IL92000A - The Leads of Acids 0) -3-Amino-2-Hydroxypropyl (Hydroxymic, Their Preparation and Pharmaceutical Preparations Containing Them - Google Patents
The Leads of Acids 0) -3-Amino-2-Hydroxypropyl (Hydroxymic, Their Preparation and Pharmaceutical Preparations Containing ThemInfo
- Publication number
- IL92000A IL92000A IL9200089A IL9200089A IL92000A IL 92000 A IL92000 A IL 92000A IL 9200089 A IL9200089 A IL 9200089A IL 9200089 A IL9200089 A IL 9200089A IL 92000 A IL92000 A IL 92000A
- Authority
- IL
- Israel
- Prior art keywords
- general formula
- reaction
- compounds
- salts
- hydrogen
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 150000004820 halides Chemical class 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 25
- 230000008569 process Effects 0.000 claims description 22
- 206010012601 diabetes mellitus Diseases 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 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 10
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 238000009835 boiling Methods 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000002346 iodo group Chemical group I* 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000012954 diazonium Substances 0.000 claims description 2
- 150000001989 diazonium salts Chemical class 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 238000002955 isolation Methods 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 48
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- 239000002585 base Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 229940095990 inderal Drugs 0.000 description 7
- 230000000053 inderal effect Effects 0.000 description 7
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 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
- 239000011541 reaction mixture Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 201000009101 diabetic angiopathy Diseases 0.000 description 4
- 201000002249 diabetic peripheral angiopathy Diseases 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 3
- -1 1-ethy l-phenoxy Chemical group 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002876 beta blocker Substances 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 229910000039 hydrogen halide Inorganic materials 0.000 description 3
- 239000012433 hydrogen halide Substances 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- IGMZDGBNMCELOE-UHFFFAOYSA-N 1-chloro-3-piperidin-1-ylpropan-2-ol Chemical compound ClCC(O)CN1CCCCC1 IGMZDGBNMCELOE-UHFFFAOYSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 241001465754 Metazoa Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- OGNVQLDIPUXYDH-ZPKKHLQPSA-N (2R,3R,4S)-3-(2-methylpropanoylamino)-4-(4-phenyltriazol-1-yl)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid Chemical compound CC(C)C(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(O)=O)=C[C@@H]1N1N=NC(C=2C=CC=CC=2)=C1 OGNVQLDIPUXYDH-ZPKKHLQPSA-N 0.000 description 1
- VTWKXBJHBHYJBI-SOFGYWHQSA-N (ne)-n-benzylidenehydroxylamine Chemical compound O\N=C\C1=CC=CC=C1 VTWKXBJHBHYJBI-SOFGYWHQSA-N 0.000 description 1
- HEYSRYRYZNGDRS-ODZAUARKSA-N (z)-but-2-enedioic acid;hydrobromide Chemical compound Br.OC(=O)\C=C/C(O)=O HEYSRYRYZNGDRS-ODZAUARKSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- FBEHFRAORPEGFH-UHFFFAOYSA-N Allyxycarb Chemical compound CNC(=O)OC1=CC(C)=C(N(CC=C)CC=C)C(C)=C1 FBEHFRAORPEGFH-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101000687911 Homo sapiens Transcription factor SOX-3 Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010054805 Macroangiopathy Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 101100313649 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) POT1 gene Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 102100024276 Transcription factor SOX-3 Human genes 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 101100161758 Yarrowia lipolytica (strain CLIB 122 / E 150) POX3 gene Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000023852 carbohydrate metabolic process Effects 0.000 description 1
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- BICAGYDGRXJYGD-UHFFFAOYSA-N hydrobromide;hydrochloride Chemical compound Cl.Br BICAGYDGRXJYGD-UHFFFAOYSA-N 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 206010062198 microangiopathy Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(I) nitrate Inorganic materials [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 208000024891 symptom Diseases 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
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/08—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU885405A HU207988B (en) | 1988-10-20 | 1988-10-20 | Process for producing halogenides of o-/3-amino-2-hydroxy-propyl/hydroximic acid and pharmaceutical compositions containing them as active components |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL92000A0 IL92000A0 (en) | 1990-07-12 |
| IL92000A true IL92000A (en) | 1994-06-24 |
Family
ID=10970243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9200089A IL92000A (en) | 1988-10-20 | 1989-10-16 | The Leads of Acids 0) -3-Amino-2-Hydroxypropyl (Hydroxymic, Their Preparation and Pharmaceutical Preparations Containing Them |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US5147879A (es) |
| EP (1) | EP0417210B1 (es) |
| JP (1) | JPH0819078B2 (es) |
| KR (1) | KR0154117B1 (es) |
| AU (1) | AU620460B2 (es) |
| CA (1) | CA2000830C (es) |
| DE (1) | DE68913737T2 (es) |
| DK (1) | DK175584B1 (es) |
| ES (1) | ES2020030A6 (es) |
| FI (1) | FI93214C (es) |
| GR (1) | GR1002253B (es) |
| HU (1) | HU207988B (es) |
| IE (1) | IE65113B1 (es) |
| IL (1) | IL92000A (es) |
| NO (1) | NO178148C (es) |
| PL (1) | PL164547B1 (es) |
| PT (1) | PT92041B (es) |
| RU (1) | RU2093508C1 (es) |
| UA (1) | UA34412C2 (es) |
| WO (1) | WO1990004584A1 (es) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ285151A (en) * | 1994-05-06 | 1998-09-24 | Biorex Kutato Fejlesztoe Kft | Hydroximic acid derivatives |
| US5665756A (en) * | 1994-08-03 | 1997-09-09 | Hoechst Marion Roussel, Inc. | Aminoalkyloximes useful in the treatment of depression and obsessive compulsive disorders |
| HU9502843D0 (en) * | 1995-09-29 | 1995-11-28 | Livigene Ltd | Pharmaceutical composition |
| HU222994B1 (hu) * | 1995-11-02 | 2004-01-28 | BIOREX Kutató és Fejlesztő Rt. | Hidroxilaminszármazékok és azok alkalmazása sejtek molekuláris chaperon-termelésének fokozására alkalmas gyógyszerkészítmények előállítására |
| AU745987B2 (en) * | 1995-12-22 | 2002-04-11 | N-Gene Research Laboratories Inc. | A cosmetic composition and a method for reducing the ageing processes of skin |
| US6884424B2 (en) | 1995-12-22 | 2005-04-26 | N-Gene Research Laboratories Inc. | Method for treating the pathological lesions of the skin that develop by ultraviolet radiation of the sunlight |
| HUT78139A (hu) * | 1995-12-22 | 2000-11-28 | BIOREX Kutató és Fejlesztő Rt. | Készítmény, különösen a bőr öregedési folyamatainak mérséklésére |
| US6458371B1 (en) | 1995-12-22 | 2002-10-01 | Medgene, Limited | Cosmetic composition and a method for the prevention and/or reduction of the photoaging processes of the skin |
| HUT78138A (hu) | 1995-12-22 | 2000-09-28 | BIOREX Kutató és Fejlesztő Rt | Hidroximsavszármazékot tartalmazó készítmény a növénytermesztés elősegítésére és alkalmazása |
| DE19607960A1 (de) * | 1996-03-01 | 1997-09-04 | Hoechst Schering Agrevo Gmbh | Verfahren zur Herstellung von Ketonoximether durch Boronsäurekupplung |
| GB9613339D0 (en) * | 1996-06-26 | 1996-08-28 | Kritzinger Ann C | Limp bookbinding assembly technique for two books in one pass |
| UA64716C2 (en) * | 1996-08-09 | 2004-03-15 | Pharmaceuticals for therapy or prevention of illnesses connected with dysfunction of vascular endothelial cells | |
| HU220971B1 (hu) * | 1997-04-03 | 2002-07-29 | BIOREX Kutató és Fejlesztő Rt. | Eljárás 0-(3-amino-2-hidroxi-propil)-hidroximsav-halogenidek előállítására |
| HU9701081D0 (en) | 1997-06-23 | 1997-08-28 | Gene Research Lab Inc N | Pharmaceutical composition of antitumoral activity |
| WO2000007580A2 (en) * | 1998-08-03 | 2000-02-17 | N-Gene Kutató Kft. | Pharmaceutical compositions against autoimmune diseases |
| HUP9900475D0 (en) * | 1999-02-26 | 1999-04-28 | Biorex Kutato Fejlesztoe Kft | O-(3-piperidino-2-hydroxy-1-propyl)-hiyroximic acid-halogenid derivative, it's use for treating insulin resistance, and pharmaceutical compositions containing them as active component |
| US6933104B1 (en) | 1999-04-23 | 2005-08-23 | Shiva Biomedical, Llc | Diagnosis and treatment of human kidney diseases |
| HUP0001583A2 (hu) * | 2000-04-18 | 2002-11-28 | BIOREX Kutató és Fejlesztő Rt. | Egy piridin-1-oxid-származék és eljárás annak átalakítására gyógyászati hatású vegyületekké |
| PT1408966E (pt) * | 2001-07-17 | 2008-05-02 | N Gene Res Lab Inc | Combinações farmacêuticas sinergísticas para a prevenção ou tratamento da diabetes |
| HUP0105205A2 (hu) * | 2001-11-29 | 2003-08-28 | BIOREX Kutató és Fejlesztő Rt. | Metformint és egy hidroxilaminszármazékot tartalmazó, gyógyászati készítmény |
| DE60224841T2 (de) * | 2001-12-21 | 2009-01-22 | Rhodia Inc. | Kombinierte stabile kationische und anionische tensidzusammensetzungen |
| JP2005514418A (ja) * | 2002-01-11 | 2005-05-19 | ビオレックス クタトー エス フェイレストェー アールテー． | カルボキサミジン誘導体及び血管疾患の治療におけるそれらの使用 |
| HUP0303584A3 (en) | 2003-10-30 | 2009-12-28 | Cytrx Corp | Use of a hydroximic acid halide derivative in the treatment of neurodegenerative diseases |
| DE10351448A1 (de) * | 2003-11-04 | 2005-06-09 | Bayer Healthcare Ag | Geschmackstoffhaltige Arzneimittelformulierungen mit verbesserten pharmazeutischen Eigenschaften |
| WO2008039514A1 (en) * | 2006-09-26 | 2008-04-03 | Cytrx Corporation | Pharmaceutical compositions and methods for treating diseases associated with neurodegeneration |
| US7763601B2 (en) * | 2006-11-02 | 2010-07-27 | N-Gene Research Laboratories, Inc. | Prevention and treatment of obesity |
| WO2010058779A1 (ja) | 2008-11-18 | 2010-05-27 | 参天製薬株式会社 | ピリジン－３－カルバルデヒド ｏ－（ピペリジン－１－イル－プロピル）－オキシム誘導体を有効成分として含有する網脈絡膜変性疾患の治療剤 |
| HUP1100535A2 (en) | 2011-09-26 | 2013-04-29 | Bracelia Invest Ltd | Pharmaceutical composition for enhancement of stem cell treatment |
| HUP1100534A2 (en) | 2011-09-26 | 2013-04-29 | Balazs Dr Hazay | Pharmaceutical composition for the treatment of muscle atrophy |
| US20210145815A1 (en) | 2017-09-22 | 2021-05-20 | The University Of Adelaide | Methods and products for improving sperm quality |
| KR101995300B1 (ko) | 2018-03-30 | 2019-10-17 | 주식회사 아세아텍 | 다목적 관리기용 작업기 탈부착장치 |
| HUP1800298A1 (hu) | 2018-08-30 | 2020-05-28 | N Gene Res Laboratories Inc | Gyógyszerkombináció béta-receptor blokkolók hatásának módosítására és a mellékhatások csökkentésére |
| CN112174853B (zh) * | 2020-11-03 | 2023-07-25 | 湖南经世新材料有限责任公司 | 一种氨解法制备（z）-n-羟基苯脒的方法 |
| IL303026A (en) | 2020-11-19 | 2023-07-01 | Zevra Denmark As | Processes for preparing arimoclomol citrate and intermediates thereof |
| US20240383853A1 (en) * | 2021-09-28 | 2024-11-21 | Zevra Denmark A/S | Oximes and their use in treatment of gba-related diseases |
| AU2023454616A1 (en) | 2023-07-10 | 2026-01-22 | N-Gene Research Laboratories, Inc. | Increasing telomere length and/or suppressing telomere shortening |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670497C3 (de) * | 1967-06-06 | 1973-12-20 | Chinoin Gyogyszer- Es Vegyeszeti Termekek Gyara Rt, Budapest | Isochinohnderivate und Verfahren zu deren Herstellung |
| HU177578B (en) * | 1976-08-27 | 1981-11-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing new 0-/3-amino-2-hydroxy-propyl/-amidoxime derivatives |
| US4187220A (en) * | 1977-08-30 | 1980-02-05 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara R.T. | New O-(3-amino-2-hydroxy-propyl)-amidoxime derivatives, process for the preparation thereof and pharmaceutical compositions containing same |
| US4308399A (en) * | 1977-08-30 | 1981-12-29 | Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt. | O-(3-Amino-2-hydroxy-propyl)-amidoxime derivatives, process for the preparation thereof and pharmaceutical compositions containing same |
| EP0369944A1 (de) * | 1988-11-18 | 1990-05-23 | Ciba-Geigy Ag | Substituierte Oxadiaminobutane |
| FR2639942B1 (fr) * | 1988-12-02 | 1991-03-29 | Sanofi Sa | Ethers oximes de propenone, procede pour leur preparation et compositions pharmaceutiques les contenant |
| HUT54347A (en) * | 1989-01-10 | 1991-02-28 | Chinoin Gyogyszer Es Vegyeszet | Improved process for producing amidoximes |
-
1988
- 1988-10-20 HU HU885405A patent/HU207988B/hu unknown
-
1989
- 1989-10-16 IL IL9200089A patent/IL92000A/en not_active IP Right Cessation
- 1989-10-17 CA CA002000830A patent/CA2000830C/en not_active Expired - Lifetime
- 1989-10-19 KR KR1019900701346A patent/KR0154117B1/ko not_active Expired - Fee Related
- 1989-10-19 AU AU44186/89A patent/AU620460B2/en not_active Expired
- 1989-10-19 GR GR890100669A patent/GR1002253B/el not_active IP Right Cessation
- 1989-10-19 WO PCT/HU1989/000048 patent/WO1990004584A1/en not_active Ceased
- 1989-10-19 IE IE336489A patent/IE65113B1/en not_active IP Right Cessation
- 1989-10-19 RU SU894830570A patent/RU2093508C1/ru active
- 1989-10-19 PT PT92041A patent/PT92041B/pt not_active IP Right Cessation
- 1989-10-19 PL PL89281898A patent/PL164547B1/pl unknown
- 1989-10-19 UA UA4830570A patent/UA34412C2/uk unknown
- 1989-10-19 DE DE68913737T patent/DE68913737T2/de not_active Expired - Lifetime
- 1989-10-19 JP JP1510821A patent/JPH0819078B2/ja not_active Expired - Fee Related
- 1989-10-19 EP EP89911590A patent/EP0417210B1/en not_active Expired - Lifetime
- 1989-10-19 US US07/499,318 patent/US5147879A/en not_active Expired - Lifetime
- 1989-10-20 ES ES8903542A patent/ES2020030A6/es not_active Expired - Fee Related
-
1990
- 1990-06-18 NO NO902703A patent/NO178148C/no unknown
- 1990-06-19 FI FI903075A patent/FI93214C/fi active IP Right Grant
- 1990-06-19 DK DK199001497A patent/DK175584B1/da not_active IP Right Cessation
-
1992
- 1992-07-01 US US07/906,402 patent/US5296606A/en not_active Expired - Lifetime
-
1993
- 1993-06-07 US US08/072,765 patent/US5328906A/en not_active Expired - Lifetime
Also Published As
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Legal Events
| Date | Code | Title | Description |
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| HC | Change of name of proprietor(s) | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| EXP | Patent expired |