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US 10,239,908 B2Granted
Cytidine-5-carboxamide modified nucleotide compositions and methods related thereto
AssigneeSomaLogic, Inc.
InventorsJohn Rohloff, Nebojsa Janjic, Bharat Nathu Gawande
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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).
Claims13
A compound comprising the structure shown in Formula I:
- wherein
- R is independently a —(CH2)n—, wherein n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
- RX1 comprises
- * denotes the point of attachment of the RX1 group to the —(CH2)n— group;
- and
- RX4 is independently selected from the group consisting of a branched or linear lower alkyl (C1-C20);
- a hydroxyl group;
- F, Cl, Br, I;
- nitrile (CN);
- boronic acid (BO2H2);
- carboxylic acid (COOH);
- carboxylic acid ester (COORX2);
- primary amide (CONH2);
- secondary amide (CONHRX2);
- tertiary amide (CONRX2RX3);
- sulfonamide (SO2NH2);
- N-alkylsulfonamide (SONHRX2);
- RX2 and RX3 are independently, for each occurrence, selected from the group consisting of a branched or linear lower alkyl (C1-C20);
- phenyl (C6H5);
- an RX4 substituted phenyl ring (RX4C6H4), wherein RX4 is defined above;
- a carboxylic acid (COOH);
- a carboxylic acid ester (COORX5), wherein RX5 is a branched or linear lower alkyl (C1-C20);
- and cycloalkyl, wherein RX2=RX3=(CH2)n;
- X is independently selected from the group consisting of —H, —OH, —OMe, —O-allyl, —F, —OEt, —OPr, —OCH2CH2OCH3 and -azido;
- R′ is independently selected from the group consisting of a —H, —OAc;
- —OBz;
- —P(NiPr2)(OCH2CH2CN);
- and —OSiMe2tBu;
- R″ is independently selected from the group consisting of a hydrogen, 4,4′-dimethoxytrityl (DMT) and triphosphate (—P(O)(OH)—O—P(O)(OH)—O—P(O)(OH)2) or a salt thereof;
- and salts thereof.
27 more elements
A method for making a compound having Formula I:
- wherein
- R is independently a —(CH2)n—, wherein n is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
- RX1 is independently selected from the group consisting of
- * denotes the point of attachment of the RX1 group to the —(CH2)n— group;
- RX4 is independently selected from the group consisting of a branched or linear lower alkyl (C1-C20);
- a hydroxyl group;
- F, Cl, Br, I;
- nitrile (CN);
- boronic acid (BO2H2);
- carboxylic acid (COOH);
- carboxylic acid ester (COORX2);
- primary amide (CONH2);
- secondary amide (CONHRX2);
- tertiary amide (CONRX2RX3);
- sulfonamide (SO2NH2);
- N-alkylsulfonamide (SONHRX2);
- RX2 and RX3 are independently, for each occurrence, selected from the group consisting of a branched or linear lower alkyl (C1-C20);
- phenyl (C6H5);
- an RX4 substituted phenyl ring (RX4C6H4), wherein RX4 is defined above;
- a carboxylic acid (COOH);
- a carboxylic acid ester (COORX5), wherein RX5 is a branched or linear lower alkyl (C1-C20);
- and cycloalkyl, wherein RX2=RX3=(CH2)n;
- X is independently selected from the group consisting of —H, —OH, —OMe, —O-allyl, —F, —OEt, —OPr, —OCH2CH2OCH3 and -azido;
- R′ is independently selected from the group consisting of a —H, —OAc;
- —OBz;
- —P(NiPr2)(OCH2CH2CN);
- and —OSiMe2tBu;
- R″ is independently selected from the group consisting of an hydrogen, 4,4′-dimethoxytrityl (DMT) and triphosphate (—P(O)(OH)—O—P(O)(OH)—O—P(O)(OH)2) or a salt thereof;
- the method comprising providing a compound having Formula IX
- wherein,
- RX6 is an iodine or bromine group;
- RX7 and RX8 axe independently, for each occurrence, a hydrogen or protecting group;
- X is independently selected from the group consisting of —H, —OH, —OMe, —O-allyl, —F, —OEt, —OPr, —OCH2CH2OCH3 and -azido;
- and
- transforming the compound having Formula IX by a palladium(0) catalyzed reaction in the presence of RX1—R—NH2, carbon monoxide and a solvent;
- and
- isolating the compound having Formula I.
34 more elements
Dependencies are inferred from the claim text.