6-MODIFIED BICYCLIC NUCLEIC ACID ANALOGS

• US 20090012281A1
• Filed: 05/29/2008
• Published: 01/08/2009
• Est. Priority Date: 01/27/2006
• Status: Active Grant

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Seth, Punit P., Swayze, Eric E.
• Granted Patent: US 7,741,457 B2
• Time in Patent Office: Days
• US Class Current: 536/23.100
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention provides 6-modified bicyclic nucleoside analogs and oligomeric compounds comprising these nucleoside analogs. In preferred embodiments the nucleoside analogs have either (R) or (S)-chirality at the 6-position. These bicyclicnucleoside analogs are useful for enhancing properties of oligomeric compounds including nuclease resistance.

Claims

1-50. -50. (canceled)

51. An oligomeric compound having at least one monomer of formula:

52. The oligomeric compound of claim 51 wherein each of said modified sugar moieties is, independently, selected from a 2′

-F modified sugar moiety, a 2′

-OCH₃ modified sugar moiety, a 2′

-O—

(CH₂)₂—

OCH₃ modified sugar moiety, a 2′

-O—

CH₂-4′

bicyclic modified sugar moiety or a 4′

-S modified sugar moiety.

53. The oligomeric compound of claim 51 wherein each Z is, independently, C₁-C₆ alkyl or substituted C₁-C₆ alkyl.

54. The oligomeric compound of claim 53 wherein each Z is methyl.

55. The oligomeric compound of claim 53 wherein each Z is substituted C₁-C₆ alkyl.

56. The oligomeric compound of claim 55 wherein each of said substituent groups is C₁-C₆ alkoxy.

57. The oligomeric compound of claim 56 wherein each Z is CH₃OCH₂—

.

58. The oligomeric compound of claim 51 wherein the Z group of each monomer of said formula has the configuration represented by formula:

59. The oligomeric compound of claim 51 wherein the Z group of each monomer of said formula has the configuration represented by formula:

60. The oligomeric compound of claim 51 wherein each internucleoside linking group is selected from phosphodiester or phosphorothioate.

61. The oligomeric compound of claim 51 wherein each internucleoside linking group is a phosphorothioate.

62. An oligomeric compound having the formula:

[T-L]_j-[R-L]_q-R-[L-T]_r

wherein;

each T is a monomer of formula I;

63. The oligomeric compound of claim 62 wherein each Z is, independently, C₁-C₆ alkyl or substituted C₁-C₆ alkyl.

64. The oligomeric compound of claim 63 wherein each Z is methyl.

65. The oligomeric compound of claim 63 wherein each Z is substituted C₁-C₆ alkyl.

66. The oligomeric compound of claim 65 wherein each of said substituent groups is C₁-C₆ alkoxy.

67. The oligomeric compound of claim 66 wherein each Z is CH₃OCH₂—

.

68. The oligomeric compound of claim 62 wherein the Z group of each monomer of said formula has the configuration represented by formula:

69. The oligomeric compound of claim 62 wherein the Z group of each monomer of said formula has the configuration represented by formula:

70. The oligomeric compound of claim 62 wherein each internucleoside linking group is selected from phosphodiester or phosphorothioate.

71. The oligomeric compound of claim 62 wherein each internucleoside linking group is a phosphorothioate.

72. The oligomeric compound of claim 62 wherein j is 0.

73. The oligomeric compound of claim 62 wherein r is 0.

74. The oligomeric compound of claim 62 wherein j and r are each other than 0.