JPS6175A - 神経弛緩剤、１‐フルオロフェニルブチル‐４‐（５‐ハロ‐２‐ピリミジニル）ピペラジン誘導体 - Google Patents
神経弛緩剤、１‐フルオロフェニルブチル‐４‐（５‐ハロ‐２‐ピリミジニル）ピペラジン誘導体Info
- Publication number
- JPS6175A JPS6175A JP60043555A JP4355585A JPS6175A JP S6175 A JPS6175 A JP S6175A JP 60043555 A JP60043555 A JP 60043555A JP 4355585 A JP4355585 A JP 4355585A JP S6175 A JPS6175 A JP S6175A
- Authority
- JP
- Japan
- Prior art keywords
- pyrimidinyl
- fluoro
- piperazinyl
- fluorophenyl
- compound according
- 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.)
- Granted
Links
- 230000000561 anti-psychotic effect Effects 0.000 title claims description 18
- UUQHPHIBIJWHMU-UHFFFAOYSA-N 2-[4-[4-(1-fluorocyclohexa-2,4-dien-1-yl)butyl]piperazin-1-yl]pyrimidine Chemical class FC1(CC=CC=C1)CCCCN1CCN(CC1)C1=NC=CC=N1 UUQHPHIBIJWHMU-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 89
- 238000000034 method Methods 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 17
- ZXUYYZPJUGQHLQ-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanol Chemical compound C=1C=C(F)C=CC=1C(O)CCCN(CC1)CCN1C1=NC=C(F)C=N1 ZXUYYZPJUGQHLQ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- -1 (-)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]butanol hydrate Chemical compound 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 238000007910 systemic administration Methods 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 4
- RYDHMLSALDHJBP-UHFFFAOYSA-N 4-[4-(5-bromopyrimidin-2-yl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-ol hydrochloride Chemical compound C1CN(CCN1CCCC(C2=CC=C(C=C2)F)O)C3=NC=C(C=N3)Br.Cl RYDHMLSALDHJBP-UHFFFAOYSA-N 0.000 claims 1
- MBIHDGYRMUPLFM-UHFFFAOYSA-N 4-[4-(5-chloropyrimidin-2-yl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-ol hydrochloride Chemical compound C1CN(CCN1CCCC(C2=CC=C(C=C2)F)O)C3=NC=C(C=N3)Cl.Cl MBIHDGYRMUPLFM-UHFFFAOYSA-N 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- GMBHLHMRHUMBHU-UHFFFAOYSA-N butan-2-one;hydrochloride Chemical compound Cl.CCC(C)=O GMBHLHMRHUMBHU-UHFFFAOYSA-N 0.000 claims 1
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
- IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 239000000203 mixture Substances 0.000 description 23
- 230000000694 effects Effects 0.000 description 19
- 239000000543 intermediate Substances 0.000 description 18
- 238000012360 testing method Methods 0.000 description 14
- 239000003814 drug Substances 0.000 description 13
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000000921 elemental analysis Methods 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 208000009132 Catalepsy Diseases 0.000 description 9
- 206010047853 Waxy flexibility Diseases 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- MRBFGEHILMYPTF-UHFFFAOYSA-N 1-(2-Pyrimidyl)piperazine Chemical group C1CNCCN1C1=NC=CC=N1 MRBFGEHILMYPTF-UHFFFAOYSA-N 0.000 description 7
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 7
- 229960004046 apomorphine Drugs 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000012948 isocyanate Substances 0.000 description 7
- 150000002513 isocyanates Chemical class 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000001143 conditioned effect Effects 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical class CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000003176 neuroleptic agent Substances 0.000 description 5
- 230000000701 neuroleptic effect Effects 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
- 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 4
- 208000027776 Extrapyramidal disease Diseases 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- GXXFECFLKWGTNP-UHFFFAOYSA-N 5-fluoro-2-piperazin-1-ylpyrimidine Chemical compound N1=CC(F)=CN=C1N1CCNCC1 GXXFECFLKWGTNP-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 description 3
- 239000005052 trichlorosilane Substances 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- YHWLBBPOKRHVAR-UHFFFAOYSA-N 5-bromo-2-piperazin-1-ylpyrimidine Chemical compound N1=CC(Br)=CN=C1N1CCNCC1 YHWLBBPOKRHVAR-UHFFFAOYSA-N 0.000 description 2
- DITGPXZBELUIBR-UHFFFAOYSA-N 5-iodo-2-piperazin-1-ylpyrimidine Chemical compound N1=CC(I)=CN=C1N1CCNCC1 DITGPXZBELUIBR-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- 239000003693 atypical antipsychotic agent Substances 0.000 description 2
- 229940127236 atypical antipsychotics Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 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
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 229960004170 clozapine Drugs 0.000 description 2
- 208000026725 cyclothymic disease Diseases 0.000 description 2
- 238000006477 desulfuration reaction Methods 0.000 description 2
- 230000023556 desulfurization Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 239000012259 ether extract Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 150000003512 tertiary amines Chemical class 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
- NIBVEFRJDFVQLM-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[4-(5-fluoropyrimidin-2-yl)piperazin-1-yl]butan-1-ol;hydrochloride Chemical compound Cl.C=1C=C(F)C=CC=1C(O)CCCN(CC1)CCN1C1=NC=C(F)C=N1 NIBVEFRJDFVQLM-UHFFFAOYSA-N 0.000 description 1
- JORGKVXNFHVPKA-UHFFFAOYSA-N 2-chloro-5-fluoro-4-methylsulfanylpyrimidine Chemical compound CSC1=NC(Cl)=NC=C1F JORGKVXNFHVPKA-UHFFFAOYSA-N 0.000 description 1
- GKEDZBGZXKTTDZ-UHFFFAOYSA-N 2-piperazin-2-ylpyrimidine Chemical compound C1NCCNC1C1=NC=CC=N1 GKEDZBGZXKTTDZ-UHFFFAOYSA-N 0.000 description 1
- HXAOUYGZEOZTJO-UHFFFAOYSA-N 4-chloro-1-(4-fluorophenyl)butan-1-one Chemical compound FC1=CC=C(C(=O)CCCCl)C=C1 HXAOUYGZEOZTJO-UHFFFAOYSA-N 0.000 description 1
- JISRESLIZZDWPK-UHFFFAOYSA-N 4-chloro-1-(4-fluorophenyl)butan-1-one;ethene Chemical group C=C.FC1=CC=C(C(=O)CCCCl)C=C1 JISRESLIZZDWPK-UHFFFAOYSA-N 0.000 description 1
- CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 1
- CNHDTJAPQFANKE-UHFFFAOYSA-N 5-chloro-2-piperazin-1-ylpyrimidine Chemical compound N1=CC(Cl)=CN=C1N1CCNCC1 CNHDTJAPQFANKE-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
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Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58658084A | 1984-03-06 | 1984-03-06 | |
| US586580 | 1984-03-06 | ||
| US683309 | 1984-12-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6175A true JPS6175A (ja) | 1986-01-06 |
| JPS6334152B2 JPS6334152B2 (enrdf_load_stackoverflow) | 1988-07-08 |
Family
ID=24346326
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60043555A Granted JPS6175A (ja) | 1984-03-06 | 1985-03-05 | 神経弛緩剤、１‐フルオロフェニルブチル‐４‐（５‐ハロ‐２‐ピリミジニル）ピペラジン誘導体 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6175A (enrdf_load_stackoverflow) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01157979A (ja) * | 1987-10-26 | 1989-06-21 | Pfizer Inc | １―アシル―３―［４―（２―ピリミジニル）―１―ピペラジニル］プロパン類 |
| JPH01502832A (ja) * | 1987-04-02 | 1989-09-28 | アクチエボラゲツト・レオ | 新規なピリジルおよびピリミジル誘導体 |
| JP2001519432A (ja) * | 1997-10-14 | 2001-10-23 | グラクソ グループ リミテッド | クロロプリン中間体の合成法 |
| JP2010526870A (ja) * | 2007-05-14 | 2010-08-05 | エスケー ホルディングス カンパニー リミテッド | 新規なカルバモイルオキシアリールアルカンアリールピペラジン系化合物、該化合物を含む薬剤組成物、並びに該化合物の投与による痛み、不安症及びうつ病の治療方法 |
| JP2015512951A (ja) * | 2012-04-14 | 2015-04-30 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
-
1985
- 1985-03-05 JP JP60043555A patent/JPS6175A/ja active Granted
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01502832A (ja) * | 1987-04-02 | 1989-09-28 | アクチエボラゲツト・レオ | 新規なピリジルおよびピリミジル誘導体 |
| JPH01157979A (ja) * | 1987-10-26 | 1989-06-21 | Pfizer Inc | １―アシル―３―［４―（２―ピリミジニル）―１―ピペラジニル］プロパン類 |
| JP2001519432A (ja) * | 1997-10-14 | 2001-10-23 | グラクソ グループ リミテッド | クロロプリン中間体の合成法 |
| JP2010526870A (ja) * | 2007-05-14 | 2010-08-05 | エスケー ホルディングス カンパニー リミテッド | 新規なカルバモイルオキシアリールアルカンアリールピペラジン系化合物、該化合物を含む薬剤組成物、並びに該化合物の投与による痛み、不安症及びうつ病の治療方法 |
| JP2010526871A (ja) * | 2007-05-14 | 2010-08-05 | エスケー ホルディングス カンパニー リミテッド | 新規なカルバモイルオキシアリールアルカノイルアリールピペラジン化合物、該化合物を含む薬剤組成物及び該化合物の投与による疼痛、不安神経症及びうつ病を治療する方法 |
| US8541409B2 (en) | 2007-05-14 | 2013-09-24 | Sk Biopharmaceuticals Co., Ltd. | Carbamoyloxy arylalkanoyl arylpiperazine analgesics |
| US8815852B2 (en) | 2007-05-14 | 2014-08-26 | Sk Biopharmaceuticals Co., Ltd. | Carbamoyloxy arylalkan arylpiperazine analgesics |
| US8901116B2 (en) | 2007-05-14 | 2014-12-02 | Sk Biopharmaceuticals Co., Ltd. | Method for treating pain, anxiety or depression using carbamoyloxy alkanoyl piperazine compound |
| JP2015512951A (ja) * | 2012-04-14 | 2015-04-30 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6334152B2 (enrdf_load_stackoverflow) | 1988-07-08 |
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