JP2006525276A5 - - Google Patents

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Publication number

JP2006525276A5

JP2006525276A5 JP2006505375A JP2006505375A JP2006525276A5 JP 2006525276 A5 JP2006525276 A5 JP 2006525276A5 JP 2006505375 A JP2006505375 A JP 2006505375A JP 2006505375 A JP2006505375 A JP 2006505375A JP 2006525276 A5 JP2006525276 A5 JP 2006525276A5

Authority

JP

Japan

Prior art keywords

pharmaceutical composition

disease

group

composition according

impaired

Prior art date

2004-05-05

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

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• Espacenet
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• 150000001875 compounds Chemical class 0.000 claims description 15
• 239000003112 inhibitor Substances 0.000 claims description 8
• -1 benzoxiathiol Chemical compound 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
• 201000010099 disease Diseases 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 3
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims 9
• 230000001771 impaired effect Effects 0.000 claims 5
• 239000003814 drug Substances 0.000 claims 4
• 229960002429 proline Drugs 0.000 claims 3
• 235000013930 proline Nutrition 0.000 claims 3
• 150000003839 salts Chemical class 0.000 claims 3
• 239000005541 ACE inhibitor Substances 0.000 claims 2
• 208000024827 Alzheimer disease Diseases 0.000 claims 2
• 201000010374 Down Syndrome Diseases 0.000 claims 2
• 102000004190 Enzymes Human genes 0.000 claims 2
• 108090000790 Enzymes Proteins 0.000 claims 2
• 208000023105 Huntington disease Diseases 0.000 claims 2
• 208000018737 Parkinson disease Diseases 0.000 claims 2
• 206010044688 Trisomy 21 Diseases 0.000 claims 2
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
• 230000001537 neural effect Effects 0.000 claims 2
• 150000003148 prolines Chemical group 0.000 claims 2
• ORZXYSPOAVJYRU-HOTGVXAUSA-N z-pro-prolinal Chemical compound O=C[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)OCC=2C=CC=CC=2)CCC1 ORZXYSPOAVJYRU-HOTGVXAUSA-N 0.000 claims 2
• RICKQPKTSOSCOF-HKUYNNGSSA-N (3s)-2-[(2s)-2-amino-3-(1h-indol-3-yl)propanoyl]-3,4-dihydro-1h-isoquinoline-3-carboxylic acid Chemical compound C1C2=CC=CC=C2C[C@@H](C(O)=O)N1C(=O)[C@@H](N)CC1=CNC2=CC=CC=C12 RICKQPKTSOSCOF-HKUYNNGSSA-N 0.000 claims 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims 1
• GWHQHAUAXRMMOT-MERQFXBCSA-N 2,3-dihydroxybutanedioic acid;[3-[(1s)-1-(dimethylamino)ethyl]phenyl] n-ethyl-n-methylcarbamate Chemical group OC(=O)C(O)C(O)C(O)=O.CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 GWHQHAUAXRMMOT-MERQFXBCSA-N 0.000 claims 1
• FSUYMKXZLQOFQY-UHFFFAOYSA-N 3,4-dihydro-1,2-benzodithiine Chemical compound C1=CC=C2SSCCC2=C1 FSUYMKXZLQOFQY-UHFFFAOYSA-N 0.000 claims 1
• NTOIMCSZPGZTND-UHFFFAOYSA-N 3,4-dihydro-1,2-benzoxathiine Chemical compound C1=CC=C2OSCCC2=C1 NTOIMCSZPGZTND-UHFFFAOYSA-N 0.000 claims 1
• YKRQYGZEUVWOFN-UHFFFAOYSA-N 3a,4,5,9b-tetrahydro-1h-benzo[e]indol-2-amine Chemical group C1CC2=CC=CC=C2C2C1N=C(N)C2 YKRQYGZEUVWOFN-UHFFFAOYSA-N 0.000 claims 1
• WHGMHGPIJZTKTI-UHFFFAOYSA-N 3h-1,2-benzodithiole Chemical compound C1=CC=C2CSSC2=C1 WHGMHGPIJZTKTI-UHFFFAOYSA-N 0.000 claims 1
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• VFFZWMWTUSXDCB-ZDUSSCGKSA-N 6-[2-[[2-[(2s)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]ethylamino]pyridine-3-carbonitrile Chemical compound N1([C@@H](CCC1)C#N)C(=O)CNCCNC1=CC=C(C#N)C=N1 VFFZWMWTUSXDCB-ZDUSSCGKSA-N 0.000 claims 1
• GEDJUAKXFJRZSG-UHFFFAOYSA-N 7-[3-[(3-acetylphenoxy)methyl]-1,5-dimethylpyrazol-4-yl]-3-(3-naphthalen-1-yloxypropyl)-1H-indole-2-carboxylic acid Chemical compound CC(=O)c1cccc(OCc2nn(C)c(C)c2-c2cccc3c(CCCOc4cccc5ccccc45)c([nH]c23)C(O)=O)c1 GEDJUAKXFJRZSG-UHFFFAOYSA-N 0.000 claims 1
• QSAIYEIQUKKBDM-VYRBHSGPSA-N 9H-fluoren-9-ylmethyl N-[(2S)-1-(2-cyanopyrrolidin-1-yl)-1-oxopropan-2-yl]carbamate Chemical group C1=CC=CC=2C3=CC=CC=C3C(C1=2)COC(=O)N[C@@H](C)C(=O)N1C(CCC1)C#N QSAIYEIQUKKBDM-VYRBHSGPSA-N 0.000 claims 1
• 208000007848 Alcoholism Diseases 0.000 claims 1
• 208000019901 Anxiety disease Diseases 0.000 claims 1
• 208000028698 Cognitive impairment Diseases 0.000 claims 1
• 206010012289 Dementia Diseases 0.000 claims 1
• 108010016626 Dipeptides Proteins 0.000 claims 1
• 206010013752 Drug withdrawal convulsions Diseases 0.000 claims 1
• 206010020772 Hypertension Diseases 0.000 claims 1
• ULEBESPCVWBNIF-BYPYZUCNSA-N L-arginine amide Chemical compound NC(=O)[C@@H](N)CCCNC(N)=N ULEBESPCVWBNIF-BYPYZUCNSA-N 0.000 claims 1
• 229930182821 L-proline Natural products 0.000 claims 1
• 125000000174 L-prolyl group Chemical class [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims 1
• DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical class OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 claims 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 1
• 208000028017 Psychotic disease Diseases 0.000 claims 1
• 206010037660 Pyrexia Diseases 0.000 claims 1
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 1
• 125000002252 acyl group Chemical group 0.000 claims 1
• 239000000556 agonist Substances 0.000 claims 1
• 201000007930 alcohol dependence Diseases 0.000 claims 1
• 208000022531 anorexia Diseases 0.000 claims 1
• 239000005557 antagonist Substances 0.000 claims 1
• 230000036506 anxiety Effects 0.000 claims 1
• 230000037007 arousal Effects 0.000 claims 1
• 230000037424 autonomic function Effects 0.000 claims 1
• KUWBXRGRMQZCSS-HSZRJFAPSA-N bibp-3226 Chemical compound N([C@H](CCCN=C(N)N)C(=O)NCC=1C=CC(O)=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 KUWBXRGRMQZCSS-HSZRJFAPSA-N 0.000 claims 1
• 210000001124 body fluid Anatomy 0.000 claims 1
• 239000010839 body fluid Substances 0.000 claims 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
• 208000010877 cognitive disease Diseases 0.000 claims 1
• 125000004093 cyano group Chemical group *C#N 0.000 claims 1
• 206010061428 decreased appetite Diseases 0.000 claims 1
• 230000003412 degenerative effect Effects 0.000 claims 1
• 208000035475 disorder Diseases 0.000 claims 1
• 230000008482 dysregulation Effects 0.000 claims 1
• 230000037149 energy metabolism Effects 0.000 claims 1
• 206010015037 epilepsy Diseases 0.000 claims 1
• 230000037406 food intake Effects 0.000 claims 1
• 235000012631 food intake Nutrition 0.000 claims 1
• 230000003284 homeostatic effect Effects 0.000 claims 1
• 230000003054 hormonal effect Effects 0.000 claims 1
• CPVQJXZBSGXTGJ-TZDLBHCHSA-N juvenile hormone II Chemical compound CC[C@]1(C)O[C@@H]1CC\C(C)=C\CC\C(C)=C\C(=O)OC CPVQJXZBSGXTGJ-TZDLBHCHSA-N 0.000 claims 1
• 150000002576 ketones Chemical class 0.000 claims 1
• 239000003446 ligand Substances 0.000 claims 1
• GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• KGDFDVHLEYUZLN-AWEZNQCLSA-N n-[(4-chlorophenyl)methyl]-4-[(2s)-2-formylpyrrolidin-1-yl]-4-oxobutanamide Chemical compound C1=CC(Cl)=CC=C1CNC(=O)CCC(=O)N1[C@H](C=O)CCC1 KGDFDVHLEYUZLN-AWEZNQCLSA-N 0.000 claims 1
• 210000005036 nerve Anatomy 0.000 claims 1
• 239000002660 neuropeptide Y receptor antagonist Substances 0.000 claims 1
• 230000001717 pathogenic effect Effects 0.000 claims 1
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• 102000004196 processed proteins & peptides Human genes 0.000 claims 1
• HDLWINONZUFKQV-QMMMGPOBSA-N pyrrolidin-1-yl-[(2s)-pyrrolidin-2-yl]methanone Chemical class C1CCCN1C(=O)[C@@H]1CCCN1 HDLWINONZUFKQV-QMMMGPOBSA-N 0.000 claims 1
• 229950010673 rivastigmine hydrogen tartrate Drugs 0.000 claims 1
• GWHQHAUAXRMMOT-MBANBULQSA-N rivastigmine tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 GWHQHAUAXRMMOT-MBANBULQSA-N 0.000 claims 1
• 201000000980 schizophrenia Diseases 0.000 claims 1
• 239000000126 substance Substances 0.000 claims 1
• 125000001424 substituent group Chemical group 0.000 claims 1
• 229940124597 therapeutic agent Drugs 0.000 claims 1
• 150000003548 thiazolidines Chemical class 0.000 claims 1
• 239000004474 valine Substances 0.000 claims 1
• SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 claims 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• 229920001577 copolymer Polymers 0.000 description 3
• 229920002721 polycyanoacrylate Polymers 0.000 description 3
• 229920000642 polymer Polymers 0.000 description 3
• OPJKGTJXHVPYIM-UHFFFAOYSA-N 2-methylprop-2-enamide;phenol Chemical compound CC(=C)C(N)=O.OC1=CC=CC=C1 OPJKGTJXHVPYIM-UHFFFAOYSA-N 0.000 description 2
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
• 108010039918 Polylysine Proteins 0.000 description 2
• 229920001710 Polyorthoester Polymers 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 238000013267 controlled drug release Methods 0.000 description 2
• 239000000017 hydrogel Substances 0.000 description 2
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 229920000747 poly(lactic acid) Polymers 0.000 description 2
• 229920001610 polycaprolactone Polymers 0.000 description 2
• 239000004626 polylactic acid Substances 0.000 description 2
• 229920000656 polylysine Polymers 0.000 description 2
• 229920006324 polyoxymethylene Polymers 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• OIFZBOXCSQOOQR-UHFFFAOYSA-N (1-cyclopentyl-3,3-dimethyl-1-oxobutan-2-yl)azanium;chloride Chemical compound [Cl-].CC(C)(C)C([NH3+])C(=O)C1CCCC1 OIFZBOXCSQOOQR-UHFFFAOYSA-N 0.000 description 1
• NGHKPFDSWWVQRM-UHFFFAOYSA-N (1-cyclopentyl-3-methyl-1-oxobutan-2-yl)azanium;chloride Chemical compound [Cl-].CC(C)C([NH3+])C(=O)C1CCCC1 NGHKPFDSWWVQRM-UHFFFAOYSA-N 0.000 description 1
• QOMLWUOJCBLHPI-UHFFFAOYSA-N (1-cyclopentyl-3-methyl-1-oxopentan-2-yl)azanium;chloride Chemical compound [Cl-].CCC(C)C([NH3+])C(=O)C1CCCC1 QOMLWUOJCBLHPI-UHFFFAOYSA-N 0.000 description 1
• GEIXJNSDCIKYHU-IXDGSTSKSA-N (2s)-2-amino-n-[(2s)-1-[(2s)-2-[2-[(2,6-dichlorophenyl)methylsulfanyl]acetyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]propanamide Chemical compound C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)CSCC1=C(Cl)C=CC=C1Cl GEIXJNSDCIKYHU-IXDGSTSKSA-N 0.000 description 1
• AYEVWCRIXBNNME-LFELFHSZSA-N (2s)-2-amino-n-[(2s)-3-methyl-1-oxo-1-[(2s)-2-(1,3-thiazole-2-carbonyl)pyrrolidin-1-yl]butan-2-yl]propanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)C1=NC=CS1 AYEVWCRIXBNNME-LFELFHSZSA-N 0.000 description 1
• ZRGFWRVNUPJBTR-JGAZGGJJSA-N (2s)-2-amino-n-[2-[(2s)-2-(1,3-benzothiazole-2-carbonyl)pyrrolidin-1-yl]-2-oxoethyl]propanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(=O)C1=NC2=CC=CC=C2S1 ZRGFWRVNUPJBTR-JGAZGGJJSA-N 0.000 description 1
• CRYXXTXWUCPIMU-WNQIDUERSA-N (2s)-2-aminobutanediamide;phenol Chemical compound OC1=CC=CC=C1.NC(=O)[C@@H](N)CC(N)=O CRYXXTXWUCPIMU-WNQIDUERSA-N 0.000 description 1
• VCODUTUPBPSXRA-LBRAPMIBSA-N (2s)-n-[(2s)-1-[(2s)-2-acetylpyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-aminopropanamide;hydrobromide Chemical compound Br.C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(C)=O VCODUTUPBPSXRA-LBRAPMIBSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
• GEAXDQGWIUNDBZ-NPLJWMOXSA-N [2-[(2s)-1-[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-3-methylbutanoyl]pyrrolidin-2-yl]-2-oxoethyl] acetate;hydrobromide Chemical compound Br.C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)COC(C)=O GEAXDQGWIUNDBZ-NPLJWMOXSA-N 0.000 description 1
• 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 125000006638 cyclopentyl carbonyl group Chemical group 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 238000000034 method Methods 0.000 description 1
• 239000000203 mixture Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• CKNYWTABPYGPEX-UHFFFAOYSA-N pyrrolidin-1-ium;2,2,2-trifluoroacetate Chemical compound C1CC[NH2+]C1.[O-]C(=O)C(F)(F)F CKNYWTABPYGPEX-UHFFFAOYSA-N 0.000 description 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1