Prostaglandin agonists

A compound having the Formula I

• 32
• prodrugs thereof and the pharmaceutically acceptable salts of said compounds and said prodrugs, wherein
• A is SO2 or CO;
• G is Ar, Ar1—V—Ar2, Ar—(C1-C6)alkylene, Ar—CONH—(C1-C6)alkylene, R1R2-amino, oxy(C1-C6)alkylene, amino substituted with Ar, or amino substituted with Ar(C1-C4)alkylene and R11, wherein R11 is H or (C1-C8)alkyl, R1 and R2 may be taken separately and are independently selected from H and (C1-C8)alkyl, or R1 and R2are taken together with the nitrogen atom of the amino group to form a five- or six-membered azacycloalkyl, said azacycloalkyl optionally containing an oxygen atom and optionally mono-, di- or tri-substituted independently with up to two oxo, hydroxy, (C1-C4)alkyl, fluoro or chloro;
• B is N or CH;
• Q is
• -(C2-C6)alkylene-W—(C1-C3)alkylene-, said alkylenes each optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
• -(C4-C8)alkylene-, said alkylene optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
• -X—(C1-C5)alkylene-, said alkylene optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
• -(C1-C5)alkylene-X—, said alkylene optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
• -(C1-C3)alkylene-X—(C1-C3)alkylene-, said alkylenes each optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
• -(C2-C4)alkylene-W—X—(C0-C3)alkylene-, said alkylenes each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl,
• -(C0-C4)alkylene-X—W—(C1-C3)alkylene-, said alkylenes each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl,
• -(C2-C5)alkylene-W—X—W—(C1-C3)alkylene-, wherein the two occurrences of W are independent of each other, said alkylenes each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl,
• -(C1-C4)alkylene-ethenylene-(C1-C4)alkylene-, said alkylenes and said ethenylene each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl,
• -(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X-(Co-C5)alkylene-, said alkylenes and said ethenylene each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl,
• -(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X-W—(C1-C3)alkylene-, said alkylenes and said ethenylene each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl,
• -(C1-C4)alkylene-ethynylene-(C1-C4)alkylene-, said alkylenes and said ethynylene each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl, or
• -(C1-C4)alkylene-ethynylene-X—(C0-C3)alkylene-, said alkylenes and said ethynylene each optionally substituted with up to four substituents each independently selected from fluoro or (C1-C4)alkyl;
• Z is carboxyl, (C1-C6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl, 5-oxo-1,2,4-oxadiazolyl, 5-oxo-1,2,4-thiadiazolyl, (C1-C4)alkylsulfonylcarbamoyl or phenylsulfonylcarbamoyl;
• K is a bond, (C1-C9)alkylene, thio(C1-C4)alkylene, (C1-C4)alkylenethio(C1-C4)alkylene, (C1-C4)alkyleneoxy(C1-C4)alkylene or oxy(C1-C4)alkylene, said (C1-C9)alkylene optionally mono-unsaturated and wherein, when K is not a bond, K is optionally mono-, di- or tri-substituted independently with chloro, fluoro, hydroxy or methyl;
• M is —Ar3, —Ar4—V1—Ar5, —Ar4—S—Ar5, —Ar4—SO—Ar5, —Ar4—SO2—Ar5 or —Ar4—O—Ar5;
• Ar is a partially saturated or fully unsaturated five to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused independently partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, or a tricyclic ring consisting of three fused independently partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, said partially or fully saturated ring, bicyclic ring or tricyclic ring optionally having one or two oxo groups substituted on carbon or one or two oxo groups substituted on sulfur;
• or Ar is a fully saturated five to seven membered ring having one or two heteroatoms selected independently from oxygen, sulfur and nitrogen;
• Ar1 and Ar2 are each independently a partially saturated, fully saturated or fully unsaturated five to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused independently partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, or a tricyclic ring consisting of three fused independently partially saturated, fully saturated or fully unsaturated five or six membered rings, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, said partially or fully saturated ring, bicyclic ring or tricyclic ring optionally having one or two oxo groups substituted on carbon or one or two oxo groups substituted on sulfur;
• said Ar, Ar1 and Ar2 moieties are optionally substituted on carbon or nitrogen, on one ring if the moiety is monocyclic, on one or both rings if the moiety is bicyclic, or on one, two or three rings if the moiety is tricyclic, with up to three substituents per moiety independently selected from R3, R4 and R5 wherein R3, R4 and R5 are independently hydroxy, nitro, halo, carboxy, (C1-C7)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (C2-C7)alkenyl, (C2-C7)alkynyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, (C3-C7)cycloalkyl(C1-C4)alkanoyl, formyl, (C1-C8)alkanoyl, (C1-C6)alkanoyl(C1-C6)alkyl, (C1-C4)alkanoylamino, (C1-C4)alkoxycarbonylamino, hydroxysulfonyl, aminocarbonylamino or mono-N-, di-N,N-, di-N,N′- or tri-N,N,N′-(C1-C4)alkyl substituted aminocarbonylamino, sulfonamido, (C1-C4)alkylsulfonamido, amino, mono-N- or di-N,N-(C1-C4)alkylamino, carbamoyl, mono-N- or di-N,N-(C1-C4)alkylcarbamoyl, cyano, thiol, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C4)alkylsulfonyl or mono-N- or di-N,N-(C1-C4)alkylaminosulfinyl;
• Ar3, Ar4 and Ar5 are each independently a partially saturated, fully saturated or fully unsaturated five to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused independently partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, or a tricyclic ring consisting of three fused independently partially saturated, fully saturated or fully unsaturated five or six membered rings, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, said partially or fully saturated ring, bicyclic ring or tricyclic ring optionally having one or two oxo groups substituted on carbon or one or two oxo groups substituted on sulfur;
• said Ar3, Ar4 and Ar5 moieties are optionally substituted on carbon or nitrogen, on one ring if the moiety is monocyclic, on one or both rings if the moiety is bicyclic, or on one, two or three rings if the moiety is tricyclic, with up to three substituents per moiety independently selected from R31, R41 and R51 wherein R31 R41 and R51 are independently hydroxy, nitro, halo, carboxy, (C1-C7)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (C2-C7)alkenyl, (C2-C7)alkynyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, (C3-C7)cycloalkyl(C1-C4)alkanoyl, formyl, (C1-C8)alkanoyl, (C1-C6)alkanoyl(C1-C6)alkyl, (C1-C4)alkanoylamino, (C1-C4)alkoxycarbonylamino, hydroxysulfonyl, aminocarbonylamino or mono-N-, di-N,N-, di-N,N′- or tri-N,N,N′-(C1-C4)alkyl substituted aminocarbonylamino, sulfonamido, (C1-C4)alkylsulfonamido, amino, mono-N- or di-N,N-(C1-C4)alkylamino, carbamoyl, mono-N- or di-N,N-(C1-C4)alkylcarbamoyl, cyano, thiol, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C4)alkylsulfonyl or mono-N- or di-N,N-(C1-C4)alkylaminosulfinyl;
• W is oxy, thio, sulfino, sulfonyl, aminosulfonyl-, -mono-N-(C1-C4)alkyleneaminosulfonyl-, sulfonylamino, N-(C1-C4)alkylenesulfonylamino, carboxamido, N-(C1-C4)alkylenecarboxamido, carboxamidooxy, N-(C1-C4)alkylenecarboxamidooxy, carbamoyl, -mono-N-(C1-C4)alkylenecarbamoyl, carbamoyloxy, or -mono-N-(C1-C4)alkylenecarbamoyloxy, wherein said W alkyl groups are optionally substituted on carbon with one to three fluorines;
• X is a five or six membered aromatic ring optionally having one or two heteroatoms selected independently from oxygen, nitrogen, and sulfur;
• said ring optionally mono-, di- or tri-substituted independently with halo, (C1-C3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C1-C4)alkoxy, or carbamoyl;
• R1, R2, R3, R4, R5, R11, R31, R41 and R51, when containing an alkyl, alkylene, alkenylene or alkynylene moiety, are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy;
• and
• V and V1 are each independently a bond, thio(C1-C4)alkylene, (C1-C4)alkylenethio, (C1-C4)alkyleneoxy, oxy(C1-C4)alkylene or (C1-C3)alkylene optionally mono- or di-substituted independently with hydroxy or fluoro;
• with the provisos that:
• a. when K is (C2-C4)alkylene and M is Ar3 and Ar3 is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cyclooct-1-yl then said (C5-C8)cycloalkyl substituents are not substituted at the one position with hydroxy;
• and
• b. when K is a bond;
• G is phenyl, phenylmethyl, substituted phenyl or substituted phenylmethyl;
• Q is (C3-C8)alkylene;
• and M is Ar3 or Ar4—Ar5, then A is sulfonyl.