DE3877124T2 - Imidazol-derivate, verfahren zu deren herstellung und deren anwendung als alpha-2-adrenoceptor-antagonisten. - Google Patents
Imidazol-derivate, verfahren zu deren herstellung und deren anwendung als alpha-2-adrenoceptor-antagonisten.Info
- Publication number
- DE3877124T2 DE3877124T2 DE8888309710T DE3877124T DE3877124T2 DE 3877124 T2 DE3877124 T2 DE 3877124T2 DE 8888309710 T DE8888309710 T DE 8888309710T DE 3877124 T DE3877124 T DE 3877124T DE 3877124 T2 DE3877124 T2 DE 3877124T2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- compound
- pharmaceutically acceptable
- acceptable salt
- represent
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 24
- 238000004519 manufacturing process Methods 0.000 title claims description 7
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 title description 5
- 102000015006 alpha2-adrenergic receptor activity proteins Human genes 0.000 title description 5
- 239000005557 antagonist Substances 0.000 title description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 113
- 150000003839 salts Chemical class 0.000 claims description 38
- 238000011282 treatment Methods 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 13
- 238000011321 prophylaxis Methods 0.000 claims description 12
- 206010020772 Hypertension Diseases 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 201000001421 hyperglycemia Diseases 0.000 claims description 7
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000007363 ring formation reaction Methods 0.000 claims description 3
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- -1 alkyl radical Chemical class 0.000 description 17
- 239000000203 mixture Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- 239000012320 chlorinating reagent Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 230000001242 postsynaptic effect Effects 0.000 description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 230000003345 hyperglycaemic effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 229960002896 clonidine Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 229960002748 norepinephrine Drugs 0.000 description 3
- 230000003518 presynaptic effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- SGYJLHHTMIHSDV-UHFFFAOYSA-N 1,2-bis(bromomethyl)-3-phenylmethoxybenzene Chemical compound BrCC1=CC=CC(OCC=2C=CC=CC=2)=C1CBr SGYJLHHTMIHSDV-UHFFFAOYSA-N 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical group CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- YBOFYEVSDXTITK-UHFFFAOYSA-N [2-(hydroxymethyl)-3-phenylmethoxyphenyl]methanol Chemical compound OCC1=CC=CC(OCC=2C=CC=CC=2)=C1CO YBOFYEVSDXTITK-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- HXXFSFRBOHSIMQ-VFUOTHLCSA-N alpha-D-glucose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HXXFSFRBOHSIMQ-VFUOTHLCSA-N 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- SZRUPVPCSHJMJG-UHFFFAOYSA-N dimethyl 3-phenylmethoxybenzene-1,2-dicarboxylate Chemical compound COC(=O)C1=CC=CC(OCC=2C=CC=CC=2)=C1C(=O)OC SZRUPVPCSHJMJG-UHFFFAOYSA-N 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 229950010772 glucose-1-phosphate Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- BRWZPVRDOUWXKE-UHFFFAOYSA-N methylsulfanylmethane;trifluoroborane Chemical compound CSC.FB(F)F BRWZPVRDOUWXKE-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229910052722 tritium Inorganic materials 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
- IQAAAXGSGUMSBG-BTJKTKAUSA-N (z)-but-2-enedioic acid;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O IQAAAXGSGUMSBG-BTJKTKAUSA-N 0.000 description 1
- LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
- YXZFFTJAHVMMLF-UHFFFAOYSA-N 1-bromo-3-methylbutane Chemical compound CC(C)CCBr YXZFFTJAHVMMLF-UHFFFAOYSA-N 0.000 description 1
- XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000670 adrenergic alpha-2 receptor antagonist Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- HITBOAGYESUOFH-UHFFFAOYSA-N boric acid hydrochloride Chemical compound Cl.OB(O)O HITBOAGYESUOFH-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- BQGDDMMXPRJQHZ-UHFFFAOYSA-N dimethyl 3-hydroxybenzene-1,2-dicarboxylate Chemical compound COC(=O)C1=CC=CC(O)=C1C(=O)OC BQGDDMMXPRJQHZ-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical group 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 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
- 125000002560 nitrile group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 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
- 210000000056 organ Anatomy 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical group ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical group CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent 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
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878724441A GB8724441D0 (en) | 1987-10-19 | 1987-10-19 | Compounds |
| GB878726197A GB8726197D0 (en) | 1987-11-09 | 1987-11-09 | Compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3877124D1 DE3877124D1 (de) | 1993-02-11 |
| DE3877124T2 true DE3877124T2 (de) | 1993-04-29 |
Family
ID=26292917
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8888309710T Expired - Lifetime DE3877124T2 (de) | 1987-10-19 | 1988-10-17 | Imidazol-derivate, verfahren zu deren herstellung und deren anwendung als alpha-2-adrenoceptor-antagonisten. |
Country Status (14)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8916150D0 (en) * | 1989-07-14 | 1989-08-31 | Beecham Group Plc | Novel compounds |
| GB9123857D0 (en) * | 1991-11-09 | 1992-01-02 | Smithkline Beecham Plc | Novel compounds |
| JP3355081B2 (ja) * | 1995-02-16 | 2002-12-09 | 矢崎総業株式会社 | 防水ケース |
| JPH10243523A (ja) * | 1997-02-24 | 1998-09-11 | Yazaki Corp | 電気接続箱の水抜き構造 |
| FR2846328B1 (fr) * | 2002-10-23 | 2004-12-10 | Servier Lab | Nouveaux derives de l'imidazoline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| WO2008016007A1 (fr) * | 2006-07-31 | 2008-02-07 | Meiji Seika Kaisha, Ltd. | INHIBITEUR DE LA MÉTALLO-β-LACTAMASE |
| JP2009131088A (ja) * | 2007-11-26 | 2009-06-11 | Furukawa Electric Co Ltd:The | 電気接続箱 |
| JP6407457B2 (ja) | 2016-02-08 | 2018-10-17 | 株式会社エス・ディー・エス バイオテック | １，２−ベンゼンジメタノール化合物の製造方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3473210D1 (en) * | 1983-08-09 | 1988-09-15 | Ciba Geigy Ag | Controlling agent against insects and representatives of the akarine order, containing 2-(1-indolinyl-methyl)-imidazoline or its salts as the active component |
| GB8529546D0 (en) * | 1985-11-30 | 1986-01-08 | Beecham Group Plc | Compounds |
| ES2051750T3 (es) * | 1986-11-27 | 1994-07-01 | Beecham Group Plc | Procedimiento para la preparacion de nuevos compuestos. |
| US4878940A (en) * | 1987-04-02 | 1989-11-07 | Janssen Pharmaceutica N.V. | Herbicidal 1,5-substituted 1H-imidazoles |
-
1988
- 1988-10-17 DE DE8888309710T patent/DE3877124T2/de not_active Expired - Lifetime
- 1988-10-17 DK DK578088A patent/DK578088A/da not_active Application Discontinuation
- 1988-10-17 NZ NZ226594A patent/NZ226594A/xx unknown
- 1988-10-17 ES ES88309710T patent/ES2053755T3/es not_active Expired - Lifetime
- 1988-10-17 EP EP88309710A patent/EP0313288B1/en not_active Expired - Lifetime
- 1988-10-17 IE IE313688A patent/IE61028B1/en not_active IP Right Cessation
- 1988-10-17 AU AU23938/88A patent/AU601877B2/en not_active Expired
- 1988-10-17 PT PT88780A patent/PT88780B/pt not_active IP Right Cessation
- 1988-10-17 CA CA000580324A patent/CA1330663C/en not_active Expired - Lifetime
- 1988-10-18 KR KR1019880013600A patent/KR890008129A/ko not_active Application Discontinuation
- 1988-10-18 JP JP63260726A patent/JPH01135783A/ja active Pending
-
1990
- 1990-09-10 US US07/581,202 patent/US5021445A/en not_active Expired - Lifetime
-
1993
- 1993-02-25 GR GR930400405T patent/GR3007168T3/el unknown
-
1997
- 1997-12-19 HK HK97102521A patent/HK1001174A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JPH01135783A (ja) | 1989-05-29 |
| US5021445A (en) | 1991-06-04 |
| AU601877B2 (en) | 1990-09-20 |
| IE61028B1 (en) | 1994-09-07 |
| IE883136L (en) | 1989-05-19 |
| EP0313288B1 (en) | 1992-12-30 |
| ES2053755T3 (es) | 1994-08-01 |
| DK578088A (da) | 1989-04-20 |
| EP0313288A1 (en) | 1989-04-26 |
| DE3877124D1 (de) | 1993-02-11 |
| GR3007168T3 (US20020095090A1-20020718-M00002.png) | 1993-07-30 |
| KR890008129A (ko) | 1989-07-08 |
| NZ226594A (en) | 1991-09-25 |
| HK1001174A1 (en) | 1998-05-29 |
| CA1330663C (en) | 1994-07-12 |
| AU2393888A (en) | 1989-04-20 |
| DK578088D0 (da) | 1988-10-17 |
| PT88780B (pt) | 1992-12-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2203373C3 (de) | Neue 2- [(2- Alkylbenzofuran-3-yl)-methyl] -A2 -imidazoline | |
| DD273833A5 (de) | N 9 - cyclopentylsubstituierte adeninderivate | |
| CH664567A5 (de) | Aromatische carbonsaeure- und sulfonsaeureester oder -amide. | |
| DE10046029A1 (de) | Indazole | |
| DE2359536C2 (de) | 2,6-Diaminonebularinderivate | |
| DE3877124T2 (de) | Imidazol-derivate, verfahren zu deren herstellung und deren anwendung als alpha-2-adrenoceptor-antagonisten. | |
| DE1720019A1 (de) | Pyrrylaminoketonderivate und Verfahren zu ihrer Herstellung | |
| DE2523103A1 (de) | Neue propargyl-2-phenylamino-imidazoline-(2), deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zur herstellung derselben | |
| EP0256400B1 (de) | Pyrimidinderivate, ihre Herstellung und Medikamente die diese Derivate enthalten | |
| DE3853958T2 (de) | Substituierte Pyridin-Verbindungen, ihre Herstellung und sie enthaltende pharmazeutische Zusammensetzungen. | |
| AT391316B (de) | Neue thienyloxy-alkylamin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| DE2128375B2 (de) | Basische substituierte Alkylidenamino-oxyalkyl-carbonsäureester, deren Säureadditionssalze, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Präparate | |
| DE2106038C3 (de) | 2-Imidazolin-2-ylamino-benzo [b] thiophene und diese enthaltende pharmazeutische Präparate | |
| DE2427272C3 (de) | 1-(2-(β-Naphthyloxy)-äthyl)-3-methyl -pyrazolon-(5), Verfahren sowie Verwendung als Antithrombotikum | |
| DE68903019T2 (de) | 4,5,6,7-tetrahydroisothiazolo (4,5-c)pyridin-derivate und isomere. | |
| DE1076691B (de) | Verfahren zur Herstellung von Phenthiazinderivaten | |
| DE2511316A1 (de) | Imidazo-eckige klammer auf 1,2 c eckige klammer zu -pyrimidinderivate, verfahren zu deren herstellung und deren verwendung | |
| DE3878578T2 (de) | Benzimidazol-derivate und verfahren zu ihrer herstellung. | |
| DE2030314A1 (US20020095090A1-20020718-M00002.png) | ||
| DE2828528A1 (de) | 1-oxo-1,2-dihydroisochinolinderivate | |
| DE1095836B (de) | Verfahren zur Herstellung von in 10-Stellung basisch substituierten Phenthiazinderivaten | |
| DE2142792A1 (de) | Heterocyclische Verbindungen | |
| EP0069953A1 (de) | Triazino-(2,1-a)isochinolinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel | |
| DE2605824B2 (de) | N-Acylaniline, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zubereitungen | |
| DE2740852A1 (de) | Basische 1-acylindol-3-acetocyessigsaeureester, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |