14-02-2013 дата публикации
Номер: US20130041144A1
Provided herein are novel 5′-(S)—CHsubstituted bicyclic nucleosides, oligomeric compounds prepared therefrom and methods of using the oligomeric compounds. More particularly, the furanose ring of each of the novel 5′-(S)—CHsubstituted bicyclic nucleosides includes a 2′ to 4′ bridging group. The 5′-(S)—CHsubstituted bicyclic nucleosides are expected to be useful for enhancing one or more properties of the oligomeric compounds they are incorporated into such as for example increasing the binding affinity. In certain embodiments, the oligomeric compounds provided herein hybridize to a portion of a target RNA resulting in loss of normal function of the target RNA. 2. The bicyclic nucleoside of wherein:{'sub': 1', '2', 'n', '1', '2', '1', '2', '3', '4', '1', '2', '3', '4', '1', '2', '3', '4, 'G is —[C(RR)]—, —C(R)═C(R)—, —C(R)═C(R)—C(RR)—, —C[═C(RR)]-C(RR)— or —C(RR)—C[═C(RR)]—;'}{'sub': 1', '2', '3', '4', '1', '6', '1', '6', '2', '6', '2', '6', '2', '6', '2', '6', '1, 'R, R, Rand Rare each independently, H, F, C-Calkyl, substituted C-Calkyl, C-Calkenyl, substituted C-Calkenyl, C-Calkynyl, substituted C-Calkynyl, CN or OJ;'}{'sub': '1', 'each substituted group comprises one or more optionally protected substituent groups independently selected from halogen and OJ; and'}{'sub': 1', '1', '6, 'Jis H or C-Calkyl.'}3. The bicyclic nucleoside of wherein:{'sub': 2', '2', '2', '3', '2', '3', '2', '3', '2', '2', '2', '2', '3', '3', '2', '3', '2', '2', '3', '2, 'G is —C(H)(CN)—, —(CH)—, —CH—C(H)(CH)—, —CH—C(H)[(R)—CH]—, —CH—C(H)[(S)—CH]—, —CH—C(═CH)—, —C(═CH)—CH—, —C(H)═C(H)—, —C(CH)═C(H)—, —C(H)═C(CH)—, —(CH)—, —(CH)—C*(H)(CH)— or —CH═CH—CH—.'}4. The bicyclic nucleoside of wherein:{'sub': 7', '1', '2', '1', '2', '7', '3', '4', '1', '2', '7', '1', '2', '7', '1', '2', '3', '1', '2', '3', '4', '7', '1', '2', '3', '4', '1', '2', '3', '4', '1', '2', '3', '4', '1', '2', '3', '4', '5', '6, 'G is —C(═O)—N(R)—C(RR)—, —C(RR)—N(R)—C(RR)—, —C(RR)—N(R)—O—, —C(RR)—O—N(R)—, —C(RR)—N(OR)—, —C(RR ...
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