CN1286833C - 吲哚和2,3－二氢吲哚衍生物、它们的制备及用途 - Google Patents

吲哚和2,3－二氢吲哚衍生物、它们的制备及用途 Download PDF

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Publication number: CN1286833C
Authority: CN; China
Prior art keywords: indoles; ethyl; compound; benzo; alkane
Prior art date: 1997-07-25
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.): Expired - Fee Related

Application number

CN 03106002

Other languages

English (en)

Chinese (zh)

Other versions

CN1515568A (zh

Inventor

E·K·莫尔特岑

J·K·珀雷加尔德

I·米克尔森

G·P·史密斯

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

H Lundbeck AS

Original Assignee

H Lundbeck AS

Priority date (The priority date 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 date listed.)

1997-07-25

Filing date

1998-07-20

Publication date

2006-11-29

1998-07-20 Application filed by H Lundbeck AS filed Critical H Lundbeck AS

2004-07-28 Publication of CN1515568A publication Critical patent/CN1515568A/zh

2006-11-29 Application granted granted Critical

2006-11-29 Publication of CN1286833C publication Critical patent/CN1286833C/zh

2018-07-20 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

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SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 21
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title abstract description 5
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title abstract description 3
238000002360 preparation method Methods 0.000 title description 16
150000001875 compounds Chemical class 0.000 claims abstract description 74
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 72
239000002253 acid Substances 0.000 claims abstract description 23
150000003839 salts Chemical class 0.000 claims abstract description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 127
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
239000003814 drug Substances 0.000 claims description 16
230000000697 serotonin reuptake Effects 0.000 claims description 14
230000000452 restraining effect Effects 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
150000002475 indoles Chemical class 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
208000019901 Anxiety disease Diseases 0.000 claims description 8
230000008485 antagonism Effects 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
230000035945 sensitivity Effects 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
208000020016 psychiatric disease Diseases 0.000 claims description 5
208000028017 Psychotic disease Diseases 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
208000019899 phobic disease Diseases 0.000 claims description 4
208000024891 symptom Diseases 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
239000000203 mixture Substances 0.000 abstract description 13
230000003042 antagnostic effect Effects 0.000 abstract description 6
239000003112 inhibitor Substances 0.000 abstract description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract 1
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical class C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 abstract 1
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
238000000034 method Methods 0.000 description 43
238000005481 NMR spectroscopy Methods 0.000 description 38
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
239000000243 solution Substances 0.000 description 18
238000005160 1H NMR spectroscopy Methods 0.000 description 17
208000035475 disorder Diseases 0.000 description 15
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
125000000217 alkyl group Chemical group 0.000 description 13
230000000694 effects Effects 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
-1 alkoxycarbonyl amido Chemical group 0.000 description 12
235000019439 ethyl acetate Nutrition 0.000 description 12
208000024732 dysthymic disease Diseases 0.000 description 11
125000003118 aryl group Chemical group 0.000 description 10
239000003153 chemical reaction reagent Substances 0.000 description 10
238000006722 reduction reaction Methods 0.000 description 10
238000003756 stirring Methods 0.000 description 10
238000002955 isolation Methods 0.000 description 9
239000000935 antidepressant agent Substances 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
238000012360 testing method Methods 0.000 description 8
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 7
239000003513 alkali Substances 0.000 description 7
239000003480 eluent Substances 0.000 description 7
238000003818 flash chromatography Methods 0.000 description 7
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
239000000654 additive Substances 0.000 description 6
150000004982 aromatic amines Chemical class 0.000 description 6
235000006408 oxalic acid Nutrition 0.000 description 6
230000009467 reduction Effects 0.000 description 6
230000000996 additive effect Effects 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
239000003999 initiator Substances 0.000 description 5
239000012280 lithium aluminium hydride Substances 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
229960002508 pindolol Drugs 0.000 description 5
JZQKKSLKJUAGIC-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=C1C=CN2 JZQKKSLKJUAGIC-UHFFFAOYSA-N 0.000 description 5
238000010992 reflux Methods 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
239000000556 agonist Substances 0.000 description 4
150000001335 aliphatic alkanes Chemical class 0.000 description 4
125000003368 amide group Chemical group 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
235000015320 potassium carbonate Nutrition 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
229940126570 serotonin reuptake inhibitor Drugs 0.000 description 4
239000003772 serotonin uptake inhibitor Substances 0.000 description 4
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
238000005903 acid hydrolysis reaction Methods 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
125000003282 alkyl amino group Chemical group 0.000 description 3
125000000304 alkynyl group Chemical group 0.000 description 3
230000001430 anti-depressive effect Effects 0.000 description 3
239000002585 base Substances 0.000 description 3
210000004556 brain Anatomy 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
238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
229910052801 chlorine Inorganic materials 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
125000000753 cycloalkyl group Chemical group 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000001530 fumaric acid Substances 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000000047 product Substances 0.000 description 3
239000002464 receptor antagonist Substances 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 2
BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
ZSTKHSQDNIGFLM-UHFFFAOYSA-N 5-methoxy-N,N-dimethyltryptamine Chemical compound COC1=CC=C2NC=C(CCN(C)C)C2=C1 ZSTKHSQDNIGFLM-UHFFFAOYSA-N 0.000 description 2
ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methylindole Natural products CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
125000004949 alkyl amino carbonyl amino group Chemical group 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
229940005513 antidepressants Drugs 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 2
230000008713 feedback mechanism Effects 0.000 description 2
238000013467 fragmentation Methods 0.000 description 2
238000006062 fragmentation reaction Methods 0.000 description 2
229950006191 gluconic acid Drugs 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000001939 inductive effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
LVHBHZANLOWSRM-UHFFFAOYSA-N itaconic acid Chemical compound OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000013507 mapping Methods 0.000 description 2
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HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
229910000510 noble metal Inorganic materials 0.000 description 2
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239000003960 organic solvent Substances 0.000 description 2
CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 description 2
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239000000825 pharmaceutical preparation Substances 0.000 description 2
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BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000005932 reductive alkylation reaction Methods 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
238000007634 remodeling Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
229940076279 serotonin Drugs 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
238000007614 solvation Methods 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000000725 suspension Substances 0.000 description 2
210000003568 synaptosome Anatomy 0.000 description 2
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238000004885 tandem mass spectrometry Methods 0.000 description 2
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HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
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238000001890 transfection Methods 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
URLVCROWVOSNPT-XOTOMLERSA-N (2s)-4-[(13r)-13-hydroxy-13-[(2r,5r)-5-[(2r,5r)-5-[(1r)-1-hydroxyundecyl]oxolan-2-yl]oxolan-2-yl]tridecyl]-2-methyl-2h-furan-5-one Chemical compound O1[C@@H]([C@H](O)CCCCCCCCCC)CC[C@@H]1[C@@H]1O[C@@H]([C@H](O)CCCCCCCCCCCCC=2C(O[C@@H](C)C=2)=O)CC1 URLVCROWVOSNPT-XOTOMLERSA-N 0.000 description 1
NQBWNECTZUOWID-UHFFFAOYSA-N (E)-cinnamyl (E)-cinnamate Natural products C=1C=CC=CC=1C=CC(=O)OCC=CC1=CC=CC=C1 NQBWNECTZUOWID-UHFFFAOYSA-N 0.000 description 1
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
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CN 03106002 1997-07-25 1998-07-20 吲哚和2,3－二氢吲哚衍生物、它们的制备及用途 Expired - Fee Related CN1286833C (zh)

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DK0892/97		1997-07-25
DK89297		1997-07-25
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CN 98807554 Expired - Fee Related CN1127501C (zh)	1997-07-25	1998-07-20	吲哚和2,3－二氢吲哚衍生物、它们的制备及用途
CNB03106003XA Expired - Fee Related CN1293075C (zh)	1997-07-25	1998-07-20	吲哚和2,3－二氢吲哚衍生物、它们的制备及用途

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CNB03106003XA Expired - Fee Related CN1293075C (zh)	1997-07-25	1998-07-20	吲哚和2,3－二氢吲哚衍生物、它们的制备及用途

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AR (1)	AR013206A1 (is)
BR (1)	BR9810790A (is)
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IL (1)	IL133990A (is)
IS (1)	IS2024B (is)
NO (1)	NO318610B1 (is)
PL (1)	PL190924B1 (is)
SK (1)	SK284866B6 (is)
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1998
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- 1998-07-14 ZA ZA986237A patent/ZA986237B/xx unknown
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- 1998-07-20 IL IL13399098A patent/IL133990A/xx not_active IP Right Cessation
- 1998-07-20 TR TR2000/00231T patent/TR200000231T2/xx unknown
- 1998-07-20 CN CN 03106002 patent/CN1286833C/zh not_active Expired - Fee Related
- 1998-07-20 CN CN 98807554 patent/CN1127501C/zh not_active Expired - Fee Related
- 1998-07-20 UA UA2000020949A patent/UA59408C2/uk unknown
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- 1998-07-20 EA EA200000162A patent/EA001890B1/ru not_active IP Right Cessation
- 1998-07-20 SK SK95-2000A patent/SK284866B6/sk not_active IP Right Cessation
2000
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Publication number	Publication date
BR9810790A (pt)	2000-07-25
ZA986237B (en)	1999-03-31
HK1066806A1 (en)	2005-04-01
IL133990A0 (en)	2001-04-30
IS5334A (is)	2000-01-11
EA001890B1 (ru)	2001-10-22
HK1066807A1 (en)	2005-04-01
AR013206A1 (es)	2000-12-13
UA59408C2 (uk)	2003-09-15
SK952000A3 (en)	2001-03-12
CN1515568A (zh)	2004-07-28
SK284866B6 (sk)	2006-01-05
NO20000372D0 (no)	2000-01-25
PL338194A1 (en)	2000-10-09
IS2024B (is)	2005-08-15
CN1127501C (zh)	2003-11-12
CN1515569A (zh)	2004-07-28
NO20000372L (no)	2000-03-21
CN1265107A (zh)	2000-08-30
CN1293075C (zh)	2007-01-03
IL133990A (en)	2003-09-17
PL190924B1 (pl)	2006-02-28
EA200000162A1 (ru)	2000-10-30
TR200000231T2 (tr)	2000-07-21
NO318610B1 (no)	2005-04-18
HK1030220A1 (en)	2001-04-27

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