Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same

A method for treating a serotonin-related disease or disorder comprising administering to a patient in need thereof an effective amount of a compound or a pharmaceutically acceptable salt thereof, wherein the serotonin-related disease or disorder is Crohn's disease, ulcerative colitis, inflammatory bowel disease, or systemic sclerosis, and wherein the compound has the Formula (I):

• wherein:
• R1 and R2 are each an optionally substituted group independently selected from the group consisting of a hydrogen (—H), one of a (C1-C10)-alkyl group, a (C2-C10)-alkenyl group, a (C2-C10)-alkynyl group, a (C6-C14)-aryl group, a (C6-C14)-heteroaryl group, a (C7-C15)-alkyl-arylene group, a (C7-C15)-alkyl-heteroarylene group, a (C8-C15)-alkenyl-arylene group, a (C8-C15)-alkenyl-heteroarylene group, a (C8-C15)-alkynyl-arylene group, a (C8-C15)-alkynyl-heteroarylene group, a (C7-C15)-aryl-alkylene group, a (C7-C15)-heteroaryl-alkylene group, a (C8-C15)-aryl-alkenylene group, a (C8-C15)-heteroaryl-alkenylene group, a (C8-C15)-aryl-alkynylene group, and a (C8-C15)-heteroaryl-alkynylene group, wherein alkyl, alkenyl, alkynyl, alkylene, alkenylene, and alkynylene, when present in the aforementioned groups, may comprise one or more bivalent groups substituting a carbon moiety —C— and the one or more bivalent groups is selected from the group consisting of —O—, —S—, —S(O)—, —SO2—, —N═, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R)—, —N(R)C(O)—, —OC(O)N(R)—, —N(R)C(O)O—, —N(R)C(O)N(R)—, (C3-C12)-heterocyclic alkylene, and (C3-C12)-heterocyclic alkenylene;
• R3 is a group independently selected from the group consisting of hydrogen (—H), fluoro (—F), bromo (—Br), chloro (—Cl), a hydroxyl group (—OH), an acyl group (—C(O)R), a carboxyl group (—C(O)OH), a carboxy ester group (—CO2R), an alkoxy group (—OR), an aldehyde group (—C(O)H), a trihalide methyl ester group (—OCX3), a primary amine group (—NH2), a secondary amine group (—N(R)H), a tertiary amine group (—NR(R′)), an amide group (—N(R)—C(O)—R), an imide group (—C(O)—N(R)—C(O)—R′), a carbamate group (—N(R)—C(O)—OR′), a carboxamide group (—C(O)N(R)R′), a carbimide group (—N(R)—C(O)—N(R′)R″), a primary ketimine group —C(R)═NH, a secondary ketimine group (—C(R)═NR′), a nitrile group (—CN), an isonitrile group (—NC), a nitroxy group (—ONO), a nitro group (—NO2), a nitrate group (—ONO2), a nitroso group (—NO), a cyanate group (—OCN), an isocyanate group (—NCO), a sulfhydryl group (—SH), a sulfide group (—SR), a sulfurtrihalide group (—SX3), a sulfurpentahalide group (—SX5), a sulfinyl group (—S(O)R), a sulfonyl group (—SO2R), a sulfino group (—SO2H), and a sulfo group (—SO3H), or an optionally substituted and/or optionally linked group selected from the group consisting of a (C1-C10)-alkyl group, a (C2-C10)-alkenyl group, a (C2-C10)-alkynyl group, a (C6-C14)-aryl group, a (C6-C14)-heteroaryl group, a (C7-C15)-alkyl-arylene group, a (C7-C15)-alkyl-heteroarylene group, a (C8-C15)-alkenyl-arylene group, a (C8-C15)-alkenyl-heteroarylene group, a (C8-C15)-alkynyl-arylene group, a (C8-C15)-alkynyl-heteroarylene group, a (C7-C15)-aryl-alkylene group, a (C7-C15)-heteroaryl-alkylene group, a (C8-C15)-aryl-alkenylene group, a (C8-C15)-heteroaryl-alkenylene group, a (C8-C15)-aryl-alkynylene group, and a (C8-C15)-heteroaryl-alkynylene group, wherein alkyl, alkenyl, alkynyl, alkylene, alkenylene, or alkynylene, when present in the aforementioned groups of R3, may comprise one or more bivalent groups substituting a carbon moiety —C— and the one or more bivalent groups is selected from the group consisting of —O—, —S—, —S(O)—, —SO2—, —N═, —N(R)—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R)—, —N(R)C(O)—, —OC(O)N(R)—, —N(R)C(O)O—, —N(R)C(O)N(R)—, (C3-C12)-heterocyclic alkylene, and (C3-C12)-heterocyclic alkenylene, and wherein X is a halide;
• Q is selected from the group consisting of hydrogenated carbon, non-hydrogenated carbon, hydrogenated nitrogen, and non-hydrogenated nitrogen, oxygen, sulfur, —*CH2—CH(R′″)—, —*CH═C(R′″)—, —*CH2—O—, and —*CH2—N(R′″)—, wherein:
• R′″ represents hydrogen, a methyl group, an ethyl group, a cyclopropyl group,
• a —CH2-cyclopropyl group, or a halogen;
• and
• the carbon marked with an asterisk is covalently linked to the imidazole group set forth in Formula (I);
• Z is selected from the group consisting of hydrogenated carbon, and non-hydrogenated carbon, hydrogenated nitrogen, non-hydrogenated nitrogen, oxygen and sulfur;
• the ring member A is a saturated, unsaturated, or aromatic ring;
• the substituents for the optionally substituted groups are selected from the group consisting of a fluoro (—F), a bromo (—Br), a chloro (—CI), a hydroxyl group (—OH), a (C1-C3)-alkyl group, a (C2-C3)-alkenyl group, an acyl group (—C(O)R), a carboxyl group (—C(O)OH), a carboxylate group (—C(O)O−), a carboxy ester group (—CO2R), an alkoxy group (—OR), an aldehyde group (—C(O)H), a trihalide methyl ester group (—OCX3), a primary amine group (—NH2), a secondary amine group (—N(R)H), a tertiary amine group (—NR(R′)), an amide group (—N(R)—C(O)—R), an imide group (—C(O)—N(R)—C(O)—R′), a carbamate group (—N(R)—C(O)—OR′), a carboxamide group (—C(O)N(R)(R′)), a carbimide group (—N(R)—C(O)—N(R′)R″), a primary ketimine group(—C(R)═NH), a secondary ketimine group (—C(R)═NR′), a nitrile group (—CN), an isonitrile group (—NC), a nitroxy group (—ONO), a nitro group (—NO2), a nitrate group (—ONO2), a nitroso group (—NO), a cyanate group (—OCN), an isocyanate group (—NCO), a sulfhydryl group (—SH), a sulfide group (—SR), a sulfurtrihalide group (—SX3), a sulfurpentahalide group (—SX5), a sulfinyl group (—S(O)R), a sulfonyl group (—SO2R), a sulfino group (—SO2H), a sulfo group (—SO3H), and combinations thereof, and wherein X is a halide;
• R is independently hydrogen, a (C1-C3)-alkyl group, or a (C2-C3)-alkenyl group;
• R′ is independently hydrogen, a (C1-C3)-alkyl group, or a (C2-C3)-alkenyl group;
• and
• R″ is independently hydrogen, a (C1-C3)-alkyl group, or a (C2-C3)-alkenyl group.