Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing
|Title:||Prodrugs of phosphonates|
|Abstract:||There are disclosed novel oral prodrugs of phosphonate nucleotide analogs which are hydrolyzable under physiological conditions to yield compounds which are useful as antiviral agents, especially as agents effective against RNA and DNA viruses. They may also find use as antitumor agents.|
|Inventor(s):||Starrett, Jr.; John E. (Middletown, CT), Mansuri; Muzammil M. (Cheshire, CT), Martin; John C. (Cheshire, CT), Tortolani; David R. (Meriden, CT), Bronson; Joanne J. (Madison, CT)|
|Assignee:||Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic (CZ) N/A (BE) Rega Stichting v.z.w. (N/A)|
|Filing Date:||Jun 07, 1995|
|Claims:||1. The compound having formula II ##STR25## wherein B is cytosine or Z; |
R.sup.1 and R.sup.2 are independently OH or OR.sup.4 provided that at least one of R.sup.1 or R.sup.2, is OR.sup.4, or one of R.sup.1 or R.sup.2 is linked to X to form a cyclic compound having Formula V ##STR26## * stereochemistry R, S, or RS; R.sup.13 is OR.sup.4 ;
X is CH.sub.2 OR.sup.6 (R, S or RS stereochemistry) or hydroxymethyl with the proviso that when X is CH.sub.2 OR.sup.6, then R.sup.1 and R.sup.2 may additionally be independently chosen from OH;
R.sup.6 is a hydrolyzable ester;
R.sup.4 is CH.sub.2 C(O)NR.sup.5.sub.2, CH.sub.2 C(O)OR.sup.5, CH.sub.2 OC(O)R.sup.5, CH(R.sup.5)OC(O)R.sup.5 (R, S, or RS stereochemistry), CH.sub.2 C(R.sup.5.sub.2 CH.sub.2 OH, or CH.sub.2 OR.sup.5 ; R.sup.4 may also be R.sup.5' ;
R.sup.5 is C.sub.1 -C.sub.20 alkyl, aryl or aryl-alkyl which is unsubstituted or is substituted by hydroxy, oxygen, nitrogen or halogen;
R.sup.5' is C.sub.4 -C.sub.20 alkyl, aryl or aryl-alkyl which is substituted by hydroxy, oxygen, nitrogen or halogen;
Z is ##STR27## O is independently H, Cl, NHR.sup.5, NR.sup.5.sub.2, NHC(O)R.sup.5, N(C(O)R.sup.5).sub.2, OH or NCHN(R.sup.5).sub.2 provided that when O is NCHN(R.sup.5).sub.2, then R.sup.5 is not CH.sub.3.
2. A method for the treatment of human cytomegalovirus viral infection in a mammal which comprises administering an antiviral effective non-toxic dose of a compound of claim 1 to the infected mammal for a treatment period of sufficient duration to mitigate said infection provided, however, that B is cytosine and X is hydroxymethyl.
3. The method of claim 2 wherein the compound is administered orally.
4. A pharmaceutical composition which comprises an antiviral effective amount of at least one compound of claim 1 in association with a pharmaceutically acceptable substantially non-toxic carrier or excipient.
5. The compound of claim 1 wherein B is cytosine.
6. The compound of claim 1 wherein R.sup.5' is C.sub.4 -C.sub.20 alkyl, aryl or aryl-alkyl any one of which is substituted by hydroxy or halogen.
7. The compound of claim 1 wherein R.sup.5' is aryl or aryl-alkyl which is unsubstituted or either of which is substituted by substituents independently selected from the group consisting of hydroxy, oxygen, nitrogen and halogen.
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.