CH625790A5 - - Google Patents

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Publication number: CH625790A5
Authority: CH; Switzerland
Prior art keywords: dibenzo; cyclohepten; piperidine; ylidene; cyclopropylmethyl
Prior art date: 1975-12-22

Application number

CH1571276A

Other languages

German (de)

English (en)

Inventor

David Carroll Remy

George Gal

Seemon Hayden Pines

Original Assignee

Merck & Co Inc

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.)

1975-12-22

Filing date

1976-12-14

Publication date

1981-10-15

1976-12-14 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

1981-10-15 Publication of CH625790A5 publication Critical patent/CH625790A5/de

Links

UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 56
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 50
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
150000001875 compounds Chemical class 0.000 description 47
239000000243 solution Substances 0.000 description 43
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
238000000034 method Methods 0.000 description 39
239000000203 mixture Substances 0.000 description 29
230000003287 optical effect Effects 0.000 description 28
238000002360 preparation method Methods 0.000 description 27
-1 hydroxyethyl group Chemical group 0.000 description 26
150000003839 salts Chemical class 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000000463 material Substances 0.000 description 18
239000000047 product Substances 0.000 description 18
230000008569 process Effects 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
238000007514 turning Methods 0.000 description 14
238000001914 filtration Methods 0.000 description 12
239000012458 free base Substances 0.000 description 12
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 11
239000007787 solid Substances 0.000 description 11
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
238000000926 separation method Methods 0.000 description 9
239000002904 solvent Substances 0.000 description 9
239000007858 starting material Substances 0.000 description 9
238000007792 addition Methods 0.000 description 8
0 *CCC(CCNC(*)=O)=O Chemical compound *CCC(CCNC(*)=O)=O 0.000 description 7
239000002253 acid Substances 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
GCRUXZKMBCLCMN-UHFFFAOYSA-N 1-(cyclopropylmethyl)-4-[2-(trifluoromethylsulfanyl)dibenzo[1,3-e:1',2'-f][7]annulen-11-ylidene]piperidine Chemical compound C12=CC(SC(F)(F)F)=CC=C2C=CC2=CC=CC=C2C1=C(CC1)CCN1CC1CC1 GCRUXZKMBCLCMN-UHFFFAOYSA-N 0.000 description 6
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
229910052740 iodine Chemical group 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
230000000561 anti-psychotic effect Effects 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
QHACEJBZGFEEJE-UHFFFAOYSA-L bis(trifluoromethylsulfanyl)mercury Chemical compound [Hg+2].FC(F)(F)[S-].FC(F)(F)[S-] QHACEJBZGFEEJE-UHFFFAOYSA-L 0.000 description 5
BCCLDZVXWYCMMP-UHFFFAOYSA-M copper(1+);trifluoromethanethiolate Chemical compound [Cu+].FC(F)(F)[S-] BCCLDZVXWYCMMP-UHFFFAOYSA-M 0.000 description 5
230000000694 effects Effects 0.000 description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
HGVGNPKRFNFLET-UHFFFAOYSA-N 2-iododibenzo[1,3-e:1',2'-f][7]annulen-11-one Chemical compound C1=CC2=CC=CC=C2C(=O)C2=CC(I)=CC=C21 HGVGNPKRFNFLET-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
238000004458 analytical method Methods 0.000 description 4
230000001078 anti-cholinergic effect Effects 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
238000003756 stirring Methods 0.000 description 4
238000005406 washing Methods 0.000 description 4
NSACTPSEUXHIES-UHFFFAOYSA-N 1-(cyclopropylmethyl)-4-(2-iododibenzo[1,3-e:1',2'-f][7]annulen-11-ylidene)piperidine Chemical compound C12=CC(I)=CC=C2C=CC2=CC=CC=C2C1=C(CC1)CCN1CC1CC1 NSACTPSEUXHIES-UHFFFAOYSA-N 0.000 description 3
DBIYSCYMSMBEDP-UHFFFAOYSA-N 2-aminodibenzo[1,3-e:1',2'-f][7]annulen-11-one Chemical compound C1=CC2=CC=CC=C2C(=O)C2=CC(N)=CC=C21 DBIYSCYMSMBEDP-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
235000011114 ammonium hydroxide Nutrition 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000006227 byproduct Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
XHRNQDMNINGCES-UHFFFAOYSA-N cyclohept-4-en-1-one Chemical compound O=C1CCC=CCC1 XHRNQDMNINGCES-UHFFFAOYSA-N 0.000 description 3
JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical class C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
239000011630 iodine Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000002002 slurry Substances 0.000 description 3
FGMQVDLQCNGLNG-UHFFFAOYSA-N 1-[4-(2-iododibenzo[1,3-e:1',2'-f][7]annulen-11-ylidene)piperidin-1-yl]ethanol Chemical compound C1CN(C(O)C)CCC1=C1C2=CC(I)=CC=C2C=CC2=CC=CC=C21 FGMQVDLQCNGLNG-UHFFFAOYSA-N 0.000 description 2
NSFIAKFOCAEBER-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylphenyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=C(C)C=C1 NSFIAKFOCAEBER-UHFFFAOYSA-N 0.000 description 2
PIURDPRFWBLREG-UHFFFAOYSA-N 4-chloro-1-(cyclopropylmethyl)piperidine;hydrochloride Chemical compound Cl.C1CC(Cl)CCN1CC1CC1 PIURDPRFWBLREG-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
JXKKVDCUKQTGHA-UHFFFAOYSA-N C=C1CC1CN2CCC(=C3C4=CC=CC=C4C=CC5=C3C=C(C=C5)SC(F)(F)F)CC2 Chemical compound C=C1CC1CN2CCC(=C3C4=CC=CC=C4C=CC5=C3C=C(C=C5)SC(F)(F)F)CC2 JXKKVDCUKQTGHA-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
208000028017 Psychotic disease Diseases 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000000164 antipsychotic agent Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000002036 chloroform fraction Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
238000001035 drying Methods 0.000 description 2
238000000605 extraction Methods 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
125000002768 hydroxyalkyl group Chemical group 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
230000003993 interaction Effects 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
238000002156 mixing Methods 0.000 description 2
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
230000006340 racemization Effects 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000000126 substance Substances 0.000 description 2
125000001424 substituent group Chemical class 0.000 description 2
239000000725 suspension Substances 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-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
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
NSFIAKFOCAEBER-QZTJIDSGSA-N (2s,3s)-2,3-dihydroxy-2,3-bis(4-methylphenyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1[C@@](O)(C(O)=O)[C@](O)(C(O)=O)C1=CC=C(C)C=C1 NSFIAKFOCAEBER-QZTJIDSGSA-N 0.000 description 1
HZRVRLPHTTUVOK-UHFFFAOYSA-N 1-(cyclobutylmethyl)-4-[2-(trifluoromethylsulfanyl)dibenzo[1,3-e:1',2'-f][7]annulen-11-ylidene]piperidine Chemical compound C12=CC(SC(F)(F)F)=CC=C2C=CC2=CC=CC=C2C1=C(CC1)CCN1CC1CCC1 HZRVRLPHTTUVOK-UHFFFAOYSA-N 0.000 description 1
DESLMARWPGBONL-UHFFFAOYSA-N 1-(cyclopropylmethyl)-4-(9-fluoro-2-iododibenzo[1,3-a:1',3'-e][7]annulen-11-ylidene)piperidine Chemical compound C12=CC(F)=CC=C2C=CC2=CC=C(I)C=C2C1=C(CC1)CCN1CC1CC1 DESLMARWPGBONL-UHFFFAOYSA-N 0.000 description 1
IWYFGTGOZKQLLH-UHFFFAOYSA-N 1-(cyclopropylmethyl)piperidin-4-ol Chemical compound C1CC(O)CCN1CC1CC1 IWYFGTGOZKQLLH-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
SMCFRFSUHRUHLI-UHFFFAOYSA-N 2-amino-9-methyldibenzo[1,2-a:1',3'-e][7]annulen-11-one Chemical compound C1=CC2=CC=C(N)C=C2C(=O)C2=CC(C)=CC=C21 SMCFRFSUHRUHLI-UHFFFAOYSA-N 0.000 description 1
UVCLCDTZZWKCIP-UHFFFAOYSA-N 2-bromo-9-methyldibenzo[1,2-a:1',3'-e][7]annulen-11-one Chemical compound C1=CC2=CC=C(Br)C=C2C(=O)C2=CC(C)=CC=C21 UVCLCDTZZWKCIP-UHFFFAOYSA-N 0.000 description 1
BQDFITRQVPPUFP-UHFFFAOYSA-N 2-iodo-11h-dibenzo[1,3-e:1',2'-f][7]annulen-11-ol Chemical compound C1=CC2=CC=C(I)C=C2C(O)C2=CC=CC=C21 BQDFITRQVPPUFP-UHFFFAOYSA-N 0.000 description 1
WDOTUNJZHDVLNU-UHFFFAOYSA-N 2-iodo-9-methyldibenzo[1,2-a:1',3'-e][7]annulen-11-one Chemical compound C1=CC2=CC=C(I)C=C2C(=O)C2=CC(C)=CC=C21 WDOTUNJZHDVLNU-UHFFFAOYSA-N 0.000 description 1
MAUGPVACEMTUDE-UHFFFAOYSA-N 4-(2-iododibenzo[1,3-e:1',2'-f][7]annulen-11-ylidene)piperidine Chemical compound C12=CC(I)=CC=C2C=CC2=CC=CC=C2C1=C1CCNCC1 MAUGPVACEMTUDE-UHFFFAOYSA-N 0.000 description 1
XDDLQFQETMZSEW-UHFFFAOYSA-N 4-[2-(trifluoromethylsulfanyl)dibenzo[1,3-e:1',2'-f][7]annulen-11-ylidene]piperidine Chemical compound C12=CC(SC(F)(F)F)=CC=C2C=CC2=CC=CC=C2C1=C1CCNCC1 XDDLQFQETMZSEW-UHFFFAOYSA-N 0.000 description 1
JMSQZKKRLAHUCK-UHFFFAOYSA-N 9-amino-2-fluorodibenzo[1,3-a:1',3'-e][7]annulen-11-one Chemical compound C1=CC2=CC=C(F)C=C2C(=O)C2=CC(N)=CC=C21 JMSQZKKRLAHUCK-UHFFFAOYSA-N 0.000 description 1
OPCFGTAYNKZIEQ-UHFFFAOYSA-N 9-fluoro-2-iododibenzo[1,3-a:1',3'-e][7]annulen-11-one Chemical compound C1=CC2=CC=C(I)C=C2C(=O)C2=CC(F)=CC=C21 OPCFGTAYNKZIEQ-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
BYKAKDUVRJSACF-UHFFFAOYSA-N C1(CC1)N1CCC(CC1)[Mg]C Chemical compound C1(CC1)N1CCC(CC1)[Mg]C BYKAKDUVRJSACF-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
VRJHQPZVIGNGMX-UHFFFAOYSA-N O=C1CCNCC1 Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
102100029645 UBX domain-containing protein 11 Human genes 0.000 description 1
NLXGHSZDAYFJLI-UHFFFAOYSA-M [Cl-].C1CC([Mg+])CCN1CC1CC1 Chemical compound [Cl-].C1CC([Mg+])CCN1CC1CC1 NLXGHSZDAYFJLI-UHFFFAOYSA-M 0.000 description 1
MVWIFTGDWIRTIB-UHFFFAOYSA-M [Cl-].C1CC([Mg+])CCN1CC1CCC1 Chemical compound [Cl-].C1CC([Mg+])CCN1CC1CCC1 MVWIFTGDWIRTIB-UHFFFAOYSA-M 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000000746 allylic group Chemical group 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
150000001555 benzenes Chemical class 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
230000008859 change Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
235000014510 cooky Nutrition 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
229960001140 cyproheptadine Drugs 0.000 description 1
229960001270 d- tartaric acid Drugs 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
150000002497 iodine compounds Chemical class 0.000 description 1
229940045996 isethionic acid Drugs 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
229940098895 maleic acid Drugs 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
125000005487 naphthalate group Chemical group 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical class C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
150000004728 pyruvic acid derivatives Chemical class 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000010959 steel Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000004448 titration Methods 0.000 description 1
239000003204 tranquilizing agent Substances 0.000 description 1
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/38—Halogen atoms or nitro radicals
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/02—Magnesium compounds

Landscapes

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)
Psychiatry (AREA)
Pharmacology & Pharmacy (AREA)
Neurosurgery (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)

CH1571276A 1975-12-22 1976-12-14 CH625790A5 (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US05/642,863 US4031222A (en)	1975-12-22	1975-12-22	Trifluoromethylthio (and sulfonyl) derivatives of cyproheptadine analogs

Publications (1)

Publication Number	Publication Date
CH625790A5 true CH625790A5 (fr)	1981-10-15

Family

ID=24578354

Family Applications (7)

Application Number	Title	Priority Date	Filing Date
CH1571276A CH625790A5 (fr)	1975-12-22	1976-12-14
CH876880A CH627167A5 (fr)	1975-12-22	1980-11-26
CH877280A CH626346A5 (fr)	1975-12-22	1980-11-26
CH877180A CH626345A5 (fr)	1975-12-22	1980-11-26
CH877080A CH626344A5 (fr)	1975-12-22	1980-11-26
CH876980A CH626343A5 (fr)	1975-12-22	1980-11-26
CH357381A CH631164A5 (de)	1975-12-22	1981-06-01	Verfahren zur herstellung von neuem 1-cyclopropylmethyl-4-(3-jod-5h-dibenzo(a,d)cyclohepten-5-yliden)piperidin.

Family Applications After (6)

Application Number	Title	Priority Date	Filing Date
CH876880A CH627167A5 (fr)	1975-12-22	1980-11-26
CH877280A CH626346A5 (fr)	1975-12-22	1980-11-26
CH877180A CH626345A5 (fr)	1975-12-22	1980-11-26
CH877080A CH626344A5 (fr)	1975-12-22	1980-11-26
CH876980A CH626343A5 (fr)	1975-12-22	1980-11-26
CH357381A CH631164A5 (de)	1975-12-22	1981-06-01	Verfahren zur herstellung von neuem 1-cyclopropylmethyl-4-(3-jod-5h-dibenzo(a,d)cyclohepten-5-yliden)piperidin.

Country Status (26)

Country	Link
US (1)	US4031222A (fr)
JP (1)	JPS5278880A (fr)
AT (1)	AT363936B (fr)
AU (1)	AU506996B2 (fr)
BE (1)	BE849678A (fr)
CA (1)	CA1085823A (fr)
CH (7)	CH625790A5 (fr)
DE (1)	DE2657978C3 (fr)
DK (1)	DK550976A (fr)
ES (6)	ES454468A1 (fr)
FI (1)	FI763545A7 (fr)
FR (1)	FR2336133A1 (fr)
GB (1)	GB1519080A (fr)
GR (1)	GR62010B (fr)
HU (1)	HU175018B (fr)
IE (1)	IE44362B1 (fr)
IL (1)	IL51103A (fr)
LU (1)	LU76382A1 (fr)
NL (1)	NL7613713A (fr)
NO (1)	NO146359C (fr)
NZ (1)	NZ182868A (fr)
PH (1)	PH14088A (fr)
PL (4)	PL116947B1 (fr)
PT (1)	PT65956B (fr)
SE (1)	SE7613796L (fr)
ZA (1)	ZA767579B (fr)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4148903A (en) *	1977-07-28	1979-04-10	Merck & Co., Inc.	Antipsychotic, antiserotonin and antihistaminic pyrrolo[2,1-b][3]benzazepines
US4132796A (en) *	1977-12-01	1979-01-02	Merck & Co., Inc.	Antipsychotic 3-trifluoromethylsulfinyl analogs of cyproheptadine
US4285956A (en) *	1978-05-12	1981-08-25	Kefalas A/S	Xanthene and thioxanthene derivatives, compositions thereof and treatment therewith
US4195091A (en) *	1978-11-15	1980-03-25	Merck & Co., Inc.	Appetite stimulating pyrrolo[2,1-b][3]benzazepines
ATE3150T1 (de) *	1979-01-02	1983-05-15	Merck & Co. Inc.	Links- und rechtsdrehende enantiomere von 3halocyproheptadinen, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zusammensetzung.
US4220651A (en) *	1979-05-21	1980-09-02	Merck & Co., Inc.	Antipsychotic levorotatory enantiomers of 3-halocyproheptadines, analogs and derivatives
US4275070A (en) *	1979-05-21	1981-06-23	Merck & Co., Inc.	Antipsychotic pharmaceutical compositions of the levorotatory enantiomers of 3-methoxycyproheptadine and an analog thereof
EP0019797A1 (fr) *	1979-05-21	1980-12-10	Merck & Co. Inc.	Enantiomères lévogyres et dextrogyres de 3-méthoxycyproheptadine et leurs analogues, procédé pour leur préparation et compositions pharmaceutiques à activité antipsychotique
US5231105A (en) *	1987-06-02	1993-07-27	Ajinomoto Co., Inc.	Ethylamine derivatives and antihypertensives containing the same
US5250681A (en) *	1988-06-02	1993-10-05	Ajinomoto Co., Inc.	Piperidine derivatives and hypotensives containing the same
US5393890A (en) *	1988-06-02	1995-02-28	Ajinomoto Co., Inc.	Piperidine derivatives and hypotensives containing the same
US5021426A (en) *	1990-02-26	1991-06-04	Merck & Co., Inc.	Method of traeting malaria with cyproheptadine derivatives
US4996321A (en) *	1990-02-26	1991-02-26	Merck & Co., Inc.	Dibenzo[a,d]cycloheptenylidene compounds
US5114919A (en) *	1990-02-26	1992-05-19	Merck & Co., Inc.	Adjuncts in cancer chemotherapy
CN103130708B (zh) *	2011-12-01	2016-08-10	上海药明康德新药开发有限公司	一种n-叔丁氧羰基-4-硝基哌啶的制备方法
WO2022235813A1 (fr) *	2021-05-04	2022-11-10	The Texas A&M University System	Inhibiteurs de sars-cov-2

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3851059A (en) *	1970-02-05	1974-11-26	Merck & Co Inc	Method for the stimulation of appetite in patients

1975
- 1975-12-22 US US05/642,863 patent/US4031222A/en not_active Expired - Lifetime
1976
- 1976-12-08 DK DK550976A patent/DK550976A/da unknown
- 1976-12-08 SE SE7613796A patent/SE7613796L/xx not_active Application Discontinuation
- 1976-12-09 NO NO764188A patent/NO146359C/no unknown
- 1976-12-09 FI FI763545A patent/FI763545A7/fi not_active Application Discontinuation
- 1976-12-09 NL NL7613713A patent/NL7613713A/xx unknown
- 1976-12-13 NZ NZ182868A patent/NZ182868A/xx unknown
- 1976-12-13 PT PT65956A patent/PT65956B/pt unknown
- 1976-12-13 HU HU76ME2035A patent/HU175018B/hu unknown
- 1976-12-14 AU AU20528/76A patent/AU506996B2/en not_active Expired
- 1976-12-14 LU LU76382A patent/LU76382A1/xx unknown
- 1976-12-14 CH CH1571276A patent/CH625790A5/de not_active IP Right Cessation
- 1976-12-14 IL IL51103A patent/IL51103A/xx unknown
- 1976-12-16 GR GR52418A patent/GR62010B/el unknown
- 1976-12-16 FR FR7637940A patent/FR2336133A1/fr active Granted
- 1976-12-16 CA CA267,998A patent/CA1085823A/fr not_active Expired
- 1976-12-16 GB GB52626/76A patent/GB1519080A/en not_active Expired
- 1976-12-17 IE IE2771/76A patent/IE44362B1/en unknown
- 1976-12-20 PL PL1976222973A patent/PL116947B1/pl unknown
- 1976-12-20 PL PL1976222975A patent/PL116941B1/pl unknown
- 1976-12-20 PL PL1976222974A patent/PL122145B1/pl unknown
- 1976-12-20 PL PL1976194577A patent/PL116346B1/pl unknown
- 1976-12-20 AT AT0943376A patent/AT363936B/de not_active IP Right Cessation
- 1976-12-21 BE BE173486A patent/BE849678A/fr not_active IP Right Cessation
- 1976-12-21 ZA ZA00767579A patent/ZA767579B/xx unknown
- 1976-12-21 PH PH19273A patent/PH14088A/en unknown
- 1976-12-21 DE DE2657978A patent/DE2657978C3/de not_active Expired
- 1976-12-21 ES ES454468A patent/ES454468A1/es not_active Expired
- 1976-12-22 JP JP51153529A patent/JPS5278880A/ja active Pending
1978
- 1978-02-01 ES ES466553A patent/ES466553A1/es not_active Expired
- 1978-02-01 ES ES466550A patent/ES466550A1/es not_active Expired
- 1978-02-01 ES ES466549A patent/ES466549A1/es not_active Expired
- 1978-02-01 ES ES466551A patent/ES466551A1/es not_active Expired
- 1978-02-01 ES ES466552A patent/ES466552A1/es not_active Expired
1980
- 1980-11-26 CH CH876880A patent/CH627167A5/de not_active IP Right Cessation
- 1980-11-26 CH CH877280A patent/CH626346A5/de not_active IP Right Cessation
- 1980-11-26 CH CH877180A patent/CH626345A5/de not_active IP Right Cessation
- 1980-11-26 CH CH877080A patent/CH626344A5/de not_active IP Right Cessation
- 1980-11-26 CH CH876980A patent/CH626343A5/de not_active IP Right Cessation
1981
- 1981-06-01 CH CH357381A patent/CH631164A5/de not_active IP Right Cessation

Also Published As

Publication number	Publication date
SE7613796L (sv)	1977-06-23
IE44362L (en)	1977-06-22
PT65956A (en)	1977-01-01
FI763545A7 (fr)	1977-06-23
PL116941B1 (en)	1981-07-31
ES454468A1 (es)	1978-04-16
NL7613713A (nl)	1977-06-24
LU76382A1 (fr)	1977-06-28
BE849678A (fr)	1977-06-21
ES466549A1 (es)	1978-10-01
CH626343A5 (fr)	1981-11-13
US4031222A (en)	1977-06-21
FR2336133A1 (fr)	1977-07-22
PT65956B (en)	1978-11-07
ES466553A1 (es)	1978-10-01
ES466550A1 (es)	1978-10-01
ZA767579B (en)	1978-08-30
CH631164A5 (de)	1982-07-30
FR2336133B1 (fr)	1978-11-17
ES466551A1 (es)	1978-10-01
NO146359C (no)	1982-09-15
PL122145B1 (en)	1982-06-30
PL116947B1 (en)	1981-07-31
IL51103A0 (en)	1977-02-28
AU506996B2 (en)	1980-01-31
JPS5278880A (en)	1977-07-02
ES466552A1 (es)	1978-10-01
CH626345A5 (fr)	1981-11-13
PL194577A1 (fr)	1980-01-28
HU175018B (hu)	1980-04-28
NO146359B (no)	1982-06-07
CH626346A5 (fr)	1981-11-13
IE44362B1 (en)	1981-11-04
PL116346B1 (en)	1981-06-30
GB1519080A (en)	1978-07-26
DK550976A (da)	1977-06-23
AT363936B (de)	1981-09-10
NO764188L (fr)	1977-06-23
DE2657978C3 (de)	1981-02-12
CH627167A5 (fr)	1981-12-31
CH626344A5 (fr)	1981-11-13
CA1085823A (fr)	1980-09-16
PH14088A (en)	1981-02-10
DE2657978A1 (de)	1977-06-23
GR62010B (en)	1979-02-15
NZ182868A (en)	1979-03-28
ATA943376A (de)	1981-02-15
DE2657978B2 (de)	1980-06-04
IL51103A (en)	1980-11-30
AU2052876A (en)	1978-06-22

Legal Events

Date	Code	Title	Description
1983-08-31	PL	Patent ceased
2024-10-31	PL	Patent ceased

Publication	Publication Date	Title
DE29724281U1 (de)	2000-08-10	4-Phenylpiperidin-Verbindungen
DE2657978C3 (de)	1981-02-12	Linksdrehende Enantiomere und Racemate von Trifluormethylthio(und -sulfonyl)cyproheptadinderivaten, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel
DE60002733T2 (de)	2004-03-18	Diester prodrugs von decahydroischinoline-3-carbonsäure
DE3402601A1 (de)	1984-08-02	Neue pharmazeutisch aktive 1,2,3,4,4a,5,10,10a-octahydrobenzo(g)chinolinderivate, deren herstellung und verwendung
EP0189370A2 (fr)	1986-07-30	Spiro-dioxolanes, -dithiolanes et -oxothiolanes
DD300105A5 (de)	1992-05-21	Neue R(-)3-Quinuliclidinol - Derivate
DE2318002A1 (de)	1973-10-31	Eckige klammer auf alpha-(3-trifluormethylphenoxy)-4-chlorbenzyl eckige klammer zu -heterocyclen
DE2514914A1 (de)	1975-10-09	Verfahren zur herstellung tertiaerer amine
CH417574A (de)	1966-07-31	Verfahren zur Herstellung therapeutisch wirksamer Dibenzocycloheptanderivate
DE3204403A1 (de)	1983-08-11	Neue pyridobenzodiazepinone, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE4131584A1 (de)	1993-03-25	Imidazolylmethyl-pyridine, ihre herstellung und anwendung als pharmazeutika
DE3320616A1 (de)	1983-12-15	1,4-dihydropyridinderivate in optisch aktiver oder in racemat-form, und deren herstellung und pharmazeutische zusammensetzung
EP0770082A1 (fr)	1997-05-02	Derives d'acide carboxylique de dioxo-thiopyrano-pyridine et leur utilisation comme medicaments
CH625789A5 (fr)	1981-10-15
DE2717001A1 (de)	1978-10-19	Arzneimittel mit antithrombotischer wirkung
DE10162442A1 (de)	2003-07-03	Monocyclische N-Aryl-amide
DE2736259C2 (fr)	1988-01-07
DE2848926C3 (de)	1981-09-10	Derivate des 1,6,11,11a-Tetrahydro-[1,3-thiazino][3,4-b]isochinolins, ihre Herstellung und die sie enthaltenden Zusammensetzungen
AT371448B (de)	1983-06-27	Verfahren zur herstellung von neuen cis-4a-phenyl -isochinolin-derivaten und ihren saeureadditionssalzen
EP0014996B1 (fr)	1982-04-28	Spiro-amidines hétérocycliques, leurs stéréoisomères et isomères optiques, procédés pour leur préparation et médicaments les contenant
CH647755A5 (de)	1985-02-15	Cyclododecanderivate, verfahren zu ihrer herstellung und solche verbindungen enthaltende arzneimittel.
EP0483063B1 (fr)	1994-09-07	Dérivés d'ergoline
EP0182271B1 (fr)	1990-01-17	Dérivés dibromo Nb-quaternaires d'ajmaline, isoajmaline, sandwicine et isosandwicine et compositions pharmaceutiques contenant ces dérivés, produits intermédiaires et procédé pour leur préparation
AT377519B (de)	1985-03-25	Verfahren zur herstellung von neuen derivaten von (alkyl-(4-chinolyl))-piperidin oder -pyrroldin und ihren salzen
AT376671B (de)	1984-12-27	Verfahren zur herstellung von neuen 2(4-piperidyl)-1-(4-chinolyl)-aethanderivaten und ihren salzen