JPS58500713A - １，４―チアザンカルボン酸誘導体及びその製造方法並びに該誘導体を含有する医薬組成物 - Google Patents
１，４―チアザンカルボン酸誘導体及びその製造方法並びに該誘導体を含有する医薬組成物Info
- Publication number
- JPS58500713A JPS58500713A JP57501451A JP50145182A JPS58500713A JP S58500713 A JPS58500713 A JP S58500713A JP 57501451 A JP57501451 A JP 57501451A JP 50145182 A JP50145182 A JP 50145182A JP S58500713 A JPS58500713 A JP S58500713A
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- branched
- derivative
- linear
- 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.)
- Granted
Links
- 239000002253 acid Substances 0.000 title claims description 54
- 238000000034 method Methods 0.000 title claims description 46
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 75
- 239000000243 solution Substances 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 39
- 238000006243 chemical reaction Methods 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- 150000001875 compounds Chemical class 0.000 claims description 24
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 21
- -1 bromine Chemical compound 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 238000007363 ring formation reaction Methods 0.000 claims description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000007254 oxidation reaction Methods 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical group O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- 230000003647 oxidation Effects 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000011591 potassium Chemical group 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 150000003462 sulfoxides Chemical class 0.000 claims description 4
- 239000006188 syrup Substances 0.000 claims description 4
- 235000020357 syrup Nutrition 0.000 claims description 4
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 239000000908 ammonium hydroxide Substances 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 150000001944 cysteine derivatives Chemical class 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 229910000000 metal hydroxide Inorganic materials 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 239000000052 vinegar Substances 0.000 claims description 3
- 235000021419 vinegar Nutrition 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 235000014676 Phragmites communis Nutrition 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 229940091173 hydantoin Drugs 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 claims description 2
- 239000008223 sterile water Substances 0.000 claims description 2
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims 1
- SUFUDUDHGOHFHW-UHFFFAOYSA-N 2h-1,4-thiazine-3-carboxylic acid Chemical class OC(=O)C1=NC=CSC1 SUFUDUDHGOHFHW-UHFFFAOYSA-N 0.000 claims 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- 125000006538 C11 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- VCJGHWPKYYOHIG-UHFFFAOYSA-N CC1=CSC(C(N1C)C(=O)O)(C)C Chemical compound CC1=CSC(C(N1C)C(=O)O)(C)C VCJGHWPKYYOHIG-UHFFFAOYSA-N 0.000 claims 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
- 239000005642 Oleic acid Substances 0.000 claims 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims 1
- 235000019483 Peanut oil Nutrition 0.000 claims 1
- 238000006136 alcoholysis reaction Methods 0.000 claims 1
- 230000015271 coagulation Effects 0.000 claims 1
- 238000005345 coagulation Methods 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000000266 injurious effect Effects 0.000 claims 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims 1
- 239000000312 peanut oil Substances 0.000 claims 1
- 230000010412 perfusion Effects 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
- 239000000047 product Substances 0.000 description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000002904 solvent Substances 0.000 description 26
- 235000019441 ethanol Nutrition 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- 239000007787 solid Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 16
- 238000000921 elemental analysis Methods 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
- 235000011054 acetic acid Nutrition 0.000 description 15
- 229920005989 resin Polymers 0.000 description 15
- 239000011347 resin Substances 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
- 239000002585 base Substances 0.000 description 12
- 230000003480 fibrinolytic effect Effects 0.000 description 12
- 238000001819 mass spectrum Methods 0.000 description 12
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 11
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 11
- 150000007513 acids Chemical class 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- 230000001788 irregular Effects 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000003109 Karl Fischer titration Methods 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000000740 bleeding effect Effects 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 235000008504 concentrate Nutrition 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229940032147 starch Drugs 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 239000005973 Carvone Substances 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 229960001639 penicillamine Drugs 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 239000001856 Ethyl cellulose Substances 0.000 description 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 208000007536 Thrombosis Diseases 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003153 chemical reaction reagent 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
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 235000019325 ethyl cellulose Nutrition 0.000 description 3
- 229920001249 ethyl cellulose Polymers 0.000 description 3
- 230000020764 fibrinolysis Effects 0.000 description 3
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- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 150000003283 rhodium Chemical class 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000005049 silicon tetrachloride Substances 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide 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
- 239000012265 solid product Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229960003967 suloctidil Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 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
- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- IBYSTTGVDIFUAY-UHFFFAOYSA-N vanadium monoxide Chemical compound [V]=O IBYSTTGVDIFUAY-UHFFFAOYSA-N 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- UIYCHXAGWOYNNA-UHFFFAOYSA-N vinyl sulfide Chemical compound C=CSC=C UIYCHXAGWOYNNA-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003754 zirconium Chemical class 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
- C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
- C07D279/16—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/10—Spiro-condensed systems
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)
- Hematology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Facsimiles In General (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU83327 | 1981-04-29 | ||
| LU83327A LU83327A1 (fr) | 1981-04-29 | 1981-04-29 | Procede de preparation de derives de 1,4-thiazine,leur utilisation ainsi que compositions contenant ces derives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58500713A true JPS58500713A (ja) | 1983-05-06 |
| JPH0330592B2 JPH0330592B2 (enExample) | 1991-04-30 |
Family
ID=19729637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57501451A Granted JPS58500713A (ja) | 1981-04-29 | 1982-04-21 | １，４―チアザンカルボン酸誘導体及びその製造方法並びに該誘導体を含有する医薬組成物 |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS58500713A (enExample) |
| KR (1) | KR830010089A (enExample) |
| BE (1) | BE893025A (enExample) |
| ES (1) | ES8307233A1 (enExample) |
| FI (1) | FI66366C (enExample) |
| FR (1) | FR2509303A1 (enExample) |
| GB (1) | GB2111056B (enExample) |
| GR (1) | GR75996B (enExample) |
| IT (1) | IT1190794B (enExample) |
| LU (1) | LU83327A1 (enExample) |
| NL (1) | NL8220153A (enExample) |
| NO (1) | NO824398L (enExample) |
| PT (1) | PT74813B (enExample) |
| SE (1) | SE8207294L (enExample) |
| WO (1) | WO1982003860A1 (enExample) |
| ZA (1) | ZA822926B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3436386A1 (de) * | 1984-10-04 | 1986-04-10 | Merck Patent Gmbh, 6100 Darmstadt | (thio)morpholine |
| FR2618434B1 (fr) * | 1987-07-21 | 1991-02-08 | Oreal | Esters d'acide thiamorpholinone carboxylique et de ses derives, leur procede de preparation et leur utilisation dans le domaine cosmetique et dermo-pharmaceutique |
| AU4750990A (en) * | 1988-12-14 | 1990-07-10 | Hicks, Richard | Method for predicting biological activity of antibiotics, and novel non beta-lactam antibacterial agents derived therefrom |
| JP6126135B2 (ja) | 2012-02-03 | 2017-05-10 | サノフイ | 縮合ピロールカルボキサミド及びその医薬としてのその使用 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5540658A (en) * | 1978-09-19 | 1980-03-22 | Tanabe Seiyaku Co Ltd | 1,4-thiazan-3-carboxylic ester derivative and its preparation |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2187327B1 (enExample) * | 1972-06-15 | 1975-06-20 | Rech Pharm Scientifiques | |
| US4179276A (en) * | 1977-02-01 | 1979-12-18 | E. I. Du Pont De Nemours And Company | Novel imidazothiazine-1,3 (2H)-diones |
-
1981
- 1981-04-29 LU LU83327A patent/LU83327A1/fr unknown
-
1982
- 1982-04-21 NL NL8220153A patent/NL8220153A/nl unknown
- 1982-04-21 WO PCT/BE1982/000009 patent/WO1982003860A1/fr not_active Ceased
- 1982-04-21 GB GB08235353A patent/GB2111056B/en not_active Expired
- 1982-04-21 JP JP57501451A patent/JPS58500713A/ja active Granted
- 1982-04-28 ES ES82511759A patent/ES8307233A1/es not_active Expired
- 1982-04-28 PT PT74813A patent/PT74813B/pt unknown
- 1982-04-29 KR KR1019820001874A patent/KR830010089A/ko not_active Ceased
- 1982-04-29 ZA ZA822926A patent/ZA822926B/xx unknown
- 1982-04-29 IT IT20998/82A patent/IT1190794B/it active
- 1982-04-29 FR FR8207461A patent/FR2509303A1/fr not_active Withdrawn
- 1982-04-29 GR GR68018A patent/GR75996B/el unknown
- 1982-04-29 BE BE0/207967A patent/BE893025A/fr not_active IP Right Cessation
- 1982-12-14 FI FI771226A patent/FI66366C/fi not_active IP Right Cessation
- 1982-12-21 SE SE8207294A patent/SE8207294L/xx not_active Application Discontinuation
- 1982-12-28 NO NO824398A patent/NO824398L/no unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5540658A (en) * | 1978-09-19 | 1980-03-22 | Tanabe Seiyaku Co Ltd | 1,4-thiazan-3-carboxylic ester derivative and its preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2111056A (en) | 1983-06-29 |
| NL8220153A (nl) | 1983-03-01 |
| WO1982003860A1 (fr) | 1982-11-11 |
| FI66366B (fi) | 1984-06-29 |
| ZA822926B (en) | 1983-03-30 |
| PT74813A (fr) | 1982-05-01 |
| GB2111056B (en) | 1985-03-06 |
| GR75996B (enExample) | 1984-08-03 |
| FI824279A0 (fi) | 1982-12-14 |
| PT74813B (fr) | 1983-10-26 |
| IT8220998A0 (it) | 1982-04-29 |
| NO824398L (no) | 1982-12-28 |
| SE8207294D0 (sv) | 1982-12-21 |
| ES511759A0 (es) | 1983-07-01 |
| FR2509303A1 (fr) | 1983-01-14 |
| KR830010089A (ko) | 1983-12-26 |
| FI66366C (fi) | 1984-10-10 |
| SE8207294L (sv) | 1982-12-21 |
| JPH0330592B2 (enExample) | 1991-04-30 |
| IT1190794B (it) | 1988-02-24 |
| LU83327A1 (fr) | 1983-03-24 |
| BE893025A (fr) | 1982-10-29 |
| FI824279L (fi) | 1982-12-14 |
| ES8307233A1 (es) | 1983-07-01 |
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