CZ260494A3 - Indole derivatives, process of their preparation, intermediates for their preparation and medicaments based thereon - Google Patents

Indole derivatives, process of their preparation, intermediates for their preparation and medicaments based thereon Download PDF

Info

Publication number: CZ260494A3
Authority: CZ; Czechia
Prior art keywords: mmol; disorders; stirred; mixture; solution
Prior art date: 1993-10-22

Application number

CZ942604A

Other languages

Czech (cs)

English (en)

Inventor

Michael Bos

Original Assignee

Hoffmann La Roche

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.)

1993-10-22

Filing date

1994-10-21

Publication date

1995-10-18

1994-10-21 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1995-10-18 Publication of CZ260494A3 publication Critical patent/CZ260494A3/cs

Links

150000002475 indoles Chemical class 0.000 title claims description 28
238000000034 method Methods 0.000 title claims description 25
229940054051 antipsychotic indole derivative Drugs 0.000 title claims description 14
238000002360 preparation method Methods 0.000 title claims description 12
239000003814 drug Substances 0.000 title claims description 10
239000000543 intermediate Substances 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 79
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 42
239000001257 hydrogen Substances 0.000 claims abstract description 42
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 35
150000003839 salts Chemical class 0.000 claims abstract description 30
239000002253 acid Substances 0.000 claims abstract description 25
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
125000000217 alkyl group Chemical group 0.000 claims abstract description 14
238000011282 treatment Methods 0.000 claims abstract description 11
208000035475 disorder Diseases 0.000 claims abstract description 10
229910052736 halogen Inorganic materials 0.000 claims abstract description 8
150000002367 halogens Chemical class 0.000 claims abstract description 8
208000020016 psychiatric disease Diseases 0.000 claims abstract description 8
150000002431 hydrogen Chemical class 0.000 claims abstract description 7
208000019901 Anxiety disease Diseases 0.000 claims abstract description 6
208000020925 Bipolar disease Diseases 0.000 claims abstract description 6
208000032841 Bulimia Diseases 0.000 claims abstract description 6
206010006550 Bulimia nervosa Diseases 0.000 claims abstract description 6
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 6
208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 6
208000008589 Obesity Diseases 0.000 claims abstract description 6
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 6
208000002193 Pain Diseases 0.000 claims abstract description 6
206010033664 Panic attack Diseases 0.000 claims abstract description 6
206010041250 Social phobia Diseases 0.000 claims abstract description 6
208000007536 Thrombosis Diseases 0.000 claims abstract description 6
230000004064 dysfunction Effects 0.000 claims abstract description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
235000020824 obesity Nutrition 0.000 claims abstract description 6
208000019906 panic disease Diseases 0.000 claims abstract description 6
208000022821 personality disease Diseases 0.000 claims abstract description 6
208000012201 sexual and gender identity disease Diseases 0.000 claims abstract description 6
208000015891 sexual disease Diseases 0.000 claims abstract description 6
208000019116 sleep disease Diseases 0.000 claims abstract description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
206010019233 Headaches Diseases 0.000 claims abstract description 5
208000019695 Migraine disease Diseases 0.000 claims abstract description 5
208000028017 Psychotic disease Diseases 0.000 claims abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
231100000869 headache Toxicity 0.000 claims abstract description 5
206010027599 migraine Diseases 0.000 claims abstract description 5
230000002265 prevention Effects 0.000 claims abstract description 5
201000000980 schizophrenia Diseases 0.000 claims abstract description 5
125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
230000007958 sleep Effects 0.000 claims abstract description 3
208000006011 Stroke Diseases 0.000 claims abstract 6
210000001035 gastrointestinal tract Anatomy 0.000 claims abstract 2
230000004899 motility Effects 0.000 claims abstract 2
208000015122 neurodegenerative disease Diseases 0.000 claims abstract 2
208000023516 stroke disease Diseases 0.000 claims abstract 2
-1 amino compound Chemical class 0.000 claims description 42
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 32
238000004519 manufacturing process Methods 0.000 claims description 15
229910021529 ammonia Inorganic materials 0.000 claims description 12
239000008194 pharmaceutical composition Substances 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
206010026749 Mania Diseases 0.000 claims description 5
239000013543 active substance Substances 0.000 claims description 5
230000016571 aggressive behavior Effects 0.000 claims description 5
230000036772 blood pressure Effects 0.000 claims description 5
208000015114 central nervous system disease Diseases 0.000 claims description 5
230000003340 mental effect Effects 0.000 claims description 5
210000000653 nervous system Anatomy 0.000 claims description 5
230000008447 perception Effects 0.000 claims description 5
230000000472 traumatic effect Effects 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
230000005176 gastrointestinal motility Effects 0.000 claims description 4
XJJZQXUGLLXTHO-ZETCQYMHSA-N (2S)-1-(6-chloro-5-fluoroindol-1-yl)-propan-2-amine Chemical compound FC1=C(Cl)C=C2N(C[C@@H](N)C)C=CC2=C1 XJJZQXUGLLXTHO-ZETCQYMHSA-N 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
230000036506 anxiety Effects 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
BJHBBPWFHWHWOG-SSDOTTSWSA-N (2r)-1-(4-chloro-5-fluoroindol-1-yl)propan-2-amine Chemical compound FC1=CC=C2N(C[C@H](N)C)C=CC2=C1Cl BJHBBPWFHWHWOG-SSDOTTSWSA-N 0.000 claims description 2
MYZDBEVPJGKIQS-SSDOTTSWSA-N (2r)-1-(5,6-difluoroindol-1-yl)propan-2-amine Chemical compound FC1=C(F)C=C2N(C[C@H](N)C)C=CC2=C1 MYZDBEVPJGKIQS-SSDOTTSWSA-N 0.000 claims description 2
XJJZQXUGLLXTHO-SSDOTTSWSA-N (2r)-1-(6-chloro-5-fluoroindol-1-yl)propan-2-amine Chemical compound FC1=C(Cl)C=C2N(C[C@H](N)C)C=CC2=C1 XJJZQXUGLLXTHO-SSDOTTSWSA-N 0.000 claims description 2
YQZSYPKWHRXTCN-ZETCQYMHSA-N (2s)-1-[5-fluoro-4-(trifluoromethyl)indol-1-yl]propan-2-amine Chemical compound FC1=CC=C2N(C[C@@H](N)C)C=CC2=C1C(F)(F)F YQZSYPKWHRXTCN-ZETCQYMHSA-N 0.000 claims description 2
YMEHSPLPRQDLLW-UHFFFAOYSA-N 1-(4-methylindol-1-yl)propan-2-amine Chemical compound C1=CC=C2N(CC(N)C)C=CC2=C1C YMEHSPLPRQDLLW-UHFFFAOYSA-N 0.000 claims description 2
XXCLNSYNUQMDML-UHFFFAOYSA-N 1-(5-chloroindol-1-yl)propan-2-amine Chemical compound ClC1=CC=C2N(CC(N)C)C=CC2=C1 XXCLNSYNUQMDML-UHFFFAOYSA-N 0.000 claims description 2
XJJZQXUGLLXTHO-UHFFFAOYSA-N 1-(6-chloro-5-fluoroindol-1-yl)-propan-2-amine Chemical compound FC1=C(Cl)C=C2N(CC(N)C)C=CC2=C1 XJJZQXUGLLXTHO-UHFFFAOYSA-N 0.000 claims description 2
JZEVZCLHZQYZMU-UHFFFAOYSA-N 2-(3-methoxy-4-methylindol-1-yl)ethanamine Chemical compound C1=CC(C)=C2C(OC)=CN(CCN)C2=C1 JZEVZCLHZQYZMU-UHFFFAOYSA-N 0.000 claims description 2
YVJOCSNROXMPCD-UHFFFAOYSA-N 2-(4-chloro-5-fluoro-3-methoxyindol-1-yl)ethanamine Chemical compound C1=C(F)C(Cl)=C2C(OC)=CN(CCN)C2=C1 YVJOCSNROXMPCD-UHFFFAOYSA-N 0.000 claims description 2
MTKMOBVGAFBBKJ-UHFFFAOYSA-N 2-(4-chloro-5-fluoroindol-1-yl)ethanamine Chemical compound FC1=CC=C2N(CCN)C=CC2=C1Cl MTKMOBVGAFBBKJ-UHFFFAOYSA-N 0.000 claims description 2
LYEMDBHRTLIDHR-UHFFFAOYSA-N 2-(5-chloroindol-1-yl)ethanamine Chemical compound ClC1=CC=C2N(CCN)C=CC2=C1 LYEMDBHRTLIDHR-UHFFFAOYSA-N 0.000 claims description 2
HBDGGXQOJCCOCL-UHFFFAOYSA-N 2-(5-fluoro-3-methoxyindol-1-yl)ethanamine Chemical compound C1=C(F)C=C2C(OC)=CN(CCN)C2=C1 HBDGGXQOJCCOCL-UHFFFAOYSA-N 0.000 claims description 2
UEPNGPGBALZHNM-UHFFFAOYSA-N 2-(5-fluoroindol-1-yl)ethanamine Chemical compound FC1=CC=C2N(CCN)C=CC2=C1 UEPNGPGBALZHNM-UHFFFAOYSA-N 0.000 claims description 2
FOEBPVIQQCLQDC-UHFFFAOYSA-N 2-(6-chloro-5-fluoroindol-1-yl)ethanamine Chemical compound FC1=C(Cl)C=C2N(CCN)C=CC2=C1 FOEBPVIQQCLQDC-UHFFFAOYSA-N 0.000 claims description 2
VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 claims description 2
DUUXOYARAAZWLV-MRVPVSSYSA-N (2r)-1-(5-fluoroindol-1-yl)propan-2-amine Chemical compound FC1=CC=C2N(C[C@H](N)C)C=CC2=C1 DUUXOYARAAZWLV-MRVPVSSYSA-N 0.000 claims 1
BJHBBPWFHWHWOG-ZETCQYMHSA-N (2s)-1-(4-chloro-5-fluoroindol-1-yl)propan-2-amine Chemical compound FC1=CC=C2N(C[C@@H](N)C)C=CC2=C1Cl BJHBBPWFHWHWOG-ZETCQYMHSA-N 0.000 claims 1
DUUXOYARAAZWLV-UHFFFAOYSA-N 1-(5-fluoroindol-1-yl)propan-2-amine Chemical compound FC1=CC=C2N(CC(N)C)C=CC2=C1 DUUXOYARAAZWLV-UHFFFAOYSA-N 0.000 claims 1
WZMZEXSQEAPONX-UHFFFAOYSA-N 1-(6-fluoroindol-1-yl)propan-2-amine Chemical compound C1=C(F)C=C2N(CC(N)C)C=CC2=C1 WZMZEXSQEAPONX-UHFFFAOYSA-N 0.000 claims 1
230000006399 behavior Effects 0.000 claims 1
239000012876 carrier material Substances 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
230000004770 neurodegeneration Effects 0.000 claims 1
206010000117 Abnormal behaviour Diseases 0.000 abstract 1
206010001488 Aggression Diseases 0.000 abstract 1
206010012335 Dependence Diseases 0.000 abstract 1
208000020401 Depressive disease Diseases 0.000 abstract 1
206010020772 Hypertension Diseases 0.000 abstract 1
208000026139 Memory disease Diseases 0.000 abstract 1
208000027626 Neurocognitive disease Diseases 0.000 abstract 1
210000003169 central nervous system Anatomy 0.000 abstract 1
208000014674 injury Diseases 0.000 abstract 1
230000008733 trauma Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 392
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 312
239000000243 solution Substances 0.000 description 307
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 282
239000000203 mixture Substances 0.000 description 213
239000012074 organic phase Substances 0.000 description 148
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 128
239000002904 solvent Substances 0.000 description 123
229910052938 sodium sulfate Inorganic materials 0.000 description 118
235000011152 sodium sulphate Nutrition 0.000 description 118
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
239000013078 crystal Substances 0.000 description 110
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 110
239000011541 reaction mixture Substances 0.000 description 98
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 94
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 93
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 89
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 84
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 80
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
239000000741 silica gel Substances 0.000 description 76
229910002027 silica gel Inorganic materials 0.000 description 76
239000008346 aqueous phase Substances 0.000 description 73
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 64
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 62
239000000725 suspension Substances 0.000 description 62
239000003480 eluent Substances 0.000 description 55
239000003921 oil Substances 0.000 description 43
235000019198 oils Nutrition 0.000 description 43
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 42
239000001530 fumaric acid Substances 0.000 description 39
239000002585 base Substances 0.000 description 37
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
239000003054 catalyst Substances 0.000 description 35
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 32
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 32
239000012312 sodium hydride Substances 0.000 description 32
229910000104 sodium hydride Inorganic materials 0.000 description 32
239000012359 Methanesulfonyl chloride Substances 0.000 description 31
239000006185 dispersion Substances 0.000 description 31
229910000029 sodium carbonate Inorganic materials 0.000 description 31
239000012298 atmosphere Substances 0.000 description 21
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
238000006243 chemical reaction Methods 0.000 description 18
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 18
229910003446 platinum oxide Inorganic materials 0.000 description 18
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 16
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
GOOHAUXETOMSMM-GSVOUGTGSA-N R-propylene oxide Chemical compound C[C@@H]1CO1 GOOHAUXETOMSMM-GSVOUGTGSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 13
239000012230 colorless oil Substances 0.000 description 13
238000003756 stirring Methods 0.000 description 13
229960001701 chloroform Drugs 0.000 description 11
GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
102000005962 receptors Human genes 0.000 description 10
108020003175 receptors Proteins 0.000 description 10
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 9
238000000354 decomposition reaction Methods 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
239000012954 diazonium Substances 0.000 description 8
150000001989 diazonium salts Chemical class 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 8
ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
229910052751 metal Inorganic materials 0.000 description 7
239000002184 metal Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 7
ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methyl-1h-indole Chemical compound CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
239000012267 brine Substances 0.000 description 6
239000000969 carrier Substances 0.000 description 6
239000005457 ice water Substances 0.000 description 6
239000012071 phase Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
ANGRSSWNBDJESO-UHFFFAOYSA-N 6-chloro-5-fluoro-1h-indole Chemical compound C1=C(Cl)C(F)=CC2=C1NC=C2 ANGRSSWNBDJESO-UHFFFAOYSA-N 0.000 description 5
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
GOOHAUXETOMSMM-VKHMYHEASA-N S-propylene oxide Chemical compound C[C@H]1CO1 GOOHAUXETOMSMM-VKHMYHEASA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000000839 emulsion Substances 0.000 description 5
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
239000008101 lactose Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
238000000159 protein binding assay Methods 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000011734 sodium Substances 0.000 description 5
TUZFHNWMUXXNGF-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(5-chloroindol-1-yl)propan-2-amine Chemical compound OC(=O)\C=C\C(O)=O.ClC1=CC=C2N(CC(N)C)C=CC2=C1 TUZFHNWMUXXNGF-WLHGVMLRSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000012300 argon atmosphere Substances 0.000 description 4
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 4
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 4
239000003446 ligand Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
CRWWKSCULSZJKF-UHFFFAOYSA-N 1-(2-azidopropyl)-5-methylindole Chemical compound CC1=CC=C2N(CC(C)N=[N+]=[N-])C=CC2=C1 CRWWKSCULSZJKF-UHFFFAOYSA-N 0.000 description 3
MQEQTBNFWHGSRJ-UHFFFAOYSA-N 3-ethyl-5-fluoro-1h-indole-2-carboxylic acid Chemical compound C1=C(F)C=C2C(CC)=C(C(O)=O)NC2=C1 MQEQTBNFWHGSRJ-UHFFFAOYSA-N 0.000 description 3
FKKWFQULHCAHAQ-UHFFFAOYSA-N 3-methoxy-4-methyl-1h-indole-2-carboxylic acid Chemical compound C1=CC(C)=C2C(OC)=C(C(O)=O)NC2=C1 FKKWFQULHCAHAQ-UHFFFAOYSA-N 0.000 description 3
TUYZSKJQXNCPLN-UHFFFAOYSA-N 4-chloro-5-fluoro-1h-indole Chemical compound FC1=CC=C2NC=CC2=C1Cl TUYZSKJQXNCPLN-UHFFFAOYSA-N 0.000 description 3
VPXADRLFOWLPHM-UHFFFAOYSA-N 4-chloro-5-fluoro-1h-indole-2-carboxylic acid Chemical compound FC1=CC=C2NC(C(=O)O)=CC2=C1Cl VPXADRLFOWLPHM-UHFFFAOYSA-N 0.000 description 3
YCVSNMPGFSFANR-UHFFFAOYSA-N 5,6-difluoro-1h-indole Chemical compound C1=C(F)C(F)=CC2=C1NC=C2 YCVSNMPGFSFANR-UHFFFAOYSA-N 0.000 description 3
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LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
OHBYPJWPRMBNED-JQSSHNOQSA-N ClC1=C(C=C2C=CN(C2=C1)C[C@H](C)N)F.FC=1C=C2C=CN(C2=CC1)C[C@@H](C)N Chemical compound ClC1=C(C=C2C=CN(C2=C1)C[C@H](C)N)F.FC=1C=C2C=CN(C2=CC1)C[C@@H](C)N OHBYPJWPRMBNED-JQSSHNOQSA-N 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
ICMAFTSLXCXHRK-UHFFFAOYSA-N Ethyl pentanoate Chemical compound CCCCC(=O)OCC ICMAFTSLXCXHRK-UHFFFAOYSA-N 0.000 description 1
238000006783 Fischer indole synthesis reaction Methods 0.000 description 1
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
125000003047 N-acetyl group Chemical group 0.000 description 1
SJDOMIRMMUGQQK-UHFFFAOYSA-N NAN 190 Chemical compound COC1=CC=CC=C1N1CCN(CCCCN2C(C3=CC=CC=C3C2=O)=O)CC1 SJDOMIRMMUGQQK-UHFFFAOYSA-N 0.000 description 1
241001611408 Nebo Species 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
RJGVPVVPKPNWOE-QPXDRINRSA-N OC(=O)\C=C\C(O)=O.c1c(F)c(F)cc2c1ccn2C[C@H](N)C Chemical compound OC(=O)\C=C\C(O)=O.c1c(F)c(F)cc2c1ccn2C[C@H](N)C RJGVPVVPKPNWOE-QPXDRINRSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
150000003934 aromatic aldehydes Chemical class 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000002051 biphasic effect Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
239000003086 colorant Substances 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000010586 diagram Methods 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
YHDPTFUBKZJBRC-UHFFFAOYSA-N ethyl 3-ethyl-5-fluoro-1h-indole-2-carboxylate Chemical compound C1=C(F)C=C2C(CC)=C(C(=O)OCC)NC2=C1 YHDPTFUBKZJBRC-UHFFFAOYSA-N 0.000 description 1
KKJPCLMOJKUILK-UHFFFAOYSA-N ethyl 3-methoxy-4-methyl-1h-indole-2-carboxylate Chemical compound C1=CC(C)=C2C(OC)=C(C(=O)OCC)NC2=C1 KKJPCLMOJKUILK-UHFFFAOYSA-N 0.000 description 1
MKPIGDPELRNWBB-UHFFFAOYSA-N ethyl 4,5-difluoro-1h-indole-2-carboxylate Chemical compound FC1=CC=C2NC(C(=O)OCC)=CC2=C1F MKPIGDPELRNWBB-UHFFFAOYSA-N 0.000 description 1
OVSOYWROLOCQIS-UHFFFAOYSA-N ethyl 5,6-difluoro-1h-indole-2-carboxylate Chemical compound FC1=C(F)C=C2NC(C(=O)OCC)=CC2=C1 OVSOYWROLOCQIS-UHFFFAOYSA-N 0.000 description 1
BSJGKIJHMRRTDI-UHFFFAOYSA-N ethyl 5-fluoro-6-(trifluoromethyl)-1h-indole-2-carboxylate Chemical compound FC1=C(C(F)(F)F)C=C2NC(C(=O)OCC)=CC2=C1 BSJGKIJHMRRTDI-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000003925 fat Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
238000001033 granulometry Methods 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229950008693 mesulergine Drugs 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
RNEYRDIYQLBSMW-UHFFFAOYSA-N methyl 7-chloro-6-fluoro-1h-indole-2-carboxylate Chemical compound C1=C(F)C(Cl)=C2NC(C(=O)OC)=CC2=C1 RNEYRDIYQLBSMW-UHFFFAOYSA-N 0.000 description 1
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
238000005580 one pot reaction Methods 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
150000005331 phenylglycines Chemical class 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
JUQLTPCYUFPYKE-UHFFFAOYSA-N ritanserin Chemical compound CC=1N=C2SC=CN2C(=O)C=1CCN(CC1)CCC1=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 JUQLTPCYUFPYKE-UHFFFAOYSA-N 0.000 description 1
229950009626 ritanserin Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
230000007017 scission Effects 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
241000894007 species Species 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WQPVLAGBTJWVLF-UHFFFAOYSA-L tetrabutylazanium bromide hydroxide Chemical compound [OH-].[Br-].CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC WQPVLAGBTJWVLF-UHFFFAOYSA-L 0.000 description 1
238000001149 thermolysis Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Psychiatry (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pain & Pain Management (AREA)
Hematology (AREA)
Diabetes (AREA)
Hospice & Palliative Care (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Organic Insulating Materials (AREA)
Materials For Medical Uses (AREA)

CZ942604A 1993-10-22 1994-10-21 Indole derivatives, process of their preparation, intermediates for their preparation and medicaments based thereon CZ260494A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CH320193		1993-10-22

Publications (1)

Publication Number	Publication Date
CZ260494A3 true CZ260494A3 (en)	1995-10-18

Family

ID=4250849

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CZ942604A CZ260494A3 (en)	1993-10-22	1994-10-21	Indole derivatives, process of their preparation, intermediates for their preparation and medicaments based thereon

Country Status (19)

Country	Link
US (1)	US5494928A (2)
EP (1)	EP0655440A3 (2)
JP (1)	JP2638752B2 (2)
KR (1)	KR950011406A (2)
CN (1)	CN1061341C (2)
AU (1)	AU685841B2 (2)
BR (1)	BR9404203A (2)
CA (1)	CA2132883A1 (2)
CO (1)	CO4290356A1 (2)
CZ (1)	CZ260494A3 (2)
FI (1)	FI944969A7 (2)
HU (1)	HU218669B (2)
IL (1)	IL111314A (2)
NO (1)	NO301369B1 (2)
NZ (1)	NZ264713A (2)
PL (1)	PL179561B1 (2)
RU (1)	RU2136662C1 (2)
TW (1)	TW270114B (2)
ZA (1)	ZA948094B (2)

Families Citing this family (79)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9523999D0 (en)	1995-11-23	1996-01-24	Lilly Co Eli	Indolyl neuropeptide y receptor antagonists
WO1997009308A1 (en) *	1995-09-01	1997-03-13	Eli Lilly And Company	Indolyl neuropeptide y receptor antagonists
WO1997047598A1 (en) *	1996-06-12	1997-12-18	F. Hoffmann-La Roche Ag	A process for the manufacture of 1-(amino-alkyl)-indoles
AU727654B2 (en)	1997-06-13	2000-12-21	Yamanouchi Pharmaceutical Co., Ltd.	Tricyclic pyrazole derivative
DE69835004T2 (de) *	1997-08-07	2007-03-01	Fujimoto Brothers Co., Ltd., Matubara	Neue ethylaminderivate
US6960579B1 (en) *	1998-05-19	2005-11-01	Alcon Manufacturing, Ltd.	Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders
IT1314185B1 (it) *	1998-08-21	2002-12-06	Novartis Ag	Composizione farmaceutica per somministrazione di sostanze attivescarsamente solubili in mezzi acquosi
GB9819033D0 (en) *	1998-09-01	1998-10-28	Cerebrus Ltd	Chemical compounds VI
GB9819019D0 (en)	1998-09-01	1998-10-28	Cerebrus Ltd	Chemical compounds II
GB9819032D0 (en) *	1998-09-01	1998-10-28	Cerebrus Ltd	Chemical compounds IV
US6326379B1 (en)	1998-09-16	2001-12-04	Bristol-Myers Squibb Co.	Fused pyridine inhibitors of cGMP phosphodiesterase
CN1269484C (zh)	1998-09-18	2006-08-16	艾尔科实验室公司	用于治疗青光眼的5－羟色胺激活性激动剂
FR2788772B1 (fr) *	1999-01-26	2001-03-02	Adir	Nouveaux composes cyano-indoles inhibiteurs de recapture de serotonine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR2792313A1 (fr) *	1999-04-13	2000-10-20	Synthelabo	Derives de 2-aminoethyl-indole, leur preparation et leur application en therapeutique
US6465467B1 (en)	1999-05-21	2002-10-15	Biovitrum Ab	Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases
GB9918965D0 (en) *	1999-08-11	1999-10-13	Cerebrus Ltd	Chemical compounds xxi
GB9918962D0 (en)	1999-08-11	1999-10-13	Cerebrus Ltd	Chemical compounds xxii
KR100788970B1 (ko) *	1999-11-05	2007-12-27	에미스페어 테크놀로지스, 인코포레이티드	활성제 전달용 페녹시 카르복시산 화합물 및 조성물
WO2001040183A1 (en) *	1999-12-03	2001-06-07	Alcon Universal Ltd.	1-aminoalkyl-1h-indoles for treating glaucoma
JP3585796B2 (ja)	1999-12-17	2004-11-04	新光電気工業株式会社	多層配線基板の製造方法、及び半導体装置
DE19963178A1 (de) *	1999-12-27	2001-07-05	Gruenenthal Gmbh	Substituierte Indol-Mannichbasen
EP1132389A1 (en) *	2000-03-06	2001-09-12	Vernalis Research Limited	New aza-indolyl derivatives for the treatment of obesity
AU2001219185A1 (en)	2000-03-17	2001-10-03	Alcon, Inc.	2-acylaminobenzimidazole derivatives for treating glaucoma
US6956036B1 (en)	2000-03-17	2005-10-18	Alcon, Inc.	6-hydroxy-indazole derivatives for treating glaucoma
US6806285B1 (en)	2000-03-17	2004-10-19	Alcon, Inc.	5-Hydroxyl indole derivatives for treating glaucoma
BR0109193A (pt) *	2000-03-17	2003-05-27	Alcon Inc	Compostos com atividade agonista 5-ht2 e 5-ht1a para tratamento do glaucoma
US7012090B1 (en)	2000-03-17	2006-03-14	Alcon, Inc.	Pyranoindoles for treating glaucoma
US7005443B1 (en) *	2000-03-17	2006-02-28	Alcon, Inc.	5-Hydroxy indazole derivatives for treating glaucoma
US6903081B2 (en) *	2000-03-31	2005-06-07	Purdue Research Foundation	Phosphoramidates and methods therefor
TWI290136B (en)	2000-04-05	2007-11-21	Daiichi Seiyaku Co	Ethylenediamine derivatives
WO2001083487A1 (en) *	2000-04-28	2001-11-08	Yamanouchi Pharmaceutical Co., Ltd.	Froindazole derivative
WO2002044152A1 (en)	2000-10-16	2002-06-06	F. Hoffmann-La Roche Ag	Indoline derivatives and their use as 5-ht2 receptor ligands
SE0004245D0 (sv)	2000-11-20	2000-11-20	Pharmacia Ab	Novel compounds and their use
IL155875A0 (en)	2000-11-20	2003-12-23	Biovitrum Ab	Piperazinylpyrazines compounds as antagonists of serotonin 5-ht2 receptor
WO2004098807A1 (en) *	2000-11-21	2004-11-18	Barsplice Products, Inc.	Method of making steel couplers for joining concrete reinforcing bars
GB0030710D0 (en) *	2000-12-15	2001-01-31	Hoffmann La Roche	Piperazine derivatives
HUP0303316A2 (hu)	2000-12-20	2004-01-28	Bristol-Myers Squibb Pharma Company	Aril- és amino-aril-szubsztituált szerotoninreceptor agonista és antagonista ligandumok és ezeket tartalmazó gyógyszerkészítmények
WO2002051844A1 (en)	2000-12-27	2002-07-04	F. Hoffmann-La Roche Ag	Indole derivatives and their use as 5-ht2b and 5-ht2c receptor ligands
WO2002072548A2 (en)	2001-03-09	2002-09-19	Ortho-Mcneil Pharmaceutical, Inc.	Heterocyclic compounds and their use as histamine h4 ligands.
JP2004534781A (ja) *	2001-06-01	2004-11-18	アルコン，インコーポレイテッド	新規なアリールアミノプロパン類似体および緑内障治療へのこれらの使用
JP2004532887A (ja) *	2001-06-01	2004-10-28	アルコン，インコーポレイテッド	新規な融合インダゾールおよびインドールおよび緑内障治療へのこれらの使用
CA2447480A1 (en) *	2001-06-01	2002-12-12	Alcon, Inc.	Pyranoindazoles and their use for the treatment of glaucoma
US7365205B2 (en)	2001-06-20	2008-04-29	Daiichi Sankyo Company, Limited	Diamine derivatives
JP4128138B2 (ja)	2001-06-20	2008-07-30	第一三共株式会社	ジアミン誘導体
US6884816B2 (en) *	2001-08-31	2005-04-26	Alcon, Inc.	Hydroxy substituted fused naphthyl-azoles and fused indeno-azoles and their use for the treatment of glaucoma
TW593302B (en) *	2001-12-20	2004-06-21	Alcon Inc	Novel benzodifuranimidazoline and benzofuranimidazoline derivatives and their use for the treatment of glaucoma
CN100484933C (zh)	2002-06-19	2009-05-06	比奥维特罗姆股份公开公司	新的吡嗪化合物及其在制备用于治疗与5-羟色胺相关的疾病的药物中的用途
JP2006501245A (ja) *	2002-08-30	2006-01-12	アルコン，インコーポレイテッド	置換された５−クロマン−５−イル−エチルアミン化合物および緑内障の治療のためのその使用
US20040127395A1 (en) *	2002-09-06	2004-07-01	Desai Pragnya J.	Use of histamine H4 receptor modulators for the treatment of allergy and asthma
WO2004022060A2 (en)	2002-09-06	2004-03-18	Janssen Pharmaceutica, N.V.	(1h-benzoimidazol-2-yl)-(piperazinyl)-methanone derivatives and related compounds as histamine h4-receptor antagonists for the treatment of inflammatory and allergic disorders
BR0316775A (pt) *	2002-12-13	2005-11-01	Alcon Inc	Novos análogos de benzopirano e seu uso para o tratamento de glaucoma
CL2004000826A1 (es)	2003-04-25	2005-03-04	Pfizer	Uso de un agonista para el receptor 5-ht2c para preparar un medicamento util en el tratamiento de la incontinencia urinaria provocada por estres, con la condicion de que el agonista no sea 1-[6-cloro-5-(trifluorometil)-2-piridinil]piperazina (org-129
GB0314967D0 (en)	2003-06-26	2003-07-30	Hoffmann La Roche	Piperazine derivatives
US7476687B2 (en) *	2003-11-26	2009-01-13	Alcon, Inc.	Substituted furo[2,3-g]indazoles for the treatment of glaucoma
US7129257B1 (en) *	2003-12-15	2006-10-31	Alcon, Inc.	Pyrazolo[3,4- e]benzoxazoles for the treatment of glaucoma
TW200520760A (en) *	2003-12-15	2005-07-01	Alcon Inc	Substituted [1,4] oxazino [2,3-g] indazoles for the treatment of glaucoma
US7338972B1 (en)	2003-12-15	2008-03-04	Alcon, Inc.	Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma
EP2248524A3 (en)	2004-08-25	2011-03-09	Takeda Pharmaceutical Company Limited	Preventives/remedies for stress urinary incontinence and method of screening the same
US20060073172A1 (en) *	2004-10-01	2006-04-06	Schneider L W	Stabilized ophthalmic solution for the treatment of glaucoma and lowering intraocular pressure
US7425572B2 (en) *	2004-12-08	2008-09-16	Alcon, Inc.	Use of dioxindoindazoles and dioxoloindazoles for treating glaucoma
AP2007004144A0 (en)	2005-03-31	2007-08-31	Pfizer Prod Inc	Cyclopentapyridine and tetrahydroquinoline derivatives
TW200744567A (en) *	2005-09-23	2007-12-16	Alcon Inc	Phenylethylamine analogs and their use for treating glaucoma
EP2742936A1 (en)	2006-05-16	2014-06-18	Takeda Pharmaceutical Company Limited	Fused heterocyclic compound and use thereof
US20070293475A1 (en) *	2006-06-20	2007-12-20	Alcon Manufacturing Ltd.	Aryl and heteroaryl tetrahydrobenzazepine derivatives and their use for treating glaucoma
AU2007274710A1 (en) *	2006-07-14	2008-01-24	Pfizer Products Inc.	Tartrate salt of (7S)-7-[(5-fluoro-2-methyl-benzyl)oxy]-2-[(2R)-2-methylpiperazin-1-yl]-6,7-dihydro-5H-cyclopenta[b]pyridine
EP2789338A3 (en)	2007-11-15	2015-01-14	Takeda Pharmaceutical Company Limited	Condensed pyridine derivate and use thereof
DE102008009609A1 (de)	2008-02-18	2009-08-20	Freie Universität Berlin	Substituierte 4-(Indol-3-yl)chinazoline und deren Verwendung und Herstellung
KR101062376B1 (ko)	2008-04-10	2011-09-06	한국화학연구원	신규 인돌 카르복실산 비스피리딜 카르복사마이드 유도체,이의 제조방법 및 이를 유효성분으로 함유하는 조성물
JPWO2011071136A1 (ja)	2009-12-11	2013-04-22	アステラス製薬株式会社	線維筋痛症治療剤
US20130267500A1 (en)	2010-09-01	2013-10-10	Arena Pharmaceuticals, Inc.	5-ht2c receptor agonists in the treatment of disorders ameliorated by reduction of norepinephrine level
CN102702066A (zh) *	2011-03-28	2012-10-03	苏州百灵威超精细材料有限公司	一种用于合成抗癌和减肥药物中间体6-氯-5-氟吲哚的制备新方法
CN105120863B (zh) *	2013-03-14	2021-06-04	奥斯特克有限公司	促进骨生长的烷基胺骆驼蓬碱衍生物
WO2018064465A1 (en)	2016-09-29	2018-04-05	The Regents Of The University Of California	Compounds for increasing neural plasticity
EP3733204A4 (en)	2017-12-27	2021-09-15	Takeda Pharmaceutical Company Limited	THERAPEUTIC AGENT FOR URINARY INCONTINENCE OF STRESS AND FECAL INCONTINENCE
CA3109104A1 (en)	2018-08-14	2020-02-20	Osteoqc Inc.	Fluoro .beta.-carboline compounds
CA3108714A1 (en)	2018-08-14	2020-02-20	Osteoqc Inc.	Pyrrolo - dipyridine compounds
CN113784962B (zh)	2019-02-27	2025-04-25	加利福尼亚大学董事会	用于治疗脑部疾病的氮杂环庚三烯并-吲哚类和其他杂环
AU2020228289B2 (en)	2019-02-27	2026-02-05	The Regents Of The University Of California	N-substituted indoles and other heterocycles for treating brain disorders
TW202333668A (zh)	2021-12-15	2023-09-01	美商德利克斯醫療公司	經苯氧基及苄氧基取代之精神成形素(psychoplastogen)及其用途

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE791899A (fr) *	1971-11-26	1973-05-24	Ciba Geigy	Procede de preparation d'indoles n-substitues
US3904617A (en) *	1972-10-12	1975-09-09	Ayerst Mckenna & Harrison	Process for preparing new heterocyclic derivatives
IE37234B1 (en) *	1972-02-14	1977-06-08	Ayerst Mckenna & Harrison	Fused-ring indole derivatives
DE2430682A1 (de) *	1974-06-26	1976-01-15	Bayer Ag	Indolyl-mono-azofarbstoffe
FR2355006A1 (fr) *	1976-06-17	1978-01-13	Labaz	Nouveaux derives d'indole et procedes pour les preparer
DE2824447A1 (de) *	1978-06-03	1979-12-13	Cassella Ag	Pyrazino-carbazole, verfahren zu ihrer herstellung und sie enthaltendes pharmazeutisches mittel
DE3022648A1 (de) *	1979-06-29	1981-01-15	Sandoz Ag	Neue organische verbindungen, ihre herstellung und pharmazeutischen praeparate, welche diese verbindungen enthalten
FR2564465B1 (fr) *	1984-05-16	1986-10-03	Cortial	Nouveaux diamino-1,3 propanols-2, leurs methodes de preparation et leurs applications therapeutiques
PH23498A (en) *	1984-08-06	1989-08-16	Sterling Drug Inc	3-carbonyl-1-aminoalkyl-1h-indoles,composition and use thereof
US4660060A (en) *	1985-06-17	1987-04-21	The Hilton-Davis Chemical Co.	Imaging systems containing 3-(indol-3-yl)-3-(4-substituted aminophenyl)phthalides
CZ280738B6 (cs) *	1988-02-10	1996-04-17	F. Hoffmann - La Roche And Co., Aktiengesellschaft	Substituované pyrroly, jejich použití pro výrobu léčiv a léčiva na jejich bázi
FR2679561A1 (fr) *	1991-07-26	1993-01-29	Schneider Marc	Nouveaux derives de l'(indolyl-1) alkylamine substituee par une chaine presentant des groupements carbonyles conjugues a un noyau aromatique.
US5252732A (en) *	1991-09-09	1993-10-12	Merck & Co., Inc.	D-heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynylheteroarylmacrolides having immunosuppressive activity
EP0572863A1 (de) *	1992-06-05	1993-12-08	F. Hoffmann-La Roche Ag	ZNS Pyrazinoindole
US5310901A (en) *	1993-03-05	1994-05-10	Merck & Co., Inc.	O-heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynlheteroarylrapamycin derivatives

1994
- 1994-09-07 TW TW083108265A patent/TW270114B/zh active
- 1994-09-21 CA CA002132883A patent/CA2132883A1/en not_active Abandoned
- 1994-10-03 US US08/317,259 patent/US5494928A/en not_active Expired - Fee Related
- 1994-10-07 EP EP94115800A patent/EP0655440A3/de not_active Withdrawn
- 1994-10-14 AU AU75837/94A patent/AU685841B2/en not_active Ceased
- 1994-10-14 ZA ZA948094A patent/ZA948094B/xx unknown
- 1994-10-17 NZ NZ264713A patent/NZ264713A/en unknown
- 1994-10-17 HU HU9402983A patent/HU218669B/hu not_active IP Right Cessation
- 1994-10-17 IL IL11131494A patent/IL111314A/xx not_active IP Right Cessation
- 1994-10-19 CO CO94047587A patent/CO4290356A1/es unknown
- 1994-10-20 CN CN94117149A patent/CN1061341C/zh not_active Expired - Fee Related
- 1994-10-20 RU RU94037964A patent/RU2136662C1/ru active
- 1994-10-21 PL PL94305543A patent/PL179561B1/pl unknown
- 1994-10-21 BR BR9404203A patent/BR9404203A/pt not_active Application Discontinuation
- 1994-10-21 NO NO943999A patent/NO301369B1/no not_active IP Right Cessation
- 1994-10-21 CZ CZ942604A patent/CZ260494A3/cs unknown
- 1994-10-21 FI FI944969A patent/FI944969A7/fi unknown
- 1994-10-22 KR KR1019940027045A patent/KR950011406A/ko not_active Ceased
- 1994-10-24 JP JP6257775A patent/JP2638752B2/ja not_active Expired - Lifetime

Also Published As

Publication number	Publication date
IL111314A0 (en)	1994-12-29
EP0655440A3 (de)	1996-11-06
KR950011406A (ko)	1995-05-15
NZ264713A (en)	1996-05-28
CN1105988A (zh)	1995-08-02
ZA948094B (en)	1995-04-24
CO4290356A1 (es)	1996-04-17
CA2132883A1 (en)	1995-04-23
HU218669B (hu)	2000-10-28
US5494928A (en)	1996-02-27
EP0655440A2 (de)	1995-05-31
NO943999L (no)	1995-04-24
RU2136662C1 (ru)	1999-09-10
IL111314A (en)	1999-08-17
TW270114B (2)	1996-02-11
RU94037964A (ru)	1996-09-10
FI944969A0 (fi)	1994-10-21
NO943999D0 (no)	1994-10-21
FI944969A7 (fi)	1995-04-23
CN1061341C (zh)	2001-01-31
AU685841B2 (en)	1998-01-29
PL179561B1 (pl)	2000-09-29
HUT70848A (en)	1995-11-28
HU9402983D0 (en)	1995-02-28
BR9404203A (pt)	1995-07-04
PL305543A1 (en)	1995-05-02
NO301369B1 (no)	1997-10-20
AU7583794A (en)	1995-05-11
JP2638752B2 (ja)	1997-08-06
JPH07149723A (ja)	1995-06-13

Legal Events

Date	Code	Title	Description
2000-06-30	PD00	Pending as of 2000-06-30 in czech republic

Publication	Publication Date	Title
CZ260494A3 (en)	1995-10-18	Indole derivatives, process of their preparation, intermediates for their preparation and medicaments based thereon
AU655456B2 (en)	1994-12-22	5-heteroyl indole derivatives
JP2755560B2 (ja)	1998-05-20	三環式ピラゾール誘導体
US4634705A (en)	1987-01-06	Adrenergic amidines
JP2978566B2 (ja)	1999-11-15	ノイロキニンレセプター拮抗薬としての５−アザビシクロ［３．１．０］ヘキシルアルキル−２−ピペリドンおよび−グルタルイミド
US6350757B1 (en)	2002-02-26	Beta-carboline compounds
US4731358A (en)	1988-03-15	β-carbolines and their use as tranquilizers
IE59140B1 (en)	1994-01-12	Heterocyclic amide derivatives
JP5070042B2 (ja)	2012-11-07	選択的アンドローゲン受容体モジュレーター（ｓａｒｍｓ）としての新規インドール化合物
JPH07149762A (ja)	1995-06-13	ピペリジン類およびピペラジン類
EP0657426A2 (de)	1995-06-14	Tricyclische Pyrrol-Derivate
CA2330796A1 (en)	1999-11-18	Indole derivatives as 5-ht2a ligands and as serotonine reuptake inhibitors
DK157995B (da)	1990-03-12	Analogifremgangsmaade til fremstilling af indolderivater
US5563147A (en)	1996-10-08	Serotonerbic tetrahydropyridoindoles
JP4917018B2 (ja)	2012-04-18	選択的アンドローゲン受容体モジュレーター（ｓａｒｍｓ）としての新規インドール化合物
JP5070041B2 (ja)	2012-11-07	選択的アンドローゲン受容体モジュレーター（ｓａｒｍｓ）としての新規インドール化合物
US20080004268A1 (en)	2008-01-03	Inhibitors of soluble adenylate cyclase
Nagarathnam	1992	A facile synthesis of 3‐substituted indoles
IE65569B1 (en)	1995-11-01	Aliphatic carboxamides
JPS60158170A (ja)	1985-08-19	エテニルフェノールインドール誘導体及びそれらの塩、これらの製造方法並びにこれらを含有する薬剤
US20070232605A1 (en)	2007-10-04	Inhibitors of soluble adenylate cyclase
GB2126230A (en)	1984-03-21	Substituted 1-pyridyloxy-3- indolylakylamino-2-propanols, preparation, and use thereof
JPH09508637A (ja)	1997-09-02	５ｈｔ２ｂレセプタ拮抗薬縮合インドール
AU680562B2 (en)	1997-07-31	Tricyclic compounds having affinity for the 5-ht1a receptor
EP1874777B1 (fr)	2011-06-08	Dérivés de 1h-pyrimido[4,5-b]indole, leur préparation et leur application en thérapeutique