CS245792B2 - Production method of new substituted phenylalkyl(piperazinyl or homopiperazinyl)-alkylthioles and-thiocarbomates - Google Patents

Production method of new substituted phenylalkyl(piperazinyl or homopiperazinyl)-alkylthioles and-thiocarbomates Download PDF

Info

Publication number: CS245792B2
Authority: CS; Czechoslovakia
Prior art keywords: dihydrochloride; group; piperazin; carbon atoms; alkyl
Prior art date: 1983-05-31

Application number

CS844059A

Other languages

Czech (cs)

English (en)

Other versions

CS405984A2 (en

Inventor

Karl Hargrave

John P Devlin

Edward L Barsumian

Original Assignee

Boehringer Ingelheim Ltd

Priority date (The priority date 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 date listed.)

1983-05-31

Filing date

1984-05-30

Publication date

1986-10-16

1984-05-30 Application filed by Boehringer Ingelheim Ltd filed Critical Boehringer Ingelheim Ltd

1985-09-17 Publication of CS405984A2 publication Critical patent/CS405984A2/cs

1986-10-16 Publication of CS245792B2 publication Critical patent/CS245792B2/cs

Links

-1 homopiperazinyl Chemical group 0.000 title claims abstract description 55
125000003884 phenylalkyl group Chemical group 0.000 title claims description 4
125000004193 piperazinyl group Chemical group 0.000 title claims description 4
238000004519 manufacturing process Methods 0.000 title description 3
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 25
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 23
150000003839 salts Chemical class 0.000 claims abstract description 20
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 15
239000001257 hydrogen Substances 0.000 claims abstract description 15
125000000217 alkyl group Chemical group 0.000 claims abstract description 14
239000002253 acid Substances 0.000 claims abstract description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 10
125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
231100000252 nontoxic Toxicity 0.000 claims abstract description 9
230000003000 nontoxic effect Effects 0.000 claims abstract description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 8
125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 4
238000000034 method Methods 0.000 claims description 54
238000002360 preparation method Methods 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
150000001350 alkyl halides Chemical class 0.000 claims description 5
FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
239000012948 isocyanate Substances 0.000 claims description 4
150000002513 isocyanates Chemical class 0.000 claims description 4
150000001356 alkyl thiols Chemical class 0.000 claims description 3
150000003558 thiocarbamic acid derivatives Chemical class 0.000 claims description 3
150000001875 compounds Chemical class 0.000 abstract description 34
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 5
238000011282 treatment Methods 0.000 abstract description 4
229910052736 halogen Inorganic materials 0.000 abstract description 3
150000002367 halogens Chemical class 0.000 abstract description 3
230000000172 allergic effect Effects 0.000 abstract description 2
230000001900 immune effect Effects 0.000 abstract description 2
230000002757 inflammatory effect Effects 0.000 abstract description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 2
150000002431 hydrogen Chemical class 0.000 abstract 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 2
208000010668 atopic eczema Diseases 0.000 abstract 1
125000001589 carboacyl group Chemical group 0.000 abstract 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 100
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
239000007787 solid Substances 0.000 description 51
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 46
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 39
239000000243 solution Substances 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
239000000203 mixture Substances 0.000 description 30
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 30
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 24
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 23
235000019441 ethanol Nutrition 0.000 description 22
ATLKRPODWOIJSC-UHFFFAOYSA-N carbamothioic s-acid;dihydrochloride Chemical compound Cl.Cl.NC(S)=O ATLKRPODWOIJSC-UHFFFAOYSA-N 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 15
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 15
230000007062 hydrolysis Effects 0.000 description 14
238000006460 hydrolysis reaction Methods 0.000 description 14
RZABQBDRXJHLFP-UHFFFAOYSA-N 3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propane-1-thiol;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCS)CCN1CC1=CC=C(Cl)C=C1 RZABQBDRXJHLFP-UHFFFAOYSA-N 0.000 description 12
239000004480 active ingredient Substances 0.000 description 12
229960001760 dimethyl sulfoxide Drugs 0.000 description 12
MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 11
IQSFXLGBVCPLRY-UHFFFAOYSA-N propane-1-thiol dihydrochloride Chemical compound Cl.Cl.CCCS IQSFXLGBVCPLRY-UHFFFAOYSA-N 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 9
239000004615 ingredient Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 7
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
239000007788 liquid Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
230000000699 topical effect Effects 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 5
239000003937 drug carrier Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
239000002674 ointment Substances 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000003826 tablet Substances 0.000 description 5
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 4
ITEYMWHNAIPIIR-UHFFFAOYSA-N Cl.Cl.C(CC)NC(O)=S Chemical compound Cl.Cl.C(CC)NC(O)=S ITEYMWHNAIPIIR-UHFFFAOYSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
239000013543 active substance Substances 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
208000026935 allergic disease Diseases 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
230000001413 cellular effect Effects 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
ANJPRQPHZGHVQB-UHFFFAOYSA-N hexyl isocyanate Chemical compound CCCCCCN=C=O ANJPRQPHZGHVQB-UHFFFAOYSA-N 0.000 description 4
230000008018 melting Effects 0.000 description 4
238000002844 melting Methods 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000003755 preservative agent Substances 0.000 description 4
SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 4
239000000126 substance Substances 0.000 description 4
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
LJJRXPXDTAUVQU-UHFFFAOYSA-N 1-butyl-4-isocyanatobenzene Chemical compound CCCCC1=CC=C(N=C=O)C=C1 LJJRXPXDTAUVQU-UHFFFAOYSA-N 0.000 description 3
FMDGXCSMDZMDHZ-UHFFFAOYSA-N 1-isocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1 FMDGXCSMDZMDHZ-UHFFFAOYSA-N 0.000 description 3
SOHSIJKUSUBJPR-UHFFFAOYSA-N 3-(4-benzylpiperazin-1-yl)propane-1-thiol;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCS)CCN1CC1=CC=CC=C1 SOHSIJKUSUBJPR-UHFFFAOYSA-N 0.000 description 3
WGYSLPAPDFLUDT-UHFFFAOYSA-N 3-[4-[(4-methylphenyl)methyl]piperazin-1-yl]propane-1-thiol;dihydrochloride Chemical compound Cl.Cl.C1=CC(C)=CC=C1CN1CCN(CCCS)CC1 WGYSLPAPDFLUDT-UHFFFAOYSA-N 0.000 description 3
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
241000282414 Homo sapiens Species 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
210000001789 adipocyte Anatomy 0.000 description 3
239000003963 antioxidant agent Substances 0.000 description 3
235000006708 antioxidants Nutrition 0.000 description 3
210000003651 basophil Anatomy 0.000 description 3
229960000686 benzalkonium chloride Drugs 0.000 description 3
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 3
125000001246 bromo group Chemical group Br* 0.000 description 3
239000000872 buffer Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
239000003795 chemical substances by application Substances 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
239000013078 crystal Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000002245 particle Substances 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 3
235000010262 sodium metabisulphite Nutrition 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
SPLUIOPIOHZUHU-UHFFFAOYSA-N 1-(3-chloropropyl)-4-(1-phenylethyl)piperazine;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=CC=1C(C)N1CCN(CCCCl)CC1 SPLUIOPIOHZUHU-UHFFFAOYSA-N 0.000 description 2
TYTJYXHYLDTDAU-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-4-(3-chloropropyl)-2,5-dimethylpiperazine Chemical compound CC1CN(CCCCl)C(C)CN1CC1=CC=C(Cl)C=C1 TYTJYXHYLDTDAU-UHFFFAOYSA-N 0.000 description 2
ANLJZMORYZBOLI-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]-4-(3-chloropropyl)piperazine;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCCl)CCN1CC1=CC=C(Cl)C=C1 ANLJZMORYZBOLI-UHFFFAOYSA-N 0.000 description 2
GSJXJZOWHSTWOX-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]piperazine Chemical compound C1=CC(Cl)=CC=C1CN1CCNCC1 GSJXJZOWHSTWOX-UHFFFAOYSA-N 0.000 description 2
RNAXUUAJNMDESG-UHFFFAOYSA-N 1-[(4-methylphenyl)methyl]piperazine Chemical compound C1=CC(C)=CC=C1CN1CCNCC1 RNAXUUAJNMDESG-UHFFFAOYSA-N 0.000 description 2
PZPFCXFBXLZYMQ-UHFFFAOYSA-N 1-benzyl-4-(3-chloropropyl)piperazine;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCCl)CCN1CC1=CC=CC=C1 PZPFCXFBXLZYMQ-UHFFFAOYSA-N 0.000 description 2
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 2
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
BEJYIJDBQVZOKO-UHFFFAOYSA-N 3-[4-(2-phenylethyl)piperazin-1-yl]propane-1-thiol;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCS)CCN1CCC1=CC=CC=C1 BEJYIJDBQVZOKO-UHFFFAOYSA-N 0.000 description 2
IMIBHFOQMLTJPL-UHFFFAOYSA-N 3-[4-(3-phenylprop-2-enyl)piperazin-1-yl]propane-1-thiol;dihydrochloride Chemical compound Cl.Cl.C1CN(CCCS)CCN1CC=CC1=CC=CC=C1 IMIBHFOQMLTJPL-UHFFFAOYSA-N 0.000 description 2
MAKDIBPKKMUEET-UHFFFAOYSA-N 3-[4-[(4-chlorophenyl)methyl]-1,4-diazepan-1-yl]propane-1-thiol Chemical compound C1CN(CCCS)CCCN1CC1=CC=C(Cl)C=C1 MAKDIBPKKMUEET-UHFFFAOYSA-N 0.000 description 2
JQHSBOUPRFLDLK-UHFFFAOYSA-N 3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propane-1-thiol Chemical compound C1CN(CCCS)CCN1CC1=CC=C(Cl)C=C1 JQHSBOUPRFLDLK-UHFFFAOYSA-N 0.000 description 2
MEQIIRRZIAXLFC-UHFFFAOYSA-N 3-[4-[(4-fluorophenyl)methyl]piperazin-1-yl]propane-1-thiol Chemical compound C1=CC(F)=CC=C1CN1CCN(CCCS)CC1 MEQIIRRZIAXLFC-UHFFFAOYSA-N 0.000 description 2
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
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241001465754 Metazoa Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 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
239000004372 Polyvinyl alcohol Substances 0.000 description 2
102100027467 Pro-opiomelanocortin Human genes 0.000 description 2
241000700159 Rattus Species 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000654 additive Substances 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
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235000019691 monocalcium phosphate Nutrition 0.000 description 1
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235000019799 monosodium phosphate Nutrition 0.000 description 1
GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
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235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
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230000001376 precipitating effect Effects 0.000 description 1
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OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
MUXMKICPRJIZCX-UHFFFAOYSA-N propane-1,1-diol;dihydrochloride Chemical compound Cl.Cl.CCC(O)O MUXMKICPRJIZCX-UHFFFAOYSA-N 0.000 description 1
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238000011321 prophylaxis Methods 0.000 description 1
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IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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239000011734 sodium Substances 0.000 description 1
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CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000008347 soybean phospholipid Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
238000011146 sterile filtration Methods 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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238000011200 topical administration Methods 0.000 description 1
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CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/04—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- 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
- C07D295/08—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 singly bound oxygen or sulfur atoms
- C07D295/084—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 singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

CS844059A 1983-05-31 1984-05-30 Production method of new substituted phenylalkyl(piperazinyl or homopiperazinyl)-alkylthioles and-thiocarbomates CS245792B2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US49918883A	1983-05-31	1983-05-31

Publications (2)

Publication Number	Publication Date
CS405984A2 CS405984A2 (en)	1985-09-17
CS245792B2 true CS245792B2 (en)	1986-10-16

Family

ID=23984207

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS844059A CS245792B2 (en)	1983-05-31	1984-05-30	Production method of new substituted phenylalkyl(piperazinyl or homopiperazinyl)-alkylthioles and-thiocarbomates

Country Status (24)

Country	Link
EP (1)	EP0127182B1 (de)
JP (1)	JPS59227868A (de)
KR (1)	KR900001188B1 (de)
AT (1)	ATE24502T1 (de)
AU (1)	AU566668B2 (de)
CA (1)	CA1215979A (de)
CS (1)	CS245792B2 (de)
DD (1)	DD224591A5 (de)
DE (1)	DE3461797D1 (de)
DK (1)	DK163921C (de)
ES (1)	ES532930A0 (de)
FI (1)	FI77238C (de)
GR (1)	GR82001B (de)
HU (1)	HU192405B (de)
IE (1)	IE57841B1 (de)
IL (1)	IL71970A (de)
NO (1)	NO169895C (de)
NZ (1)	NZ208334A (de)
PH (1)	PH21555A (de)
PL (1)	PL142332B1 (de)
PT (1)	PT78667B (de)
SU (1)	SU1355128A3 (de)
YU (1)	YU43569B (de)
ZA (1)	ZA844101B (de)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4692448A (en) *	1984-11-20	1987-09-08	Boehringer Ingelheim Pharmaceuticals, Inc.	Bis(arylpiperazinyl)sulfur compounds
CA2180190A1 (en) *	1995-07-10	1997-01-11	Kazumi Ogata	Benzylpiperazine derivatives

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR1286198A (fr) *	1961-04-07	1962-03-02	Bayer Ag	Procédé de fabrication d'esters s-alkyliques, à substituants basiques, de l'acide phénylthiocarbamique
GB952142A (en) *	1961-05-26	1964-03-11	Miles Lab	Phenylpiperazinylalkyl carbamates

1984
- 1984-05-29 GR GR74863A patent/GR82001B/el unknown
- 1984-05-29 FI FI842141A patent/FI77238C/fi not_active IP Right Cessation
- 1984-05-30 CS CS844059A patent/CS245792B2/cs unknown
- 1984-05-30 KR KR1019840003003A patent/KR900001188B1/ko not_active Expired
- 1984-05-30 IE IE1346/84A patent/IE57841B1/en not_active IP Right Cessation
- 1984-05-30 CA CA000455423A patent/CA1215979A/en not_active Expired
- 1984-05-30 ZA ZA844101A patent/ZA844101B/xx unknown
- 1984-05-30 DD DD84263572A patent/DD224591A5/de not_active IP Right Cessation
- 1984-05-30 DK DK268484A patent/DK163921C/da not_active IP Right Cessation
- 1984-05-30 PH PH30739A patent/PH21555A/en unknown
- 1984-05-30 AT AT84106160T patent/ATE24502T1/de not_active IP Right Cessation
- 1984-05-30 DE DE8484106160T patent/DE3461797D1/de not_active Expired
- 1984-05-30 ES ES532930A patent/ES532930A0/es active Granted
- 1984-05-30 EP EP84106160A patent/EP0127182B1/de not_active Expired
- 1984-05-30 IL IL71970A patent/IL71970A/xx unknown
- 1984-05-30 SU SU843745557A patent/SU1355128A3/ru active
- 1984-05-30 YU YU925/84A patent/YU43569B/xx unknown
- 1984-05-30 NO NO842154A patent/NO169895C/no unknown
- 1984-05-30 HU HU842102A patent/HU192405B/hu not_active IP Right Cessation
- 1984-05-30 PL PL1984247953A patent/PL142332B1/pl unknown
- 1984-05-31 NZ NZ208334A patent/NZ208334A/en unknown
- 1984-05-31 PT PT78667A patent/PT78667B/pt not_active IP Right Cessation
- 1984-05-31 AU AU28878/84A patent/AU566668B2/en not_active Ceased
- 1984-05-31 JP JP59109807A patent/JPS59227868A/ja active Pending

Also Published As

Publication number	Publication date
DK268484A (da)	1984-12-01
AU2887884A (en)	1984-12-20
EP0127182B1 (de)	1986-12-30
PT78667A (en)	1984-06-01
PT78667B (en)	1986-09-08
EP0127182A1 (de)	1984-12-05
HUT34740A (en)	1985-04-28
YU92584A (de)	1986-06-30
YU43569B (en)	1989-08-31
ES8505981A1 (es)	1985-06-16
NZ208334A (en)	1987-02-20
JPS59227868A (ja)	1984-12-21
IE57841B1 (en)	1993-04-21
DK163921B (da)	1992-04-21
ATE24502T1 (de)	1987-01-15
PH21555A (en)	1987-12-11
FI77238B (fi)	1988-10-31
DK268484D0 (da)	1984-05-30
NO169895C (no)	1992-08-19
NO169895B (no)	1992-05-11
AU566668B2 (en)	1987-10-29
FI842141A0 (fi)	1984-05-29
ZA844101B (en)	1986-02-26
ES532930A0 (es)	1985-06-16
SU1355128A3 (ru)	1987-11-23
IL71970A (en)	1988-02-29
CS405984A2 (en)	1985-09-17
PL247953A1 (en)	1985-03-26
FI842141A7 (fi)	1984-12-01
IE841346L (en)	1984-11-30
IL71970A0 (en)	1984-09-30
CA1215979A (en)	1986-12-30
FI77238C (fi)	1989-02-10
NO842154L (no)	1984-12-03
PL142332B1 (en)	1987-10-31
DE3461797D1 (en)	1987-02-05
KR900001188B1 (ko)	1990-02-27
HU192405B (en)	1987-06-29
DD224591A5 (de)	1985-07-10
DK163921C (da)	1992-09-21
GR82001B (de)	1984-12-12
KR840009089A (ko)	1984-12-24

Publication	Publication Date	Title
EP0079545B1 (de)	1986-05-21	Benzimidazol-Derivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
DK154078B (da)	1988-10-10	Analogifremgangsmaade til fremstilling af 2-(2-(4-(diphenyl-methyl)-1-piperazinyl)ethoxy)-acetamider eller syreadditionssalte heraf
CZ220399A3 (cs)	1999-11-17	Sulfonamidové deriváty, způsob jejich přípravy a jejich použití v léčivých prostředcích
EP0129207B1 (de)	1988-03-16	Substituierte Phenylalkyl(Piperazinyl oder Homopiperazinyl)-Propyl-(Urea oder Thiourea)
KR890000487B1 (ko)	1989-03-18	비스(피페라지닐 또는 호모피페라지닐)알칸 및 그의 제조방법
US4579947A (en)	1986-04-01	Substituted phenylalkylpiperazinylpropyl (ureas or thioureas) useful for treatment of immunological, inflammatory and allergic disorder
CS245792B2 (en)	1986-10-16	Production method of new substituted phenylalkyl(piperazinyl or homopiperazinyl)-alkylthioles and-thiocarbomates
GB2120234A (en)	1983-11-30	Triazole and imidazole derivates having fungicidal and plant-growth regulating activity
US3538090A (en)	1970-11-03	1-(4-tertiaryaminophenyl)-3-(piperazino)-propanols
CA1086758A (en)	1980-09-30	Amino-alkyl-isothioureas and processes for their preparation
DK155883B (da)	1989-05-29	Analogifremgangsmaade til fremstilling af triazoloquinazolinonderivater
EP0423524A2 (de)	1991-04-24	Propiophenonderivate und ihre Herstellung und pharmazeutische Verwendung
US4618677A (en)	1986-10-21	Substituted phenylalkyl-(piperazinyl or homopiperazinyl)alkyl-thiols and -thiocarbamates useful for the treatment of immunological, inflammatory, and allergic disorders
US4722926A (en)	1988-02-02	Substituted phenylalkyl-(piperazinyl or homopiperazinyl)alkyl thiols and thiocarbamates useful for the treatment of immunological, inflammatory, and allergic disorders
CS254998B2 (cs)	1988-02-15	Zpusob výroby nových bia-(piperazinyl-, popřípadě homopiperazinyl)alkanů
CS244847B2 (cs)	1986-08-14	Způsob výroby nových substituovaných fenylalkyHpiperazinyl nebo homopiperazinyOpropylmočovin nebo -thiomočovin