Anticipate generic drug launch
Drug patents …
… from Kazakhstan to Kalamazoo
Manage your formulary budget
Deep knowledge on
small-molecule drugs and
the 110,000 global patents
Find generic entry opportunities
Proactively manage your pharmacy inventory
Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing
|Title:||Prodrugs of phosphonate nucleotide analogues|
|Abstract:||A novel method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) ##STR00001## having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided.|
|Inventor(s):||Becker; Mark W. (Belmont, CA), Chapman; Harlan H. (La Honda, CA), Cihlar; Tomas (Foster City, CA), Eisenberg; Eugene J. (San Carlos, CA), He; Gong-Xin (Fremont, CA), Kernan; Michael R. (Pacifica, CA), Lee; William A. (Los Altos, CA), Prisbe; Ernest J. (Los Altos, CA), Rohloff; John C. (Mountain View, CA), Sparacino; Mark L. (Morgan Hill, CA)|
|Assignee:||Gilead Sciences, Inc. (Foster City, CA)|
1. A diastereomerically enriched compound having the structure (3) ##STR00034## which contains less than 40% by weight of the diastereomer (4) ##STR00035## wherein
R.sup.1 is an oxyester which is hydrolyzable in vivo, or hydroxyl; B is a heterocyclic base; R.sup.2 is hydroxyl, or the residue of an amino acid bonded to the P atom through an amino group of the amino acid and having each carboxy substituent of the
amino acid optionally esterified, but not both of R.sup.1 and R.sup.2 are hydroxyl; E is --(CH.sub.2).sub.2--, --CH(CH.sub.3)CH.sub.2--, --CH(CH.sub.2F)CH.sub.2--, --CH(CH.sub.2OH)CH.sub.2--, --CH(CH.dbd.CH.sub.2)CH.sub.2--, --CH(C.ident.CH)CH.sub.2--,
--CH(CH.sub.2N.sub.3)CH.sub.2--, ##STR00036## --CH(R.sup.6)OCH(R.sup.6)--, --CH(R.sup.9)CH.sub.2O-- or --CH(R.sup.8)O--, wherein the right hand bond is linked to the heterocyclic base; the broken line represents an optional double bond; R.sup.4 and
R.sup.5 are independently hydrogen, hydroxy, halo, amino or a substituent having 1-5 carbon atoms selected from acyloxy, alkyoxy, alkylthio, alkylamino and dialkylamino; R.sup.6 and R.sup.6'are independently H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6
hydroxyalkyl, or C.sub.2-C.sub.7 alkanoyl; R.sup.7 is independently H, C.sub.1-C.sub.6 alkyl, or are taken together to form --O-- or --CH.sub.2--; R.sup.8 is H, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 hydroxyalkyl or C.sub.1-C.sub.6 haloalkyl; and
R.sup.9 is H, hydroxymethyl or acyloxymethyl; and their salts, free base, and solvates.
2. The compound of claim 1 containing less than 20% by weight of the diastereomer (4).
3. The compound of claim 1 containing less than 5% by weight of the diastereomer (4).
4. A diastereomerically enriched compound having the structure (5a) ##STR00037## which contains less than 40% by weight of diastereomer (5b) ##STR00038## wherein R.sup.5 is methyl or hydrogen; R.sup.6 independently is H, alkyl, alkenyl, alkynyl, aryl or arylalkyl, or R.sup.6 independently is alkyl, alkenyl, alkynyl, aryl or arylalkyl which is substituted with from 1 to 3 substituents selected from alkylamino, alkylaminoalkyl, dialkylaminoalkyl, dialkylamino, hydroxyl, oxo, halo, amino, alkylthio, alkoxy, alkoxyalkyl, aryloxy, aryloxyalkyl, arylalkoxy, arylalkoxyalkyl, haloalkyl, nitro, nitroalkyl, azido, azidoalkyl, alkylacyl, alkylacylalkyl, carboxyl, or alkylacylamino; R.sup.7 is the side chain of any naturally-occurring or pharmaceutically acceptable amino acid and which, if the side chain comprises carboxyl, the carboxyl group is optionally esterified with an alkyl or aryl group; R.sup.11 is amino, alkylamino, oxo, or dialkylamino; and R.sup.12 is amino or H; and its salts, tautomers, free base and solvates.
5. The compound of claim 4 containing less than 20% by weight of the diastereomer (5b).
6. The compound of claim 4 containing less than 5% by weight of the diastereomer (5b).
7. A diastereomerically enriched compound of structure (6) ##STR00039## and its salts, tautomers, free base and solvates.
8. A diastereomerically enriched compound of structure (7) ##STR00040## which contains less than 40% of diastereomer (7a) ##STR00041##
9. The compound of claim 8 containing less than 20% by weight of the diastereomer (7a).
10. The compound of claim 8 containing less than 5% by weight of the diastereomer (7a).
11. A composition comprising a compound of any of claims 1-8 or 2-10 and a pharmaceutically effective excipient.
12. The composition of claim 11 wherein the excipient is a gel.
13. The composition of claim 11 which is suitable for topical administration.
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.