Derivatives of peptide nucleic acids with good cell penetration and strong affinity for nucleic acid

摘要

A peptide nucleic acid derivative of Formula I or a pharmaceutically acceptable salt thereof: ** Formula ** wherein n is an integer equal to or greater than; S1, S2, .... Sn-1, Sn, T1, T2, ..., Tn-1, and Tn independently represent hydrogen, deuterium, substituted or unsubstituted alkyl radicals, or substituted or unsubstituted aryl; X and Y independently represent hydrogen, deuterium, substituted or unsubstituted alkyl, substituted or unsubstituted acyl, substituted or unsubstituted sulfonyl, or substituted or unsubstituted aryl radicals; Z represents hydroxy, substituted or unsubstituted alkyloxy, substituted or unsubstituted aryloxy, or substituted or unsubstituted amino radicals; B1, B2, ..., Bn-1, and Bn are independently selected from natural nucleobases that include adenine, thymine, guanine, cytosine and uracil, and unnatural nucleobases; and, at least one of B1, B2, ..., Bn-1, and Bn is independently selected from unnatural nucleobases represented by Formula II, Formula III, or Formula IV: ** Formula ** wherein R1, R2 , R3, R4, R5 and R6 are independently selected from substituted or unsubstituted alkyl radicals, and hydrogen; and, L1, L2 and L3 are a covalent linker represented by Formula V that connects a basic amino group to the portion responsible for the pairing properties of nucleobases: ** Formula ** wherein Q1 and Qm are substituted methylene radicals or unsubstituted (-CH2-), and Qm is directly linked to the basic amino group; Q2, Q3, ..., and Q m-1 are independently selected from substituted or unsubstituted methylene radicals, oxygen (-O-), sulfur (-S-), and substituted or unsubstituted amino [-N (H) -, or -N (substituent) -]; and, m is an integer from 2 to 15.