CA1279645C - Aryl-substituted (n-piperidinyl)methyl- and (n-piperazinyl)methylazoles having antipsychotic properties - Google Patents
Aryl-substituted (n-piperidinyl)methyl- and (n-piperazinyl)methylazoles having antipsychotic propertiesInfo
- Publication number
- CA1279645C CA1279645C CA000530424A CA530424A CA1279645C CA 1279645 C CA1279645 C CA 1279645C CA 000530424 A CA000530424 A CA 000530424A CA 530424 A CA530424 A CA 530424A CA 1279645 C CA1279645 C CA 1279645C
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- formula
- group
- piperazine
- compound
- 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.)
- Expired - Lifetime
Links
- 230000000561 anti-psychotic effect Effects 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- -1 benzo-dioxanyl Chemical group 0.000 claims abstract description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 239000000651 prodrug Substances 0.000 claims abstract description 6
- 229940002612 prodrug Drugs 0.000 claims abstract description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 9
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 8
- 150000001408 amides Chemical class 0.000 claims description 3
- 210000003169 central nervous system Anatomy 0.000 claims description 3
- 229940125898 compound 5 Drugs 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 150000003335 secondary amines Chemical class 0.000 claims description 3
- 150000003511 tertiary amides Chemical class 0.000 claims description 3
- DLQBHDBDXYVEIZ-UHFFFAOYSA-N (4-fluorophenyl)-[2-methyl-1-(5-phenyl-1h-pyrrol-2-yl)piperidin-4-yl]methanone Chemical compound CC1CC(C(=O)C=2C=CC(F)=CC=2)CCN1C(N1)=CC=C1C1=CC=CC=C1 DLQBHDBDXYVEIZ-UHFFFAOYSA-N 0.000 claims description 2
- SLFMZXPSPCFQKW-UHFFFAOYSA-N 1-[5-(3-chlorophenyl)-1h-pyrrol-2-yl]-4-(2-methoxyphenyl)-2-methylpiperazine Chemical compound COC1=CC=CC=C1N1CC(C)N(C=2NC(=CC=2)C=2C=C(Cl)C=CC=2)CC1 SLFMZXPSPCFQKW-UHFFFAOYSA-N 0.000 claims description 2
- NOPVYUPLXAWPQK-UHFFFAOYSA-N 1-[5-(4-fluorophenyl)-1h-pyrrol-2-yl]-4-(2-methoxyphenyl)-2,2-dimethylpiperazine Chemical compound COC1=CC=CC=C1N1CC(C)(C)N(C=2NC(=CC=2)C=2C=CC(F)=CC=2)CC1 NOPVYUPLXAWPQK-UHFFFAOYSA-N 0.000 claims description 2
- FEUCIFGSWOPEBP-UHFFFAOYSA-N 1-[5-(4-fluorophenyl)-1h-pyrrol-2-yl]-4-(2-methoxyphenyl)-2-methylpiperazine Chemical compound COC1=CC=CC=C1N1CC(C)N(C=2NC(=CC=2)C=2C=CC(F)=CC=2)CC1 FEUCIFGSWOPEBP-UHFFFAOYSA-N 0.000 claims description 2
- FDTSGCHRSCCCHM-UHFFFAOYSA-N 4-(2-methoxyphenyl)-1-[5-(2-methoxyphenyl)-1h-pyrrol-2-yl]-2-methylpiperazine Chemical compound COC1=CC=CC=C1N1CC(C)N(C=2NC(=CC=2)C=2C(=CC=CC=2)OC)CC1 FDTSGCHRSCCCHM-UHFFFAOYSA-N 0.000 claims description 2
- AUKYTIFTSRUUAY-UHFFFAOYSA-N 4-(2-methoxyphenyl)-2-methyl-1-(5-phenyl-1h-pyrrol-2-yl)piperazine Chemical compound COC1=CC=CC=C1N1CC(C)N(C=2NC(=CC=2)C=2C=CC=CC=2)CC1 AUKYTIFTSRUUAY-UHFFFAOYSA-N 0.000 claims description 2
- ZYLSDKVOFIPHHZ-UHFFFAOYSA-N 4-(2-methoxyphenyl)-2-methyl-1-(5-phenyl-1h-pyrrol-2-yl)piperidine Chemical compound COC1=CC=CC=C1C1CC(C)N(C=2NC(=CC=2)C=2C=CC=CC=2)CC1 ZYLSDKVOFIPHHZ-UHFFFAOYSA-N 0.000 claims description 2
- VOPRHDIATJGRCS-UHFFFAOYSA-N 4-(4-fluoro-2-methoxyphenyl)-2-methyl-1-(5-phenyl-1h-pyrrol-2-yl)piperazine Chemical compound COC1=CC(F)=CC=C1N1CC(C)N(C=2NC(=CC=2)C=2C=CC=CC=2)CC1 VOPRHDIATJGRCS-UHFFFAOYSA-N 0.000 claims description 2
- RXXJKLJKFHCJLU-UHFFFAOYSA-N 4-(4-fluorophenyl)-1-[5-(4-fluorophenyl)-1h-pyrrol-2-yl]-2-methylpiperazine Chemical compound CC1CN(C=2C=CC(F)=CC=2)CCN1C(N1)=CC=C1C1=CC=C(F)C=C1 RXXJKLJKFHCJLU-UHFFFAOYSA-N 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- SCUYFJIVDHAGQL-UHFFFAOYSA-N 1-[5-(2,6-dichlorophenyl)-1h-pyrrol-2-yl]-4-(2-methoxyphenyl)-2-methylpiperazine Chemical compound COC1=CC=CC=C1N1CC(C)N(C=2NC(=CC=2)C=2C(=CC=CC=2Cl)Cl)CC1 SCUYFJIVDHAGQL-UHFFFAOYSA-N 0.000 claims 1
- XZXGXEOZVTUZTM-UHFFFAOYSA-N 1-[5-(2,6-difluorophenyl)-1h-pyrrol-2-yl]-4-(2-methoxyphenyl)-2-methylpiperazine Chemical compound COC1=CC=CC=C1N1CC(C)N(C=2NC(=CC=2)C=2C(=CC=CC=2F)F)CC1 XZXGXEOZVTUZTM-UHFFFAOYSA-N 0.000 claims 1
- IFRWCHDMMUMFBO-UHFFFAOYSA-N 4-(2-methoxyphenyl)-2-methyl-1-(1-phenylpyrazol-4-yl)piperazine Chemical compound COC1=CC=CC=C1N1CC(C)N(C2=CN(N=C2)C=2C=CC=CC=2)CC1 IFRWCHDMMUMFBO-UHFFFAOYSA-N 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- PSYYAZQIHPXSMS-UHFFFAOYSA-N 1-(1h-pyrrol-2-ylmethyl)piperazine Chemical class C=1C=CNC=1CN1CCNCC1 PSYYAZQIHPXSMS-UHFFFAOYSA-N 0.000 abstract 1
- 239000002585 base Substances 0.000 description 28
- 235000013350 formula milk Nutrition 0.000 description 28
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229960005141 piperazine Drugs 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002199 base oil Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 230000002903 catalepsic effect Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
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- 230000001143 conditioned effect Effects 0.000 description 2
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- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZYXMVSPWOATGIW-UHFFFAOYSA-N 1-(2-methoxyphenyl)-4-methylpiperazine Chemical compound COC1=CC=CC=C1N1CCN(C)CC1 ZYXMVSPWOATGIW-UHFFFAOYSA-N 0.000 description 1
- VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 1
- IRTLROCMFSDSNF-UHFFFAOYSA-N 2-phenyl-1h-pyrrole Chemical class C1=CNC(C=2C=CC=CC=2)=C1 IRTLROCMFSDSNF-UHFFFAOYSA-N 0.000 description 1
- 150000005357 2-phenylpyrroles Chemical class 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000006683 Mannich reaction Methods 0.000 description 1
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- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
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- 239000003480 eluent Substances 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL8600488 | 1986-02-27 | ||
| NL8600488 | 1986-02-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1279645C true CA1279645C (en) | 1991-01-29 |
Family
ID=19847632
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000530424A Expired - Lifetime CA1279645C (en) | 1986-02-27 | 1987-02-24 | Aryl-substituted (n-piperidinyl)methyl- and (n-piperazinyl)methylazoles having antipsychotic properties |
Country Status (15)
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE82281T1 (de) * | 1986-02-27 | 1992-11-15 | Duphar Int Res | Aryl-substituierte(n-piperidinyl)methyl und (npiperazinyl)methylazole mit antipsychotischer wirkung. |
| US4992441A (en) * | 1987-10-14 | 1991-02-12 | Mcneilab, Inc. | 1-[[5-[[4-substituted-1-piperazinyl]methyl]-pyrrol-2-yl or furan-2-yl]methyl-2-piperidinones useful in treating schizophrenia |
| FR2672052B1 (fr) * | 1991-01-28 | 1995-05-24 | Esteve Labor Dr | Derives d'aryl (ou heteroaryl)-piperazinyl-alkyl-azoles, leur preparation et leur application en tant que medicaments. |
| GB9021453D0 (en) * | 1990-10-03 | 1990-11-14 | Wyeth John & Brother Ltd | Piperazine derivatives |
| US5159083A (en) * | 1990-12-28 | 1992-10-27 | Neurogen Corporation | Certain aminomethyl phenylimidazole derivatives; a class of dopamine receptor subtype specific ligands |
| FR2673628B1 (fr) * | 1991-03-07 | 1993-07-09 | Esteve Labor Dr | Procede de preparation de derives d'aryl (ou heteroaryl)-piperazinyl-butyl-azoles. |
| US5569659A (en) * | 1991-09-11 | 1996-10-29 | Mcneilab, Inc. | 4-arylpiperazines and 4-arylpiperidines |
| IE914218A1 (en) * | 1991-09-11 | 1993-03-24 | Mcneilab Inc | Novel 4-arylpiperazines and 4-arylpiperidines |
| JPH05255089A (ja) * | 1991-12-18 | 1993-10-05 | Sanwa Kagaku Kenkyusho Co Ltd | 抗ウイルス剤 |
| FR2692264B1 (fr) * | 1992-06-12 | 1994-08-05 | Adir | Nouvelles piperazines 1,4-disubstituees, leur procede de preparation et les compositions pharmaceutiques les contenant. |
| US5523299A (en) * | 1992-08-06 | 1996-06-04 | Smithkline Beecham Plc | 5-(2-oxyphenyl)-pyrrole derivatives as dopamine D3 receptor antagonists |
| US5314885A (en) * | 1992-09-11 | 1994-05-24 | Mcneilab, Inc. | Cyclic benzylamino, benzylamido, and benzylimido antipsychotic agents |
| GB9305644D0 (en) * | 1993-03-18 | 1993-05-05 | Merck Sharp & Dohme | Therapeutic agents |
| GB9306578D0 (en) * | 1993-03-30 | 1993-05-26 | Merck Sharp & Dohme | Therapeutic agents |
| GB9307400D0 (en) * | 1993-04-08 | 1993-06-02 | Smithkline Beecham Plc | Compounds |
| JPH08511789A (ja) * | 1993-06-25 | 1996-12-10 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | フェニルピロール誘導体およびドーパミンｄ３拮抗薬としてのそれらの使用 |
| GB9315800D0 (en) * | 1993-07-30 | 1993-09-15 | Smithkline Beecham Plc | Compounds |
| GB9315801D0 (en) * | 1993-07-30 | 1993-09-15 | Smithkline Beecham Plc | Compounds |
| GB9320855D0 (en) * | 1993-10-09 | 1993-12-01 | Smithkline Beecham Plc | Compounds |
| GB9325827D0 (en) * | 1993-12-17 | 1994-02-23 | Smithkline Beecham Plc | Compounds |
| GB9402197D0 (en) * | 1994-02-04 | 1994-03-30 | Smithkline Beecham Plc | Compounds |
| GB9403199D0 (en) * | 1994-02-19 | 1994-04-13 | Smithkline Beecham Plc | Compounds |
| US5478934A (en) * | 1994-11-23 | 1995-12-26 | Yuan; Jun | Certain 1-substituted aminomethyl imidazole and pyrrole derivatives: novel dopamine receptor subtype specific ligands |
| WO1996016057A1 (en) * | 1994-11-23 | 1996-05-30 | Neurogen Corporation | Certain 1-substituted aminomethyl imidazole and pyrrole derivatives; novel dopamine receptor subtype specific ligands |
| GB9512129D0 (en) * | 1995-06-15 | 1995-08-16 | Smithkline Beecham Plc | Compounds |
| EP0839144B1 (en) * | 1995-07-13 | 2001-09-19 | Knoll GmbH | Piperazine derivatives as therapeutic agents |
| ATE340173T1 (de) * | 1996-03-29 | 2006-10-15 | Duphar Int Res | Piperazin- und piperidin- derivate |
| EP0946508B1 (en) | 1996-12-23 | 2009-09-23 | Bristol-Myers Squibb Pharma Company | NITROGEN CONTAINING HETEROAROMATICS AS FACTOR Xa INHIBITORS |
| CA2278677A1 (en) * | 1997-01-27 | 1998-07-30 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| US6169086B1 (en) | 1997-01-27 | 2001-01-02 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| TW530054B (en) * | 1997-09-24 | 2003-05-01 | Duphar Int Res | New piperazine and piperidine compounds |
| ATE381549T1 (de) | 2000-07-04 | 2008-01-15 | Kyoyu Agri Co Ltd | Benzoxazol-derivative, verfahren zu ihrer herstellung und herbizide |
| EP1408976B3 (en) | 2001-07-20 | 2010-08-25 | Psychogenics Inc. | Treatment for attention-deficit hyperactivity disorder |
| US7589199B2 (en) * | 2002-06-12 | 2009-09-15 | Chemocentryx, Inc. | Substituted piperazines |
| US7842693B2 (en) * | 2002-06-12 | 2010-11-30 | Chemocentryx, Inc. | Substituted piperazines |
| US20050256130A1 (en) * | 2002-06-12 | 2005-11-17 | Chemocentryx, Inc. | Substituted piperazines |
| ES2329356T3 (es) | 2002-06-12 | 2009-11-25 | Chemocentryx, Inc. | Derivados de piperazina 1-arilo-4-sustituidos utilizados como antagonistas de ccr1 para el tratamiento de enfermedades inflamatorias e inmunitarias. |
| CA2558211C (en) * | 2004-03-03 | 2013-09-03 | Chemocentryx, Inc. | Bicyclic and bridged nitrogen heterocycles |
| US7435831B2 (en) * | 2004-03-03 | 2008-10-14 | Chemocentryx, Inc. | Bicyclic and bridged nitrogen heterocycles |
| BRPI0405418A (pt) * | 2004-09-02 | 2006-05-02 | Univ Rio De Janeiro | uso de derivados n-fenilperazìnicos e composições farmacêuticas contendo os mesmos |
| TW200800946A (en) * | 2005-08-15 | 2008-01-01 | Astrazeneca Ab | Substituted piperazines as metabotropic glutamate receptor antagonists |
| KR100654328B1 (ko) | 2005-08-26 | 2006-12-08 | 한국과학기술연구원 | 피페라지닐알킬피라졸계 ｔ-타입 칼슘 채널 억제 화합물 및이의 제조방법 |
| US9066903B2 (en) | 2006-02-28 | 2015-06-30 | The United States Of America As Represented By The Department Of Veterans Affairs | Pharmacological treatment of Parkinson's disease |
| CN103570705B (zh) * | 2012-07-18 | 2017-01-25 | 中国医学科学院医药生物技术研究所 | 取代的n‑((1＇,3＇‑杂唑‑4＇‑基)‑甲基)‑4‑苯甲酰基六氢吡啶类化合物及其用途 |
| EP3083563A1 (en) * | 2013-12-20 | 2016-10-26 | Laboratorios Del. Dr. Esteve, S.A. | Piperazine derivatives having multimodal activity against pain |
| MX2016006603A (es) * | 2013-12-20 | 2016-09-06 | Esteve Labor Dr | Compuestos piperidinicos con actividad multimodal contra el dolor. |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3407199A (en) * | 1966-01-18 | 1968-10-22 | Endo Lab | Tertiaryamino ethyl or propyl pyrrol-2-yl ketones |
| DE2261351A1 (de) * | 1972-12-15 | 1974-06-20 | Merck Patent Gmbh | Pyrazolderivate und verfahren zu ihrer herstellung |
| DE2526469A1 (de) * | 1975-06-13 | 1976-12-30 | Bayer Ag | 1-substituierte pyrazolderivate, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| US4032526A (en) * | 1975-10-02 | 1977-06-28 | American Cyanamid Company | 1,2-dimethyl-3 or 5-piperazinyl-pyrazolium salts |
| US4123529A (en) * | 1976-04-23 | 1978-10-31 | Lilly Industries Limited | Phenylpiperazine derivatives |
| DE2747531A1 (de) * | 1977-10-22 | 1979-04-26 | Basf Ag | Substituierte 3-aminopyrazole |
| FR2537133A1 (fr) * | 1982-12-07 | 1984-06-08 | Rhone Poulenc Sante | Nouveaux derives de la (piperazinyl-1)-5 pyrrolidine, leur preparation et les medicaments qui les contiennent |
| DK169601B1 (da) * | 1983-10-17 | 1994-12-19 | Duphar Int Res | Piperazinderivater og farmaceutisk præparat indeholdende et sådant derivat, samt piperazinderivater med mellemproduktanvendelse |
| US4562189A (en) * | 1984-10-09 | 1985-12-31 | American Cyanamid Company | Pyrazolylpiperazines |
| DE3442860A1 (de) * | 1984-11-24 | 1986-05-28 | Kali-Chemie Pharma Gmbh, 3000 Hannover | 5-alkyl-1-phenyl-2-piperazinoalkylpyrazolin-3- on-verbindungen sowie verfahren und zwischenprodukte zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| ATE82281T1 (de) * | 1986-02-27 | 1992-11-15 | Duphar Int Res | Aryl-substituierte(n-piperidinyl)methyl und (npiperazinyl)methylazole mit antipsychotischer wirkung. |
-
1987
- 1987-02-24 AT AT87200296T patent/ATE82281T1/de not_active IP Right Cessation
- 1987-02-24 PH PH34901A patent/PH22783A/en unknown
- 1987-02-24 IL IL81669A patent/IL81669A/xx not_active IP Right Cessation
- 1987-02-24 DE DE8787200296T patent/DE3782525T2/de not_active Expired - Fee Related
- 1987-02-24 DK DK093087A patent/DK93087A/da not_active Application Discontinuation
- 1987-02-24 US US07/018,164 patent/US4772604A/en not_active Expired - Lifetime
- 1987-02-24 ES ES87200296T patent/ES2052545T3/es not_active Expired - Lifetime
- 1987-02-24 NZ NZ219380A patent/NZ219380A/xx unknown
- 1987-02-24 EP EP87200296A patent/EP0241053B1/en not_active Expired - Lifetime
- 1987-02-24 ZA ZA871335A patent/ZA871335B/xx unknown
- 1987-02-24 IE IE46687A patent/IE61724B1/en not_active IP Right Cessation
- 1987-02-24 CA CA000530424A patent/CA1279645C/en not_active Expired - Lifetime
- 1987-02-25 JP JP62040530A patent/JPH0798800B2/ja not_active Expired - Lifetime
- 1987-02-25 AU AU69247/87A patent/AU585131B2/en not_active Ceased
-
1988
- 1988-07-01 US US07/214,310 patent/US4874770A/en not_active Expired - Lifetime
-
1992
- 1992-12-28 GR GR920403153T patent/GR3006689T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0798800B2 (ja) | 1995-10-25 |
| EP0241053B1 (en) | 1992-11-11 |
| EP0241053A1 (en) | 1987-10-14 |
| PH22783A (en) | 1988-12-12 |
| NZ219380A (en) | 1990-06-26 |
| JPS62205058A (ja) | 1987-09-09 |
| IE61724B1 (en) | 1994-11-30 |
| DE3782525T2 (de) | 1993-05-27 |
| DE3782525D1 (de) | 1992-12-17 |
| US4772604A (en) | 1988-09-20 |
| AU585131B2 (en) | 1989-06-08 |
| ATE82281T1 (de) | 1992-11-15 |
| ZA871335B (en) | 1987-09-30 |
| DK93087A (da) | 1987-08-28 |
| IE870466L (en) | 1987-08-27 |
| DK93087D0 (da) | 1987-02-24 |
| ES2052545T3 (es) | 1994-07-16 |
| IL81669A (en) | 1990-11-29 |
| US4874770A (en) | 1989-10-17 |
| IL81669A0 (en) | 1987-09-16 |
| AU6924787A (en) | 1987-09-03 |
| GR3006689T3 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-06-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed | ||
| MKEC | Expiry (correction) |
Effective date: 20121205 |