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US 2004/0157914 A1Published application
Pyrrolidinone derivatives
AssigneeUcb, S.A.
InventorsDong Zou, Olivier Dasse, Janelle Evans, Paul Higgins, Jeremy Kintigh, Rama Kondru, Eric Schwartz, Laurent Knerr, Hai-Xiao Zhai
Life of this patent
Estimating the term…
Abstract
The present invention provides pharmaceutical compositions and novel compounds useful in the treatment of conditions mediated by CCR2, MCP-1 or the interaction thereof. The compounds of the present invention are pyrrolidinones and pyrrolidine-thiones.
Claims19
A pharmaceutical composition comprising a compound according to formula I
- 3
- wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R3 is —(O)R3a, —C(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or —SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3,4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof, together with a pharmaceutically acceptable diluent or carrier.
9 more elements
A compound of formula I
- 4
- wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R3 is —C(O)R3a, —(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3, 4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof.
9 more elements
A compound of formula
- 5
- wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R3 is —C(O)R3a, —(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or —SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3,4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof.
9 more elements
A compound of formula I
- 6
- wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R1 is —C(O)R3a, —C(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or —SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3, 4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof, provided that R1 is not hydrogen, C1-7-alkyl, phenyl, C3-5-cycloalkyl, or methylene (C3-5-cycloalkyl), each alkyl or phenyl group is optionally substituted with one or two methyl, methoxy, ethyl or trifluoromethyl, or up to three halogens.
9 more elements
A compound of formula
- 7
- wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R3 is —C(O)R3a, —C(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or —SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3, 4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof;
- provided that one of R1 and R2 is other than hydrogen.
10 more elements
A compound of formula
- 8
- wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R3 is —((O)R3a, —C(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or —SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3, 4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof, provided that R3 is not —C(O)R3a wherein R3a is hydrogen, C1-7-alkyl, C2-3-alkenyl, phenyl, C3-5-cycloalkyl, or methylene (C3-5-cycloalkyl), wherein each alkyl, phenyl or alkenyl group is optionally substituted with (a) one nitro, methoxy or ethoxy, (b) one or two methyl, ethyl or trifluoromethyl, or (c) up to three halogens.
9 more elements
A compound of formula
- 9
- wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R3 is —C(O)R3a, —C(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or —SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3, 4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof, and wherein when
- Y is oxygen;
- and
- G and G′, together with the bond linking them, are C═C;
- then
- R1 is other than hydrogen, C1-7-alkyl, phenyl, C3-5-cycloalkyl, or methylene (C3-5-cycloalkyl), each alkyl or phenyl group optionally substituted with one or two methyl, methoxy, ethyl or trifluoromethyl, or up to three halogens when R2 is hydrogen;
- or
- R3 is other than —C(O)R3a wherein R3a is hydrogen, C1-7-alkyl, C2-3-alkenyl, phenyl, C3-5-cycloalkyl, or methylene (C3-5-cycloalkyl), each alkyl, phenyl or alkenyl group optionally substituted with one nitro, methoxy or ethoxy, with one or two methyl, ethyl or trifluoromethyl, or with up to three halogens.
16 more elements
A compound of formula
- 10
- in fully or partially resolved isomeric form wherein,
- Y is oxygen or sulfur;
- G and G′, together with the bond linking them, are HC—CH or C═C;
- V is heterocycle;
- Z is halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, alkoxy, aryloxy, nitro or cyano;
- R1 is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R2 is hydrogen or hydroxy;
- R3 is —C(O)R3a, —C(O)OR3a, —C(O)N(R3a)(R3b), —S(O)2R3a, —S(O)R3a or —SR3a wherein R3a and R3b is hydrogen, halogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl or heterocycle;
- R4 is hydroxy, sulfanyl or amino;
- t is 1, 2, 3, 4 or 5;
- or a pharmaceutically acceptable salt or metabolically cleavable derivative thereof.
9 more elements
Dependencies are inferred from the claim text.