6-1h-imidazo-quinazoline and quinolines derivatives, new potent analgesics and anti-inflammatory agents

A method for the pharmacological treatment of pain and inflammatory related disorders, comprising administering, to a subject in need thereof, an effective amount of a compound of Formula (I):

• wherein:
• X is a nitrogen atom;
• W is independently selected from an aryl group or an heteroaryl group of Formula II:
• when W is an aryl group, it is an unsubstituted phenyl of or phenyl substituted with one or more substituents independently selected from halogen (—F, —Cl, —Br), trifluoromethyl (—CF3), alkyl, hydroxyl (—OH), alkoxy, trifluoromethoxy (—OCF3), cyano (—CN), carboxamido (—CONHR3 or —NHCOR3 or —CONR2R3), carbonyl (—CO—R3), alkylthio (—SR3), sulfonyl (—SOR3) and sulfonyl (—SO2R3), wherein R2 and R3 groups are as defined below;
• when W is an heteroaryl group of Formula II, it is a benzocondensed -5 or -6 membered heterocycle, wherein:
• Z and Y are independently selected from:
• an oxygen atom (—O—), a sulphur atom (—S—), or the groups:
• —SO2—, —CHR3—, —CR3═, —NH—, —N═;
• Q is independently selected from the groups:
• —CHR3—, —CH═, —CR3═, —CHR3—CH2—;
• provided that the combination of Y, Z, Q groups give rise to:
• 1,3-benzodioxole, 1,3-benzodithiol, benzofuran, 2,3-dihydrobenzofuran, benzothiophene, 2,3-dihydrobenzothiophene, 2,3-dihydrobenzothiophene S,S-dioxide, indole, 2,3-dihydroindole, benzimidazole, benzoxazole, benzothiazole, 2H-3,4-dihydrobenzopyran, 2H-3,4-dihydrobenzothiopyran, 2H-3,4-dihydrobenzothiopyran S,S-dioxide, 2,3-dihydro-[1,4]-benzodioxine (1,4-benzodioxan), 2,3-dihydro-[1,4]-benzothiazine, 2,3-dihydro-[1,4]-benzothiazine S,S-dioxide, [2,3-dihydro-[1,4]-benzoxazine;
• R1 is independently selected from hydrogen (—H) or C1-C4 alkyl or hydroxymethyl (—CH2OH), aminomethyl (—CH2NH2), dimethylaminomethyl (—CH2NMe2), trifluoromethyl (—CF3);
• the C1-C4 alkyl group is a linear or branched hydrocarbon chain;
• provided that in compounds of Formula (I) not more than two R1 groups are simultaneously C1-C4 alkyl or trifluoromethyl (—CF3) and only one R1 group is hydroxymethyl (—CH2OH), aminomethyl (—CH2NH2) or dimethylaminomethyl (—CH2NMe2);
• R2 is independently selected from C1-C6 alkyl or aryl;
• C1-C6 alkyl is a linear or branched, saturated or unsaturated C1-C6 hydrocarbon chain, optionally substituted with an aryl, aryl being as defined above;
• R3 is independently selected from hydrogen, C1-C6 alkyl and aryl;
• C1-C6 alkyl is a linear or branched, saturated or unsaturated C1-C6 hydrocarbon chain optionally substituted with an aryl, aryl being as defined above,
• or a pharmaceutically acceptable salt thereof.

A method for the pharmacological treatment of acute and chronic pain selected from the group consisting of inflammatory pain and associated hyperalgesia and allodynia, osteoarthritis and rheumatoid arthritis pain, postoperative pain, visceral pain, pain associated with cancer, trigeminal neuralgia, acute herpetic and post herpetic neuralgia, neuropathic pain, and diabetic neuropathy, comprising administering, to a subject in need thereof, an effective amount of a compound of Formula (I):

• wherein:
• X is a nitrogen atom;
• W is independently selected from an aryl group or an heteroaryl group of Formula II:
• when W is an aryl group, it is an unsubstituted phenyl of or phenyl substituted with one or more substituents independently selected from halogen (—F, —Cl, —Br), trifluoromethyl (—CF3), alkyl, hydroxyl (—OH), alkoxy, trifluoromethoxy (—OCF3), cyano (—CN), carboxamido (—CONHR3 or —NHCOR3 or —CONR2R3), carbonyl (—CO—R3), alkylthio (—SR3), sulfinyl (—SOR3) and sulfonyl (—SO2R3), wherein R2 and R3 groups are as defined below;
• when W is an heteroaryl group of Formula II, it is a benzocondensed -5 or -6 membered heterocycle, wherein:
• Z and Y are independently selected from:
• an oxygen atom (—O—), a sulphur atom (—S—), or the groups:
• —SO2—, —CHR3—, —CR3═, —NH—, —N═;
• Q is independently selected from the groups:
• —CHR3—, —CH═, —CR3═, —CHR3—CH2—;
• provided that the combination of Y, Z, Q groups give rise to:
• 1,3-benzodioxole, 1,3-benzodithiol, benzofuran, 2,3-dihydrobenzofuran, benzothiophene, 2,3-dihydrobenzothiophene, 2,3-dihydrobenzothiophene S,S-dioxide, indole, 2,3-dihydroindole, benzimidazole, benzoxazole, benzothiazole, 2H-3,4-dihydrobenzopyran, 2H-3,4-dihydrobenzothiopyran, 2H-3,4-dihydrobenzothiopyran S,S-dioxide, 2,3-dihydro-[1,4]-benzodioxine (1,4-benzodioxan), 2,3-dihydro-[1,4]-benzothiazine, 2,3-dihydro-[1,4]-benzothiazine S,S-dioxide, [2,3-dihydro-[1,4]-benzoxazine;
• R1 is independently selected from hydrogen (—H) or C1-C4 alkyl or hydroxymethyl (—CH2OH), aminomethyl (—CH2NH2), dimethylaminomethyl (—CH2NMe2), trifluoromethyl (—CF3);
• the C1-C4 alkyl group is a linear or branched hydrocarbon chain;
• provided that in compounds of Formula (I) not more than two R1 groups are simultaneously C1-C4 alkyl or trifluoromethyl (—CF3) and only one R1 group is hydroxymethyl (—CH2OH), aminomethyl (—CH2NH2) or dimethylaminomethyl (—CH2NMe2);
• R2 is independently selected from C1-C6 alkyl or aryl;
• C1-C6 alkyl is a linear or branched, saturated or unsaturated C1-C6 hydrocarbon chain, optionally substituted with an aryl, aryl being as defined above;
• R3 is independently selected from hydrogen, C1-C6 alkyl and aryl;
• C1-C6 alkyl is a linear or branched, saturated or unsaturated C1-C6 hydrocarbon chain optionally substituted with an aryl, aryl being as defined above,
• or a pharmaceutically acceptable salt thereof.