5′ modified nucleosides and oligomeric compounds prepared therefrom

摘要

The present invention provides 5′ modified nucleosides and oligomeric compounds prepared therefrom. More particularly, the present invention provides modified nucleosides having at least one 5′-substituent and an optional 2′ substituent, oligomeric compounds comprising at least one of these modified nucleosides and methods of using the oligomeric compounds. In some embodiments, the oligomeric compounds provided herein are expected to hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA.

主权项

1. A 5′ modified nucleoside having Formula Ic: wherein:
Bx is a heterocyclic base moiety;M1 is H, hydroxyl or OR1;M2 is hydroxyl, OR1 or N(R1)(R2);each R1 and R2 is, independently, C1-C6 alkyl or substituted C1-C6 alkyl;r is 0 or 1;each of q1, q2, q3 and q4 is, independently, H, halogen, protected hydroxyl, substituted oxy, acyloxy, azido, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl, substituted C2-C6 alkynyl, O—C1-C6 alkyl, substituted O—C1-C6 alkyl, S—C1-C6 alkyl, substituted S—C1-C6 alkyl, N(R3)—C1-C6 alkyl or substituted N(R3)—C1-C6 alkyl wherein at least one of q1, q2, q3 and q4 is protected hydroxyl, substituted oxy, acyloxy, O—C1-C6 alkyl, substituted O—C1-C6 alkyl, S—C1-C6 alkyl, substituted S—C1-C6 alkyl, N(R3)—C1-C6 alkyl or substituted N(R3)—C1-C6 alkyl or an optionally protected phosphate moiety;R3 is H, C1-C6 alkyl or substituted C1-C6 alkyl;q5 and q7 are each, independently, hydroxyl, protected hydroxyl, thiol, protected thiol, C1-C6 alkyl, substituted C1-C6 alkyl, C1-C6 alkoxy, substituted C1-C6 alkoxy, amino or substituted amino;q6 is O or S;G is H, protected hydroxyl, halogen or O—[C(R4)(R5)]n—[(C═O)m—X]j—Z;each R4 and R5 is, independently, H, halogen, C1-C6 alkyl or substituted C1-C6 alkyl;X is O, S or N(E1);Z is H, halogen, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl, substituted C2-C6 alkynyl or N(E2)(E3);E1, E2 and E3 are each, independently, H, C1-C6 alkyl or substituted C1-C6 alkyl;n is from 1 to about 6;m is 0 or 1;j is 0 or 1;g is 0 or 1;each substituted group has one or more optionally protected substituent groups independently selected from halogen, OJ1, N(J1)(J2), =NJ1, SJ1, N3, CN, OC(=L)J1, OC(=L)N(J1)(J2), OC(=L)J1, C(=L)N(J1)(J2), C(=L)O(J1), C(=L)N(H)—(CH2)2N(J1)(J2), a heterocyclic radical, and an aryl group;L is O, S or NJ3;each J1, J2 and J3 is, independently, H, C1-C6 alkyl or a protecting group; andwhen j is 1 then Z is other than halogen or N(E2)(E3).