Oligonucleotide prodrugs based on cyclic disulfide modified phosphate esters

• Main Authors: NAIR JAYAPRAKASH K, TANG CHRISTOPH, MAIER MARTIN A, BUSBY ANDREW, PEARSON, JOHN, M, KEL 'IN ALEXANDER V
• Format: Patent
• Language: Chinese; English
• Published: 29.09.2023
• Subjects: CHEMISTRY; DERIVATIVES THEREOF; METALLURGY; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; SUGARS

The present invention relates to compounds comprising the structure of formula (I): a cyclic disulfide moiety-phosphorus coupling group (I). The cyclic disulfide moiety has a structure of (C-I), (C-II) or (C-III). The invention also relates to oligonucleotides comprising one or more compounds comprising the structure of formula (I), wherein at least one phosphorus coupling group comprises a nucleoside or oligonucleotide. The invention also relates to pharmaceutical compositions comprising the oligonucleotides described herein and methods of reducing or inhibiting expression of a target gene by administering to a subject a therapeutically effective amount of the oligonucleotides described herein. # imgabs0 # 本发明涉及包含式(I)结构的化合物：环状二硫化物部分-磷偶联基团(I)。环状二硫化物部分具有(C-I)、(C-II)或(C-III)的结构。本发明还涉及包含一种或多种含式(I)结构的化合物的寡核苷酸，其中至少一个磷偶联基团含有核苷或寡核苷酸。本发明还涉及包含本文所述的寡核苷酸的药物组合物和通过向受试者施用施用治疗有效量的本文所述的寡核苷酸来减少或抑制靶基因表达的方法。#imgabs0#