332099-35-1Relevant articles and documents
Synthetic studies of centromere-associated protein-E (CENP-E) inhibitors: 1.Exploration of fused bicyclic core scaffolds using electrostatic potential map
Hirayama, Takaharu,Okaniwa, Masanori,Imada, Takashi,Ohashi, Akihiro,Ohori, Momoko,Iwai, Kenichi,Mori, Kouji,Kawamoto, Tomohiro,Yokota, Akihiro,Tanaka, Toshimasa,Ishikawa, Tomoyasu
, p. 5488 - 5502 (2013/09/02)
Centromere-associated protein-E (CENP-E), a mitotic kinesin that plays an important role in mitotic progression, is an attractive target for cancer therapeutic drugs. For the purpose of developing novel CENP-E inhibitors as cancer therapeutics, we investigated a fused bicyclic compound identified by high throughput screening, 4-oxo-4,5-dihydrothieno[3,4-c]pyridine-6-carboxamide 1a. Based on this scaffold, we designed inhibitors for efficient binding at the L5 site in CENP-E utilizing homology modeling as well as electrostatic potential map (EPM) analysis to enhance CENP-E inhibitory activity. This resulted in a new lead, 5-bromoimidazo[1,2-a]pyridine 7, which showed potent CENP-E enzyme inhibition (IC50: 50 nM) and cellular activity with accumulation of phosphorylated histone H3 in HeLa cells. Our homology model and EPM analysis proved to be useful tools for the rational design of CENP-E inhibitors.
FLUORO-SUBSTITUTED INHIBITORS OF D-AMINO ACID OXIDASE
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Page/Page column 37, (2008/06/13)
This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. The invention also provides methods for the treatment and prevention of neurological disorders, such as neuropsychiatric and neurodegenerative diseases, as well as pain, ataxia and convulsion. The compounds of the invention have the general structure: wherein A is NH or S. Q is a member selected from CR1 and N. X and Y are members independently selected from O, S, CR2, N and NH. R1, R2 and R4 are members independently selected from H and F, provided that at least one member selected from R1, R2 and R4 is F. R6 is a member selected from O?X+ and OH, wherein X+ is a positive ion, which is a member selected from inorganic positive ions and organic positive ions.
Heterocyclic compounds
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Page/Page column 12, (2010/02/05)
Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H4 receptor, including allergic rhinitis.