171763-19-2

Upstream product

• 22423-26-3 O-2,2'-cyclo-5-methyluridine 
• 58479-61-1 tert-butylchlorodiphenylsilane 
• 26879-47-0 1-(β-L-ribofuranosyl)thymine 
• 1463-10-1 5-Methyluridine 

Downstream Products

• 187733-61-5 Thiocarbonic acid O-[(2R,3R,3aS,9aR)-2-(tert-butyl-diphenyl-silanyloxymethyl)-7-methyl-6-oxo-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5]oxazolo[3,2-a]pyrimidin-3-yl] ester O-p-tolyl ester 
• 212061-24-0 5'-O-(tert-butyldiphenylsilyl)-2'-O-(2-hydroxyethyl)-5-methyluridine 
• 317820-41-0 5'-O-tert-butyldiphenlsilyl-2'-O-[2-(acetaldoximinooxy)ethyl]-5-methyluridine 
• 317820-42-1 5'-O-(tert-butyldiphenylsilyl)-2'-O-[2-[(N,N-diethylamino)oxy]ethyl]-5-methyluridine 
• 212061-29-5 5'-O-(4,4'-dimethoxytrityl)-2'-O-(2-N,N-dimethylaminooxyethyl)-5-methyluridine 
• 317820-44-3 5'-O-(4,4'-dimethoxytrityl)-2'-O-[2-[(N,N-diethylamino)oxy]ethyl]-5-methyluridine 
• 1244971-56-9 C₃₅H₄₀N₂O₉ 
• 1244973-39-4 C₄₄H₅₇N₄O₁₀P 
• 1244969-84-3 C₃₀H₄₀N₂O₇Si 
• 1244969-86-5 C₃₆H₄₄N₄O₁₀Si 
• 171762-75-7 1-[(2R,3R,4S,5S)-4-Allyl-5-(tert-butyl-diphenyl-silanyloxymethyl)-3-hydroxy-tetrahydro-furan-2-yl]-3-benzyloxymethyl-5-methyl-1H-pyrimidine-2,4-dione 
• 171762-73-5 1-[(2R,3S,4S,5S)-4-Allyl-5-(tert-butyl-diphenyl-silanyloxymethyl)-3-hydroxy-tetrahydro-furan-2-yl]-3-benzyloxymethyl-5-methyl-1H-pyrimidine-2,4-dione 
• 171762-81-5 C₅₅H₆₇N₅O₁₀Si₂ 

Relevant academic research and scientific papers

METHODS FOR THE PREVENTION AND TREATMENT OF MAJOR ADVERSE CARDIOVASCULAR EVENTS USING COMPOUNDS THAT MODULATE APOLIPOPROTEIN B

Provided herein, for example, are methods generally relating to preventing, treating and/or managing a major adverse cardiovascular event in a subject with a disease or condition at risk for a major adverse cardiovascular event, e.g., familial hypercholesterolemia. Also provided herein are methods relating to administering to the patient a therapeutically effective amount of an antisense oligonucleotide having a nucleobase SEQ ID NO: 247 (e.g., mipomersen).

EFFECTS OF APOLIPOPROTEIN B INHIBITION ON GENE EXPRESSION PROFILES IN ANIMALS

Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for treatment of diseases associated with expression of apolipoprotein B are provided. Methods are provided for modulating the expression of genes involved in lipid metabolism, useful in the treatment of conditions associated with cardiovascular risk. Antisense oligonucleotides targeted to apolipoprotein B reduce the level of apolipoprotein B mRNA, lower serum cholesterol and shift liver gene expression profiles from those of an obese animal towards those of a lean animal. Further provided are methods for improving the cardiovascular risk of a subject through antisense inhibition of apolipoprotein B. Also provided are methods for employing antisense oligonucleotides targeted to apolipoprotein B to modulate a cellular pathway or metabolic process.

Synthesis and antisense properties of 2′-O-(2S-methoxypropyl)-RNA- modified gapmer antisense oligonucleotides

To ascertain whether increasing hydrophobicity can enhance the activity of second-generation antisense oligonucleotides (ASOs) in muscle, we investigated the antisense properties of 2′-O-(2S-methoxypropyl)-RNA (2S-MOP)-modified ASOs. Synthesis of the 2S-MOP 5-methyl uridine phosphoramidite was accomplished on a multi-gram scale by Lewis-acid-catalyzed ring opening of 5′-O-tert-butyldiphenylsilyl ether-protected 2,2′-anhydro-5-methyl uridine with 2S-methoxy-1-propanol. Synthesis of the 2S-MOP 5-methyl cytidine nucleoside from the corresponding 5-methyl uridine nucleoside was accomplished by formation and displacement of a 4-triazolide intermediate with aqueous ammonia. 2S-MOP-modified oligonucleotides were prepared on an automated DNA synthesizer and showed similar enhancements in duplex thermal stability as 2′-O-methoxyethyl RNA (MOE)-modified oligonucleotides. 2S-MOP-containing antisense oligonucleotides were evaluated in Balb-c mice and showed good activity for decreasing the expression levels of scavenger receptor B1 (Srb1) and phosphatase and tensin homologue (PTEN) mRNA in liver and muscle tissue.

Antisense inhibition via RNAse H-independent reduction in mRNA

The present invention provides compositions and methods for reducing levels of a preselected mRNA, using antisense compounds targeted to a splice site or a region up to 50 nucleobases upstream of an exon/intron junction on said mRNA. Preferably, said antisense compounds do not elicit RNAse H cleavage of the mRNA.

Antisense modulation of cyclin-dependent kinase 6 expression

Antisense compounds, compositions and methods are provided for modulating the expression of cyclin-dependent kinase 6. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding cyclin-dependent kinase 6. Methods of using these compounds for modulation of cyclin-dependent kinase 6 expression and for treatment of diseases associated with expression of cyclin-dependent kinase 6 are provided.

Antisense modulation of hypothetical protein LOC51249 expression

Antisense compounds, compositions and methods are provided for modulating the expression of hypothetical protein LOC51249. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding hypothetical protein LOC51249. Methods of using these compounds for modulation of hypothetical protein LOC51249 expression and for treatment of diseases associated with expression of hypothetical protein LOC51249 are provided.

Antisense modulation of selenophosphate synthetase 2 expression

Antisense compounds, compositions and methods are provided for modulating the expression of selenophosphate synthetase 2. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding selenophosphate synthetase 2. Methods of using these compounds for modulation of selenophosphate synthetase 2 expression and for treatment of diseases associated with expression of selenophosphate synthetase 2 are provided.

Antisense modulation of ADAM12 expression

Antisense compounds, compositions and methods are provided for modulating the expression of ADAM12. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding ADAM12. Methods of using these compounds for modulation of ADAM12 expression and for treatment of diseases associated with expression of ADAM12 are provided.

Antisense modulation of SMRT expression

Antisense compounds, compositions and methods are provided for modulating the expression of SMRT. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding SMRT. Methods of using these compounds for modulation of SMRT expression and for treatment of diseases associated with expression of SMRT are provided.

Antisense modulation of cyclin-dependent kinase 4 expression

Antisense compounds, compositions and methods are provided for modulating the expression of cyclin-dependent kinase 4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding cyclin-dependent kinase 4. Methods of using these compounds for modulation of cyclin-dependent kinase 4 expression and for treatment of diseases associated with expression of cyclin-dependent kinase 4 are provided.