CA2084531A1 - Antimigraine 4-pyrimidinyl and pyridinyl derivatives of indol-3yl-alkyl piperazines - Google Patents
Antimigraine 4-pyrimidinyl and pyridinyl derivatives of indol-3yl-alkyl piperazinesInfo
- Publication number
- CA2084531A1 CA2084531A1 CA002084531A CA2084531A CA2084531A1 CA 2084531 A1 CA2084531 A1 CA 2084531A1 CA 002084531 A CA002084531 A CA 002084531A CA 2084531 A CA2084531 A CA 2084531A CA 2084531 A1 CA2084531 A1 CA 2084531A1
- Authority
- CA
- Canada
- Prior art keywords
- methoxy
- indol
- propyl
- pyrimidinyl
- piperazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000002460 anti-migrenic effect Effects 0.000 title description 8
- 125000004076 pyridyl group Chemical group 0.000 title description 4
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 title description 2
- 208000001407 Vascular Headaches Diseases 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims description 95
- 150000001875 compounds Chemical class 0.000 claims description 94
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 60
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 45
- -1 cyano, hydroxy Chemical group 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 208000019695 Migraine disease Diseases 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 5
- PTXVSDKCUJCCLC-UHFFFAOYSA-N 1-hydroxyindole Chemical compound C1=CC=C2N(O)C=CC2=C1 PTXVSDKCUJCCLC-UHFFFAOYSA-N 0.000 claims description 4
- 208000006561 Cluster Headache Diseases 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- IBTDQBCNOPVYCJ-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-amine Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(N)=CC=C3NC=2)CC1 IBTDQBCNOPVYCJ-UHFFFAOYSA-N 0.000 claims description 3
- 206010027603 Migraine headaches Diseases 0.000 claims description 3
- WRZVGHXUPBWIOO-UHFFFAOYSA-N avitriptan Chemical compound C12=CC(CS(=O)(=O)NC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC WRZVGHXUPBWIOO-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 238000007910 systemic administration Methods 0.000 claims description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 3
- RTPGEMPUQWTOTJ-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carbonitrile Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)C#N)CC1 RTPGEMPUQWTOTJ-UHFFFAOYSA-N 0.000 claims description 2
- SYVBXSCDUSJDPO-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-5-nitro-1h-indole Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)[N+]([O-])=O)CC1 SYVBXSCDUSJDPO-UHFFFAOYSA-N 0.000 claims description 2
- HIQHYSPKBHAPAT-UHFFFAOYSA-N n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CNC(C)=O)=CC=C3NC=2)CC1 HIQHYSPKBHAPAT-UHFFFAOYSA-N 0.000 claims description 2
- IADMRNYXCINVAD-UHFFFAOYSA-N n-benzyl-n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]ethanesulfonamide Chemical compound C=1C=C2NC=C(CCCN3CCN(CC3)C=3C(=CN=CN=3)OC)C2=CC=1CN(S(=O)(=O)CC)CC1=CC=CC=C1 IADMRNYXCINVAD-UHFFFAOYSA-N 0.000 claims description 2
- DHFOXXSSNOLXLQ-UHFFFAOYSA-N n-butyl-3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxamide Chemical compound C12=CC(C(=O)NCCCC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC DHFOXXSSNOLXLQ-UHFFFAOYSA-N 0.000 claims description 2
- STTZIYOGYXNCJJ-UHFFFAOYSA-N 1,1,1-trifluoro-n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)N(C)S(=O)(=O)C(F)(F)F)CC1 STTZIYOGYXNCJJ-UHFFFAOYSA-N 0.000 claims 1
- OVXCQLRRCQNGBY-UHFFFAOYSA-N 1-[3-[3-[4-(3-methoxypyridin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound C12=CC(CS(=O)(=O)NC)=CC=C2NC=C1CCCN(CC1)CCN1C1=CC=NC=C1OC OVXCQLRRCQNGBY-UHFFFAOYSA-N 0.000 claims 1
- AKGZJDYNQGZZKQ-UHFFFAOYSA-N 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound C12=CC(CS(=O)(=O)NC)=CC=C2NC=C1CCCN(CC1C)CCN1C1=NC=NC=C1OC AKGZJDYNQGZZKQ-UHFFFAOYSA-N 0.000 claims 1
- QKBUNBGWOJHAOI-UHFFFAOYSA-N 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]-n,n-dimethylmethanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CS(=O)(=O)N(C)C)=CC=C3NC=2)CC1 QKBUNBGWOJHAOI-UHFFFAOYSA-N 0.000 claims 1
- JMNJPZYYLUALFK-UHFFFAOYSA-N 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]ethanone Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)C(C)=O)CC1 JMNJPZYYLUALFK-UHFFFAOYSA-N 0.000 claims 1
- GIEJMDKFKNPLOV-UHFFFAOYSA-N 2,2,2-trifluoro-n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(NC(=O)C(F)(F)F)=CC=C3NC=2)CC1 GIEJMDKFKNPLOV-UHFFFAOYSA-N 0.000 claims 1
- HYHYARGSQDRKBV-UHFFFAOYSA-N 2-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CC(N)=O)=CC=C3NC=2)CC1 HYHYARGSQDRKBV-UHFFFAOYSA-N 0.000 claims 1
- WIESNRIAUAAAKN-UHFFFAOYSA-N 2-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]oxy]acetonitrile Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(OCC#N)=CC=C3NC=2)CC1 WIESNRIAUAAAKN-UHFFFAOYSA-N 0.000 claims 1
- IZKSPDDPCCFXFI-UHFFFAOYSA-N 3-[3-[4-(3-methoxypyridin-4-yl)piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CN=CC=C1N1CCN(CCCC=2C3=CC=CC=C3NC=2)CC1 IZKSPDDPCCFXFI-UHFFFAOYSA-N 0.000 claims 1
- WZKOGWNTMBGKHG-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indole-5-carboxamide Chemical compound COC1=CN=CN=C1N1C(C)CN(CCCC=2C3=CC(=CC=C3NC=2)C(N)=O)CC1 WZKOGWNTMBGKHG-UHFFFAOYSA-N 0.000 claims 1
- VBTUHIJWHRUHJA-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-5-(2-methylsulfonylethyl)-1h-indole Chemical compound COC1=CN=CN=C1N1C(C)CN(CCCC=2C3=CC(CCS(C)(=O)=O)=CC=C3NC=2)CC1 VBTUHIJWHRUHJA-UHFFFAOYSA-N 0.000 claims 1
- GAFUZWCJMTXSDI-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-n-methyl-1h-indole-5-carboxamide Chemical compound C12=CC(C(=O)NC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC GAFUZWCJMTXSDI-UHFFFAOYSA-N 0.000 claims 1
- VPWKKLQAJWALMT-UHFFFAOYSA-N [3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CS(N)(=O)=O)=CC=C3NC=2)CC1 VPWKKLQAJWALMT-UHFFFAOYSA-N 0.000 claims 1
- AVGNIAXJZABVOT-UHFFFAOYSA-N benzyl n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]carbamate Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(NC(=O)OCC=4C=CC=CC=4)=CC=C3NC=2)CC1 AVGNIAXJZABVOT-UHFFFAOYSA-N 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- NIKWZIOCGGZIQE-UHFFFAOYSA-N ethyl 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxylate Chemical compound C12=CC(C(=O)OCC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC NIKWZIOCGGZIQE-UHFFFAOYSA-N 0.000 claims 1
- GDJRVMWAHVYIST-UHFFFAOYSA-N methyl 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC GDJRVMWAHVYIST-UHFFFAOYSA-N 0.000 claims 1
- ZBKOFVZDJIPULR-UHFFFAOYSA-N methyl n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]carbamate Chemical compound C12=CC(NC(=O)OC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC ZBKOFVZDJIPULR-UHFFFAOYSA-N 0.000 claims 1
- KFCIVNWEXGPJDC-UHFFFAOYSA-N n-(ethylsulfonylmethyl)-3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-amine Chemical compound C12=CC(NCS(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC KFCIVNWEXGPJDC-UHFFFAOYSA-N 0.000 claims 1
- HXDRKCWISZTWQP-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-2-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylethanesulfonamide Chemical compound C12=CC(N(C)S(=O)(=O)CC)=CC=C2NC=C1CCCN(C(C1)C)CCN1C1=NC=NC=C1OC HXDRKCWISZTWQP-UHFFFAOYSA-N 0.000 claims 1
- CBTZBEWYHRJTSX-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-2-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]ethanesulfonamide Chemical compound C12=CC(NS(=O)(=O)CC)=CC=C2NC=C1CCCN(C(C1)C)CCN1C1=NC=NC=C1OC CBTZBEWYHRJTSX-UHFFFAOYSA-N 0.000 claims 1
- SGGOWYQGSMJOGP-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]ethanesulfonamide Chemical compound C12=CC(NS(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1C)CCN1C1=NC=NC=C1OC SGGOWYQGSMJOGP-UHFFFAOYSA-N 0.000 claims 1
- JBOOOOMNYZLORK-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]methanesulfonamide Chemical compound COC1=CN=CN=C1N1C(C)CN(CCCC=2C3=CC(NS(C)(=O)=O)=CC=C3NC=2)CC1 JBOOOOMNYZLORK-UHFFFAOYSA-N 0.000 claims 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- FMLPQHJYUZTHQS-UHFFFAOYSA-N tert-butyl 3-methylpiperazine-1-carboxylate Chemical compound CC1CN(C(=O)OC(C)(C)C)CCN1 FMLPQHJYUZTHQS-UHFFFAOYSA-N 0.000 description 1
- UHUZMAHDOFEXQY-UHFFFAOYSA-N tert-butyl-dimethyl-(5-trimethylsilylpent-4-ynoxy)silane Chemical compound CC(C)(C)[Si](C)(C)OCCCC#C[Si](C)(C)C UHUZMAHDOFEXQY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- CIXRWXTXQKQWBW-UHFFFAOYSA-N trimethyl(pent-4-ynyl)silane Chemical compound C[Si](C)(C)CCCC#C CIXRWXTXQKQWBW-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen 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
- 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
- A61P25/06—Antimigraine agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81066191A | 1991-12-19 | 1991-12-19 | |
| US810,661 | 1991-12-19 | ||
| US95959292A | 1992-10-13 | 1992-10-13 | |
| US959,592 | 1992-10-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2084531A1 true CA2084531A1 (en) | 1993-06-20 |
Family
ID=27123378
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002084531A Abandoned CA2084531A1 (en) | 1991-12-19 | 1992-12-04 | Antimigraine 4-pyrimidinyl and pyridinyl derivatives of indol-3yl-alkyl piperazines |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5434154A (cg-RX-API-DMAC7.html) |
| EP (1) | EP0548813A1 (cg-RX-API-DMAC7.html) |
| JP (1) | JPH05262762A (cg-RX-API-DMAC7.html) |
| CN (1) | CN1085556A (cg-RX-API-DMAC7.html) |
| AU (1) | AU661527B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2084531A1 (cg-RX-API-DMAC7.html) |
| CZ (1) | CZ359292A3 (cg-RX-API-DMAC7.html) |
| FI (1) | FI925737L (cg-RX-API-DMAC7.html) |
| IL (1) | IL104024A (cg-RX-API-DMAC7.html) |
| MX (1) | MX9207114A (cg-RX-API-DMAC7.html) |
| NO (1) | NO302522B1 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ245439A (cg-RX-API-DMAC7.html) |
| PH (1) | PH30988A (cg-RX-API-DMAC7.html) |
| RU (1) | RU2114111C1 (cg-RX-API-DMAC7.html) |
| TW (1) | TW221420B (cg-RX-API-DMAC7.html) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5521188A (en) * | 1993-09-16 | 1996-05-28 | Bristol-Myers Squibb Company | Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines |
| CA2130078A1 (en) * | 1993-09-16 | 1995-03-17 | Jonas A. Gylys | Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines |
| US5468768A (en) * | 1994-01-06 | 1995-11-21 | Bristol-Myers Squibb Company | Antimigraine derivatives of indolylcycloalkanylamines |
| JPH10501212A (ja) * | 1994-05-19 | 1998-02-03 | メルク シヤープ エンド ドーム リミテツド | ５−ｈｔ▲下１ｄ▼−アルファ作働薬としてのインドール−３−イルアルキルのピペラジン、ピペリジンおよびテトラヒドロピリジン誘導体 |
| GB9410031D0 (en) * | 1994-05-19 | 1994-07-06 | Merck Sharp & Dohme | Therapeutic agents |
| US5552402A (en) * | 1994-05-19 | 1996-09-03 | Merck, Sharp & Dohme Ltd. | Five-membered heteroaromatic compounds as 5-HT receptor agonists |
| US5567824A (en) * | 1994-05-24 | 1996-10-22 | Merck & Co., Inc. | Palladium catalyzed ring closure of triazolyltryptamine |
| ES2079323B1 (es) * | 1994-06-21 | 1996-10-16 | Vita Invest Sa | Derivados de indol utiles para el tratamiento de la migraña, composicion y uso correspondientes. |
| GB9415575D0 (en) * | 1994-08-02 | 1994-09-21 | Merck Sharp & Dohme | Therapeutic agents |
| US5550239A (en) * | 1994-11-08 | 1996-08-27 | Bristol-Myers Squibb Company | Process for large-scale production of indolyl alkyl pyrimidinyl piperazine compounds |
| GB9423682D0 (en) * | 1994-11-23 | 1995-01-11 | Merck Sharp & Dohme | Therapeutic agents |
| GB9501865D0 (en) * | 1995-01-31 | 1995-03-22 | Merck Sharp & Dohme | Therapeutic agents |
| US5618816A (en) * | 1995-03-02 | 1997-04-08 | Bristol-Myers Squibb Company | Antimigraine 1,2,5-thiadiazole derivatives of indolylalkyl-pyridnyl and pyrimidinylpiperazines |
| US5889010A (en) * | 1995-05-18 | 1999-03-30 | Pfizer Inc. | Benzimidazole derivatives having dopaminergic activity |
| CA2228286A1 (en) * | 1995-08-07 | 1997-02-20 | Merck Sharp & Dohme Limited | Substituted 1-indolylpropyl-4-phenethylpiperazine derivatives |
| JPH09124643A (ja) * | 1995-08-14 | 1997-05-13 | Bristol Myers Squibb Co | 抗うつ作用を有する１−アリールアルキル−４−（アルコキシピリジニル）−又は４−（アルコキシピリミジニル）ピペラジン誘導体 |
| GB9519563D0 (en) * | 1995-09-26 | 1995-11-29 | Merck Sharp & Dohme | Therapeutic agents |
| EP0854714A1 (en) * | 1995-09-28 | 1998-07-29 | MERCK SHARP & DOHME LTD. | Substituted indolylpropyl-piperazine derivatives as 5-ht 1dalpha? agonists |
| US5998415A (en) * | 1995-11-02 | 1999-12-07 | Merck Sharp & Dohme Ltd. | Bicyclic heteroaryl-alkylene-(homo)piperazinones and thione analogues thereof, their preparation, and their use of as selective agonists of 5-HT1 -like receptors |
| GB9523250D0 (en) * | 1995-11-14 | 1996-01-17 | Merck Sharp & Dohme | Therapeutic agents |
| GB9609374D0 (en) * | 1996-05-03 | 1996-07-10 | Merck Sharp & Dohme | Therapeutic agents |
| US5808064A (en) * | 1996-08-13 | 1998-09-15 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5877329A (en) * | 1996-08-13 | 1999-03-02 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5811551A (en) * | 1996-08-13 | 1998-09-22 | Merck & Co., Inc. | Palladium catalyzed indolization |
| US5891885A (en) * | 1996-10-09 | 1999-04-06 | Algos Pharmaceutical Corporation | Method for treating migraine |
| GB9714383D0 (en) * | 1997-07-08 | 1997-09-10 | Pfizer Ltd | Improved process |
| DE19756036A1 (de) | 1997-12-17 | 1999-06-24 | Merck Patent Gmbh | Amid- und Harnstoffderivate |
| JP2004517081A (ja) * | 2000-11-29 | 2004-06-10 | イーライ・リリー・アンド・カンパニー | １−（２−ｍ−メタンスルホンアミドフェニルエチル）−４−（ｍ−トリフルオロメチルフェニル）ピペラジンならびにその医薬的に許容しうる塩および溶媒和物 |
| DE10102944A1 (de) * | 2001-01-23 | 2002-07-25 | Merck Patent Gmbh | Verfahren zur Herstellung von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon und dessen Salzen |
| US6685951B2 (en) | 2001-07-05 | 2004-02-03 | R. T. Alamo Ventures I, Inc. | Administration of dihydroergotamine as a sublingual spray or aerosol for the treatment of migraine |
| US20030198669A1 (en) * | 2001-07-05 | 2003-10-23 | R.T. Alamo Ventures I, Llc | Compositions and methods for rapid dissolving formulations of dihydroergotamine and caffeine for the treatment of migraine |
| US20030017175A1 (en) * | 2001-07-05 | 2003-01-23 | R.T. Alamo Ventures I, Inc. | Sublingual administration of dihydroergotamine for the treatment of migraine |
| DE60233076D1 (de) | 2002-02-13 | 2009-09-03 | Meiji Dairies Corp | Indolderivate substituiert mit langkettigen alcoholen und sie enthaltende arzneimittel |
| DE102004047517A1 (de) * | 2004-09-28 | 2006-03-30 | Merck Patent Gmbh | Neuartige Kristallform von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon, Hydrochlorid |
| WO2006129190A1 (en) * | 2005-06-03 | 2006-12-07 | Glenmark Pharmaceuticals Limited | Process for the preparation of almotriptan |
| RU2461556C2 (ru) * | 2006-12-30 | 2012-09-20 | Эбботт Гмбх Унд Ко. Кг | Замещенные производные оксидола и их применение в качестве лигандов рецептора вазопрессина |
| ES2538082T3 (es) | 2007-02-11 | 2015-06-17 | Map Pharmaceuticals Inc | Método de administración terapéutica de DHE para permitir el rápido alivio de migraña mientras que se minimiza el perfil de efectos secundarios |
| EP2036888A1 (en) * | 2007-09-17 | 2009-03-18 | Laboratorios del Dr. Esteve S.A. | Naphthyl-substituted sulfonamides |
| ES2751388T3 (es) | 2011-07-22 | 2020-03-31 | Univ Chicago | IGF-1 para su uso en el tratamiento de la jaqueca |
| AU2013361337A1 (en) | 2012-12-21 | 2015-07-09 | Map Pharmaceuticals, Inc. | 8'-Hydroxy-Dihydroergotamine compounds and compositions |
| CN104163813B (zh) * | 2013-05-16 | 2017-02-01 | 广东东阳光药业有限公司 | 取代的吲哚化合物及其使用方法和用途 |
| CN104337812B (zh) | 2013-07-29 | 2018-09-14 | 广东东阳光药业有限公司 | 取代的杂芳基化合物及其使用方法和用途 |
| CN104725363B (zh) * | 2013-12-20 | 2019-03-01 | 广东东阳光药业有限公司 | 取代的哌嗪化合物及其使用方法和用途 |
| US9714232B2 (en) * | 2013-12-20 | 2017-07-25 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use thereof |
| CN106243088B (zh) * | 2015-06-03 | 2019-01-04 | 广东东阳光药业有限公司 | 取代的哌嗪化合物及其使用方法和用途 |
| WO2019082143A1 (en) * | 2017-10-27 | 2019-05-02 | Fresenius Kabi Oncology Ltd. | IMPROVED PROCESS FOR THE PREPARATION OF RIBOCICLIB AND ITS SALTS |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB944443A (cg-RX-API-DMAC7.html) * | 1959-09-25 | 1900-01-01 | ||
| GB1189064A (en) | 1967-05-01 | 1970-04-22 | Sterling Drug Inc | Indole Derivatives |
| GR79215B (cg-RX-API-DMAC7.html) | 1982-06-07 | 1984-10-22 | Glaxo Group Ltd | |
| GB2162522B (en) | 1984-08-01 | 1988-02-24 | Glaxo Group Ltd | An indole derivative |
| US4954502A (en) * | 1988-06-10 | 1990-09-04 | Bristol-Myers Squibb Company | 1-indolyalkyl-4-(substituted-pyridinyl)piperazines |
| FR2635104B1 (fr) | 1988-08-03 | 1992-04-30 | Synthelabo | Derives d'indolone, leur preparation et leur application en therapeutique |
| GB8830312D0 (en) | 1988-12-28 | 1989-02-22 | Lundbeck & Co As H | Heterocyclic compounds |
| JP2871811B2 (ja) | 1990-02-28 | 1999-03-17 | サントリー株式会社 | 縮合７員環系化合物 |
| US5077293A (en) | 1990-06-29 | 1991-12-31 | Bristol-Myers Squibb Co. | 1-indolyalkyl-4-(alkoxypyrimidinyl)piperazines |
| CA2043709C (en) * | 1990-06-29 | 2002-01-22 | David W. Smith | Antimigraine alkoxypyrimidine derivatives |
-
1992
- 1992-12-04 CA CA002084531A patent/CA2084531A1/en not_active Abandoned
- 1992-12-07 CZ CS923592A patent/CZ359292A3/cs unknown
- 1992-12-08 IL IL104024A patent/IL104024A/xx not_active IP Right Cessation
- 1992-12-09 MX MX9207114A patent/MX9207114A/es unknown
- 1992-12-10 NO NO924764A patent/NO302522B1/no unknown
- 1992-12-10 AU AU30034/92A patent/AU661527B2/en not_active Ceased
- 1992-12-11 NZ NZ245439A patent/NZ245439A/xx unknown
- 1992-12-14 TW TW081110009A patent/TW221420B/zh active
- 1992-12-15 PH PH45427A patent/PH30988A/en unknown
- 1992-12-17 EP EP92121519A patent/EP0548813A1/en not_active Ceased
- 1992-12-17 RU RU92016241A patent/RU2114111C1/ru active
- 1992-12-17 FI FI925737A patent/FI925737L/fi not_active Application Discontinuation
- 1992-12-18 JP JP4361763A patent/JPH05262762A/ja active Pending
-
1993
- 1993-01-02 CN CN93101186A patent/CN1085556A/zh active Pending
-
1994
- 1994-04-26 US US08/233,545 patent/US5434154A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1085556A (zh) | 1994-04-20 |
| JPH05262762A (ja) | 1993-10-12 |
| RU2114111C1 (ru) | 1998-06-27 |
| AU3003492A (en) | 1994-03-24 |
| NZ245439A (en) | 1995-07-26 |
| FI925737A0 (fi) | 1992-12-17 |
| CZ359292A3 (en) | 1994-01-19 |
| FI925737A7 (fi) | 1993-06-20 |
| FI925737L (fi) | 1993-06-20 |
| US5434154A (en) | 1995-07-18 |
| MX9207114A (es) | 1993-07-01 |
| IL104024A (en) | 1997-04-15 |
| TW221420B (cg-RX-API-DMAC7.html) | 1994-03-01 |
| PH30988A (en) | 1997-12-23 |
| AU661527B2 (en) | 1995-07-27 |
| EP0548813A1 (en) | 1993-06-30 |
| NO924764L (no) | 1993-06-21 |
| NO302522B1 (no) | 1998-03-16 |
| NO924764D0 (no) | 1992-12-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |