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US 2003/0191107 A1Published application
3-(Imidazolyl)-2-aminopropanoic acids
AssigneePfizer Inc.
InventorsCharlotte Moira Norfor Allerton, Mark Edward Bunnage, John Steele
Life of this patent
Estimating the term…
Abstract
Compounds according to formula (I) wherein n is 1-4, R1 is optionally substituted C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl, Heterocycle, Aromatic heterocycle, Aryl or hydrogen and R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen and optionally substituted C1-6 alkyl are novel. They are useful in the treatment of thrombotic conditions and other pathologies associated with fibrin deposition. 1
Claims21
A compound according to formula (I)
- 88
- wherein:
- n is 1, 2, 3 or 4;
- 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, OR9, NR9R10, S(O)pR9, OC(O)R10, CO2R9, CONR9R10, SO2NR9R10, halo and NHSO2R9, and where p is 0, 1 or 2;
- R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR9 or halo;
- R9 and R10 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 R11, halo, OR12, NR12R13, NR12CO2R11, CO2R12, NR12SO2R11, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, SO2NR12R13 and C(O)NR12R13, where R11 is straight chain or branched chain C1-6 alkyl and R12 and R13 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl;
- 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 OR12, NR12R13, CO2R12, NR12CO2R11, R11, halo, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, NR12SO2R11, SO2NR12R13 and C(O)NR12R13;
- 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 OR12, NR12R13, CO2R12, NR12CO2R13, R11, halo, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, NR12SO2R11, SO2NR12R13 and C(O)NR12R13,
- or a tautomer thereof, or a pharmaceutically acceptable salt or solvate of said or said tautomer.
17 more elements
A compound according to any preceding claim wherein n is 2 or 3.
A compound according to any preceding claim wherein R1 is hydrogen, Aryl or C1-6 alkyl optionally substituted by C3-7 cycloalkyl or Aryl.
A compound according to any preceding claim wherein R2, R3, R4, R5, R6, R7, and R8 are each independently hydrogen or C1-3 alkyl.
A process for the preparation of a compound according to formula (I)
- 91
- wherein:
- n is 1, 2, 3 or 4;
- 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 C2-6alkynyl 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, OR9, NR9R10, S(O)pR9, OC(O)R10, CO2R9, CONR9R10, SO2NR9R10, halo and NHSO2R9, and where p is 0, 1 or 2;
- R2, R3, R4, R5, R6, R7 and R8 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl optionally substituted by OR9 or halo;
- R9 and R10 are each independently selected from hydrogen and straight chain or branched chain C1-6alkyl;
- Aryl is a 6-14 membered aromatic monocyclic or fused polycyclic carbocyclic group optionally substituted with one or more groups selected from R11, halo, OR12, NR12R13, NR12CO2R11, CO2R12, NR12SO2R11, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, SO2NR12R13 and C(O)NR12R13, where R11 is straight chain or branched chain C1-6 alkyl and R12 and R13 are each independently selected from hydrogen and straight chain or branched chain C1-6alkyl;
- 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 OR12, NR12R13, CO2R12, NR12CO2R11, R11, halo, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, NR12SO2R11, SO2NR12R13 and C(O)NR12R13;
- 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 OR12, NR12R13, CO2R12, NR12CO2R13, R11, halo, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, NR12SO12R11, SO2NR12R13 and C(O)NR12R13,
- or a tautomer thereof, comprising the steps of:
- (i) preparing a compound according to formula (II)
- 92
- 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 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.
25 more elements
A process for the preparation of a compound according to formula (I)
- 93
- wherein:
- n is 1,2, 3 or 4;
- 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, OR9, NR9R10, S(O)pR9, OC(O)R10, CO2R9, CONR9R10, SO2NR9R10, halo and NHSO2R9, and where p is 0, 1 or 2;
- R2, R3, R4, R5, R6, and R7 are each independently selected from hydrogen and straight chain or branched chain C6 alkyl optionally substituted by OR9 or halo;
- R8 is hydrogen;
- R9 and R10 are each independently selected from hydrogen and straight chain or branched chain C1-6alkyl;
- Aryl is a 6-14 membered aromatic monocyclic or fused polycyclic carbocyclic group optionally substituted with one or more groups selected from R11, halo, OR12, NR12R13, NR12CO2R11, CO2R12, NR12SO2R11, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, SO2NR12R13 and C(O)NR12R13,where R11 is straight chain or branched chain C1-6 alkyl and R12 and R13 are each independently selected from hydrogen and straight chain or branched chain C1-6 alkyl;
- 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 OR12, NR12R—, CO2R12, NR12CO2R11, R11, halo, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, NR12SO2R11, SO2NR12R—and C(O)NR12R13;
- 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 OR12, NR12R13, CO2R12, NR12CO2R11, R13, halo, CN, haloalkyl, O(haloalkyl), SR12, S(O)R11, SO2R11, OC(O)R12, NR12SO2R11, SO2NR12 R13 and C(O)NR12R13,
- or a tautomer thereof, comprising the steps of:
- (i) preparing a compound according to formula (IV)
- 94
- wherein:
- P2 is an (optionally substituted C1-6 alkyl)oxycarbonyl group, an (optionally substituted C4-7 cycloalkyl)oxycarbonyl group, an (optionally substituted benzyl)oxycarbonyl group or an (optionally substituted fluorenylmethyl)oxycarbonyl group;
- and
- R1, R2, R3, R4, R5, R6, R7 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 P2 group.
26 more elements
Dependencies are inferred from the claim text.