DE2854341A1 - Neue derivate der 2- eckige klammer auf (4-chinolinyl)-amino eckige klammer zu -5-fluorbenzoesaeure, verfahren zu deren herstellung, deren verwendung als arzneimittel und die sie enthaltenden pharmazeutischen zusammensetzungen - Google Patents
Neue derivate der 2- eckige klammer auf (4-chinolinyl)-amino eckige klammer zu -5-fluorbenzoesaeure, verfahren zu deren herstellung, deren verwendung als arzneimittel und die sie enthaltenden pharmazeutischen zusammensetzungenInfo
- Publication number
- DE2854341A1 DE2854341A1 DE19782854341 DE2854341A DE2854341A1 DE 2854341 A1 DE2854341 A1 DE 2854341A1 DE 19782854341 DE19782854341 DE 19782854341 DE 2854341 A DE2854341 A DE 2854341A DE 2854341 A1 DE2854341 A1 DE 2854341A1
- Authority
- DE
- Germany
- Prior art keywords
- radical
- formula
- carbon atoms
- trifluoromethyl
- acid
- 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
- -1 (4-QUINOLINYL) -AMINO Chemical class 0.000 title claims description 72
- 238000000034 method Methods 0.000 title claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 238000004519 manufacturing process Methods 0.000 title description 3
- 229940126601 medicinal product Drugs 0.000 title 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 29
- 150000007513 acids Chemical class 0.000 claims description 16
- 150000003254 radicals Chemical class 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 150000004702 methyl esters Chemical class 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- JBAFPLJQMLMGAH-UHFFFAOYSA-N 5-fluoro-2-[[8-(trifluoromethyl)quinolin-4-yl]amino]benzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=C(C(F)(F)F)C=CC=C12 JBAFPLJQMLMGAH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 238000005809 transesterification reaction Methods 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- XLEJHSGYBLEMCI-UHFFFAOYSA-N 2,3-dihydroxypropyl 5-fluoro-2-[[8-(trifluoromethyl)quinolin-4-yl]amino]benzoate Chemical compound OCC(O)COC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=C(C(F)(F)F)C=CC=C12 XLEJHSGYBLEMCI-UHFFFAOYSA-N 0.000 claims description 3
- 150000005840 aryl radicals Chemical class 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 238000007127 saponification reaction Methods 0.000 claims description 3
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical group [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 2
- DCBSHORRWZKAKO-UHFFFAOYSA-N rac-1-monomyristoylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(O)CO DCBSHORRWZKAKO-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 239000007789 gas Substances 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 239000000047 product Substances 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 14
- 239000013078 crystal Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 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 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- LYEAUCRITXBJTG-UHFFFAOYSA-N methyl 2-[(7-chloroquinolin-4-yl)amino]-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 LYEAUCRITXBJTG-UHFFFAOYSA-N 0.000 description 3
- PUDDYSBKCDKATP-UHFFFAOYSA-N methyl 2-amino-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1N PUDDYSBKCDKATP-UHFFFAOYSA-N 0.000 description 3
- FRLHRTUBWUUAFG-UHFFFAOYSA-N methyl 5-fluoro-2-[[8-(trifluoromethyl)quinolin-4-yl]amino]benzoate Chemical compound COC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=C(C(F)(F)F)C=CC=C12 FRLHRTUBWUUAFG-UHFFFAOYSA-N 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- UAJCXPLDRIQWRP-UHFFFAOYSA-N 2-[(7-chloroquinolin-4-yl)amino]-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 UAJCXPLDRIQWRP-UHFFFAOYSA-N 0.000 description 2
- HXEWMTXDBOQQKO-UHFFFAOYSA-N 4,7-dichloroquinoline Chemical compound ClC1=CC=NC2=CC(Cl)=CC=C21 HXEWMTXDBOQQKO-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 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
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000010425 asbestos Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229960002887 deanol Drugs 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229940087646 methanolamine Drugs 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 229910052895 riebeckite Inorganic materials 0.000 description 2
- RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- QOOQLKSEGVNYLA-UHFFFAOYSA-N 1-$l^{1}-oxidanylbutane Chemical compound CCCC[O] QOOQLKSEGVNYLA-UHFFFAOYSA-N 0.000 description 1
- LXLBQCWPMHIPMU-UHFFFAOYSA-N 2,3-dihydroxypropyl 2-[(7-chloroquinolin-4-yl)amino]-5-fluorobenzoate Chemical compound OCC(O)COC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 LXLBQCWPMHIPMU-UHFFFAOYSA-N 0.000 description 1
- XAABQOXNZOODQY-UHFFFAOYSA-N 2-(dimethylamino)ethyl 5-fluoro-2-[[8-(trifluoromethyl)quinolin-4-yl]amino]benzoate Chemical compound CN(C)CCOC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=C(C(F)(F)F)C=CC=C12 XAABQOXNZOODQY-UHFFFAOYSA-N 0.000 description 1
- NPHULPIAPWNOOH-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(2,3-dihydroindol-1-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCC2=CC=CC=C12 NPHULPIAPWNOOH-UHFFFAOYSA-N 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 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
- LLRQVSZVVAKRJA-UHFFFAOYSA-N 4-chloro-7-(trifluoromethyl)quinoline Chemical compound ClC1=CC=NC2=CC(C(F)(F)F)=CC=C21 LLRQVSZVVAKRJA-UHFFFAOYSA-N 0.000 description 1
- HQYCQIWWCBOKKI-UHFFFAOYSA-N 5-fluoro-2-[[7-(trifluoromethyl)quinolin-4-yl]amino]benzoic acid Chemical compound FC(C1=CC=C2C(=CC=NC2=C1)NC1=C(C(=O)O)C=C(C=C1)F)(F)F HQYCQIWWCBOKKI-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241001237754 Algia Species 0.000 description 1
- 239000004475 Arginine Chemical class 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical class NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Chemical class OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001723 carbon free-radicals Chemical class 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical class C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- UKPBEPCQTDRZSE-UHFFFAOYSA-N cyclizine hydrochloride Chemical compound Cl.C1CN(C)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 UKPBEPCQTDRZSE-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WGRQWIFSBUXXBX-UHFFFAOYSA-N methyl 5-fluoro-2-[[7-(trifluoromethyl)quinolin-4-yl]amino]benzoate Chemical compound COC(=O)C1=CC(F)=CC=C1NC1=CC=NC2=CC(C(F)(F)F)=CC=C12 WGRQWIFSBUXXBX-UHFFFAOYSA-N 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 235000013311 vegetables Nutrition 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR7737835A FR2411832A1 (fr) | 1977-12-15 | 1977-12-15 | Nouveaux derives de l'acide 2/(4-quinoleinyl) amino/5-fluorobenzoique, leur procede de preparation et leur application comme medicament. |
FR7737836A FR2411833A1 (fr) | 1977-12-15 | 1977-12-15 | Nouveaux derives de l'acide 2(/4-quinoleinyl/amino) 5-fluoro benzoique, leur procede de preparation et leur application comme medicament |
Publications (2)
Publication Number | Publication Date |
---|---|
DE2854341A1 true DE2854341A1 (de) | 1979-06-28 |
DE2854341C2 DE2854341C2 (en, 2012) | 1990-05-23 |
Family
ID=26220343
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19782854341 Granted DE2854341A1 (de) | 1977-12-15 | 1978-12-15 | Neue derivate der 2- eckige klammer auf (4-chinolinyl)-amino eckige klammer zu -5-fluorbenzoesaeure, verfahren zu deren herstellung, deren verwendung als arzneimittel und die sie enthaltenden pharmazeutischen zusammensetzungen |
Country Status (21)
Country | Link |
---|---|
US (1) | US4233305A (en, 2012) |
JP (1) | JPS5488277A (en, 2012) |
AR (1) | AR224116A1 (en, 2012) |
AT (1) | AT365578B (en, 2012) |
AU (1) | AU520983B2 (en, 2012) |
CA (1) | CA1115276A (en, 2012) |
CH (1) | CH636350A5 (en, 2012) |
DE (1) | DE2854341A1 (en, 2012) |
DK (1) | DK149845C (en, 2012) |
ES (1) | ES475686A1 (en, 2012) |
FI (1) | FI70574C (en, 2012) |
GB (1) | GB2010243B (en, 2012) |
HU (1) | HU177031B (en, 2012) |
IE (1) | IE47618B1 (en, 2012) |
IL (1) | IL56156A (en, 2012) |
IT (1) | IT1107671B (en, 2012) |
LU (1) | LU80660A1 (en, 2012) |
NL (1) | NL7812206A (en, 2012) |
PT (1) | PT68916A (en, 2012) |
SE (1) | SE448091B (en, 2012) |
SU (1) | SU837322A3 (en, 2012) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6322584A (ja) * | 1986-07-15 | 1988-01-30 | Senjiyu Seiyaku Kk | 1−ハイドロキシ−5−オキソ−5H−ピリド〔3,2−a〕フエノキサジン−3−カルボン酸エステル類 |
IL89029A (en) * | 1988-01-29 | 1993-01-31 | Lilly Co Eli | Fungicidal quinoline and cinnoline derivatives, compositions containing them, and fungicidal methods of using them |
IS4164A (is) * | 1993-06-11 | 1994-12-12 | Ab Astra | Efnasambönd sem hindra flæði magasýru |
US5578607A (en) * | 1993-12-17 | 1996-11-26 | The Procter & Gamble Company | 6-(2-imidazolinylamino)quinoline compounds useful as alpha-2 adrenoceptor agonists |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2428201A1 (de) * | 1973-06-13 | 1975-01-09 | Roussel Uclaf | Anthranilsaeurederivate, verfahren zu deren herstellung und diese derivate enthaltende arzneimittel |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3232944A (en) * | 1966-02-01 | Monoglycerides 0f (carbgxy pl-ienyl amtno) chlgroqukngltnes | ||
CH408915A (fr) * | 1962-02-16 | 1966-03-15 | Roussel Uclaf | Procédé de préparation d'un nouveau composé utilisable, notamment, pour le traitement des manifestations inflammatoires et/ou douloureuses |
CA731646A (en) * | 1962-05-08 | 1966-04-05 | Roussel-Uclaf | 4-(2'(.beta.-MORPHOLYLETHOXYCARBONYL) PHENYLAMINE) 7-CHLORO QUINOLEINE ET SES SELS, AINSI QUE LEUR PROCEDE DE PREPARATION |
FR6935M (en, 2012) * | 1967-12-29 | 1969-05-05 | ||
FR7870M (en, 2012) * | 1968-11-08 | 1970-04-27 | ||
ZA726593B (en) * | 1971-10-19 | 1973-06-27 | Abbott Lab | Novel derivatives of 2,3-dihydroxypropyl-n-(7 or 8-chloro-4-quinolinyl)anthranilate |
CH585221A5 (en, 2012) * | 1972-07-28 | 1977-02-28 | Synthelabo | |
US3971789A (en) * | 1972-10-21 | 1976-07-27 | John Wyeth & Brother Limited | O-(4-Quinolylamino)benzamides |
GB1474296A (en) * | 1975-01-23 | 1977-05-18 | Wyeth John & Brother Ltd | 4-aminoquinoline derivatives |
-
1978
- 1978-11-16 SE SE7811839A patent/SE448091B/sv not_active IP Right Cessation
- 1978-12-04 ES ES475686A patent/ES475686A1/es not_active Expired
- 1978-12-06 US US05/966,964 patent/US4233305A/en not_active Expired - Lifetime
- 1978-12-07 SU SU782696357A patent/SU837322A3/ru active
- 1978-12-08 IL IL56156A patent/IL56156A/xx unknown
- 1978-12-13 FI FI783833A patent/FI70574C/fi not_active IP Right Cessation
- 1978-12-14 DK DK561278A patent/DK149845C/da not_active IP Right Cessation
- 1978-12-14 HU HU78RO1003A patent/HU177031B/hu not_active IP Right Cessation
- 1978-12-14 PT PT68916A patent/PT68916A/pt unknown
- 1978-12-14 JP JP15380478A patent/JPS5488277A/ja active Granted
- 1978-12-14 LU LU80660A patent/LU80660A1/xx unknown
- 1978-12-14 IE IE2476/78A patent/IE47618B1/en unknown
- 1978-12-14 AU AU42528/78A patent/AU520983B2/en not_active Expired
- 1978-12-14 GB GB7848546A patent/GB2010243B/en not_active Expired
- 1978-12-14 AR AR274807A patent/AR224116A1/es active
- 1978-12-14 IT IT52296/78A patent/IT1107671B/it active
- 1978-12-14 CA CA317,952A patent/CA1115276A/fr not_active Expired
- 1978-12-15 AT AT0897378A patent/AT365578B/de not_active IP Right Cessation
- 1978-12-15 CH CH1279478A patent/CH636350A5/fr not_active IP Right Cessation
- 1978-12-15 DE DE19782854341 patent/DE2854341A1/de active Granted
- 1978-12-15 NL NL7812206A patent/NL7812206A/xx not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2428201A1 (de) * | 1973-06-13 | 1975-01-09 | Roussel Uclaf | Anthranilsaeurederivate, verfahren zu deren herstellung und diese derivate enthaltende arzneimittel |
Also Published As
Publication number | Publication date |
---|---|
AT365578B (de) | 1982-01-25 |
SE448091B (sv) | 1987-01-19 |
DK561278A (da) | 1979-06-16 |
CA1115276A (fr) | 1981-12-29 |
DK149845B (da) | 1986-10-13 |
ES475686A1 (es) | 1979-04-16 |
FI70574C (fi) | 1986-09-24 |
SE7811839L (sv) | 1979-06-16 |
SU837322A3 (ru) | 1981-06-07 |
AR224116A1 (es) | 1981-10-30 |
DE2854341C2 (en, 2012) | 1990-05-23 |
GB2010243A (en) | 1979-06-27 |
LU80660A1 (fr) | 1979-07-20 |
GB2010243B (en) | 1982-05-19 |
HU177031B (hu) | 1981-06-28 |
US4233305A (en) | 1980-11-11 |
JPS5488277A (en) | 1979-07-13 |
FI70574B (fi) | 1986-06-06 |
DK149845C (da) | 1987-03-02 |
IE47618B1 (en) | 1984-05-02 |
NL7812206A (nl) | 1979-06-19 |
AU520983B2 (en) | 1982-03-11 |
IL56156A0 (en) | 1979-03-12 |
IT7852296A0 (it) | 1978-12-14 |
AU4252878A (en) | 1979-06-21 |
IE782476L (en) | 1979-06-15 |
JPS631305B2 (en, 2012) | 1988-01-12 |
ATA897378A (de) | 1981-06-15 |
CH636350A5 (fr) | 1983-05-31 |
PT68916A (fr) | 1979-01-01 |
IL56156A (en) | 1984-11-30 |
FI783833A7 (fi) | 1979-06-16 |
IT1107671B (it) | 1985-11-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE1518002C3 (de) | Isoflavane und Isoflavene und Verfahren zu Ihrer Herstellung sowie diese enthaltende Arzneimittel | |
DE2907217C2 (de) | 3-Phenyl-3-phenoxypropylamin-Derivate und deren Salze, deren Herstellung und diese enthaltende Arzneimittel | |
DE1543715A1 (de) | Verfahren zur Herstellung von basischen Derivaten von Phthalanen und Isochromanen | |
DE2738646C2 (de) | Piperidyl-indol-Derivate, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen | |
WO2003086407A1 (de) | Verwendung von stimulatoren der löslichen guanylatcyclase zur behandlung von glaukom | |
EP1399423A2 (de) | Anthranilsäureamide mit heteroarylsulfonyl-seitenkette und ihre verwendung als antiarrhythmische wirkstoffe | |
DE2065636B2 (de) | Tricyclische Verbindungen, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel | |
DE2802493C2 (en, 2012) | ||
DE3133185A1 (de) | "4h-1,2,4-triazolderivate, verfahren zu deren herstellung und deren verwendung" | |
CH622248A5 (en, 2012) | ||
DE2248596A1 (de) | Neue derivate der aminoisophtalsaeure | |
DE2854341A1 (de) | Neue derivate der 2- eckige klammer auf (4-chinolinyl)-amino eckige klammer zu -5-fluorbenzoesaeure, verfahren zu deren herstellung, deren verwendung als arzneimittel und die sie enthaltenden pharmazeutischen zusammensetzungen | |
EP0621037A1 (de) | Pyrido-pyrimidindione, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel | |
DE3320102A1 (de) | Neue, in 2-stellung substituierte derivate der 4-hydroxy-3-chinolincarbonsaeure, deren herstellung, deren verwendung als arzneimittel, die sie enthaltenden zusammensetzungen und erhaltene zwischenprodukte | |
DE1926359A1 (de) | oxylkansaeuren | |
DE2800015A1 (de) | Neue chromderivate, verfahren zu deren herstellung und diese enthaltende arzneimittel | |
DE2701095A1 (de) | Neue substituierte indole, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen | |
DE2734270C2 (en, 2012) | ||
DE2456098A1 (de) | Xanthen- und thioxanthen-derivate und deren saeureadditionssalze, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische mittel | |
DE3245950A1 (de) | Verfahren zur herstellung substituierter pyridine | |
AT299202B (de) | Verfahren zur Herstellung von neuen substituierten Isochinolinen und von deren Säureadditionssalzen | |
DE2824291A1 (de) | Neue benzylalkoholderivate und verfahren zu ihrer herstellung | |
EP0462150B1 (de) | Neue aryloxy-alkylamine, deren herstellung und diese enthaltende arzneimittel | |
DE2154867A1 (de) | Neue tricyclische Derivate von aliphatischen omega-Aminoalkoholen und Verfahren zu deren Herstellung | |
DE2145682C3 (de) | 1,4-disubstituierte Piperazin-Derivate und deren Säureadditionsverbindungen |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
8110 | Request for examination paragraph 44 | ||
8128 | New person/name/address of the agent |
Representative=s name: ZUMSTEIN SEN., F., DR. ASSMANN, E., DIPL.-CHEM. DR |
|
D2 | Grant after examination | ||
8364 | No opposition during term of opposition | ||
8339 | Ceased/non-payment of the annual fee |