PROCESS FOR ALKALINE HYDROLYSIS OF CARBOXYLIC ACID DERIVATIVES TO CARBOXYLIC ACIDS
申请人:Krause Eberhard
公开号:US20090270649A1
公开(公告)日:2009-10-29
The invention relates to a process for alkaline hydrolysis of carboxylic acid derivatives, especially carboxylic esters, to carboxylic acids, wherein, for the alkaline hydrolysis of the carboxylic acid derivatives, red mud which is produced by the Bayer process used for aluminum production is used as a reaction-promoting component, especially as a hydroxide ion source.
The current invention provides peptide nucleic acid derivatives targeting the 3′ splice site of exon 4 in the human SCN9A pre-mRNA. The peptide nucleic acid derivatives potently induce SCN9A mRNA splice variant(s) lacking the SCN9A exon 4 in cells, and are useful to safely treat pains or conditions involving Nav1.7 activity.
A peptide nucleic acid derivative of Formula I is provided to tightly bind to a splice site within a pre-mRNA in a sequence specific manner. Given with excellent cell membrane permeability and strong affinity for RNA, the said peptide nucleic acid derivative induces exon skipping in cells treated with the peptide nucleic acid at sub-femtomolar concentration as “naked” oligonucleotide. The said compound shows therapeutic activity in subjects upon systemic administration even at 1 μg/Kg or less, and therefore is useful to treat a disease or symptom at affordable treatment cost.