Purine derivatives having phosphodiesterase IV inhibition activity

A compound selected from the group consisting of 8-cyclopropyl-3,7-dihydro-3-propyl-6(4-pyridylmethylamino)-2-thio-2H-purin-2-one;

• 6-cyclopentylamino-8-cyclopropyl-3,7-dihydro-3-propyl-2-thio-2H-purin-2-one;
• 8-cyclopropyl-3,7-dihydro-6-(2-hydroxyethylamino)-3-propyl-2-thio-2H-purin-2-one;
• 3-benzyl-3,7-dihydro-6-methylamino-2-thio-2H-purin-2-one;
• 3-butyl-3,7-dihydro-6-ethylamino-2-thio-2H-purin-2-one;
• 6-ethylamino-3,7-dihydro-3-propyl-2-thio-2H-purin-2-one;
• 3-benzyl-6-ethylamino-3,7-dihydro-2-thio-2H-purin-2-one;
• 3-((2-methyl)butyl))-6-(2-(piperazine-1-yl)ethylamino)-3,7-dihydro-2-thio-2H-purin-2-one;
• 3-cyclohexylmethyl-3,7-dihydro-6-ethylamino-2-thio-2H-purin-2-one;
• and their pharmaceutically acceptable salts.

A compound selected from the group consisting of:

• 3,8-diethyl-3,7-dihydro-6-morpholino-2H-2-thio-purin-2-one;
• 3-(cyclopropylmethyl)-3,7-dihydro-8-isopropyl-6-propylamino-2-thio-2H-purin-2-one;
• 3,7-dihydro-6-ethylamino-3-hexyl-2-thio-2H-purin-2-one;
• 3,7-Dihydro-3-hexyl-6-methylamino-2-thio-2H-purin-2-one;
• 8-cyclopropyl-3,7-dihydro-6-ethylamino-3-(3-methylbutyl)-2-thio-2H-purin-2-one;
• 8-cyclopropyl-3,7-dihydro-3-ethyl-6-propylamino-2-thio-2H-purin-2-one;
• 3-butyl-8-cyclopropyl-3,7-dihydro-6-ethylamino-2-thio-2H-purin-2-one;
• 6-ethylamino-3,7-dihydro-3-propyl-2-thio-2H-purin-2-one;
• 8-cyclopropyl-6-ethylamino-3,7-dihydro-3-propyl-2-thio-2H-purin-2-one;
• 8-cyclopropyl-3-cyclopropylmethyl-6-ethylamino-3,7-dihydro-2-thio-2H-purin-2-one;
• 3-benzyl-6-ethylamino-3,7-dihydro-2-thio-2H-purin-2-one;
• 8-cyclopropyl-6-cyclopropylamino-3-propyl-3,7-dihydro-2-thio-2H-purin-2-one hydrochloride;
• 3-((2-methyl)butyl))-6-(2-(piperazine-1-yl)ethylamino)-3,7-dihydro-2-thio-2H-purin-2-one;
• 3-cyclohexylmethyl-3,7-dihydro-6-ethylamino-2-thio-2H-purin-2-one;
• 3-benzyl-6-ethylamino-3,7-dihydro-8-(1-methylethyl)-2-thio-2H-purin-2-one;
• 3-cyclohexylmethyl-8-cyclopropyl-3,7-dihydro-6-ethylamino-2-thio-2H-purin-2-one;
• 6-benzylamino-8-(cyclopropyl)-3,7-dihydro-3-(propyl)-2-thio-2H-purin-2-one hydrochloride;
• 8-(cyclopropyl)-3,7-dihydro-6-hexylamino-3-(propyl)-2-thio-2H-purin-2-one hydrochloride;
• 6-butylamino-8-cyclopropyl-3,7-dihydro-3-propyl-2-thio-2H-purine-2-one;
• 6-cyclopropyl-3,7-dihydro-6-(2-hydroxyethylamino)-2-thio-2H-purine-2-one;
• 6-amino-8-cyclopropyl-3,7-dihydro-3-propyl-2-thio-2H-purine-2-one;
• 6-cyclopentylamino-3-ethyl-3,7-dihydro-8-isopropyl-2-thio-2H-purine-2-one;
• 6-cyclohexylamino-3,7-dihydro-8-isopropyl-3-propyl-2-thio-2H-purine-2-one;
• 6-cyclopentylamino-3,7-dihydro-8-isopropyl-3-propyl-2-thio-2H-purine-2-one;
• 6-cyclopentylamino-3-ethyl-8-cyclopropyl-3,7-dihydro -2-thio-2H-purine-2-one;
• 3-(4-chlorobenzyl)-6-cyclopentylamino-3,7-dihydro -8-isopropyl-2-thio-2H-purine-2-one;
• 6-cyclopentylamino-3-(3-cyclopentyl-4-methoxybenzyl)-3,7-dihydro-8-isopropyl-2-thio-2H-purine-2-one;
• 3-(2-chlorobenzyl)-6-cyclopentylamino-3,7-dihydro-8-isopropyl-2-thio-purine-2-one;
• 8-cyclopropyl-3,7-dihydro-6-(3-pentyl)-3-propyl-2-thio-2H-purin-2-one;
• 6-ethyl-8-isopropyl-3,7-dihydro-3-(4-pyridylmethyl, -2-thio-2H-purin-2-one;
• 3-(cyclopropylmethyl)-3,7-dihydro-8-( 1-methyl-ethyl)-6-propylamino-2-thio-2H-purin-2-one hydrochloride;
• 8-cyclopropyl-3-ethyl-6-ethylamino-3,7-dihydro-2-thio-2H-purin-2-one;
• 8-cyclopropyl-3,7-dihydro-3-propyl-6-(4-pyridylmethylamino)-2-thio-2H-purin-2-one;
• 6-cyclopentylamino-8-cyclopropyl-3,7-dihydro-3-propyl-2-thio-2H-purin-2-one hydrochloride;
• 3-ethyl-6-cyclopentylamino-3,7-dihydro-8-isopropyl-2-thio-2H-purin-2-one;
• 3-ethyl-6-cyclopentylamino-8-cyclopropyl-3,7-dihydro-2-thio-2H-purin-2-one;
• and
• their pharmaceutically acceptable salts.

A compound of the formula (II):

• wherein
• R2 is O or S;
• R6a represents H 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, 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-C3 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;
• R3, represents a C4-8 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, 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-C3 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 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, 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-C3 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;
• R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon atom, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring optionally substituted with alkoxy, CO2H, CONH2, ═NOH, ═NOCONH2, ═O;
• and
• where the heterocyclyl is optionally substitutable as in aryl on the carbons or nitrogens of that ring;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula (II):

• wherein
• R2 is O or S;
• R6a represents H 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, 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-C3 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;
• 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, 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-C3 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 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;
• C6-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, 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-C3 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;
• R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon atom, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring optionally substituted with alkoxy, CO2H, CONH2, ═NOH, ═NOCONH2, ═O;
• and
• where the heterocyclyl is optionally substitutable as in aryl on the carbons or nitrogens of that ring;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula (II):

• wherein
• R2 is O or S;
• R6a represents H 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, 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-C3 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;
• R3 represents a C3-8 cycloalkyl which is unsubstituted or substituted with OH, C1-6 alkoxy, C3-6 cycloalkoxy, halogen, 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-C3 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 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, 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-C3 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;
• R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon atom, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring optionally substituted with alkoxy, CO2H, CONH2, ═NOH, ═NOCONH2, ═O;
• and pharmaceutically acceptable salts thereof.

A compound of the formula (II):

• wherein
• R2 is O or S;
• R6a represents H a C1-8 alkyl which is unbranched or branched and unsubstituted or substituted with 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, 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-C3 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;
• 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, 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-C3 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 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, 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-C3 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;
• R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon atom, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring optionally substituted with alkoxy, CO2H, CONH2, ═NOH, ═NOCONH2, ═O;
• and pharmaceutically acceptable salts thereof.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of the formula (II):

• wherein
• R2 is O or S;
• R3, R6a and R8 are the same or different and each 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, haloalkyl, CO2H, ═NOH, ═NOCONH2, or ═O;
• C4 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-C3 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;
• R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon atom, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring optionally substituted with alkoxy, CO2H, CONH2, ═NOH, ═NOCONH2, ═O;
• and
• pharmaceutically acceptable salts thereof.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound selected from the group consisting of 8-cyclopropyl-3,7-dihydro-3-propyl-6(4-pyridylmethylamino)-2-thio-2H-purin-2-one;

• 6-cyclopentylamino-8-cyclopropyl-3,7-dihydro-3-propyl-2-thio-2H-purin-2-one;
• 8-cyclopropyl-3,7-dihydro-6-(2-hydroxyethylamino)-3-propyl-2-thio-2H-purin-2-one;
• 3-benzyl-3,7-dihydro-6-methylamino-2-thio-2H-purin-2-one;
• 3-butyl-3,7-dihydro-6-ethylamino-2-thio-2H-purin-2-one;
• 6-ethylamino-3,7-dihydro-3-propyl-2-thio-2H-purin-2-one;
• 3-benzyl-6-ethylamino-3,7-dihydro-2-thio-2H-purin-2-one;
• 3-((2-methyl)butyl))-6-(2-(piperazine-1-yl)ethylamino)-3,7-dihydro-2-thio-2H-purin-2-one;
• 3-cyclohexylmethyl-3,7-dihydro-6-ethylamino-2-thio-2H-purin-2-one;
• and their pharmaceutically acceptable salts.

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 (II):

• wherein
• R2 is O or S;
• R3, R6a and R8 are the same or different and each 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, 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-C3 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;
• R6b represents a H or R6a, or together R6b, N, and R6a make a 3 to 8 member ring containing at least one carbon atom, from one to three nitrogen atoms, from zero to two oxygen atoms, from zero to two sulfur atoms, said ring optionally substituted with alkoxy, CO2H, CONH2, ═NOH, ═NOCONH2, ═O;
• and
• pharmaceutically acceptable salts thereof.