NO972190L - Hydrat for medisinsk anvendelse - Google Patents

Hydrat for medisinsk anvendelse

Info

Publication number: NO972190L
Authority: NO; Norway
Prior art keywords: hydrate; dimethoxy; chloro; ethyl; methylphenyl
Prior art date: 1994-11-14

Application number

NO972190A

Other languages

English (en)

Norwegian (no)

Other versions

NO972190D0 (no

Inventor

Kenjiro Yamamoto

Akihiko Miyadera

Hiroaki Kitaoka

Original Assignee

Daiichi Seiyaku Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1994-11-14

Filing date

1997-05-13

Publication date

1997-07-14

1997-05-13 Application filed by Daiichi Seiyaku Co filed Critical Daiichi Seiyaku Co

1997-05-13 Publication of NO972190D0 publication Critical patent/NO972190D0/no

1997-07-14 Publication of NO972190L publication Critical patent/NO972190L/no

Links

239000013078 crystal Substances 0.000 claims abstract description 54
238000002441 X-ray diffraction Methods 0.000 claims abstract description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 98
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 49
KSWPGVNFLOBEBO-UHFFFAOYSA-N 3-[2-[4-(3-chloro-2-methylphenyl)piperazin-1-yl]ethyl]-1-(1h-imidazol-5-ylmethyl)-5,6-dimethoxyindazole Chemical compound N=1N(CC=2N=CNC=2)C=2C=C(OC)C(OC)=CC=2C=1CCN(CC1)CCN1C1=CC=CC(Cl)=C1C KSWPGVNFLOBEBO-UHFFFAOYSA-N 0.000 claims description 28
238000000034 method Methods 0.000 claims description 26
238000011282 treatment Methods 0.000 claims description 18
NSCWUFNNLDMDJJ-UHFFFAOYSA-N 3-[2-[4-(3-chloro-2-methylphenyl)piperazin-1-yl]ethyl]-1-(1h-imidazol-5-ylmethyl)-5,6-dimethoxyindazole;hydrate;hydrochloride Chemical compound O.Cl.N=1N(CC=2N=CNC=2)C=2C=C(OC)C(OC)=CC=2C=1CCN(CC1)CCN1C1=CC=CC(Cl)=C1C NSCWUFNNLDMDJJ-UHFFFAOYSA-N 0.000 claims description 12
IHRBZSIEWFFJQW-UHFFFAOYSA-N 3-[2-[4-(3-chloro-2-methylphenyl)piperazin-1-yl]ethyl]-1-(1h-imidazol-5-ylmethyl)-5,6-dimethoxyindazole;dihydrochloride Chemical compound Cl.Cl.N=1N(CC=2N=CNC=2)C=2C=C(OC)C(OC)=CC=2C=1CCN(CC1)CCN1C1=CC=CC(Cl)=C1C IHRBZSIEWFFJQW-UHFFFAOYSA-N 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
IWKCLHUCYFCZJQ-UHFFFAOYSA-N 3-[2-[4-(3-chloro-2-methylphenyl)piperazin-1-yl]ethyl]-1-(1h-imidazol-5-ylmethyl)-5,6-dimethoxyindazole;hydrochloride Chemical compound Cl.N=1N(CC=2N=CNC=2)C=2C=C(OC)C(OC)=CC=2C=1CCN(CC1)CCN1C1=CC=CC(Cl)=C1C IWKCLHUCYFCZJQ-UHFFFAOYSA-N 0.000 claims description 4
239000000463 material Substances 0.000 abstract description 12
238000003860 storage Methods 0.000 abstract description 6
229910052739 hydrogen Inorganic materials 0.000 description 77
239000000243 solution Substances 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
150000001875 compounds Chemical class 0.000 description 25
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 18
230000000694 effects Effects 0.000 description 14
239000007787 solid Substances 0.000 description 14
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
238000004519 manufacturing process Methods 0.000 description 11
239000000203 mixture Substances 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
239000000825 pharmaceutical preparation Substances 0.000 description 11
239000002904 solvent Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
102000000584 Calmodulin Human genes 0.000 description 8
108010041952 Calmodulin Proteins 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
238000010438 heat treatment Methods 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000000843 powder Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
239000003814 drug Substances 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
208000014644 Brain disease Diseases 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
238000000921 elemental analysis Methods 0.000 description 5
210000002569 neuron Anatomy 0.000 description 5
230000000144 pharmacologic effect Effects 0.000 description 5
239000000725 suspension Substances 0.000 description 5
201000006474 Brain Ischemia Diseases 0.000 description 4
206010008120 Cerebral ischaemia Diseases 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
206010008118 cerebral infarction Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
238000001914 filtration Methods 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
238000010253 intravenous injection Methods 0.000 description 4
239000004005 microsphere Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
238000010992 reflux Methods 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 3
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
210000001168 carotid artery common Anatomy 0.000 description 3
230000002490 cerebral effect Effects 0.000 description 3
201000010099 disease Diseases 0.000 description 3
239000012153 distilled water Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
239000004570 mortar (masonry) Substances 0.000 description 3
238000000634 powder X-ray diffraction Methods 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
238000000967 suction filtration Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
ADCUCAMWCWNHJA-UHFFFAOYSA-N 4-(chloromethyl)-1-tritylimidazole Chemical compound C1=NC(CCl)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ADCUCAMWCWNHJA-UHFFFAOYSA-N 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
208000018152 Cerebral disease Diseases 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
HJZFWMNFDJAWHV-UHFFFAOYSA-N N1C=NC(=C1)CN1N=CC2=CC=CC=C12 Chemical compound N1C=NC(=C1)CN1N=CC2=CC=CC=C12 HJZFWMNFDJAWHV-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
102000010856 Type 1 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 2
108010037572 Type 1 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 2
239000002260 anti-inflammatory agent Substances 0.000 description 2
230000030833 cell death Effects 0.000 description 2
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
XPOKVXBWCOMJNO-UHFFFAOYSA-N ethyl 5,6-dimethoxy-1-[(1-tritylimidazol-4-yl)methyl]indazole-3-carboxylate Chemical compound C12=CC(OC)=C(OC)C=C2C(C(=O)OCC)=NN1CC(N=C1)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XPOKVXBWCOMJNO-UHFFFAOYSA-N 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
210000001320 hippocampus Anatomy 0.000 description 2
239000012456 homogeneous solution Substances 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 2
238000006386 neutralization reaction Methods 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
230000001681 protective effect Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000002076 thermal analysis method Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
231100000820 toxicity test Toxicity 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
-1 was used Chemical compound 0.000 description 2
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
XSWFFTOMNHATMS-UHFFFAOYSA-N 1-(3-chloro-2-methylphenyl)piperazine Chemical compound CC1=C(Cl)C=CC=C1N1CCNCC1 XSWFFTOMNHATMS-UHFFFAOYSA-N 0.000 description 1
GNPFLWOOROYWLQ-UHFFFAOYSA-N 1-[4-(3-chloro-2-methylphenyl)piperazin-1-yl]-2-[4-[[5-methoxy-1-[(2-methoxyphenyl)-diphenylmethyl]imidazol-4-yl]methyl]-2h-indazol-3-yl]ethanone Chemical compound N1=CN(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C(=CC=CC=2)OC)C(OC)=C1CC(C1=2)=CC=CC=2NN=C1CC(=O)N(CC1)CCN1C1=CC=CC(Cl)=C1C GNPFLWOOROYWLQ-UHFFFAOYSA-N 0.000 description 1
RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-UHFFFAOYSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
YEXWKCLXINFBDI-UHFFFAOYSA-N 2-(1-methylindazol-3-yl)acetic acid Chemical compound C1=CC=C2N(C)N=C(CC(O)=O)C2=C1 YEXWKCLXINFBDI-UHFFFAOYSA-N 0.000 description 1
QTCYTLBIKPSQFP-UHFFFAOYSA-N 2-[5,6-dimethoxy-1-[(1-tritylimidazol-4-yl)methyl]indazol-3-yl]acetonitrile Chemical compound C1=2C=C(OC)C(OC)=CC=2C(CC#N)=NN1CC(N=C1)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 QTCYTLBIKPSQFP-UHFFFAOYSA-N 0.000 description 1
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
YZZVGZYJWZCBPU-UHFFFAOYSA-N 3-(chloromethyl)-5,6-dimethoxy-1-[(1-tritylimidazol-4-yl)methyl]indazole Chemical compound C1=2C=C(OC)C(OC)=CC=2C(CCl)=NN1CC(N=C1)=CN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 YZZVGZYJWZCBPU-UHFFFAOYSA-N 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
208000031104 Arterial Occlusive disease Diseases 0.000 description 1
239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
206010015548 Euthanasia Diseases 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
206010022998 Irritability Diseases 0.000 description 1
241000282560 Macaca mulatta Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
206010028851 Necrosis Diseases 0.000 description 1
206010038669 Respiratory arrest Diseases 0.000 description 1
231100000643 Substance intoxication Toxicity 0.000 description 1
102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
206010070863 Toxicity to various agents Diseases 0.000 description 1
GSNOZLZNQMLSKJ-UHFFFAOYSA-N Trapidil Chemical compound CCN(CC)C1=CC(C)=NC2=NC=NN12 GSNOZLZNQMLSKJ-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000002730 additional effect Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000003501 anti-edematous effect Effects 0.000 description 1
230000003556 anti-epileptic effect Effects 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
229940127219 anticoagulant drug Drugs 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940127088 antihypertensive drug Drugs 0.000 description 1
229940127218 antiplatelet drug Drugs 0.000 description 1
239000000164 antipsychotic agent Substances 0.000 description 1
239000003699 antiulcer agent Substances 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
208000021328 arterial occlusion Diseases 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
239000002473 artificial blood Substances 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
210000000269 carotid artery external Anatomy 0.000 description 1
210000004004 carotid artery internal Anatomy 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000004720 cerebrum Anatomy 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 1
230000004087 circulation Effects 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
230000006837 decompression Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
229960003529 diazepam Drugs 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
FIHSLNDIKXNHHG-UHFFFAOYSA-N ethyl 5,6-dimethoxy-1h-indazole-3-carboxylate Chemical compound COC1=C(OC)C=C2C(C(=O)OCC)=NNC2=C1 FIHSLNDIKXNHHG-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
229940029575 guanosine Drugs 0.000 description 1
RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
229960003132 halothane Drugs 0.000 description 1
230000000004 hemodynamic effect Effects 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
230000000971 hippocampal effect Effects 0.000 description 1
210000004295 hippocampal neuron Anatomy 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 description 1
229960004135 idebenone Drugs 0.000 description 1
150000002473 indoazoles Chemical class 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
239000010410 layer Substances 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
229910001629 magnesium chloride Inorganic materials 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
230000017074 necrotic cell death Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
150000004885 piperazines Chemical class 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
238000001144 powder X-ray diffraction data Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
229960003912 probucol Drugs 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
SAALQYKUFCIMHR-UHFFFAOYSA-N propan-2-ol;2-propan-2-yloxypropane Chemical compound CC(C)O.CC(C)OC(C)C SAALQYKUFCIMHR-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000003998 snake venom Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
238000011146 sterile filtration Methods 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
239000003826 tablet Substances 0.000 description 1
PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
229960005001 ticlopidine Drugs 0.000 description 1
YDLQKLWVKKFPII-UHFFFAOYSA-N timiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC(N2C(NC3=CC=CC=C32)=S)CC1 YDLQKLWVKKFPII-UHFFFAOYSA-N 0.000 description 1
229950000809 timiperone Drugs 0.000 description 1
229960000187 tissue plasminogen activator Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
201000010875 transient cerebral ischemia Diseases 0.000 description 1
229960000363 trapidil Drugs 0.000 description 1
230000000472 traumatic effect Effects 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Neurology (AREA)
Engineering & Computer Science (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pain & Pain Management (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Materials For Medical Uses (AREA)
Medicinal Preparation (AREA)

NO972190A 1994-11-14 1997-05-13 Hydrat for medisinsk anvendelse NO972190L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP27820494		1994-11-14
PCT/JP1995/002317 WO1996015124A1 (en)	1994-11-14	1995-11-14	Hydrate for medicinal use

Publications (2)

Publication Number	Publication Date
NO972190D0 NO972190D0 (no)	1997-05-13
NO972190L true NO972190L (no)	1997-07-14

Family

ID=17594052

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO972190A NO972190L (no)	1994-11-14	1997-05-13	Hydrat for medisinsk anvendelse

Country Status (16)

Country	Link
US (1)	US5948913A (de)
EP (1)	EP0792879B1 (de)
KR (1)	KR100372188B1 (de)
CN (1)	CN1067998C (de)
AT (1)	ATE199375T1 (de)
AU (1)	AU698464B2 (de)
CA (1)	CA2205206A1 (de)
DE (1)	DE69520225T2 (de)
DK (1)	DK0792879T3 (de)
ES (1)	ES2156605T3 (de)
FI (1)	FI972035A7 (de)
GR (1)	GR3035820T3 (de)
NO (1)	NO972190L (de)
PT (1)	PT792879E (de)
RU (1)	RU2152941C1 (de)
WO (1)	WO1996015124A1 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE510650C2 (sv) *	1997-05-30	1999-06-14	Astra Ab	Ny förening
WO1999024432A1 (fr)	1997-11-12	1999-05-20	Mitsubishi Chemical Corporation	Derives de purine et medicament les renfermant en tant qu'ingredient actif
WO2000068231A1 (en) *	1999-05-11	2000-11-16	Mitsubishi Chemical Corporation	Purine derivative dihydrate, drugs containing the same as the active ingredient and intermediate in the production thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3362956A (en) *	1965-08-19	1968-01-09	Sterling Drug Inc	1-[(heterocyclyl)-lower-alkyl]-4-substituted-piperazines
WO1993018030A1 (en) *	1992-03-03	1993-09-16	Fujisawa Pharmaceutical Co., Ltd.	Benzimidazole derivatives as angiotensin ii antagonists
JPH07501834A (ja) *	1992-10-06	1995-02-23	チバーガイギー　アクチェンゲゼルシャフト	新規チオセミカルバゾンチオン
US5681954A (en) *	1993-05-14	1997-10-28	Daiichi Pharmaceutical Co., Ltd.	Piperazine derivatives
RU2124511C1 (ru) *	1993-05-14	1999-01-10	Фармасьютикал Ко., Лтд	Производные пиперазина
JPH0741431A (ja) *	1993-05-25	1995-02-10	Dai Ichi Seiyaku Co Ltd	脳保護薬
RU2135162C1 (ru) *	1993-05-25	1999-08-27	Дайити Фармасьютикалз Ко., ЛТД	Лекарственный препарат для нейропротекции (варианты)

1995
- 1995-11-14 AU AU38565/95A patent/AU698464B2/en not_active Ceased
- 1995-11-14 DK DK95936786T patent/DK0792879T3/da active
- 1995-11-14 RU RU97110091/04A patent/RU2152941C1/ru not_active IP Right Cessation
- 1995-11-14 FI FI972035A patent/FI972035A7/fi not_active IP Right Cessation
- 1995-11-14 CN CN95197248A patent/CN1067998C/zh not_active Expired - Fee Related
- 1995-11-14 AT AT95936786T patent/ATE199375T1/de not_active IP Right Cessation
- 1995-11-14 US US08/836,583 patent/US5948913A/en not_active Expired - Fee Related
- 1995-11-14 WO PCT/JP1995/002317 patent/WO1996015124A1/ja not_active Ceased
- 1995-11-14 ES ES95936786T patent/ES2156605T3/es not_active Expired - Lifetime
- 1995-11-14 KR KR1019970703310A patent/KR100372188B1/ko not_active Expired - Fee Related
- 1995-11-14 CA CA002205206A patent/CA2205206A1/en not_active Abandoned
- 1995-11-14 EP EP95936786A patent/EP0792879B1/de not_active Expired - Lifetime
- 1995-11-14 DE DE69520225T patent/DE69520225T2/de not_active Expired - Fee Related
- 1995-11-14 PT PT95936786T patent/PT792879E/pt unknown
1997
- 1997-05-13 NO NO972190A patent/NO972190L/no not_active Application Discontinuation
2001
- 2001-04-30 GR GR20010400668T patent/GR3035820T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
FI972035L (fi)	1997-07-11
AU3856595A (en)	1996-06-06
KR100372188B1 (ko)	2003-05-12
FI972035A0 (fi)	1997-05-13
AU698464B2 (en)	1998-10-29
CA2205206A1 (en)	1996-05-23
PT792879E (pt)	2001-08-30
ATE199375T1 (de)	2001-03-15
US5948913A (en)	1999-09-07
GR3035820T3 (en)	2001-07-31
WO1996015124A1 (en)	1996-05-23
DE69520225T2 (de)	2001-10-11
EP0792879B1 (de)	2001-02-28
CN1067998C (zh)	2001-07-04
FI972035A7 (fi)	1997-07-11
DK0792879T3 (da)	2001-03-26
ES2156605T3 (es)	2001-07-01
DE69520225D1 (de)	2001-04-05
EP0792879A4 (de)	1998-02-25
NO972190D0 (no)	1997-05-13
KR970707118A (ko)	1997-12-01
CN1171786A (zh)	1998-01-28
RU2152941C1 (ru)	2000-07-20
EP0792879A1 (de)	1997-09-03

Legal Events

Date	Code	Title	Description
2002-09-30	FC2A	Withdrawal, rejection or dismissal of laid open patent application

Publication	Publication Date	Title
NO329855B1 (no)	2011-01-10	Kystallforbindelse for fast oralt medikament samt fast oralt medikament omfattende denne til behandling av dysuria
ES2217580T3 (es)	2004-11-01	Composiciones orales de levosimendan.
CN101402565B (zh)	2012-07-04	卤代2－（a－羟基戊基）苯甲酸盐及其制法和用途
RU2233278C9 (ru)	2009-11-27	Пиримидиноновые соединения, способ их получения и фармацевтическая композиция
KR102418211B1 (ko)	2022-07-08	일시적 수용체 전위 a1 이온 채널의 억제
EP3390392B1 (de)	2021-10-06	Alkyl-dihydrochinolin-sulfonamid-verbindungen
US5837706A (en)	1998-11-17	Drug for neuroprotection
CA3197092A1 (en)	2022-05-19	1-(2-(4-cyclopropyl-1h-1,2,3-triazol-1-yl)acetyl)-4-hydroxy-n-(benzyl)pyrrolidin e-2-carboxamide derivatives as vhl inhibitors for the treatment of anemia and cancer
NO972190L (no)	1997-07-14	Hydrat for medisinsk anvendelse
EP0944612B1 (de)	2001-09-05	N-(4-acetyl-1-piperazinyl)-4-fluorobenzamidhydrat
JP3784868B2 (ja)	2006-06-14	医薬用水和物
HRP20030653A2 (en)	2005-06-30	Novel benzoylguanidine salt
JPWO1996015124A1 (ja)	1997-11-25	医薬用水和物
JP2611803B2 (ja)	1997-05-21	脳機能改善剤及び脳代謝賦活・保護剤
CH641775A5 (fr)	1984-03-15	N-(1-methyl 2-pyrrolidinyl methyl) 2,3-dimethoxy 5-methylsulfamoyl benzamide et ses derives, son procede de preparation et composition le renferment.
CA3101143A1 (en)	2019-12-12	Salt form
JP2611802B2 (ja)	1997-05-21	カルバモイル−２−ピロリジノン化合物
JP3571114B2 (ja)	2004-09-29	麻薬拮抗剤
JPS59231057A (ja)	1984-12-25	カルボン酸アミド化合物およびその誘導体
AU2024229006A1 (en)	2025-09-18	Crystal form of 8-chloro-3-pentyl-3,7-dihydro-1h-purin-2,6-dione compound and preparation method therefor
WO2025169150A1 (en)	2025-08-14	Crystalline forms, crystalline salt forms, compositions containing the same, and methods of using the same
JPH01146820A (ja)	1989-06-08	イミダゾール−２−チオンカルボキサミドによる再潅流傷害の軽減法
JPS59112985A (ja)	1984-06-29	クマリン誘導体、その製造法およびそれを有効成分とする抗アレルギ−剤
WO2013103004A1 (ja)	2013-07-11	（２ｅ）－３－（１ｈ－インダゾール－３－イル）－ｎ－（３－メトキシフェニル）－ｎ－［３－（メチルスルホニル）プロピル］ブト－２－エンアミドの結晶形
JPH08208481A (ja)	1996-08-13	脳障害治療剤