JPH0379357B2 - - Google Patents
Info
- Publication number
- JPH0379357B2 JPH0379357B2 JP8891583A JP8891583A JPH0379357B2 JP H0379357 B2 JPH0379357 B2 JP H0379357B2 JP 8891583 A JP8891583 A JP 8891583A JP 8891583 A JP8891583 A JP 8891583A JP H0379357 B2 JPH0379357 B2 JP H0379357B2
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- group
- alkyl
- formula
- carbon atoms
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 19
- -1 nitro, hydroxyl group Chemical group 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 210000003141 lower extremity Anatomy 0.000 description 4
- 210000001541 thymus gland Anatomy 0.000 description 4
- 235000019786 weight gain Nutrition 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000978776 Senegalia senegal Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 208000018631 connective tissue disease Diseases 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 210000005069 ears Anatomy 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-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
- RNJOKCPFLQMDEC-UHFFFAOYSA-N 4(R),8-dimethyl-trans-2-nonenoyl-CoA Chemical compound COC(=O)CC(=O)CC(=O)OC RNJOKCPFLQMDEC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- SFWNPLLGXKJESA-UHFFFAOYSA-N 4-oxochromene-3-carbonitrile Chemical compound C1=CC=C2C(=O)C(C#N)=COC2=C1 SFWNPLLGXKJESA-UHFFFAOYSA-N 0.000 description 1
- GRYXAOXVOYEENX-UHFFFAOYSA-N 6-ethyl-4-oxochromene-3-carbonitrile Chemical compound O1C=C(C#N)C(=O)C2=CC(CC)=CC=C21 GRYXAOXVOYEENX-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 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
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- CSTBBLHIGMTEAZ-UHFFFAOYSA-N chloroform;ethyl acetate;hexane Chemical compound ClC(Cl)Cl.CCCCCC.CCOC(C)=O CSTBBLHIGMTEAZ-UHFFFAOYSA-N 0.000 description 1
- KWFWIGXYOMVRSA-UHFFFAOYSA-N chromeno[2,3-b]pyridin-5-one Chemical class C1=CC=C2C(=O)C3=CC=CC=C3OC2=N1 KWFWIGXYOMVRSA-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- RWWJZKRAEKAIAI-UHFFFAOYSA-L disodium;2-(carboxylatomethyl)-7-ethyl-5-oxochromeno[2,3-b]pyridine-3-carboxylate Chemical compound [Na+].[Na+].[O-]C(=O)CC1=C(C([O-])=O)C=C2C(=O)C3=CC(CC)=CC=C3OC2=N1 RWWJZKRAEKAIAI-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 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 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 210000001625 seminal vesicle Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 201000010653 vesiculitis Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は一般式（）
〔式中、Ｒは、同一または異なつて、水素、ア
ルキル、アルコキシ、ニトロ、水酸基、アシル、
ヒドロキシアルキル、ハロゲンまたは環上の隣接
する２個の炭素原子と共に６員環を形成するテト
ラメチレン基（−（CH2）4−）あるいはブタジエ
ニレン基（−CH＝CH−CH＝CH−）を、ｍは
１，２または３を、ｎは１または２をそれぞれ表
す〕で示される５−オキソ−5H−〔１〕ベンゾピ
ラノ〔２，３−ｂ〕ピリジン誘導体またはその塩
またはエステル、その製造法および慢性関節リウ
マチ治療剤に関する。
本発明の一般式（）で示される化合物または
その塩またはエステルは、一般式（）
〔式中、Ｒおよびｍは前記と同意義を表わす〕
で示される４−オキソ−4H−１−ベンゾピラン
−３−カルボニトリルに、一般式（）
R1OOC−（CH2）o−COCH2COOR1 （）
〔式中、R1はアルキルを、ｎは１または２を
それぞれ表わす〕で示される化合物を反応させ、
必要により加水分解反応に付すことによつて製造
することができる。
このようにして製造される一般式（）で示さ
れる本発明の化合物は、慢性関節リウマチなどの
各種結合組織疾患、免疫反応に基いて起る各種炎
症性疾患の治療剤として有用である。
前記式中の置換基ＲおよびR1について説明す
る。Ｒで示されるアルキル基としては、たとえば
メチル、エチル、プロピル、イソプロピル、ブチ
ル、ｔ−ブチル、ペンチル、ヘキシル基などの炭
素数１〜６の直鎖、あるいは分枝アルキル基があ
げられる。また、アルコキシ基としては、例えば
メトオキシ、エトオキシ、プロポキシ、ブトオキ
シ基などのアルキル部分の炭素数が１−４のアル
コキシ基が、またアシル基としては、アセチル、
プロピオニル、ブチリル基などの炭素数２−４の
ものが、また、ヒドロキシアルキル基としては、
ヒドロキシメチル，１−ヒドロキシエチル，１−
ヒドロキシプロピル，１−ヒドロキシ−１−メチ
ル−エチル，１−ヒドロキシブチル基等の炭素数
１−４のものが、またハロゲン原子としては塩
素、臭素、ヨウ素、フツ素があげられる。これら
の置換基のうち、アルキル、ハロゲンおよびヒド
ロキシアルキルが実用上好ましい。特に炭素数１
〜３のアルキル、クロルおよび炭素数１〜３のヒ
ドロキシアルキルが好ましい。一般式（）にお
けるR1のアルキル基としては、メチル、エチル、
プロピル、イソプロピル、ブチル、ｔ−ブチルな
どの炭素数１−４のものがあげられる。
一般式（）で示される化合物の塩としては、
たとえばナトリウム、カタウム等の薬理的に許容
されうるアルカリ金属塩などがあげられる。
さらに詳しくは、本発明の一般式（）で示さ
れる化合物は、次の方法により製造される。即
ち、一般式（）の化合物に一般式（）で示さ
れる活性メチレン化合物を反応させることによ
り、一般式（）の化合物が製造される。この反
応に用いられる活性メチレン化合物の使用量は、
通常一般式（）の原料化合物１モルに対して、
実用上１〜５倍モル程度である。
上記の反応は一般に塩基の存在が望ましく、用
いられる塩基としては有機アミン類が、たとえ
ば、ピペリジン、ピロリジン、モルホリン、ジエ
チルアミン、ジプロピルアミン、ジブチルアミン
類の第２級アミン、１，８−ジアザビシクロ
〔５，４，０〕−７−ウンデセンやトリエチルアミ
ンのような第３級アミンやイミダゾール，２−メ
チルイミダゾールのような異項環塩基があげられ
る。これらの有機塩基の使用量は通常、一般式
（）の原料化合物１モルに対し、触媒量〜５倍
モル程度である。
反応は一般に有機溶媒中で行うのが望ましく、
溶媒としては、たとえば、メタノール、エタノー
ル、プロパノール、ブタノール等のアルコール類
やジメチルホルムアミド等があげられる。反応温
度、反応時間など、その他の反応条件に特に制限
はないが、室温〜用いた溶媒の沸点付近で約１〜
24時間程度反応させるのが一般的である。
以上のようにして得られる一般式（）のジエ
ステル化合物のうち、Ｒが１−ヒドロキシアルキ
ルを有する化合物の場合には、この化合物を常法
の酸化法、例えはアセトン中でのジヨーンズ酸化
等により相当するアシル基に導くことができる。
一般式（）のジエステル化合物を必要に応じ
て加水分解することにより、一般式（）の化合
物またはその塩に導くことができる。加水分解の
条件としては、通常の酸加水分解法あるいはアル
カル加水分解法が用いられる。たとえば酸加水分
解法では、硫酸、塩酸、りん酸等を過剰に用い、
その酸のみで、あるいは有機酸、たとえばギ酸、
酢酸等の有機酸類と共に、あるいはメタノール、
エタノール、プロパノール等のアルコール類ある
いはテトラヒドロフランやジオキサン等のエーテ
ル類と共に、通常室温〜150℃付近の温度条件で
行われる。またアルカリ加水分解法では、水酸化
ナトリウム、水酸化カリウム、水酸化バリウム等
を過剰に用い、単独にあるいは前記のアルコール
類やエーテル類を溶媒に用いて、通常室温〜150
℃付近の温度条件で行われる。反応時間は化合物
により異なるが、通常１時間〜数日程度である。
また、場合に応じて、酸加水分解とアルカリ加水
分解を組み合せて、目的化合物を製造することも
出来る。
かくして製造される一般式（）の化合物は、
慢性関節リウマチなどの各種結合組織疾患、免疫
反応に基いて起こる各種炎症性疾患の治療剤とし
て用いることができる。
一般式（）の化合物は常法により、補助剤と
共に医薬として用いられる担体と混合して、たと
えば錠剤、顆粒剤、散剤あるいはカプセル剤など
の経口剤として、、また蒸留水に溶解し、注射用
剤としても用いることができる。錠剤、顆粒剤、
散剤とする場合には、乳糖、でんぷん、デキスト
リン、白糖、結晶セルロース、カオリン、炭酸カ
ルシウム、タルク等が医薬担体として好ましく、
また注射用剤とするには、塩化ナトリウムあるい
は塩化カリウムで等張化するのが好ましい。
医薬組成物中の一般式（）の化合物の量は、
経口剤としては通常成人の１日量として10〜2000
mg、好ましくは50−500mg、また注射剤としては
通常成人の１日量として１−500mg、好ましくは
５−100mgである。
急性毒性
７−エチル−３−カルボキシ−５−オキソ−
5H−〔１〕ベンゾピラノ〔２，３−ｂ〕ピリジン
−２−酢酸・二ナトリウム塩の４％アラビアゴム
懸濁液をJcl：ICR系雄マウス（５週令）に経口
で投与した結果、２，000mg／Kgで何ら異状がみ
られなかつた。
以下に本発明の実験例、実施例を示すが、本発
明はこれに限定されるものではない。
実験例１ アジユバント関節炎抑制作用
動物はスプラグ・ダウレイ系雄ラツト（６週
令）を用いた。
アジユバント関節炎は結核死菌体（M.butyri
−cum株）を流動パラフインに懸濁し、ラツト右
後肢皮内に注射して発症せしめた。検体（７−エ
チル−３−カルボキシ−５−オキソ−5H−〔１〕
ベンゾピラノ〔２，３−ｂ〕ピリジン−２−酢
酸・二ナトリウム塩）70mgを４％アラビアゴム液
７mlに懸濁して得た懸濁液を体重100gあたり0.5
mlの割合で１日１回、アジユバント注射日から14
日間連続経口投与した。アジユバント非注射側後
肢、前肢、尾および耳に発現する炎症の程度を１
〜５と採点し、各動物について合計した。最高点
数は４ヶ所合計で20である。その他、体重増加
（14日後と感作日の体重の差）に及ぼす影響、胸
腺重量に及ぼす影響をしらべ、対照群と比較し
た。結果は表１に示す通りである。検体は全身性
炎症スコアー、それに伴なつて起る体重増加抑制
を改善するとともに、胸腺重量を増加させた。
The present invention is based on the general formula () [In the formula, R is the same or different and is hydrogen, alkyl, alkoxy, nitro, hydroxyl group, acyl,
A tetramethylene group (-(CH 2 ) 4 -) or a butadienylene group (-CH=CH-CH=CH-) that forms a 6-membered ring together with hydroxyalkyl, halogen, or two adjacent carbon atoms on the ring, 5-oxo-5H-[1]benzopyrano[2,3-b]pyridine derivative represented by m represents 1, 2 or 3, and n represents 1 or 2, respectively, or a salt or ester thereof, a method for producing the same, and Regarding a therapeutic agent for chronic rheumatoid arthritis. The compound represented by the general formula () or its salt or ester of the present invention is a compound represented by the general formula () [In the formula, R and m represent the same meanings as above]
4-oxo-4H-1-benzopyran-3-carbonitrile represented by the general formula () R 1 OOC-(CH 2 ) o -COCH 2 COOR 1 () [where R 1 is alkyl, represents 1 or 2 respectively] is reacted,
It can be produced by subjecting it to a hydrolysis reaction if necessary. The compound of the present invention represented by the general formula () thus produced is useful as a therapeutic agent for various connective tissue diseases such as rheumatoid arthritis and various inflammatory diseases caused by immune reactions. The substituents R and R 1 in the above formula will be explained. Examples of the alkyl group represented by R include straight chain or branched alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, and hexyl groups. Examples of alkoxy groups include alkoxy groups whose alkyl moiety has 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, and butoxy groups; examples of acyl groups include acetyl,
Those with 2 to 4 carbon atoms such as propionyl and butyryl groups, and hydroxyalkyl groups include
Hydroxymethyl, 1-hydroxyethyl, 1-
Examples include those having 1 to 4 carbon atoms such as hydroxypropyl, 1-hydroxy-1-methyl-ethyl, and 1-hydroxybutyl groups, and halogen atoms include chlorine, bromine, iodine, and fluorine. Among these substituents, alkyl, halogen and hydroxyalkyl are practically preferred. Especially carbon number 1
-3 alkyl, chloro and hydroxyalkyl having 1 to 3 carbon atoms are preferred. The alkyl group for R 1 in general formula () includes methyl, ethyl,
Examples include those having 1 to 4 carbon atoms such as propyl, isopropyl, butyl, and t-butyl. As a salt of the compound represented by the general formula (),
Examples include pharmacologically acceptable alkali metal salts such as sodium and cataum. More specifically, the compound represented by the general formula () of the present invention is produced by the following method. That is, the compound of general formula () is produced by reacting the compound of general formula () with the active methylene compound represented by general formula (). The amount of active methylene compound used in this reaction is
Usually, for 1 mole of the starting compound of general formula (),
In practical terms, it is about 1 to 5 times the mole. The presence of a base is generally desirable for the above reaction, and examples of the base used include organic amines such as piperidine, pyrrolidine, morpholine, diethylamine, dipropylamine, secondary amines such as dibutylamine, 1,8-diazabicyclo[ Examples include tertiary amines such as 5,4,0]-7-undecene and triethylamine, and heterocyclic bases such as imidazole and 2-methylimidazole. The amount of these organic bases to be used is usually from a catalytic amount to about 5 times the mole of the raw material compound of general formula (). It is generally desirable to carry out the reaction in an organic solvent.
Examples of the solvent include alcohols such as methanol, ethanol, propanol, butanol, and dimethylformamide. There are no particular restrictions on other reaction conditions such as reaction temperature and reaction time, but the
It is common to react for about 24 hours. Among the diester compounds of the general formula () obtained as above, in the case of a compound in which R is 1-hydroxyalkyl, this compound is oxidized by a conventional oxidation method, such as dionez oxidation in acetone. This can lead to the corresponding acyl group. By hydrolyzing the diester compound of general formula () as required, it is possible to lead to a compound of general formula () or a salt thereof. As conditions for hydrolysis, a conventional acid hydrolysis method or an alkali hydrolysis method is used. For example, in the acid hydrolysis method, sulfuric acid, hydrochloric acid, phosphoric acid, etc. are used in excess,
The acid alone, or an organic acid such as formic acid,
With organic acids such as acetic acid, or with methanol,
It is usually carried out at temperatures ranging from room temperature to around 150°C with alcohols such as ethanol and propanol or ethers such as tetrahydrofuran and dioxane. In addition, in the alkaline hydrolysis method, sodium hydroxide, potassium hydroxide, barium hydroxide, etc. are used in excess, and the above-mentioned alcohols and ethers are used as a solvent.
It is carried out under temperature conditions around ℃. The reaction time varies depending on the compound, but is usually about 1 hour to several days.
Further, depending on the case, the target compound can also be produced by combining acid hydrolysis and alkaline hydrolysis. The compound of general formula () produced in this way is
It can be used as a therapeutic agent for various connective tissue diseases such as rheumatoid arthritis and various inflammatory diseases caused by immune reactions. The compound of general formula () can be mixed with a pharmaceutical carrier together with adjuvants in a conventional manner to form oral preparations such as tablets, granules, powders, or capsules, or dissolved in distilled water for injection. It can also be used as an agent. tablets, granules,
When used as a powder, preferred pharmaceutical carriers include lactose, starch, dextrin, white sugar, crystalline cellulose, kaolin, calcium carbonate, talc, etc.
In addition, when preparing an injectable preparation, it is preferable to make the tonicity isotonic with sodium chloride or potassium chloride. The amount of the compound of general formula () in the pharmaceutical composition is
Oral dosage is usually 10 to 2000 per day for adults.
mg, preferably 50-500 mg, and for injections, the daily dose for adults is usually 1-500 mg, preferably 5-100 mg. Acute toxicity 7-ethyl-3-carboxy-5-oxo-
5H-[1]Benzopyrano[2,3-b]pyridine-2-acetic acid disodium salt suspension in 4% gum arabic was orally administered to Jcl:ICR male mice (5 weeks old). ,000mg/Kg, no abnormalities were observed. Experimental examples and examples of the present invention are shown below, but the present invention is not limited thereto. Experimental Example 1 Adjuvant Arthritis Inhibitory Effect The animals used were male Sprague-Dowley rats (6 weeks old). Adijuvant arthritis is caused by dead tuberculosis bacteria (M.butyri).
-cum strain) was suspended in liquid paraffin and injected intracutaneously into the right hind limb of rats to induce the disease. Specimen (7-ethyl-3-carboxy-5-oxo-5H-[1]
A suspension obtained by suspending 70 mg of benzopyrano[2,3-b]pyridine-2-acetic acid disodium salt) in 7 ml of 4% gum arabic solution was added at a concentration of 0.5 per 100 g of body weight.
ml once a day from the day of adjuvant injection.
It was orally administered continuously for several days. The degree of inflammation that occurs in the hind limbs, forelimbs, tail, and ears on the non-injected side of the adjuvant is 1.
Scores were ˜5 and summed for each animal. The maximum score is 20 for the four locations. In addition, the effects on body weight gain (difference between body weight after 14 days and on the day of sensitization) and thymus weight were examined and compared with the control group. The results are shown in Table 1. The sample improved systemic inflammation scores and associated suppression of weight gain, as well as increased thymus weight.
【表】
なお検体はラツトカラゲニン浮腫法における消
炎作用およびマウスフエニルキノンライジング法
における鎮痛作用を示さず、ウシ精嚢由来のプロ
スタグランジン合成酵素に作用を及ぼさなかつ
た。
実験例２ アジユバント関節炎抑制作用
動物はスプラグ・ダウレイ系雄ラツト（６週
令）を用いた。
アジユバント関節炎は結核死菌体（M.butyri
−cum株）を流動パラフインに懸濁し、ラツト右
後肢皮内に注射して発症せしめた。検体〔エチル
（７−エチル−３−エトキシカルボニル−５−オ
キソ−5H−〔１〕ベンゾピラノ〔２，３−ｂ〕ピ
リジン−２−イル）アセテート〕70mgを４％アラ
ビアゴム液７mlに懸濁して得た懸濁液を体重
100gあたり0.5mlの割合で１日１回、アジユバン
ト注射日から14日間連続経口投与した。アジユバ
ント非注射側後肢、前肢、尾および耳に発現する
炎症の程度を１〜５と採点し、各動物について合
計した。最高点数は４ヶ所合計で20ある。その
他、体重増加（14日後と感作日の体重の差）に及
ぼす影響、胸腺重量に及ぼす影響をしらべ、対照
群と比較した。結果は表２に示す通りである。検
体は全身性炎症スコアー、それに伴なつて起る体
重増加抑制を改善するとともに、胸腺重量を増大
させる傾向を示した。[Table] The sample did not show any anti-inflammatory effect in the rat carrageenan edema method or analgesic effect in the mouse phenylquinone rising method, and had no effect on prostaglandin synthase derived from bovine seminal vesicles. Experimental Example 2 Adjuvant Arthritis Inhibitory Effect The animals used were male Sprague-Dowley rats (6 weeks old). Adijuvant arthritis is caused by dead tuberculosis bacteria (M.butyri).
-cum strain) was suspended in liquid paraffin and injected intracutaneously into the right hind limb of rats to induce the disease. 70 mg of the sample [ethyl (7-ethyl-3-ethoxycarbonyl-5-oxo-5H-[1] benzopyrano[2,3-b] pyridin-2-yl) acetate] was suspended in 7 ml of 4% gum arabic solution. Weigh the suspension obtained
It was orally administered once a day at a rate of 0.5 ml per 100 g for 14 consecutive days from the day of the adjuvant injection. The degree of inflammation developed in the hind limbs, forelimbs, tail, and ears on the non-adjuvant-injected side was scored from 1 to 5 and summed for each animal. The maximum score is 20 in total for the four locations. In addition, the effects on body weight gain (difference between body weight after 14 days and on the day of sensitization) and thymus weight were examined and compared with the control group. The results are shown in Table 2. The specimens showed a tendency to improve systemic inflammation scores and associated suppression of weight gain, as well as increase thymus weight.
【表】
実施例 １
６−エチル−４−オキソ−4H−１−ベンゾピ
ラン−３−カルボニトリル（1.99g）、ジメチル
１，３−アセトンジカルボキシレート（2g）、メ
タノール（20ml）、ピペリジン（0.2ml）の混合物
を３時間加熱還流したのち、濃縮し、残留物にエ
タノールを加え、黄色結晶をろ取した。これをシ
リカゲル（50g）のカラムにかけ、ヘキサン−ク
ロロホルム−酢酸エチルエステル（10：10：１）
で溶出後、メタノールから再結晶すると、メチル
（７−エチル−３−メトオキシカルボニル−５−
オキソ−5H−〔１〕ベンゾピラノ〔２，３−ｂ〕
ピリジン−２−イル）アセテートの淡黄色針状晶
1.04gが得られた。融点142−143℃。
以下同様にして（３−アルコキシカルボニル−
５−オキソ−5H−〔１〕ベンゾピラノ〔２，３−
ｂ〕ピリジン−２−イル）酢酸のジエステル誘導
体を製造した。[Table] Example 1 6-ethyl-4-oxo-4H-1-benzopyran-3-carbonitrile (1.99g), dimethyl 1,3-acetonedicarboxylate (2g), methanol (20ml), piperidine (0.2g) ml) was heated under reflux for 3 hours, concentrated, ethanol was added to the residue, and yellow crystals were collected by filtration. This was applied to a column of silica gel (50 g), and hexane-chloroform-ethyl acetate (10:10:1) was added.
After recrystallization from methanol, methyl (7-ethyl-3-methoxycarbonyl-5-
Oxo-5H-[1]benzopyrano[2,3-b]
pale yellow needles of pyridin-2-yl)acetate
1.04g was obtained. Melting point 142-143℃. Similarly, (3-alkoxycarbonyl-
5-oxo-5H-[1]benzopyrano[2,3-
b] A diester derivative of pyridin-2-yl)acetic acid was produced.
【表】
カルボニトリル
[Table] Carbonitrile
Claims (1)
ルキル、アルコキシ、ニトロ、水酸基、アシル、
ヒドロキシアルキル、ハロゲンまたは環上の隣接
する２個の炭素原子と共に６員環を形成するテト
ラメチレン基（−（CH2）4−）あるいはブタジエ
ニレン基（−CH＝CH−CH＝CH−）を、ｍは
１，２または３を、ｎは１または２をそれぞれ表
す〕で示される化合物またはその塩またはエステ
ル。 ２ 一般式 〔式中、Ｒは、同一または異なつて、水素、ア
ルキル、アルコキシ、ニトロ、水酸基、アシル、
ヒドロキシアルキル、ハロゲンまたは環上の隣接
する２個の炭素原子と共に６員環を形成するテト
ラメチレン基（−（CH2）4−）あるいはブタジエ
ニレン基（−CH＝CH−CH＝CH−）を、ｍは
１，２または３をそれぞれ表す〕で示される化合
物に、一般式 R1OOC−（CH2）o−COCH2COOR1 〔式中、Ｒはアルキルを、ｎは１または２をそ
れぞれ表す〕で示される化合物を反応させ、必要
により加水分解反応に付すことを特徴とする一般
式 〔式中、Ｒ，ｍおよびｎは前記と同意義を表
す〕で示される化合物またはその塩またはエステ
ルの製造法。 ３ 一般式 〔式中、Ｒは、同一または異なつて、水素、ア
ルキル、アルコキシ、ニトロ、水酸基、アシル、
ヒドロキシアルキル、ハロゲンまたは環上の隣接
する２個の炭素原子と共に６員環を形成するテト
ラメチレン基（−（CH2）4−）あるいはブタジエ
ニレン基（−CH＝CH−CH＝CH−）を、ｍは
１，２または３を、ｎは１または２をそれぞれ表
す〕で示される化合物またはその塩またはエステ
ルを含有する慢性関節リウマチ治療剤。[Claims] 1. General formula [In the formula, R is the same or different and is hydrogen, alkyl, alkoxy, nitro, hydroxyl group, acyl,
A tetramethylene group (-( CH2 ) 4- ) or a butadienylene group (-CH=CH-CH=CH-) that forms a 6-membered ring together with hydroxyalkyl, halogen, or two adjacent carbon atoms on the ring, m represents 1, 2 or 3, and n represents 1 or 2, respectively] or a salt or ester thereof. 2 General formula [In the formula, R is the same or different and is hydrogen, alkyl, alkoxy, nitro, hydroxyl group, acyl,
A tetramethylene group (-( CH2 ) 4- ) or a butadienylene group (-CH=CH-CH=CH-) that forms a 6-membered ring together with hydroxyalkyl, halogen, or two adjacent carbon atoms on the ring, m represents 1, 2 or 3, respectively] to a compound represented by the general formula R 1 OOC-(CH 2 ) o -COCH 2 COOR 1 [wherein R represents alkyl and n represents 1 or 2, respectively] A general formula characterized by reacting a compound represented by ] and subjecting it to a hydrolysis reaction if necessary A method for producing a compound represented by the formula [wherein R, m and n have the same meanings as defined above] or a salt or ester thereof. 3 General formula [In the formula, R is the same or different and is hydrogen, alkyl, alkoxy, nitro, hydroxyl group, acyl,
A tetramethylene group (-( CH2 ) 4- ) or a butadienylene group (-CH=CH-CH=CH-) that forms a 6-membered ring together with hydroxyalkyl, halogen, or two adjacent carbon atoms on the ring, m represents 1, 2 or 3, and n represents 1 or 2, respectively] or a salt or ester thereof.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8891583A JPS59216888A (en) | 1983-05-19 | 1983-05-19 | 5-oxo-5h-(1)benzopyrano(2,3-b)pyridine derivative, its preparation and medicinal composition |
| US06/510,723 US4539326A (en) | 1982-08-20 | 1983-07-05 | 5-Oxo-5H-(1)benzopyrano(2,3-b)pyridine derivatives, their production and use as anti-inflammatory agents |
| EP83304208A EP0102175A1 (en) | 1982-08-20 | 1983-07-20 | 5-Oxo-5H-(1)benzopyrano(2,3-b)pyridine derivatives, their production and use |
| CA000434690A CA1200243A (en) | 1982-08-20 | 1983-08-16 | 5-oxo-5h-¬1|benzopyrano¬2,3-b|pyridine derivatives, their production and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8891583A JPS59216888A (en) | 1983-05-19 | 1983-05-19 | 5-oxo-5h-(1)benzopyrano(2,3-b)pyridine derivative, its preparation and medicinal composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59216888A JPS59216888A (en) | 1984-12-06 |
| JPH0379357B2 true JPH0379357B2 (en) | 1991-12-18 |
Family
ID=13956222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8891583A Granted JPS59216888A (en) | 1982-08-20 | 1983-05-19 | 5-oxo-5h-(1)benzopyrano(2,3-b)pyridine derivative, its preparation and medicinal composition |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59216888A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61215393A (en) * | 1985-03-20 | 1986-09-25 | Takeda Chem Ind Ltd | 2-amino-5-oxo-5h-(1)benzopyrano(2,3-b)pyridine-3-carboxylic acid derivative and production thereof |
| JPS61172880A (en) * | 1985-01-28 | 1986-08-04 | Takeda Chem Ind Ltd | 2-amino-5-oxo-5h-(1)benzopyrano(2,3-b)pyridine-3-carboxylic acid derivative and production thereof |
-
1983
- 1983-05-19 JP JP8891583A patent/JPS59216888A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59216888A (en) | 1984-12-06 |
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