98795-96-1Relevant academic research and scientific papers
Discovery of a potent, cell penetrant, and selective p300/CBP-associated factor (PCAF)/general control nonderepressible 5 (GCN5) bromodomain chemical probe
Humphreys, Philip G.,Bamborough, Paul,Chung, Chun-Wa,Craggs, Peter D.,Gordon, Laurie,Grandi, Paola,Hayhow, Thomas G.,Hussain, Jameed,Jones, Katherine L.,Lindon, Matthew,Michon, Anne-Marie,Renaux, Jessica F.,Suckling, Colin J.,Tough, David F.,Prinjha, Rab K.
, p. 695 - 709 (2017)
P300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and ≥18000-fold selectivity over the BET family, together with ≥70-fold selectivity over the wider bromodomain families.
A Novel Synthesis of 2-Arylaminothiazolopyridazinones
Yamasaki, Tetsuo,Kawaminami, Eiji,Uchimura, Fumi,Okawara, Tadashi,Furukawa, Mitsuru
, p. 859 - 865 (2007/10/02)
The reaction of 5(4)-amino-4(5)-chloropyridazin-3(2H)-ones 1 (9) with methyl dithiocarbamates 2 gave 2-arylaminothiazolopyridazinones 3 (10).Treatment of 5(4)-alkylamino-4(5)-chloropyridazin-3(2H)-ones 5 (12) with 2 afforded the corresponding 2-aryliminothiazolopyridazinones 6 (13).Cyclization of 1a with phenylisothiocyanate produced 2-amino- and 2-iminothiazolopyridazinones 3a and 16.
SYNTHESIS, SPECTRAL PROPERTIES, AND PESTICIDAL ACTIVITY OF 4-AMINO(ALKYLAMINO, DIALKYLAMINO)-5-CHLORO-2-SUBSTITUTED-3-OXO-2H-PYRIDAZINES AND 5-AMINO(ALKYLAMINO, DIALKYLAMINO)-4-CHLORO-2-SUBSTITUTED-3-OXO-2H-PYRIDAZINES
Konecny, Vaclav,Kovac, Stefan,Varkonda, Stefan
, p. 492 - 502 (2007/10/02)
4-Amino(alkylamino)-5-chloro-2-substituted-3-oxo-2H-pyridazines and 5-amino(alkylamino, dialkylamino)-4-chloro-2-substituted-3-oxo-2H-pyridazines have been prepared by nucleophilic substitution reactions of 4,5-dichloro-2-substituted-3-oxo-2H-pyridazines with amines in aprotic solvent.Structure of the compounds prepared has been proved by IR and UV spectra.Fungicidal and herbicidal activity of the compounds prepared have been tested.None of the compounds prepared exceeds the standard Vitavax in the fungicidal activity tests.Compounds VIII and XII show equal or better activity on the Hill reaction as compared with the standard pyrazone.
