Cytidine-5-carboxamide modified nucleotide compositions and methods related thereto

• US 9,938,314 B2
• Filed: 11/19/2014
• Issued: 04/10/2018
• Est. Priority Date: 11/21/2013
• Status: Active Grant

• Current Assignee: SomaLogic Operating Co., Inc. (Somalogic Incorporated)
• Original Assignee: Somalogic Incorporated
• Inventors: Rohloff, John, Janjic, Nebojsa, Gawande, Bharat Nathu
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US14/917,056
• Publication Number:
  US 20160215013A1
• Time in Patent Office: 1,238 Days
• Field of Search: None
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• 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: C12Q 1/6811 Selection methods for production or design of target specific oligonucleotides or binding molecules
• CPC Class Codes: C12Q 2525/117 incorporating modified base
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Described herein are 5-position modified cytosine nucleotides and nucleosides as well as phosphoramidites and triphosphates derivatives thereof. Further provided are methods of making and using the same, and compositions and uses of the modified nucleosides as part of a nucleic acid molecule (e.g., aptamer).

Claims

1. A compound comprising the structure shown in Formula I:

2. The compound of claim 1, wherein R^X4 is independently selected from the group consisting of a branched or linear lower alkyl (C1-C6);

a —

OH;

a —

F and carboxylic acid (COOH).

3. The compound of claim 1, wherein X is independently selected from the group consisting of —

H, —

OH, —

OMe and —

F.

4. The compound of claim 1, wherein R′

is selected from the group consisting of a —

H, —

OAc and —

P(NiPr₂)(OCH₂CH₂CN).

5. The compound of claim 1, R″

is a triphosphate (—

P(O)(OH)—

O—

P(O)(OH)—

O—

P(O)(OH)₂).

6. The compound of claim 1, wherein n is 0, 1, 2 or 3.

7. A nucleic acid molecule comprising the compound of claim 1.

8. A method for making a compound having Formula I:

9. The method of claim 8, wherein R^X4 is independently selected from the group consisting of a branched or linear lower alkyl (C1-C6);

a —

OH;

a —

F and carboxylic acid (COOH).

10. The method of claim 8, wherein R′

is selected from the group consisting of a —

H, —

OAc and —

P(NiPr₂)(OCH₂CH₂CN).

11. The method of claim 8, R″

is a hydrogen or triphosphate (—

P(O)(OH)—

O—

P(O)(OH)—

O—

P(O)(OH)₂);

or salt thereof.

12. The method of claim 8, wherein n is 1, 2 or 3.

13. The method of claim 8, wherein the protecting group is selected from the group consisting of triphenylmethyl, p-anisyldiphenylmethyl, di-p-anisyldiphenylmethyl, p-dimethoxy trityltrityl, formyl, t-butyloxycarbonyl, benzyloxycarbonyl, 2-chlorobenzyloxycarbonyl, 4-chlorobenzoyloxycarbonyl, 2,4-dichlorobenzyloxycarbonyl, furfurylcarbonyl, t-amyloxycarbonyl, adamantyloxycarbonyl, 2-phenylpropyl-(2)-oxycarbonyl, 2-(4-biphenyl)propyl-(2)-oxycarbonyl, 2-nitrophenylsulfenyl and diphenylphosphinyl.