Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-12-29
1997-07-08
Berch, Mark L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514262, 514266, 544276, 544277, A61K 3152, C07D47332, C07D47318, C07D47316
Patent
active
056461550
ABSTRACT:
N.sup.2 -substituted alkylguanine and N.sup.2 -substituted phenylguanine compounds which prevent recurrent herpes simplex infections are disclosed. By virtue of their ability to inhibit herpes virus thymidine kinase in vivo, such compounds will prevent, reduce the frequency of, or reduce the severity of recurring HSV infections in humans. The N.sup.2 -alkylguanine compounds are of the formula: ##STR1## where R.sub.1 is a normal or branched chain C.sub.n H.sub.2n+1 (where n is 1-12); R.sub.2 is H, 2-deoxyribofuranosyl, (CH.sub.2).sub.n OH (where n is 2-5), CH.sub.2 CH(OH)CH.sub.2 OH, (CH.sub.2).sub.n --COOH (where n is 1-4), CH.sub.2 CH(OH)CH.sub.2 --O--COR.sub.4, (CH.sub.2).sub.n --O--COR.sub.4 (where n is 2-5), or (CH.sub.2).sub.n CO--OR.sub.4 (where n is 1-4); R.sub.4 is CH.sub.3, CH.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 NH.sub.2, CH.sub.2 CH.sub.2 N(C.sub.2 H.sub.5).sub.2 or CH.sub.2 CH.sub.2 CO.sub.2 H; and R.sub.3 is OH, H, Cl or NH.sub.2, or a tautomer or a pharmaceutically acceptable salt thereof. The N.sup.2 -substituted phenylguanine compounds are of similar structure, where R.sub.1 is a phenyl or a phenyl substituted at the 3 and 4 positions with an H, a hydrophobic or electron extracting group, or a CH.sub.2 CH.sub.3.
REFERENCES:
patent: 4663446 (1987-05-01), Wright
Kazimierczuk, J. Med Chem 33, 1683 (1990).
F. Focher, et al., A Novel Pharmacological Approach to Herpes Virus Infections; J. of Chemotherapy--Supplement n.4--1989, pp. 1107-1108.
F. Focher, et al., Nucleoside Analogs As Non-Substrate Inhibitors of Herpes Simplex Viruses Thymidine Kinase; Meth. and Find Exp. Clin. Pharmacol. 11:577-82, 1989.
F. Focher, et al., N.sup.2 -Substituted Guanine Derivatives Act As Selective Non Substrate Inhibitors Of HSV I Thymidine Kinase; Biochemical Pharmacology, 37:1877-78; 1988.
J. Gambino, et al., Quantitative Structure-Activity Relationships of N.sup.2 -Phenylguanines As Inhibitors Of Herpes Simplex Virus Thymidine Kinases; J. Med. Chem. 35:2979-83, 1992.
N. Bourne, et al., Assessment Of A Selective Inhibitor Of HSV Thymidine Kinase (L-653,180) As Therapy For Experimental Recurrent Genital Herpes; Antimicrobial Agents and Chemotherapy, 36:2020-24, 1992.
F. Focher, et al., N.sup.2 -Phenyldeoxyguanosine: A Novel Selective Inhibitor Of Herpes Simplex Thymidine Kinase; J. Med. Chem. 31:1496-1500, 1988.
C. Hildebrand, et al., Structure-Activity Relationships of N.sup.2 -Substituted Guanines As Inhibitors Of HSV1 and HSV2 Thymidine Kinases; J. Med. Chem. 33:203-06, 1990.
H.E. Kaufman, et al., Suppression Of Ocular Herpes Recurrences By A Thymidine Kinase Inhibitor In Squirrel Monkeys; Antiviral Res., 16 (1991), pp. 227-232.
D.A. Leib, et al., Specific Inhibitors Of HSV Thymidine Kinase Diminish Reactivation Of Latent Virus From Explanted Murine Ganglia, Antimicrobial Agents and Chemotherapy; 34:1285-86, 1990.
S. Spadari and G. Wright, Antivirals Based On Inhibition Of Herpesvirus Thymidine Kinases; Drugs, News & Perspectives 2:333-36, 1989.
Harnden et al., Analogues of the Antiviral Acyclonucleoside 9-(4-Hydroxy-3-hydroxymethylbutyl)guanine, Pt. 4, Substitution on the 2-Amino Group; J. Chem. Soc. Perkin Trans. I:2207-2213, 1989.
Wright, Herpesivrus Thymidine Kinase Inhibitors, International Antiviral News, 2(6):84-86, 1994.
Xu et al., Synthesis, Properties, and Pharmacokinetic Studies of N.sup.2 -Phenylguanine Derivatives as Inhibitors of Herpes Simplex Virus Thymidine Kinases, Journal of Medicinal Chemistry 38(1):49-57, 1995.
Berch Mark L.
University of Massachusetts Medical Center
LandOfFree
Drugs to prevent recurrent herpes virus infections does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Drugs to prevent recurrent herpes virus infections, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Drugs to prevent recurrent herpes virus infections will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2409026