# US 6,294,541 B1 · Purine derivatives having phosphodiesterase IV inhibition activity > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,294,541 B1 - Document ID: US6294541B1 - Status: Granted - Kind: B1 - Application number: 09/418,330 - Filed: 1999-10-14 - Granted: 2001-09-25 - Earliest claimed: 1996-06-06 - Assignees: Euro-Celtique S.A. - Inventors: David J. Cavalla; Mark Chasin; Peter Hofer; Andre Gehrig; Peter Wintergerst - Web page: https://patentgrep.com/patent/US6294541B1 ## CPC - C07D 473/24: one nitrogen and one sulfur atom - A61P 11/06: Antiasthmatics - A61P 25/24: Antidepressants - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - C07D 473/18: one oxygen and one nitrogen atom, e.g. guanine - C07D 473/20: two sulfur atoms - C07D 473/30: attached in position 6, e.g. hypoxanthine - C07D 473/34: attached in position 6, e.g. adenine - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A compound of the formula: wherein R3 represent a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, alkoxy, HC═NOH, HC═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4); heterocyclyl; heterocyclylalkyl (C1-C4); and heteroaryl; R8 represents H or a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, alkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, alkoxy, HC═NOH, HC═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4); heterocyclyl; heterocyclylalkyl (C1-C4); and heteroaryl. ## Claims ### Claim 1 A compound of the formula (III): wherein R3 represents a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, C1-10 haloalkyl, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2,or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, C1-6 alkoxy, C3-6 cycloalkoxy, CH═NOH, CH═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4), optionally substituted with halogen, C1-C4 alkyl, nitro, trifluoromethyl, C1-C6 alkoxy or C3-C6 cycloalkoxy; a five to seven membered heterocyclyl ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; and heterocyclylalkyl (C1-C4) wherein said heterocyclyl moiety is a five to seven membered ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; R8 represents H or a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, C1-10 haloalkyl, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2,or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, C1-6 alkoxy, C3-6 cycloalkoxy, CH═NOH, CH═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4), optionally substituted with halogen, C1-C4 alkyl, nitro, trifluoromethyl, C1-C6 alkoxy or C3-C6 cycloalkoxy; a five to seven membered heterocyclyl ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; and heterocyclylalkyl (C1-C4) wherein said heterocyclyl moiety is a five to seven membered ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; provided that when R8 is H, R3 is not methyl; and pharmaceutically acceptable salts thereof. ### Claim 2 (depends on 1) The compound of claim 1, wherein R3 represnets a C1-8 alkyl, C3-7 cycloalkyl, C4-8 cycloalkylalkyl, aryl or ar(C1-4)alkyl group; and R8 represnets a hydrogen atom or a C1-8 alkyl, C3-7 cycloalkyl, C4-8 cycloalkylalkyl, aryl, arC1-4)alkyl, pyridyl or pyridylC1-4)alkyl group. ### Claim 3 (depends on 1) The compound of claim 1, wherein R3 represents a C2-8 alkyl group, an arC1-4) alkyl group, or a C3-7 cycloalkyl group. ### Claim 4 (depends on 1) The compound of claim 1, wherein R8 represents a hydrogen atom. ### Claim 5 (depends on 1) The compound of claim 1, wherein R8 represents a C3-7 cycloalkyl group. ### Claim 6 (depends on 1) The compound of claim 1, wherein R8 represents a cyclopropyl group. ### Claim 7 (depends on 1) The compound of claim 1, wherein R8 represents a C1-8 alkyl group. ### Claim 8 (depends on 1) The compound of claim 1, wherein R8 represents an isopropyl group. ### Claim 9 (depends on 1) The compound of claim 1, wherein R3 represents a C2-4 alkyl group. ### Claim 10 (depends on 1) The compound of claim 1, wherein R3 represents propyl. ### Claim 11 (depends on 1) The compound of claim 1, wherein R3 represents unsubstituted or substituted benzyl. ### Claim 12 (depends on 1) The compound of claim 1, wherein R3 represents cyclopropylmethyl. ### Claim 13 (depends on 1) A compound according to claim 1, selected from the group consisting of 3-benzyl-3,7-dihydro-8-(1-methylethyl)-2,6-dithio-1H-purin-2,6-dione; 3-cyclohexlmethyl-8-cyclopropyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-(4-chlorobenzyl)-8-isopropyl-3,7-dihydro-2,6-dithio-3,7-purin-2,6-dione; 8-cyclopropyl-3-cyclopropylmethyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3,8-diethyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3-ethyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3-propyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-8-ethyl-3-propyl-2,6-dithio-1H-purin-2,6-dione; 3-butyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-butyl-3,7-dihydro-8-ethyl-2,6-dithio-1H-purine-2,6-dione; 3-benzyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-3-hexyl-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-(3-methylbutyl)-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-ethyl-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-3-(2-methylbutyl)-2,6-dithio-1H-purine-2,6-dione; 3-butyl-8-cyclopropyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-propyl-2,6-dithio-1H-purine-2,6-dione 8-cyclopropyl-3-cyclopropylmethyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione 3-butyl-3,7-dihydro-8-(1-methylethyl)-2,6-dithio-1H-purine-2,6-dione 3-cyclohexylmethyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3-ethyl-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-8-isopropyl-3-propyl-2,6-dithio-1H-purine-2,6-dione; 3-(2-chlorobenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purine-2,6-dione; 8-isopropyl-3-(4-pyridylmethyl)-2,6-dithio-1H-purine-2,6-dione; and their pharmaceutically acceptable salts. ### Claim 14 (depends on 1) A compound according to claim 1, selected from the group consisting of 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purin-2,6-dione and pharmaceutically acceptable salts thereof. ### Claim 15 (depends on 1) The compound of claim 1 wherein R3 represents a C2-8 alkyl which is which is unbranched or branched and unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, C1-10 haloalkyl, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2,or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, C1-6 alkoxy, C3-6 cycloalkoxy, CH═NOH, CH═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4), optionally substituted with halogen, C1-C4 alkyl, nitro, trifluoromethyl, C1-C6 alkoxy or C3-C6 cycloalkoxy; a five to seven membered heterocyclyl ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; and heterocyclylalkyl (C1-C4) wherein said heterocyclyl moiety is a five to seven membered ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms. ### Claim 16 A pharmaceutical composition comprising a pharmaceutically acceptable arrier and a compound of the formula (III): wherein R3 represents a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, C1-10 haloalkyl, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2,or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, C1-6 alkoxy, C3-6 cycloalkoxy, CH═NOH, CH═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4), optionally substituted with halogen, C1-C4 alkyl, nitro, trifluoromethyl, C1-C6 alkoxy or C3-C6 cycloalkoxy; a five to seven membered heterocyclyl ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; and heterocyclylalkyl (C1-C4) wherein said heterocyclyl moiety is a five to seven membered ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; R8 represents H or a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, C1-10 haloalkyl, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2,or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, C1-6 alkoxy, C3-6 cycloalkoxy, CH═NOH, CH═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4), optionally substituted with halogen, C1-C4 alkyl, nitro, trifluoromethyl, C1-C6 alkoxy or C3-C6 cycloalkoxy; a five to seven membered heterocyclyl ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; and heterocyclylalkyl (C1-C4) wherein said heterocyclyl moiety is a five to seven membered ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms. ### Claim 17 (depends on 16) The pharmaceutical composition of claim 16, wherein R3 represents a C1-8 alkyl, C3-7 cycloalkyl, C4-8 cycloalkylalkyl, aryl or ar(C1-4)alkyl group; and R8 represents a hydrogen atom or a C1-8 alkyl, C3-7 cycloalkyl, C4-8 cycloalkylalkyl, aryl, ar(C1-4)alkyl, pyridyl or pyridylC1-4)alkyl group. ### Claim 18 (depends on 16) The pharmaceutical composition of claim 16, wherein R3 represents a C2-8 alkyl group, an ar(C1-4) alkyl group, or a C3-7 cycloalkyl group. ### Claim 19 (depends on 16) The pharmaceutical composition of claim 16, wherein R8 represents a hydrogen atom. ### Claim 20 (depends on 16) The pharmaceutical composition of claim 16, wherein R8 represents a C3-7 cycloalkyl group. ### Claim 21 (depends on 16) The pharmaceutical composition of claim 16, wherein R8 represents a cyclopropyl group. ### Claim 22 (depends on 16) The pharmaceutical composition of claim 16, wherein R8 represents a C1-8 alkyl group. ### Claim 23 (depends on 16) The pharmaceutical composition of claim 16, wherein R8 represents an isopropyl group. ### Claim 24 (depends on 16) The pharmaceutical composition of claim 16, wherein R3 represents a C2-4 alkyl group. ### Claim 25 (depends on 16) The pharmaceutical composition of claim 16, wherein R3 represents a propyl. ### Claim 26 (depends on 16) The pharmaceutical composition of claim 16, wherein R3 represents unsubstituted or substituted benzyl. ### Claim 27 (depends on 16) The pharmaceutical composition of claim 16, wherein R3 represents cyclopropylmethyl. ### Claim 28 (depends on 16) The pharmaceutical composition of claim 16, selected from 3-benzyl-3,7-dihydro-8-(1-methylethyl)-2,6-dithio-1H-purin-2,6-dione; 3-cyclohexlmethyl-8-cyclopropyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-(4-chlorobenzyl)-8-isopropyl-3,7-dihydro-2,6-dithio-3,7-purin-2,6-dione; 8-cyclopropyl-3-cyclopropylmethyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3,8-diethyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3-ethyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3-propyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-8-ethyl-3-propyl-2,6-dithio-1H-purin-2,6-dione; 3-butyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-butyl-3,7-dihydro-8-ethyl-2,6-dithio-1H-purine-2,6-dione; 3-benzyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-3-hexyl-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-(3-methylbutyl)-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-ethyl-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-3-(2-methylbutyl)-2,6-dithio-1H-purine-2,6-dione; 3-butyl-8-cyclopropyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-propyl-2,6-dithio-1H-purine-2,6-dione 8-cyclopropyl-3-cyclopropylmethyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione 3-butyl-3,7-dihydro-8-(1-methylethyl)-2,6-dithio-1H-purine-2,6-dione 3-cyclohexylmethyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3-ethyl-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-8-isopropyl-3-propyl-2,6-dithio-1H-purine-2,6-dione; 3-(2-chlorobenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purine-2,6-dione; 8-isopropyl-3-(4-pyridylmethyl)-2,6-dithio-1H-purine-2,6-dione; and their pharmaceutically acceptable salts. ### Claim 29 (depends on 16) A pharmaceutical composition according to claim 16, wherein said compound is selected from the group consisting of 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purin-2,6-dione and pharmaceutically acceptable salts thereof. ### Claim 30 A method of treating a mammal suffering from a disease state selected from the group consisting of asthma, allergies, inflammation, depression, atopic diseases and rhinitis, comprising administering to the mammal an effective amount of a compound of the formula (III): wherein R3 and R8 are the same or different and each represent H or a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2, or ═O; C3-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, C1-10 haloalkyl, CO2H, ═NOH, ═NOCONH2, or ═O; C4-8 cycloalkylalkyl wherein the cycloalkyl portion is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, CO2H, ═NOH, ═NOCONH2,or ═O; aryl which is unsubstituted or substituted with Cl, NH2, alkylamino, dialkylamino, amido, C1-C8 alkylamido, C1-C3 dialkylamido, OH, C1-6 alkoxy, C3-6 cycloalkoxy, CH═NOH, CH═NOCONH2, C1-C3 alkyl, phenyl or benzyl; aralkyl (C1-4), optionally substituted with halogen, C1-C4 alkyl, nitro, trifluoromethyl, C1-C6 alkoxy or C3-C6 cycloalkoxy; a five to seven membered heterocyclyl ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; and heterocyclylalkyl (C1-C4) wherein said heterocyclyl moiety is a five to seven membered ring having at least one carbon atom and up to three nitrogen atoms, up to two oxygen atoms, and up to two sulfur atoms; and pharmaceutically acceptable salts thereof. ### Claim 31 (depends on 30) The method of claim 30, wherein R3 represents a C1-8 alkyl, C3-7 cycloalkyl, C4-8 cycloalkylalkyl, aryl or ar(C1-4)alkyl group; and R8 represents a hydrogen atom or a C1-8 alkyl, C3-7 cycloalkyl, C4-8 cycloalkylalkyl, aryl, ar(C1-4)alkyl, pyridyl or pyridylC1-4)alkyl group. ### Claim 32 (depends on 30) The method of claim 30, wherein R3 represents a C2-8 alkyl group, an ar(C1-4) alkyl group, or a C3-7 cycloalkyl group. ### Claim 33 (depends on 30) The method of claim 30, wherein R8 represents a hydrogen atom. ### Claim 34 (depends on 30) The method of claim 30, wherein R8 represents a C3-7 cycloalkyl group. ### Claim 35 (depends on 30) The method of claim 30, wherein R8 represents a cyclopropyl group. ### Claim 36 (depends on 30) The method of claim 30, wherein R8 represents a C1-8 alkyl group. ### Claim 37 (depends on 30) The method of claim 30, wherein R8 represents an isopropyl group. ### Claim 38 (depends on 30) The method of claim 30, wherein R3 represents a C2-4 alkyl group. ### Claim 39 (depends on 30) The method of claim 30, wherein R3 represents propyl. ### Claim 40 (depends on 30) The method of claim 30, wherein R3 represents unsubstituted or substituted benzyl. ### Claim 41 (depends on 30) The method of claim 30, wherein R3 represents cyclopropylmethyl. ### Claim 42 (depends on 16) The pharmaceutical composition of claim 16, selected from 3-benzyl-3,7-dihydro-8-(1-methylethyl)-2,6-dithio-1H-purin-2,6-dione; 3-cyclohexlmethyl-8-cyclopropyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-(4-chlorobenzyl)-8-isopropyl-3,7-dihydro-2,6-dithio-3,7-purin-2,6-dione; 8-cyclopropyl-3-cyclopropylmethyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3,8-diethyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3-ethyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-3-propyl-2,6-dithio-1H-purin-2,6-dione; 3,7-dihydro-8-ethyl-3-propyl-2,6-dithio-1H-purin-2,6-dione; 3-butyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione; 3-butyl-3,7-dihydro-8-ethyl-2,6-dithio-1H-purine-2,6-dione; 3-benzyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-3-hexyl-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-(3-methylbutyl)-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-ethyl-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-3-(2-methylbutyl)-2,6-dithio-1H-purine-2,6-dione; 3-butyl-8-cyclopropyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 8-cyclopropyl-3,7-dihydro-3-propyl-2,6-dithio-1H-purine-2,6-dione 8-cyclopropyl-3-cyclopropylmethyl-3,7-dihydro-2,6-dithio-1H-purin-2,6-dione 3-butyl-3,7-dihydro-8-(1-methylethyl)-2,6-dithio-1H-purine-2,6-dione 3-cyclohexylmethyl-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-2,6-dithio-1H-purine-2,6-dione; 3-ethyl-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purine-2,6-dione; 3,7-dihydro-8-isopropyl-3-propyl-2,6-dithio-1H-purine-2,6-dione; 3-(2-chlorobenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H-purine-2,6-dione; 8-isopropyl-3-(4-pyridylmethyl)-2,6-dithio-1H-purine-2,6-dione; and their pharmaceutically acceptable salts. ### Claim 43 (depends on 30) The method of claim 30, wherein said composition is selected from the group consisting of 3-(3-cyclopentyloxy-4-methoxybenzyl)-3,7-dihydro-8-isopropyl-2,6-dithio-1H- purin-2,6-dione and ppharmaceutically acceptable salts thereof.