159173-77-0

Upstream product

• 17996-12-2 N-benzyloxycarbonyl-6-amino-1-hexanol 
• 3068-34-6 Acetic acid (2R,3S,4R,5R,6R)-3-acetoxy-2-acetoxymethyl-5-acetylamino-6-chloro-tetrahydro-pyran-4-yl ester 
• 10378-06-0 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-D-glucopyranoso)[1,2-d]-2-oxazoline 
• 501-53-1 benzyl chloroformate 
• 4048-33-3 6-amino-1-hexanol 
• 41355-44-6 2-acetamido-2,4,6,-tri-O-acetyl-1-chloro-1,2-dideoxy-α-D-galactopyranose 
• 3006-60-8 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-galactopyranose 
• 108-24-7 acetic anhydride 
• 10378-06-0 acetic acid (3aR,5R,6R,7R,7aR)-6-acetoxy-5-acetoxymethyl-2-methyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]oxazol-7-yl ester 
• 3006-60-8 Acetic acid (2R,3R,4R,5S,6R)-2,5-diacetoxy-6-acetoxymethyl-3-acetylamino-tetrahydro-pyran-4-yl ester 
• 10385-50-9 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-α-D-galactopyranoside 

Relevant academic research and scientific papers

TRIPTOLIDE CONJUGATES AND USES THEREOF

This disclosure provides triptolide-conjugates, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, as well methods of using such compounds in the treatment of conditions/diseases, such as those relating to cancer, immunomodulation and/or inflammation.

LIGAND CLUSTERS AND METHODS OF THEIR USE AND PREPARATION

Disclosed are compounds of formula (I): Yp–X–L2–Z, (I) or a salt thereof, where p is 1 to 5; X is a monosaccharide; each Y is independently –L1–T, H, protecting group, optionally substituted hydrocarbon, or optionally substituted heteroorganic group, wherein each T is independently a ligand or a protected ligand, and each L1 is independently a covalent linker; L2 is a conjugation linker; Z is a therapeutically active agent, protecting group, or a conjugation moiety. Also disclosed are methods of use of the compounds of the invention and methods of their preparation.

OLIGONUCLEOTIDE THERAPY FOR WOLMAN DISEASE AND CHOLESTERYL ESTER STORAGE DISEASE

The present disclosure provides antisense oligonucleotides, compositions, and methods that target a LIPA intron flanking exon 8, thereby modulating splicing of LIPA pre-mRNA to increase the level of LIPA mRNA molecules having exon 8, e.g., to provide a therapy for Wolman Disease or Cholesteryl Ester Storage Disease. The present disclosure provides an antisense oligonucleotide including a nucleobase sequence at least 70% complementary to a LIPA pre-mRNA target sequence in a 5'-flanking intron, a 3'-flanking intron, or a combination of exon 8 and the 5'-flanking or 3'-flanking intron.

METHOD OF CONJUGATING OLIGOMERIC COMPOUNDS

Provided herein are solid phase methods for the synthesis of conjugated oligomeric compounds and intermediates used in such methods. In particular, the solid phase methods provide for addition of a phosphoramidite functionalized conjugate group to a solid support bound oligomeric compound. The methods also provide an increase in overall yield and a cost benefit over existing methods.

Method for synthesis of reactive conjugate clusters

Provided herein are improved methods for the synthesis of reactive conjugate clusters and intermediates used in such methods. In particular, improvements are provided that enhance the synthesis of reactive conjugate clusters by reducing the number of synthetic steps required. The reactive conjugate clusters prepared using the improved methods don't include any transacylation impurities that are formed using existing methods. The improved methods also provide an increase in overall yield and a cost benefit over existing methods.

Comprehensive Structure-Activity Relationship of Triantennary N-Acetylgalactosamine Conjugated Antisense Oligonucleotides for Targeted Delivery to Hepatocytes

The comprehensive structure-activity relationships of triantennary GalNAc conjugated ASOs for enhancing potency via ASGR mediated delivery to hepatocytes is reported. Seventeen GalNAc clusters were assembled from six distinct scaffolds and attached to ASOs. The resulting ASO conjugates were evaluated in ASGR binding assays, in primary hepatocytes, and in mice. Five structurally distinct GalNAc clusters were chosen for more extensive evaluation using ASOs targeting SRB-1, A1AT, FXI, TTR, and ApoC III mRNAs. GalNAc-ASO conjugates exhibited excellent potencies (ED50 0.5-2 mg/kg) for reducing the targeted mRNAs and proteins. This work culminated in the identification of a simplified tris-based GalNAc cluster (THA-GN3), which can be efficiently assembled using readily available starting materials and conjugated to ASOs using a solution phase conjugation strategy. GalNAc-ASO conjugates thus represent a viable approach for enhancing potency of ASO drugs in the clinic without adding significant complexity or cost to existing protocols for manufacturing oligonucleotide drugs.

COMPOSITIONS AND METHODS FOR MODULATING COMPLEMENT FACTOR B EXPRESSION

The present embodiments provide methods, compounds, and compositions for treating, preventing, or ameliorating a disease associated with dysregulation of the complement alternative pathway by administering a Complement Factor B (CFB) specific inhibitor to a subject.

COMPOSITIONS AND METHODS FOR MODULATING GROWTH HORMONE RECEPTOR EXPRESSION

The present embodiments provide methods, compounds, and compositions for treating, preventing, ameliorating a disease associated with excess growth hormone using antisense compounds oligonucleotides targeted to growth hormone receptor (GHR).

TARGETED THERAPEUTIC NUCLEOSIDES AND THEIR USE

Provided herein are compounds comprising one or more therapeutic nucleosides and one or more targeting groups. In certain embodiments, the compounds further comprise one or more oligonucleotides. In certain embodiments, a targeting group comprises one or more N-Acetylgalactosamine.