Diarylthiophenes as inhibitors of the pore-forming protein perforin
Evolution from a furan-containing high-throughput screen (HTS) hit (1) resulted in isobenzofuran-1(3H)-one (2) as a potent inhibitor of the function of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 NK cells. In the current study, structure-activity relationship (SAR) development towards a novel series of diarylthiophene analogues has continued through the use of substituted-benzene and -pyridyl moieties as bioisosteres for 2-thioxoimidazolidin-4-one (A) on a thiophene (B) -isobenzofuranone (C) scaffold. The resulting compounds were tested for their ability to inhibit perforin lytic activity in vitro. Carboxamide (23) shows a 4-fold increase(2) in lytic activity against isolated perforin and provides good rationale for continued development within this class.
Miller, Christian K.,Huttunen, Kristiina M.,Denny, William A.,Jaiswal, Jagdish K.,Ciccone, Annette,Browne, Kylie A.,Trapani, Joseph A.,Spicer, Julie A.
p. 355 - 360
(2016/01/09)
PROCESSES FOR THE PREPARATION OF CITALOPRAM AND ITS INTERMEDIATE 5-AMINOPHTHALIDE
The invention relates to processes for the preparation of 5-amino-2-benzofuran- l(3H)-one of Formula (I), and to the use of this compound as an intermediate for the preparation of citalopram. The invention also relates to a process for the preparation of citalopram or a salt thereof, and pharmaceutical compositions that include the citalopram or a salt thereof.
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Page/Page column 9
(2010/11/24)
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