# US 2008/0188503 A1 · New Compounds II > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2008/0188503 A1 - Document ID: US20080188503A1 - Status: Published application - Kind: A1 - Application number: 11/769,113 - Filed: 2007-06-27 - Published: 2008-08-07 - Earliest claimed: 2006-06-27 - Assignees: AstraZenaca AB - Inventors: Jeremy Burrows; Fernando Huerta; Tobias Rein; Didier Rotticci; Karin Staaf; Dominika Turek - Web page: https://patentgrep.com/patent/US20080188503A1 ## CPC - C07D 403/14: containing three or more hetero rings - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 17/14: for baldness or alopecia - A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease - A61P 19/10: for osteoporosis - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia - A61P 25/16: Anti-Parkinson drugs - A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia - A61P 25/24: Antidepressants - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D 403/04: directly linked by a ring-member-to-ring-member bond - C07D 405/14: containing three or more hetero rings - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to a compound of formula (I): as a free base or a pharmaceutically acceptable salt thereof. The present invention also relates to pharmaceutical formulations containing said compound and to the use of said compound in therapy. The present invention further relates to a process for the preparation of the compound of formula (I). ## Claims ### Claim at position 1 1-84. (canceled) ### Claim 85 A compound of formula (I): wherein: A is heterocyclyl or carbocyclyl; wherein said heterocyclyl or carbocyclyl is optionally substituted on carbon by one or more R1 and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group —R5—R7, with the proviso that said carbocyclyl is not phenyl; R1 is selected from halo, nitro, cyano, hydroxy, amino, sulphamoyl, carbamoyl, C1-3alkyl, a carbocyclyl, a heterocyclyl and a group —R6—R7, wherein said C1-3alkyl is optionally substituted by one or more halo and wherein said carbocyclyl or heterocyclyl optionally forms a conjugated ring system together with A; R2 is selected from halo, nitro, trifluoromethyl, trifluoromethoxy and cyano; R3 is selected from methyl, C6alkyl, C6alkenyl, C6alkynyl, a 6-membered non-aromatic carbocyclyl and a 6-membered non-aromatic heterocyclyl, wherein said C6alkyl, C6alkenyl, C6alkynyl, carbocyclyl or heterocyclyl is optionally substituted by one or more halo, cyano, trifluoromethoxy, C1-3haloalkyl or C1-3alkyl; R4 is selected from hydrogen, C1-3alkyl, cyano and C1-3haloalkyl, wherein said C1-3alkyl or C1-3haloalkyl is optionally substituted with one or more OR8; wherein R8 is independently selected from hydrogen, C1-6alkyl or C1-6haloalkyl; R5 is selected from —C(O)N(R9)—, —S(O)Z—, —SO2N(R10)—, —SO2O—, —C(O)—, —C(O)O— and (—CH2—)m; wherein R9 and R10 are independently selected from hydrogen or C1-6alkyl and wherein said C1-6alkyl is optionally substituted by one or more R19; and wherein m is 0, 1, 2 or 3 and wherein z is 1 or 2; R6 is selected from —O—, —N(R11)C(O)—, —C(O)N(R12)—, —S(O)r—, —SO2N(R13)—, —N(R14)SO2—, —(CH2)pN(R15)—, —OSO2—, —C(O)—, —C(O)O—, —N(R16)C(O)O—, —N(R17)C(O)N(R18)—, and (—CH2—)n; wherein R11, R12, R13, R14, R15, R16, R17 and R18 are independently selected from hydrogen or C1-6alkyl and wherein said C1-6alkyl is optionally substituted by one or more R19; and wherein n is 0, 1, 2 or 3 and wherein p is 0, 1, 2 or 3 and wherein r is 0, 1 or 2; R7 is selected from hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, —C1-4alkylcarbocyclyl, —C1-4alkylheterocyclyl, carbocyclyl and heterocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21; R19 and R20 are independently selected from halo, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, sulphamoyl, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkoxyC1-6alkoxy, C1-6alkanoyl, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a, C1-6alkoxycarbonyl, N—(C1-6alkyl)sulphamoyl, N,N—(C1-6alkyl)2sulphamoyl, C1-6alkylsulphonylamino, carbocyclyl, heterocyclyl, carbocyclylC1-6alkyl-R22—, heterocyclylC1-6alkyl-R23—, carbocyclyl-R24— and heterocyclyl-R25—; wherein a is 0, 1 or 2; and wherein R19 and R20 independently of each other is optionally substituted on carbon by one or more R26; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen is optionally substituted by a group selected from R27; R22, R23, R24 and R25 are independently selected from —O—, —N(R28)—, —C(O)—, —N(R29)C(O)—, —C(O)N(R30)—, —S(O)S—, —SO2N(R31)— and —N(R32)SO2—; wherein R23, R29, R30, R31 and R32 are independently selected from hydrogen or C1-6alkyl and s is 0, 1 or 2; R21 and R27 are independently selected from C1-6alkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)carbamoyl, carbocyclyl, heterocyclyl, —C1-6alkylcarbocylyl, —C1-6alkylheterocyclyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl; wherein R21 and R27 independently of each other is optionally substituted on carbon by one or more R33; and R26 and R33 are independently selected from halo, nitro, cyano, —C1-3alkylhydroxy, —C1-3alkylmethoxy, —C1-3alkylethoxy, —C1-3alkylisopropoxy, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, cyclopropyl, cyclobutyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulphinyl, ethylsulphinyl, mesyl, ethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N-methylsulphamoyl, N-ethylsulphamoyl, N,N-dimethylsulphamoyl, N,N-diethylsulphamoyl, N-methyl-N-ethylsulphamoyl, carbocycle and heterocycle; wherein said carbocycle or heterocycle is optionally substituted by halo, methyl, trifluoromethyl, cyano or ethyl; as a free base or a pharmaceutically acceptable salt thereof. ### Claim 86 (depends on 85) A compound according to claim 85, wherein A is heterocyclyl or carbocyclyl; wherein said heterocyclyl or carbocyclyl is optionally substituted on carbon by one or more R1 and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by —R5—R7, with the proviso that said carbocycle is not phenyl; R1 is selected from halo, nitro, cyano, hydroxy, amino, sulphamoyl, carbamoyl, C1-3alkyl, a carbocyclyl, a heterocyclyl and a group —R6—R7, wherein said C1-3alkyl is optionally substituted by one or more halo and wherein said carbocyclyl or heterocyclyl optionally forms a conjugated ring system together with A; R2 is selected from halo, trifluoromethyl, trifluoromethoxy and cyano; R3 is selected from methyl, C6alkyl, C6alkenyl, C6alkynyl, a 6-membered non-aromatic carbocyclyl and a 6-membered non-aromatic heterocyclyl, wherein said C6alkyl, C6alkenyl, C6alkynyl, carbocyclyl or heterocyclyl is optionally substituted by one or more halo, cyano, trifluoromethoxy, C1-3haloalkyl or C1-3alkyl; R4 is selected from hydrogen, C1-3alkyl, cyano and C1-3haloalkyl, wherein said C1-3alkyl or C1-3haloalkyl is optionally substituted with one or more OR8; wherein R8 is independently selected from hydrogen, C1-6alkyl or C1-6haloalkyl; R5 is selected from —C(O)N(R9)—, —S(O)Z—, —SO2N(R10)—, —SO2O—, —C(O)—, —C(O)O— and (—CH2—)m; wherein R9 and R10 are independently selected from hydrogen or C1-6alkyl and wherein said C1-6alkyl is optionally substituted by one or more R19; and wherein m is 0, 1, 2 or 3 and wherein z is 1 or 2; R6 is selected from —O—, —N(R11)C(O)—, —C(O)N(R12)—, —S(O)r—, —SO2N(R13)—, —N(R14)SO2—, —(CH2)pN(R15)—, —OSO2—, —C(O)—, —C(O)O—, —N(R16)C(O)O—, —N(R17)C(O)N(R18)—, and (—CH2—)n; wherein R11, R12, R13, R14, R15, R16, R17 and R18 are independently selected from hydrogen or C1-6alkyl and wherein said C1-6alkyl is optionally substituted by one or more R19; wherein n is 0, 1, 2 or 3 and wherein p is 0, 1, 2 or 3 and wherein r is 0, 1 or 2; R7 is selected from hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, —C1-4alkylcarbocyclyl, —C1-4alkylheterocyclyl, carbocyclyl and heterocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21; R19 and R20 are independently selected from halo, nitro, cyano, hydroxy, amino, carboxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkoxyC1-6alkoxy, C1-6alkanoyl, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, C1-6alkylS(O)a, carbocyclyl, heterocyclyl, carbocyclylC1-6alkyl-R22—, heterocyclylC1-6alkyl-R23—, carbocyclyl-R24— and heterocyclyl-R25—; wherein a is 0, 1 or 2; and wherein R19 and R20 independently of each other is optionally substituted on carbon by one or more R26; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen is optionally substituted by a group selected from R27; R22, R23, R24 and R25 are independently selected from —O—, —N(R28)—, —C(O)—, —N(R29)C(O)—, —C(O)N(R30)—, —S(O)S—, —SO2N(R31)— and —N(R32)SO2—; wherein R23, R29, R30, R31 and R32 are independently selected from hydrogen or C1-6alkyl and s is 0, 1 or 2; R21 and R27 are independently selected from C1-6alkyl, C1-6alkanoyl, C1-6alkylsulphonyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)carbamoyl, carbocyclyl, heterocyclyl, —C1-6alkylcarbocylyl, —C1-6alkylheterocyclyl, benzyloxycarbonyl, benzoyl and phenylsulphonyl; wherein R21 and R27 independently of each other is optionally substituted on carbon by one or more R33; and R26 and R33 are independently selected from halo, nitro, cyano, —C1-3alkylhydroxy, —C1-3alkylmethoxy, —C1-3alkylethoxy, —C1-3alkylisopropoxy, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, cyclopropyl, cyclobutyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, methylthio, ethylthio, methylsulphinyl, ethylsulphinyl, mesyl, ethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N,N-dimethylsulphamoyl, N,N-diethylsulphamoyl, N-methyl-N-ethylsulphamoyl, carbocycle and heterocycle; wherein said carbocycle or heterocycle is optionally substituted by halo, methyl, trifluoromethyl, cyano or ethyl. ### Claim 87 (depends on 85, 86) A compound according to claim 85 or 86, wherein A is heterocyclyl or carbocyclyl; wherein said heterocyclyl or carbocyclyl is optionally substituted on carbon by one or more R1 and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by —R5—R7 with the proviso that said carbocyclyl is not phenyl; R1 is selected from C1-3alkyl, a carbocyclyl, a heterocyclyl and a group —R5—R7, wherein said C1-3alkyl is optionally substituted by one or more halo and wherein said carbocyclyl or heterocyclyl optionally forms a conjugated ring system together with A; R2 is selected from halo, trifluoromethyl, trifluoromethoxy and cyano; R3 is selected from methyl, C6alkyl, a 6-membered non-aromatic carbocyclyl and a 6-membered non-aromatic heterocyclyl, wherein said C6alkyl, carbocyclyl or heterocyclyl is optionally substituted by one or more halo, cyano, trifluoromethoxy, C1-3haloalkyl or C1-3alkyl; R4 is selected from hydrogen, C1-3alkyl, cyano and C1-3haloalkyl, wherein said C1-3alkyl or C1-3haloalkyl is optionally substituted with one or more OR8; wherein R8 is independently selected from hydrogen, C1-6alkyl or C1-6haloalkyl; R5 is selected from —C(O)N(R9)—, —S(O)Z—, —SO2N(R11)—, —SO2O—, —C(O)—, —C(O)O— and (—CH2—)m; wherein R9 and R10 are independently selected from hydrogen or C1-6alkyl and wherein said C1-6alkyl is optionally substituted by one or more R19; and wherein m is 0, 1, 2 or 3 and wherein z is 1 or 2; R6 is selected from —O—, —N(R11)C(O)—, —C(O)N(R12)—, —S(O)r—, —SO2N(R13)—, —N(R14)SO2—, —(CH2)pN(R15)—, —OSO2—, —C(O)—, —C(O)O—, —N(R16)C(O)O—, —N(R17)C(O)N(R18)—, and (—CH2—)n; wherein R11, R12, R13, R14, R15, R16, R17 and R18 are independently selected from hydrogen or C1-6alkyl and wherein said C1-6alkyl is optionally substituted by one or more R19; and wherein n is 0, 1, 2 or 3 and wherein p is 0, 1, 2 or 3 and wherein r is 0, 1 or 2; R7 is selected from hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, —C1-4alkylcarbocyclyl, —C1-4alkylheterocyclyl, carbocyclyl and heterocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21; R19 and R20 are independently selected from halo, nitro, cyano, hydroxy, amino, carboxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, C1-6alkoxyC1-6alkoxy, C1-6alkanoyl, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, C1-6alkanoylamino, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)2carbamoyl, carbocyclyl, heterocyclyl, carbocyclylC1-6alkyl-R22—, heterocyclylC1-6alkyl-R23—, carbocyclyl-R24— and heterocyclyl-R25—; and wherein R19 and R20 independently of each other is optionally substituted on carbon by one or more R26; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen is optionally substituted by a group selected from R27; R22, R23, R24 and R25 are independently selected from —O—, —N(R28)—, —C(O)—, —N(R29)C(O)—, —C(O)N(R30)—, —S(O)S—, —SO2N(R31)— and —N(R32)SO2—; wherein R23, R29, R30, R31 and R32 are independently selected from hydrogen or C1-6alkyl and s is 0, 1 or 2; R21 and R27 are independently selected from C1-6alkyl, C1-6alkanoyl, C1-6alkoxycarbonyl, carbamoyl, N—(C1-6alkyl)carbamoyl, N,N—(C1-6alkyl)carbamoyl, carbocyclyl, heterocyclyl, —C1-6alkylcarbocylyl, —C1-6alkylheterocyclyl, benzoyl and phenylsulphonyl; wherein R21 and R27 independently of each other is optionally substituted on carbon by one or more R33; and R26 and R33 are independently selected from halo, nitro, cyano, —C1-3alkylhydroxy, —C1-3alkylmethoxy, —C1-3alkylethoxy, —C1-3alkylisopropoxy, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulphamoyl, methyl, ethyl, cyclopropyl, cyclobutyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, methylthio, ethylthio, methylsulphinyl, mesyl, ethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N,N-diethylsulphamoylcarbocycle and heterocycle; wherein said carbocycle or heterocycle is optionally substituted by halo, methyl, trifluoromethyl, cyano or ethyl. ### Claim 88 (depends on 85) A compound according to claim 85, wherein R2 is halo or cyano. ### Claim 89 (depends on 85) A compound according to claim 85, wherein R2 is halo. ### Claim 90 (depends on 89) A compound according to claim 89, wherein R2 is fluoro. ### Claim 91 (depends on 85) A compound according to claim 85, wherein R3 is selected from a 6-membered non-aromatic carbocyclyl or a 6-membered non-aromatic heterocyclyl, wherein said carbocyclyl or heterocyclyl is optionally substituted by one or more halo, cyano, trifluoromethoxy, C1-3haloalkyl or C1-3alkyl. ### Claim 92 (depends on 90) A compound according to claim 90, wherein R3 is selected from a 6-membered non-aromatic carbocyclyl or a 6-membered non-aromatic heterocyclyl, wherein said carbocyclyl or heterocyclyl is optionally substituted by one or more halo, cyano, trifluoromethoxy, C1-3haloalkyl or C1-3alkyl. ### Claim 93 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R3 is a non-aromatic 6-membered heterocyclyl. ### Claim 94 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R3 is 3-tetrahydropyranyl or 4-tetrahydropyranyl. ### Claim 95 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R3 is 4-tetrahydropyranyl. ### Claim 96 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R4 is C1-3alkyl or C1-3haloalkyl, wherein said C1-3alkyl or C1-3haloalkyl is optionally substituted with one or more OR8; wherein R8 is independently selected from hydrogen, C1-6alkyl or C1-6haloalkyl. ### Claim 97 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R4 is C1-3alkyl. ### Claim 98 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R4 is methyl. ### Claim 99 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein A is heterocyclyl; wherein said heterocyclyl is optionally substituted on carbon by one or more R1 and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by —R5—R7. ### Claim 100 (depends on 98) A compound according to claim 98, wherein A is 4-piperidinyl, 4-tetrahydropyranyl, 3-pyridyl, 4-pyridyl, 5-pyrimidinyl, 4-isoquinolinyl or 2-pyridyl. ### Claim 101 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein A is a non-aromatic carbocyclyl; wherein said carbocyclyl is optionally substituted on carbon by one or more R1. ### Claim 102 (depends on 101) A compound according to claim 101, wherein said non-aromatic carbocyclyl is cyclohexyl. ### Claim 103 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R1 is C1-3alkyl, wherein said C1-3alkyl may be optionally substituted by one or more halo. ### Claim 104 (depends on 103) A compound according to claim 103, wherein R1 is methyl. ### Claim 105 (depends on 103) A compound according to claim 103, wherein R1 is C1-3alkyl substituted by one or more halo. ### Claim 106 (depends on 105) A compound according to claim 105, wherein R1 is trifluoromethyl. ### Claim 107 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R1 is selected from a group —R6—R7. ### Claim 108 (depends on 107) A compound according to claim 107, wherein R6 is selected from —O—, —(CH2)pN(R15)—, —C(O)—, —C(O)O—, —N(R16)C(O)O—, and (—CH2—)n. ### Claim 109 (depends on 108) A compound according to claim 108, wherein R6 is selected from —O—, —(CH2)pN(R15)—, —C(O)— and (—CH2—)n. ### Claim 110 (depends on 108) A compound according to claim 108, wherein R6 is (—CH2—)n and n is 0 or 1. ### Claim 111 (depends on 109) A compound according to claim 109, wherein R6 is (—CH2—)n and n is 0 or 1. ### Claim 112 (depends on 108) A compound according to claim 108, wherein R6 is —(CH2)pN(R15)— and p is 1. ### Claim 113 (depends on 109) A compound according to claim 109, wherein R6 is —(CH2)pN(R15)— and p is 1. ### Claim 114 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R5 is selected from —C(O)N(R9)—, —S(O)Z—, —C(O)—, —C(O)O— and (—CH2—)m; and wherein m is 0 or 1 and wherein z is 2. ### Claim 115 (depends on 114) A compound according to claim 114, wherein R5 is selected from, —S(O)Z—, —C(O)—, —C(O)O— and (—CH2—)m; and wherein m is 0 or 1 and wherein z is 2. ### Claim 116 (depends on 85, 92) A compound according to claim 85 or claim 92, wherein R7 is selected from hydrogen, C1-6alkyl, —C1-4alkylcarbocyclyl, —C1-4alkylheterocyclyl, carbocyclyl and heterocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21. ### Claim 117 (depends on 107) A compound according to claim 107, wherein R7 is selected from hydrogen, C1-6alkyl, —C1-4alkylcarbocyclyl, —C1-4alkylheterocyclyl, carbocyclyl and heterocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21. ### Claim 118 (depends on 116) A compound according to claim 116, wherein R7 is C1-6alkyl, heterocyclyl or carbocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21. ### Claim 119 (depends on 117) A compound according to claim 117, wherein R7 is C1-6alkyl, heterocyclyl or carbocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21. ### Claim 120 (depends on 117, 118) A compound according to claim 117 or 118, wherein R7 is C1-6alkyl. ### Claim 121 (depends on 117, 118) A compound according to claim 117 or 118, wherein R7 is methyl. ### Claim 122 (depends on 98, 99) A compound according to claim 98 or claim 99, wherein A is not substituted. ### Claim 123 (depends on 85) A compound according to claim 85, wherein A is heterocyclyl or carbocyclyl; wherein said heterocyclyl or carbocyclyl is optionally substituted on carbon by one or more R1 and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group —R5—R7, with the proviso that said carbocyclyl is not phenyl; R1 is selected from C1-3alkyl, a carbocyclyl, and a group —R6—R7, wherein said C1-3alkyl is optionally substituted by one or more halo; R2 is halo; R3 is a 6-membered non-aromatic heterocyclyl; R4 is C1-3alkyl; R5 is selected from —S(O)Z—, —C(O)—, —C(O)O— and (—CH2—)m; and wherein m is 0 or 1 and wherein z is 2; R6 is selected from —O—, —(CH2)pN(R15)—, —C(O)—, and (—CH2—)n; wherein R15 is selected from hydrogen or C1-6alkyl and wherein said C1-6alkyl is optionally substituted by one or more R19; and wherein n is 0 or 1 and wherein p is 1; R7 is selected from hydrogen, C1-6alkyl, —C1-4alkylcarbocyclyl, —C1-4alkylheterocyclyl, carbocyclyl and heterocyclyl; wherein R7 may be optionally substituted on carbon by one or more R20; and wherein if said heterocyclyl contains an —NH— moiety that nitrogen may be optionally substituted by a group selected from R21; R19 and R20 are independently selected from halo, cyano, C1-6alkyl, C1-6alkoxy, N—(C1-6alkyl)amino, N,N—(C1-6alkyl)2amino, carbocyclyl and heterocyclyl; and wherein R19 and R20 independently of each other is optionally substituted on carbon by one or more R26; R21 is C1-6alkanoyl or heterocyclyl; and R26 is selected from halo, cyano, —C1-3alkylmethoxy, hydroxy, methyl, heterocycle and methoxy; wherein said carbocycle or heterocycle is optionally substituted by halo. ### Claim 124 (depends on 123) A compound according to claim 123, wherein R2 is fluoro. ### Claim 125 (depends on 123) A compound according to claim 123, wherein R3 is 4-tetrahydropyranyl. ### Claim 126 (depends on 123) A compound according to claim 123, wherein R4 is methyl. ### Claim 127 (depends on 85) A compound according to claim 85, wherein A is heterocyclyl wherein said heterocyclyl is optionally substituted, on carbon, by one or more R1; R1 is C1-3alkyl or a group —R6—R7, wherein said C1-3alkyl may be optionally substituted by one or more halo; R2 is halo; R3 is a 6-membered non-aromatic heterocyclyl; R4 is C1-3alkyl; R6 is —O—, or —C(O)—; and R7 is C1-6alkyl. ### Claim 128 (depends on 85) A pharmaceutical formulation comprising as active ingredient a therapeutically effective amount of a compound according to claim 85 in association with pharmaceutically acceptable excipients, carriers or diluents. ### Claim 129 (depends on 85) A method of prevention and/or treatment of conditions associated with glycogen synthase kinase-3, comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound salt as defined in claim 85. ### Claim 130 (depends on 85) A method of prevention and/or treatment of cognitive disorders, comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a salt compound as defined in claim 85. ### Claim 131 (depends on 130) The method according to claim 130, wherein the cognitive disorder is dementia, Cognitive Deficit in Schizophrenia (CDS), Mild Cognitive Impairment (MCI), Age-Associated Memory Impairment (AAMI), Age-Related Cognitive Decline (ARCD) or Cognitive Impairement No Dementia (CIND). ### Claim 132 (depends on 131) The method according to claim 131, wherein the disease is Cognitive Deficit in Schizophrenia. ### Claim 133 (depends on 131) The method according to claim 131, wherein the dementia is associated with neurofibrillar tangle pathologies. ### Claim 134 (depends on 131) The method according to claim 131, wherein the dementia is Frontotemporal dementia (FTD), Frontotemporal dementia Parkinson's Type (FTDP), progressive supranuclear palsy (PSP), Pick's Disease, Niemann-Pick's Disease, corticobasal degeneration, traumatic brain injury (TBI) or dementia pugilistica. ### Claim 135 (depends on 131) The method according to claim 131, wherein the dementia is Alzheimer's Disease (AD), Down syndrome, vascular dementia, Parkinson's Disease (PD), postencephelatic parkinsonism, dementia with Lewy bodies, HIV dementia, Huntington's Disease, amyotrophic lateral sclerosis (ALS), motor neuron diseases (MND), Creuztfeld-Jacob's disease or prion diseases. ### Claim 136 (depends on 135) The method according to claim 135, wherein the dementia is Alzheimer's Disease. ### Claim 137 (depends on 135) The method according to claim 135, wherein the treatment is in the delay of the disease progression of Alzheimer's Disease. ### Claim 138 (depends on 85) A method of prevention and/or treatment of attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD) or affective disorders, comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound salt as defined in claim 85. ### Claim 139 (depends on 138) The method according to claim 138, wherein the affective disorders are Bipolar Disorder including acute mania, bipolar depression, bipolar maintenance, major depressive disorders (MDD) including depression, major depression, mood stabilization, schizoaffective disorders including schizophrenia, or dysthymia. ### Claim 140 (depends on 85) A method of prevention and/or treatment of Type I diabetes, Type II diabetes, diabetic neuropathy, alopecia, inflammatory diseases or cancer, comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a salt compound as defined in claim 85. ### Claim 141 (depends on 85) A method of prevention and/or treatment of bone related disorders or conditions comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a salt compound as defined in claim 85. ### Claim 142 (depends on 85) A method of prevention and/or treatment of osteoporosis comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound as defined in claim 85. ### Claim 143 (depends on 85) A method of increasing bone formation comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound as defined in claim 85. ### Claim 144 (depends on 85) A method of increasing cancellous bone formation and/or new bone formation comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound as defined in claim 85. ### Claim 145 (depends on 85) A method of increasing bone mineral density comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound as defined in claim 85. ### Claim 146 (depends on 85) A method of reducing the incidence of fracture comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound as defined in claim 85. ### Claim 147 (depends on 85) A method of enhancing fracture healing comprising administering to a human in need of such prevention and/or treatment a therapeutically effective amount of a compound as defined in claim 85. ### Claim 148 (depends on 85) A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof comprising the following steps: a) reacting a pyrimidine of formula (II): with a compound of formula (III): wherein R1, R2, R3, R4 and A are, unless otherwise specified, as defined in claim 85; wherein A contains an aromatic mono- or bicyclic heterocycle; wherein Y is a displaceable group; and thereafter optionally: b) converting a compound of formula (I) into another compound of formula (I); c) removing any protecting groups; and d) forming a pharmaceutically acceptable salt or in vivo hydrolysable ester.