AP535A - Indoline derivatives, method of preparation and use. - Google Patents

Indoline derivatives, method of preparation and use. Download PDF

Info

Publication number: AP535A
Authority: AP; ARIPO
Prior art keywords: formula; compound; compounds; pharmaceutically acceptable; mixture
Prior art date: 1993-12-22

Application number

APAP/P/1994/000706A

Other languages

English (en)

Other versions

AP9400706A0 (en

Inventor

Peter Charles North

Malcom Clive Carter

Original Assignee

Glaxo Group Ltd

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.)

1993-12-22

Filing date

1994-12-20

Publication date

1996-09-16

1994-12-20 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1995-01-31 Publication of AP9400706A0 publication Critical patent/AP9400706A0/xx

1996-09-16 Application granted granted Critical

1996-09-16 Publication of AP535A publication Critical patent/AP535A/en

Links

238000000034 method Methods 0.000 title claims description 26
238000002360 preparation method Methods 0.000 title claims description 16
125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 156
150000003839 salts Chemical class 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 14
DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 14
229960003987 melatonin Drugs 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 12
239000008194 pharmaceutical composition Substances 0.000 claims description 11
150000002367 halogens Chemical class 0.000 claims description 10
230000008569 process Effects 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 9
239000012453 solvate Substances 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
239000000460 chlorine Chemical group 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
238000002156 mixing Methods 0.000 claims description 6
230000010933 acylation Effects 0.000 claims description 5
238000005917 acylation reaction Methods 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
238000002560 therapeutic procedure Methods 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 3
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
LTYWTNUOUBBVNZ-UHFFFAOYSA-N n-[2-(2,3,7,8-tetrahydrofuro[2,3-g]indol-1-yl)ethyl]acetamide Chemical compound C1=C2OCCC2=C2N(CCNC(=O)C)CCC2=C1 LTYWTNUOUBBVNZ-UHFFFAOYSA-N 0.000 claims description 3
GNBKDTKDTLHXLV-UHFFFAOYSA-N n-[2-(2,3,7,8-tetrahydrofuro[2,3-g]indol-1-yl)ethyl]cyclopropanecarboxamide Chemical compound C1CC2=CC=C3OCCC3=C2N1CCNC(=O)C1CC1 GNBKDTKDTLHXLV-UHFFFAOYSA-N 0.000 claims description 2
VFDGXIWZUURKKF-UHFFFAOYSA-N n-[2-(3,7,8,9-tetrahydro-2h-pyrano[2,3-g]indol-1-yl)ethyl]acetamide Chemical compound O1CCCC2=C3N(CCNC(=O)C)CCC3=CC=C21 VFDGXIWZUURKKF-UHFFFAOYSA-N 0.000 claims description 2
KDXSVVJYMBFMHU-UHFFFAOYSA-N n-[2-(5-chloro-2,3,7,8-tetrahydrofuro[2,3-g]indol-1-yl)ethyl]acetamide Chemical compound ClC1=C2OCCC2=C2N(CCNC(=O)C)CCC2=C1 KDXSVVJYMBFMHU-UHFFFAOYSA-N 0.000 claims description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
239000000203 mixture Substances 0.000 description 73
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
235000019439 ethyl acetate Nutrition 0.000 description 50
239000000543 intermediate Substances 0.000 description 50
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
239000004480 active ingredient Substances 0.000 description 42
239000000243 solution Substances 0.000 description 42
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
239000000284 extract Substances 0.000 description 22
238000010992 reflux Methods 0.000 description 20
239000002904 solvent Substances 0.000 description 20
239000003826 tablet Substances 0.000 description 20
238000010828 elution Methods 0.000 description 19
239000007787 solid Substances 0.000 description 19
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000000377 silicon dioxide Substances 0.000 description 18
239000002253 acid Substances 0.000 description 17
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
239000000741 silica gel Substances 0.000 description 16
229910002027 silica gel Inorganic materials 0.000 description 16
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 14
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
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 12
235000019441 ethanol Nutrition 0.000 description 12
239000008101 lactose Substances 0.000 description 12
229960001375 lactose Drugs 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000000725 suspension Substances 0.000 description 12
229910000069 nitrogen hydride Inorganic materials 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
229910052681 coesite Inorganic materials 0.000 description 10
229910052906 cristobalite Inorganic materials 0.000 description 10
239000008187 granular material Substances 0.000 description 10
229910052682 stishovite Inorganic materials 0.000 description 10
229910052905 tridymite Inorganic materials 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
238000009472 formulation Methods 0.000 description 9
229910000029 sodium carbonate Inorganic materials 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
239000000443 aerosol Substances 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
239000000843 powder Substances 0.000 description 8
-1 hydrates) thereof Chemical class 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
239000002775 capsule Substances 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 6
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
239000008213 purified water Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 5
239000012267 brine Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000000796 flavoring agent Substances 0.000 description 5
230000008570 general process Effects 0.000 description 5
238000001990 intravenous administration Methods 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
229920002261 Corn starch Polymers 0.000 description 4
235000019759 Maize starch Nutrition 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
206010028980 Neoplasm Diseases 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
238000007906 compression Methods 0.000 description 4
230000006835 compression Effects 0.000 description 4
235000019634 flavors Nutrition 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
238000001802 infusion Methods 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
239000008107 starch Substances 0.000 description 4
229940032147 starch Drugs 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
238000011200 topical administration Methods 0.000 description 4
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 3
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 3
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
206010012289 Dementia Diseases 0.000 description 3
239000004338 Dichlorodifluoromethane Substances 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
229920000168 Microcrystalline cellulose Polymers 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
239000005642 Oleic acid Substances 0.000 description 3
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
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YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
230000037396 body weight Effects 0.000 description 3
239000011248 coating agent Substances 0.000 description 3
238000000576 coating method Methods 0.000 description 3
239000003240 coconut oil Substances 0.000 description 3
235000019864 coconut oil Nutrition 0.000 description 3
BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 3
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
235000019404 dichlorodifluoromethane Nutrition 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000012467 final product Substances 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
235000003599 food sweetener Nutrition 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
150000004677 hydrates Chemical class 0.000 description 3
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000012669 liquid formulation Substances 0.000 description 3
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208000015706 neuroendocrine disease Diseases 0.000 description 3
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
210000001525 retina Anatomy 0.000 description 3
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239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
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VODKOOOHHCAWFR-UHFFFAOYSA-N 2-iodoacetonitrile Chemical compound ICC#N VODKOOOHHCAWFR-UHFFFAOYSA-N 0.000 description 2
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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 description 2
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239000003513 alkali Substances 0.000 description 2
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239000000605 aspartame Substances 0.000 description 2
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 2
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229910052794 bromium Inorganic materials 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
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239000000969 carrier Substances 0.000 description 2
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230000003280 chronobiological effect Effects 0.000 description 2
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DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Child & Adolescent Psychology (AREA)
Obesity (AREA)
Hematology (AREA)
Anesthesiology (AREA)
Urology & Nephrology (AREA)
Psychiatry (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Furan Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

APAP/P/1994/000706A 1993-12-22 1994-12-20 Indoline derivatives, method of preparation and use. AP535A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB939326192A GB9326192D0 (en)	1993-12-22	1993-12-22	Chemical compounds

Publications (2)

Publication Number	Publication Date
AP9400706A0 AP9400706A0 (en)	1995-01-31
AP535A true AP535A (en)	1996-09-16

Family

ID=10747030

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1994/000706A AP535A (en)	1993-12-22	1994-12-20	Indoline derivatives, method of preparation and use.

Country Status (15)

Country	Link
US (1)	US5633276A (is)
EP (1)	EP0736028A1 (is)
JP (1)	JPH09507057A (is)
AP (1)	AP535A (is)
AU (1)	AU684877B2 (is)
CA (1)	CA2179402A1 (is)
CO (1)	CO4340623A1 (is)
GB (1)	GB9326192D0 (is)
IL (1)	IL112097A (is)
IS (1)	IS4244A (is)
MY (1)	MY131641A (is)
SV (1)	SV1994000083A (is)
TW (1)	TW291479B (is)
WO (1)	WO1995017405A1 (is)
ZA (1)	ZA9410056B (is)

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EP1199304A1 (en) *	1997-03-05	2002-04-24	Takeda Chemical Industries, Ltd.	Bicyclic compounds and pharmaceutical composition containing tricyclic compound for treating or preventing sleep disorders
US6034239A (en) *	1996-03-08	2000-03-07	Takeda Chemical Industries, Ltd.	Tricyclic compounds, their production and use
ZA9711051B (en) *	1996-12-10	1999-06-09	Bristol Myers Squibb Co	Benzodioxole benzofuran dihydrobenzofuran and benzodioxane melatonergic agents
WO1998038991A1 (en) *	1997-03-05	1998-09-11	Bristol-Myers Squibb Company	Polycyclic ethyl alkylamide melatonergic agents
FR2763335B1 (fr) *	1997-05-16	2000-11-24	Adir	Nouveaux composes heterocycliques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
AU727654B2 (en) *	1997-06-13	2000-12-21	Yamanouchi Pharmaceutical Co., Ltd.	Tricyclic pyrazole derivative
CA2334299A1 (en)	1998-06-05	1999-12-09	Pierre Dextraze	Heterocyclic cis cyclopropane derivatives as melatonergic agents
EP1189900B1 (en)	1999-06-30	2004-01-14	Bristol-Myers Squibb Company	Heterocyclic aminopyrrolidine derivatives as melatonergic agents
GB9918965D0 (en) *	1999-08-11	1999-10-13	Cerebrus Ltd	Chemical compounds xxi
CA2382418A1 (en)	1999-08-20	2001-03-01	Shigenori Ohkawa	Dihydrobenzofuran derivatives, process for preparing thereof and agents
US7012090B1 (en)	2000-03-17	2006-03-14	Alcon, Inc.	Pyranoindoles for treating glaucoma
DK1268482T3 (da) *	2000-03-17	2003-12-22	Alcon Inc	Pyranoindoler til behandling af glaukom
ES2172415B2 (es)	2000-07-28	2003-11-16	Univ Madrid Complutense	Tratamiento del glaucoma y la hipertension ocular por medio de un analogo de la melatonina.
US6743448B2 (en) *	2000-12-11	2004-06-01	Abraham H. Kryger	Topical testosterone formulations and associated methods
WO2002079153A1 (en) *	2001-03-28	2002-10-10	Biocatalytics, Inc.	Method for producing tryptamine derivatives
CA2644181A1 (en) *	2006-03-20	2007-09-27	Takeda Pharmaceutical Company Limited	Prophylactic or therapeutic agent for irritable bowel syndrome
ATE548371T1 (de)	2006-12-08	2012-03-15	Takeda Pharmaceutical	Tricyclische verbindung und deren medizinische verwendung
ES2331274B1 (es) *	2007-10-25	2010-10-21	Ferrer Internacional, S.A.	Compuesto de indolina.
JP2011529477A (ja) *	2008-07-30	2011-12-08	フエルレルインターナショナル，ソシエダッドアノニマ	１，６−ジヒドロ−２ｈ−３−オキサ−６−アザ−ａｓ−インダセン化合物
BR102016024814A2 (pt)	2016-10-24	2018-05-08	Aché Laboratórios Farmacêuticos S.A.	composto, processo de obtenção do composto, composição farmacêutica, uso do composto e método de tratamento de desordens psiquiátricas e/ou distúrbios do sono

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1993
- 1993-12-22 GB GB939326192A patent/GB9326192D0/en active Pending
1994
- 1994-12-08 TW TW083111439A patent/TW291479B/zh active
- 1994-12-16 IS IS4244A patent/IS4244A/is unknown
- 1994-12-19 ZA ZA9410056A patent/ZA9410056B/xx unknown
- 1994-12-19 MY MYPI94003410A patent/MY131641A/en unknown
- 1994-12-20 WO PCT/EP1994/004220 patent/WO1995017405A1/en not_active Ceased
- 1994-12-20 CA CA002179402A patent/CA2179402A1/en not_active Abandoned
- 1994-12-20 EP EP95903817A patent/EP0736028A1/en not_active Ceased
- 1994-12-20 AU AU12743/95A patent/AU684877B2/en not_active Ceased
- 1994-12-20 AP APAP/P/1994/000706A patent/AP535A/en active
- 1994-12-20 JP JP7517174A patent/JPH09507057A/ja active Pending
- 1994-12-20 US US08/652,460 patent/US5633276A/en not_active Expired - Fee Related
- 1994-12-21 CO CO94057739A patent/CO4340623A1/es unknown
- 1994-12-21 IL IL112097A patent/IL112097A/en not_active IP Right Cessation
- 1994-12-21 SV SV1994000083A patent/SV1994000083A/es unknown

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EP0207605A1 (en) *	1985-05-21	1987-01-07	Pfizer Inc.	Hypoglycemic thiazolidinediones

Also Published As

Publication number	Publication date
WO1995017405A1 (en)	1995-06-29
CA2179402A1 (en)	1995-06-29
JPH09507057A (ja)	1997-07-15
ZA9410056B (en)	1995-10-18
AP9400706A0 (en)	1995-01-31
GB9326192D0 (en)	1994-02-23
IS4244A (is)	1995-06-23
AU684877B2 (en)	1998-01-08
US5633276A (en)	1997-05-27
CO4340623A1 (es)	1996-07-30
EP0736028A1 (en)	1996-10-09
SV1994000083A (es)	1995-07-24
MY131641A (en)	2007-08-30
TW291479B (is)	1996-11-21
IL112097A0 (en)	1995-03-15
AU1274395A (en)	1995-07-10
IL112097A (en)	1998-06-15

Publication	Publication Date	Title
AP535A (en)	1996-09-16	Indoline derivatives, method of preparation and use.
JP2941309B2 (ja)	1999-08-25	化合物
JP5271903B2 (ja)	2013-08-21	オピオイド受容体系に作用する、４−ヘテロアリール置換された１−アミノシクロヘキサン−１−及びシクロヘキセン−１−誘導体
RU2095360C1 (ru)	1997-11-10	Производные индола, их оптические изомеры и фармацевтически приемлемые соли
JP3033076B2 (ja)	2000-04-17	カンナビノイド受容体への親和性を有するインドール誘導体
KR930003759B1 (ko)	1993-05-10	인돌 유도체의 제조방법
EP0690843B1 (en)	2000-08-30	Formyl- or cyano- substituted indole derivatives having dopaminergic activity
US5981572A (en)	1999-11-09	Benzofurans and benzopyrans as chronobiological agents
LU85743A1 (fr)	1986-08-04	Composes heterocycliques
JPH06199784A (ja)	1994-07-19	新規なアリールエチアミン化合物、その製法、及びこれを含有する医薬組成物。
JP2000510153A (ja)	2000-08-08	スピロ―ピペリジン誘導体及び該誘導体の治療薬としての使用
JPS6277383A (ja)	1987-04-09	複素環式化合物
JPH10508297A (ja)	1998-08-18	ニューロキニンアンタゴニストとしての置換アリールピペラジン
JPH08506823A (ja)	1996-07-23	アザ環式化合物、該化合物を含む組成物及びタキキニン拮抗剤としての該化合物の使用
JP2000515136A (ja)	2000-11-14	プロテインチロシンキナーゼ阻害剤としての二環式ヘテロ芳香族化合物
KR20000023812A (ko)	2000-04-25	단백질 티로신 키나제의 억제제인 비시클릭 헤테로방향족 화합물
JP2001521925A (ja)	2001-11-13	Ｐｄｅ４阻害剤におけるカテコールのインダゾールバイオイソステル置換に基づく治療学的に活性な化合物
US7060710B2 (en)	2006-06-13	Isoxazole pyrazoloindane derivatives as cognition enhancing GABAA α5 subtype ligands
JPH10502336A (ja)	1998-03-03	ナフタレン誘導体、製造方法および使用
CH667454A5 (fr)	1988-10-14	Derives d'indoles.
US20030073832A1 (en)	2003-04-17	Novel aminophenyl ketone derivatives
JP2001504501A (ja)	2001-04-03	５−ｈｔ▲下１ｄ▼レセプターのリガンドとしての５−シクロインドール化合物
JP2941333B2 (ja)	1999-08-25	インドール誘導体
JPH09512034A (ja)	1997-12-02	５ｈｔ１−様作動薬としてのインドール誘導体
JP2791069B2 (ja)	1998-08-27	シクロオクタン神経保護剤