Phosphoramidite synthones for the synthesis of self-neutralizing oligonucleotide compounds
AssigneeZata Pharmaceuticals, Inc.
InventorsDavid R. Tabatadze, Ivan Yanachkov
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Abstract
Compositions and compounds having nucleoside phosphoramidites, and methods of making the same are provided. The compounds can also have one or more amino groups that each can be positively charged. The compounds described permit facile attachment of certain neutralizing moieties with positive charges at their terminal ends on the backbones of oligonucleotides. The compounds can be used for the treatment of cancer, autoimmune, genetic and infectious diseases.
Claims23
A compound of having structure (I):
- wherein R1 is a nucleic acid moiety, a spacer group, or a combination thereof;
- wherein R2 is, independently for each occurrence, selected from the group consisting of H, CH3, CH2CH3, an alkyl, a substituted alkyl, a branched chain alkyl, formyl, acetyl, CF3, trifluoroacetyl, allyl, triphenylmethyl, and tert-butyloxycarbonyl;
- wherein R3 is, independently for each occurrence, selected from the group consisting of H, F, CH3, CH2CH3, an alkyl, a substituted alkyl, a branched chain alkyl, formyl, acetyl, CF3, trifluoroacetyl, allyl, triphenylmethyl, tert-butyloxycarbonyl, N-PAC, N-iPrPAC, N-benzoyl, and N-Ac, or wherein each R3 pair bonded to a single nitrogen together form a 5 membered ring, 6 membered ring, or a 7 membered ring;
- wherein R4 is selected from the group consisting of H, F, CH3, CH2CH3, OCH3, OCH2CH3, OCH(CH3)2, CH(CH3)2, and C(CH3)3;
- wherein Xi, X2, and X3 are, independently for each occurrence, selected from the group consisting of O, S, CH2, and CH2CH2;
- and
- wherein m is, independently for each occurrence, 0, 1, 2, 3, 4 or 5;
- or a pharmaceutically acceptable salt, hydrate, or solvate thereof.
6-7. (canceled)
(canceled)
12-13. (canceled)
16-30. (canceled)
An oligonucleotide comprising:
- an oligonucleotide sugar-phosphate backbone;
- a plurality of nitrogenous bases, each nitrogenous base covalently bonded to a sugar unit of the sugar-phosphate backbone;
- and
- at least one neutralizing moiety covalently bonded to a phosphorus of the sugar-phosphate backbone;
- wherein the at least one neutralizing moiety has structure (V):
- wherein R2 and R3 are, independently for each occurrence, selected from the group consisting of H, CH3, CH2CH3, an alkyl, a substituted alkyl, and a branched chain alkyl;
- wherein R4 is selected from the group consisting of H, F, CH3, CH2CH3, OCH3, OCH2CH3, OCH(CH3)2, CH(CH3)2, and C(CH3)3;
- wherein Xi, X2, and X3 are, independently for each occurrence, selected from the group consisting of O, S, CH2, and CH2CH2;
- and
- wherein m is, independently for each occurrence, 0, 1, 2, 3, 4 or 5.
A method of treating a disease or a disorder in a person in need thereof comprising:
- administering an oligonucleotide to the person;
- wherein the oligonucleotide comprises at least one neutralizing moiety having structure (V);
- wherein R2 and R3 are, independently for each occurrence, selected from the group consisting of H, CH3, CH2CH3, an alkyl, a substituted alkyl, and a branched chain alkyl;
- wherein R4 is selected from the group consisting of H, F, CH3, CH2CH3, OCH3, OCH2CH3, OCH(CH3)2, CH(CH3)2, and C(CH3)3;
- wherein Xi, X2, and X3 are, independently for each occurrence, selected from the group consisting of O, S, CH2, and CH2CH2;
- and
- wherein m is, independently for each occurrence, 0, 1, 2, 3, 4 or 5;
- wherein the oligonucleotide is delivered to a cell and modulates a cellular response.
Dependencies are inferred from the claim text.