NO752811L - - Google Patents
Info
- Publication number
- NO752811L NO752811L NO752811A NO752811A NO752811L NO 752811 L NO752811 L NO 752811L NO 752811 A NO752811 A NO 752811A NO 752811 A NO752811 A NO 752811A NO 752811 L NO752811 L NO 752811L
- Authority
- NO
- Norway
- Prior art keywords
- group
- hydrogen atom
- general formula
- lower alkyl
- propyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- -1 ketone compound Chemical class 0.000 claims description 32
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000004442 acylamino group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000001589 carboacyl group Chemical group 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 150000002367 halogens Chemical class 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 239000001257 hydrogen Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- PKUPAJQAJXVUEK-UHFFFAOYSA-N 2-phenoxyacetyl chloride Chemical compound ClC(=O)COC1=CC=CC=C1 PKUPAJQAJXVUEK-UHFFFAOYSA-N 0.000 description 2
- 208000009132 Catalepsy Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010047853 Waxy flexibility Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- OWXJKYNZGFSVRC-NSCUHMNNSA-N (e)-1-chloroprop-1-ene Chemical compound C\C=C\Cl OWXJKYNZGFSVRC-NSCUHMNNSA-N 0.000 description 1
- WOGITNXCNOTRLK-VOTSOKGWSA-N (e)-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CC=C1 WOGITNXCNOTRLK-VOTSOKGWSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- XOCDAQOEMPXEGG-UHFFFAOYSA-N 1-phenyl-5-(4-phenylpiperazin-1-yl)pentan-1-one Chemical compound C=1C=CC=CC=1C(=O)CCCCN(CC1)CCN1C1=CC=CC=C1 XOCDAQOEMPXEGG-UHFFFAOYSA-N 0.000 description 1
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
- ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 2-ethoxyacetyl chloride Chemical compound CCOCC(Cl)=O ZPMWWAIBJJFPPQ-UHFFFAOYSA-N 0.000 description 1
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 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
- 239000002841 Lewis acid Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 229920001615 Tragacanth Polymers 0.000 description 1
- ZLLYKJWRVATEKK-UHFFFAOYSA-N acetyl acetate;propanoyl propanoate Chemical compound CC(=O)OC(C)=O.CCC(=O)OC(=O)CC ZLLYKJWRVATEKK-UHFFFAOYSA-N 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-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
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 230000001466 anti-adreneric effect Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 230000001410 anti-tremor Effects 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000003826 tablet 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- 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
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Abstract
Fremgangsmåte for fremstilling av acylhydrazonforbindelser.
Description
Foreliggende oppfinnelse vedrorer en fremgangsmåte for fremstilling av nye acyl- hydrazonforbindelser med den generelle formel I
og deres ikke-giftige farmasoytisk tålbare salter, hvori 12 R og R hver er hydrogen, halogen, lavere alkyl, lavere alkoksy, acylamino,N-lavere alkylacylamino, N-ar(lavere)-alkylacylamino, N,N-di(lavere)alkylamino, nitro eller trifluormetyl, R 3 er hydrogen eller lavere alkyl, R<4>er en acylgryppe, A er en lavere alkylengruppe og Z er en gruppe enten med formel
hvori R 5 er hydrogen, acyloksy eller hydroksyl og R 6 er hydrogen eller en fenyl- eller benzyl-gruppe som eventuelt er substituert med en eller to substituenter valgt fra gruppen bestående av halogen, lavere alkyl, lavere alkoksy og trifluormetyl på benzenringen,
eller en gruppe med formel
hvori den prikkede strek betegner en eventuell ytterligere enkelt binding, R 7 er et hydrogenatom eller en lavere alkylgruppe og R<8>og R<9>er hver et hydrogenatom, et halogenatom eller en lavere alkylgruppe, eller en gruppe med formel hvori R"^ er et hydrogenatom eller en lavere alkylgruppe og R^ er et hydrogenatom, et halogenatom, en lavere alkylgruppe eller en lavere alkoksygruppe, eller en gruppe med formel
12
hvori R er et hydrogenatom, et Jhalogenatom, en lavere alkylgruppe, en lavere alkoksygruppe eller en trifluormetylgruppe og n er et helt tall fra 0 til 2.
I de anvendte betegnelser betyr betegnelsen "lavere alkyl" lavere alkylgrupper med ett til fire karbonatomer som f.eks.
metyl, etyl, n-propyl, isopropyl, n-butyl, sec-rbutyl og tert-butyl. Betegnelsen "lavere alkoksy" betyr alkoksygrupper med ett til
fire karbonatomer som f.eks. metoksy, etoksy, n-propoksy, isopropoksy, n-butoksy, sec.-butoksy og t-butoksy. Betegnelsen "halogen" omfatter fluor, klor, brom og jod. Ved betegnelsen "acyl" i acylamino, lavere alkylacylamino, ar(lavere)alkylacylamino, acyloksy og acyl menes folgende grupper: benzoyl som eventuelt er substituert med en eller to substituenter valgt fra gruppen bestående av halogen, lavere alkyl og lavere alkoksy, lavere alkanoyl (f.eks. acetyl, n-propionyl, isobutyryl, n-butyryl), cykloalkylkarbonyl (f.eks. cyklopropylkarbonyl, cykloheksylkarbonyl), lavere alkenoyl (f.eks. propenoyl, butenoyl), fenyl(lavere)-alkanoyl, halo(lavere) alkanoyl, amino(lavere)alkanoyl, fenoksy-(lavere)alkanoyl, lavere alkylamino(lavere)alkanoyl, lavere alkoksy (lavere ) alkanoyl,f enyl (lavere) alkenoyl (f. eks. cinnamoyl) , etc. Betegnelsen "lavere alkylen" betegner kjeder med ett til -fire karbonatomer, og står for metylen, etylen, trimetylen, tetrametylen, etc.
Som et resultat av om fattende undersokelser vedrorende acylhydrazon-derivater, er det funnet at acylhydrazon-forbindelsene med formel (I) har utmerkede farmakologiske egenskaper som anti-psykotiske midler uten å bevirke noen særlige bivirkninger.
Blandt acylhydrazon-forbindelsene.medrformel (I) fremviser forbindelsene hvori A er trimetylen spesielt utmerkede anti-psykotiske egenskaper bedomt ut fra sentral-antikatecholaminergiske og cholinergiske aktivitetsforsok med dyr. Forbindelsene fremviser f.eks. hoyere ahti-apomorfin aktivitet med mye svakere eller ingen katalepsi i rotter i forhold til klorpromazin. (Katalepsi betraktes som et mål på den ekstrapyramidale bivirkning som er vanlig for konvensjonelle anti-psykotiske. midler) .
Acylhydrazon-forbindelsene med formel (I) hvori A er metylen, etylen,eller tetrametylen fremviser terapeutisk onskelige sentral- anticholinergiske egenskaper bedomt ut fra anti-tremor-forsok med dyr.
Acylhydrazon-forbindelsene med formel (I) har generelt en rekke nyttige farmakologiske egenskaper som f.eks. aktivitet på det sentrale og autonomiske nervesystem, anti-adrenergiske, og analgetiske egenskaper. Fra dette synspunkt foretrekkes•de forbindelser hvori A er trimetylen, R''' er halogen i p-stillingén og R 2 er halogen, hydrogen eller acylamino. Mest foretrekkes de forbindelser hvori A er trimetylen, R''' er fluor i p-stillingen,
2 3 4
R er hydrogen eller halogen, R er hydrogen, R er benzoyl, lavere alkanoyl, fenyl(lavere) alkanoyl, cykloalkylkarbonyl eller fenoksy(lavere)alkanoyl.
Det særegne ved fremgangsmåten i henhold til oppfinnelsen for fremstilling av de nevnte forbindelser med formel (I) er at
(A) en hydrazonforbindelse med den generelle formel II
1' 2 '
hvori R og R hver er et hydrogenatom, et halogenatom, en lavere alkylgruppe, en lavere alkoksygruppe og en aminogruppe,
en N.N-di(lavere)alkylamino gruppe, en N-lavere alkylaminogruppe, en N-ar(lavere)alkylamino gruppe, en acylamino gruppe, en N-lavere alkylacylamino gruppe, en nitro gruppe eller en trifluormetyl gruppe og R 3, A og Z hver har den ovennevnte betydning, omsettes med et acylerende"middel, eller
(B) en ketonforbindelse med den generelle formel III
hvori R 1 og R 2, A og Z har den ovennevnte betydning, omsettes med en acylhydrazin-forbindelse med den generelle formel IV
3 4
hvori R og R har den ovennevnte betydning,
hvoretter de erholdte forbindelser eventuelt omsettes for dannelse av deres farmasdytisk tålbare salter.
Hydrazonforbindelsen med formel (II) kan fremstilles ved å omsette ketonforbindelsen med formel (III) med en hydrazinforbindelse med formel NH2NHR 3 hvori R 3 har den ovennevnte betydning.
Reaksjonen mellom hydrazonforbindelsen med formel (II) og det acylerende middel gjennomfores vanlig i et inært løsningsmiddel som fii-eks;; et aromatisk hydrokarbon som benzen, toluen eller xylen, et amid som f.eks. dimetylformamid, dimetylacetamid eller en eter f.eks. dioksan, dietyleter, tetrahydrofuran, ved en temperatur i området fra -50°C til koketemperaturen for losningsmidlet Videre er det mulig å anvende en basisk substans som f.eks. et alkalikarbonat som natriumkarbonat, kaliumkarbonat, et alkali- . hydrogenkarbonat som f.eks. natriumhydrogenkarbonat, kaliumhydrogen-karbonat et alkalihydroksyd som f.eks. natriumhydroksyd, kalium-hydroksyd, eller et organisk amin som f.eks. pyridin, trietylamin som et syrebindende middel. Selv om en slik basisk substans ikke anvendes foregår reaksjonen på gunstig måte.
Det acylerende middel kan være det tilsvarende syrehalogenid eller syreanhydrid, f.eks. lavere alkanoyl-halogenid som f.eks. acetyl-klorid, acetylbromid, propionylklorid, videre benzoylha&ogenid, substituert benzoylhalogenid, lavere alkenoylhalogenid som f.eks. propenylklorid, videre fenyl(lavertalkanoylhalogenid som fenylacetyl-klorid, fenoksy(lavere) alkanoylhalogenid som fenoksyacetylklorid, fenyl(lavere)alkenoylhaiogenid som f.eks. cinnamoylklorid, lavere alkoksy(lavere)alkanoylhalogenid som f.eks. metoksyacetylklorid, etoksyacetylklorid, eamt lavere alkansyreanhydrid som eddiksyreanhydric propionsyreanhydrid, eller benzosyreanhydrid, etc.
Når R<11>og R 2 1hver betyr en aminogruppe, en N-lavere alkylamino-gruppe eller N-ar(lavere)alkylaminogruppe, fremstilles den tilsvarende acylhydrazonforbindelsen med formel (I) hvori R 1 og R<2>hver er en.acylaminogruppe, en N-lavere alkylacylamino-gruppe eller en N-ar(lavere)alkylacylamino-gruppe.
Reaksjonen mellom ketonforbindelsen med formel (III) og acyl-hydrazinforbindelsen med formel (IV) gjennomfores vanlig i et inært løsningsmiddel som f.eks. et aromatisk hydrokarbon som benzen, toluen, xylen, et amid som f.eks. dimetylformamid, dimetylacetamid, en eter som f.eks. dioksan, tetrahydrofuran, en alkohol som f.eks. etanol. n-propanol, butanol eller dimetylsulfoksyd ved en temperatur fra romtemperaturen til koketemperaturen for losningsmidlet. I reaksjonssystemet foretrekkes vanlig som katalysator nærvær av en sur substans som f.eks. en mineralsyre som saltsyre eller svovelsyre, en organisk syre som f.eks. eddiksyre eller-en Lewis-syre, eller en basisk substans som f.eks. alkali-metallkarbonat, et alkalimetalibikarbonat, et alkalimetallhydroksyd eller et organisk amin.
Som er resultat av den ovennevnte reaksjon fremstilles acylhydrazonforbindelsen med formel (I). Eksempler på slike forbindelser er acetylhydrazonj. n^-propionylhydrazon, cyklopropylkarbonylhydrazon, cykloheksylkarbonylhydrazon, benzoylhydrazon, kloroacetylhydrazon, bromacetylhydrazon, fenylacetylhydrazon, fenoksuacetylhydrazon, cinnamoylhydrazon, trifluoroacetylhydrazon, isobutyrylhydrazon og N,N-dimetylkarbamoylhydrazon av de folgende ketoner:
l-[y- (4-f luorobenzoyl) propyl] -4-p-klorof enyl-4-hydroksypiperidin; 1-Ty -(2-acetamino-4-fluorobenzoyl)propyl] -4-p-klorofenyl-4-hydroksypiperidin; l-jy - (2-nitro-4-f luorobenzoyl) propyl] -4-p-klorof enyl-4-hydroksypiperin; l-£y -(4-fluorobenzoyl)propy]J - 4-m-trifluoro-metylfenyl-4-hydroksypiperidin; l-[y-(2,4-difluorobenzoyl)propyl -4-m-trifluoro-metylf enyl-4-hydroksypiperin : , l-[y-(2-dimetylamino-4-f luorobenzoyl) propyl] -4-m-trif luorometylf enyl- 4-hydroksypiperi din;
1-Ty - (2-acetamino-4-f luorobenzoyl) propyl -4-m-trif liorometylfenyl-4-hydroksypiperidin; 8-|""y -(4-fluorobenzoyl)propyl] -4-okso-l-fenyl-1,3,8-triazaspiro [4,5jdekan;
8—Qy - (2, 4-dif luorobenzoyl) propyl*] -4-okso-l-f enyl-1, 3, 8-triazazpiro C4,5~]dekan; 8-£y - (2-acetamino-4-f luorobenzoyl) propyl] -4-okso-l-fenyl-1, 3, 8-triazaspiro£4, 5^Jdekan;
1-fy- (4-f luorobenzoyl) propy]J - 4- (2-keto-l-benzimidazolinyl) piperidin;
1-fy - (2, 4-dif luorobenzoyl) propyl] -4- (2-keto-l-benzimidazolinyl) piperidin;
1-Qy - (4-f luorobenzoyl).propyl] - (2-keto-l-benzimidazolinyl) - 1,2,3,6-tetrahydropyridin;
1-fcy - (4-f luorobenzoyl) propyl] -4-o-metoksyf enylpiperazin; 1-ty - (2 / 4-dif luorobenzoyl) propyl] -4-o-metoksyf enylpiperazin; l-£ |3-(4-f luorobenzoyl) etyl] 4-o-metoksyf enylpiperazin; l-fy - (4-f luorobenzoyl);propyl]—44-fenylpiperazin;
1-ty - (4-f luorobenzoyl) propyl]^ -4-benzyl-4-hydroksypiperidin; 1-^Y - (4-f luorobenzoyl) propyl] -4-p-tolyl-4-hydroksypiperidin; 1_£ (3_(4-fluorobenzoyl)etyl]-4-p-klorofenyl-4-hydroksypiperidin; l_£y -Benzoylprppyl)-4-m-trifluorometylfenyl-4-hydrokspiperidin; l-[ (3- (4-f luorobenzoyl) etyl piperidin; 1~[ 4-(4-fluorobenzoyl)butylj -4-p-klorofenyl-4-hydroksyp±peridin; l-£y- (4-f luorobenzoyl) propylj-4-m-trif luorometylf enyl-4-acetyloksypiperidin; 1-^Y -(2-propionylamino-4-fluorobenzoyl)propyll-4-m-trifluorometyl-fenyl-4-hydroksypiperidin; 1-[Y -(2-benzoylamirié-4-fluorobenzoyl)propyl] -4-m-trifluorometyl-fenyl-4-hydroksypiperidin;
1-Cy -(2-fenoksyacetylamino-4-fluorobenzoyl)-propyl] -4-p-klorof enyl-4-hydroksypiperidin; l-^Yr (2-f enylacetylamino-4-f luorobenzoyl) propyl] -4-m-trif luorometylf enyl-4-hydroksypiperidin;
1-CY -(4-fluorobenzoyl)propyl] -4-m-trifluorometyl-4-propionyl-oksypiperidin;
1-(4-bensoylbutyl)-4-fenylpiperazin;
1-((3-benzoyletyl)piperidin;
1- ((3-benzoyletyl) -4-f enylpiperazin, etG.
Disse acylhydrazon-forbindelsene med formel (I) i fri baseform kan omdannes til deres farmasoytisk tålbare salter som f.eks. syreaddisjonssaltene ved behandling" med mineralsyrer som saltsyre;;; bronihydrogensyre, organiske syrer som f .eks. eddiksyre, sitronsyre, oksalsyre, melkesyre, ravsyre, vinsyre, kanelsyre, askorbinsyre og lignende.
Hver av acylhydrazon-forbindelsene med formel (I) og deres farmasoytisk tålbare salter kan bringes i en egned form for tilforsel ved i og for seg kjente metoder. For fremstilling av slike preparatformer kan forbindelsene blandes med bærere eller fortynningsmidler som f.eks. vann, sesamolje, kalsiumfosfat, stivelse, talkum, kasein, magnesiumstearat, metylcellulose, polyglykoler, tragant og lignende, enkelte ganger sammen med stabiliseringsmidler og/eller emulgeringsmidler. Den resulterende blanding kan behandles på vanlig måte for fremstilling av tabletter, kapsler, piller, ampuller og,, lignende. Den vanlige orale dosering er o,5 til 200 mg pr. os daglig.
Praktiske og foretrukne utforelsesformer for oppfinnelsen fremgår av de folgende eksempler;
EKSEMPEL 1.
Til en omrortt opplosning av 1,5 g hydrazon av 1-jy -(2-f luorobenzoyl) propylj-4-m-trifluorometylfenyl-4-hydroksypiperidin i 30 ml tort tetrahydrofuran tilsettes en opplosning av 0,8 g propionylklorid i 10 ml tort tetrahydrofuran ved 0 - 10°C. Etter at omroringen var fortsatt ytterligere 5 timer under avkjoling under 10°C ble den resulterende blanding helt ut i isblandet vann, gjort alkalisk med 28% vandig ammoniakk og ekstrahert med benzen. Ekstrakten ble vasket i rekkefolge med fortynnet vandig ammoniakk og mettet vandig natriumklorid, torret over vannfritt natriumsulfat og inndampet under redusert trykk. Det resterende faststoff ble omkrystallisert fra etanol-vann og gav propionylhydrazonet av l-{/ - (4-f luotobenzoyl)>propyl] -4-m-trif luorometylf enyl-4-hydroksypiperidin med smeltepunkt fra 128 - 129°C.
EKSEMPEL 2.
Til en omrort opplosning av 1-, 5 g av hydrazonet av l-[ y~ (4-f luorobenzoyl) propyl^-4-m-trifluorometylfenyl-4-hydroksypiperidin i 30 ml tort tetrahydrofuran ble det tilsatt en opplosning av 1,5 g fenoksyacetylklorid i 10 ml tort tetra-hydrof uran ved 0 - 10°C. Etter fortsatt omroring i ytterligere 3 timer under avkjoling under 10°C ble den resultende blanding helt ut i isblandet vann, gjort alkalisk med 28% vandig ammoniakk og ekstrahert med benzen. Ekstrakten ble vasket i rekkefolge med fortynnet vandig ammoniakk og mettet vandig natrium-klorid, torret ever vannf ritt natriumsulfat og inndampet under redusert trykk. Det resterende faststoff ble omkrystallisert fra etanol og gav f enoksyacetylhydrazonet av l- fc- (4-f luorobenzoyl) propyl]-4-m-trif luorometylfenyl-4-hydroksypiperidin, med smeltepunkt 75 - 78°C.
EKSEMPEL 3.
På samme måte som i eksemplene 1 og 2 ble folgende forbindelser fremstilt: fenylacetylhydrazonet av 1-^ -(4-fluorobenzoyl)-propyl]-4-m-trifluorometylfenyl-4-hydroksypiperidin, smeltepunkt 150 - 151°C; Acetylhydrazonet av l-[^-(4-fluorobenzoyl)propylJ-4-m-trifluorometylfenyl-4-hydroksypiperin, smeltepunkt 163 - 164,5°C; Benzoylhydrazonet av 1- |V- (4-fluorobenzoyl)propyl]-4-m-trifluorometylfenyl-4-hydroksypiperidin,smeltepunkt 157 - 166°C; Fenoksyacetylhydrazonet av l-Q/-(4-fluorobenzoyl)propy]J-4-p-klorof enyl-4-hydroksypiperidin, smeltepunkt 151 - 153,5°C. Propionylhydrazonet av 1-/V-(4-fluorobenzoyl)-propyl]-4-p-klorof enyl-4-hydroksypiperidin, smeltepunkt 143 - 145°C.
Claims (12)
- Cyklopropylkarbonylhydrazonet av 1-CY-(4-fluorobenzoyl)propyl]-4-p-klorofényl-4-hydroksypiperidin, smeltepunkt 134 - 144°C.
- Cyklopropylkarbonylhydrazonet av 1-E.
- V- (4-f luorobenzoyl) propyl) 4-m-trifluorometylfenyl-4-hydroksypiperidin, smeltepunkt 178,5 - 182°C.
- PATENTKRAV Fremgangsmåte for fremstilling av acylhydrazon-forbindelser med den generelle formel I
- 1 2 hvori R og R hver er et hydrogenatom, et halogenatom, en lavere alkylgruppe, en lavere alkoksygruppe, en acylaminogruppe, en N-lavere alkylacylamino-gruppe, en N-ar(lavere) alkylacylamino-gruppe, en N,N-di(lavere)alkylamino-gruppe, en nitfogruppe eller en trifluorometylgruppe, R <3> er et hydrogenatom eller en lavere . alkylgruppe, R 4er en acylgruppe,A er en lavere alkylengruppe og Z er en gruppe med enten den generelle formel
- hvori R 5 er et hydrogenatom en acyloksygruppe eller en hydroksyl-gruppe og R er et hydrogenatom eller en fenyl- eller benzyl-gruppe som eventuelt er substituert med en eller to substituenter valgt fra gruppen bestående av halogen, lavere alkyl,lavere alkosky og trifluorometyl på benzenringen, eller en gruppe med den generelle formel
- hvori den strek-prikkede linje angir en eventuell ytterligere enkelt binding, R 7 er et hydrogenatom eller en lavere alkylgruppe og R 8 og R 9 er hver et hydrogenatom, et halogenatom eller eh lavere alkylgruppe, eller en gruppe med den generelle formel
- hvori R er et hydrogenatom eller en lavere alkylgruppe og R er et hydrogenatom, et halogenatom, en lavere alkylgruppe eller en lavere alkoksygruppe, eller en gruppe med den generelle formel
- 12 hvori R er et hydrogenatom, et halogenatom, en lavere alkylgruppe, en lavere alkoksygruppe eller en trifluorometylgruppe og n er et helt tall fra 0-2, og deres farmasoytisk tålbare salter, karakterisert ved at en forbindelse med den generelle formel II
- hvori R <11> og.
- R 2 1hver er et hydrogenatom, et halogenatom, en lavere alkylgruppe, en lavere alkoksygruppe, en aminogruppe, en NviN-di-?( lavere) alkylamino-gruppe,, en N-lavere alkyl aminogruppe, en N-ar(lavere)alkylamino gruppe, en acylaminogruppe, • en N-lavere alkylacylamino gruppe, en nitrogruppe eller en trifluorogruppe -v--.-og R , A og- Z har. den ovennevnté^b.etydning, omsettes med et acylerende middel, eller en ketonforbindelse med den generellé formel III
- 1 2 hvori R , R , A og Z har den ovennevnte betydning, omsettes med en acylhydrazinforbindelse med den generelle formel IV3 4 hvori R og R har den ovennevnte betydning.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP49092985A JPS5922704B2 (ja) | 1974-08-13 | 1974-08-13 | 新規なアシルヒドラゾン誘導体及びその塩の製法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO752811L true NO752811L (no) | 1976-02-16 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO752811A NO752811L (no) | 1974-08-13 | 1975-08-12 |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4065565A (no) |
| JP (1) | JPS5922704B2 (no) |
| AT (1) | AT347461B (no) |
| BE (1) | BE832161A (no) |
| CA (1) | CA1059515A (no) |
| CH (1) | CH616661A5 (no) |
| DE (1) | DE2536164A1 (no) |
| DK (1) | DK365175A (no) |
| FI (1) | FI752254A (no) |
| FR (3) | FR2288519A1 (no) |
| GB (1) | GB1483544A (no) |
| HU (1) | HU169276B (no) |
| NL (1) | NL7509332A (no) |
| NO (1) | NO752811L (no) |
| SE (1) | SE7509024L (no) |
| SU (1) | SU656512A3 (no) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5112382A (en) * | 1990-05-24 | 1992-05-12 | Rohm And Haas Company | Halopropargyl compounds, compositions, uses and processes of preparation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE792187A (fr) * | 1971-12-03 | 1973-03-30 | Sumitomo Chemical Co | Nouveaux derives d'alkylamines |
| JPS5760335B2 (no) * | 1972-06-14 | 1982-12-18 | Sumitomo Chemical Co |
-
1974
- 1974-08-13 JP JP49092985A patent/JPS5922704B2/ja not_active Expired
-
1975
- 1975-08-04 GB GB32550/75A patent/GB1483544A/en not_active Expired
- 1975-08-05 NL NL7509332A patent/NL7509332A/xx not_active Application Discontinuation
- 1975-08-06 BE BE158968A patent/BE832161A/xx unknown
- 1975-08-07 AT AT611375A patent/AT347461B/de not_active IP Right Cessation
- 1975-08-08 FI FI752254A patent/FI752254A/fi not_active Application Discontinuation
- 1975-08-12 SU SU752163136A patent/SU656512A3/ru active
- 1975-08-12 US US05/603,813 patent/US4065565A/en not_active Expired - Lifetime
- 1975-08-12 SE SE7509024A patent/SE7509024L/xx unknown
- 1975-08-12 CH CH1048575A patent/CH616661A5/de not_active IP Right Cessation
- 1975-08-12 CA CA233,314A patent/CA1059515A/en not_active Expired
- 1975-08-12 FR FR7525127A patent/FR2288519A1/fr active Granted
- 1975-08-12 NO NO752811A patent/NO752811L/no unknown
- 1975-08-12 DK DK365175A patent/DK365175A/da not_active Application Discontinuation
- 1975-08-13 DE DE19752536164 patent/DE2536164A1/de not_active Ceased
- 1975-08-13 HU HUSU898A patent/HU169276B/hu unknown
-
1976
- 1976-04-12 FR FR7610727A patent/FR2313051A1/fr active Granted
- 1976-04-12 FR FR7610726A patent/FR2313044A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| FR2288519A1 (fr) | 1976-05-21 |
| FI752254A (no) | 1976-02-14 |
| JPS5922704B2 (ja) | 1984-05-28 |
| AU8394075A (en) | 1977-02-17 |
| FR2288519B1 (no) | 1980-03-14 |
| BE832161A (fr) | 1976-02-06 |
| SE7509024L (sv) | 1976-02-16 |
| GB1483544A (en) | 1977-08-24 |
| FR2313051B1 (no) | 1980-07-25 |
| FR2313044A1 (fr) | 1976-12-31 |
| SU656512A3 (ru) | 1979-04-05 |
| US4065565A (en) | 1977-12-27 |
| FR2313044B1 (no) | 1980-06-06 |
| NL7509332A (nl) | 1976-02-17 |
| DE2536164A1 (de) | 1976-03-04 |
| ATA611375A (de) | 1978-05-15 |
| DK365175A (da) | 1976-02-14 |
| CA1059515A (en) | 1979-07-31 |
| AT347461B (de) | 1978-12-27 |
| JPS51125087A (en) | 1976-11-01 |
| CH616661A5 (no) | 1980-04-15 |
| FR2313051A1 (fr) | 1976-12-31 |
| HU169276B (no) | 1976-10-28 |
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