NO319793B1 - N-[2-hydroksy-3-(1-piperidinyl)propoksy]pyridin-1-oksid-3-karboksimidoylklorid og dets anvendelse til fremstilling av et farmasoytisk preparat, samt farmasoytisk preparat. - Google Patents
N-[2-hydroksy-3-(1-piperidinyl)propoksy]pyridin-1-oksid-3-karboksimidoylklorid og dets anvendelse til fremstilling av et farmasoytisk preparat, samt farmasoytisk preparat. Download PDFInfo
- Publication number
- NO319793B1 NO319793B1 NO20014103A NO20014103A NO319793B1 NO 319793 B1 NO319793 B1 NO 319793B1 NO 20014103 A NO20014103 A NO 20014103A NO 20014103 A NO20014103 A NO 20014103A NO 319793 B1 NO319793 B1 NO 319793B1
- Authority
- NO
- Norway
- Prior art keywords
- pyridine
- hydroxy
- oxide
- propoxy
- piperidinyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 title description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 title 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 title 1
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 50
- 230000001575 pathological effect Effects 0.000 claims abstract description 41
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 29
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 28
- SGEIEGAXKLMUIZ-PEZBUJJGSA-N (3z)-n-(2-hydroxy-3-piperidin-1-ylpropoxy)-1-oxidopyridin-1-ium-3-carboximidoyl chloride Chemical compound C1CCCCN1CC(O)CO\N=C(/Cl)C1=CC=C[N+]([O-])=C1 SGEIEGAXKLMUIZ-PEZBUJJGSA-N 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 230000001684 chronic effect Effects 0.000 claims abstract description 9
- 230000035771 neuroregeneration Effects 0.000 claims abstract description 9
- 230000002093 peripheral effect Effects 0.000 claims abstract description 9
- 208000033808 peripheral neuropathy Diseases 0.000 claims abstract description 8
- 230000007823 neuropathy Effects 0.000 claims abstract description 7
- 201000001119 neuropathy Diseases 0.000 claims abstract description 6
- 208000017442 Retinal disease Diseases 0.000 claims abstract description 5
- 206010038923 Retinopathy Diseases 0.000 claims abstract description 5
- 208000017169 kidney disease Diseases 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 5
- 230000001771 impaired effect Effects 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 36
- 230000003247 decreasing effect Effects 0.000 abstract 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 49
- 150000001875 compounds Chemical class 0.000 description 31
- 238000002474 experimental method Methods 0.000 description 29
- 229940126062 Compound A Drugs 0.000 description 28
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 28
- 230000000694 effects Effects 0.000 description 25
- 229940125396 insulin Drugs 0.000 description 25
- 102000004877 Insulin Human genes 0.000 description 24
- 108090001061 Insulin Proteins 0.000 description 24
- 229950002409 bimoclomol Drugs 0.000 description 20
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 19
- 239000008103 glucose Substances 0.000 description 19
- NMOVJBAGBXIKCG-VKAVYKQESA-N (3z)-n-(2-hydroxy-3-piperidin-1-ylpropoxy)pyridine-3-carboximidoyl chloride Chemical compound C1CCCCN1CC(O)CO\N=C(/Cl)C1=CC=CN=C1 NMOVJBAGBXIKCG-VKAVYKQESA-N 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 17
- 238000012360 testing method Methods 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 241000700157 Rattus norvegicus Species 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- -1 hydroxy acid halide Chemical class 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 206010012689 Diabetic retinopathy Diseases 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 210000002700 urine Anatomy 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 230000037213 diet Effects 0.000 description 6
- 230000004190 glucose uptake Effects 0.000 description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000036732 histological change Effects 0.000 description 5
- 230000007830 nerve conduction Effects 0.000 description 5
- 239000002504 physiological saline solution Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 229960001052 streptozocin Drugs 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 206010061666 Autonomic neuropathy Diseases 0.000 description 4
- 208000002249 Diabetes Complications Diseases 0.000 description 4
- 206010012655 Diabetic complications Diseases 0.000 description 4
- 230000006735 deficit Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 238000011835 investigation Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 239000013558 reference substance Substances 0.000 description 4
- 230000001953 sensory effect Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000003178 anti-diabetic effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000023852 carbohydrate metabolic process Effects 0.000 description 3
- 230000001610 euglycemic effect Effects 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- NMOVJBAGBXIKCG-UHFFFAOYSA-N n-(2-hydroxy-3-piperidin-1-ylpropoxy)pyridine-3-carboximidoyl chloride Chemical compound C1CCCCN1CC(O)CON=C(Cl)C1=CC=CN=C1 NMOVJBAGBXIKCG-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000002485 urinary effect Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 238000013293 zucker diabetic fatty rat Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
- 208000002705 Glucose Intolerance Diseases 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108010006519 Molecular Chaperones Proteins 0.000 description 2
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000021256 carbohydrate metabolism Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 208000033679 diabetic kidney disease Diseases 0.000 description 2
- 230000035487 diastolic blood pressure Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000007446 glucose tolerance test Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 201000009104 prediabetes syndrome Diseases 0.000 description 2
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 210000003497 sciatic nerve Anatomy 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical group O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
- CUCJJMLDIUSNPU-UHFFFAOYSA-N 1-oxidopiperidin-1-ium Chemical compound [O-][NH+]1CCCCC1 CUCJJMLDIUSNPU-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 206010012645 Diabetic autonomic neuropathy Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 125000000815 N-oxide group Chemical group 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 1
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 1
- 241000473945 Theria <moth genus> Species 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 235000019577 caloric intake Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 201000002249 diabetic peripheral angiopathy Diseases 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- IVLVTNPOHDFFCJ-UHFFFAOYSA-N fentanyl citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 IVLVTNPOHDFFCJ-UHFFFAOYSA-N 0.000 description 1
- 229960004207 fentanyl citrate Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- IRYFCWPNDIUQOW-UHFFFAOYSA-N fluanisone Chemical compound COC1=CC=CC=C1N1CCN(CCCC(=O)C=2C=CC(F)=CC=2)CC1 IRYFCWPNDIUQOW-UHFFFAOYSA-N 0.000 description 1
- 229960005220 fluanisone Drugs 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000000910 hyperinsulinemic effect Effects 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 102000005861 leptin receptors Human genes 0.000 description 1
- 108010019813 leptin receptors Proteins 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000003018 neuroregenerative effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000007474 nonparametric Mann- Whitney U test Methods 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000022558 protein metabolic process Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 210000002972 tibial nerve Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 230000003442 weekly effect Effects 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
- C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Ophthalmology & Optometry (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9900475A HUP9900475D0 (en) | 1999-02-26 | 1999-02-26 | 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 |
| PCT/HU2000/000015 WO2000050403A1 (en) | 1999-02-26 | 2000-02-24 | N-[2-hydroxy-3-(1-piperidinyl)propoxy]pyridine-1-oxide-3-carboximidoyl chloride and its use in the treatment of insulin resistance |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20014103D0 NO20014103D0 (no) | 2001-08-23 |
| NO20014103L NO20014103L (no) | 2001-10-22 |
| NO319793B1 true NO319793B1 (no) | 2005-09-12 |
Family
ID=90014224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20014103A NO319793B1 (no) | 1999-02-26 | 2001-08-23 | N-[2-hydroksy-3-(1-piperidinyl)propoksy]pyridin-1-oksid-3-karboksimidoylklorid og dets anvendelse til fremstilling av et farmasoytisk preparat, samt farmasoytisk preparat. |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6649628B1 (cs) |
| EP (1) | EP1163224B1 (cs) |
| JP (1) | JP4689838B2 (cs) |
| KR (1) | KR100676124B1 (cs) |
| AT (1) | ATE237590T1 (cs) |
| AU (1) | AU779096B2 (cs) |
| BG (1) | BG65178B1 (cs) |
| BR (1) | BR0008969A (cs) |
| CA (1) | CA2360451C (cs) |
| CZ (1) | CZ297386B6 (cs) |
| DE (1) | DE60002187T2 (cs) |
| DK (1) | DK1163224T3 (cs) |
| EE (1) | EE04961B1 (cs) |
| ES (1) | ES2193055T3 (cs) |
| HR (1) | HRP20010584B1 (cs) |
| HU (1) | HUP9900475D0 (cs) |
| IL (2) | IL144866A0 (cs) |
| NO (1) | NO319793B1 (cs) |
| PL (1) | PL197692B1 (cs) |
| PT (1) | PT1163224E (cs) |
| RS (1) | RS50083B (cs) |
| RU (1) | RU2250901C2 (cs) |
| SI (1) | SI1163224T1 (cs) |
| SK (1) | SK287063B6 (cs) |
| UA (1) | UA72495C2 (cs) |
| WO (1) | WO2000050403A1 (cs) |
| ZA (1) | ZA200106488B (cs) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| HU0103939D0 (en) * | 2001-09-27 | 2001-11-28 | Biorex Kutato Fejlesztoe Kft | Pharmaceutical composition containing methformin and n-[2-hydroxy-3-(1-piperidinyl)-propoxy]-pyridine-1-oxide-3-carboximidoyl chloride |
| PL371251A1 (en) | 2002-01-11 | 2005-06-13 | Biorex Kutato Es Fejlesztö Rt. | Carboxamidine derivatives and their use in the treatment of vascular diseases |
| HUP0303584A3 (en) * | 2003-10-30 | 2009-12-28 | Cytrx Corp | Use of a hydroximic acid halide derivative in the treatment of neurodegenerative diseases |
| US20080227813A1 (en) * | 2006-09-26 | 2008-09-18 | Jack Raymond Barber | Pharmaceutical compositions and methods for treating diseases associated with neurodegeneration |
| EP2318032B1 (en) | 2008-06-26 | 2012-04-04 | Orphazyme APS | Use of hsp70 as a regulator of enzymatic activity |
| US20110224200A1 (en) | 2008-11-18 | 2011-09-15 | Shin-Ichiro Hirai | Therapeutic agent for chorioretinal degenerative disease containing pyridine-3-carbaldehyde 0-(piperidin-1-yl-propyl)-oxime derivative as active ingredient |
| BR112013013143A2 (pt) | 2010-11-30 | 2016-08-23 | Orphazyme Aps | composto, e, método de tratamento de uma doença de armazenagem lisossômica |
| HUP1100534A2 (en) | 2011-09-26 | 2013-04-29 | Balazs Dr Hazay | Pharmaceutical composition for the treatment of muscle atrophy |
| HUP1100535A2 (en) | 2011-09-26 | 2013-04-29 | Bracelia Invest Ltd | Pharmaceutical composition for enhancement of stem cell treatment |
| PL2892540T3 (pl) * | 2012-09-06 | 2018-12-31 | Mcpharma Biotech Inc. | Leczenie biegunki i biegunki po odsadzeniu przy pomocy opornej skrobi ziemniaczanej |
| CN104620674B (zh) | 2012-09-14 | 2017-03-15 | 法国圣戈班玻璃厂 | 具有电连接元件的窗玻璃 |
| WO2015015248A1 (en) * | 2013-07-30 | 2015-02-05 | Debreceni Egyetem 67% | The use of compounds showing heat shock protein (hsp) co-inducing properties to enhance the insulin sensitizing effect in the treatment of type 2 diabetes |
| EP3193840B1 (en) * | 2014-09-15 | 2021-05-19 | Orphazyme A/S | Arimoclomol formulation |
| EP3442530A1 (en) | 2016-04-13 | 2019-02-20 | Orphazyme A/S | Heat shock proteins and cholesterol homeostasis |
| PT3448382T (pt) | 2016-04-29 | 2020-11-20 | Orphazyme As C/O Cobis As | Arimoclomol para o tratamento de distúrbios associados à glucocerebrosidase |
| CN110753544A (zh) | 2017-05-24 | 2020-02-04 | 奥菲泽米有限公司 | 热激蛋白诱导物和额颞病况 |
| CA3101241A1 (en) | 2018-05-28 | 2019-12-05 | Orphazyme A/S | Hsp70 protein levels in pbmc samples as biomarker for disease |
| HUP1800298A1 (hu) | 2018-08-30 | 2020-05-28 | N Gene Res Laboratories Inc | Gyógyszerkombináció béta-receptor blokkolók hatásának módosítására és a mellékhatások csökkentésére |
| WO2021116487A1 (en) | 2019-12-13 | 2021-06-17 | Som Innovation Biotech, S.A. | Compounds for use in the treatment of niemann-pick c disease |
| CN116075305A (zh) | 2020-06-24 | 2023-05-05 | 柯姆药物丹麦股份公司 | 用于治疗戈谢病的阿瑞洛莫 |
| US20230416224A1 (en) | 2020-11-19 | 2023-12-28 | Zevra Denmark A/S | Processes for preparing arimoclomol citrate and intermediates thereof |
| CN116783164A (zh) * | 2020-11-19 | 2023-09-19 | 泽维拉丹麦股份有限公司 | 制备柠檬酸阿瑞洛莫及其中间体的方法 |
| IL303968A (en) | 2020-12-24 | 2023-08-01 | Zevra Denmark As | Arimoclomol for the treatment of niemann pick disease, type c, in patients with er type missense mutations |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU207988B (en) * | 1988-10-20 | 1993-07-28 | Biorex Kutato Fejlesztoe Kft | Process for producing halogenides of o-/3-amino-2-hydroxy-propyl/hydroximic acid and pharmaceutical compositions containing them as active components |
| 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 |
| HUT78138A (hu) * | 1995-12-22 | 2000-09-28 | BIOREX Kutató és Fejlesztő Rt | Hidroximsavszármazékot tartalmazó készítmény a növénytermesztés elősegítésére és alkalmazása |
| 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 |
| 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 |
-
1999
- 1999-02-26 HU HU9900475A patent/HUP9900475D0/hu unknown
-
2000
- 2000-02-24 AU AU31824/00A patent/AU779096B2/en not_active Expired
- 2000-02-24 RU RU2001126126/04A patent/RU2250901C2/ru active
- 2000-02-24 RS YUP-603/01A patent/RS50083B/sr unknown
- 2000-02-24 DE DE60002187T patent/DE60002187T2/de not_active Expired - Lifetime
- 2000-02-24 AT AT00909542T patent/ATE237590T1/de active
- 2000-02-24 US US09/913,263 patent/US6649628B1/en not_active Expired - Lifetime
- 2000-02-24 PT PT00909542T patent/PT1163224E/pt unknown
- 2000-02-24 ES ES00909542T patent/ES2193055T3/es not_active Expired - Lifetime
- 2000-02-24 CZ CZ20013053A patent/CZ297386B6/cs not_active IP Right Cessation
- 2000-02-24 CA CA2360451A patent/CA2360451C/en not_active Expired - Lifetime
- 2000-02-24 EP EP00909542A patent/EP1163224B1/en not_active Expired - Lifetime
- 2000-02-24 KR KR1020017010932A patent/KR100676124B1/ko not_active Expired - Fee Related
- 2000-02-24 SI SI200030080T patent/SI1163224T1/xx unknown
- 2000-02-24 HR HR20010584A patent/HRP20010584B1/xx not_active IP Right Cessation
- 2000-02-24 UA UA2001085933A patent/UA72495C2/uk unknown
- 2000-02-24 DK DK00909542T patent/DK1163224T3/da active
- 2000-02-24 WO PCT/HU2000/000015 patent/WO2000050403A1/en not_active Ceased
- 2000-02-24 JP JP2000600986A patent/JP4689838B2/ja not_active Expired - Lifetime
- 2000-02-24 EE EEP200100447A patent/EE04961B1/xx not_active IP Right Cessation
- 2000-02-24 BR BR0008969-9A patent/BR0008969A/pt not_active IP Right Cessation
- 2000-02-24 IL IL14486600A patent/IL144866A0/xx active IP Right Grant
- 2000-02-24 PL PL350915A patent/PL197692B1/pl unknown
- 2000-02-24 SK SK1158-2001A patent/SK287063B6/sk not_active IP Right Cessation
-
2001
- 2001-08-07 ZA ZA200106488A patent/ZA200106488B/xx unknown
- 2001-08-13 IL IL144866A patent/IL144866A/en not_active IP Right Cessation
- 2001-08-22 BG BG105837A patent/BG65178B1/bg unknown
- 2001-08-23 NO NO20014103A patent/NO319793B1/no not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO319793B1 (no) | N-[2-hydroksy-3-(1-piperidinyl)propoksy]pyridin-1-oksid-3-karboksimidoylklorid og dets anvendelse til fremstilling av et farmasoytisk preparat, samt farmasoytisk preparat. | |
| RU2188015C2 (ru) | Способ ингибирования нейропептида y | |
| RS60301B1 (sr) | Kombinacija protiv regurgitacije za održavanje motiliteta creva | |
| US6486177B2 (en) | Methods for treatment of cognitive and menopausal disorders with D-threo methylphenidate | |
| CN110167562A (zh) | Dmpc、dmpg、dmpc/dmpg、lysopg和lysopc针对引起离子通道病的药物的保护作用 | |
| CA2449922C (en) | Pharmaceutical composition for therapy of interstitial cystitis | |
| NO178696B (no) | Akridinforbindelse og farmasöytisk preparat inneholdende denne | |
| WO2003082270A1 (en) | Method for treating cognitive disorders | |
| EP1772149A1 (en) | Drug for prevention or treatment of diabetes | |
| De Simoni et al. | Different effects of fenfluramine isomers and metabolites on extracellular 5-HIAA in nucleus accumbens and hippocampus of freely moving rats | |
| CA2270119A1 (en) | Drugs for ameliorating ocular circulatory disorders | |
| KR20250110947A (ko) | 화합물의 약학적으로 사용 가능한 염 및 이의 제조 방법 | |
| HU227343B1 (en) | O-(3-piperidino-2-hydroxy-1-propyl)-hydroxymic acid halogenide derivative, its use and medicament containing it | |
| KR20100080550A (ko) | Ｔｒｐｖ1 매개성 질환 치료제 | |
| JPH0541603B2 (cs) | ||
| EP1709966A1 (en) | Preventive and/or therapeutic agent for higher brain dysfunction | |
| JP2022552162A (ja) | 物質使用障害の処置のための１８－ｍｃ | |
| NO750733L (cs) | ||
| Babayan et al. | Neuroleptics and antipsychotic drugs | |
| JPH0196133A (ja) | 脳循環改善剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |