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US 6,713,496 B2Granted
3-(imidazolyl)-2-alkoxypropanoic acids
AssigneePfizer Inc.
InventorsCharlotte Moira Norfor Allerton, David John Bull, Mark Edward Bunnage, Robert John Maguire, John Steele
Life of this patent
Estimating the term…
Abstract
Compounds according to formula (I) wherein n is 0-3, R1 is optionally substituted C1-8 alkyl, C2-6 alkenyl, or C2-6 alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R2, R3, R4, R5, R6, R7, R8 and R9 are each independently selected from hydrogen and optionally substituted C1-6 alkyl, or R5 and R8 are an alkylene chain, are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition.
Claims26
A compound according to formula (I)
- wherein:
- n is 0, 1, 2 or 3;
- R1 is selected from
- a. an optionally substituted straight chain or branched chain C1-6 alkyl group,
- b. an optionally substituted straight chain or branched chain C2-6 alkenyl group,
- c. an optionally substituted straight chain or branched chain C2-6 alkynyl group,
- d. Aryl,
- e. Aromatic heterocycle,
- f. Heterocycle, and
- g. hydrogen;
- where the optional substituents in groups (a), (b) and (c) above are selected from:
- C3-7 cycloalkyl, Aryl, Aromatic heterocycle, Heterocycle, OR10, NR10R11, S(O)pR10, OC(O)R11, CO2R10, CONR10R11, SO2NR10R11, halo and NHSO2R10, and where p is 0, 1 or 2;
- R2, R3, R4, R6, R7 and R9 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR10 or halo;
- R5 and R8 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR10 or halo, or together are a C2-6 alkylene chain;
- R10 and R11 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl;
- Aryl is a 6-14 membered aromatic monocyclic or fused polycyclic carbocyclic group optionally substituted with one or more groups selected from R12, halo, OR13, NR13R14, NR13CO2R12, CO2R13, NR13SO2R12, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, SO2NR13R14, C(O)NR13R14, C3-7 cycloakyl, O(C3-7 cycloalkyl), R15 and OR15, where R12 is straight chain or branched chain C1-6 alkyl, R13 and R14 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl, and R15 is phenyl optionally substituted by R12, OR13, halo or haloalkyl;
- Aromatic heterocycle is a 5 to 7 membered aromatic ring containing from 1 to 3 heteroatoms, each independently selected from O, S and N, said ring being optionally substituted with one or more groups selected from OR13, NR13R14, CO2R13, NR13CO2R12, R12, halo, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, NR13SO2R12, SO2NR13R14 and C(O)NR13R14;
- and
- Heterocycle is a 3 to 8 membered ring containing from 1 to 3 heteroatoms, each independently selected from O, S and N, said ring being saturated or partially saturated, said ring further being optionally substituted with one or more groups selected from OR13, NR13R14, CO2R13, NR13CO2R14, R12, halo, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, NR13SO2R12, SO2NR13R14 and C(O)NR13R14,
- or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
17 more elements
A compound according to any preceding claim wherein n is 0 or 1.
A process for the preparation of a compound according to formula (I)
- wherein:
- n is 0, 1, 2 or 3;
- R1 is selected from
- a. an optionally substituted straight chain or branched chain C1-6 alkyl group,
- b. an optionally substituted straight chain or branched chain C2-6 alkenyl group,
- c. an optionally substituted straight chain or branched chain C2-6 alkynyl group,
- d. Aryl,
- e. Aromatic heterocycle,
- f. Heterocycle, and
- g. hydrogen;
- where the optional substituents in groups (a), (b) and (c) above are selected from:
- C3-7 cycloalkyl, Aryl, Aromatic heterocycle, Heterocycle, OR10, NR10R11, S(O)pR10, OC(O)R11, CO2R10, CONR10R11, SO2NR10R11, halo and NHSO2R10, and where p is 0, 1 or 2;
- R2, R3, R4, R6, R7 and R9 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR10 or halo;
- R5 and R8 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR10 or halo, or together are a C2-6 alkylene chain;
- R10 and R11 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl;
- Aryl is a 6-14 membered aromatic monocyclic or fused polycyclic carbocyclic group optionally substituted with one or more groups selected from R12, halo, OR13, NR13R14, NR13CO2R12, CO2R13, NR13SO2R12, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, SO2NR13R14, C(O)NR13R14, C3-7 cycloakyl, O(C3-7 cycloalkyl), R15 and OR15, where R12 is straight chain or branched chain C1-6 alkyl, R13 and R14 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl, and R15 is phenyl optionally substituted by R12, OR13, halo or haloalkyl;
- Aromatic heterocycle is a 5 to 7 membered aromatic ring containing from 1 to 3 heteroatoms, each independently selected from O, S and N, said ring being optionally substituted with one or more groups selected from OR13, NR13R14, CO2R13, NR13CO2R12, R12, halo, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, NR13SO2R12, SO2NR13R14 and C(O)NR13R14;
- and
- Heterocycle is a 3 to 8 membered ring containing from 1 to 3 heteroatoms, each independently selected from O, S and N, said ring being saturated or partially saturated, said ring further being optionally substituted with one or more groups selected from OR13, NR13R14, CO2R13, NR13CO2R14, R12, halo, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, NR13SO2R12, SO2NR13R14 and C(O)NR13R14,
- or a tautomer thereof, comprising the steps of:
- (i) preparing a compound according to formula (II)
- wherein:
- P1 is an optionally substituted C1-6 alkyl group, an optionally substituted C4-7 cycloalkyl group, an optionally substituted benzyl group or a tri(C1-6 alkyl)silyl group;
- and
- R1, R2, R3, R4, R5, R6, R7, R8, R9 and n are as defined for formula (I);
- and
- (ii) treating said compound of formula (II) with a reagent or combination of reagents suitable for removing the P1 group.
24 more elements
A process for the preparation of a compound according to formula (I)
- wherein:
- n is 0, 1, 2 or 3;
- R1 is selected from
- a. an optionally substituted straight chain or branched chain C1-6 alkyl group,
- b. an optionally substituted straight chain or branched chain C2-6 alkenyl group,
- c. an optionally substituted straight chain or branched chain C2-6 alkynyl group,
- d. Aryl,
- e. Aromatic heterocycle,
- f. Heterocycle, and
- g. hydrogen;
- where the optional substituents in groups (a), (b) and (c) above are selected from:
- C3-7 cycloalkyl, Aryl, Aromatic heterocycle, Heterocycle, OR10, NR10R11, S(O)pR10, OC(O)R11, CO2R10, CONR10R11, SO2NR10R11, halo and NHSO2R10, and where p is 0, 1 or 2;
- R2, R3, R4, R6 and R7 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR10 or halo;
- R5 and R8 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR10 or halo, or together are a C2-6 alkylene chain;
- R9 is hydrogen;
- R10 and R11 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl;
- Aryl is a 6-14 membered aromatic monocyclic or fused polycyclic carbocyclic group optionally substituted with one or more groups selected from R12, halo, OR13, NR13R14, NR13CO2R12, CO2R13, NR13SO2R12, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, SO2NR13R14, C(O)NR13R14, C3-7 cycloakyl, O(C3-7 cycloalkyl), R15 and OR15, where R12 is straight chain or branched chain C1-6 alkyl, R13 and R14 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl, and R15 is phenyl optionally substituted by R12, OR13, halo or haloalkyl;
- Aromatic heterocycle is a 5 to 7 membered aromatic ring containing from 1 to 3 heteroatoms, each independently selected from O, S and N, said ring being optionally substituted with one or more groups selected from OR13, NR13R14, CO2R13, NR13CO2R12, R12, halo, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, NR13SO2R12, SO2NR13R14 and C(O)NR13R14;
- and
- Heterocycle is a 3 to 8 membered ring containing from 1 to 3 heteroatoms, each independently selected from O, S and N, said ring being saturated or partially saturated, said ring further being optionally substituted with one or more groups selected from OR13, NR13R14, CO2R13, NR13CO2R14, R12, halo, CN, haloalkyl, O(haloalkyl), SR13, S(O)R12, SO2R12, OC(O)R13, NR13SO2R12, SO2NR13R14 and C(O)NR13R14,
- or a tautomer thereof, comprising the steps of:
- (i) preparing a compound according to formula (XIV)
- wherein:
- R1, R2, R3, R4, R5, R6, R7, R8 and n are as defined for formula (I);
- and
- (ii) treating said compound of formula (II) with a reagent or combination of reagents suitable for hydrolyzing the amide bond of the lactam ring.
23 more elements
Dependencies are inferred from the claim text.