Tricyclic compounds and method of treating herpes virus

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C549S043000, C549S460000, C514S468000, C544S037000, C544S102000, C544S348000, C546S104000, C540S468000, C540S479000, C540S557000, C540S577000, C540S471000, C540S586000

Reexamination Certificate

active

06800656

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to compounds possessing antiviral activity against viruses of the herpes family, or a composition containing them. These compounds provide a method for treating herpes viral infections, including condition caused by herpes simplex I such as cold sores, herpes simplex II such as genital herpes, as well as shingles caused by herpes zoster and infections caused by cytomegalovirus, Epstein Barr Virus.
BACKGROUND OF INVENTION
Various subfamilies of herpes viruses (Herpes viridae) exist: &agr;-herpesvirinae, &bgr;-herpesvirinae, &ggr;-herpesvirinae and cercopithecing Herpes virus I (3 virus); some specific viruses are: Herpes simplex virus-I (HSV-1), Herpes simplex virus-2 HSV-2), Cytomegalovirus (CMV), Varicella Zoster virus (VZV), Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6), human herpes virus-7 (HHV-7), human herpes virus-8 (HHV) as well as others which may not yet be defined.
The incidence of infections by Herpes simplex virus is very high throughout the world. Serological studies showed that herpes viral infections affect a substantial percentage of the population. Reactivation of herpes virus infections may lead to recurrent infections. The risk of severe diseases increases with decreasing immunocompetence of the host. There is a pressing need for improved therapy for treating this disease. Currently, exclusive of vaccines, treat involves primarily nucleoside drugs such as acyclovir, which target thymidine kinase and suffer from development of resistance.
SUMMARY OF THE INVENTION
The present invention provides a compound of the formula and its pharmaceutically acceptable salts, or the compound and its pharmaceutical composition having useful antiviral activity against viruses of the herpes family.
wherein:
X=O, (CH
2
)
m
, S, SO, SO
2
, NR
8
or a chemical bond;
Y=O, (CH
2
)
m
, S, SO, SO
2
, NH, NR
8
;
Z=N, NH, O, NHR
8
, S, SO, SO
2
;
n=an integer of from 0 to 2;
m=an integer of 1, 2, or 3;
R
1
, R
2
, R
3
, R
4
, R
5
independently are hydrogen, halogen, hydroxyl amino, mono or dialkylamino, cyano, nitro, alkyl groups (1-6 carbon atoms), alkoxy groups (1-6 carbon atoms), CF
3
, OCF
3
, aminoalkyl (1-6 carbon atoms), aminoaryl, Oaryl, or a heterocyclic ring having 5-7 atoms with 1-4 hetero atoms of N, O, or S;
Ar=phenyl,
substituted phenyl,
benzoheterocyclic ring,
substituted benzoheterocyclic ring,
heterocyclic ring, or
substituted heterocyclic ring, which have substitutions R
6
or R
7
;
R
4
and R
7
are independently hydrogen, alkyl group (1-6 carbon atoms), cycloalkyl (3-12 carbon atoms), halogen, alkoxy, CF
3
, aminoalkyl (1-6 carbon atoms), aminoaryl, or a heterocyclic ring of from 5-7 atoms with 1-4 heteroatoms of N, O or S;
R
6
and R
7
may also form a ring, optionally cycloalkyl or aryl or substituted aryl; R
8
is hydrogen, alkyl (1-6 carbon atoms), cycloalkyl (3-12 carbon atoms), phenyl or substituted phenyl wherein the substituents are as defined above.
The invention also provides for a pharmaceutical composition for the treatment of infection or disease caused by a virus, optionally a Herpes virus which comprises an amount of the compound of claim
1
sufficient to provide an antivirally effective dosage of the compound of Formula I and a pharmaceutically effective carrier.
The invention also provides for a method of treatment of infection or disease caused by a virus, optionally a Herpes virus which comprises administering to a subject in need of such treatment an effective antivirally dosage of a composition of formula I.


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International Search Report for PCT/US00/32571 filed on Nov. 30, 2000.

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