CS271571B1 - Piperazine derivatives, their salts and method of their preparation - Google Patents
Piperazine derivatives, their salts and method of their preparation Download PDFInfo
- Publication number
- CS271571B1 CS271571B1 CS879045A CS904587A CS271571B1 CS 271571 B1 CS271571 B1 CS 271571B1 CS 879045 A CS879045 A CS 879045A CS 904587 A CS904587 A CS 904587A CS 271571 B1 CS271571 B1 CS 271571B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- chloro
- ethyl
- dihydrodibenzo
- compounds
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 18
- 150000003839 salts Chemical class 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 150000004885 piperazines Chemical class 0.000 title claims abstract description 10
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- SAHNLJYZUASUNV-UHFFFAOYSA-N 6-(2-bromoethoxy)-3-chloro-5,6-dihydrobenzo[b][1]benzothiepine Chemical compound BrCCOC1CC2=CC(Cl)=CC=C2SC2=CC=CC=C21 SAHNLJYZUASUNV-UHFFFAOYSA-N 0.000 claims abstract description 10
- -1 2-(2-chloro-10,11-dihydrodibenzo(b,f)thiepin-10-yloxy)ethyl residue Chemical group 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 5
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims abstract description 3
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 claims abstract description 3
- 150000001414 amino alcohols Chemical class 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 51
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- IPIVAXLHTVNRBS-UHFFFAOYSA-N decanoyl chloride Chemical compound CCCCCCCCCC(Cl)=O IPIVAXLHTVNRBS-UHFFFAOYSA-N 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 claims description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 claims description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 2
- 239000012346 acetyl chloride Substances 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 1
- 229940080818 propionamide Drugs 0.000 claims 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 abstract description 10
- 238000006386 neutralization reaction Methods 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 abstract description 6
- 230000001090 anti-dopaminergic effect Effects 0.000 abstract description 4
- 230000002908 adrenolytic effect Effects 0.000 abstract description 3
- 150000001805 chlorine compounds Chemical class 0.000 abstract description 3
- LWEOFVINMVZGAS-UHFFFAOYSA-N 3-piperazin-1-ylpropan-1-ol Chemical compound OCCCN1CCNCC1 LWEOFVINMVZGAS-UHFFFAOYSA-N 0.000 abstract description 2
- 108090001111 Dopamine D2 Receptors Proteins 0.000 abstract description 2
- 102000004980 Dopamine D2 Receptors Human genes 0.000 abstract description 2
- 230000001078 anti-cholinergic effect Effects 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract description 2
- 230000001624 sedative effect Effects 0.000 abstract description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 abstract 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 abstract 1
- 230000010933 acylation Effects 0.000 abstract 1
- 238000005917 acylation reaction Methods 0.000 abstract 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 abstract 1
- 239000000164 antipsychotic agent Substances 0.000 abstract 1
- 150000003840 hydrochlorides Chemical class 0.000 abstract 1
- 150000002688 maleic acid derivatives Chemical class 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 239000000932 sedative agent Substances 0.000 abstract 1
- 150000003890 succinate salts Chemical class 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
- 239000002585 base Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 241000700159 Rattus Species 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- KDYFGRWQOYBRFD-UHFFFAOYSA-M succinate(1-) Chemical compound OC(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-M 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229960004046 apomorphine Drugs 0.000 description 4
- 230000002903 catalepsic effect Effects 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 210000001577 neostriatum Anatomy 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- RPXLXENSKHJVFW-UHFFFAOYSA-N 3-[4-[2-[(3-chloro-5,6-dihydrobenzo[b][1]benzothiepin-6-yl)oxy]ethyl]piperazin-1-yl]propan-1-ol Chemical compound C1CN(CCCO)CCN1CCOC1C2=CC=CC=C2SC2=CC=C(Cl)C=C2C1 RPXLXENSKHJVFW-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- RGXWDWUGBIJHDO-UHFFFAOYSA-N ethyl decanoate Chemical compound CCCCCCCCCC(=O)OCC RGXWDWUGBIJHDO-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
- 239000001384 succinic acid Substances 0.000 description 3
- IVTDFWJPURCKJY-UHFFFAOYSA-N 1-[2-[(3-chloro-5,6-dihydrobenzo[b][1]benzothiepin-6-yl)oxy]ethyl]-4-methylpiperazine Chemical compound C1CN(C)CCN1CCOC1C2=CC=CC=C2SC2=CC=C(Cl)C=C2C1 IVTDFWJPURCKJY-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 108050004812 Dopamine receptor Proteins 0.000 description 2
- 102000015554 Dopamine receptor Human genes 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000003389 potentiating 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
- 239000002904 solvent Substances 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
- 230000007306 turnover Effects 0.000 description 2
- IKMKMRYGRAHTEF-UHFFFAOYSA-N 1-[2-[(3-chloro-5,6-dihydrobenzo[b][1]benzothiepin-6-yl)oxy]ethyl]piperazine Chemical compound C1C2=CC(Cl)=CC=C2SC2=CC=CC=C2C1OCCN1CCNCC1 IKMKMRYGRAHTEF-UHFFFAOYSA-N 0.000 description 1
- HTGCVLNFLVVCST-UHFFFAOYSA-N 1-piperazin-1-ylethanol Chemical class CC(O)N1CCNCC1 HTGCVLNFLVVCST-UHFFFAOYSA-N 0.000 description 1
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 description 1
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
- VVWMANLRLRFZIZ-UHFFFAOYSA-N 3-piperazin-1-ylpropanamide Chemical compound NC(=O)CCN1CCNCC1 VVWMANLRLRFZIZ-UHFFFAOYSA-N 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical group C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000009132 Catalepsy Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 1
- 102000004076 Dopamine D1 Receptors Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010042008 Stereotypy Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 206010047853 Waxy flexibility Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- NBZANZVJRKXVBH-GYDPHNCVSA-N alpha-Cryptoxanthin Natural products O[C@H]1CC(C)(C)C(/C=C/C(=C\C=C\C(=C/C=C/C=C(\C=C\C=C(/C=C/[C@H]2C(C)=CCCC2(C)C)\C)/C)\C)/C)=C(C)C1 NBZANZVJRKXVBH-GYDPHNCVSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003354 anti-apomorphinic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960003328 benzoyl peroxide Drugs 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- INLLPKCGLOXCIV-UHFFFAOYSA-N bromoethene Chemical group BrC=C INLLPKCGLOXCIV-UHFFFAOYSA-N 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- SXDQRQUWNQKZBL-UHFFFAOYSA-N butanedioic acid;hydrate Chemical compound O.OC(=O)CCC(O)=O SXDQRQUWNQKZBL-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 210000001653 corpus striatum Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000706 effect on dopamine Effects 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 230000000966 norepinephrine reuptake Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 108010092215 spiroperidol receptor Proteins 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 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
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D337/14—[b,f]-condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS879045A CS271571B1 (en) | 1987-12-10 | 1987-12-10 | Piperazine derivatives, their salts and method of their preparation |
| JP63291117A JPH01153685A (ja) | 1987-12-10 | 1988-11-19 | ピペラジン誘導体類及びそれらの酸付加塩類、及びそれらの調製方法 |
| EP88310976A EP0321100A3 (de) | 1987-12-10 | 1988-11-21 | Piperazin-Derivate, deren Säure-Additionssalze und Verfahren zu deren Herstellung |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS879045A CS271571B1 (en) | 1987-12-10 | 1987-12-10 | Piperazine derivatives, their salts and method of their preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS904587A1 CS904587A1 (en) | 1990-02-12 |
| CS271571B1 true CS271571B1 (en) | 1990-10-12 |
Family
ID=5441754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS879045A CS271571B1 (en) | 1987-12-10 | 1987-12-10 | Piperazine derivatives, their salts and method of their preparation |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0321100A3 (de) |
| JP (1) | JPH01153685A (de) |
| CS (1) | CS271571B1 (de) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69426771T2 (de) * | 1993-06-25 | 2001-06-13 | Pola Chemical Industries, Inc. | Dopaminreinkorporationshemmer zur behandlung des parkinsonschen syndroms |
| AU4376997A (en) * | 1996-10-04 | 1998-05-05 | Novo Nordisk A/S | N-substituted azaheterocyclic compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO129043B (de) * | 1968-02-16 | 1974-02-18 | Fujisawa Pharmaceutical Co |
-
1987
- 1987-12-10 CS CS879045A patent/CS271571B1/cs unknown
-
1988
- 1988-11-19 JP JP63291117A patent/JPH01153685A/ja active Pending
- 1988-11-21 EP EP88310976A patent/EP0321100A3/de not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0321100A3 (de) | 1990-08-01 |
| CS904587A1 (en) | 1990-02-12 |
| JPH01153685A (ja) | 1989-06-15 |
| EP0321100A2 (de) | 1989-06-21 |
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