Biarylurea derivatives

A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

• wherein Ar is a nitrogen-containing heteroaromatic ring group selected from the group consisting of a pyridyl group, a pyrimidinyl group, a pyrazinyl group, a pyridazinyl group, a thiazolyl group, an isothiazolyl group, an oxazolyl group, an isoxazolyl group, a pyrazolyl group, a pyrrolyl group, an imidazolyl group, an indolyl group, an isoindolyl group, a quinolyl group, an isoquinolyl group, a benzothiazolyl group, and a benzoxazolyl group,
• wherein:
• (1) Ar is optionally substituted with one to three of the same or different substituent(s) selected from (1-1) and (1-2):
• (1-1) a substituent selected from the group consisting of a lower alkyl group, a hydroxyl group, a cyano group, a halogen atom, a nitro group, a carboxyl group, a carbamoyl group, a formyl group, a lower alkanoyl group, a lower alkanoyloxy group, a hydroxy lower alkyl group, a cyano lower alkyl group, a halo lower alkyl group, a carboxy lower alkyl group, a carbamoyl lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkoxycarbonylamino group, a lower alkoxycarbonylamino lower alkyl group, a lower alkylcarbamoyl group, a di-lower alkylcarbamoyl group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, a di-lower alkylcarbamoyloxy group, an amino group, a lower alkylamino group, a di-lower alkylamino group, a tri-lower alkylammonio group, an amino lower alkyl group, a lower alkylamino lower alkyl group, a di-lower alkylamino lower alkyl group, a tri-lower alkylammonio lower alkyl group, a lower alkanoylamino group, an aroylamino group, a lower alkanoylamidino lower alkyl group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a lower alkylsulfonylamino group, a hydroxyimino group and a lower alkoxyimino group,
• and
• (1-2) a substituent which is a group represented by the formula Y1—W1—Y2—Rp, wherein:
• Rp is:
• (i) a hydrogen atom;
• (ii) a lower alkyl group, a lower alkenyl group or a lower alkynyl group, each of which is optionally substituted with one to three of said substituent(s) defined in (1-1) above;
• or
• (iii) a cyclo lower alkyl group, an aryl group, a heteroaromatic ring group selected from the group consisting of an imidazolyl group, an isoxazolyl group, an isoquinolyl group, an isoindolyl group, an indazolyl group, an indolyl group, an indolizinyl group, an isothiazolyl group, an ethylenedioxyphenyl group, an oxazolyl group, a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazolyl group, a quinoxalinyl group, a quinolyl group, a dihydroisoindolyl group, a dihydroindolyl group, a thionaphthenyl group, a naphthyridinyl group, a phenazinyl group, a benzoimidazolyl group, a benzoxazolyl group, a benzothiazolyl group, a benzotriazolyl group, a benzofuranyl group, a thiazolyl group, a thiadiazolyl group, a thienyl group, a pyrrolyl group, a furyl group, a furazanyl group, a triazolyl group, a benzodioxanyl group and a methylenedioxyphenyl group, or an aliphatic heterocyclic group selected from the group consisting of an isoxazolinyl group, an isoxazolidinyl group, a tetrahydropyridyl group, an imidazolidinyl group, a tetrahydrofuranyl group, a tetrahydropyranyl group, a piperazinyl group, a piperidinyl group, a pyrrolidinyl group, a pyrrolinyl group, a morpholino group, a tetrahydroquinolinyl group and a tetrahydroisoquinolinyl group;
• each of which cyclic groups is optionally substituted with one to three of said substituent(s) as defined in (1-1) above, or furthermore, has optionally a bicyclic or tricyclic fused ring of a partial structure selected from the group consisting of:
• W1 is a single bond, an oxygen atom, a sulfur atom, SO, SO2, NRq, SO2NRq, N(Rq)SO2NRr, N(Rq)SO2, CH(ORq), CONRq, N(Rq)CO, N(Rq)CONRr, N(Rq)COO, N(Rq)CSO, N(Rq)COS, C(Rq)═CRr, C≡C, CO, CS, OC(O), OC(O)NRq, OC(S)NRq, SC(O), SC(O)Nq or C(O)O, wherein:
• Rq and Rr are each independently:
• (iv) a hydrogen atom, or
• (v) a substituent selected from the group consisting of a lower alkyl group, a cyclo lower alkyl group, a hydroxyl group, a cyano group, a halogen atom, a nitro group, a carboxyl group, a carbamoyl group, a formyl group, a lower alkanoyl group, a lower alkanoyloxy group, a hydroxy lower alkyl group, a cyano lower alkyl group, a halo lower alkyl group, a carboxy lower alkyl group, a carbamoyl lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkoxycarbonylamino group, a lower alkoxycarbonylamino lower alkyl group, a lower alkylcarbamoyl group, a di-lower alkylcarbamoyl group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, a di-lower alkylcarbamoyloxy group, an amino group, a lower alkylamino group, a di-lower alkylamino group, a tri-lower alkylammonio group, an amino lower alkyl group, a lower alkylamino lower alkyl group, a di-lower alkylamino lower alkyl group, a tri-lower alkylammonio lower alkyl group, a lower alkanoylamino group, an aroylamino group, a lower alkanoylamidino lower alkyl group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a lower alkylsulfonylamino group, a hydroxyimino group and a lower alkoxyimino group, or
• (vi) a lower alkyl group, an aryl group or an aralkyl group which is optionally substituted with one to three of said substituent(s) as defined in (v);
• Y1 and Y2 are each, the same or different, a single bond or a straight-chain or branched lower alkylene group which optionally has said bicyclic or tricyclic fused ring;
• or,
• (2) Ar is optionally fused to a five- to seven-membered ring selected from the group consisting of:
• which ring is formed by two adjacent carbon atoms of said nitrogen-containing heteroaromatic cyclic group, which carbon atoms are each bonded to a ring-substituent through a carbon atom, an oxygen atom and/or a nitrogen atom of said ring-substituent selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a lower alkanoyloxy group, a hydroxy lower alkyl group, a cyano lower alkyl group, a halo lower alkyl group, a carboxy lower alkyl group, a carbamoyl lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkoxycarbonylamino group, a lower alkoxycarbonylamino lower alkyl group, a lower alkylcarbamoyl group, a di-lower alkylcarbamoyl group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, di-lower alkylcarbamoyloxy group, an amino group, a lower alkylamino group, a di-lower alkylamino group, a tri-lower alkylammonio group, an amino lower alkyl group, a lower alkylamino lower alkyl group, a di-lower alkylamino lower alkyl group, a tri-lower alkylammonio lower alkyl group, a lower alkanoylamino group, an aroylamino group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a lower alkylsulfonylamino group, and a lower alkanoylamidino lower alkyl group;
• or,
• (3) Ar is optionally fused to a five- to seven-membered ring selected from the group consisting of:
• which ring is formed by two adjacent carbon atoms of said nitrogen-containing heteroaromatic cyclic group, which carbon atoms are each bonded to a ring-substituent through a carbon atom, an oxygen atom and/or a nitrogen atom of said ring-substituent represented by the formula Y1—W1—Y2-Rp, wherein Y1, W1, Y2 and Rp have the same meanings as stated above;
• Y is CO, SO or SO2;
• wherein the 1,3-oxazine ring in the compound of Formula (1) is optionally further fused with any one of a cyclo lower alkyl group, an aryl group, a heteroaromatic ring group selected from the group consisting of an imidazolyl group, an isoxazolyl group, an isoquinolyl group, an isoindolyl group, an indazolyl group, an indolyl group, an indolydinyl group, an isothiazolyl group, an ethylenedioxyphenyl group, an oxazolyl group, a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazolyl group, a quinoxalinyl group, a quinolyl group, a dihydroisoindolyl group, a dihydroindolyl group, a thionaphthenyl group, a naphthyridinyl group, a phenazinyl group, a benzoimidazolyl group, a benzoxazolyl group, a benzothiazolyl group, a benzotriazolyl group, a benzofuranyl group, a thiazolyl group, a thiadiazolyl group, a thienyl group, a pyrrolyl group, a furyl group, a furazanyl group, a triazolyl group, a benzodioxanyl group and a methylenedioxyphenyl group, or an aliphatic heterocyclic group(s) selected from the group consisting of an isoxazolinyl group, an isoxazolidinyl group, a tetrahydropyridyl group, an imidazolidinyl group, a tetrahydrofuranyl group, a tetrahydropyranyl group, a piperazinyl group, a piperidinyl group, a pyrrolidinyl group, a pyrrolinyl group, a morpholino group, a tetrahydroquinolinyl group and a tetrahydroisoquinolinyl group,
• and
• wherein the 1,3-oxazine ring in the compound of the Formula (I) is optionally substituted with one to three of the same or different substituent(s) selected from the group consisting of a lower alkyl group, a spiro cyclo lower alkyl group which is optionally substituted, a hydroxyl group, a cyano group, a halogen atom, a nitro group, a carboxyl group, a carbamoyl group, a formyl group, a lower alkanoyl group, a lower alkanoyloxy group, a hydroxy lower alkyl group, a cyano lower alkyl group, a halo lower alkyl group, a carboxy lower alkyl group, a carbamoyl lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkoxycarbonylamino group, a lower alkoxycarbonylamino lower alkyl group, a lower alkylcarbamoyl group, a di-lower alkylcarbamoyl group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, a di-lower alkylcarbamoyloxy group, an amino group, a lower alkylamino group, a di-lower alkylamino group, a tri-lower alkylammonio group, an amino lower alkyl group, a lower alkylamino lower alkyl group, a di-lower alkylamino lower alkyl group, a tri-lower alkylammonio lower alkyl group, a lower alkanoylamino group, an aroylamino group, a lower alkanoylamidino lower alkyl group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a lower alkylsulfonylamino group, a hydroxyimino group and a lower alkoxyimino group;
• or a substituent represented by the formula Y1—W1—Y2-Rp, wherein Rp, W1, Y1 and Y2 have the same meanings as stated above,
• R4 and R5 are each, the same or different, a hydrogen atom, a halogen atom, a hydroxy group, an amino group, or a substituent represented by the formula Y3—W2—Y4—Rs,
• wherein:
• Rs is a hydrogen atom;
• a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a cyclo lower alkyl group, an aryl group;
• a heteroaromatic ring group selected from the group consisting of an imidazolyl group, an isoxazolyl group, an isoquinolyl group, an isoindolyl group, an indazolyl group, an indolyl group, an indolizinyl group, an isothiazolyl group, an ethylenedioxyphenyl group, an oxazolyl group, a pyridyl group, a pyradinyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazolyl group, a quinoxalinyl group, a quinolyl group, a dihydroisoindolyl group, a dihydroindolyl group, a thionaphthenyl group, a naphthyridinyl group, a phenazinyl group, a benzoimidazolyl group, a benzoxazolyl group, a benzothiazolyl group, a benzotriazolyl group, a benzofuranyl group, a thiazolyl group, a thiadiazolyl group, a thienyl group, a pyrrolyl group, a furyl group, a furazanyl group, a triazolyl group, a benzodioxanyl group and a methylenedioxyphenyl group;
• or an aliphatic heterocyclic group selected from the group consisting of an isoxazolinyl group, an isoxazolidinyl group, a tetrahydropyridyl group, an imidazolidinyl group, a tetrahydrofuranyl group, a piperazinyl group, a piperidinyl group, a pyrrolidinyl group, pyrrolinyl group, a morpholino group, a tetrahydroquinolinyl group and a tetrahydroisoquinolinyl group;
• each of which is optionally substituted with one to three of said substituent(s) as defined in (1-1) above;
• W2 is a single bond, an oxygen atom, a sulfur atom, SO, SO2, NRt, SO2NRt, N(Rt)SO2NRu, N(Rt)SO2, CH(ORt), CONRt, N(Rt)CO, N(Rt)CONRu, N(Rt)COO, N(Rt)CSO, N(Rt)COS, C(Rv)=CRt, C≡C, CO, CS, OC(O), OC(O)Nt, OC(S)NRt, SC(O), SC(O)NRt and C(O)O, wherein:
• Rt and Ru are each independently:
• (vii) a hydrogen atom, or
• (viii) a substituent selected from the group consisting of a lower alkyl group, a hydroxy group, a cyano group, a halogen atom, a nitro group, a carboxyl group, a carbamoyl group, a formyl group, a lower alkanoyl group, a lower alkanoyloxy group, a hydroxy lower alkyl group, a cyano lower alkyl group, a halo lower alkyl group, a carboxy lower alkyl group, a carbamoyl lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkoxycarbonylamino group, a lower alkoxycarbonylamino lower alkyl group, a lower alkylcarbamoyl group, a di-lower alkylcarbamoyl group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, a di-lower alkylcarbamoyloxy group, an amino group, a lower alkylamino group, a di-lower alkylamino group, a tri-lower alkylammonio group, an amino lower alkyl group, a lower alkylamino lower alkyl group, a di-lower alkylamino lower alkyl group, a tri-lower alkylammonio lower alkyl group, a lower alkanoylamino group, an aroylamino group, a lower alkanoylamidino lower alkyl group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a lower alkylsulfonylamino group, a hydroxyimino group and a lower alkoxyimino group;
• or
• (ix) a lower alkyl group, an aryl group or an aralkyl group which is optionally substituted with one to three of said substituent(s)) as defined in (1-1) above;
• Y3 and Y4 are each, the same or different, a single bond or a straight-chain or branched lower alkylene group, or
• a substituent selected from the group consisting of a lower alkyl group, an aryl group or an aralkyl group which is optionally substituted with one to three of the same or different substituent(s) selected from the groups consisting of a lower alkyl group, a cyano group, a nitro group, a carboxyl group, a carbamoyl group, a formyl group, a lower alkanoyl group, a lower alkanoyloxy group, a hydroxy lower alkyl group, a cyano lower alkyl group, a halo lower alkyl group, a carboxy lower alkyl group, a carbamoyl lower alkyl group, a lower alkoxy group, a lower alkoxycarbonyl group, a lower alkoxycarbonylamino group, a lower alkoxycarbonylamino lower alkyl group, a lower alkylcarbamoyl group, a di-lower alkylcarbamoyl group, a carbamoyloxy group, a lower alkylcarbamoyloxy group, di-lower alkylcarbamoyloxy group, an amino group, a lower alkylamino group, a di-lower alkylamino group, a tri-lower alkylammonio group, an amino lower alkyl group, a lower alkylamino lower alkyl group, a di-lower alkylamino lower alkyl group, a tri-lower alkylammonio lower alkyl group, a lower alkanoylamino group, an aroylamino group, a lower alkanoylamidino lower alkyl group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, a lower alkylsulfonylamino group, a hydroxyimino group and a lower alkoxyimino group, and the group represented by the formula Y3—W2—Y4—Rs, wherein Rs, W2, Y3 and Y4 have the same meanings as stated above.