Organic compounds -- part of the class 532-570 series – Organic compounds – Four or more ring nitrogens in the bicyclo ring system
Reexamination Certificate
2001-01-08
2002-06-25
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Four or more ring nitrogens in the bicyclo ring system
C544S324000, C514S273000, C514S235800
Reexamination Certificate
active
06410726
ABSTRACT:
STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
Not applicable
FIELD OF THE INVENTION
The field of the invention is in salts of substituted pyrimidine compounds and their use as pharmacologically active agents capable of suppressing and inhibiting viruses (e.g., herpes viruses). The subject compounds and compositions are particularly useful in treating and suppressing human Cytomegalovirus.
BACKGROUND OF THE INVENTION
Cytomegalovirus (CMV) is a member of the herpes virus family. Other well-known members of the herpes virus family include, for example, herpes simplex virus, types I and II, Epstein-Barr virus and varicella zoster virus. These viruses are related taxonomically, but each manifests in a clinically distinct manner. In the case of CMV, medical conditions arising from congenital infection include jaundice, respiratory distress and convulsive seizures which may result in mental retardation, neurologic disability or death. Infection in adults is frequently asymptomatic, but may manifest as mononucleosis, hepatitis, pneumonitis or retinitis, particularly in immunocompromised patients such as AIDS sufferers, chemotherapy patients, and organ transplant patients undergoing tissue rejection therapy.
A variety of drugs have been developed to treat herpes virus infections, including naturally occurring proteins and synthetic nucleoside analogs. For example, the natural anti-viral protein interferon has been used in the treatment of herpes virus infections, as have the nucleoside analogs cytosine-arabinoside, adenine-arabinoside, iodoxyuridine and acyclovir, which is presently the treatment of choice for herpes simplex type II infection.
Unfortunately, drugs such as acyclovir that have proven sufficiently effective to treat infection by certain herpes viruses are not sufficiently effective to treat CMV. Additionally, drugs currently used to treat CMV infection, such as 9-((1,3-dihydroxy-2-propoxy)methyl)guanidine (ganciclovir, DHPG) and phosphonoformic acid (foscarnet), lack the acceptable side effect and safety profiles of the drugs approved for treatment of other herpes viruses. Moreover, such drugs are ineffective to treat certain strains of CMV that have acquired drug resistance. Thus, despite advances in the development of anti-herpes virus drugs, there remains a need for therapeutic agents effective in treating CMV infection with an increased safety margin. Recently, PCT US99/03136 described the use of pyrimidine derivatives for the treatment of antiviral infections.
The present invention provides salts of certain pyrimidine derivatives which are surprisingly effective in treating viral infection and which have properties suitable for clinical use.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides compounds having the formula:
In this formula, R represents hydrogen, methyl or ethyl; Z represents a substituted or unsubstituted 1-piperidinyl, a substituted or unsubstituted 4-morpholinyl, or a substituted or unsubstituted 1-pyrrolidinyl; and Ar represents a substituted or unsubstituted phenyl or a substituted or unsubstituted naphthyl.
The compounds of the present invention are useful in therapeutic as well as prophylactic and diagnostic applications. Accordingly, the present invention provides compositions containing the above compounds and pharmaceutically acceptable excipients or diagnostically acceptable excipients. The invention further provides methods of inhibiting or suppressing certain viruses, and methods of treating individuals infected with such viruses, particularly CMV. In addition to treatments for existing conditions, the present invention also provides methods for prophylactic treatments to prevent the onset of viral infection in patients undergoing, for example, organ transplants.
Other objects, features and advantages of the present invention will become apparent to those skilled in the art from the following description and claims.
REFERENCES:
patent: 3178432 (1965-04-01), Druey et al.
patent: 4696928 (1987-09-01), Ellames et al.
patent: 4698340 (1987-10-01), Takaya et al.
patent: 4788195 (1988-11-01), Torley et al.
patent: 4929726 (1990-05-01), Strekowski et al.
patent: 4983608 (1991-01-01), Effland et al.
patent: 4987146 (1991-01-01), Rohde et al.
patent: 5147876 (1992-09-01), Mizuchi et al.
patent: 5223505 (1993-06-01), Hargreaves et al.
patent: 5304647 (1994-04-01), Strekowski et al.
patent: 5525724 (1996-06-01), Hunds
patent: 5602252 (1997-02-01), Davey et al.
patent: 5854419 (1998-12-01), Davey et al.
patent: 6200977 (2001-03-01), Cushing et al.
patent: 23 41 925 (1975-03-01), None
patent: 143 615 (1980-09-01), None
patent: 429149 (1991-05-01), None
patent: 0 640 599 (1995-03-01), None
patent: 0 806 418 (1997-11-01), None
patent: WO 98 23597 (1998-06-01), None
patent: WO 99/41253 (1999-08-01), None
Berge et al. J. of Pharmaceutial Science, 1977, 66, 1-19.
Higel Floyd D.
Saeed Kamal
Townsend and Townsend / and Crew LLP
Tularik Inc.
LandOfFree
Arylsulfonic acid salts of pyrimidine-based antiviral does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Arylsulfonic acid salts of pyrimidine-based antiviral, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Arylsulfonic acid salts of pyrimidine-based antiviral will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2961755