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US 2002/0177599 A1Published application
Pharmaceutically active compounds
AssigneePfizer Inc.
InventorsCharlotte Moira Norfor Allerton, Kevin Neil Dack, Mark Ian Kemp
Life of this patent
Estimating the term…
Abstract
Compounds of general formula (I): 1 wherein R1, R2, R3, R4, X, Y and A have the meanings given herein which are useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.
Claims18
A compound of general formula I:
- 44
- or pharmaceutically or veterinarily acceptable salts, solvates, polymorphs or pro-drugs thereof wherein:
- A represents CHOH or C═O;
- X represents O or NR5;
- Y represents CH or N;
- R1 and R2 independently represent H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl, C1-C6 alkylaryl, halo, cyano, nitro, OR6, OC(O)R6, C(O)R6, C(O)OR6, NR6C(O)NR7R8, NR6C(O)OR6, OC(O)NR7R8, C(O)NR9R10, NR9R10, SO2NR9R10 or SO2R11;
- R3, R4 and R5 independently represent H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R3 and R5 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- wherein when R1, R2, R3, R4 or R5 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group, such C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group may be optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR6, OC(O)R6, C(O)R6, C(O)OR6, NR6C(O)NR7R8, NR6C(O)OR6, OC(O)NR7R8, C(O)NR9R10, NR9R10, SO2NR9R10, SO2R11, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- wherein when R1, R2, R3, R4 or R5 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group which is substituted and/or terminated with one or more substituents selected from:
- C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl, such substituent groups are optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R6, R7 and R8 independently represent H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R7 and R8 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R9 and R10 independently represent H, C(O)R6, SO2R11, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R9 and R10 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R11 represents C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- wherein when R6, R7, R8, R9, R10 or R11 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group, such C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group may be optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR15R16, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R12, R13 and R14 independently represent H or C1-C6 alkyl;
- or R13 and R14 together with the nitrogen atom to which they are bound can form a heterocyclic ring;
- R15 and R16 independently represent H, C(O)R12, SO2R17 or C1-C6 alkyl;
- or
- R15 and R16 together with the nitrogen atom to which they are bound can form a heterocyclic ring;
- R17 represents CG-C6 alkyl;
- and wherein Het represents an optionally substituted four- to twelve-membered heterocyclic group, which group contains one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof;
- with the proviso that when Y is CH and X is O and A is C(O) then R1, R3 and R4 each do not represent C1-C6 alkyl and R2 does not represent C1-C6 alkyl or C3-C6 cycloalkyl and
- with the further proviso that when Y is CH and X is O and A is CH(OH) then R1 and R3 each do not represent C1-C6 alkyl and R2 does not represent C1-C6 alkyl or C3-C6 cycloalkyl and R4 is not phenyl or C1-C5 alkyl optionally substituted with up to 2 substituents selected from hydroxy, phenyl, NR9R10 or OC(O)R6 wherein R9 and R10 are H, (C1-C6)alkyl, (C1-C6)alkylphenyl or phenyl groups optionally substituted by hydroxy or OR12 and R6 is (C1-C6)alkyl optionally substituted by halogen or OR12 and wherein OR12 is O(C1-C6)alkyl.
29 more elements
Compounds of general formula (I) as defined hereinbefore wherein:
- A represents C═O;
- X represents O or NR5;
- Y represents CH or N;
- R1 and R2 independently represent H, Het, C1-C6 alkylHet, aryl, C1-C6 alkylaryl, halo, cyano, nitro, OR6, OC(O)R6, C(O)R6, C(O)OR6, NR6C(O)NR7R8, NR6C(O)OR6, OC(O)NR7R8, C(O)NR9R10, NR9R10, SO2NR9R10 or SO2R11;
- R3 and R4 independently represent H, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- R5 independently represents H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R3 and R5 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16, SO2R17;
- wherein when R1, R2, R3 or R4 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group, such C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group may be optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR6, OC(O)R6, C(O)R6, C(O)OR6, NR6C(O)NR7R8, NR6C(O)OR6, OC(O)NR7R8, C(O)NR9R10, NR9R10, SO2NR9R10, SO2R11, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- wherein when R1, R2, R3 or R4 is a Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group which is substituted and/or terminated with one or more substituents selected from:
- C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl, such substituent groups are optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- wherein when R4 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group, such C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group may be optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR6, OC(O)R6, C(O)R6, C(O)OR6, NR6C(O)NR7R8, NR6C(O)OR6, OC(O)NR7R8, C(O)NR9R10, NR9R10, SO2NR9R10, SO2R11, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- wherein when R5 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group which is substituted and/or terminated with one or more substituents selected from:
- C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl, such substituent groups are optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R6, R7 and R8 independently represent H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R7 and R8 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13 R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R9 and R10 independently represent H, C(O)R6, SO2R11, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R9 and R10 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R11 represents C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- wherein when R6, R7, R8, R9, R10 or R11 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group, such C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group may be optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R12, R13 and R14 independently represent H or C1-C6 alkyl;
- or R13 and R14 together with the nitrogen atom to which they are bound can form a heterocyclic ring;
- R15 and R16 independently represent H, C(O)R12, SO2R17 or C1-C6 alkyl;
- or
- R15 and R16 together with the nitrogen atom to which they are bound can form a heterocyclic ring;
- R17 represents C1-C6 alkyl;
- wherein Het represents an optionally substituted four- to twelve-membered heterocyclic group, which group contains one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof.
31 more elements
Compounds according to any of the preceding claims selected from:
- 2-(5-Acetyl-2-butoxy-3-pyridinyl)-7-ethyl-5-methylimidazo[5,1-f][1,2,4]triazin-4(3H)-one;
- 2-(5-Acetyl-2-butoxy-3-pyridinyl)-7-ethyl-5-propylimidazo[5, 1-f][1,2,4]triazin-4(3H)-one;
- 2-(5-Acetyl-2-butoxy-3-pyridinyl)-7-ethyl-5-(4-morpholinylmethyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one;
- or
- 2-(5-Acetyl-2-butoxy-3-pyridinyl)-7-ethyl-5-(4-morpholinylethyl)imidazo[5,1-f][1,2,4]triazin-4(3H)-one
- and pharmaceutically acceptable salts, solvates and prodrugs thereof.
3 more elements
Compounds of general formula (I):
- 45
- or pharmaceutically or veterinarily acceptable salts, solvates, polymorphs or pro-drugs thereof wherein:
- A represents CHOH or C═O;
- X represents O or NR5;
- Y represents CH or N;
- R1 and R2 independently represent H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl, C1-C6 alkylaryl, halo, cyano, nitro, OR6, OC(O)R6, C(O)R6, C(O)OR6, NR6C(O)NR7R8, NR6C(O)OR6, OC(O)NR7R8, C(O)NR9R10, NR9R10, SO2NR9R10 or SO2R11;
- R3, R4 and R5 independently represent H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R3 and R5 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- wherein when R1, R2, R3, R4 or R5 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group, such C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group may be optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR6, OC(O)R6, C(O)R6, C(O)OR6, NR6C(O)NR7R8, NR6C(O)OR6, OC(O)NR7R8, C(O)NR9R10, NR9R10, SO2NR9R10, SO2R11, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- wherein when R1, R2, R3, R4 or R5 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl and C1-C6 alkylaryl group which is substituted and/or terminated with one or more substituents selected from:
- C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl, such substituent groups are optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R6, R7 and R8 independently represent H, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R7 and R8 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R11;
- R9 and R10 independently represent H, C(O)R6, SO2R11, C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- or R9 and R10 together with the nitrogen atom to which they are bound can form a heterocyclic ring which is optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13R14, NR12C(O)OR12, OC(O)NR13 R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R11 represents C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl;
- wherein when R6, R7, R8, R9, R10 or R11 is a C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group, such C1-C6 alkyl, Het, C1-C6 alkylHet, aryl or C1-C6 alkylaryl group may be optionally substituted and/or terminated with one or more substituents selected from:
- halo, cyano, nitro, OR12, OC(O)R12, C(O)R12, C(O)OR12, NR12C(O)NR13 R14, NR12C(O)OR12, OC(O)NR13R14, C(O)NR15R16, NR15R16, SO2NR15R16 or SO2R17;
- R12, R13 and R14 independently represent H or C1-C6 alkyl;
- or R13 and R14 together with the nitrogen atom to which they are bound can form a heterocyclic ring;
- R15 and R16 independently represent H, C(O)R12, SO2R17 or C1-C6 alkyl or R15 and R16 together with the nitrogen atom to which they are bound can form a heterocyclic ring;
- R17 represents C1-C6 alkyl;
- Het represents an optionally substituted four- to twelve-membered heterocyclic group, which group contains one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof.
25 more elements
Compounds according to any of the preceding claims for use as a pharmaceutical.
Compounds as defined in any of the preceding claims for use as an animal medicament.
A formulation comprising a compound as defined in any of the preceding claims in admixture with a pharmaceutically or veterinarily acceptable adjuvant, diluent or carrier.
The use of a compound as defined in any of the preceding claims in the manufacture of a medicament for the curative or prophylactic treatment of a medical condition for which inhibition of cGMP PDE5 is desired.
A method of treating or preventing a medical condition for which inhibition of cGMP PDE5 is desired, which comprises administering a therapeutically effective amount of a compound as claimed in any of the preceding claims to a patient in need of such treatment.
Dependencies are inferred from the claim text.