摘要:
Resolved enantiomers of the formula ##STR1## wherein B is a purine or pyrimidine base or aza and/or deaza analogs thereof are useful in antiviral pharmaceutical compositions to treat retroviral infections.
摘要:
Novel compounds are provided that comprise esters of antiviral phosphonomethoxy nucleotide analogs with carbonates and/or carbamates having the structure --OC(R.sup.2).sub.2 OC(O)X(R).sub.a, wherein R.sup.2 independently is H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro or OR.sup.3 in which R.sup.3 is C.sub.1 -C12 alkyl; X is N or O; R is independently H, C.sub.1 -C.sub.12 alkyl, aryl, alkenyl, alkynyl, alkyenylaryl, alkynylaryl, alkaryl, arylalkynyl, arylalkenyl or arylalkyl which is unsubstituted or is substituted with halo, azido, nitro, --O--, --N.dbd., --NR.sup.4 --, --N(R.sup.4).sub.2 -- or OR.sup.3, R.sup.4 independently is --H or C.sub.1 -C.sub.8 alkyl, provided that at least one R is not H; and a is 1 or 2, with the proviso that when a is 2 and X is N, (a) two R groups can be taken together to form a carbocycle or oxygen-containing heterocycle, or (b) one R additionally can be OR.sup.3. The compounds are useful as intermediates for the preparation of antiviral compounds or oligonucleotides, or are useful for administration directly to patients for antiviral therapy or prophylaxis. Embodiments are particularly useful when administered orally.
摘要:
Nucleotide phosphonate esters characterized by the presence of an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise an ester bond that is hydrolyzed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for their synthesis and use are described.
摘要:
This invention relates to new nucleotide analogues and solves the technical problem of their use as biologically active compounds. The subject of this invention are N-(2-phosphonylmethoxyethyl) and N-(3-hydroxy-2-phosphonylmethoxypropyl) derivatives of pyrimidine and purine bases, easily accessible from heterocyolic bases and their N-(2-hydroxyethyl) or N-(2,3-dihydroxypropyl) derivatives. Some of the compounds, according to this invention, exhibit a marked antiviral activity or can be converted into such active compounds by chemical transformations.
摘要:
Nucleotide analogs characterized by the presence of an amidate lirked amino acid or an ester linked group which is bonded to the phosphorus atom of phosphonate nucleotide analogs are disclosed. The analogs comprise a phosphoamidate or ester bond that is hydrolysed in vivo to yield a corresponding phosphonate nucleotide analog. Methods and intermediates for the synthesis and use are described.
摘要:
Intermediates for fluorescent dyes based on 9-carboxyethyl-6-hydroxy-3-oxo-3H-xanthene which are useful as reporters for reporter-labeled DNA fragments are described. The intermediates are protected fluorescent dyes bearing acyloxy groups at the 3 and 9 positions and an alkoxy group at the 9 position. Deprotection of the protected fluorescent dye by treatment with aqueous ammonia regenerates free dye.
摘要:
A DNA sequencing system and method are described to detect the presence of radiant energy emitted from different excited reporter dye-labeled species (DNA fragments) following separation in time and/or space, and the identity of the species which emit radiant energy closely spaced in wavelength. Functions of the emitted energy are obtained which vary over the wavelengths of the closely spaced spectra in different senses and the functions ratioed, whereby the ratio is indicative of the identity of the DNA fragments.The emitting portion of the reporter-labeled DNA fragment is preferably one of a family of fluorescent dyes based on 9-carboxyethyl-6-hydroxy-3-oxo-3H-xanthene. These xanthene dyes are covalently attached to the DNA fragments through the carboxylic acid functionality, preferably via an amide linkage. The dyes may be protected by including an alkoxy group at the 9-position. A spacer may be inserted between the dye and the amine. The fluorescent dye preferably is attached to the DNA chain terminators and provides many advantages. Thus only DNA sequencing fragments resulting from bona fide termination events will carry a reporter. The DNA sequencing may also be labeled using the xanthene dyes which have general utility as fluorescent labels. Also acyclonucleoside triphosphates are described as being useful as chain terminators in DNA sequencing using a modification of the Sanger method.
摘要:
The invention provides compounds of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein [D] is the residue of a drug having a reactive functional group, said functional group being attached, directly or through a bridging group, via an oxygen-phosphorus bond to the phosphorus atom of the ##STR2## moiety; R.sub.1 is C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.10 aryl or C.sub.7 -C.sub.12 aralkyl; R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.10 aryl, C.sub.4 -C.sub.9 heteroaryl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloheteroalkyl or C.sub.7 -C.sub.12 aralkyl; and R.sub.3 is selected from the group consisting of C.sub.1 -C.sub.8 alkyl; C.sub.2 -C.sub.8 alkenyl having one or two double bonds; (C.sub.3 -C.sub.7 cycloalkyl)--C.sub.r H.sub.2r --wherein r is zero, one, two or three, the cycloalkyl portion being unsubstituted or bearing 1 or 2 C.sub.1 -C.sub.4 alkyl substituents on the ring portion; (C.sub.6 -C.sub.10 aryloxy)C.sub.1 -C.sub.8 alkyl; 2--, 3-- or 4-- pyridyl; and phenyl-C.sub.r H.sub.2r -- wherein r is zero, one, two or three and phenyl is unsubstituted, or is substituted by 1 to 3 alkyl each having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halo, trifluoromethyl, dialkylamino having 2 to 8 carbon atoms or alkanoylamino having 2 to 6 carbon atoms. The compounds are adapted for targeted drug delivery, especially to the brain.
摘要:
Compounds to general formula ##STR1## in which R and R' are hydrogen or benzyl and X represents a purine on pyrimidine base group selected from isoguanine, guanine, cytosine, 5-fluorouracil, S-methyl uracil (thymine) and chloroguanine, exhibit anti-viral properties.