Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1993-03-01
1995-01-03
Daus, Donald G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514 63, 514312, 514432, 514456, 514682, 546 14, 546 25, 546155, 549 23, 549283, 549285, 568328, C07D21556, A61K 3147
Patent
active
053786947
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND
EP 595698 discloses heterocyclic carboxamides which increase the activity of the immune system. U.S. Pat. No. 3,960,668 discloses derivatives of 6, 7, or 8 cycloalkyl 4oxo quinoline 3 carboxylic acid which possess analgesic, anti-inflammatory anti-microbial and histamine liberation inhibiting properties.
This invention relates to compounds having antiviral activity and to compounds having antihypertensive activity, pharmaceutical compositions thereof, and methods of treatment utilizing the compositions. In particular, this invention is related to compounds having antiviral activity against viruses of the herpes group, pharmaceutical compositions containing the compounds, and methods of treating viruses of the herpes group using the pharmaceutical compositions.
There are four separate viruses of the herpes group which infect and cause disease in humans. These are (1) herpes simplex virus 1 and 2 (HSV-1 and HSV-2. respectively): (2) cytomegalovirus (CMV); (3) varicella-zoster virus (VZ); and (4) Epstein-Barr virus (EB). Examples of diseases associated with herpes simplex virus infection include herpes labialis, genital herpes (herpes progenitalis), neonatal herpes, herpetic keratitis, eczema herpeticum, disseminated herpes, occupational herpes, herpetic gingivostomatitis, meningitis (aseptic), and encephalitis.
CMV is widespread in humans and numerous other mammals. The great majority of human CMV infections are subclinical; that is, the primary infection occurs with no signs or symptoms. An exception to this is a congenital infection which occasionally gives rise to cytomegalic inclusion body disease in infants. There is also a mononucleosis-like syndrome caused by the virus. The great majority of serious cases due to CMV infection come from recurring infections in immuno-compromised patients such as transplant patients and cancer patients. It has been estimated that silent CMV infections have occurred in a majority of humans by the time adulthood is reached.
VZ virus is associated with chicken-pox (varicella) and shingles (zoster) in humans.
EB virus is quite common and causes glandular fever; it is also believed to be responsible for genetic damage that leads to Burkitt's lymphoma.
Examples of drugs used to treat herpes infections include: (1) IUDR (5'-iodo-2'-deoxyuridine); (2) Ara-C (1-[beta-D-arabinofuranosyl]-cytosine); (3) Ara-A (9-[beta-D-arabinofuranosyl]adenine); and (4) Acyclovir (9-[(2-hydroxyethoxy)methyl]guanine). Also Haines et al. (U.S. Pat. No. 4,757,088 issued Jul. 12, 1988) disclose that lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide) is an antiviral agent in cell culture against HSV-1 and HSV-2, and is able to treat herpes virus infections of mammals. Haines et al. also disclose that lidocaine is particularly effective in the treatment of HSV oral and genital lesions in humans. According to Haines et al., the addition of pantothenic acid or its alcohol and salt forms, dexpanthenol and pantothenate respectively, to lidocaine or lidocaine hydrochloride significantly enhances the antiviral activity of those drugs.
Human hypertension is a disease of multiple etiologies. Drugs that act to control one form may not be effective in controlling another. Therefore, further drugs that can be useful in treating hypertension are desirable.
In view of current interest in the an for finding useful antihypertensive agents and useful antiviral agents, in particular, useful agents against viruses of the herpes group, any new compounds exhibiting antihypertensive activity or antiviral activity would be a welcome contribution to the art. This invention provides such a contribution.
SUMMARY OF THE INVENTION
This invention provides compounds which are useful as antiviral agents against DNA-containing viruses such as herpes group viruses. In particular, the compounds of this invention are useful against HSV-1 and HSV-2 and may also prove useful against CMV and EB.
The compounds of this invention are advantageous over known viral compounds because they inhibit early events in viral r
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Afonso Adriano
Gentles Margaret J.
Rosenblum Stuart B.
Weinstein Jay
Boxer Matthew
Daus Donald G.
Dicker Eric S.
Maitner John J.
Schering Corporation
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