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US 2004/0176461 A1Published application
Prevention of loss and restoration of bone mass by certain prostaglandin agonists
AssigneePfizer Inc.
InventorsKimberly O. Cameron, Hua Z. Ke, Bruce A. Lefker, Robert L. Rosati, David D. Thompson
Life of this patent
Estimating the term…
Abstract
Prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.
Claims141
A compound having the Formula I
- 29
- or a pharmaceutically acceptable salt or prodrug thereof wherein either (i):
- B is N;
- A is (C1-C6)alkylsulfonyl, (C3-C7)cycloalkylsulfonyl, (C3-C7)cycloalkyl(C1-C6)alkylsulfonyl, said A moieties optionally mono-, di- or tri-substituted on carbon independently with hydroxy, (C1-C4)alkyl or halo;
- Q is
- —(C2-C6)alkylene-W—(C1-C3)alkylene-,
- —(C3-C8)alkylene-, said —(C3-C8)alkylene- optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
- —X—(C1-C5)alkylene-,
- —(C1-C5)alkylene-X-,
- —(C1-C3)alkylene-X—(C1-C3)alkylene-,
- —(C2-C4)alkylene-W—X—(C0-C3)alkylene-,
- —(C0-C4)alkylene-X—W—(C1-C3)alkylene-,
- —(C2-C5)alkylene-W—X—W—(C1-C3)alkylene-, wherein the two occurrences of W are independent of each other,
- —(C1-C4)alkylene-ethenylene-(C1-C4)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—(Co-C5)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—W—(C1-C3)alkylene-,
- —(C1-C4)alkylene-ethynylene-(C1-C4)alkylene-, or
- —(C, -C4)alkylene-ethynylene-X—(C0-C3)alkylene-;
- 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-, or di-substituted independently with halo, (C1-C3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C1-C4)alkoxy, or carbamoyl;
- Z is carboxyl, (C1-C6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl, 5-oxo-1,2,4-oxadiazolyl, (C1-C4)alkylsulfonylcarbamoyl or phenylsulfonylcarbamoyl;
- K is a bond, (C1-C8)alkylene, thio(C1-C4)alkylene or oxy(C1-C4)alkylene, said (C1-C8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with fluoro, methyl or chloro;
- M is —Ar, —Ar1—V—Ar2, —Ar1—S—Ar2 or —Ar1—O—Ar2 wherein Ar, 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 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 Ar, Ar1 and Ar2 moieties optionally substituted, on one ring if the moiety is monocyclic, or one or both rings if the moiety is bicyclic, on carbon with up to three substituents independently selected from R1, R2 and R3 wherein R1, R2 and R3 are hydroxy, nitro, halo, (C1-C6)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (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, 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;
- R1, R2 and R3 are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy;
- and
- V is a bond or (C1-C3)alkylene optionally mono- or di-substituted independently with hydroxy or fluoro
- with the proviso that when K is (C2-C4)alkylene and M is Ar and Ar 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;
- or (ii):
- B is N;
- A is (C1-C6)alkanoyl, or (C3-C7)cycloalkyl(C1-C6)alkanoyl, said A moieties optionally mono-, di- or tri-substituted independently on carbon with hydroxy or halo;
- Q is
- —(C2-C6)alkylene-W—(C1-C3)alkylene-,
- —(C4-C8)alkylene-, said —(C4-C8)alkylene- optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
- —X—(C2-C5)alkylene-,
- —(C1-C5)alkylene-X-,
- —(C1-C3)alkylene-X—(C1-C3)alkylene-,
- —(C2-C4)alkylene-W—X—(C0-C3)alkylene-,
- —(C0-C4)alkylene-X—W—(C1-C3)alkylene-,
- —(C2-C5)alkylene-W—X—W—(C1-C3)alkylene-, wherein the two occurrences of W are independent of each other,
- —(C1-C4)alkylene-ethenylene-(C1-C4)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—(Co-C5)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—W—(C1-C3)alkylene-,
- —(C1-C4)alkylene-ethynylene-(C1-C4)alkylene-, or
- —(C1-C4)alkylene-ethynylene-X—(C0-C3)alkylene-;
- 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-, or di-substituted independently with halo, (C1-C3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C1-C4)alkoxy, or carbamoyl;
- Z is carboxyl, (C1-C6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl, 5-oxo-1,2,4-oxadiazolyl, (C1-C4)alkylsulfonylcarbamoyl or phenylsulfonylcarbamoyl;
- K is (C1-C8)alkylene, thio(C1-C4)alkylene or oxy(C1-C4)alkylene, said (C1-C8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with fluoro, methyl or chloro;
- M is —Ar, —Ar1—V—Ar, —Ar1—S—Ar2 or —Ar1—O—Ar wherein Ar, 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 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 Ar, Ar1 and Ar2 moieties optionally substituted, on one ring if the moiety is monocyclic, or one or both rings if the moiety is bicyclic, on carbon with up to three substituents independently selected from R1, R2 and R3 wherein R1, R2 and R3 are H, hydroxy, nitro, halo, (C1-C6)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (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, 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;
- R1, R2 and R3 are optionally mono-, di- or tri-substituted independently on carbon with halo or hydroxy;
- and
- V is a bond or (C1-C3)alkylene optionally mono- or di-substituted independently with hydroxy or fluoro
- with the proviso that when K is (C2-C4)alkylene and M is Ar and Ar is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cycloct-1-yl then said (C5-C8)cycloalkyl substituents are not substituted at the one position with hydroxy and with the proviso that 6-[(3-phenyl-propyl)-(2-propyl-pentanoyl)-amino]-hexanoic acid and its ethyl ester are not included
- or (iii):
- B is C(H);
- A is (C1-C6)alkanoyl, or (C3-C7)cycloalkyl(C1-C6)alkanoyl, said A moieties optionally mono-, di- or tri-substituted on carbon independently with hydroxy or halo;
- Q is
- —(C2-C6)alkylene-W—(C1-C3)alkylene-,
- —(C4-C8)alkylene-, said —(C4-C8)alkylene- optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
- —X—(C1-C5)alkylene-,
- —(C1-C5)alkylene-X-,
- —(C1-C3)alkylene-X—(C1-C3)alkylene-,
- —(C2-C4)alkylene-W—X—(C0-C3)alkylene-,
- —(C0-C4)alkylene-X—W—(C1-C3)alkylene-,
- —(C2-C5)alkylene-W—X—W—(C1-C3)alkylene-, wherein the two occurrences of W are independent of each other,
- —(C1-C4)alkylene-ethenylene-(C1-C4)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—(C0-C5)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—W—(C1-C3)alkylene-,
- —(C1-C4)alkylene-ethynylene-(C1-C4)alkylene-, or
- —(C1-C4)alkylene-ethynylene-X—(C0-C3)alkylene-;
- 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-, or di-substituted independently with halo, (C1-C3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C1-C4)alkoxy, or carbamoyl;
- Z is carboxyl, (C1-C6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl, 5oxo-1,2,4-oxadiazolyl, (C1-C4)alkylsulfonylcarbamoyl or phenylsulfonylcarbamoyl;
- K is a bond, (C1-C8)alkylene, thio(C1-C4)alkylene, (C4-C7)cycloalkyl(C1-C6)alkylene or oxy(C1-C4)alkylene, said (C1-C8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with fluoro, methyl or chloro;
- M is —Ar, —Ar1—V—Ar2, —Ar1—S—Ar2 or —Ar1-O—Ar2 wherein Ar, 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 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 Ar, Ar1 and Ar2 moieties optionally substituted, on one ring if the moiety is monocyclic, or one or both rings if the moiety is bicyclic, on carbon with up to three substituents independently selected from R1, R2 and R3 wherein R1, R2 and R3 are H, hydroxy, nitro, halo, (C1-C6)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (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, 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;
- R1, R2 and R3 are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy;
- and
- V is a bond or (C1-C3)alkylene optionally mono- or di-substituted independently with hydroxy or fluoro
- with the proviso that when K is (C2-C4)alkylene and M is Ar and Ar2 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.
82 more elements
The kit as recited in 114 wherein the anti-resorptive agent is tiludronic acid, alendronic acid, ibandronic acid, risedronic acid, etidronic acid, clodronic acid, and pamidronic acid or a pharmaceutically acceptable salt thereof.
123 A compound as recited in claim 1 wherein
- B is N;
- A is (C1-C3) alkylsulfonyl;
- Q is
- —(C3-C5)alkylene-O—(C1-C3)alkylene-,
- —(C5-C7)alkylene-, said —(C5-C7)alkylene- optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
- —(C2-C4)alkylene-X-,
- —(CH2)-meta-phenylene-O—(CH2)— optionally mono- or di-substituted independently with methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, chloro or fluoro
- or
- —(CH2)-meta-phenylene-(CH2)— optionally mono- or di-substituted independently with methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, chloro or fluoro;
- M is —Ar1—V—Ar2 or —Ar1—O—Ar2;
- V is a bond or —CH2—;
- Z is carboxyl, (C1-C4)alkoxycarbonyl or tetrazolyl;
- X is thienyl, thiazolyl, or furanyl;
- K is methylene;
- Ar1 is phenyl, (C5-C7)cycloalkyl , furanyl, thienyl, thiazolyl, or pyridyl;
- Ar2 is (C5-C7)cycloalkyl, phenyl, thienyl, thiazolyl, pyridyl, pyrimidyl, oxazolyl, furanyl, imidazolyl, isoxazolyl, pyrazinyl, triazolyl or pyrazolyl;
- R1 is chloro, fluoro, (C1-C4)alkyl or (C1-C4)alkoxy, said (C1-C4)alkyl and (C1-C4)alkoxy optionally mono-, di- or tri-substituted independently with hydroxy or fluoro;
- and
- R2 and R3 are each independently, methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, chloro or fluoro.
16 more elements
A compound as recited in claim 123 wherein
- Q is
- —(CH2)-meta-phenylene-(CH2)—,
- M is —Ar1—Ar2,
- Ar1 is phenyl;
- Ar2 is (C5-C7)cycloalkyl, phenyl, thienyl, thiazolyl, pyridyl, pyrimidyl, oxazolyl, furanyl, imidazolyl, isoxazolyl, pyrazinyl or pyrazolyl, said Ar2 optionally mono- or di-substituted independently with R1 or R2;
- R1 is chloro, fluoro, methyl, methoxy, trifluoromethyl, difluoromethoxy or trifluoromethoxy;
- and
- R2 is methoxy, chloro or fluoro.
5 more elements
A compound as recited in claim 123 wherein
- Q is
- —(CH2)-meta-phenylene-O—(CH2)—,
- M is —Ar1—Ar2,
- Ar1 is phenyl;
- Ar2 is (C5-C7)cycloalkyl, phenyl, thienyl, thiazolyl, pyridyl, pyrimidyl, oxazolyl, furanyl, imidazolyl, isoxazolyl, pyrazinyl or pyrazolyl, said Ar2 optionally mono- or di-substituted independently with R1 or R2;
- R1 is chloro, fluoro, methyl, methoxy, trifluoromethyl, difluoromethoxy or trifluoromethoxy;
- and
- R2 is methoxy, chloro or fluoro.
5 more elements
A compound having the Formula IA
- 30
- or a pharmaceutically acceptable salt or prodrug thereof wherein either (i):
- B is N;
- A is (C1-C6)alkylsulfonyl, (C3-C7)cycloalkylsulfonyl, (C3-C7)cycloalkyl(C1-C6)alkylsulfonyl, said A moieties optionally mono-, di- or tri-substituted on carbon independently with hydroxy, (C1-C4)alkyl or halo;
- Q is
- —(C2-C6)alkylene-W—(C1-C3)alkylene-,
- —(C3-C8)alkylene-, said —(C3-C8)alkylene- optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
- —X—(C1-C5)alkylene-,
- —(C1-C5)alkylene-X-,
- —(C1-C3)alkylene-X—(C1-C3)alkylene-,
- —(C2-C4)alkylene-W—X—(C0-C3)alkylene-,
- —(C0-C4)alkylene-X—W—(C1-C3)alkylene-,
- —(C2-C5)alkylene-W—X—W—(C1-C3)alkylene-, wherein the two occurrences of W are independent of each other,
- —(C1-C4)alkylene-ethenylene-(C1-C4)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—(Co-C5)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—W—(C1-C3)alkylene-,
- —(C1-C4)alkylene-ethynylene-(C1-C4)alkylene-, or
- —(C1-C4)alkylene-ethynylene-X—(C0-C3)alkylene-;
- 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 tetrahydrofuranyl or a five or six membered aromatic ring optionally having one or two heteroatoms selected independently from oxygen, nitrogen, and sulfur;
- said ring optionally mono-, or di-substituted independently with halo, (C1-C3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C1-C4)alkoxy, or carbamoyl;
- 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-C8)alkylene, thio(C1-C4)alkylene or oxy(C1-C4)alkylene, said (C1-C8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with fluoro, methyl or chloro;
- M is —Ar, —Ar1—V—Ar2, —Ar1—S—Ar2, —Ar1—O—Ar2, —Ar1—S—(C1-C3)—Ar2—, —Ar1—(C1-C3)-S—Ar2— or —Ar1—(C1-C3)—S—(C1-C3)—Ar2, wherein Ar, 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 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 Ar, Ar1 and Ar2 moieties optionally substituted, on one ring if the moiety is monocyclic, or one or both rings if the moiety is bicyclic, on carbon, nitrogen or sulfur with up to three substituents independently selected from R1, R2 and R3 wherein R1, R2 and R3 are oxo, hydroxy, nitro, halo, (C1-C6)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (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, 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;
- R1, R2 and R3 are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy;
- and
- V is a bond or (C1-C3)alkylene optionally mono-unsaturated and optionally mono- or di-substituted independently with hydroxy or fluoro,
- with the proviso that when K is (C2-C4)alkylene and M is Ar and Ar 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;
- or (ii):
- B is N;
- A is (C1-C6)alkanoyl, or (C3-C7)cycloalkyl(C1-C6)alkanoyl, said A moieties optionally mono-, di- or tri-substituted independently on carbon with hydroxy or halo;
- Q is
- —(C2-C6)alkylene-W—(C1-C3)alkylene-,
- —(C4-C8)alkylene-, said —(C4-C8)alkylene- optionally substituted with up to four substituents independently selected from fluoro or (C1-C4)alkyl,
- —X—(C2-C5)alkylene-,
- —(C1-C5)alkylene-X-,
- —(C1-C3)alkylene-X—(C1-C3)alkylene-,
- —(C2-C4)alkylene-W—X—(C0-C3)alkylene-,
- —(C0-C4)alkylene-X—W—(C1-C3)alkylene-,
- —(C2-C5)alkylene-W—X—W—(C1-C3)alkylene-, wherein the two occurrences of W are independent of each other,
- —(C1-C4)alkylene-ethenylene-(C1-C4)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—(Co-C5)alkylene-,
- —(C1-C4)alkylene-ethenylene-(C0-C2)alkylene-X—W—(C1-C3)alkylene-,
- —(C1-C4)alkylene-ethynylene-(C1-C4)alkylene-, or
- —(C1-C4)alkylene-ethynylene-X—(C0-C3)alkylene-;
- 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 tetrahydrofuranyl or a five or six membered aromatic ring optionally having one or two heteroatoms selected independently from oxygen, nitrogen, and sulfur;
- said ring optionally mono-, or di-substituted independently with halo, (C1-C3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C1-C4)alkoxy, or carbamoyl;
- 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 (C1-C8)alkylene, thio(C1-C4)alkylene or oxy(C1-C4)alkylene, said (C1-C8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with fluoro, methyl or chloro;
- M is —Ar, —Ar1—V—Ar, —Ar1—S—Ar2, —Ar1—O—Ar2, —Ar1—S—(C1-C3)—Ar2—, —Ar1—(C1-C3)-S—Ar2— or —Ar1—(C1-C3)—S—(C1-C3)—Ar2 wherein Ar, 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 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 Ar, Ar1 and Ar2 moieties optionally substituted, on one ring if the moiety is monocyclic, or one or both rings if the moiety is bicyclic, on carbon, nitrogen or sulfur with up to three substituents independently selected from R1, R2 and R3 wherein R1, R2 and R3 are oxo, H, hydroxy, nitro, halo, (C1-C6)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (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, 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;
- R1, R2 and R3 are optionally mono-, di- or tri-substituted independently on carbon with halo or hydroxy;
- and
- V is a bond or (C1-C3)alkylene optionally mono-unsaturated and optionally mono- or di-substituted independently with hydroxy or fluoro with the proviso that when K is (C2-C4)alkylene and M is Ar and Ar is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cycloct-1-yl then said (C5-C8)cycloalkyl substituents are not substituted at the one position with hydroxy and with the proviso that 6-[(3-phenyl-propyl)-(2-propyl-pentanoyl)-amino]-hexanoic acid and its ethyl ester are not included.
53 more elements
Dependencies are inferred from the claim text.