Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1988-04-08
1990-05-22
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544280, 544243, C07D40104, A61K 3140
Patent
active
049278304
DESCRIPTION:
BRIEF SUMMARY
R.sub.2? 5-(1-methoxyethyl); (2-ethoxy)methyl, (2-acetoxyethoxy)methyl, 2-hydroxy-1-(1,3-dihydroxy-2-propoxy)ethyl, (2-phosphonylmethoxy)ethyl or 3-hydroxy-2-phosphonylmethoxypropyl.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1 and 2 are graphs showing HCMV titer reduction by antiviral compounds.
DESCRIPTION OF THE INVENTION
A. Chemical Structure of Compounds
The present invention relates to the treatment of viral infections with pyrrolo[2,3-d]pyrimidine analogs of the following formula and pharmaceutically acceptable salts thereof: ##STR2## where R.sub.1 is NH.sub.2 or NHOH; 5-(1-methoxyethyl); (2-ethoxy)methyl, (2-acetoxyethoxy)methyl, 2-hydroxy-1-(1,3-dihydroxy-2-propoxy)ethyl, (2-phosphonylmethoxy)ethyl or 3-hydroxy-2-phosphonylmethoxypropyl.
Preferred specific compounds include the following: where R.sub.1 is NH.sub.2, R.sub.2 is Cl, R.sub.3 is H and R.sub.4 is --CH.sub.2 --OCH.sub.2 --CH.sub.2 OH; where R.sub.1 is NH.sub.2, R.sub.2 is Br, R.sub.3 is H and R.sub.4 is --CH.sub.2 --OCH.sub.2 --CH.sub.2 OH; R.sub.1 is NH.sub.2, R.sub.2 is I, R.sub.3 is H and R.sub.4 is --CH.sub.2 --OCH.sub.2 --CH.sub.2 OH; 4-amino-5-chloro-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3-d]pyrimidi ne, where R.sub.1 is NH.sub.2, R.sub.2 is Cl, R.sub.3 is H and R.sub.4 is --CH.sub.2 --O--CH(CH.sub.2 OH).sub.2 ; 4-amino-5-bromo-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3-d]pyrimidin e, where R.sub.1 is NH.sub.2, R.sub.2 is Br, R.sub.3 is H and R.sub.4 is --CH.sub.2 --O--CH(CH.sub.2 OH).sub.2 ; 4-amino-5-iodo-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3-d]pyrimidine , where R.sub.1 is NH.sub.2, R.sub.2 is I R.sub.3 is H and R.sub.4 is --CH.sub.2 --O--CH(CH.sub.2 OH).sub.2 ; 4-amino-5-thiocarboxamide-7-[(1,3-dihydroxy-2-propoxy)methyl]pyrrolo[2,3-d ]pyrimidine, where R.sub.1 is NH.sub.2, R.sub.2 is CSNH.sub.2, R.sub.3 is H and R.sub.4 is --CH.sub.2 --O--CH(CH.sub.2 OH).sub.2 ; and 4-amino-5-thiocarboxamide-7-(2-hydroxyethoxymethyl)pyrrolo[2,3-d]pyrimidin e, where R.sub.1 is NH.sub.2, R.sub.2 is CSNH.sub.2, R.sub.3 is H and R.sub.4 is --CH.sub.2 --OCH.sub.2 --CH.sub.2 OH.
B. Method of Use of Compounds
The compounds of the present invention exhibit antiviral activity and acceptable cytotoxicity for use as therapeutic agents. In particular, it has been found that these compounds are effective against HCMV and HSV-1. The compounds are thus useful in the treatment of viral infections caused by the HCMV and HSV-1 viruses as well as other viruses. A partial list of the viruses contemplated to be treatable with the compounds of the present invention includes: herpes simplex virus types 1 and 2; human cytomegalovirus; varicella-zoster virus; Epstein-Barr virus; herpesvirus simian (virus of monkeys); equine herpesvirus-1, 2 and 3; neurolymphomatosis (Marek's disease); influenza viruses A, B and C; parainfluenza viruses-1, 2, 3 and 4; adenovirus; rheovirus; respiratory syncytial virus; rhinovirus; coxsackie virus; echo virus; rubeola virus; hepatitis viruses; and papovavirus.
A compound of the present invention can be used in the treatment of viral infections in animals in accordance with conventional procedures, such as an active ingredient in pharmaceutical compositions, which can be administered topically, or parentally. The pharmaceutical compositions may take the form of tablets, lozenges, granules, capsules, pills, ampoules or suppositories. They may also take the form of ointments, gels, pastes, creams, sprays, lotions, suspensions, solutions and emulsions of the active ingredient in aqueous or nonaqueous diluents, syrups, granulates or powders. In addition to a compound of the present invention, the pharmaceutical compositions can also contain other pharmaceutically active compounds or a plurality of compounds of the invention.
C. Method of Synthesis
1. General Synthesis Schemes
The compounds of the present invention can be synthesized in accordance with the procedures described vide infra. As shown in the following general synthesis Schemes the appropriate pyrrolo[2,3-d]pyrimidine analog can be condensed with
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Gadler, H., '
Drach John C.
Townsend Leroy B.
Cseh C. L.
Shah Mukund J.
The Regents of the University of Michigan
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