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Nucleoside metabolism inhibitorsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Heterocyclic Carbon Compounds Containing A Hetero Ring Having Chalcogen (i.e., O,s,se Or Te) Or Nitrogen As The Only Ring Hetero Atoms Doai, Hetero Ring Is Six-membered Consisting Of Two Nitrogens And Four Carbon Atoms (e.g., Pyridazines, Etc.), 1,4-diazine As One Of The Cyclos, Polycyclo Ring System Having 1,3-diazine As One Of The Cyclos, A Ring Nitrogen Is Shared By The Two Cyclos Of The Bicyclo Ring System (e.g., Pyrrolo [1,2-a]pyrimidine, Imidazo[1,2-a]pyrimidine, Etc.),Nucleoside metabolism inhibitors description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070015772, Nucleoside metabolism inhibitors. Brief Patent Description - Full Patent Description - Patent Application Claims
TECHNICAL FIELD [0001] This invention relates to certain nucleoside analogues, pharmaceutical compositions containing the compounds and processes for preparing the compounds. BACKGROUND OF THE INVENTION [0002] Purine nucleoside phosphorylase (PNP) catalyses the phosphorolytic cleavage of ribo- and deoxyribonucleosides, for example, those of guanine and hypoxanthine to give the corresponding sugar-1-phosphate and guanine, hypoxanthine, or other purine bases. [0003] Humans deficient in purine nucleoside phosphorylase (PNP) suffer a specific T-cell immunodeficiency due to an accumulation of dGTP and its toxicity to stimulated T lymphocytes. Because of this, inhibitors against PNP are immunosuppressive, and are active against T-cell malignancies. Clinical trials are now in progress using 9-(3-pyridylmethyl)-9-deazaguanine in topical form against psoriasis and in oral form for T-cell lymphoma and immunosuppression (BioCryst Pharmaceuticals, Inc). The compound has an IC.sub.50 of 35 nM for the enzyme. In animal studies, a 50 mg/kg oral dose is required for activity in a contact sensitivity ear swelling assay in mice. For human doses, this would mean approximately 3.5 grams for a 70 kg human. With this inhibitor, PNP is difficult to inhibit due to the relatively high activity of the enzyme in blood and mammalian tissues. [0004] Nucleoside and deoxynucleoside hydrolases catalyse the hydrolysis of nucleosides and deoxynucleosides. These enzymes are not found in mammals but are required for nucleoside salvage in some protozoan parasites. Purine phosphoribosyltransferases (PPRT) catalyze the transfer of purine bases to 5-phospho-.alpha.-D-ribose-1-pyrophosphate to form purine nucleotide 5'-phosphates. Protozoan and other parasites contain PPRT which are involved in essential purine salvage pathways. Malignant tissues also contain PPRT. Some protozoan parasites contain purine nucleoside phosphorylases which also function in purine salvage pathways. Inhibitors of nucleoside hydrolases, purine nucleoside phosphorylases and PPRT can be expected to interfere with the metabolism of parasites and therefore be usefully employed against protozoan parasites. Inhibitors of PNP and PPRT can be expected to interfere with purine metabolism in malignant tissues and therefore be usefully employed against malignant tissues. [0005] The applicants' PCT International Patent publication WO 99/19338 describes compounds which are potent inhibitors of PNP, PPRT and/or nucleoside hydrolases. [0006] It is an object of the present invention to provide further compounds which are effective inhibitors of PNP, PPRT and/or nucleoside hydrolases, or at least to provide the public with a useful choice. SUMMARY OF THE INVENTION [0007] Accordingly, in a first aspect, the present invention provides a compound of the formula: wherein: A is selected from N, CH and CR, where R is selected from halogen, optionally substituted alkyl, aralkyl and aryl, OH, NH.sub.2, NHR.sup.1, NR.sup.1R.sup.2 and SR.sup.3, where R.sup.1, R.sup.2 and R.sup.3 are each optionally substituted alkyl, aralkyl or aryl groups; B is selected from OH, NH.sub.2, NHR.sup.4, H and halogen, where R.sup.4 is an optionally substituted alkyl, aralkyl or aryl group; D is selected from OH, NH.sub.2, NHR.sup.5, H, halogen and SCH.sub.3, where R.sup.5 is an optionally substituted alkyl, aralkyl or aryl group; X and Y are independently selected from H, OH and halogen, with the proviso that when one of X and Y is hydroxy or halogen, the other is hydrogen; Z is OH, or, when X is hydroxy, Z is selected from hydrogen, halogen, hydroxy, SQ and OQ, where Q is an optionally substituted alkyl, aralkyl or aryl group; and W is OH or H, with the proviso that when W is OH, then A is CR where R is as defined above; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof. [0008] Preferably when B is NHR.sup.4 and/or D is NHR.sup.5, then R.sup.4 and/or R.sup.5 are C.sup.1-C.sup.4 alkyl. [0009] Preferably when one or more halogens are present they are chosen from chlorine and fluorine. [0010] Preferably when Z is SQ or OQ, Q is C.sub.1-C.sub.5 alkyl or phenyl. [0011] Preferably D is H, or when D is other than H, B is OH. [0012] More preferably, B is OH, D is H, OH or NH.sub.2, X is OH or H, Y is H, most preferably with Z as OH, H, or methylthio, especially OH. [0013] In certain preferred embodiments W is OH, Y is H, X is OH, and A is CR where R is methyl or halogen, preferably fluorine. [0014] In other preferred embodiments, W is H, Y is H, X is OH and A is CH. [0015] It will be appreciated that the representation of a compound of formula (I) wherein B and/or D is a hydroxy group used herein is of the enol-type tautomeric form of a corresponding amide, and this will largely exist in the amide form. The use of the enol-type tautomeric representation is simply to allow fewer structural formulae to represent the compounds of the invention. According to another aspect of the invention, there is provided a pharmaceutical composition comprising a pharmaceutically effective amount of a compound of the formula (I) as defined above. [0016] In another aspect, the invention provides methods for treatment of diseases or conditions in which it is desirable to decrease the level of T lymphocyte activity, the method comprising administering to a mammal in need of such treatment a pharmaceutically effective amount of a compound as defined above. [0017] In a further aspect, the invention provides methods for treatment and/or prophylaxis of parasitic infections, particularly those caused by protozoan parasites, the method comprising administering to a mammal in need of such treatment a pharmaceutically effective amount of a compound as defined above. [0018] In further aspects, the invention provides methods of preparing compounds of formula (I) as defined above. [0019] While the invention is broadly as defined above, it is not limited thereto and also includes embodiments of which the following description provides examples. DESCRIPTION OF THE INVENTION [0020] This invention provides novel compounds of the formula (I) as defined above, which are potent inhibitors of purine nucleoside phosphorylase, nucleoside hydrolases and/or phosphoribosyltransferases. Continue reading about Nucleoside metabolism inhibitors... Full patent description for Nucleoside metabolism inhibitors Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Nucleoside metabolism inhibitors patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. 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