TRICYCLIC NUCLEIC ACID ANALOGS

摘要

The present disclosure provides tricyclic nucleosides and oligomeric compounds prepared therefrom. The tricyclic nucleosides each have a tricyclic ribosyl sugar moiety wherein a bridge between the 2′ and 4′ ribosyl ring carbon atoms further comprises a fused carbocyclic or heterocyclic ring. The tricyclic nucleosides are expected to be useful for enhancing properties of oligomeric compounds including for example binding affinity and nuclease resistance.

主权项

1. A tricyclic nucleoside having Formula I: wherein:
Bx is a heterocyclic base moiety;Q is CH2—CH2, CH═CH, O, S, or NR1;R1 is H, C1-C6 alkyl, substituted C1-C6 alkyl, C2-C6 alkenyl, substituted C2-C6 alkenyl, C2-C6 alkynyl, substituted C2-C6 alkynyl or a protecting group;one of q1 and q2 is hydroxyl or a protected hydroxyl and the other of q1 and q2 is H;one of q3 and q4 is hydroxyl, a protected hydroxyl or a reactive phosphorus group selected from a phosphoramidite, H-phosphonate and phosphate triester and the other of q3 and q4 is H;wherein each substituted group is, independently, mono or poly substituted with substituent groups independently selected from halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, OJ1, SJ1, NJ1J2, N3, CN, C(═O)OJ1, C(═O)NJ1J2, C(═O)J1, O—C(═O)NJ1J2, N(H)C(═O)—NJ1J2, N(H)C(═S)NJ1J2 and a protecting group;each J1 and J2 is, independently, H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 aminoalkyl or a protecting group;n is 1 or 2; andm is 0 when Q is CH2—CH2 or CH═CH and m is 1 when Q is O, S, or NR1.