Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines

An oligomer of the formula (16):

• 12
• wherein each R1 is independently H, PO3−2, or a blocking group;
• each R3 is independently selected from the group consisting of H, OH, F, NH2, OCH3, OC2H5, SCH3, SC2H5, SC3H7, OC3H5, and SC3H5;
• each X1 is independently a substitute linkage selected from the group consisting of —P(S)(O)—, —P(O)(O)—, —P(Me)(O)— and —P(Me)(S)—.
• Pr is a protecting group;
• n is an integer from 0 to 98;
• and
• B is a purine or pyrimidine base, provided that at least one B is of formula (1) or (2):
• 13
• wherein each X is independently O or S;
• R2 is a group comprising at least one pi bond connected through a carbon attached to the base;
• and
• Pr is H2 or a protecting group and with the proviso that when at least one of said nucleomonomers of said oligomer comprises deoxyuridine 5-substituted by vinyl, 1-butenyl, 1-pentenyl, 1-hexenyl, 1-heptenyl, 1-octenyl, 1-propynyl, 1-butynyl, 1-hexynyl, 1-heptynyl, or 1-octynyl, then the remainder of the nucleomonomers comprising said oligomer are not solely comprised of phosphodiester linked 2′-deoxyadenosine, 2′-deoxyguanosine, 2′-deoxycytidine, thymidine or a combination thereof.

A nucleomonomer having the structural formula (3) or (4):

• 14
• wherein each R1 is independently H or a blocking group;
• R2 is a group comprising at least one pi bond connected through a carbon atom attached to the base;
• Pr is (H2) or a protecting group;
• and
• R3 is selected from the group consisting of H, OH, F, OCH3, OC2H5, OC3H7, SCH3, SC2H5, SC3H7, OC3H5, and SC3H5,
• with the proviso that if R3 is H or OH, and both R1 are H, R2 is 1,3-pentadiynyl, 2-, 3-, and 4-pyridine-ethynyl, 2-pyrimidine-ethynyl, 4-pyrimidine-ethynyl, 5-pyrimidine-ethynyl, triazine-ethynyl, 2-pyrimidinyl, 2- and 4-imidazolyl, 2- and 3-pyrrolyl-ethynyl, 2- and 3-furanyl-ethynyl, 2- and 3-thienyl-ethynyl, 2-, 4- and 5-imidazolyl-ethynyl, 2-, 4-, and 5-thiazolyl-ethynyl, 2-, 4- and 5-oxazolyl-ethynyl, 4- and 5-thiazolyl, 4- and 5-oxazolyl, or 3-pyrrolyl.

An o-xyloso dimer of the formula (5):

• 15
• wherein
• each Y is independently R1 or
• an oligomer;
• R1 is H, PO3−2 or a blocking group;
• and
• each B is independently a purine or pyrimidine base, provided that at least one B is a base of formula (1) or (2), wherein R2 is a group comprising at least one pi bond connected through a carbon atom attached to the base;
• and Pr is (H)2 or a protecting group.

A dimer of the formula (6), (7) or (8):

• 16
• wherein
• X is selected from the group consisting of O and S;
• X2 is selected from the group consisting of CO, CS and SO2;
• X3 is independently selected from the group consisting of O, S, CH2, CF2 and CFH;
• X4 is independently Selected from the group consisting of O, S, SO, SO2, CH2, CO, CF2, CS, NH and NR4 wherein R4 is lower alkyl (C1-4;
• methyl, ethyl, propyl, isopropyl, butyl or isobutyl);
• X5 is selected from the group consisting of O, CO, S, CH2, CS, SO2, CO, NH and NR4;
• X6 is selected from the group consisting of CH, N, CF, CCl, and CR5 wherein R5 is lower alkyl (C1-4) fluoromethyl, difluoromethyl, trifluoromethyl or lower fluoroalkyl (C2-4, F1-5);
• X7 is selected from the group consisting of O, S, CH2, CO, CF2 and CS;
• each Y independently is an oligomer or R1 wherein R1 is PO3−2 or a blocking group;
• each R3 is independently selected from the group consisting of H, OH, F, NH2, OCH3, OC2H5, OC3H7, SCH3, SC2H5, SC3H7, OC3H5, and SC3H5;
• each B is independently a purine or pyrimidine base, provided that at least one B is of formula (1) or (2) wherein each X is O or S;
• R2 is a group comprising at least one pi bond connected through a carbon atom attached to the base;
• and
• Pr is (H)2 or a protecting group;
• and further provided that X5 and X7 are not both O.