# US 5,705,491 A · Adenosine deaminase inhibitor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,705,491 A - Document ID: US5705491A - Status: Granted - Kind: A - Application number: 08/141,597 - Filed: 1993-10-27 - Granted: 1998-01-06 - Earliest claimed: 1992-10-27 - Assignees: Nippon Zoki Pharmaceutical Co., Ltd. - Inventors: Toshio Yamada - Web page: https://patentgrep.com/patent/US5705491A ## CPC - A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) - C07H 19/16: Purine radicals - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) ## Abstract The present invention relates to adenosine deaminase inhibitors containing at least one O-alkylated moiety and the pharmaceutically acceptable salts thereof. The pharmaceutical compositions of the present invention include adenosine deaminase inhibitors containing at least one of the compounds represented by Formula (I): ##STR1## wherein each of R.sub.1, R.sub.2, and R.sub.3 are the same or different and is hydrogen or alkyl; R is hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkynyl, alkoxy, phenyl, hydroxy, amino, alkylamino, phenylamino or halogen; X is hydrogen, alkyl, alkynyl, allyl, methallyl, cycloalkyl, alkyl having one or more hydroxy groups, phenyl, substituted phenyl, alkyl having one or more phenyl groups, alkyl having one or more substituted phenyl groups, bicycloalkyl, naphthylalkyl, acenaphthylenylalkyl or a compound represented by Formula (II) or Formula (III) ##STR2## wherein Z is hydrogen, hydroxy or lower alkoxy; Q is hydrogen or hydroxy; A is --CH.sub.2 --, --O--, --S-- or a mere linkage; Y is (CH.sub.2).sub.n -- or a mere linkage; n is an integer from 1 to 3; and any of R.sub.1, R.sub.2, and R.sub.3 is R.sub.3 lower alkyl. ## Claims ### Claim 1 An adenosine derivative represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR13## wherein each of R.sub.1 a, R.sub.2 a and Xa may be the same or different and is hydrogen or alkyl, at least one of R.sub.1 a and R.sub.2 a being an alkyl; and Ra is an alkyl having more than 6 carbons, alkenyl, alkynyl, hydroxyalkynyl, alkoxy, phenyl, hydroxy, alkylamino or phenylamino. ### Claim 2 An adenosine derivative represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR14## wherein R.sub.1 b and R.sub.2 b are the same and each is methyl or ethyl; Rb and Xb is hydrogen or methyl; and at least one of Rb and Xb is methyl. ### Claim 3 An adenosine derivative represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR15## wherein one of R.sub.1 c and R.sub.2 c is methyl and the other is hydrogen; when Xc is hydrogen, Rc is iodo; and when Xc is methyl, Rc is bromo or iodo. ### Claim 4 An adenosine derivative represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR16## wherein R.sub.1 d is an alkyl having 2 to 8 carbons. ### Claim 5 (depends on 1) An adenosine derivative as claimed in claim 1 wherein R.sub.1 a is alkyl. ### Claim 6 (depends on 3) An adenosine derivative as claimed in claim 3 wherein R.sub.1 c is methyl. ### Claim 7 A pharmaceutical composition comprising: (a) at least one adenosine deaminase inhibitor comprising at least one of the compounds represented by the formula (I) or a pharmaceutically effective salt thereof: ##STR17## wherein each of R.sub.1, R.sub.2 and R.sub.3 may be the same or different and R.sub.1, R.sub.2 and R.sub.3 is hydrogen or alkyl, at least one of R.sub.1, R.sub.2 and R.sub.3 being an alkyl; R is hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkynyl, alkoxy, phenyl, hydroxy, amino, alkylamino, phenylamino or halogen; and X is hydrogen, alkyl, alkynyl, allyl, methallyl, cycloalkyl, an alkyl having one or more hydroxy groups, phenyl, substituted phenyl, alkyl having one or more phenyl groups, alkyl having one or more substituted phenyl groups, bicycloalkyl, naphthalkyl, acenaphthylenylalkyl or a group represented by Formula (II) or Formula (III): ##STR18## wherein Z is hydrogen, hydroxy or lower alkoxy; Q is hydrogen or hydroxy; A is --CH.sub.2 --, --O--, --S-- or a single bond forming a five-membered ring; Y is --(CH.sub.2).sub.n -- or a single bond; n is an integer from 1 to 3; and (b) adenosine or at least one therapeutically useful adenosine analogous drug which is different from (a) and which is metabolized or deaminated by adenosine deaminase; as active ingredients wherein said adenosinedeaminase inhibitor inhibits loss of activity of said adenosine or said adenosine analogous drug. ### Claim 8 (depends on 7) The composition of claim 7 wherein said adenosine analogous drug is an anticancer drug, or an antiviral drug, or a combination of an anticancer drug with an antiviral drug. ### Claim 9 (depends on 8) The composition of claim 8 wherein said anticancer drug is 3'-deoxyadenosine or xylosyladenine and said antiviral drug is arabinosyladenine. ### Claim 10 (depends on 7) The composition of claim 7 wherein R.sub.3 is hydrogen. ### Claim 11 (depends on 10) The composition of claim 10 wherein X is hydrogen. ### Claim 12 (depends on 10) The composition of claim 10 wherein X is an alkyl having 1 to 3 carbon atoms. ### Claim 13 (depends on 7) The composition of claim 7 wherein R.sub.1 is an alkyl.