IL92990A - Piperazinyl butyl indole derivatives, process for their preparation and pharmaceutical compositions containing them - Google Patents

Piperazinyl butyl indole derivatives, process for their preparation and pharmaceutical compositions containing them

Info

Publication number: IL92990A
Authority: IL; Israel
Prior art keywords: compound; piperazinyl; hydrogen; butyl; formula
Prior art date: 1988-12-28

Application number

IL9299090A

Other languages

English (en)

Other versions

IL92990A0 (en

Original Assignee

Lundbeck & Co As H

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.)

1988-12-28

Filing date

1990-01-07

Publication date

1995-01-24

1990-01-07 Application filed by Lundbeck & Co As H filed Critical Lundbeck & Co As H

1990-09-17 Publication of IL92990A0 publication Critical patent/IL92990A0/xx

1995-01-24 Publication of IL92990A publication Critical patent/IL92990A/en

Links

238000000034 method Methods 0.000 title claims abstract description 36
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
238000002360 preparation method Methods 0.000 title claims description 5
CTZAPLFAGBFSKK-UHFFFAOYSA-N 2-butyl-3-piperazin-1-yl-1H-indole Chemical class N1(CCNCC1)C1=C(NC2=CC=CC=C12)CCCC CTZAPLFAGBFSKK-UHFFFAOYSA-N 0.000 title description 2
230000008569 process Effects 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 55
150000003839 salts Chemical class 0.000 claims abstract description 32
239000002253 acid Substances 0.000 claims abstract description 20
238000007792 addition Methods 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 19
150000002431 hydrogen Chemical group 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
230000005764 inhibitory process Effects 0.000 claims description 10
230000002152 alkylating effect Effects 0.000 claims description 7
150000002473 indoazoles Chemical class 0.000 claims description 7
231100000252 nontoxic Toxicity 0.000 claims description 7
230000003000 nontoxic effect Effects 0.000 claims description 7
-1 2,3-dihydro-7-benzofuranyl Chemical group 0.000 claims description 6
241001465754 Metazoa Species 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 6
239000012458 free base Substances 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical group 0.000 claims description 6
150000005623 oxindoles Chemical class 0.000 claims description 6
241000282414 Homo sapiens Species 0.000 claims description 5
125000003342 alkenyl group Chemical group 0.000 claims description 5
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
239000002552 dosage form Substances 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
150000002475 indoles Chemical class 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
230000009467 reduction Effects 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
150000001408 amides Chemical class 0.000 claims description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 2
230000010933 acylation Effects 0.000 claims description 2
238000005917 acylation reaction Methods 0.000 claims description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 2
125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 2
230000000116 mitigating effect Effects 0.000 claims description 2
230000003287 optical effect Effects 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims description 2
238000007363 ring formation reaction Methods 0.000 claims description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims 1
239000008024 pharmaceutical diluent Substances 0.000 claims 1
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 36
230000000694 effects Effects 0.000 abstract description 13
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230000002526 effect on cardiovascular system Effects 0.000 abstract description 2
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210000005095 gastrointestinal system Anatomy 0.000 abstract description 2
210000005227 renal system Anatomy 0.000 abstract description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000000203 mixture Substances 0.000 description 23
235000013350 formula milk Nutrition 0.000 description 21
238000012360 testing method Methods 0.000 description 19
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
239000012074 organic phase Substances 0.000 description 15
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229940079593 drug Drugs 0.000 description 14
239000003814 drug Substances 0.000 description 14
239000000243 solution Substances 0.000 description 12
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 11
229960004132 diethyl ether Drugs 0.000 description 11
239000002904 solvent Substances 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
238000010992 reflux Methods 0.000 description 9
230000004044 response Effects 0.000 description 9
238000003756 stirring Methods 0.000 description 9
230000027455 binding Effects 0.000 description 8
238000001816 cooling Methods 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
208000011580 syndromic disease Diseases 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
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 4
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
235000011054 acetic acid Nutrition 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
150000003891 oxalate salts Chemical class 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000000600 sorbitol Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
TZJUVVIWVWFLCD-UHFFFAOYSA-N 1,1-dioxo-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzothiazol-3-one Chemical compound O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 TZJUVVIWVWFLCD-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
239000001828 Gelatine Substances 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
230000008485 antagonism Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 3
229960002495 buspirone Drugs 0.000 description 3
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239000012043 crude product Substances 0.000 description 3
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235000019322 gelatine Nutrition 0.000 description 3
229960000647 gepirone Drugs 0.000 description 3
QOIGKGMMAGJZNZ-UHFFFAOYSA-N gepirone Chemical compound O=C1CC(C)(C)CC(=O)N1CCCCN1CCN(C=2N=CC=CN=2)CC1 QOIGKGMMAGJZNZ-UHFFFAOYSA-N 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
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239000008101 lactose Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
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229920001592 potato starch Polymers 0.000 description 3
239000000454 talc Substances 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
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HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
229910010082 LiAlH Inorganic materials 0.000 description 2
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000700157 Rattus norvegicus Species 0.000 description 2
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239000005557 antagonist Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
210000001638 cerebellum Anatomy 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 2
235000013681 dietary sucrose Nutrition 0.000 description 2
238000001035 drying Methods 0.000 description 2
150000007857 hydrazones Chemical class 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
JTEDVYBZBROSJT-UHFFFAOYSA-N indole-3-butyric acid Chemical class C1=CC=C2C(CCCC(=O)O)=CNC2=C1 JTEDVYBZBROSJT-UHFFFAOYSA-N 0.000 description 2
238000002955 isolation Methods 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
239000002858 neurotransmitter agent Substances 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000006408 oxalic acid Nutrition 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
239000008188 pellet Substances 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
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229940069328 povidone Drugs 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
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SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
IJCLNXZKUXGTRV-UHFFFAOYSA-N 2-(4-piperazin-1-ylbutyl)-1h-indole Chemical class C=1C2=CC=CC=C2NC=1CCCCN1CCNCC1 IJCLNXZKUXGTRV-UHFFFAOYSA-N 0.000 description 1
LCISFYAQKHOWBP-UHFFFAOYSA-N 2-chloro-5-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=C(Cl)C(C#N)=C1 LCISFYAQKHOWBP-UHFFFAOYSA-N 0.000 description 1
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
XWWOOJHKRZCEBN-UHFFFAOYSA-N 3-[4-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazin-1-yl]butyl]-5-fluoro-1h-indole Chemical compound O1CCOC2=C1C=CC=C2N(CC1)CCN1CCCCC1=CNC2=CC=C(F)C=C21 XWWOOJHKRZCEBN-UHFFFAOYSA-N 0.000 description 1
YPGUAJGTMSMNMY-UHFFFAOYSA-N 4-(1h-indol-2-yl)butanamide Chemical class C1=CC=C2NC(CCCC(=O)N)=CC2=C1 YPGUAJGTMSMNMY-UHFFFAOYSA-N 0.000 description 1
HXHGULXINZUGJX-UHFFFAOYSA-N 4-chlorobutanol Chemical compound OCCCCCl HXHGULXINZUGJX-UHFFFAOYSA-N 0.000 description 1
MIANLSMIRRRMJS-UHFFFAOYSA-N 5-meo-dmt Chemical compound [CH]1C(OC)=CC=C2N=CC(CCN(C)C)=C21 MIANLSMIRRRMJS-UHFFFAOYSA-N 0.000 description 1
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208000007848 Alcoholism Diseases 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
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COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical class CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
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KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
208000001953 Hypotension Diseases 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical class CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
IWTAOFMMRILLBR-UHFFFAOYSA-N N1C(=CC2=CC=CC=C12)C(CCO)C Chemical compound N1C(=CC2=CC=CC=C12)C(CCO)C IWTAOFMMRILLBR-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 1
241001494479 Pecora Species 0.000 description 1
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000004913 activation Effects 0.000 description 1
230000008484 agonism Effects 0.000 description 1
239000000556 agonist Substances 0.000 description 1
206010001584 alcohol abuse Diseases 0.000 description 1
208000025746 alcohol use disease Diseases 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
230000003326 anti-histaminergic effect Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
101150024767 arnT gene Proteins 0.000 description 1
230000006399 behavior Effects 0.000 description 1
UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
239000012267 brine Substances 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000006735 deficit Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
210000004744 fore-foot Anatomy 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
238000006197 hydroboration reaction Methods 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
208000021822 hypotensive Diseases 0.000 description 1
230000001077 hypotensive effect Effects 0.000 description 1
QNLOWBMKUIXCOW-UHFFFAOYSA-N indol-2-one Chemical class C1=CC=CC2=NC(=O)C=C21 QNLOWBMKUIXCOW-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000012528 membrane Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004899 motility Effects 0.000 description 1
HHQJWDKIRXRTLS-UHFFFAOYSA-N n'-bromobutanediamide Chemical compound NC(=O)CCC(=O)NBr HHQJWDKIRXRTLS-UHFFFAOYSA-N 0.000 description 1
230000010807 negative regulation of binding Effects 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
229960001779 pargyline Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
125000004193 piperazinyl group Chemical class 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000005057 refrigeration Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
238000003375 selectivity assay Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000000862 serotonergic effect Effects 0.000 description 1
239000000952 serotonin receptor agonist Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000011343 solid material Substances 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000003826 tablet Substances 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
230000001519 thymoleptic effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
239000003204 tranquilizing agent Substances 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
238000007514 turning Methods 0.000 description 1
JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
238000009941 weaving Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- A61P25/20—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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Anesthesiology (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

IL9299090A 1988-12-28 1990-01-07 Piperazinyl butyl indole derivatives, process for their preparation and pharmaceutical compositions containing them IL92990A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB888830312A GB8830312D0 (en)	1988-12-28	1988-12-28	Heterocyclic compounds

Publications (2)

Publication Number	Publication Date
IL92990A0 IL92990A0 (en)	1990-09-17
IL92990A true IL92990A (en)	1995-01-24

Family

ID=10649223

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9299090A IL92990A (en)	1988-12-28	1990-01-07	Piperazinyl butyl indole derivatives, process for their preparation and pharmaceutical compositions containing them

Country Status (17)

Country	Link
US (1)	US5002948A (fr)
EP (1)	EP0376607B1 (fr)
JP (1)	JP2895121B2 (fr)
AT (1)	ATE102184T1 (fr)
AU (1)	AU637991B2 (fr)
CA (1)	CA2006356C (fr)
DE (1)	DE68913487T2 (fr)
DK (1)	DK169266B1 (fr)
ES (1)	ES2062050T3 (fr)
FI (1)	FI93005C (fr)
GB (1)	GB8830312D0 (fr)
IE (1)	IE62668B1 (fr)
IL (1)	IL92990A (fr)
NO (1)	NO174772C (fr)
NZ (1)	NZ231855A (fr)
PT (1)	PT92728B (fr)
ZA (1)	ZA899960B (fr)

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1988
- 1988-12-28 GB GB888830312A patent/GB8830312D0/en active Pending
1989
- 1989-12-12 IE IE397689A patent/IE62668B1/en not_active IP Right Cessation
- 1989-12-19 NZ NZ231855A patent/NZ231855A/en unknown
- 1989-12-19 DK DK645689A patent/DK169266B1/da not_active IP Right Cessation
- 1989-12-20 DE DE68913487T patent/DE68913487T2/de not_active Expired - Fee Related
- 1989-12-20 AT AT89313371T patent/ATE102184T1/de not_active IP Right Cessation
- 1989-12-20 EP EP89313371A patent/EP0376607B1/fr not_active Expired - Lifetime
- 1989-12-20 ES ES89313371T patent/ES2062050T3/es not_active Expired - Lifetime
- 1989-12-21 CA CA002006356A patent/CA2006356C/fr not_active Expired - Lifetime
- 1989-12-22 AU AU47198/89A patent/AU637991B2/en not_active Ceased
- 1989-12-26 US US07/456,938 patent/US5002948A/en not_active Expired - Lifetime
- 1989-12-27 NO NO895281A patent/NO174772C/no not_active IP Right Cessation
- 1989-12-27 PT PT92728A patent/PT92728B/pt not_active IP Right Cessation
- 1989-12-27 JP JP1336755A patent/JP2895121B2/ja not_active Expired - Fee Related
- 1989-12-28 FI FI896300A patent/FI93005C/fi active IP Right Grant
- 1989-12-28 ZA ZA899960A patent/ZA899960B/xx unknown
1990
- 1990-01-07 IL IL9299090A patent/IL92990A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
DK645689A (da)	1990-06-29
NO895281L (no)	1990-06-29
CA2006356C (fr)	1999-09-14
PT92728A (pt)	1990-06-29
JP2895121B2 (ja)	1999-05-24
EP0376607A1 (fr)	1990-07-04
JPH02225460A (ja)	1990-09-07
ES2062050T3 (es)	1994-12-16
NZ231855A (en)	1992-02-25
AU4719889A (en)	1990-07-05
DE68913487D1 (de)	1994-04-07
NO174772B (no)	1994-03-28
DK645689D0 (da)	1989-12-19
DK169266B1 (da)	1994-09-26
DE68913487T2 (de)	1994-08-04
ZA899960B (en)	1990-11-28
IE893976L (en)	1990-06-13
AU637991B2 (en)	1993-06-17
FI93005C (fi)	1995-02-10
IE62668B1 (en)	1995-02-22
FI93005B (fi)	1994-10-31
CA2006356A1 (fr)	1990-06-28
FI896300A0 (fi)	1989-12-28
PT92728B (pt)	1995-12-29
NO895281D0 (no)	1989-12-27
EP0376607B1 (fr)	1994-03-02
ATE102184T1 (de)	1994-03-15
GB8830312D0 (en)	1989-02-22
IL92990A0 (en)	1990-09-17
NO174772C (no)	1994-07-06
US5002948A (en)	1991-03-26

Legal Events

Date	Code	Title
1996-03-31	KB	Patent renewed
2000-07-16	FF	Patent granted
2000-08-31	KB	Patent renewed
2004-02-19	KB	Patent renewed
2008-02-10	KB	Patent renewed
2010-11-30	EXP	Patent expired

Publication	Publication Date	Title
IL92990A (en)	1995-01-24	Piperazinyl butyl indole derivatives, process for their preparation and pharmaceutical compositions containing them
EP0200322B1 (fr)	1990-02-28	Composés hétérocycliques
HU225101B1 (en)	2006-06-28	Indole and 2,3-dihydroindole derivatives, their preparation, use, and pharmaceutical compositions containing them
US5393761A (en)	1995-02-28	3-arylindole compounds
AU765317B2 (en)	2003-09-18	4,5,6 and 7-indole and indoline derivatives, their preparation and use
WO1998031669A1 (fr)	1998-07-23	Nouvelles arylpiperazines derivees de piperidine comme medicaments antidepresseurs
NO312243B1 (no)	2002-04-15	N-substituerte 3-azabicyklo[3.2.0]heptanderivater egnet som neuroleptika
EP0110521B1 (fr)	1988-10-12	Dérivés du phénylindène, leurs sels d'addition, et leurs méthodes de préparation
JP3898219B2 (ja)	2007-03-28	フエニルインドール化合物
JPH08333362A (ja)	1996-12-17	新規インドール、インダゾール及びベンゾイソオキサゾール化合物、その製造方法ならびにそれを含む医薬組成物
US6391882B1 (en)	2002-05-21	4,5,6 and 7-indole and indoline derivatitives, their preparation and use
WO2000049017A1 (fr)	2000-08-24	Dioxydes de 1-((indoly azacycloalkyl) alkyl)-2,1, 3-benzothiadiazole 2,2 faisant montre d'une activite de recepteur 5-ht2a
US20070219209A1 (en)	2007-09-20	Piperazine Derivatives Of Alkyl Oxindoles
SK952000A3 (en)	2001-03-12	Indole and 2,3-dihydroindole derivatives, their preparation and use
MXPA00012609A (en)	2001-07-31	4,5,6 and 7-indole and indoline derivatives, their preparation and use