3'-Modified oligonucleotide derivatives

• Main Authors: CAROLUS, CAROLIN, UHLMANN, EUGEN, PEYMAN, ANUSCHIRWAN
• Format: Patent
• Language: English; French; German
• Published: 27.12.1995
• Edition: 6
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS BASED THEREON; COMPOSITIONS OR TEST PAPERS THEREFOR; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; DERIVATIVES THEREOF; ENZYMOLOGY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONSONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; ORGANIC MACROMOLECULAR COMPOUNDS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROCESSES OF PREPARING SUCH COMPOSITIONS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; STEROIDS; SUGARS; THEIR PREPARATION OR CHEMICAL WORKING-UP; VINEGAR; WINE

Es werden neue Oligonucleotidanaloga der Formeln I und II worin A, B, D, R , R , T, U, V, W, X, Y, Z, a, b, m, m', n und n' die in der Beschreibung angegebenen Bedeutungen haben, mit wertvollen physikalischen, biologischen und pharmakologischen Eigenschaften sowie ein Verfahren zu deren Herstellung beschrieben. Ihre Anwendung bezieht sich auf die Verwendung als Inhibitoren der Genexpression (Antisense Oligonucleotide, Ribozyme, Sense Oligonucleotide und Triplex Forming Oligonucleotide), als Sonden zum Nachweis von Nucleinsäuren und als Hilfsmittel in der Molekularbiologie. 3'-Derivatised oligonucleotide analogues of formula (I) and (II) and their salts are new: R -(A )n'-(B )m'-(A )n-(B )m-B (I); R -(A )n'-(B )m'-(A )n-A (II); A and A = gps. of formula (i); B and B = gps. of formula (ii); B = a gp. of formula (iii); and A = a gp. of formula (iv); a and b = 0 to 20; R = H, 1-18C alkyl, 2-18C alkenyl, 3-18C alkynyl, 2-19C alkanoyl, 3-20C alkenoyl, 4-20C alkynoyl, 6-20C aryl, (6-14C)aryl(1-8C)alkyl or P(W)ZZ'; R = H, OH, 1-18C alkoxy, halogen, azido or NH2; D = OH or OPO3<2->; B = a natural or unnatural nucleotide base; n = 1-100; n' = 0-50; m = 0-5; m' = 0-5 in (I) or 1-5 in (II); A = O, S or CH2; W = O, S or Se; V = O or S; T = O, S or NH; Y = O, S, NH or CH2; X = OH or SH; U = OH, SH, BH3 (sic), SeH, 1-18C alkoxy, 1-18C alkyl, 6-20C aryl, (6-14C)aryl(1-8C)alkyl, NHR , NR R or (OCH2CH2)pO(CH2)qCH2R ; R = 1-18C alkyl, 6-20C aryl, (6-14C)aryl(1-8C)alkyl or (CH2)c(NH(CH2)c)dNR R ; c = 2-6; d = 0-6; R = H, 1-6C alkyl or (1-4C)alkoxy(1-6C)alkyl; R = 1-18C alkyl, 6-20C aryl or (6-14C)aryl(1-8C)alkyl; or NR R = a 5- or 6-membered ring opt. contg. another N, O or S atom; p = 1-100; q = 0-22; R = H or a functional gp. such as OH, NH2, NHR , COOH, CONH2, COOR or halogen; R = 1-6C alkyl, R = 1-4C alkyl; Z and Z' = OH, SH, SeH, 1-22C alkoxy, O(CH2)bNHR 'R ', 1-18C alkyl, 6-20C aryl, (6-14)aryl(1-8C)alkyl (where aryl includes heteroaryl and is opt. substd. by 1-3 of COOH, NH2, NO2, 1-4C alkylamino, 1-6C alkoxy, OH, halogen and CN), 1-18C alkylthio, NHR , NR R , a 3'- or 5'-linked nucleoside or oligonucleotide, or a gp. which enhances intracellular uptake, serves as a DNA probe label or binds to, crosslinks with or cleaves a target nucleic acid after hybridisation; R 'R ' = as R , R ; or NR 'R = a 3- to 6-membered ring.