Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-10-24
1999-08-31
Higel, Floyd D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514345, 514394, 514385, 514397, 514398, 514417, 514336, 514337, 514339, 514341, 514342, 514322, 514307, A61K 3142, A61K 31415, A61K 31425
Patent
active
059454253
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to methods of treating subjects having viral infections. More particularly, this invention relates to the use of (H.sup.+ /K.sup.+)ATPase inhibitors for treating viral infections.
BACKGROUND OF THE INVENTION
Inhibition of the (H.sup.+ /K.sup.+)ATPase proton pump, located in the gastric secretory membranes, has been a target for controlling gastric acid secretion in the treatment of ulcers.
Several families of compounds have been described as gastric acid secretion inhibitors, including heterocyclylalkylsulfinylbenzimidazoles (see U.S. Pat. Nos. 4,472,409, 4,394,509, 4,337,257, 4,327,102, 4,255,431, 4,045,564, 4,045,563 and 4,772,619; British Patent No. 2,134,523; and German Offenlegungsschrift No. 3,415,971) and 4,248,880 and 4,182,766). Similarly, other substituted benzimidazoles having a ring fused to the benzimidazole group have been described as gastric acid secretion inhibitors and cytoprotective agents. See EP Nos. 130,729 and 127,763.
Some heterocyclylalkylsulfinylbenzimidazoles have also been described as cytoprotective agents. See U.S. Pat. No. 4,359,465 and Great Britain Application 2,161,160, published Jan. 8, 1986. Omeprazole is an example of Trends in Pharmaceutical Sciences, 399 (1987)!.
It has been described that inhibitors of sodium transport reduce virus been reports of isolated natural products which have been independently described as having (H.sup.+ /K.sup.+) ATPase inhibitors and antiviral activity. T. Hayashi et al describe the isolation of scopadulcic acid B Res., 9, 345 (1988)!. Pumilacidins are a class of heptapeptide antibiotics that have been isolated and described as being inhibitory to HSV-1 as well (1990)!.
There is a great need for new therapies active in the treatment of viral diseases. Whereas there has been great progress in developing a variety of therapies for the treatment of bacterial infections, there are few viable therapies for the treatment of viruses. Zidovudine is the primary approved treatment for human immunodeficiency virus. Ganciclovir, acyclovir and foscarnet are currently utilized for the treatment of herpesvirus infections. However, these therapies can have substantial side effects based on their deleterious effects on host cell DNA replication or effect of a limited number of viral infections. In addition, viruses are known to develop resistance to therapies which causes a progressive decline in al, J. Infect. Dis., 161, 711 (1990)!.
Herpesviridae is a family of DNA viruses which include herpes simplex virus type-1 (HSV-1), herpes simplex virus type-2 (HSV-2), cytomegalovirus (CMV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV6), human herpesvirus-7 (HHV7), pseudorabies and rhinotracheitis, among others.
It is known that herpesviruses express their genetic content by directing the synthesis of a number of proteins encoded by the herpesvirus DNA in the host cell. One of the important virus-encoded proteins is made as a precursor consisting of an amino terminal-located protease and carboxyl terminal-located assembly protein. This precursor is proteolytically processed in an autocatalytic manner at a specific amino acid sequence known as the "release" site yielding separate protease and assembly protein. The assembly protein is cleaved further by the protease at another specific amino acid sequence known as the "maturation" cleavage site. Recently, EP No. 514,830, published Nov. 25, 1992, describes a virus-specific serine protease which has a role in herpesvirus replication. Additionally, Lui and Roizman (J. Virol, 65, 5149 (1991)) describe the sequence and activity of a protease and the associated assembly protein encoded by U.sub.L 26 of HSV-1. A. R. Welch et al (Proc. Natl. Acad. Sci. USA, 88, 10792 (1991)) describe the related protease (also known as assemblin) and assembly protein encoded by U.sub.L 80 of CMV. An approach currently being investigated for potential use in the treatment of herpesvirus infections is the development of inhibitors of herpesvirus proteases.
REFERENCES:
patent: 4045563 (1977-08-01), Berntsson et al.
patent: 4045564 (1977-08-01), Berntsson et al.
patent: 4182766 (1980-01-01), Krasso et al.
patent: 4248880 (1981-02-01), Krasso et al.
patent: 4255431 (1981-03-01), Junggren et al.
patent: 4327102 (1982-04-01), Crossley
patent: 4337257 (1982-06-01), Junggren et al.
patent: 4359465 (1982-11-01), Ruwart
patent: 4371537 (1983-02-01), Markley et al.
patent: 4394509 (1983-07-01), Crossley
patent: 4472409 (1984-09-01), Senn-Bilfinger
patent: 4772619 (1988-09-01), Adelstein et al.
BO Moorman et al, Method of Using (H+/D+) ATPase Inhibitors as Antiviral Agents, US Ser. No. 08/659,098, Jun. 4, 1996 (filing date).
Okabe et al III Patent Abstracts of Japan, vol. 13, 556 (C-664) 1989.
Lindberg et al, Trends in Pharmaceutical Sciences, 399 (1987).
A.A. Altamirano et al, Virology, 199, 151 (1994).
T. Hayashi et al, Chem. Pharm. Bull., 38, 2740 (1990).
T. Hayashi et al, Chem. Pharm. Bull., 38, 239 (1990).
T. Hayashi et al, Antiviral Res., 9, 345 (1988).
N. Naruse et al., J. Antibiotics, 43, 267 (1990).
Ljungman et al., J. Infect. Dis., 162, 244 (1990).
Gately et al, J. Infect. Dis., 161, 711 (1990).
F. Liu and B. Roizman, J. Virol., 65, 5149 (1991).
A.R. Welch et al., Proc. Natl. Acad. Sci. USA, 88, 10792 (1991).
R.W. Sidwell and J.T. Witkowski, Antiviral Agents, in Burger's Medicinal Chemistry, Part II (M. Wolff, 4th Ed. 1979).
Becker Daniel P.
Flynn Daniel L.
Li Hui
Moormann Alan E.
Villamil Clara I.
Bulock Joseph W.
G.D. Searle & Co.
Higel Floyd D.
LandOfFree
Method of using (H.sup.+ /K.sup.+)ATPase inhibitors as 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 Method of using (H.sup.+ /K.sup.+)ATPase inhibitors as antiviral, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of using (H.sup.+ /K.sup.+)ATPase inhibitors as antiviral will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2426583