NO853923L - Fremgangsm¨te for fremstilling av terapeutisk aktive amid- derivater. - Google Patents
Fremgangsm¨te for fremstilling av terapeutisk aktive amid- derivater.Info
- Publication number
- NO853923L NO853923L NO853923A NO853923A NO853923L NO 853923 L NO853923 L NO 853923L NO 853923 A NO853923 A NO 853923A NO 853923 A NO853923 A NO 853923A NO 853923 L NO853923 L NO 853923L
- Authority
- NO
- Norway
- Prior art keywords
- compound
- formula
- group
- alkyl
- hydrogen
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 150000001408 amides Chemical class 0.000 title abstract description 11
- 230000001225 therapeutic effect Effects 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 93
- -1 n-octyl Chemical group 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 24
- 239000001257 hydrogen Substances 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 238000005804 alkylation reaction Methods 0.000 claims description 4
- 238000005905 alkynylation reaction Methods 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 2
- 125000005916 2-methylpentyl group Chemical group 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 claims description 2
- 125000005917 3-methylpentyl group Chemical group 0.000 claims description 2
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical group C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002843 carboxylic acid group Chemical group 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 230000000949 anxiolytic effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 27
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 15
- 239000013078 crystal Substances 0.000 description 14
- 229910052740 iodine Inorganic materials 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 238000001953 recrystallisation Methods 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 230000035939 shock Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 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 5
- KKFRXONSEIFKER-UHFFFAOYSA-N 4-amino-1-pentylpyrazolo[3,4-b]pyridine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C2N(CCCCC)N=CC2=C1N KKFRXONSEIFKER-UHFFFAOYSA-N 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- UFEFSSMVJGFEEJ-UHFFFAOYSA-N ethyl 4-ethoxy-1h-pyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2NN=CC2=C1OCC UFEFSSMVJGFEEJ-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910001220 stainless steel Inorganic materials 0.000 description 5
- 239000010935 stainless steel Substances 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 3
- 229960004782 chlordiazepoxide Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- SBDJLLYBEQCXAX-UHFFFAOYSA-N 4-(butylamino)-1-pentylpyrazolo[3,4-b]pyridine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C2N(CCCCC)N=CC2=C1NCCCC SBDJLLYBEQCXAX-UHFFFAOYSA-N 0.000 description 2
- ZATWGOYDWIJNMC-UHFFFAOYSA-N 4-amino-1-pent-3-ynylpyrazolo[3,4-b]pyridine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C2N(CCC#CC)N=CC2=C1N ZATWGOYDWIJNMC-UHFFFAOYSA-N 0.000 description 2
- LYTQEEIQIRJKGL-UHFFFAOYSA-N 4-amino-1-pent-4-enylpyrazolo[3,4-b]pyridine-5-carboxylic acid Chemical compound NC1=C(C(O)=O)C=NC2=C1C=NN2CCCC=C LYTQEEIQIRJKGL-UHFFFAOYSA-N 0.000 description 2
- XXTLMXOGRBXMQF-UHFFFAOYSA-N 5-bromopent-2-yne Chemical compound CC#CCCBr XXTLMXOGRBXMQF-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- ABBZJHFBQXYTLU-UHFFFAOYSA-N but-3-enamide Chemical compound NC(=O)CC=C ABBZJHFBQXYTLU-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- LVDLULQREFXNKL-UHFFFAOYSA-N ethyl 4-chloro-1-pentylpyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(CCCCC)N=CC2=C1Cl LVDLULQREFXNKL-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQFYIDOMCULPIW-UHFFFAOYSA-N n-methylprop-2-yn-1-amine Chemical compound CNCC#C HQFYIDOMCULPIW-UHFFFAOYSA-N 0.000 description 2
- GVWISOJSERXQBM-UHFFFAOYSA-N n-methylpropan-1-amine Chemical compound CCCNC GVWISOJSERXQBM-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- LPNANKDXVBMDKE-UHFFFAOYSA-N 5-bromopent-1-ene Chemical compound BrCCCC=C LPNANKDXVBMDKE-UHFFFAOYSA-N 0.000 description 1
- SEHFYZRHGUPLSY-UHFFFAOYSA-N 5-iodopent-1-yne Chemical compound ICCCC#C SEHFYZRHGUPLSY-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000049 anti-anxiety effect Effects 0.000 description 1
- 230000001253 anti-conflict Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000037396 body weight Effects 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
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- CMDKPGRTAQVGFQ-RMKNXTFCSA-N cinoxate Chemical compound CCOCCOC(=O)\C=C\C1=CC=C(OC)C=C1 CMDKPGRTAQVGFQ-RMKNXTFCSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- QLHDIMNXVZEJDR-UHFFFAOYSA-N ethyl 1-ethenyl-4-ethoxypyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(C=C)N=CC2=C1OCC QLHDIMNXVZEJDR-UHFFFAOYSA-N 0.000 description 1
- RCYMYKCRDUWPSP-UHFFFAOYSA-N ethyl 4-(butylamino)-1-pentylpyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(CCCCC)N=CC2=C1NCCCC RCYMYKCRDUWPSP-UHFFFAOYSA-N 0.000 description 1
- ZCIGXSARZZVBQO-UHFFFAOYSA-N ethyl 4-amino-1-pent-3-ynylpyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(CCC#CC)N=CC2=C1N ZCIGXSARZZVBQO-UHFFFAOYSA-N 0.000 description 1
- WCDKNMQWJLRFGC-UHFFFAOYSA-N ethyl 4-amino-1-pent-4-enylpyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(CCCC=C)N=CC2=C1N WCDKNMQWJLRFGC-UHFFFAOYSA-N 0.000 description 1
- ORPAXUMDACAGES-UHFFFAOYSA-N ethyl 4-amino-1-pent-4-ynylpyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(CCCC#C)N=CC2=C1N ORPAXUMDACAGES-UHFFFAOYSA-N 0.000 description 1
- QXELJTZBFUKFPV-UHFFFAOYSA-N ethyl 4-ethoxy-1-ethylpyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(CC)N=CC2=C1OCC QXELJTZBFUKFPV-UHFFFAOYSA-N 0.000 description 1
- LSMYNJCBNDTSPH-UHFFFAOYSA-N ethyl 4-ethoxy-1-pent-4-enylpyrazolo[3,4-b]pyridine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C2N(CCCC=C)N=CC2=C1OCC LSMYNJCBNDTSPH-UHFFFAOYSA-N 0.000 description 1
- NSHIYIMHYBAIEY-UHFFFAOYSA-N ethyl hypochlorite Chemical compound CCOCl NSHIYIMHYBAIEY-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- HVDONSGJXJFNRV-UHFFFAOYSA-M n,n-diphenylpyridin-1-ium-1-carboxamide;chloride Chemical compound [Cl-].C=1C=CC=C[N+]=1C(=O)N(C=1C=CC=CC=1)C1=CC=CC=C1 HVDONSGJXJFNRV-UHFFFAOYSA-M 0.000 description 1
- AQFWNELGMODZGC-UHFFFAOYSA-N o-ethylhydroxylamine Chemical compound CCON AQFWNELGMODZGC-UHFFFAOYSA-N 0.000 description 1
- NUXCOKIYARRTDC-UHFFFAOYSA-N o-ethylhydroxylamine;hydron;chloride Chemical compound Cl.CCON NUXCOKIYARRTDC-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000006187 phenyl benzyl group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011734 sodium Substances 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
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Anesthesiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Compounds Of Unknown Constitution (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB848425104A GB8425104D0 (en) | 1984-10-04 | 1984-10-04 | Amide derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO853923L true NO853923L (no) | 1986-04-07 |
Family
ID=10567707
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO853923A NO853923L (no) | 1984-10-04 | 1985-10-03 | Fremgangsm¨te for fremstilling av terapeutisk aktive amid- derivater. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4745121A (fi) |
| EP (1) | EP0180318B1 (fi) |
| JP (1) | JPS6191188A (fi) |
| KR (1) | KR860003252A (fi) |
| CN (1) | CN85107874A (fi) |
| AT (1) | ATE69228T1 (fi) |
| AU (1) | AU573899B2 (fi) |
| DE (1) | DE3584608D1 (fi) |
| DK (1) | DK454685A (fi) |
| ES (1) | ES8703464A1 (fi) |
| FI (1) | FI853859L (fi) |
| GB (2) | GB8425104D0 (fi) |
| GR (1) | GR852395B (fi) |
| HU (1) | HUT38344A (fi) |
| NO (1) | NO853923L (fi) |
| NZ (1) | NZ213697A (fi) |
| PT (1) | PT81246B (fi) |
| ZA (1) | ZA857173B (fi) |
| ZM (1) | ZM7585A1 (fi) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8610981D0 (en) * | 1986-05-06 | 1986-06-11 | Ici America Inc | Quinoline amides |
| FR2719587B1 (fr) * | 1994-05-03 | 1996-07-12 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments. |
| EP1056724B1 (en) | 1998-02-26 | 2005-05-25 | Neurogen Corporation | Substituted cycloalkyl-4-oxonicotinic carboxamides; gaba brain receptor ligands |
| US6326379B1 (en) | 1998-09-16 | 2001-12-04 | Bristol-Myers Squibb Co. | Fused pyridine inhibitors of cGMP phosphodiesterase |
| US20030220646A1 (en) * | 2002-05-23 | 2003-11-27 | Thelen Sarah L. | Method and apparatus for reducing femoral fractures |
| GB0230045D0 (en) | 2002-12-23 | 2003-01-29 | Glaxo Group Ltd | Compounds |
| EP1735314A1 (en) | 2004-03-16 | 2006-12-27 | Glaxo Group Limited | Pyrazolo[3,4-b]pyridine compound, and its use as a pde4 inhibitor |
| US7465795B2 (en) * | 2005-12-20 | 2008-12-16 | Astrazeneca Ab | Compounds and uses thereof |
| WO2007073283A1 (en) * | 2005-12-20 | 2007-06-28 | Astrazeneca Ab | Substituted cinnoline derivatives as gabaa-receptor modulators and method for their synthesis |
| MX2009009793A (es) * | 2007-03-14 | 2009-10-16 | Ranbaxy Lab Ltd | Derivados de pirazolo (3,4-b) piridina como inhibidores de fosfodiesterasa. |
| AR067028A1 (es) * | 2007-06-19 | 2009-09-30 | Astrazeneca Ab | Compuestos y usos de los mismos 849 |
| CN107501525B (zh) * | 2017-08-30 | 2020-06-09 | 本源精化环保科技有限公司 | N,n’烷基化二氨基二环己基甲烷类固化剂及制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE787249A (fr) * | 1971-08-05 | 1973-02-05 | Squibb & Sons Inc | Derives amino d'acides pyrazolopyridine carboxyliques, leurs esters et les sels de ces composes, ainsi que leurs procedes de preparation |
| US3979399A (en) * | 1972-11-15 | 1976-09-07 | E. R. Squibb & Sons, Inc. | Amino derivatives of pyrazolopyridine carboxamides |
| US3840546A (en) * | 1972-11-15 | 1974-10-08 | Squibb & Sons Inc | Amino derivatives of pyrazolopyridine carboxamides |
| US4511568A (en) * | 1982-05-12 | 1985-04-16 | Ici Americas Inc. | CNS-Depressant pyrazolopyridines |
| US4552883A (en) * | 1982-06-15 | 1985-11-12 | Ici Americas Inc. | Pyrazolo[3,4-b]pyridine carboxylic acid esters and their pharmaceutical use |
-
1984
- 1984-10-04 GB GB848425104A patent/GB8425104D0/en active Pending
-
1985
- 1985-09-11 US US06/774,905 patent/US4745121A/en not_active Expired - Lifetime
- 1985-09-12 GB GB858522642A patent/GB8522642D0/en active Pending
- 1985-09-18 ZA ZA857173A patent/ZA857173B/xx unknown
- 1985-09-19 AU AU47597/85A patent/AU573899B2/en not_active Ceased
- 1985-09-24 EP EP85306798A patent/EP0180318B1/en not_active Expired - Lifetime
- 1985-09-24 DE DE8585306798T patent/DE3584608D1/de not_active Expired - Fee Related
- 1985-09-24 AT AT85306798T patent/ATE69228T1/de not_active IP Right Cessation
- 1985-09-26 CN CN198585107874A patent/CN85107874A/zh not_active Withdrawn
- 1985-10-02 HU HU853823A patent/HUT38344A/hu unknown
- 1985-10-02 KR KR1019850007252A patent/KR860003252A/ko not_active Application Discontinuation
- 1985-10-03 NO NO853923A patent/NO853923L/no unknown
- 1985-10-03 PT PT81246A patent/PT81246B/pt not_active IP Right Cessation
- 1985-10-03 GR GR852395A patent/GR852395B/el unknown
- 1985-10-03 NZ NZ213697A patent/NZ213697A/xx unknown
- 1985-10-04 FI FI853859A patent/FI853859L/fi not_active Application Discontinuation
- 1985-10-04 JP JP60220499A patent/JPS6191188A/ja active Pending
- 1985-10-04 ES ES547620A patent/ES8703464A1/es not_active Expired
- 1985-10-04 ZM ZM75/85A patent/ZM7585A1/xx unknown
- 1985-10-04 DK DK454685A patent/DK454685A/da not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0180318A1 (en) | 1986-05-07 |
| NZ213697A (en) | 1989-03-29 |
| KR860003252A (ko) | 1986-05-21 |
| ATE69228T1 (de) | 1991-11-15 |
| GR852395B (fi) | 1985-12-03 |
| ES547620A0 (es) | 1987-02-16 |
| FI853859A0 (fi) | 1985-10-04 |
| CN85107874A (zh) | 1986-07-30 |
| AU573899B2 (en) | 1988-06-23 |
| US4745121A (en) | 1988-05-17 |
| DK454685A (da) | 1986-04-05 |
| HUT38344A (en) | 1986-05-28 |
| FI853859L (fi) | 1986-04-05 |
| ZA857173B (en) | 1986-07-30 |
| ES8703464A1 (es) | 1987-02-16 |
| JPS6191188A (ja) | 1986-05-09 |
| ZM7585A1 (en) | 1986-04-28 |
| GB8425104D0 (en) | 1984-11-07 |
| PT81246A (en) | 1985-11-01 |
| PT81246B (pt) | 1987-11-30 |
| DK454685D0 (da) | 1985-10-04 |
| DE3584608D1 (de) | 1991-12-12 |
| AU4759785A (en) | 1986-04-10 |
| GB8522642D0 (en) | 1985-10-16 |
| EP0180318B1 (en) | 1991-11-06 |
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