Novel heteropyrrole analogs acting on cannabinoid receptors

A compound represented by the following structural formula,

• and physiologically acceptable salts thereof, wherein:
• A is selected from a direct bond, O and —(CH2)IN(R5);
• B is selected from a direct bond, O and N(R5),
• R5 is selected from hydrogen, alkyl and substituted alkyl and I is 0 or 1;
• R1 and R2 are each independently —(CH2)n—Z,
• n is an integer from 0 to about 7, 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, 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-NX1X2,
• j is an integer from 0 to about 6;
• 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
• 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 -Q2-(CH2)n—Z,
• Q2 is optionally present and if present is selected from —CH2—N, —CH2—O, —CH2—S, —CH2—SO2 and —CH2—OSO2,
• n is an integer from 0 to about 7, 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, 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
• R1 and R2 are each independently —(CH2)m-Q1-(CH2)n—Z,
• Q1 is selected from N, O, S, —CH═CH—, —C≡C—, —CO, SO2 and OSO2,
• m is an integer from 1 to about 7,
• n is an integer from 0 to about 7, 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, 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-NX1X2,
• j is an integer from 0 to about 6;
• or
• Z is selected from a bicyclic ring, a heterobicyclic ring, a tricyclic ring, a heterotricyclic ring, a polycyclic ring and a heteropolycyclic ring;
• 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 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 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 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
• Z is selected from
• R1 and R2 are each independently -T-(CH2)n—Z,
• n 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, 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-NX1X2,
• 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)n—Z,
• each n is independently 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 N, O, S, CH═CH, C≡C, 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-NX1X2,
• 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 —(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 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, 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-NX1X2,
• 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
• 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-NX1X2,
• 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)m-Q1-(CH2)n—Z,
• Q1 is selected from N, O, S, CH═CH, C≡C, CO, SO2 and OSO2,
• m is an integer from 1 to about 7,
• n 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-NX1X2,
• 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;
• 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,
• J is an integer from 0 to about 6;
• with the proviso that when A is a direct bond;
• and B is N(R5);
• and 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 A is a direct bond;
• B is N(R5);
• and 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, carbomyl, acetyl and naphthyl;
• then R4 can not be H, halogen, CN, carbomyl, 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.