Heteropyrrole analogs acting on cannabinoid receptors

A compound represented by the following structural formula,

• and physiologically acceptable salts thereof, wherein:
• A is a direct bond;
• B is N(R5),
• R5 is selected from hydrogen, alkyl and substituted alkyl;
• R1 and R2 are each independently —(CH2)n—Z,
• n is 0, and
• Z is selected from a carbocyclic ring having about 4 to about 7 ring members, a heterocyclic ring having about 4 to about 7 ring members, an aromatic ring having about 5 to about 7 ring members, a heteroaromatic ring having about 5 to about 7 ring members, a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring, a heteropolycyclic ring;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)n— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from a 5 member unsaturated ring having 0 to 4 independently selected heteroatoms as ring members, a substituted 5 member unsaturated ring having 0 to 4 independently selected heteroatoms as ring members, a 6 member aromatic ring having 0 to 5 independently selected heteroatoms as ring members or a substituted 6 member aromatic ring having 0 to 5 independently selected heteroatoms;
• and wherein the connecting point between the —(CH2)n— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from 1-, 2- or 3-pyrrolidinyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, 2-, 3- or 4-thiomorpholinyl, 1-, 2- or 3-azetidinyl, 1- or 2-piperazinyl, 2- or 3-tetrahydrofuranyl;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)n— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from
• wherein X and Y are each independently selected from H, halogen, N3, NCS, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOX3, O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alcohol, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl, alkylsulfonyl and methylene dioxy when Z comprises a structure having two adjacent carbon atoms,
• X1 and X2 are each independently selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members,
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1X2;
• or
• Z is selected from a carbocyclic ring having 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms, a carbocyclic ring having 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms, a heterocyclic ring having 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms, an heterocyclic ring having 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms, an aromatic ring having 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms, an aromatic ring having 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms, a heteroaromatic ring having 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms or a heteroaromatic ring having 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms;
• or
• Z is selected from an unsaturated ring having 5 ring atoms and 0 to 2 independently selected heteroatoms as ring members fused to an unsaturated ring having 5 ring atoms and 0 to 4 independently selected heteroatoms as ring members, an unsaturated ring having 5 ring atoms and 0 to 2 independently selected heteroatoms as ring members fused to an unsaturated ring having 6 or 7 ring atoms and 0 to 3 independently selected heteroatoms as ring members or an unsaturated ring having 6 ring atoms and 0 to 4 independently selected heteroatoms as ring members fused to an unsaturated ring having 6 or 7 ring atoms and 0 to 4 independently selected heteroatoms as ring members;
• or
• R1 and R2 are each independently -T-(CH2)n—Z,
• n is 0,
• T is selected from a carbocyclic ring having 3 to about 8 ring members, an unsaturated ring having 3 to about 8 carbon atoms as ring members, an aromatic ring having 5 to about 8 carbon atoms as ring members, a heterocyclic ring having 3 to about 8 ring members, a heteroaromatic ring having 5 to about 8 ring members, a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring and a heteropolycyclic ring, and
• Z is selected from H, halogen, N3, NCS, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOH, O(CH2)jOX3, O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl and alkylsulfonyl,
• X1 and X2 each independently is selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members,
• X3 is selected from H, alkyl, hydroxyloweralkyl and or alkyl-NX1 X2,
• j is an integer from 0 to about 6;
• or
• Z is selected from a carbocyclic ring having about 4 to about 7 ring members, a heterocyclic ring having about 4 to about 7 ring members, an aromatic ring having about 5 to about 7 ring members, a heteroaromatic ring having about 5 to about 7 ring members, a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring, a heteropolycyclic ring;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)n— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from 1-, 2- or 3-pyrrolidinyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, 2-, 3- or 4-thiomorpholinyl, 1-, 2- or 3-azetidinyl, 1- or 2-piperazinyl, 2- or 3-tetrahydrofuranyl;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)n— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from
• wherein X and Y are each independently selected from H, halogen, N3, NCS, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alcohol, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl, alkylsulfonyl and methylene dioxy when Z comprises a structure having two adjacent carbon atoms,
• X1 and X2 are each independently is selected from H or alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members,
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1X2;
• or
• Z is selected from an unsaturated ring having 5 ring atoms and 0 to 2 independently selected heteroatoms as ring members fused to an unsaturated ring having 5 ring atoms and 0 to 4 independently selected heteroatoms as ring members, an unsaturated ring having 5 ring atoms and 0 to 2 independently selected heteroatoms as ring members fused to an unsaturated ring having 6 or 7 ring atoms and 0 to 4 independently selected heteroatoms as ring members and an unsaturated ring having 6 ring atoms and 0 to 3 independently selected heteroatoms as ring members fused to an unsaturated ring having 6 or 7 ring atoms and 0 to 4 independently selected heteroatoms as ring members;
• or
• R1 and R2 are each independently -T-(CH2)n-Q1-(CH2)m—Z,
• n is 0,
• m is an integer from 0 to about 7,
• T is selected from a carbocyclic ring having 3 to about 8 ring members, an unsaturated ring having 3 to about 8 carbon atoms as ring members, an aromatic ring having 5 to about 8 carbon atoms as ring members, a heterocyclic ring having 3 to about 8 ring members, a heteroaromatic ring having 5 to about 8 ring members, a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring and a heteropolycyclic ring,
• Q1 is selected from NH, O, S, CH═CH, CO, SO2 and OSO2, and
• Z is selected from H, halogen, N3, NCS, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOX3, O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alcohol, alkoxy, alkylmercapto, alkylamino or di-alkylamino, alkylsulfinyl and alkylsulfonyl,
• X1 and X2 each independently selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members,
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1 X2,
• j is an integer from 0 to about 6;
• or
• Z is selected from a carbocyclic ring having about 4 to about 7 ring members, a heterocyclic ring having about 4 to about 7 ring members, an aromatic ring having about 5 to about 7 ring members, a heteroaromatic ring having about 5 to about 7 ring members, a bicyclic ring, a heterobicyclic ring, a polycyclic ring, a heteropolycyclic ring;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the (CHO, —(CH2)m— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from 1-, 2- or 3-pyrrolidinyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, 2-, 3- or 4-thiomorpholinyl, 1-, 2- or 3-azetidinyl, 1- or 2-piperazinyl, 2- or 3-tetrahydrofuranyl;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CHz)m— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from
• wherein X and Y are each independently is selected from H, halogen, N3, NCS, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOX3O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alcohol, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl, alkylsulfonyl and methylene dioxy when Z comprises a structure having two adjacent carbon atoms,
• X1 and X2 are each independently is selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members,
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1X2;
• or
• Z is selected from an unsaturated ring having 5 ring atoms and 0 to 2 independently selected heteroatoms as ring members fused to an unsaturated ring having 5 ring atoms and 0 to 2 independently selected heteroatoms as ring members, an unsaturated ring having 5 ring atoms and 0 to 2 independently selected heteroatoms as ring members fused to an unsaturated ring having 6 or 7 ring atoms and 0 to 4 independently selected heteroatoms as ring members or an unsaturated ring having 6 ring atoms and 0 to 3 independently selected heteroatoms as ring members fused to an unsaturated ring having 6 or 7 ring atoms and 0 to 4 independently selected heteroatoms as ring members;
• or
• Z is selected from
• wherein E is selected from a C1 to about C4 linear or branched alkyl group, a phenyl group, a substituted phenyl group, a benzyl group and a substituted benzyl group;
• or
• Z is selected from
• wherein k is an integer from 1 to about 5, A1 and A2 are each independently selected from a C1 to about C4 alkyl group, a phenyl group and a substituted phenyl group;
• R3 is selected from a carbocyclic ring having about 4 to about 7 members, a heterocyclic ring having about 4 to about 7 members, an aromatic ring having about 5 to about 7 ring members, a heteroaromatic ring having about 5 to about 7 members, a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring and a heteropolycyclic ring;
• or
• R3 is
• wherein G is selected from CH and N, and L and J each independently selected from (CH2)n, O, NH and S, n is an integer from 0 to about 7;
• or
• R3 is
• wherein G, L and J are each independently selected from CH and N;
• or
• R3 is selected from
• wherein X and Y are independently selected from H, halogen, N3, NCS, phenyl, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOX3, O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alcohol, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl and alkylsulfonyl,
• X1 and X2 are each independently selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members),
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1 X2,
• j is an integer from 0 to about 6;
• or
• R3 is selected from a carbocyclic ring having 4 to 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms, a carbocyclic ring having 4 to 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms, a heterocyclic ring having 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms, a heterocyclic ring having 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms, an aromatic ring having 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms, an aromatic ring having 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms, a heteroaromatic ring having 6 ring atoms fused to a heterocyclic ring having from 5 to 7 ring atoms, and a heteroaromatic ring having 6 ring atoms fused to a heteroaromatic ring having from 5 to 7 ring atoms;
• R4 is selected from H, halogen, N3, NCS, phenyl, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOX3, O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alcohol, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl and alkylsulfonyl,
• X1 and X2 are each independently selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members),
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1X2,
• j is an integer from 0 to about 6;
• or
• R4 is selected from a carbocyclic ring having about 4 to about 7 ring members, a heterocyclic ring having about 4 to about 7 ring members, an aromatic ring having about 5 to about 7 ring members, a heteroaromatic ring having about 5 to about 7 ring members, a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring and a heteropolycyclic ring;
• or
• R4 is selected from
• or
• R4 is —(CH2)d—Z,
• d is an integer from 1 to about 6, and
• Z is selected from H, halogen, N3, NCS, phenyl, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOH, O(CH2)jOX3, O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl and alkylsulfonyl,
• X1 and X2 are each independently selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members),
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1 X2,
• j is an integer from 0 to about 6;
• or
• Z is selected from a carbocyclic ring having about 4 to about 7 ring members, a heterocyclic ring having about 4 to about 7 ring members, an aromatic ring having about 5 to about 7 ring members, a heteroaromatic ring having about 5 to about 7 ring members, a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring, a heteropolycyclic ring;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)d— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from 1-, 2- or 3-pyrrolidinyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, 2-, 3- or 4-thiomorpholinyl, 1-, 2- or 3-azetidinyl, 1- or 2-piperazinyl, 2- or 3-tetrahydrofuranyl;
• or any above group substituted on at least one ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)d— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• R4 is —(CH2)p-Q1-(CH2)q—Z,
• Q1 is selected from NH, O, S, CH═CH, CO, SO2 and OSO2,
• p is an integer from 1 to about 7,
• g is an integer from 0 to about 7, and
• Z is selected from H, halogen, N3, NCS, phenyl, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, NH-acyl, NH-aroyl, O(CH2)jOX3, O(CH2)jNX1X2, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl and alkylsulfonyl,
• X1 and X2 are each independently selected from H or alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members,
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1 X2,
• j is an integer from 0 to about 6;
• or
• Z is selected from a carbocyclic ring having about 4 to about 7 ring members, a heterocyclic ring having about 4 to about 7 ring members, an aromatic ring having about 5 to about 7 ring members, a heteroaromatic ring having about 5 to about 7 ring members;
• a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring, a heteropolycyclic ring;
• or any above group substituted on at least one available ring atom by an alkyl group;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)q— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from 1-, 2- or 3-pyrrolidinyl, 1-, 2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, 2-, 3- or 4-thiomorpholinyl, 1-, 2- or 3-azetidinyl, 1- or 2-piperazinyl, 2- or 3-tetrahydrofuranyl;
• or any above group substituted on at least one available ring atom by an alkyl;
• or any above group substituted on at least one available ring nitrogen atom by a benzyl group, a substituted benzyl group, an alkoxybenzyl group, a substituted alkoxybenzyl group, a benzhydryl group or a substituted benzhydryl group;
• and wherein the connecting point between the —(CH2)q— group and the Z group can be any available ring carbon atom or any available ring nitrogen atom;
• or
• Z is selected from
• wherein X and Y are each independently selected from H, halogen, N3, NCS, CN, NO2, NX1X2, OX3, OAc, O-acyl, O-aroyl, O(CH2)jOX3, O(CH2)jNX1X2, NH-acyl, NH-aroyl, CHO, C(halogen)3, COOX3, SO3H, SO2NX1X2, CONX1X2, alkyl, alcohol, alkoxy, alkylmercapto, alkylamino, di-alkylamino, alkylsulfinyl, alkylsulfonyl and methylene dioxy when Z comprises a structure having two adjacent carbon atoms,
• X1 and X2 are each independently selected from H and alkyl, or
• X1 and X2 together comprise part of a heterocyclic ring having about 4 to about 7 ring members and optionally one additional heteroatom selected from O, N or S, or
• X1 and X2 together comprise part of an imide ring having about 5 to about 6 members,
• X3 is selected from H, alkyl, hydroxyloweralkyl and alkyl-NX1X2,
• J is an integer from 0 to about 6;
• with the proviso that when either of R1 and R2 is phenyl [optionally substituted with one more members selected from halogen, (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl, cyano, nitro, (C1-C6) alkyl sulfonyl, (C1-C6) alkyl sulfonyl amino, (C1-C6) alkyl carbonyl-amino, (C1-C6) alkyl amino-carbonyl-amino and phenyl], (C2-C6) alkyl, cyclohexyl [optionally substituted with (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl, cyano or one or more fluorine atoms], 1-naphthyl or 2-naphthyl [optionally substituted with one or more members selected from halogen, (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl and cyano], benzyl [optionally substituted on the phenyl ring with one or more members selected from halogen, (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl and cyano], a 5- to 10-membered saturated or unsaturated heterocyclic radical [optionally substituted with one or more members selected from fluorine, (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl and cyano] and a 5- to 10-membered aromatic monocyclic or bicyclic heterocyclic radical [optionally substituted with one more members selected form halogen, (C1-C6) alkyl, (C1-C6) alkoxy, trifloromethyl, cyano, nitro and phenyl];
• then R4 can not be H, (C1-C6) alkyl, benzyl, chloro, or bromo;
• and the proviso that when either R1 or
• R2 is phenyl, thienyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl or any above group substituted with 1, 2, 3 or 4 substituents which can be the same or different, selected from C1-3 alkyl, C1-3 alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl(C1-2)-amino, mono- or dialkyl(C1-2)-amido, (C1-3)-alkoxycarbonyl, carboxyl, cyano, carbornyl, acetyl and naphthyl;
• then R4 can not be H, halogen, CN, carbornyl, formyl, acetyl, trifluoroacetyl, fluoroacetyl, propionyl, sulfamoyl, methanesulfonyl, methylsulfanyl, branched or unbranched C1-4 alkyl group, which C1-4 alkyl group may be substituted with 1 to 3 fluoro atoms or with a single bromo, chloro, iodo, cyano or hydroxy group.