Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
1991-12-06
2001-03-27
Geist, Gary (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C514S050000, C536S027140, C536S027800, C536S028200, C536S028540
Reexamination Certificate
active
06207650
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention concerns highly water soluble, stable, crystalline antiviral (including antiretroviral) salts of 2′,3′-dideoxyinosine, 2′,3′-dideoxy-2′,3′-didehydrothymidine and 2′,3′-dideoxy-2′-fluoroinosine, particularly sodium or potassium salts thereof.
Infectious viral diseases are recognized as an important medical problem. Progress against infectious viral disease requires the development of drugs with selective antiviral activity, while remaining benign to normal cell lines. A number of antiviral agents currently under study which seem to possess some selectivity are nucleoside analogs. In general, these compounds are structural analogs of the naturally occurring nucleosides. Structural modification in either the purine or pyrimidine base nucleus and/or the saccharide component results in a synthetically modified nucleoside derivative which, when incorporated into a viral nucleic acid forming process, acts to disrupt further synthesis of viral nucleic acid.
Effectiveness of these antiviral agents depends on selective conversion by viral enzymes, but not by host enzymes, to the corresponding nucleotide analog which is then converted to the triphosphate followed by incorporation into viral nucleic acid. A problem with this antiviral strategy has been the emergence of certain viral strains whose enzymes poorly promote phosphorylation of the nucleoside analogs. To circumvent this problem, intact nucleotide analogs appear to be potentially quite useful as antivirals for incorporation into viral nucleic acid.
PCT application WO 87/01284 to Mitsuya and Broder describes the use of 2′,3′-dideoxyinosine (“ddI”) for use against AIDS.
EP 0 273 277 to Lin and Prusoff discloses the use of 2′,3′-dideoxy-2′,3′-didehydrothymidine (“d4T”) in treating patients infected with a retrovirus.
Erik De Clercq, “Potential Drugs for the Treatment of AIDS”,
Journal of Antimicrobial Chemotherapy,
23, Suppl. A, 35-46, (1989), describes the use of dideoxynucleoside analogues to inhibit the infectivity and cytopathic effect of human immunodeficiency virus (“HIV”)
EP 0 287 313 discloses 2′,3′-dideoxy-2′-fluoroinosine (“F-ddI”) and its activity against HIV.
SUMMARY OF THE INVENTION
The present invention concerns very highly water soluble, stable, crystalline salts of 2′,3′-dideoxy-2′,3′-didehydrothymidine (“d4T”) of Formula (I):
2′,3′-dideoxyinosine (“DDI”) of Formula (II):
and 2′,3′-dideoxy-2′-fluoroinosine (“F-ddI”) of Formula (III):
wherein X is a cation, e.g., Na
+
, K
+
, Mg
++
, Ca
++
or amine, and n is 0.5 to 2.0.
The present invention also concerns pharmaceutical compositions comprising an antiviral effective amount of such salts and a solid, liquid or gaseous physiologically acceptable diluent.
Still further, the present invention relates to a method of treating a warm blooded animal, for example, a human, comprising administering to such warm blooded animal an antiviral effective amount of one of the aforesaid salts.
REFERENCES:
patent: 3817982 (1974-06-01), Verheyden et al.
patent: 4861759 (1989-08-01), Mitsuya et al.
patent: 4978655 (1990-12-01), Lin et al.
patent: 31973/84 (1984-08-01), None
patent: 1262132 (1989-10-01), None
patent: 0273277 (1988-07-01), None
patent: 0287313 (1988-10-01), None
patent: 2109369 (1983-06-01), None
patent: 87/01284 (1987-03-01), None
Suzuki et al.,Bull. Chem. Soc. Japan, 47,(10), 2556-2558 (1974).*
Waqar et al.,J. Cellular Physiology, 121, 402-408 (1984).*
Hamamoto et al.,Antimicrobial Agents and Chemotherapy, 31(6), 907-910 (1987).*
Baba et al.(I),Antimicrobial Agents and Chemotherapy, 31(10), 1613-1617 (1987).*
Lin et al.,Biochemical Pharmacology, 36(17), 2713-2718 (1987).*
Baba et al.(II),Biochemical Biophysical Res. Comm., 142(1), 128-134 (1987).*
Balzarini et al.,Biochemical and Biophysical Res. Comm., 158(2), 413-422 (Jan. 1989).*
March,Advanced Organic Chemistry, McGraw-Hill Book Co., New York, New York, 1968, see chapter 8.*
DeClercq, J.,Antimicrobial Chemotherapy, Suppl. A, 23, 35-46 (1989).
Bogardus Joseph B.
Kaplan Murray A.
Perrone Robert K.
Bristol--Myers Squibb Company
Crane L. Eric
Geist Gary
Morse David M.
Nolan Sandra M.
LandOfFree
Antiviral, highly water soluble, stable, crystalline salts... 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, highly water soluble, stable, crystalline salts..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antiviral, highly water soluble, stable, crystalline salts... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2525640