JP2003525850A5 - - Google Patents

Info

Publication number

JP2003525850A5

JP2003525850A5 JP2000531182A JP2000531182A JP2003525850A5 JP 2003525850 A5 JP2003525850 A5 JP 2003525850A5 JP 2000531182 A JP2000531182 A JP 2000531182A JP 2000531182 A JP2000531182 A JP 2000531182A JP 2003525850 A5 JP2003525850 A5 JP 2003525850A5

Authority

JP

Japan

Prior art keywords

compound

substituted

group

nrr

alkyl

Prior art date

1999-02-10

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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• 150000001875 compounds Chemical class 0.000 description 68
• 125000003118 aryl group Chemical group 0.000 description 25
• 125000001072 heteroaryl group Chemical group 0.000 description 25
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 21
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 21
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 18
• 229910052736 halogen Inorganic materials 0.000 description 13
• 150000002367 halogens Chemical class 0.000 description 13
• 125000003710 aryl alkyl group Chemical group 0.000 description 12
• 125000004446 heteroarylalkyl group Chemical group 0.000 description 12
• 125000004953 trihalomethyl group Chemical group 0.000 description 12
• 125000002877 alkyl aryl group Chemical group 0.000 description 11
• 125000000304 alkynyl group Chemical group 0.000 description 8
• 125000000217 alkyl group Chemical group 0.000 description 7
• -1 imidazol-2-yl-imidazolyl Chemical group 0.000 description 7
• 208000014674 injury Diseases 0.000 description 6
• 201000001119 neuropathy Diseases 0.000 description 6
• 230000007823 neuropathy Effects 0.000 description 6
• 208000033808 peripheral neuropathy Diseases 0.000 description 6
• 0 C=CC(*1)C1C(NCCC[C@@](C(N1[C@@]2CCC1)=O)NC2=O)=N Chemical compound C=CC(*1)C1C(NCCC[C@@](C(N1[C@@]2CCC1)=O)NC2=O)=N 0.000 description 5
• 125000003342 alkenyl group Chemical group 0.000 description 5
• 239000008194 pharmaceutical composition Substances 0.000 description 5
• BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical group O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 5
• 150000003839 salts Chemical class 0.000 description 5
• 210000003169 central nervous system Anatomy 0.000 description 4
• 230000001149 cognitive effect Effects 0.000 description 4
• 230000006378 damage Effects 0.000 description 4
• 239000003814 drug Substances 0.000 description 4
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 4
• 238000004519 manufacturing process Methods 0.000 description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 208000000532 Chronic Brain Injury Diseases 0.000 description 3
• 229940123457 Free radical scavenger Drugs 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 230000001154 acute effect Effects 0.000 description 3
• 210000004556 brain Anatomy 0.000 description 3
• 208000029028 brain injury Diseases 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 230000003446 memory effect Effects 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 239000002516 radical scavenger Substances 0.000 description 3
• 210000000278 spinal cord Anatomy 0.000 description 3
• 230000008733 trauma Effects 0.000 description 3
• WSLYCILIEOFQPK-UHFFFAOYSA-N 3-methyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1C(C)NC(=O)C2CCCN21 WSLYCILIEOFQPK-UHFFFAOYSA-N 0.000 description 2
• XLUAWXQORJEMBD-UHFFFAOYSA-N Pyrrolo(1,2-a)pyrazine-1,4-dione, hexahydro-3-(1-methylethyl)- Chemical compound O=C1C(C(C)C)NC(=O)C2CCCN21 XLUAWXQORJEMBD-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• SZJNCZMRZAUNQT-UHFFFAOYSA-N (3R,8aS)-hexahydro-3-(2-methylpropyl)pyrrolo[1,2-a]pyrazine-1,4-dione Natural products O=C1C(CC(C)C)NC(=O)C2CCCN21 SZJNCZMRZAUNQT-UHFFFAOYSA-N 0.000 description 1
• ZDACRNZBFJOLTC-UHFFFAOYSA-N (3S,6S)-3-[(1S)-1-methylpropyl]hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Natural products O=C1C(C(C)CC)NC(=O)C2CCCN21 ZDACRNZBFJOLTC-UHFFFAOYSA-N 0.000 description 1
• FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• DPRJPRMZJGWLHY-HNGSOEQISA-N (e,3r,5s)-7-[5-(4-fluorophenyl)-3-propan-2-yl-1-pyrazin-2-ylpyrazol-4-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)C[C@H](O)C[C@H](O)/C=C/C=1C(C(C)C)=NN(C=2N=CC=NC=2)C=1C1=CC=C(F)C=C1 DPRJPRMZJGWLHY-HNGSOEQISA-N 0.000 description 1
• YKYWUHHZZRBGMG-JWTNVVGKSA-N 1-methyl-2-[[(1r,5s)-6-[[5-(trifluoromethyl)pyridin-2-yl]methoxymethyl]-3-azabicyclo[3.1.0]hexan-3-yl]methyl]benzimidazole Chemical compound C1([C@@H]2CN(C[C@@H]21)CC=1N(C2=CC=CC=C2N=1)C)COCC1=CC=C(C(F)(F)F)C=N1 YKYWUHHZZRBGMG-JWTNVVGKSA-N 0.000 description 1
• QZBUWPVZSXDWSB-UHFFFAOYSA-N 3'-Acetamido-3'-deoxyadenosin Natural products O=C1N2CCCC2C(=O)NC1CC1=CC=CC=C1 QZBUWPVZSXDWSB-UHFFFAOYSA-N 0.000 description 1
• KUZSBKJSGSKPJH-VXGBXAGGSA-N 5-[(9R)-6-[(3R)-3-methylmorpholin-4-yl]-11-oxa-1,3,5-triazatricyclo[7.4.0.02,7]trideca-2,4,6-trien-4-yl]pyrazin-2-amine Chemical compound C[C@@H]1COCCN1c1nc(nc2N3CCOC[C@H]3Cc12)-c1cnc(N)cn1 KUZSBKJSGSKPJH-VXGBXAGGSA-N 0.000 description 1
• LDIOUQIXNSSOGU-UHFFFAOYSA-N 8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5h-cyclopenta[d]pyrazolo[1,5-a]pyrimidine Chemical compound CC1=NN2C(NC(CC)CC)=C3CCCC3=NC2=C1C1=CC=C(OC)C=C1Cl LDIOUQIXNSSOGU-UHFFFAOYSA-N 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• QUMCIHKVKQYNPA-RUZDIDTESA-N C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC Chemical compound C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC QUMCIHKVKQYNPA-RUZDIDTESA-N 0.000 description 1
• LDUBWSIVHANZFZ-IUCAKERBSA-N CC(C)(C)SC[C@@H](C(N1[C@H]2CCC1)=O)NC2=O Chemical compound CC(C)(C)SC[C@@H](C(N1[C@H]2CCC1)=O)NC2=O LDUBWSIVHANZFZ-IUCAKERBSA-N 0.000 description 1
• LSGOTAXPWMCUCK-UHFFFAOYSA-N D-prolyl-L-tyrosine anhydride Natural products C1=CC(O)=CC=C1CC1C(=O)N2CCCC2C(=O)N1 LSGOTAXPWMCUCK-UHFFFAOYSA-N 0.000 description 1
• QQKRRCFJMUFQSQ-QWRGUYRKSA-N N/C(/NCCC[C@@H](C(N1[C@H]2CCC1)=O)NC2=O)=N/C1CC1 Chemical compound N/C(/NCCC[C@@H](C(N1[C@H]2CCC1)=O)NC2=O)=N/C1CC1 QQKRRCFJMUFQSQ-QWRGUYRKSA-N 0.000 description 1
• GOFVWXHQOCJXJK-BRHZVYESSA-N N=C(NCC[C@H](C1)C1(C(N1[C@H]2CCC1)=O)NC2=O)S Chemical compound N=C(NCC[C@H](C1)C1(C(N1[C@H]2CCC1)=O)NC2=O)S GOFVWXHQOCJXJK-BRHZVYESSA-N 0.000 description 1
• UJYOQFVXMWIEBX-LURJTMIESA-N O=C([C@H]1N2CCC1)NC1(CC1)C2=O Chemical compound O=C([C@H]1N2CCC1)NC1(CC1)C2=O UJYOQFVXMWIEBX-LURJTMIESA-N 0.000 description 1
• QTPGVDQFVSPTGL-VIFPVBQESA-N O=C([C@H]1N2CCC1)NC1(CCCCC1)C2=O Chemical compound O=C([C@H]1N2CCC1)NC1(CCCCC1)C2=O QTPGVDQFVSPTGL-VIFPVBQESA-N 0.000 description 1
• GLEOIKLQBZNKJZ-WDSKDSINSA-N Pro-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 GLEOIKLQBZNKJZ-WDSKDSINSA-N 0.000 description 1
• BEPSGCXDIVACBU-IUCAKERBSA-N Pro-His Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1NCCC1)C1=CN=CN1 BEPSGCXDIVACBU-IUCAKERBSA-N 0.000 description 1
• RVQDZELMXZRSSI-IUCAKERBSA-N Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 RVQDZELMXZRSSI-IUCAKERBSA-N 0.000 description 1
• UEKYKRQIAQHOOZ-KBPBESRZSA-N Pro-Trp Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)[O-])C(=O)[C@@H]1CCC[NH2+]1 UEKYKRQIAQHOOZ-KBPBESRZSA-N 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• AEULIVPVIDOLIN-UHFFFAOYSA-N cep-11981 Chemical compound C1=C2C3=C4CNC(=O)C4=C4C5=CN(C)N=C5CCC4=C3N(CC(C)C)C2=CC=C1NC1=NC=CC=N1 AEULIVPVIDOLIN-UHFFFAOYSA-N 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• SZJNCZMRZAUNQT-IUCAKERBSA-N cyclo(L-Leu-L-Pro) Chemical compound O=C1[C@H](CC(C)C)NC(=O)[C@@H]2CCCN21 SZJNCZMRZAUNQT-IUCAKERBSA-N 0.000 description 1
• QZBUWPVZSXDWSB-RYUDHWBXSA-N cyclo(L-Phe-L-Pro) Chemical compound C([C@@H]1NC([C@@H]2CCCN2C1=O)=O)C1=CC=CC=C1 QZBUWPVZSXDWSB-RYUDHWBXSA-N 0.000 description 1
• 108010076347 cyclo(prolyl-leucyl) Proteins 0.000 description 1
• 108010007383 cyclo(prolyl-valyl) Proteins 0.000 description 1
• 108010014087 cyclo(prolylarginyl) Proteins 0.000 description 1
• GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
• LSGOTAXPWMCUCK-RYUDHWBXSA-N maculosin Chemical compound C1=CC(O)=CC=C1C[C@H]1C(=O)N2CCC[C@H]2C(=O)N1 LSGOTAXPWMCUCK-RYUDHWBXSA-N 0.000 description 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
• SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000001424 substituent group Chemical group 0.000 description 1
• FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
• 229960001295 tocopherol Drugs 0.000 description 1
• 229930003799 tocopherol Natural products 0.000 description 1
• 235000010384 tocopherol Nutrition 0.000 description 1
• 239000011732 tocopherol Substances 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1