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Vinyl ethers of nucleoside analogs
| Details |
Inventors: Kim, Choung Un; Martin, John C.; Luh, Bing Uh; Misco, Peter F.;
Assignee: Institute of Organic Chemistry and Biochemistry of the Academy of (CZ); Rega Stichting v.z.w. (BE)
Primary Examiner: Berch; Mark L.
Assistant Examiner:
Attorney, Agent or Firm: Hensley; Max D.
Provided are compounds of the following formulae: A phosphonomethoxymethyoxymethyl purine/pyrimidine derivative of the formula ##STR1## wherein X and X' are the same or different and are hydrogen or alkyl. R and R' are the same or different and are hydrogen, alkyl, hydroxyalkyl or alkanoyl and B is a purine or pyrimidine base. A 4'-phosphonomethoxytetrahydrofuranyl-1'-purine-pyrimidine of the formula ##STR2## wherein X and X' are the same or different and are hydrogen or alkyl, Y and Z are the same or different and are hydrogen, hydroxyl or alkyl or Y+Z is an alkenyl, an epoxide or cyclopropyl, and B is a purine or pyrimidine base. A compound of the formula (V) ##STR3## wherein B is cytosine, 5-ethylcytosine, 5-methylcytosine, thymine, uracil, 5-chlorouracil, 5-bromouracil, 5-ethyluracil, 5-iodouracil, 5-propyluracil, 5-vinyluracil, hypoxanthine, xanthine, guanine, 8-bromoguanine, 8-chloroguanine, 8-methylguanine, 8-thioguanine, 3-deazaguanine, purine, 2-aminopurine, 2,6-diaminopurine, adenine, 3-deazaadenine, 8-aminoguanine, 8-hydrazinoguanine, 8-hydroxyguanine, or 2-acetamido-6-diphenylcarbamoylpurine; and the pharmaceutically acceptable salts thereof. |
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DETAILED DESCRIPTION OF THE INVENTION The compounds of the present invention can exist as optical isomers. Both the racemic and diasteromeric mixtures of these isomers which may exist for certain compounds, as well as the individual optical isomers, are all within the scope of the present invention. While the racemic mixtures can be separated into their individual isomers through well-known techniques such as, for example, the separation of diastereomeric salts formed with optically active adjuncts, e. g. , acids or bases followed by conversion back to the optically active substrates, in most instances, for the compounds of the present invention, the preferred optical isomer can be synthesized by means of stereospecific reactions, beginning with the appropriate stereoisomer of the desired starting material. As indicated above, the present invention also pertains to pharmaceutically acceptable non-toxic salts of these compounds, containing, for example, Na. sup. +, Li. sup. +, K. sup. +, Ca. sup. ++ and Mg. sup. ++. Such salts may include those derived by combination of appropriate cations such as alkali and alkaline earth metal ions or ammonium and quaternary amino ions with the acid anion moiety of the phosphonic acid group. Metal salts can be prepared by reacting the metal hydroxide with a compound of this invention. Examples of metal salts which can be prepared in this way are salts containing Li. sup. +, Na. sup. +, and K. sup. +. A less soluble metal salt can be precipitated from the solution of a more soluble salt by addition of the suitable metal compound. In addition, salts may be formed from acid addition of certain organic and inorganic acids, e. g. , HCl, HBr, H. sub. 2 SO. sub. 4 or organic sulfonic acids, with basic centers of the purine, specifically guanine, or pyrimidine base. Finally, it is to be understood that compounds of the present invention in their unionized, as well as zwitterionic form, and/or in the form, of solvates are also considered part of the present invention. Compounds of the present invention also exist in subclasses, with two broad subclasses being those wherein B is either a purine or a pyrimidine base
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