JP4205559B2 - イソインドリン誘導体 - Google Patents
イソインドリン誘導体 Download PDFInfo
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- JP4205559B2 JP4205559B2 JP2003393809A JP2003393809A JP4205559B2 JP 4205559 B2 JP4205559 B2 JP 4205559B2 JP 2003393809 A JP2003393809 A JP 2003393809A JP 2003393809 A JP2003393809 A JP 2003393809A JP 4205559 B2 JP4205559 B2 JP 4205559B2
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- Japan
- Prior art keywords
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- dimethyl
- compound
- formula
- carbon atoms
- Prior art date
- 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.)
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- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical class C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 title claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 152
- -1 methylpiperazinyl Chemical group 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 40
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- 230000003444 anaesthetic effect Effects 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 230000001624 sedative effect Effects 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 235000019000 fluorine Nutrition 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 239000000932 sedative agent Substances 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 125000001153 fluoro group Chemical group F* 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 7
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 238000001990 intravenous administration Methods 0.000 claims description 7
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 114
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 52
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- 238000005160 1H NMR spectroscopy Methods 0.000 description 43
- 239000000243 solution Substances 0.000 description 41
- 229910052799 carbon Inorganic materials 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 26
- 239000000047 product Substances 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 238000010898 silica gel chromatography Methods 0.000 description 20
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 17
- 239000013078 crystal Substances 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 206010002091 Anaesthesia Diseases 0.000 description 14
- 230000037005 anaesthesia Effects 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 0 *N(C(c1cc(I)c(*)cc11)I)C1=C Chemical compound *N(C(c1cc(I)c(*)cc11)I)C1=C 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- GSCXPNAZEUKIRW-UHFFFAOYSA-N 2-(5,6-dimethyl-3-oxo-2-pyridin-3-yl-1h-isoindol-1-yl)acetic acid Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(CC(O)=O)N1C1=CC=CN=C1 GSCXPNAZEUKIRW-UHFFFAOYSA-N 0.000 description 11
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000012300 argon atmosphere Substances 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- HGHNFTPDMNDNAT-UHFFFAOYSA-N propyl 2-(5,6-dimethyl-3-oxo-2-pyridin-3-yl-1h-isoindol-1-yl)acetate Chemical compound O=C1C2=CC(C)=C(C)C=C2C(CC(=O)OCCC)N1C1=CC=CN=C1 HGHNFTPDMNDNAT-UHFFFAOYSA-N 0.000 description 7
- YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- CMQYISATYUYSAC-UHFFFAOYSA-N 5,6-dimethyl-2-benzofuran-1,3-dione Chemical compound C1=C(C)C(C)=CC2=C1C(=O)OC2=O CMQYISATYUYSAC-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- GNXKPDYSMXCAOA-UHFFFAOYSA-N 2-(5,6-dimethyl-3-oxo-2-pyridin-3-yl-1h-isoindol-1-yl)ethyl methanesulfonate Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(CCOS(C)(=O)=O)N1C1=CC=CN=C1 GNXKPDYSMXCAOA-UHFFFAOYSA-N 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 231100000111 LD50 Toxicity 0.000 description 5
- 206010039897 Sedation Diseases 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 5
- 230000011514 reflex Effects 0.000 description 5
- 230000036280 sedation Effects 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- SDJHPPZKZZWAKF-UHFFFAOYSA-N 2,3-dimethylbuta-1,3-diene Chemical compound CC(=C)C(C)=C SDJHPPZKZZWAKF-UHFFFAOYSA-N 0.000 description 4
- PJHANGBPMQJFQQ-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)-5,6-dimethyl-3-oxo-1h-isoindol-1-yl]acetic acid Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(CC(O)=O)N1C1=CC=C(F)C=C1 PJHANGBPMQJFQQ-UHFFFAOYSA-N 0.000 description 4
- SKBDLRWFSRLIPP-UHFFFAOYSA-N 4,5-Dimethoxy-1,2-benzenedicarboxylic acid Chemical compound COC1=CC(C(O)=O)=C(C(O)=O)C=C1OC SKBDLRWFSRLIPP-UHFFFAOYSA-N 0.000 description 4
- AOAQTWFVCRFMNZ-UHFFFAOYSA-N 5,6-diethyl-2-benzofuran-1,3-dione Chemical compound C1=C(CC)C(CC)=CC2=C1C(=O)OC2=O AOAQTWFVCRFMNZ-UHFFFAOYSA-N 0.000 description 4
- IMSDRBDUANUSRL-UHFFFAOYSA-N 5,6-dimethoxy-2-benzofuran-1,3-dione Chemical compound C1=C(OC)C(OC)=CC2=C1C(=O)OC2=O IMSDRBDUANUSRL-UHFFFAOYSA-N 0.000 description 4
- NKJKYAYKHJZPFZ-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[f][2]benzofuran-1,3-dione Chemical compound C1=C2C(=O)OC(=O)C2=CC2=C1CCC2 NKJKYAYKHJZPFZ-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000003193 general anesthetic agent Substances 0.000 description 4
- 239000002869 intravenous anesthetic agent Substances 0.000 description 4
- 239000002504 physiological saline solution Substances 0.000 description 4
- 235000019260 propionic acid Nutrition 0.000 description 4
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- ABQVNNFQKQQAAV-KGENOOAVSA-N (3e)-2-(4-fluorophenyl)-5,6-dimethyl-3-[2-(4-methylpiperazin-1-yl)-2-oxoethylidene]isoindol-1-one Chemical compound C1CN(C)CCN1C(=O)\C=C\1C2=CC(C)=C(C)C=C2C(=O)N/1C1=CC=C(F)C=C1 ABQVNNFQKQQAAV-KGENOOAVSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- OIXKTTOZKMRRJL-UHFFFAOYSA-N 2-(3-fluorophenyl)-5,6-dimethyl-3-oxo-1h-isoindole-1-carbonitrile Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(C#N)N1C1=CC=CC(F)=C1 OIXKTTOZKMRRJL-UHFFFAOYSA-N 0.000 description 3
- SCNRSSJYBCTXRS-UHFFFAOYSA-N 2-(3-fluorophenyl)-5,6-dimethyl-3-oxo-1h-isoindole-1-carboxylic acid Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(C(O)=O)N1C1=CC=CC(F)=C1 SCNRSSJYBCTXRS-UHFFFAOYSA-N 0.000 description 3
- GZDVRHDRMZHOMX-UHFFFAOYSA-N 3-(2-hydroxyethyl)-5,6-dimethyl-2-pyridin-3-yl-3h-isoindol-1-one Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(CCO)N1C1=CC=CN=C1 GZDVRHDRMZHOMX-UHFFFAOYSA-N 0.000 description 3
- RWMNFFVEAGSLDW-UHFFFAOYSA-N 3-[2-(4-fluorophenyl)-5,6-dimethyl-3-oxo-1h-isoindol-1-yl]propanoic acid Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(CCC(O)=O)N1C1=CC=C(F)C=C1 RWMNFFVEAGSLDW-UHFFFAOYSA-N 0.000 description 3
- XWOZJTCSFMCOBZ-UHFFFAOYSA-N 3-hexyl-5,6-dimethyl-2-pyridin-3-yl-3h-isoindol-1-one Chemical compound O=C1C2=CC(C)=C(C)C=C2C(CCCCCC)N1C1=CC=CN=C1 XWOZJTCSFMCOBZ-UHFFFAOYSA-N 0.000 description 3
- PLFXUMVRDDKJDH-UHFFFAOYSA-N 5,6-dimethyl-2-pyridin-3-ylisoindole-1,3-dione Chemical compound O=C1C=2C=C(C)C(C)=CC=2C(=O)N1C1=CC=CN=C1 PLFXUMVRDDKJDH-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 229940035674 anesthetics Drugs 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- KPFOHKBCRCNQET-UHFFFAOYSA-N ethyl 2-(5,6-dimethyl-3-oxo-2-pyridin-3-yl-1h-isoindol-1-yl)acetate Chemical compound O=C1C2=CC(C)=C(C)C=C2C(CC(=O)OCC)N1C1=CC=CN=C1 KPFOHKBCRCNQET-UHFFFAOYSA-N 0.000 description 3
- KCHNCQINIRYRBS-UHFFFAOYSA-N ethyl 2-[2-(4-fluorophenyl)-5,6-dimethyl-3-oxo-1h-isoindol-1-yl]acetate Chemical compound O=C1C2=CC(C)=C(C)C=C2C(CC(=O)OCC)N1C1=CC=C(F)C=C1 KCHNCQINIRYRBS-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000002695 general anesthesia Methods 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
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- 235000011083 sodium citrates Nutrition 0.000 description 1
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
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- 125000004377 trifluoropropoxy group Chemical group FC(CCO*)(F)F 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
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- 239000008215 water for injection Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003393809A JP4205559B2 (ja) | 2002-11-26 | 2003-11-25 | イソインドリン誘導体 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002342399 | 2002-11-26 | ||
| JP2003393809A JP4205559B2 (ja) | 2002-11-26 | 2003-11-25 | イソインドリン誘導体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004189733A JP2004189733A (ja) | 2004-07-08 |
| JP2004189733A5 JP2004189733A5 (https=) | 2007-01-18 |
| JP4205559B2 true JP4205559B2 (ja) | 2009-01-07 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2003393809A Expired - Fee Related JP4205559B2 (ja) | 2002-11-26 | 2003-11-25 | イソインドリン誘導体 |
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| JP (1) | JP4205559B2 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007053657A1 (en) * | 2005-11-01 | 2007-05-10 | Janssen Pharmaceutica N.V. | Substituted pyrrolones as allosteric modulators of glucokinase |
| WO2007053662A1 (en) * | 2005-11-01 | 2007-05-10 | Janssen Pharmaceutica N.V. | Dihydroisoindolones as allosteric modulators of glucokinase |
| CA2627910A1 (en) * | 2005-11-01 | 2007-05-10 | Janssen Pharmaceutica N.V. | Substituted cycloalkylpyrrolones as allosteric modulators of glucokinase |
| WO2007053503A1 (en) * | 2005-11-01 | 2007-05-10 | Janssen Pharmaceutica N.V. | Substituted dihydroisoindolones as allosteric modulators of glucokinase |
| CN104955456B (zh) | 2013-01-28 | 2018-07-03 | H.隆德贝克有限公司 | 作为分拣蛋白抑制剂的n-取代的-5-取代的邻氨甲酰苯甲酸 |
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| JP2004189733A (ja) | 2004-07-08 |
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