DK169721B1 - Substituerede spiro-pyridinderivater, farmaceutiske præparater indeholdende dem og fremgangsmåde til fremstilling af sådanne derivater - Google Patents

Substituerede spiro-pyridinderivater, farmaceutiske præparater indeholdende dem og fremgangsmåde til fremstilling af sådanne derivater Download PDF

Info

Publication number: DK169721B1
Authority: DK; Denmark
Prior art keywords: dione; naphthyridine; spiro; compounds; phenyl
Prior art date: 1983-12-14

Application number

DK597184A

Other languages

Danish (da)

English (en)

Other versions

DK597184A (da

DK597184D0 (da

Inventor

David John Blythin

Original Assignee

Schering Corp

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

1983-12-14

Filing date

1984-12-13

Publication date

1995-01-23

1983-12-14 Priority claimed from US06/561,416 external-priority patent/US4652564A/en

1984-08-15 Priority claimed from US06/641,076 external-priority patent/US4632923A/en

1984-12-13 Application filed by Schering Corp filed Critical Schering Corp

1984-12-13 Publication of DK597184D0 publication Critical patent/DK597184D0/da

1985-06-15 Publication of DK597184A publication Critical patent/DK597184A/da

1995-01-23 Application granted granted Critical

1995-01-23 Publication of DK169721B1 publication Critical patent/DK169721B1/da

Links

238000004519 manufacturing process Methods 0.000 title 1
239000000825 pharmaceutical preparation Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 62
238000000034 method Methods 0.000 claims description 18
238000002360 preparation method Methods 0.000 claims description 17
239000004480 active ingredient Substances 0.000 claims description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000003003 spiro group Chemical group 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
125000000217 alkyl group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
239000011593 sulfur Substances 0.000 claims description 3
OTCTWXBXWSBCEW-UHFFFAOYSA-N 1-phenylspiro[1,8-naphthyridine-3,2'-oxetane]-2,4-dione Chemical compound C12=NC=CC=C2C(=O)C2(OCC2)C(=O)N1C1=CC=CC=C1 OTCTWXBXWSBCEW-UHFFFAOYSA-N 0.000 claims description 2
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
101100295738 Gallus gallus COR3 gene Chemical group 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
238000009833 condensation Methods 0.000 claims description 2
230000005494 condensation Effects 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000006413 ring segment Chemical group 0.000 claims description 2
150000003839 salts Chemical class 0.000 claims description 2
239000012453 solvate Substances 0.000 claims description 2
HENMSTDSJQGDNP-UHFFFAOYSA-N 1-(4-methylphenyl)spiro[2,4-dihydro-1,8-naphthyridine-3,1'-cyclopentane] Chemical compound CC1=CC=C(C=C1)N1CC2(CC3=CC=CN=C13)CCCC2 HENMSTDSJQGDNP-UHFFFAOYSA-N 0.000 claims 1
JFWUVPXQMRSBHE-UHFFFAOYSA-N 1-phenylspiro[2,4-dihydro-1,8-naphthyridine-3,1'-cyclopentane] Chemical compound C1(=CC=CC=C1)N1CC2(CCCC2)CC2=CC=CN=C12 JFWUVPXQMRSBHE-UHFFFAOYSA-N 0.000 claims 1
125000004430 oxygen atom Chemical group O* 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
239000000203 mixture Substances 0.000 description 32
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
239000000243 solution Substances 0.000 description 26
239000000047 product Substances 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
239000007788 liquid Substances 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
239000007787 solid Substances 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
239000007858 starting material Substances 0.000 description 10
241001465754 Metazoa Species 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
239000013543 active substance Substances 0.000 description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
229910052794 bromium Inorganic materials 0.000 description 8
239000012299 nitrogen atmosphere Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
239000000126 substance Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
229940098773 bovine serum albumin Drugs 0.000 description 7
229920000609 methyl cellulose Polymers 0.000 description 7
239000001923 methylcellulose Substances 0.000 description 7
235000010981 methylcellulose Nutrition 0.000 description 7
239000003826 tablet Substances 0.000 description 7
-1 trifluoroacetoxy, p-toluenesulfonyloxy, methanesulfonyloxy Chemical group 0.000 description 7
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000002775 capsule Substances 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
229940073584 methylene chloride Drugs 0.000 description 6
239000000843 powder Substances 0.000 description 6
108091003079 Bovine Serum Albumin Proteins 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000010410 layer Substances 0.000 description 5
DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
241000700159 Rattus Species 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
208000025865 Ulcer Diseases 0.000 description 4
230000037396 body weight Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000001816 cooling Methods 0.000 description 4
210000002683 foot Anatomy 0.000 description 4
229910000042 hydrogen bromide Inorganic materials 0.000 description 4
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 4
XTQQEFBWUFUXSZ-UHFFFAOYSA-N methyl 2-anilinopyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1NC1=CC=CC=C1 XTQQEFBWUFUXSZ-UHFFFAOYSA-N 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
238000003756 stirring Methods 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 3
ZCYHMYDYCBVLGS-UHFFFAOYSA-N 4-hydroxy-3-(4-hydroxybutyl)-1-phenyl-1,8-naphthyridin-2-one Chemical compound O=C1C(CCCCO)=C(O)C2=CC=CN=C2N1C1=CC=CC=C1 ZCYHMYDYCBVLGS-UHFFFAOYSA-N 0.000 description 3
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
206010061218 Inflammation Diseases 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
239000003814 drug Substances 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
230000004054 inflammatory process Effects 0.000 description 3
239000000463 material Substances 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000008247 solid mixture Substances 0.000 description 3
239000000829 suppository Substances 0.000 description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
238000005303 weighing Methods 0.000 description 3
CDUGGSQWPVAZBN-UHFFFAOYSA-N 3-(4-bromobutyl)-4-hydroxy-1-phenyl-1,8-naphthyridin-2-one Chemical compound C12=NC=CC=C2C(O)=C(CCCCBr)C(=O)N1C1=CC=CC=C1 CDUGGSQWPVAZBN-UHFFFAOYSA-N 0.000 description 2
FHUCBPRJJRSQFM-UHFFFAOYSA-N 3-anilinopyrazine-2-carboxylic acid Chemical class OC(=O)C1=NC=CN=C1NC1=CC=CC=C1 FHUCBPRJJRSQFM-UHFFFAOYSA-N 0.000 description 2
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
AEXJAEADPYRPSX-UHFFFAOYSA-N 4-hydroxy-3-(2-hydroxyethyl)-1-phenyl-1,8-naphthyridin-2-one Chemical compound O=C1C(CCO)=C(O)C2=CC=CN=C2N1C1=CC=CC=C1 AEXJAEADPYRPSX-UHFFFAOYSA-N 0.000 description 2
GIBYWRCMQHCYHS-UHFFFAOYSA-N 4-hydroxy-3-(3-hydroxypropyl)-1-phenyl-1,8-naphthyridin-2-one Chemical compound O=C1C(CCCO)=C(O)C2=CC=CN=C2N1C1=CC=CC=C1 GIBYWRCMQHCYHS-UHFFFAOYSA-N 0.000 description 2
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
206010006482 Bronchospasm Diseases 0.000 description 2
241000700198 Cavia Species 0.000 description 2
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
208000007107 Stomach Ulcer Diseases 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
239000002253 acid Substances 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
230000002052 anaphylactic effect Effects 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
230000000767 anti-ulcer Effects 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
206010003246 arthritis Diseases 0.000 description 2
244000309464 bull Species 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
229940110456 cocoa butter Drugs 0.000 description 2
235000019868 cocoa butter Nutrition 0.000 description 2
239000012043 crude product Substances 0.000 description 2
230000001120 cytoprotective effect Effects 0.000 description 2
LKKOGZVQGQUVHF-UHFFFAOYSA-N diethyl heptanedioate Chemical compound CCOC(=O)CCCCCC(=O)OCC LKKOGZVQGQUVHF-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229960000905 indomethacin Drugs 0.000 description 2
230000004968 inflammatory condition Effects 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
238000011694 lewis rat Methods 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000002844 melting Methods 0.000 description 2
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
229910052753 mercury Inorganic materials 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
ANJRHIXEBGXIIV-UHFFFAOYSA-N methyl 3-anilinopyrazine-2-carboxylate Chemical compound COC(=O)C1=NC=CN=C1NC1=CC=CC=C1 ANJRHIXEBGXIIV-UHFFFAOYSA-N 0.000 description 2
CMITUAXQMWSHLL-UHFFFAOYSA-N methyl 3-bromopyrazine-2-carboxylate Chemical compound COC(=O)C1=NC=CN=C1Br CMITUAXQMWSHLL-UHFFFAOYSA-N 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
239000012071 phase Substances 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
230000002685 pulmonary effect Effects 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
CWXOAQXKPAENDI-UHFFFAOYSA-N sodium methylsulfinylmethylide Chemical compound [Na+].CS([CH2-])=O CWXOAQXKPAENDI-UHFFFAOYSA-N 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
239000002562 thickening agent Substances 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
231100000397 ulcer Toxicity 0.000 description 2
230000036269 ulceration Effects 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
NUDCZXZUVJITDE-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-hydroxy-3-(4-hydroxybutyl)-1,8-naphthyridin-2-one Chemical compound O=C1C(CCCCO)=C(O)C2=CC=CN=C2N1C1=CC=CC(Cl)=C1 NUDCZXZUVJITDE-UHFFFAOYSA-N 0.000 description 1
FCYBICHZSBNDQY-UHFFFAOYSA-N 1-(3-chlorophenyl)spiro[2,4-dihydro-1,8-naphthyridine-3,1'-cyclopentane] Chemical compound ClC=1C=C(C=CC=1)N1CC2(CC3=CC=CN=C13)CCCC2 FCYBICHZSBNDQY-UHFFFAOYSA-N 0.000 description 1
NPRUKBUWOBWOLM-UHFFFAOYSA-N 1-(4-chlorophenyl)-4-hydroxy-3-(4-hydroxybutyl)-1,8-naphthyridin-2-one Chemical compound O=C1C(CCCCO)=C(O)C2=CC=CN=C2N1C1=CC=C(Cl)C=C1 NPRUKBUWOBWOLM-UHFFFAOYSA-N 0.000 description 1
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
OBTZDIRUQWFRFZ-UHFFFAOYSA-N 2-(5-methylfuran-2-yl)-n-(4-methylphenyl)quinoline-4-carboxamide Chemical compound O1C(C)=CC=C1C1=CC(C(=O)NC=2C=CC(C)=CC=2)=C(C=CC=C2)C2=N1 OBTZDIRUQWFRFZ-UHFFFAOYSA-N 0.000 description 1
UUMMTMQODCACRH-UHFFFAOYSA-N 2-anilinopyridine-3-carboxylic acid Chemical class OC(=O)C1=CC=CN=C1NC1=CC=CC=C1 UUMMTMQODCACRH-UHFFFAOYSA-N 0.000 description 1
FUNSXMWAMPBOMJ-UHFFFAOYSA-N 3-(4-bromobutyl)-1-(3,4-dichlorophenyl)-4-hydroxy-1,8-naphthyridin-2-one Chemical compound C12=NC=CC=C2C(O)=C(CCCCBr)C(=O)N1C1=CC=C(Cl)C(Cl)=C1 FUNSXMWAMPBOMJ-UHFFFAOYSA-N 0.000 description 1
BOGHVLKCBGTLSQ-UHFFFAOYSA-N 3-(4-bromobutyl)-1-(4-chlorophenyl)-4-hydroxy-1,8-naphthyridin-2-one Chemical compound C12=NC=CC=C2C(O)=C(CCCCBr)C(=O)N1C1=CC=C(Cl)C=C1 BOGHVLKCBGTLSQ-UHFFFAOYSA-N 0.000 description 1
OFLFTVJRTPNPNT-UHFFFAOYSA-N 3-(4-bromobutyl)-4-hydroxy-1-(3-hydroxyphenyl)-1,8-naphthyridin-2-one Chemical compound OC1=CC=CC(N2C(C(CCCCBr)=C(O)C3=CC=CN=C32)=O)=C1 OFLFTVJRTPNPNT-UHFFFAOYSA-N 0.000 description 1
ZQBZXHVISIHCTK-UHFFFAOYSA-N 3-(4-bromobutyl)-4-hydroxy-1-phenylquinolin-2-one Chemical compound C12=CC=CC=C2C(O)=C(CCCCBr)C(=O)N1C1=CC=CC=C1 ZQBZXHVISIHCTK-UHFFFAOYSA-N 0.000 description 1
ZAGZIOYVEIDDJA-UHFFFAOYSA-N 3-aminopyrazine-2-carboxylic acid Chemical compound NC1=NC=CN=C1C(O)=O ZAGZIOYVEIDDJA-UHFFFAOYSA-N 0.000 description 1
JHNLZOVBAQWGQU-UHFFFAOYSA-N 380814_sial Chemical compound CS(O)(=O)=O.O=P(=O)OP(=O)=O JHNLZOVBAQWGQU-UHFFFAOYSA-N 0.000 description 1
MBTUHODCFMWHQT-UHFFFAOYSA-N 4-hydroxy-3-(3-hydroxypropyl)-1-(4-methylphenyl)-1,8-naphthyridin-2-one Chemical compound C1=CC(C)=CC=C1N1C(=O)C(CCCO)=C(O)C2=CC=CN=C21 MBTUHODCFMWHQT-UHFFFAOYSA-N 0.000 description 1
PPVHBJDFBQKUPY-UHFFFAOYSA-N 4-hydroxy-3-(4-hydroxybutyl)-1-(3-methoxyphenyl)-1,8-naphthyridin-2-one Chemical compound COC1=CC=CC(N2C(C(CCCCO)=C(O)C3=CC=CN=C32)=O)=C1 PPVHBJDFBQKUPY-UHFFFAOYSA-N 0.000 description 1
CVKVNBMPVATZCB-UHFFFAOYSA-N 4-hydroxy-3-(4-hydroxybutyl)-1-(4-methoxyphenyl)-1,8-naphthyridin-2-one Chemical compound C1=CC(OC)=CC=C1N1C(=O)C(CCCCO)=C(O)C2=CC=CN=C21 CVKVNBMPVATZCB-UHFFFAOYSA-N 0.000 description 1
WFHUVOKUVXRZLR-UHFFFAOYSA-N 4-hydroxy-3-(4-hydroxybutyl)-1-(4-methylphenyl)-1,8-naphthyridin-2-one Chemical compound C1=CC(C)=CC=C1N1C(=O)C(CCCCO)=C(O)C2=CC=CN=C21 WFHUVOKUVXRZLR-UHFFFAOYSA-N 0.000 description 1
OMXYUBWPRKKQDY-UHFFFAOYSA-N 4-hydroxy-3-(5-hydroxypent-3-ynyl)-1-phenyl-1,8-naphthyridin-2-one Chemical compound O=C1C(CCC#CCO)=C(O)C2=CC=CN=C2N1C1=CC=CC=C1 OMXYUBWPRKKQDY-UHFFFAOYSA-N 0.000 description 1
TUROZEYFVRYEHH-UHFFFAOYSA-N 4-hydroxy-3-(5-hydroxypentyl)-1-phenyl-1,8-naphthyridin-2-one Chemical compound O=C1C(CCCCCO)=C(O)C2=CC=CN=C2N1C1=CC=CC=C1 TUROZEYFVRYEHH-UHFFFAOYSA-N 0.000 description 1
GHXVYVXPBFPNLS-KXFIGUGUSA-N 4-hydroxy-3-[(Z)-5-hydroxypent-3-enyl]-1-phenyl-1,8-naphthyridin-2-one Chemical compound OC1=C(C(N(C2=NC=CC=C12)C1=CC=CC=C1)=O)CC\C=C/CO GHXVYVXPBFPNLS-KXFIGUGUSA-N 0.000 description 1
CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
SFQVHNRYBIYZPB-UHFFFAOYSA-N 9-phenyl-2,3-dihydrofuro[2,3-b][1,8]naphthyridin-4-one Chemical compound C12=NC=CC=C2C(=O)C=2CCOC=2N1C1=CC=CC=C1 SFQVHNRYBIYZPB-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
208000009079 Bronchial Spasm Diseases 0.000 description 1
208000014181 Bronchial disease Diseases 0.000 description 1
206010006811 Bursitis Diseases 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-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
239000012448 Lithium borohydride Substances 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
241000609499 Palicourea Species 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
206010070834 Sensitisation Diseases 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
208000005392 Spasm Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000000491 Tendinopathy Diseases 0.000 description 1
206010043255 Tendonitis Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
239000012042 active reagent Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
239000013566 allergen Substances 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
230000007815 allergy Effects 0.000 description 1
238000000540 analysis of variance Methods 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
230000003266 anti-allergic effect Effects 0.000 description 1
230000002804 anti-anaphylactic effect Effects 0.000 description 1
230000001078 anti-cholinergic effect Effects 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
235000021311 artificial sweeteners Nutrition 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000009395 breeding Methods 0.000 description 1
230000001488 breeding effect Effects 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
230000007885 bronchoconstriction Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000008859 change Effects 0.000 description 1
230000000973 chemotherapeutic effect Effects 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000004040 coloring Methods 0.000 description 1
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 1
KSLDDHNABYPZAI-UHFFFAOYSA-N cyclopentane;quinoline Chemical compound C1CCCC1.N1=CC=CC2=CC=CC=C21 KSLDDHNABYPZAI-UHFFFAOYSA-N 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
229960002069 diamorphine Drugs 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
239000000975 dye Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
PMIMPBYTPPRBGD-UHFFFAOYSA-N ethyl 2-chloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=CN=C1Cl PMIMPBYTPPRBGD-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
201000005917 gastric ulcer Diseases 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
244000144993 groups of animals Species 0.000 description 1
230000036541 health Effects 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
210000000548 hind-foot Anatomy 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
230000007794 irritation Effects 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000008018 melting Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
229960002009 naproxen Drugs 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 1
229920003052 natural elastomer Polymers 0.000 description 1
229920001194 natural rubber Polymers 0.000 description 1
235000021096 natural sweeteners Nutrition 0.000 description 1
230000001129 nonadrenergic effect Effects 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000003182 parenteral nutrition solution Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
210000005164 penile vein Anatomy 0.000 description 1
229960002895 phenylbutazone Drugs 0.000 description 1
VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
230000002265 prevention Effects 0.000 description 1
ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
239000000523 sample Substances 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000008313 sensitization Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
229920003051 synthetic elastomer Polymers 0.000 description 1
239000005061 synthetic rubber Substances 0.000 description 1
239000007885 tablet disintegrant Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
201000004415 tendinitis Diseases 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
229960001017 tolmetin Drugs 0.000 description 1
UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
238000012795 verification Methods 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pulmonology (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Immunology (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

DK597184A 1983-12-14 1984-12-13 Substituerede spiro-pyridinderivater, farmaceutiske præparater indeholdende dem og fremgangsmåde til fremstilling af sådanne derivater DK169721B1 (da)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US56141683		1983-12-14
US06/561,416 US4652564A (en)	1983-12-14	1983-12-14	Substituted spiro pyridine derivatives as anti-allergy and antiinflammatory agents
US64107684		1984-08-15
US06/641,076 US4632923A (en)	1984-08-15	1984-08-15	Substituted hetero spiro pyridine derivatives as anti-allergy and anti-inflammatory agents

Publications (3)

Publication Number	Publication Date
DK597184D0 DK597184D0 (da)	1984-12-13
DK597184A DK597184A (da)	1985-06-15
DK169721B1 true DK169721B1 (da)	1995-01-23

Family

ID=27072640

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK597184A DK169721B1 (da)	1983-12-14	1984-12-13	Substituerede spiro-pyridinderivater, farmaceutiske præparater indeholdende dem og fremgangsmåde til fremstilling af sådanne derivater

Country Status (18)

Country	Link
EP (1)	EP0144996B1 (fr)
JP (1)	JPH066586B2 (fr)
KR (1)	KR900004832B1 (fr)
AU (1)	AU574749B2 (fr)
CA (1)	CA1252786A (fr)
DE (1)	DE3481418D1 (fr)
DK (1)	DK169721B1 (fr)
FI (1)	FI79539C (fr)
GB (1)	GB2153348B (fr)
GR (1)	GR82463B (fr)
HK (1)	HK48890A (fr)
HU (1)	HU193913B (fr)
IL (1)	IL73823A (fr)
MY (1)	MY100602A (fr)
NO (1)	NO163896C (fr)
NZ (1)	NZ210551A (fr)
OA (1)	OA07899A (fr)
PT (1)	PT79672A (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3669656D1 (de) *	1985-06-18	1990-04-26	Schering Corp	Azanaphthalene enthaltende arzneimittelzusammensetzungen.
ES2054665T3 (es) *	1986-04-11	1994-08-16	Schering Corp	Derivados de naftiridina y piridopirazina sustituidos con arilo.
US5045542A (en) *	1986-10-20	1991-09-03	Schering Corporation	Immune suppression method employing aryl-substituted naphthyridine and pyridopyrazine derivatives
US5350755A (en) *	1986-12-05	1994-09-27	Schering Corporation	Compounds and methods for treating hyperproliferative skin disease
CA1309658C (fr) *	1986-12-05	1992-11-03	David J. Blythin	Compositions pharmaceutiques pour le traitement des maladies hyperproliferatives de la peau
TR200200118T2 (tr)	1999-07-21	2002-12-23	Astrazeneca Ab	Yeni bileşimler
US7592457B2 (en) *	2004-10-20	2009-09-22	Korea Research Institute Of Chemical Technology	3-aryl-3-methyl-quinoline-2, 4-diones, preparation method thereof, and pharmaceutical composition containing the same

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB855022A (en) *	1957-08-06	1960-11-30	Geigy Ag J R	Improvements in and relating to carbostyril derivatives
JPS5089376A (fr) *	1973-12-19	1975-07-17
US4215216A (en) *	1979-04-18	1980-07-29	American Home Products Corporation	7,8-Dihydro-2,5,8-trisubstituted-7-oxo-pyrido[2,3-d]pyrimidine-6-carboxylic acid derivatives
DE3368929D1 (de) *	1982-04-26	1987-02-12	Schering Corp	1,8-naphthyridine and 1,5,8-azanaphthyridine derivatives

1984
- 1984-12-08 EP EP84114974A patent/EP0144996B1/fr not_active Expired - Lifetime
- 1984-12-08 DE DE8484114974T patent/DE3481418D1/de not_active Expired - Lifetime
- 1984-12-11 JP JP59261664A patent/JPH066586B2/ja not_active Expired - Lifetime
- 1984-12-13 HU HU844651A patent/HU193913B/hu not_active IP Right Cessation
- 1984-12-13 PT PT79672A patent/PT79672A/pt not_active IP Right Cessation
- 1984-12-13 NO NO845016A patent/NO163896C/no unknown
- 1984-12-13 KR KR1019840007885A patent/KR900004832B1/ko not_active Expired
- 1984-12-13 AU AU36624/84A patent/AU574749B2/en not_active Ceased
- 1984-12-13 FI FI844919A patent/FI79539C/fi not_active IP Right Cessation
- 1984-12-13 NZ NZ210551A patent/NZ210551A/en unknown
- 1984-12-13 CA CA000470037A patent/CA1252786A/fr not_active Expired
- 1984-12-13 GR GR82463A patent/GR82463B/el unknown
- 1984-12-13 DK DK597184A patent/DK169721B1/da not_active IP Right Cessation
- 1984-12-13 GB GB08431542A patent/GB2153348B/en not_active Expired
- 1984-12-14 OA OA58476A patent/OA07899A/fr unknown
- 1984-12-14 IL IL73823A patent/IL73823A/xx not_active IP Right Cessation
1987
- 1987-09-22 MY MYPI87001838A patent/MY100602A/en unknown
1990
- 1990-06-21 HK HK488/90A patent/HK48890A/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
GB8431542D0 (en)	1985-01-23
JPH066586B2 (ja)	1994-01-26
NZ210551A (en)	1988-05-30
HU193913B (en)	1987-12-28
DK597184A (da)	1985-06-15
IL73823A0 (en)	1985-03-31
OA07899A (fr)	1986-11-20
FI844919A0 (fi)	1984-12-13
FI844919L (fi)	1985-06-15
DK597184D0 (da)	1984-12-13
KR850004487A (ko)	1985-07-15
AU574749B2 (en)	1988-07-14
EP0144996B1 (fr)	1990-02-28
JPS60156689A (ja)	1985-08-16
CA1252786A (fr)	1989-04-18
GB2153348A (en)	1985-08-21
GR82463B (en)	1985-04-16
KR900004832B1 (ko)	1990-07-07
IL73823A (en)	1988-03-31
DE3481418D1 (de)	1990-04-05
AU3662484A (en)	1985-06-20
NO163896C (no)	1990-08-08
PT79672A (en)	1985-01-01
NO163896B (no)	1990-04-30
HUT36477A (en)	1985-09-30
HK48890A (en)	1990-06-29
FI79539C (fi)	1990-01-10
FI79539B (fi)	1989-09-29
GB2153348B (en)	1987-08-12
EP0144996A3 (en)	1986-06-11
NO845016L (no)	1985-06-17
MY100602A (en)	1990-12-15
EP0144996A2 (fr)	1985-06-19

Legal Events

Date	Code	Title	Description
1995-01-23	B1	Patent granted (law 1993)
1997-08-25	PBP	Patent lapsed

Publication	Publication Date	Title
EP0127135B1 (fr)	1990-08-29	Dérivés condensés tricycliques de naphtyridinone et pyridone et les thiones correspondantes
DK174161B1 (da)	2002-07-29	Anellerede indolderivater, fremgangsmåde til deres fremstilling og fremgangsmåde til fremstilling af farmaceutisk præparat indeholdende dem
CA2047283C (fr)	2002-07-02	Compose a base de pyrazolopyridine et methode de preparation
JP4790703B2 (ja)	2011-10-12	環式化合物
JP3583132B2 (ja)	2004-10-27	ピリダジノキノリン化合物
CA2051697C (fr)	1996-10-08	Amines heterocycliques ayant une activite sur le systeme nerveux central
JP2016028092A (ja)	2016-02-25	ヘテロアリール化合物及びその使用方法
US5387592A (en)	1995-02-07	Substituted benzoxazole, benzthiazole, and benzimidazole derivatives as angiotensin II antagonists
EP0383465B1 (fr)	1995-05-03	Dérivés de pyrimidine tricycliques condensés, leur préparation et leur utilisation
CS258483B2 (en)	1988-08-16	Method of new thienopyridones production
US4652564A (en)	1987-03-24	Substituted spiro pyridine derivatives as anti-allergy and antiinflammatory agents
EP0144996B1 (fr)	1990-02-28	Dérivés substitués de spiro pyridine, compositions pharmaceutiques les contenant et procédés pour leur préparation et compositions
US4632923A (en)	1986-12-30	Substituted hetero spiro pyridine derivatives as anti-allergy and anti-inflammatory agents
AU591922B2 (en)	1989-12-21	Polycyclic quinoline, naphthyridine and pyrazinopyridines
KR100309215B1 (ko)	2001-12-28	항정신병제로서의피리딘이미닐-1,2-벤즈이속사졸및-벤즈이소티아졸
NO162188B (no)	1989-08-14	Analogifremgangsm te for fremstilling av terapeutisk aktive imidazokinoliner.
NZ207582A (en)	1986-10-08	(1h-tetrazol-5-yl)-tetrazolo(1,5-a)quinoline derivatives and pharmaceutical composition
US6214826B1 (en)	2001-04-10	Pyridazino quinoline compounds
IE57925B1 (en)	1993-05-19	Fused tricyclic derivatives of naphthyridinone,pyridone and quinolone and the corresponding thiones