Claims for Patent: 4,866,035

Summary for Patent: 4,866,035

Title:	Dipeptidyl saccharides as host resistance enhancers in AIDS-immuno-compromised hosts and methods of use
Abstract:	Disclosed are specific dipeptidyl saccharide derivatives which alone, or in combination with an anti-AIDS drug, e.g. azidothymidine, provide protection against opportunistic infection in human individuals whose resistance to infection has been specifically suppressed by an AIDS-related (HIV) virus, as well as help to suppress the AIDS-related infection itself.
Inventor(s):	Durette; Philippe L. (New Providence, NJ)
Assignee:	Merck & Co., Inc. (Rahway, NJ)
Application Number:	07/105,056
Patent Claims:	1. A composition for enhancing host resistance against opportunisic bacterial, fungal or viral infection in a human host immunocompromised by an AIDS-related virus comprising a compound: ##STR9## provided said glycose is not 2-amino-2-deoxy-D-glucose, wherein R.sub.1 is hydrogen; alkyl of 1 to 7 carbon atoms optionally substituted by hydroxy, mercapto, alkoxy of 1 to 3 carbon atoms, alkyl mercapto of 1 to 3 carbon atoms, hydroxy or mercapto esterified by an acid of 1 to 4 carbon atoms, halogen, carboxy; phenyl, benzyl each optionally substituted by alkyl of 1 to 3 carbon atoms, lower alkyldioxy, amino, trifluoromethyl, hydroxy, mercapto, hydroxy or mercapto etherified by alkyl of 1 to 3 carbon atoms, or hydroxy or mercapto esterified by an acid of 1 to 4 carbon atoms; R.sub.2 is alkyl of 1 to 7 carbon atoms optionally substituted by hydroxy, mercapto, alkoxy of 1 to 3 carbon atoms, alkyl mercapto of 1 to 3 carbon atoms, hydroxy or mercapto esterified by an acid of 1 to 4 carbon atoms, halogen, carboxyl, carboxyl esterified by an alcohol of 1 to 3 carbon atoms, or amidated carboxyl; phenyl, optionally substituted by alkyl of 1 to 3 carbon atoms, lower alkyldioxy, amino, trifluoromethyl, hydroxy, mercapto, hydroxy or mercapto etherified by alkyl of 1 to 3 carbon atoms, or hydroxy or mercapto esterified by an acid of 1 to 4 carbon atoms; R.sub.3 is H or alkyl of 1 to 10 carbon atoms; R.sub.4 and R.sub.5 are same or different and are hydrogen; alkanoyl of 2 to 21 carbon atoms; benzoyl, naphthoyl-1 or naphthoyl-2 each optionally substituted by halogen, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, trifluoromethyl, hydroxy or alkanoyloxy of 1 to 3 carbons; and alkanesulfonic acid of 1 to 7 carbon atoms, or a phenylsulfonic acid optionally substituted by alkyl of 1 to 3 carbon atoms; carbamoyl, alkyl carbamoyl of 1 to 3 carbon atoms, phenylcarbamoyl or napththylcarbamoyl; R.sub.6 is H or R.sub.6 -R.sub.7 together if --CH.sub.2 --CH.sub.2 --CH.sub.2 --; R.sub.7 is H, alkyl of 1 to 7 carbon atoms, hydroxymethyl, mercaptomethyl, benzyl; or substituted benzyl wherein the substituents are the same as defined for R.sub.1 ; R.sub.8 and R.sub.9 each is carboxyl, esterified carboxyl of 1 to 7 carbon atoms, amidated carboxyl, or mono- or dialkyl amidated carboxyl wherein the alkyl group has 1 to 3 carbon atoms; provided that when R.sub.3 is lower alkyl, the stereochemistry at asymmetric center I can be either D or L, but that when the aminoglycose has the 2-amino-2-deoxy-D-glucose configuration, the stereochemistry at I cannot be D; when R.sub.7 is not H, the stereochemistry at a symmetric center II is either L or D; and the stereochemistry at asymmetric center III is D; or pharmaceutically acceptable acid addition salts thereof; and an anti-viral, anti-AIDS drug selected from the group consisting of azidothymidine, ansamycin, ribavirin, deoxyytidine, HPA-23, AL-721, and foscarnet; in a physiologically acceptable medium in an amount effective to impart resistance against opportunistic bacterial, fungal or viral infection. 2. The composition according to claim 1 wherein the R.sub.1 to R.sub.2 alkyl group is optionally substituted by hydroxy, mercapto, or hydroxy or mercapto each substituted by an alkyl group of 1 to 3 carbon atoms, and wherein the R.sub.1 and R.sub.2 phenyl group and the R.sub.1 benzyl group are optionally substituted by an alkyl group of 1 to 3 carbon atoms, hydroxy, mercapto, amino, trifluoromethyl, alkyldioxy of 1 to 4 carbon atoms, cycloalkyldioxy of 5 to 7 carbon atoms, hydroxy or mercapto etherified by an alkyl group of 1 to 3 carbon atoms, or hydroxy or mercapto esterified by an acid of 1 to 4 carbon atoms. 3. The composition of claim 1 wherein R.sub.1 is H, alkyl of 1 to 3 carbon atoms, benzyl, phenyl or phenyl p-substituted by alkyl (1 to 3 carbon atoms), amino, halogen, hydroxy or trifluoromethyl; R.sub.2 is alkyl of 1 to 3 carbon atoms, or phenyl, or phenyl p-substituted by alkyl (1 to 3 carbon atoms), amino, halogen, hydroxy or trifluoromethyl; R.sub.3 is H or lower alkyl 1 to 3 carbon atoms; R.sub.4 and R.sub.5 are H, alkanoyl of 2 to 21 carbon atoms, benzoyl or naphthoyl; R.sub.7 is H, alkyl of 1 to 4 carbon atoms, hydroxymethyl, mercaptomethyl, benzyl or R.sub.6 and R.sub.7 together are --CH.sub.2 CH.sub.2 CH.sub.2 --, and R.sub.8 and R.sub.9 are carboxyl, carboxyl esterified by an alcohol of 1 to 4 carbon atoms, carboxamide or monoalkyl or dialkyl substituted carboxamide wherein the alkyl group has from 1 to 3 carbon atoms. 4. A method for enhancing host resistance against opprotunistic bacterial, fungal or viral infection in a human host immunocompromised by an AIDS related virus comprising the step of administering to said host a composition comprising a compound according to claim 1.

Details for Patent 4,866,035

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Hoffmann-la Roche Inc.	PEGASYS COPEGUS COMBINATION PACK	peginterferon alfa-2a and ribavirin		125083	June 04, 2004		2039-03-29
Schering Corporation A Subsidiary Of Merck & Co., Inc.	PEGINTRON/ REBETOL COMBO PACK	peginterferon alfa-2b and ribavirin		125196	June 13, 2008		2039-03-29