3920 results about "Protecting group" patented technology

An oligonucleotide analogue useful for the antisense method, etc., having excellent enzyme resistance, having potent selective binding affinity for single-stranded RNA, and further having an excellent triplex-forming capacity with double-stranded DNA, and a nucleoside analogue useful for its production are provided.Nucleoside analogues, which are compounds of the general formula (I) and salts thereof, and oligonucleotide analogues containing one or more of the nucleoside analogues:where Base is an aromatic heterocyclic group or the like optionally having a substituent; R1, R2 and R3 are each a hydrogen atom, a protective group for an amino group, a protective group for a hydroxyl group, a phosphate group, or —P(R4)R5 [where R4 and R5 are each a hydroxyl group, a protected hydroxyl group, a mercapto group, a protected mercapto group, etc.]; m=0 to 2; and n=1 to 3].

Compounds and a method of synthesis of compounds of formula (Ia) or (Ib): and salts, solvates, and chemically protected forms thereof, wherein the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R2 and R3 are independently selected from —H, ═O, ═CH2, —CN, —R, OR, halo, ═CH—R, O—SO2—R, CO2R and COR; R10 is a carbamate-based nitrogen protecting group; and R11 is an oxygen protecting group.

A compound of formula (I) and salts and solvates thereof, wherein: R10 is a nitrogen protecting group and R11 is either OH or O—R12, wherein R12 is an oxygen protecting group, or R10 and R11 together form a double bond between N10 and C11; and R10′ and R11′ are selected from the same options as R10 and R11 respectively.

The present inventors have developed a key intermediate for the production of C2 substituted PBDs, which has a leaving group at the C2 position, a carbamate protecting group at the N10 position and a protected hydroxy group at the C11 position. In a first aspect, the present invention comprises a compound with a the formula (I), wherein: R10 is a carbamate-based nitrogen protecting group; R11 is an oxygen protecting group; and R2 is a labile leaving group. In a further aspect, the present invention comprises a method of synthesising a compound of formula (III), or a solvate thereof, from a compound of formula (I) as defined in the first aspect, R16 is either O—R11, wherein R11 is as defined in the first aspect, or OH, or R10 and R16 together form a double bond between N10 and C11; and R15 is R. The other substituents are defined in the claims. Further aspects of the present invention relate to compounds of formula (III) (including solvates thereof when R10 and R16 form a double bond between N10 and C11, and pharmaceutical salts thereof), pharmaceutical compositions comprising these, and their use in the manufacture of a medicament for the treatment of a proliferative disease.

A compound of the formula (1):wherein R1 and R2 are the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphate group, or —P(R3)R4, wherein R3 and R4 are the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms; A represents an alkylene group having from 1 to 4 carbon atoms and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent α selected from the group consisting of a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may be substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom; or a salt thereof.

This application relates to monomers of the general formula (I) for the preparation of PNA (peptide nucleic acid) oligomers and provides method for the synthesis of both predefined sequence PNA oligomers and random sequence PNA oligomers:whereinE is sulfur or oxygen; J is nitrogen or C—R′;R1, R′ is independently H, halogen, alkyl, nitro, nitrile, alkoxy, halogenated alkyl, halogenated alkoxy or a functional group having one of following general formulae:whereinA1, A2, A3, A4, A5, is independently selected from H, halogen such as F, Cl, Br or I, CF3, alkyl, preferably C1–C4 alkyl, nitro, nitrile, alkoxy, preferably C1–C4 alkoxy, halogenated (such as F, Cl, Br and I) alkyl, preferably halogenated C1–C4 alkyl, halogenated (such as F, Cl, Br and I) alkoxy, preferably halogenated C1–C4 alkoxy, phenyl, and halogenated (such as F, Cl, Br and I phenyl;R2 is H or protected or unprotected side chain of natural or unnatural α-amino acid; andB is a natural or unnatural nucleobase, wherein when said nucleobase has an exocyclic amino function, said function is protected by protecting group which is labile to acids but stable to weak to medium bases in the presence of thiol.

Aspects of the invention include 2′ protected nucleoside monomers that are protected at the 2′ site with thiocarbon protecting groups. Thiocarbon protecting groups of interest include thiocarbonate, thionocarbonate, dithiocarbonate groups, as well as thionocarbamate protecting groups. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.

Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

Aspects of the invention include 2′ protected nucleoside monomers that are protected at the 2′ site with orthoester-type protecting groups. The 2′ protected monomers also include a second, aryl carbonate-type, protecting group. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.

Precursors for use in the synthesis of polynucleotides and methods of using the precursors in synthesizing polynucleotides are disclosed. The precursors include a heterocyclic base having an exocyclic amine group and a substituted or unsubstituted triaryl methyl protecting group bound to the exocyclic amine group.

Methods of forming an internucleotide bond are disclosed. Such methods find use in synthesis of polynucleotides. The method involves contacting a functionalized support with a precursor having an exocyclic amine triaryl methyl protecting group under conditions and for a time sufficient to result in internucleotide bond formation. The functionalized support includes a solid support, a triaryl methyl linker group, and a nucleoside moiety having a reactive site hydroxyl, the nucleoside moiety attached to the solid support via the triaryl methyl linker group. In particular embodiments, the precursor has the structure:wherein:O and H represent oxygen and hydrogen, respectivelyR1 is hydrido, hydroxyl, protected hydroxyl, lower alkyl, modified lower alkyl, or alkoxy,one of R2 or R3 is a hydroxyl protecting group; and the other of R2 or R3 is a reactive group capable of reacting with the reactive site hydroxyl,Base is a heterocyclic base having an exocyclic amine group, andTram is the exocyclic amine triaryl methyl protecting group.

Precursors for use in the synthesis of polynucleotides are disclosed. The precursors include a heterocyclic base having an exocyclic amine group and a substituted or unsubstituted triaryl methyl protecting group bound to the exocyclic amine group. In particular embodiments, the precursor has the structure:wherein:O and H represent oxygen and hydrogen, respectively,R1 is hydrido, hydroxyl, protected hydroxyl, lower alkyl, modified lower alkyl, or alkoxy,one of R2 or R3 is a hydroxyl protecting group; and the other of R2 or R3 is a reactive group capable of reacting with a reactive site hydroxyl,Base is a heterocyclic base having an exocyclic amine group, andTram is a triaryl methyl group having the structure (V)wherein the broken line represents a bond to the amino nitrogen of the exocyclic amine group, and R4, R5 and R6 are independently selected from unsubstituted or substituted aryl groups, provided that at least one of R4, R5, and R6 is an aryl group other than phenyl and other than substituted phenyl.