Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-01-11
1998-08-04
Dentz, Bernard
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514256, 514259, 514249, 514248, 514307, 514314, 514342, 514367, 514369, 548186, 544235, 544238, 544284, 544298, 544333, 544405, 544354, 5462691, 546152, 546153, 546141, 546148, A61K 31425, C07D27730, C07D21360, C07D21516
Patent
active
057894086
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to new chemical compounds which have value in the area of medical science. More particularly, this invention relates to new chemical compounds which are of value for the administration to a mammalian subject, particularly man, for the treatment of viral infectious diseases. The new chemical compounds of this invention having utility in treating viral infectious diseases are thiazole derivatives of the general formula (I), ##STR1## wherein Het, n, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined hereinbelow.
Notwithstanding the success which has been achieved in the area of antibiotic therapy, very little progress has been made in efforts to develop broad-spectrum anti-viral agents. A major problem with antiviral agents historically has been the presence of toxic side effects. Most currently known anti-viral agents have also been shown to down-regulate various immune parameters such as lymphocyte function. Accordingly, there is a clear need for a safe pharmacological agent with broad spectrum activity against viral infections.
Activated cytotoxic T cells are important in effecting the clearance of virally infected cells. An agent that can directly or indirectly increase cytotoxic T cell function should therefore enhance the clearance of virally infected cells and decrease the severity and duration of viral infection. In addition, such an agent may serve as an adjuvant for viral vaccines. Since most viral infections can be cleared by the activation of cytotoxic T cells, an agent that increases cytotoxic T cell function will have broad spectrum antiviral activity.
These new viral infectious disease treating agents are related to the medicinal agent known as tiprotimod, which is described in detail in U.S. Pat. Nos. 4,762,848 and 4,963,577. It has been reported that tiprotimod, the compound of formula (II), has a therapeutic effect on viral infectious diseases without causing adverse toxic side effects. Schorlemmer et al., U.S. Pat. No. 4,963,577. ##STR2##
SUMMARY OF THE INVENTION
This invention provides compounds of the formula ##STR3## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is --(C.sub.1 -C.sub.4)alkyl; R.sup.2 is H, --(C.sub.1 -C.sub.4)alkyl, --(C.sub.3 -C.sub.7)cycloalkyl or benzyl; R.sup.3 and R.sup.4 are taken separately and are independently H or --(C.sub.1 -C.sub.4)alkyl, or R.sup.3 and R.sup.4 are taken together to form a five- or six-membered carbocycle; n is 0, 1 or 2; Het is ##STR4## R.sup.5 is H, methyl, --CF.sub.3, --CHF.sub.2, --CH.sub.2 F, chloro, fluoro, bromo, nitro, hydroxy, --(C.sub.1 -C.sub.4)alkoxy, mercapto, --(C.sub.1 -C.sub.4)alkylthio, --(CH.sub.2).sub.p CO.sub.2 R.sup.8, amino, --(C.sub.1 -C.sub.4)alkylamino or (C.sub.1 -C.sub.4)dialkylamino; R.sup.6 and R.sup.7 are independently H, methyl, --CF.sub.3, --CH.sub.2 F, --CHF.sub.2, chloro, fluoro, bromo, nitro, hydroxy, --(C.sub.1 -C.sub.4)alkoxy, mercapto, --(C.sub.1 -C.sub.4)alkylthio, amino, --(C.sub.1 -C.sub.4)alkylamino or --(C.sub.1 -C.sub.4)dialkylamino; R.sup.8 is H, --(C.sub.1 -C.sub.4)alkyl, --(C.sub.3 -C.sub.7)cycloalkyl or benzyl; and p is 0, 1 or 2; provided that when n is 0 and R.sup.3 and R.sup.4 are H, Het is not ##STR5## and further provided that when Het is ##STR6## R.sup.5 and R.sup.6 are each not chloro, fluoro or bromo.
Preferred compounds of this invention are the compounds of formula (I) wherein Het is ##STR7##
R.sup.3, R.sup.4 and R.sup.7 are each H; R.sup.2 is H, methyl or ethyl; n is 0; R.sup.5 is H, --CO.sub.2 R.sup.8, methyl, --CH.sub.2 CO.sub.2 R.sup.8, (C.sub.1 -C.sub.4)alkylthio, methoxy or trifluoromethyl; and R.sup.1, R.sup.6 and R.sup.8 are as defined above.
More preferred compounds within this group are the compounds of the preferred group wherein Het is ##STR8## R.sup.5 is --CO.sub.2 R.sup.8 ; R.sup.6 is H, methyl or methoxy; and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.7 and n are as defined in the preferred group.
The most preferred compounds of formula (I) of this invention are the following compounds: 4-((5-carbox
REFERENCES:
patent: 4701452 (1987-10-01), Limbert et al.
patent: 4738972 (1988-04-01), Eggler
patent: 4762848 (1988-08-01), Scheunemann et al.
patent: 4963577 (1990-10-01), Schorlemmer et al.
patent: 5114939 (1992-05-01), Dreikorn
patent: 5294622 (1994-03-01), Dreikorn
Kleinman Edward Fox
Masamune Hiroko
Parikh Vinod Dipak
Benson Gregg C.
Dentz Bernard
M. Mach D. Margaret
Pfizer Inc.
Richardson Peter C.
LandOfFree
Antiviral thiazoles does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antiviral thiazoles, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antiviral thiazoles will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1177418