JP2015537003A5 - - Google Patents

Info

Publication number

JP2015537003A5

JP2015537003A5 JP2015542047A JP2015542047A JP2015537003A5 JP 2015537003 A5 JP2015537003 A5 JP 2015537003A5 JP 2015542047 A JP2015542047 A JP 2015542047A JP 2015542047 A JP2015542047 A JP 2015542047A JP 2015537003 A5 JP2015537003 A5 JP 2015537003A5

Authority

JP

Japan

Prior art keywords

pharmaceutically acceptable

prodrug

polymorph

antipsychotic

solvate

Prior art date

2013-11-14

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

• Espacenet
• Global Dossier
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• 239000003112 inhibitor Substances 0.000 claims description 71
• 150000003839 salts Chemical class 0.000 claims description 70
• 239000012453 solvate Substances 0.000 claims description 69
• 239000000651 prodrug Substances 0.000 claims description 59
• 229940002612 prodrug Drugs 0.000 claims description 59
• -1 polymorph Substances 0.000 claims description 56
• 101710084141 Synaptic vesicle glycoprotein 2A Proteins 0.000 claims description 48
• 239000000203 mixture Substances 0.000 claims description 47
• 230000000561 anti-psychotic effect Effects 0.000 claims description 38
• 150000004677 hydrates Chemical class 0.000 claims description 36
• 229940126027 positive allosteric modulator Drugs 0.000 claims description 35
• 239000000164 antipsychotic agent Substances 0.000 claims description 33
• 208000020925 Bipolar disease Diseases 0.000 claims description 15
• 201000000980 schizophrenia Diseases 0.000 claims description 15
• CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 claims description 13
• 239000000556 agonist Substances 0.000 claims description 13
• 229960004372 aripiprazole Drugs 0.000 claims description 13
• 229960005017 olanzapine Drugs 0.000 claims description 13
• KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 claims description 13
• 229960000607 ziprasidone Drugs 0.000 claims description 13
• MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 claims description 13
• 239000003795 chemical substances by application Substances 0.000 claims description 12
• 150000001875 compounds Chemical class 0.000 claims description 11
• 230000001225 therapeutic effect Effects 0.000 claims description 11
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
• 102000016193 Metabotropic glutamate receptors Human genes 0.000 claims description 10
• 108010010914 Metabotropic glutamate receptors Proteins 0.000 claims description 10
• 239000003693 atypical antipsychotic agent Substances 0.000 claims description 10
• 229940079593 drug Drugs 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims description 10
• LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 claims description 10
• LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 10
• BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-N 0.000 claims description 9
• 229940005529 antipsychotics Drugs 0.000 claims description 8
• PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 claims description 7
• 229940042053 methotrimeprazine Drugs 0.000 claims description 7
• VRQVVMDWGGWHTJ-CQSZACIVSA-N methotrimeprazine Chemical compound C1=CC=C2N(C[C@H](C)CN(C)C)C3=CC(OC)=CC=C3SC2=C1 VRQVVMDWGGWHTJ-CQSZACIVSA-N 0.000 claims description 7
• 229960003910 promethazine Drugs 0.000 claims description 7
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• MSYKRHVOOPPJKU-BDAKNGLRSA-N brivaracetam Chemical compound CCC[C@H]1CN([C@@H](CC)C(N)=O)C(=O)C1 MSYKRHVOOPPJKU-BDAKNGLRSA-N 0.000 claims description 6
• 229960004002 levetiracetam Drugs 0.000 claims description 6
• HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 claims description 6
• ANWPENAPCIFDSZ-BQBZGAKWSA-N seletracetam Chemical compound CC[C@@H](C(N)=O)N1C[C@@H](C=C(F)F)CC1=O ANWPENAPCIFDSZ-BQBZGAKWSA-N 0.000 claims description 6
• 229950000852 seletracetam Drugs 0.000 claims description 6
• 231100001274 therapeutic index Toxicity 0.000 claims description 6
• MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 claims description 5
• VSWBSWWIRNCQIJ-GJZGRUSLSA-N (R,R)-asenapine Chemical compound O1C2=CC=CC=C2[C@@H]2CN(C)C[C@H]2C2=CC(Cl)=CC=C21 VSWBSWWIRNCQIJ-GJZGRUSLSA-N 0.000 claims description 5
• WSPOMRSOLSGNFJ-AUWJEWJLSA-N (Z)-chlorprothixene Chemical compound C1=C(Cl)C=C2C(=C/CCN(C)C)\C3=CC=CC=C3SC2=C1 WSPOMRSOLSGNFJ-AUWJEWJLSA-N 0.000 claims description 5
• MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 claims description 5
• DKMFBWQBDIGMHM-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-(4-methyl-1-piperidinyl)-1-butanone Chemical compound C1CC(C)CCN1CCCC(=O)C1=CC=C(F)C=C1 DKMFBWQBDIGMHM-UHFFFAOYSA-N 0.000 claims description 5
• MDLAAYDRRZXJIF-UHFFFAOYSA-N 1-[4,4-bis(4-fluorophenyl)butyl]-4-[4-chloro-3-(trifluoromethyl)phenyl]-4-piperidinol Chemical compound C1CC(O)(C=2C=C(C(Cl)=CC=2)C(F)(F)F)CCN1CCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 MDLAAYDRRZXJIF-UHFFFAOYSA-N 0.000 claims description 5
• FEBOTPHFXYHVPL-UHFFFAOYSA-N 3-[1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidinyl]-1H-benzimidazol-2-one Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 FEBOTPHFXYHVPL-UHFFFAOYSA-N 0.000 claims description 5
• PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 claims description 5
• 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 claims description 5
• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 claims description 5
• LREQLEBVOXIEOM-UHFFFAOYSA-N 6-amino-2-methyl-2-heptanol Chemical compound CC(N)CCCC(C)(C)O LREQLEBVOXIEOM-UHFFFAOYSA-N 0.000 claims description 5
• 239000000775 AMPA receptor antagonist Substances 0.000 claims description 5
• VMIYHDSEFNYJSL-UHFFFAOYSA-N Bromazepam Chemical compound C12=CC(Br)=CC=C2NC(=O)CN=C1C1=CC=CC=N1 VMIYHDSEFNYJSL-UHFFFAOYSA-N 0.000 claims description 5
• RKLNONIVDFXQRX-UHFFFAOYSA-N Bromperidol Chemical compound C1CC(O)(C=2C=CC(Br)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 RKLNONIVDFXQRX-UHFFFAOYSA-N 0.000 claims description 5
• 229940124802 CB1 antagonist Drugs 0.000 claims description 5
• 102000017927 CHRM1 Human genes 0.000 claims description 5
• 101150073075 Chrm1 gene Proteins 0.000 claims description 5
• KAAZGXDPUNNEFN-UHFFFAOYSA-N Clotiapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2SC2=CC=C(Cl)C=C12 KAAZGXDPUNNEFN-UHFFFAOYSA-N 0.000 claims description 5
• PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 claims description 5
• 102000018899 Glutamate Receptors Human genes 0.000 claims description 5
• 108010027915 Glutamate Receptors Proteins 0.000 claims description 5
• 108010024636 Glutathione Proteins 0.000 claims description 5
• 239000004471 Glycine Substances 0.000 claims description 5
• 229940115480 Histamine H3 receptor antagonist Drugs 0.000 claims description 5
• 102000010909 Monoamine Oxidase Human genes 0.000 claims description 5
• 108010062431 Monoamine oxidase Proteins 0.000 claims description 5
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 claims description 5
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 claims description 5
• 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 5
• 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 5
• 108010025020 Nerve Growth Factor Proteins 0.000 claims description 5
• 102000007072 Nerve Growth Factors Human genes 0.000 claims description 5
• 102000050267 Neurotensin Human genes 0.000 claims description 5
• 101800001814 Neurotensin Proteins 0.000 claims description 5
• XCWPUUGSGHNIDZ-UHFFFAOYSA-N Oxypertine Chemical compound C1=2C=C(OC)C(OC)=CC=2NC(C)=C1CCN(CC1)CCN1C1=CC=CC=C1 XCWPUUGSGHNIDZ-UHFFFAOYSA-N 0.000 claims description 5
• RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 claims description 5
• KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 claims description 5
• 229960005054 acepromazine Drugs 0.000 claims description 5
• NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 claims description 5
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• 229960002507 benperidol Drugs 0.000 claims description 5
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• 229960004037 bromperidol Drugs 0.000 claims description 5
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• ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 claims description 5
• 229960001552 chlorprothixene Drugs 0.000 claims description 5
• NJMYODHXAKYRHW-DVZOWYKESA-N cis-flupenthixol Chemical compound C1CN(CCO)CCN1CC\C=C\1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C2/1 NJMYODHXAKYRHW-DVZOWYKESA-N 0.000 claims description 5
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• QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 claims description 5
• 229960003529 diazepam Drugs 0.000 claims description 5
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 5
• 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 5
• 229940005501 dopaminergic agent Drugs 0.000 claims description 5
• 229960000394 droperidol Drugs 0.000 claims description 5
• RMEDXOLNCUSCGS-UHFFFAOYSA-N droperidol Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CC=C(N2C(NC3=CC=CC=C32)=O)CC1 RMEDXOLNCUSCGS-UHFFFAOYSA-N 0.000 claims description 5
• 229960002419 flupentixol Drugs 0.000 claims description 5
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• AXKPFOAXAHJUAG-UHFFFAOYSA-N pipamperone Chemical compound C1CC(C(=O)N)(N2CCCCC2)CCN1CCCC(=O)C1=CC=C(F)C=C1 AXKPFOAXAHJUAG-UHFFFAOYSA-N 0.000 claims description 5
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