Patent ID: 6777544
Filing Date: 2004-08-17
Classification: A61P,C07H

Abstract:
A PNA derivative of Formula I whereinV is oxygen, sulfur, NR1, Uâ€”(CR3R4)uâ€²â€”CH2â€”C(O)â€”NH, or Uâ€”(CH2C2O)uâ€²â€”C(O)â€”NH; U is, independently of any other U, oxygen, sulfur, or NH; uâ€² is, independently of any other uâ€², from 1 to 10; W is, independently of any other W, oxygen, sulfur, or NR1; Y is, independently of any other Y, hydroxyl, mercapto, oxyanion, thioate, or NR1R2, R1 and R2 are, independently of each other, a radical consisting of hydrogen or C1-C6-alkyl; R3 and R4 are, independently of each other, a radical consisting of hydrogen or a C1-C6-alkyl, or the radical of an amino acid side chain; X is, independently of any other X, Uâ€”(C2-C22-alkanediyl)-U, Uâ€”(CH2CH2â€”O)uâ€², a bifunctional labeling group; a bifunctional group for crosslinking with complementary nucleic acids, a bifunctional group which promotes intracellular uptake, or a bifunctional group which increases the binding affinity of the PNA derivative for a target nucleic acid; Z is hydroxyl, mercapto, oxyanion, thioate, NR1R2, C1-C22-alkyl, C1-C8-arylalkyl, C1-C22-alkyl-U, C1-C8-arylalkyl-U, hydroxy-C1-C18â€”U, aminoalkyl-U, arylalkyl-U or mercaptoalkyl-U, a group of the formula R9(CH2CH2â€”O)m, wherein R9 is hydroxyl, amino, or C1-C22-alkoxy, and m is from 1 to 100, a monofunctional or bifunctional labeling group, a monofunctional or bifunctional crosslinking group, a monofunctional or bifunctional group which promotes intracellular uptake, or a monofunctional or bifunctional group which promotes the binding affinity of the PNA derivative for a target nucleic acid; n is from 0 to 10; Q is hydroxyl, amino, NHR7, NR7R8, an amino acid derivative, or a peptide radical, R7 and R8 are, independently of each other, C1-C18-alkyl or hydroxy-C1-C18-alkyl, and wherein (POLY) is described by Formula II wherein (BLOCK) is, independently of any other (BLOCK), described by Formula IIIA, wherein each building block {BLOCK} can be different,and wherein zâˆ  is from 0 to 100; A is, independently of any other A, (CR1R2)s, wherein s is from 1 to 3, B is, independently of any other B, an aromatic radical which optionally possesses heteroaromatic character, hydrogen, hydroxyl, C1-C18-alkyl, or a nucleobase or its prodrug form, wherein at least one B radical is a nucleobase; D is, independently of any other D, (CR3R4)t, wherein t is from 2 to 10, wherein two adjacent R3 and R4 radicals can form a C5-C8-cycloalkyl ring; E is, independently of any other E, (CR5R6)uâ€², R5 and R6 are, independently of each other, a radical consisting of hydrogen or C1-C6-alkyl, or an amino acid side chain, wherein two adjacent R5 and R6 radicals can form a C5-C8-cycloalkyl ring or a spiro compound, and wherein R1, R2, R3, R4, and uâ€² are as defined above; and physiologically tolerated salts of the PNA derivative of the Formula I, with the proviso that at least one Y or Z radical is hydroxyl, mercapto, oxyanion, or thioate.