DE3035086C2 - - Google Patents
Info
- Publication number
- DE3035086C2 DE3035086C2 DE3035086A DE3035086A DE3035086C2 DE 3035086 C2 DE3035086 C2 DE 3035086C2 DE 3035086 A DE3035086 A DE 3035086A DE 3035086 A DE3035086 A DE 3035086A DE 3035086 C2 DE3035086 C2 DE 3035086C2
- Authority
- DE
- Germany
- Prior art keywords
- trans
- hydrochloride
- group
- acid
- phenyl
- 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 - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 claims description 90
- -1 carboxylate hydrochloride Chemical class 0.000 claims description 55
- 239000002253 acid Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000017105 transposition Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 138
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 124
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- 239000000725 suspension Substances 0.000 description 37
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 238000004458 analytical method Methods 0.000 description 30
- QCVUPSYRZFNUBN-UHFFFAOYSA-N 4-[(diaminomethylideneamino)methyl]cyclohexane-1-carboxylic acid;hydrochloride Chemical compound Cl.NC(N)=NCC1CCC(C(O)=O)CC1 QCVUPSYRZFNUBN-UHFFFAOYSA-N 0.000 description 29
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 29
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 230000000694 effects Effects 0.000 description 25
- 239000000203 mixture Substances 0.000 description 24
- 239000013078 crystal Substances 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 229960001701 chloroform Drugs 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 208000025865 Ulcer Diseases 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 15
- 230000008020 evaporation Effects 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 231100000397 ulcer Toxicity 0.000 description 14
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 230000002401 inhibitory effect Effects 0.000 description 12
- 241000700159 Rattus Species 0.000 description 11
- GZWIRHPWUOSRCO-UHFFFAOYSA-N heptanoic acid;hydrochloride Chemical compound Cl.CCCCCCC(O)=O GZWIRHPWUOSRCO-UHFFFAOYSA-N 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- ZCTQGTTXIYCGGC-UHFFFAOYSA-N Benzyl salicylate Chemical compound OC1=CC=CC=C1C(=O)OCC1=CC=CC=C1 ZCTQGTTXIYCGGC-UHFFFAOYSA-N 0.000 description 10
- BNPRHGVDJVKUNM-GJTSMBTKSA-N Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=CC=C1 Chemical compound Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=CC=C1 BNPRHGVDJVKUNM-GJTSMBTKSA-N 0.000 description 8
- QCVUPSYRZFNUBN-MEZFUOHNSA-N Cl.NC(=N)NC[C@H]1CC[C@H](C(O)=O)CC1 Chemical compound Cl.NC(=N)NC[C@H]1CC[C@H](C(O)=O)CC1 QCVUPSYRZFNUBN-MEZFUOHNSA-N 0.000 description 8
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 7
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 7
- 229940125904 compound 1 Drugs 0.000 description 7
- QTLPZFIGTRQFMC-UHFFFAOYSA-N cyclohexanecarboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1CCCCC1 QTLPZFIGTRQFMC-UHFFFAOYSA-N 0.000 description 7
- 229960005356 urokinase Drugs 0.000 description 7
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 108090000317 Chymotrypsin Proteins 0.000 description 5
- 108090000190 Thrombin Proteins 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical compound C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 5
- 229960002376 chymotrypsin Drugs 0.000 description 5
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 210000001187 pylorus Anatomy 0.000 description 5
- 238000012453 sprague-dawley rat model Methods 0.000 description 5
- 229960004072 thrombin Drugs 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- JBRMEFWJFBHUKG-UHFFFAOYSA-N 4-[(diaminomethylideneamino)methyl]cyclohexane-1-carboxylic acid Chemical compound NC(N)=NCC1CCC(C(O)=O)CC1 JBRMEFWJFBHUKG-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 4
- 230000000767 anti-ulcer Effects 0.000 description 4
- 235000019445 benzyl alcohol Nutrition 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000002198 insoluble material Substances 0.000 description 4
- 230000003902 lesion Effects 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
- 229960003151 mercaptamine Drugs 0.000 description 4
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 229940086542 triethylamine Drugs 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
- 210000001015 abdomen Anatomy 0.000 description 3
- 230000037005 anaesthesia Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 150000005379 cyclohexanecarboxylic acid derivatives Chemical class 0.000 description 3
- 208000000718 duodenal ulcer Diseases 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 210000004051 gastric juice Anatomy 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 230000001175 peptic effect Effects 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical compound CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 2
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- LKXDRDCSINRPFB-IOJSEOPQSA-N Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=C(C=CC=C2)C2=C1 Chemical compound Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=C(C=CC=C2)C2=C1 LKXDRDCSINRPFB-IOJSEOPQSA-N 0.000 description 2
- XDMPHMYIUBAYBW-IOJSEOPQSA-N Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=CC2=CC=CC=C12 Chemical compound Cl.C1C[C@@H](CNC(=N)N)CC[C@@H]1C(=O)OC1=CC=CC2=CC=CC=C12 XDMPHMYIUBAYBW-IOJSEOPQSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 108010058846 Ovalbumin Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- QCLMZTCDRVMSHA-UHFFFAOYSA-N benzyl 3-hydroxybenzoate Chemical compound OC1=CC=CC(C(=O)OCC=2C=CC=CC=2)=C1 QCLMZTCDRVMSHA-UHFFFAOYSA-N 0.000 description 2
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical compound OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- HBMCQTHGYMTCOF-UHFFFAOYSA-N hydroquinone monoacetate Natural products CC(=O)OC1=CC=C(O)C=C1 HBMCQTHGYMTCOF-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- YKUCHDXIBAQWSF-UHFFFAOYSA-N methyl 3-hydroxybenzoate Chemical compound COC(=O)C1=CC=CC(O)=C1 YKUCHDXIBAQWSF-UHFFFAOYSA-N 0.000 description 2
- ZQBAKBUEJOMQEX-UHFFFAOYSA-N phenyl salicylate Chemical compound OC1=CC=CC=C1C(=O)OC1=CC=CC=C1 ZQBAKBUEJOMQEX-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 231100000456 subacute toxicity Toxicity 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 2
- 229960000401 tranexamic acid Drugs 0.000 description 2
- KSJGJXWJEDHPLZ-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl) 4-hydroxybenzoate Chemical compound CCOC(=O)COC(=O)C1=CC=C(O)C=C1 KSJGJXWJEDHPLZ-UHFFFAOYSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- KZEVSDGEBAJOTK-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[5-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CC=1OC(=NN=1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O KZEVSDGEBAJOTK-UHFFFAOYSA-N 0.000 description 1
- VWVRASTUFJRTHW-UHFFFAOYSA-N 2-[3-(azetidin-3-yloxy)-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound O=C(CN1C=C(C(OC2CNC2)=N1)C1=CN=C(NC2CC3=C(C2)C=CC=C3)N=C1)N1CCC2=C(C1)N=NN2 VWVRASTUFJRTHW-UHFFFAOYSA-N 0.000 description 1
- JVKRKMWZYMKVTQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JVKRKMWZYMKVTQ-UHFFFAOYSA-N 0.000 description 1
- MOEFFSWKSMRFRQ-UHFFFAOYSA-N 2-ethoxyphenol Chemical compound CCOC1=CC=CC=C1O MOEFFSWKSMRFRQ-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
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- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
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- 150000001649 bromium compounds Chemical class 0.000 description 1
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- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
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- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- FIGKGJVUYAFLBI-VIFPVBQESA-N methyl (2s)-2-[(2-acetamidoacetyl)amino]-6-aminohexanoate Chemical compound NCCCC[C@@H](C(=O)OC)NC(=O)CNC(C)=O FIGKGJVUYAFLBI-VIFPVBQESA-N 0.000 description 1
- 229940120152 methyl 3-hydroxybenzoate Drugs 0.000 description 1
- ZSYJMXLJNPEAGP-UHFFFAOYSA-N methyl n-cyanocarbamate Chemical compound COC(=O)NC#N ZSYJMXLJNPEAGP-UHFFFAOYSA-N 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
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- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
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- 239000011734 sodium Substances 0.000 description 1
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- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
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- 238000004809 thin layer chromatography Methods 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12014279A JPS5645454A (en) | 1979-09-20 | 1979-09-20 | Cyclohexanecarboxylic acid derivative and its preparation |
| JP16827179A JPS5692260A (en) | 1979-12-26 | 1979-12-26 | Cyclohexanecarboxylic ester and its preparation |
| JP16827279A JPS5692261A (en) | 1979-12-26 | 1979-12-26 | Novel cyclohexanecarboxylic derivative and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3035086A1 DE3035086A1 (de) | 1981-04-09 |
| DE3035086C2 true DE3035086C2 (en, 2012) | 1991-01-03 |
Family
ID=27313978
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19803035086 Granted DE3035086A1 (de) | 1979-09-20 | 1980-09-17 | Cyclohexancarbonsaeurederivate, verfahren zu ihrer herstellung und sie enthaltende mittel |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4348410A (en, 2012) |
| AR (1) | AR227525A1 (en, 2012) |
| AT (1) | AT375918B (en, 2012) |
| AU (1) | AU541738B2 (en, 2012) |
| BR (1) | BR8006052A (en, 2012) |
| CA (1) | CA1142943A (en, 2012) |
| CH (1) | CH646687A5 (en, 2012) |
| DE (1) | DE3035086A1 (en, 2012) |
| DK (1) | DK163580C (en, 2012) |
| ES (1) | ES495175A0 (en, 2012) |
| FR (1) | FR2472561B1 (en, 2012) |
| GB (1) | GB2058773B (en, 2012) |
| IN (1) | IN151297B (en, 2012) |
| IT (1) | IT1129264B (en, 2012) |
| NL (1) | NL8005238A (en, 2012) |
| PH (1) | PH17322A (en, 2012) |
| SE (1) | SE460667B (en, 2012) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4465851A (en) * | 1981-01-22 | 1984-08-14 | Nippon Chemiphar Co., Ltd. | Guanidinocyclohexanecarboxylic acid derivatives |
| JPS5838250A (ja) * | 1981-09-01 | 1983-03-05 | Teikoku Chem Ind Corp Ltd | 複合体 |
| JPS6254A (ja) * | 1985-03-08 | 1987-01-06 | Kanebo Ltd | 新規グアニジノメチルシクロヘキサンカルボン酸誘導体および該化合物を有効成分とする抗潰瘍薬 |
| JPS6229566A (ja) * | 1985-07-30 | 1987-02-07 | Taiyo Yakuhin Kogyo Kk | 新規グアニジノメチル安息香酸誘導体 |
| KR100404714B1 (ko) * | 1994-08-30 | 2004-05-31 | 데이코쿠 가가꾸 산교 가부시키가이샤 | 구아니디노메틸사이클로헥산카복실산에스테르유도체 |
| JP4191269B2 (ja) | 1996-05-17 | 2008-12-03 | 興和株式会社 | 新規なアニリド化合物及びこれを含有する医薬 |
| BR9908911A (pt) | 1998-03-19 | 2001-10-02 | Bristol Myers Squibb Co | Sistema bifásico e processo de distribuição por liberação controlada de substâncias farmacêuticas de alta solubilidade |
| ES2219607T3 (es) | 1998-07-20 | 2004-12-01 | Wilex Ag | Nuevo agente inhibidor de la urocinasa. |
| US7342018B2 (en) | 1998-07-20 | 2008-03-11 | Wilex Ag | Urokinase inhibitors and uses thereof |
| CN1203055C (zh) | 2001-09-26 | 2005-05-25 | 朱德煦 | 治疗或预防细菌感染的方法和组合物 |
| US20070134231A1 (en) * | 2005-12-13 | 2007-06-14 | Jani Dharmendra M | Method for prolonging activity of autodegradable enzymes and compositions thereof |
| KR101942590B1 (ko) | 2010-07-09 | 2019-01-25 | 비에이치브이 파르마, 인크. | 레모글리플로진을 포함하는 짧은 반감기 약제용의 즉시/지연 조합 방출 전달 시스템 |
| GB2541910B (en) | 2015-09-03 | 2021-10-27 | Thermographic Measurements Ltd | Thermochromic composition |
| JP7380693B2 (ja) * | 2018-10-22 | 2023-11-15 | キーケルト アクツィーエンゲゼルシャフト | 自動車用ロック |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5913498B2 (ja) * | 1975-07-30 | 1984-03-30 | 第一製薬株式会社 | トランス−４−アミノメチルシクロヘキサンカルボン酸エステルの製法 |
| US4147876A (en) * | 1978-05-01 | 1979-04-03 | Daiichi Seiyaku Co., Ltd. | Easily hydrolyzable esters of 4-(2-carboxyethyl)phenyl trans-4-aminomethylcyclohexanecarboxylate and process of use |
-
1980
- 1980-09-11 AU AU62320/80A patent/AU541738B2/en not_active Ceased
- 1980-09-11 SE SE8006365A patent/SE460667B/sv not_active IP Right Cessation
- 1980-09-15 US US06/186,849 patent/US4348410A/en not_active Expired - Lifetime
- 1980-09-17 DE DE19803035086 patent/DE3035086A1/de active Granted
- 1980-09-18 GB GB8030183A patent/GB2058773B/en not_active Expired
- 1980-09-19 IT IT68457/80A patent/IT1129264B/it active
- 1980-09-19 AR AR282590A patent/AR227525A1/es active
- 1980-09-19 CH CH706480A patent/CH646687A5/fr not_active IP Right Cessation
- 1980-09-19 FR FR8020263A patent/FR2472561B1/fr not_active Expired
- 1980-09-19 AT AT0470680A patent/AT375918B/de not_active IP Right Cessation
- 1980-09-19 DK DK396880A patent/DK163580C/da active
- 1980-09-19 NL NL8005238A patent/NL8005238A/nl not_active Application Discontinuation
- 1980-09-19 PH PH24606A patent/PH17322A/en unknown
- 1980-09-19 ES ES495175A patent/ES495175A0/es active Granted
- 1980-09-19 CA CA000360655A patent/CA1142943A/en not_active Expired
- 1980-09-20 IN IN1071/CAL/80A patent/IN151297B/en unknown
- 1980-09-23 BR BR8006052A patent/BR8006052A/pt unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IT1129264B (it) | 1986-06-04 |
| GB2058773A (en) | 1981-04-15 |
| PH17322A (en) | 1984-07-20 |
| AU6232080A (en) | 1981-03-26 |
| CA1142943A (en) | 1983-03-15 |
| DE3035086A1 (de) | 1981-04-09 |
| ES8200643A1 (es) | 1981-10-16 |
| US4348410A (en) | 1982-09-07 |
| DK396880A (da) | 1981-03-21 |
| FR2472561A1 (fr) | 1981-07-03 |
| IN151297B (en, 2012) | 1983-03-26 |
| ES495175A0 (es) | 1981-10-16 |
| GB2058773B (en) | 1983-03-23 |
| BR8006052A (pt) | 1981-04-07 |
| CH646687A5 (fr) | 1984-12-14 |
| ATA470680A (de) | 1984-02-15 |
| SE460667B (sv) | 1989-11-06 |
| NL8005238A (nl) | 1981-03-24 |
| AR227525A1 (es) | 1982-11-15 |
| IT8068457A0 (it) | 1980-09-19 |
| AT375918B (de) | 1984-09-25 |
| FR2472561B1 (fr) | 1985-05-31 |
| DK163580B (da) | 1992-03-16 |
| DK163580C (da) | 1992-08-03 |
| SE8006365L (sv) | 1981-03-21 |
| AU541738B2 (en) | 1985-01-17 |
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| 8180 | Miscellaneous part 1 |
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