligand, resulting in (i) less efficient ligand-to-metal energy transfer, and (ii) co-ordination of labile solvent molecules (H2O) to the metal centres.
