IL129123A - Piperzines 1, 4 - Imaging methods, methods for their preparation and their use in the preparation of medicinal preparations - Google Patents
Piperzines 1, 4 - Imaging methods, methods for their preparation and their use in the preparation of medicinal preparationsInfo
- Publication number
- IL129123A IL129123A IL12912397A IL12912397A IL129123A IL 129123 A IL129123 A IL 129123A IL 12912397 A IL12912397 A IL 12912397A IL 12912397 A IL12912397 A IL 12912397A IL 129123 A IL129123 A IL 129123A
- Authority
- IL
- Israel
- Prior art keywords
- dibenzo
- compound according
- propyl
- dihydro
- mmol
- Prior art date
Links
- -1 1,4-disubstituted piperazines Chemical class 0.000 title claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 21
- 238000000034 method Methods 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 101
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
- 150000002367 halogens Chemical class 0.000 claims abstract description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 5
- 125000004429 atom Chemical group 0.000 claims abstract description 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 5
- 101100240518 Caenorhabditis elegans nhr-12 gene Chemical group 0.000 claims abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical class 0.000 claims abstract 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 5
- 239000002253 acid Substances 0.000 claims description 21
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
- 239000003937 drug carrier Substances 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 11
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 claims description 10
- 102100025588 Calcitonin gene-related peptide 1 Human genes 0.000 claims description 10
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 9
- 239000008103 glucose Substances 0.000 claims description 9
- 229960003512 nicotinic acid Drugs 0.000 claims description 9
- 239000011664 nicotinic acid Substances 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- 206010027599 migraine Diseases 0.000 claims description 7
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- 208000003251 Pruritus Diseases 0.000 claims description 6
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- 230000007823 neuropathy Effects 0.000 claims description 6
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 3
- YZCKVPCYPYWVAJ-UHFFFAOYSA-N 2-[4-[2-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)ethyl]piperazin-1-yl]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1N1CCN(CCN2C3=CC=CC=C3CCC3=CC=CC=C32)CC1 YZCKVPCYPYWVAJ-UHFFFAOYSA-N 0.000 claims description 2
- LETUACMLMMIIEL-UHFFFAOYSA-N 2-[4-[3-(3-chlorobenzo[d][1,3,6]benzodioxazocin-5-yl)propyl]piperazin-1-yl]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1N1CCN(CCCN2C3=CC(Cl)=CC=C3OCOC3=CC=CC=C32)CC1 LETUACMLMMIIEL-UHFFFAOYSA-N 0.000 claims description 2
- NNJRSWRMFUPBQN-UHFFFAOYSA-N 6-[4-[3-(5,6-dihydrodibenzo[1,2-a:1',2'-e][7]annulen-11-ylidene)propyl]piperazin-1-yl]pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(N2CCN(CCC=C3C4=CC=CC=C4CCC4=CC=CC=C43)CC2)=N1 NNJRSWRMFUPBQN-UHFFFAOYSA-N 0.000 claims description 2
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 2
- LDJDDYHPKGIEAR-UHFFFAOYSA-N 1-[3-(5,6-dihydrodibenzo[1,2-a:1',2'-e][7]annulen-11-ylidene)propyl]-4-pyridin-2-ylpiperazine Chemical compound C12=CC=CC=C2CCC2=CC=CC=C2C1=CCCN(CC1)CCN1C1=CC=CC=N1 LDJDDYHPKGIEAR-UHFFFAOYSA-N 0.000 claims 1
- MSCRWPNAMXSGTH-UHFFFAOYSA-N 2-[4-(3-benzo[d][1,3]benzodioxocin-5-ylidenepropyl)piperazin-1-yl]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1N1CCN(CCC=C2C3=CC=CC=C3OCOC3=CC=CC=C32)CC1 MSCRWPNAMXSGTH-UHFFFAOYSA-N 0.000 claims 1
- UDZWMXPTGRAJHF-UHFFFAOYSA-N 2-[4-[3-(5,6-dihydrodibenzo[1,2-a:1',2'-e][7]annulen-11-ylidene)propyl]piperazin-1-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1CCN(CCC=C2C3=CC=CC=C3CCC3=CC=CC=C32)CC1 UDZWMXPTGRAJHF-UHFFFAOYSA-N 0.000 claims 1
- 229940125898 compound 5 Drugs 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 128
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 126
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 122
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 88
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 70
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- 239000000243 solution Substances 0.000 description 48
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 44
- 235000019441 ethanol Nutrition 0.000 description 44
- 229940093499 ethyl acetate Drugs 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 42
- 229960004756 ethanol Drugs 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 34
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- 235000011121 sodium hydroxide Nutrition 0.000 description 26
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- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 24
- 238000001816 cooling Methods 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
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- 235000011167 hydrochloric acid Nutrition 0.000 description 20
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- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 13
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 229940086542 triethylamine Drugs 0.000 description 12
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 239000012267 brine Substances 0.000 description 10
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
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- OYJQNNFWBRLZIU-UHFFFAOYSA-N ethyl 2-piperazin-1-ylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=CN=C1N1CCNCC1 OYJQNNFWBRLZIU-UHFFFAOYSA-N 0.000 description 9
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- 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
- C07D403/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/76—Ring systems containing bridged rings containing three rings containing at least one ring with more than six ring members
- C07C2603/78—Ring systems containing bridged rings containing three rings containing at least one ring with more than six ring members containing seven-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK109096 | 1996-10-04 | ||
PCT/DK1997/000422 WO1998015548A1 (en) | 1996-10-04 | 1997-10-02 | 1,4-disubstituted piperazines |
Publications (2)
Publication Number | Publication Date |
---|---|
IL129123A0 IL129123A0 (en) | 2000-02-17 |
IL129123A true IL129123A (en) | 2004-07-25 |
Family
ID=8100883
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL12912397A IL129123A (en) | 1996-10-04 | 1997-10-02 | Piperzines 1, 4 - Imaging methods, methods for their preparation and their use in the preparation of medicinal preparations |
Country Status (20)
Country | Link |
---|---|
US (4) | US5916889A (pt) |
EP (1) | EP0934312B1 (pt) |
JP (1) | JP2001502307A (pt) |
KR (1) | KR20000048899A (pt) |
CN (1) | CN1088459C (pt) |
AT (1) | ATE234831T1 (pt) |
AU (1) | AU740662B2 (pt) |
BR (1) | BR9712196A (pt) |
CA (1) | CA2267835A1 (pt) |
CZ (1) | CZ114099A3 (pt) |
DE (1) | DE69720021T2 (pt) |
DK (1) | DK0934312T3 (pt) |
ES (1) | ES2194217T3 (pt) |
HU (1) | HUP0000090A3 (pt) |
IL (1) | IL129123A (pt) |
NO (1) | NO991565L (pt) |
PL (1) | PL188338B1 (pt) |
RU (1) | RU2188197C2 (pt) |
WO (1) | WO1998015548A1 (pt) |
ZA (1) | ZA978864B (pt) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001501629A (ja) * | 1996-10-04 | 2001-02-06 | ノボ ノルディスク アクティーゼルスカブ | N―置換アザ複素環式化合物 |
US6613905B1 (en) * | 1998-01-21 | 2003-09-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
US7045519B2 (en) * | 1998-06-19 | 2006-05-16 | Chiron Corporation | Inhibitors of glycogen synthase kinase 3 |
JP4533534B2 (ja) | 1998-06-19 | 2010-09-01 | ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド | グリコーゲンシンターゼキナーゼ3のインヒビター |
US7541365B2 (en) | 2001-11-21 | 2009-06-02 | Millennium Pharmaceuticals, Inc. | Chemokine receptor antagonists and methods of use therefor |
US20040038861A1 (en) * | 2001-11-26 | 2004-02-26 | Cooper Garth J. S. | Methods and compositions for normalizing lipid levels in mammalian tissues |
TWI291467B (en) | 2002-11-13 | 2007-12-21 | Millennium Pharm Inc | CCR1 antagonists and methods of use therefor |
AU2005286593A1 (en) * | 2004-09-23 | 2006-03-30 | Reddy Us Therapeutics, Inc. | Novel pyridine compounds, process for their preparation and compositions containing them |
FR2885616B1 (fr) * | 2005-05-12 | 2007-06-22 | Servier Lab | Nouveaux derives de phenylpyridinylpiperazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
FR2885615B1 (fr) * | 2005-05-12 | 2007-06-22 | Servier Lab | Nouveaux derives de phenylpyridinylpiperazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
JP2009514969A (ja) | 2005-11-09 | 2009-04-09 | コンビナトアールエックス インコーポレーティッド | 医学的状態を治療するための方法、組成物、およびキット |
EP2420239B1 (en) * | 2007-04-13 | 2015-01-14 | Southern Research Institute | Clomipramine as anti-angiogenic agent |
CN103086898B (zh) * | 2012-07-11 | 2015-04-08 | 山东道可化学有限公司 | 二苯胺或其环上取代的衍生物的制备方法 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL102488C (pt) * | 1957-07-18 | |||
GB1013901A (en) * | 1962-01-26 | 1965-12-22 | Kefalas As | Dihydroanthracene, dibenzocycloheptadiene and dibenzocycloheptatriene derivatives |
FR88751E (pt) * | 1963-07-09 | 1967-06-07 | ||
US3435073A (en) * | 1966-04-19 | 1969-03-25 | Colgate Palmolive Co | 5-(n-benzyl-n-lower alkylaminoalkylene)-5h-dibenzo(a,d)cycloheptenes |
GB1347935A (en) * | 1971-04-10 | 1974-02-27 | Yoshitomi Pharmaceutical | Piperazine derivatives methods for their production and phar maceutical compositions containing them |
FR2186249A1 (en) * | 1972-05-31 | 1974-01-11 | Synthelabo | Phenyl piperazinoalkyl (dihydro)dibenzazepines - antidepressants having low toxicity |
HU174126B (hu) * | 1977-08-02 | 1979-11-28 | Egyt Gyogyszervegyeszeti Gyar | Sposob poluchenija novykh proizvodnykh dibenzo-kvadratnaja skobka-d,g-kvadratnaja skobka zakryta-kvadratnaja skobka-1,3,6-kvadratnaja skobka zakryta-dioksazocina |
ES524680A0 (es) * | 1983-08-02 | 1984-12-16 | Espanola Farma Therapeut | Procedimiento de obtencion de nuevos compuestos derivados de la difenil-metilen-etilamina. |
AU612437B2 (en) * | 1987-12-14 | 1991-07-11 | Kyowa Hakko Kogyo Co. Ltd. | Tricyclic compounds |
ZA914764B (en) * | 1990-06-22 | 1992-03-25 | Schering Corp | Bis-benzo or benzopyrido cyclohepta piperidene,piperidylidene and piperazine compounds,compositions and methods of use |
MY113463A (en) * | 1994-01-04 | 2002-03-30 | Novo Nordisk As | Novel heterocyclic compounds |
UA54385C2 (uk) * | 1995-04-07 | 2003-03-17 | Ново Нордіск А/С | N-заміщені азагетероциклічні карбонові кислоти та їх ефіри, спосіб їх одержання, фармацевтична композиція та спосіб лікування |
EP0851865B1 (en) * | 1995-09-19 | 2002-07-17 | Novo Nordisk A/S | 12H-Dibenzo[d,g][1,3]dioxocine derivatives |
-
1997
- 1997-10-02 IL IL12912397A patent/IL129123A/en not_active IP Right Cessation
- 1997-10-02 CA CA002267835A patent/CA2267835A1/en not_active Abandoned
- 1997-10-02 DK DK97941884T patent/DK0934312T3/da active
- 1997-10-02 PL PL97332597A patent/PL188338B1/pl not_active IP Right Cessation
- 1997-10-02 DE DE69720021T patent/DE69720021T2/de not_active Expired - Fee Related
- 1997-10-02 BR BR9712196-7A patent/BR9712196A/pt not_active IP Right Cessation
- 1997-10-02 EP EP97941884A patent/EP0934312B1/en not_active Expired - Lifetime
- 1997-10-02 CN CN97199184A patent/CN1088459C/zh not_active Expired - Fee Related
- 1997-10-02 RU RU99109024/04A patent/RU2188197C2/ru not_active IP Right Cessation
- 1997-10-02 AT AT97941884T patent/ATE234831T1/de not_active IP Right Cessation
- 1997-10-02 HU HU0000090A patent/HUP0000090A3/hu unknown
- 1997-10-02 CZ CZ991140A patent/CZ114099A3/cs unknown
- 1997-10-02 KR KR1019990702928A patent/KR20000048899A/ko not_active Application Discontinuation
- 1997-10-02 AU AU43772/97A patent/AU740662B2/en not_active Ceased
- 1997-10-02 WO PCT/DK1997/000422 patent/WO1998015548A1/en not_active Application Discontinuation
- 1997-10-02 JP JP10517093A patent/JP2001502307A/ja not_active Ceased
- 1997-10-02 ES ES97941884T patent/ES2194217T3/es not_active Expired - Lifetime
- 1997-10-03 ZA ZA9708864A patent/ZA978864B/xx unknown
- 1997-10-03 US US08/943,726 patent/US5916889A/en not_active Expired - Fee Related
-
1999
- 1999-03-18 US US09/271,565 patent/US6040302A/en not_active Expired - Fee Related
- 1999-03-18 US US09/271,785 patent/US6004961A/en not_active Expired - Fee Related
- 1999-03-18 US US09/271,564 patent/US6133268A/en not_active Expired - Fee Related
- 1999-03-30 NO NO991565A patent/NO991565L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
DE69720021D1 (de) | 2003-04-24 |
US5916889A (en) | 1999-06-29 |
DK0934312T3 (da) | 2003-07-21 |
KR20000048899A (ko) | 2000-07-25 |
HUP0000090A3 (en) | 2002-01-28 |
ATE234831T1 (de) | 2003-04-15 |
PL332597A1 (en) | 1999-09-27 |
IL129123A0 (en) | 2000-02-17 |
AU740662B2 (en) | 2001-11-08 |
CN1088459C (zh) | 2002-07-31 |
HUP0000090A2 (hu) | 2001-04-28 |
RU2188197C2 (ru) | 2002-08-27 |
BR9712196A (pt) | 1999-08-31 |
EP0934312A1 (en) | 1999-08-11 |
US6040302A (en) | 2000-03-21 |
US6004961A (en) | 1999-12-21 |
WO1998015548A1 (en) | 1998-04-16 |
ZA978864B (en) | 1998-04-06 |
CA2267835A1 (en) | 1998-04-16 |
NO991565D0 (no) | 1999-03-30 |
US6133268A (en) | 2000-10-17 |
AU4377297A (en) | 1998-05-05 |
NO991565L (no) | 1999-06-04 |
JP2001502307A (ja) | 2001-02-20 |
PL188338B1 (pl) | 2005-01-31 |
CZ114099A3 (cs) | 1999-09-15 |
CN1234799A (zh) | 1999-11-10 |
EP0934312B1 (en) | 2003-03-19 |
ES2194217T3 (es) | 2003-11-16 |
DE69720021T2 (de) | 2004-02-05 |
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Legal Events
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MM9K | Patent not in force due to non-payment of renewal fees |