FI56385C - Metod foer framstaellning av bl a som lugnande laekemedel anvaendbara s-triazolo(1,5-a)(1,4)bensodiazepinderivat - Google Patents
Metod foer framstaellning av bl a som lugnande laekemedel anvaendbara s-triazolo(1,5-a)(1,4)bensodiazepinderivat Download PDFInfo
- Publication number
- FI56385C FI56385C FI476/74A FI47674A FI56385C FI 56385 C FI56385 C FI 56385C FI 476/74 A FI476/74 A FI 476/74A FI 47674 A FI47674 A FI 47674A FI 56385 C FI56385 C FI 56385C
- Authority
- FI
- Finland
- Prior art keywords
- compound
- parts
- ethyl
- ethanol
- triazolo
- Prior art date
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- 238000000034 method Methods 0.000 title description 21
- 150000001875 compounds Chemical class 0.000 claims description 79
- -1 4-methylpiperazino ring Chemical group 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- QSZGTNZUJRNSEM-UHFFFAOYSA-N 1H-[1,2,4]triazolo[1,5-a][1,4]benzodiazepine Chemical class N1C=NC=2N1C1=C(C=NC2)C=CC=C1 QSZGTNZUJRNSEM-UHFFFAOYSA-N 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 239000000932 sedative agent Substances 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000001624 sedative effect Effects 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 239000002904 solvent Substances 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 239000013078 crystal Substances 0.000 description 23
- 239000000203 mixture Substances 0.000 description 23
- 238000002844 melting Methods 0.000 description 21
- 230000008018 melting Effects 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000002425 crystallisation Methods 0.000 description 18
- 230000008025 crystallization Effects 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- 238000000921 elemental analysis Methods 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 9
- 150000001989 diazonium salts Chemical class 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- WRQAHWMWYQDKGD-UHFFFAOYSA-N 6h-1,4-benzodiazepine-7-carboxamide Chemical compound N1=CC=NC=C2CC(C(=O)N)=CC=C21 WRQAHWMWYQDKGD-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 239000012954 diazonium Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000001773 anti-convulsant effect Effects 0.000 description 4
- 238000009835 boiling Methods 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
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 3
- ZEWJFUNFEABPGL-UHFFFAOYSA-N 1,2,4-triazole-3-carboxamide Chemical compound NC(=O)C=1N=CNN=1 ZEWJFUNFEABPGL-UHFFFAOYSA-N 0.000 description 3
- SOYOCBJBBPMAQW-UHFFFAOYSA-N 1-(2-benzoyl-4-chlorophenyl)-5-(chloromethyl)-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 SOYOCBJBBPMAQW-UHFFFAOYSA-N 0.000 description 3
- BDMLDWKLIAIPFN-UHFFFAOYSA-N 1-(2-benzoyl-4-chlorophenyl)-5-(chloromethyl)-1,2,4-triazole-3-carboxylic acid Chemical compound N1=C(C(=O)O)N=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 BDMLDWKLIAIPFN-UHFFFAOYSA-N 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000008065 acid anhydrides Chemical class 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 3
- RIIVGZNBOBCPKS-UHFFFAOYSA-N ethyl 2-[(2-benzoyl-4-chlorophenyl)diazenyl]-2-[(2-chloroacetyl)amino]acetate Chemical compound CCOC(=O)C(NC(=O)CCl)N=NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 RIIVGZNBOBCPKS-UHFFFAOYSA-N 0.000 description 3
- MCANVHHGDCRDOP-UHFFFAOYSA-N ethyl 2-[(2-benzoyl-4-chlorophenyl)diazenyl]-2-bromoacetate Chemical compound CCOC(=O)C(Br)N=NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 MCANVHHGDCRDOP-UHFFFAOYSA-N 0.000 description 3
- PQWDDWRCEARMMC-UHFFFAOYSA-N ethyl 2-amino-2-[(2-benzoyl-4-chlorophenyl)diazenyl]acetate Chemical compound CCOC(=O)C(N)N=NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 PQWDDWRCEARMMC-UHFFFAOYSA-N 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- FTOVKFVJDIQHIM-UHFFFAOYSA-N (4-methylpiperazin-2-ylidene)methanone Chemical compound CN1CCNC(=C=O)C1 FTOVKFVJDIQHIM-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
- DLDTUYIGYMNERN-UHFFFAOYSA-N 2-[(2-chloroacetyl)amino]acetic acid Chemical compound OC(=O)CNC(=O)CCl DLDTUYIGYMNERN-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 206010049816 Muscle tightness Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- KDPAWGWELVVRCH-UHFFFAOYSA-M bromoacetate Chemical compound [O-]C(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-M 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000006193 diazotization reaction Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- RYRALQYIMXDQBX-UHFFFAOYSA-N ethyl 2-[(2-benzoylphenyl)diazenyl]-2-chloroacetate Chemical compound CCOC(=O)C(Cl)N=NC1=CC=CC=C1C(=O)C1=CC=CC=C1 RYRALQYIMXDQBX-UHFFFAOYSA-N 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 2
- PAUGTBXMNTXAMM-UHFFFAOYSA-N morpholin-3-ylidenemethanone Chemical compound O=C=C1COCCN1 PAUGTBXMNTXAMM-UHFFFAOYSA-N 0.000 description 2
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Inorganic materials [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229940125723 sedative agent Drugs 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-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
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- ZUWXHHBROGLWNH-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-phenylmethanone Chemical compound NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 ZUWXHHBROGLWNH-UHFFFAOYSA-N 0.000 description 1
- GRDGBWVSVMLKBV-UHFFFAOYSA-N (2-amino-5-nitrophenyl)-(2-chlorophenyl)methanone Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C(=O)C1=CC=CC=C1Cl GRDGBWVSVMLKBV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical class N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 1
- WWOQTUNOMFBNDS-UHFFFAOYSA-N 1-(2-benzoyl-4-chlorophenyl)-5-(chloromethyl)-n-(2-hydroxyethyl)-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)NCCO)N=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1 WWOQTUNOMFBNDS-UHFFFAOYSA-N 0.000 description 1
- VRTWPIHMODRFDS-UHFFFAOYSA-N 1-(2-benzoyl-4-methylphenyl)-5-(chloromethyl)-1,2,4-triazole-3-carboxamide Chemical compound C=1C(C)=CC=C(N2C(=NC(=N2)C(N)=O)CCl)C=1C(=O)C1=CC=CC=C1 VRTWPIHMODRFDS-UHFFFAOYSA-N 0.000 description 1
- SXXRGIXHBFYDQN-UHFFFAOYSA-N 1-(2-benzoyl-4-methylphenyl)-5-(chloromethyl)-1,2,4-triazole-3-carboxylic acid Chemical compound C=1C(C)=CC=C(N2C(=NC(=N2)C(O)=O)CCl)C=1C(=O)C1=CC=CC=C1 SXXRGIXHBFYDQN-UHFFFAOYSA-N 0.000 description 1
- DOVAKSGIMSPSDW-UHFFFAOYSA-N 1-(2-benzoylphenyl)-5-(chloromethyl)-1,2,4-triazole-3-carboxylic acid Chemical compound N1=C(C(=O)O)N=C(CCl)N1C1=CC=CC=C1C(=O)C1=CC=CC=C1 DOVAKSGIMSPSDW-UHFFFAOYSA-N 0.000 description 1
- SRTPNFFWJQVKKZ-UHFFFAOYSA-N 1-(2-benzyl-4-methylphenyl)-5-(chloromethyl)-1,2,4-triazole-3-carboxamide Chemical compound C(C1=CC=CC=C1)C1=C(C=CC(=C1)C)N1N=C(N=C1CCl)C(=O)N SRTPNFFWJQVKKZ-UHFFFAOYSA-N 0.000 description 1
- UUZQLJWNLUFVAE-UHFFFAOYSA-N 1-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-(chloromethyl)-1,2,4-triazole-3-carboxamide Chemical compound N1=C(C(=O)N)N=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl UUZQLJWNLUFVAE-UHFFFAOYSA-N 0.000 description 1
- CXSQNRLNVWMBIR-UHFFFAOYSA-N 1-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-(chloromethyl)-1,2,4-triazole-3-carboxylic acid Chemical compound N1=C(C(=O)O)N=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl CXSQNRLNVWMBIR-UHFFFAOYSA-N 0.000 description 1
- LIUSZSAPZUPWNO-UHFFFAOYSA-N 1-[4-chloro-2-(4-methoxybenzoyl)phenyl]-5-(chloromethyl)-1,2,4-triazole-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC(Cl)=CC=C1N1C(CCl)=NC(C(O)=O)=N1 LIUSZSAPZUPWNO-UHFFFAOYSA-N 0.000 description 1
- MLKUHRRRGDIXQO-UHFFFAOYSA-N 1-[4-chloro-2-(4-methoxybenzoyl)phenyl]-5-(chloromethyl)-1,2,4-triazole-3-carboxylic acid;n,n-diethylethanamine Chemical compound CCN(CC)CC.C1=CC(OC)=CC=C1C(=O)C1=CC(Cl)=CC=C1N1C(CCl)=NC(C(O)=O)=N1 MLKUHRRRGDIXQO-UHFFFAOYSA-N 0.000 description 1
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
- XYOXINXVOOGYRB-UHFFFAOYSA-N 11-oxa-2,3,5,8-tetrazatetracyclo[11.4.0.02,6.08,12]heptadeca-1(17),4,6,9,13,15-hexaene-4-carboxamide Chemical compound C=1N2C=COC2C2=CC=CC=C2N2NC(C(=O)N)=NC2=1 XYOXINXVOOGYRB-UHFFFAOYSA-N 0.000 description 1
- FOJNTPMPHSOOJO-UHFFFAOYSA-N 16-methyl-13-phenyl-12-oxa-2,3,5,8-tetrazatetracyclo[12.4.0.02,6.08,13]octadeca-1(14),3,5,15,17-pentaene-4-carboxamide Chemical compound C=1C(C)=CC=C(N2N=C(N=C2CN2CCCO3)C(N)=O)C=1C23C1=CC=CC=C1 FOJNTPMPHSOOJO-UHFFFAOYSA-N 0.000 description 1
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 1
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
- TUTKZBLQYOHHJH-UHFFFAOYSA-N 2-(2-benzoylphenyl)-5-(chloromethyl)-1h-1,2,4-triazole-5-carboxylic acid Chemical compound C1=NC(C(=O)O)(CCl)NN1C1=CC=CC=C1C(=O)C1=CC=CC=C1 TUTKZBLQYOHHJH-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
- 125000003541 2-chlorobenzoyl group Chemical group ClC1=C(C(=O)*)C=CC=C1 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- PULBONHWNLERMR-UHFFFAOYSA-N 6h-1,2-benzodiazepine-7-carboxamide Chemical compound N1=NC=CC=C2CC(C(=O)N)=CC=C21 PULBONHWNLERMR-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LCNZUDCCDVINQV-UHFFFAOYSA-N [2-[5-(chloromethyl)-3-(4-methylpiperazine-1-carbonyl)-1,2,4-triazol-1-yl]phenyl]-phenylmethanone Chemical compound C1CN(C)CCN1C(=O)C1=NN(C=2C(=CC=CC=2)C(=O)C=2C=CC=CC=2)C(CCl)=N1 LCNZUDCCDVINQV-UHFFFAOYSA-N 0.000 description 1
- FWHRUGSEKDUTDT-UHFFFAOYSA-N [5-chloro-2-[5-(chloromethyl)-3-(morpholine-4-carbonyl)-1,2,4-triazol-1-yl]phenyl]-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=CC(Cl)=CC=C1N1C(CCl)=NC(C(=O)N2CCOCC2)=N1 FWHRUGSEKDUTDT-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229940089960 chloroacetate Drugs 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
- ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 1
- XXQQUDQARDWTAK-UHFFFAOYSA-N ethyl 1-(2-benzoyl-4-methylphenyl)-5-(chloromethyl)-1,2,4-triazole-3-carboxylate Chemical compound N1=C(C(=O)OCC)N=C(CCl)N1C1=CC=C(C)C=C1C(=O)C1=CC=CC=C1 XXQQUDQARDWTAK-UHFFFAOYSA-N 0.000 description 1
- GBLUEKKEMVNCGT-UHFFFAOYSA-N ethyl 1-[4-chloro-2-(2-chlorobenzoyl)phenyl]-5-(chloromethyl)-1,2,4-triazole-3-carboxylate Chemical compound N1=C(C(=O)OCC)N=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl GBLUEKKEMVNCGT-UHFFFAOYSA-N 0.000 description 1
- NLYMLUULTWPKQE-UHFFFAOYSA-N ethyl 1-[4-chloro-2-(4-methoxybenzoyl)phenyl]-5-(chloromethyl)-1,2,4-triazole-3-carboxylate Chemical compound N1=C(C(=O)OCC)N=C(CCl)N1C1=CC=C(Cl)C=C1C(=O)C1=CC=C(OC)C=C1 NLYMLUULTWPKQE-UHFFFAOYSA-N 0.000 description 1
- NBEMQPLNBYYUAZ-UHFFFAOYSA-N ethyl acetate;propan-2-one Chemical compound CC(C)=O.CCOC(C)=O NBEMQPLNBYYUAZ-UHFFFAOYSA-N 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940102253 isopropanolamine Drugs 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229960005195 morphine hydrochloride Drugs 0.000 description 1
- XELXKCKNPPSFNN-BJWPBXOKSA-N morphine hydrochloride trihydrate Chemical compound O.O.O.Cl.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O XELXKCKNPPSFNN-BJWPBXOKSA-N 0.000 description 1
- 229940068938 morphine injection Drugs 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000001874 trioxidanyl group Chemical group [*]OOO[H] 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP1993073 | 1973-02-19 | ||
| JP48019930A JPS5750797B2 (fr) | 1973-02-19 | 1973-02-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FI56385B FI56385B (fi) | 1979-09-28 |
| FI56385C true FI56385C (fi) | 1980-01-10 |
Family
ID=12012923
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI476/74A FI56385C (fi) | 1973-02-19 | 1974-02-19 | Metod foer framstaellning av bl a som lugnande laekemedel anvaendbara s-triazolo(1,5-a)(1,4)bensodiazepinderivat |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US3947417A (fr) |
| JP (1) | JPS5750797B2 (fr) |
| AT (1) | AT336623B (fr) |
| BE (1) | BE811199A (fr) |
| CA (1) | CA1043783A (fr) |
| CH (1) | CH594678A5 (fr) |
| CS (1) | CS195269B2 (fr) |
| DE (1) | DE2407731A1 (fr) |
| DK (1) | DK141727B (fr) |
| FI (1) | FI56385C (fr) |
| FR (1) | FR2218339B1 (fr) |
| GB (1) | GB1424305A (fr) |
| HU (1) | HU168871B (fr) |
| NL (1) | NL7402220A (fr) |
| SE (1) | SE414498B (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6156516A (ja) * | 1984-07-23 | 1986-03-22 | Nok Corp | アナログ・デジタル変換装置 |
| US4596799A (en) * | 1985-01-29 | 1986-06-24 | Ciba-Geigy Corporation | 9H-pyrrolo[2,1-c]-1,2,4-triazolo[4,3-a][1,4]benzodiazepines |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3755300A (en) * | 1968-10-24 | 1973-08-28 | Sankyo Co | Process for the preparation of benzodiazepine compounds |
| US3701782A (en) * | 1972-02-10 | 1972-10-31 | Upjohn Co | 1-carbolower alkoxy - 6 - phenyl-4h-s-triazolo(1,4)benzodiazepine compounds |
-
1973
- 1973-02-19 JP JP48019930A patent/JPS5750797B2/ja not_active Expired
-
1974
- 1974-02-15 CA CA192,697A patent/CA1043783A/fr not_active Expired
- 1974-02-15 AT AT122274A patent/AT336623B/de not_active IP Right Cessation
- 1974-02-15 DK DK79874AA patent/DK141727B/da unknown
- 1974-02-18 DE DE19742407731 patent/DE2407731A1/de not_active Withdrawn
- 1974-02-18 SE SE7402119A patent/SE414498B/xx unknown
- 1974-02-18 HU HUTA1291A patent/HU168871B/hu unknown
- 1974-02-18 FR FR7405424A patent/FR2218339B1/fr not_active Expired
- 1974-02-18 NL NL7402220A patent/NL7402220A/xx not_active Application Discontinuation
- 1974-02-18 CS CS741158A patent/CS195269B2/cs unknown
- 1974-02-18 BE BE141064A patent/BE811199A/fr unknown
- 1974-02-19 GB GB747974A patent/GB1424305A/en not_active Expired
- 1974-02-19 CH CH230474A patent/CH594678A5/xx not_active IP Right Cessation
- 1974-02-19 FI FI476/74A patent/FI56385C/fi active
- 1974-02-19 US US05/443,528 patent/US3947417A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DK141727B (da) | 1980-06-02 |
| HU168871B (fr) | 1976-07-28 |
| SE414498B (sv) | 1980-08-04 |
| CH594678A5 (fr) | 1978-01-13 |
| GB1424305A (en) | 1976-02-11 |
| JPS5750797B2 (fr) | 1982-10-28 |
| ATA122274A (de) | 1976-09-15 |
| AT336623B (de) | 1977-05-10 |
| US3947417A (en) | 1976-03-30 |
| FR2218339B1 (fr) | 1980-01-18 |
| CS195269B2 (en) | 1980-01-31 |
| CA1043783A (fr) | 1978-12-05 |
| NL7402220A (fr) | 1974-08-21 |
| AU6554974A (en) | 1975-08-14 |
| JPS49108099A (fr) | 1974-10-14 |
| FR2218339A1 (fr) | 1974-09-13 |
| FI56385B (fi) | 1979-09-28 |
| DE2407731A1 (de) | 1974-08-22 |
| DK141727C (fr) | 1980-10-27 |
| BE811199A (fr) | 1974-08-19 |
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