SK282080B6 - Substituované salicylové kyseliny a ich použitie - Google Patents

Substituované salicylové kyseliny a ich použitie Download PDF

Info

Publication number: SK282080B6
Authority: SK; Slovakia
Prior art keywords: hydroxy; methyl; compound; added; solution
Prior art date: 1991-11-18

Application number

SK547-94A

Other languages

English (en)

Slovak (sk)

Other versions

SK54794A3 (en

Inventor

Karl Hubert Agback

Leif Ahrgren

Thomas Berglindh

Martin Haraldsson

Lars-Inge Olsson

G�Ran Smedegard

Original Assignee

Pharmacia Aktiebolag

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.)

1991-11-18

Filing date

1992-11-04

Publication date

2001-10-08

1992-11-04 Application filed by Pharmacia Aktiebolag filed Critical Pharmacia Aktiebolag

1995-02-08 Publication of SK54794A3 publication Critical patent/SK54794A3/sk

2001-10-08 Publication of SK282080B6 publication Critical patent/SK282080B6/sk

Links

150000003870 salicylic acids Chemical class 0.000 title claims abstract description 5
150000001875 compounds Chemical class 0.000 claims abstract description 139
150000003839 salts Chemical class 0.000 claims abstract description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
239000001257 hydrogen Substances 0.000 claims abstract description 12
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
239000012453 solvate Substances 0.000 claims abstract description 12
208000023275 Autoimmune disease Diseases 0.000 claims abstract description 11
125000000217 alkyl group Chemical group 0.000 claims abstract description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
239000003814 drug Substances 0.000 claims abstract description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
125000002619 bicyclic group Chemical group 0.000 claims abstract description 4
125000005907 alkyl ester group Chemical group 0.000 claims abstract description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 73
238000002360 preparation method Methods 0.000 claims description 60
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
-1 C 1 -C 6 alkyl Chemical class 0.000 claims description 24
125000004432 carbon atom Chemical group C* 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical group 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims 1
125000002950 monocyclic group Chemical group 0.000 claims 1
239000000243 solution Substances 0.000 description 110
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 93
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
238000000034 method Methods 0.000 description 73
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 57
230000008569 process Effects 0.000 description 53
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 49
239000000203 mixture Substances 0.000 description 49
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
238000004519 manufacturing process Methods 0.000 description 42
239000011541 reaction mixture Substances 0.000 description 40
239000002904 solvent Substances 0.000 description 40
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
229960001860 salicylate Drugs 0.000 description 29
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical group OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 29
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 28
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 26
238000001816 cooling Methods 0.000 description 25
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
239000000463 material Substances 0.000 description 23
239000007787 solid Substances 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
238000003756 stirring Methods 0.000 description 20
239000000126 substance Substances 0.000 description 19
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
239000002244 precipitate Substances 0.000 description 18
238000001914 filtration Methods 0.000 description 17
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
238000009835 boiling Methods 0.000 description 15
NCEXYHBECQHGNR-UHFFFAOYSA-N chembl421 Chemical group C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
238000012360 testing method Methods 0.000 description 15
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 13
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 13
235000019253 formic acid Nutrition 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
238000001704 evaporation Methods 0.000 description 12
239000000725 suspension Substances 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 11
238000009987 spinning Methods 0.000 description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 10
239000000047 product Substances 0.000 description 10
238000010992 reflux Methods 0.000 description 10
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000002585 base Substances 0.000 description 9
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
230000002829 reductive effect Effects 0.000 description 9
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 9
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical group C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 9
UAHMKJJFOGZIDP-UHFFFAOYSA-N 2-hydroxy-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]ethenyl]benzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(C=CC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 UAHMKJJFOGZIDP-UHFFFAOYSA-N 0.000 description 8
WJLQPSZXCOYTHS-UHFFFAOYSA-N 2-hydroxy-5-[2-[4-[(3-methylpyridin-2-yl)sulfamoyl]phenyl]ethynyl]benzoic acid Chemical compound CC1=CC=CN=C1NS(=O)(=O)C1=CC=C(C#CC=2C=C(C(O)=CC=2)C(O)=O)C=C1 WJLQPSZXCOYTHS-UHFFFAOYSA-N 0.000 description 8
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 8
239000005977 Ethylene Substances 0.000 description 8
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 8
YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 8
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
VTCABGNSRBFUEN-UHFFFAOYSA-N 2-hydroxy-5-[2-[4-[(3-methylpyridin-2-yl)sulfamoyl]phenyl]ethenyl]benzoic acid Chemical compound CC1=CC=CN=C1NS(=O)(=O)C(C=C1)=CC=C1C=CC1=CC=C(O)C(C(O)=O)=C1 VTCABGNSRBFUEN-UHFFFAOYSA-N 0.000 description 7
QOIIQYGCRPHBQJ-UHFFFAOYSA-N 2-methylpropyl 2-hydroxy-5-iodobenzoate Chemical compound CC(C)COC(=O)C1=CC(I)=CC=C1O QOIIQYGCRPHBQJ-UHFFFAOYSA-N 0.000 description 7
229910021595 Copper(I) iodide Inorganic materials 0.000 description 7
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 7
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 7
238000001035 drying Methods 0.000 description 7
210000003714 granulocyte Anatomy 0.000 description 7
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
CDBVOMLNZNWSGH-UHFFFAOYSA-N 4-iodo-n-pyridin-2-ylbenzenesulfonamide Chemical compound C1=CC(I)=CC=C1S(=O)(=O)NC1=CC=CC=N1 CDBVOMLNZNWSGH-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000003610 charcoal Substances 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
229940079593 drug Drugs 0.000 description 6
SYWPABDTTZLUHM-UHFFFAOYSA-N ethyl 2-hydroxy-5-[2-[4-[(3-methylpyridin-2-yl)sulfamoyl]phenyl]ethynyl]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(C#CC=2C=CC(=CC=2)S(=O)(=O)NC=2C(=CC=CN=2)C)=C1 SYWPABDTTZLUHM-UHFFFAOYSA-N 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
229910052763 palladium Inorganic materials 0.000 description 6
150000002941 palladium compounds Chemical class 0.000 description 6
206010039073 rheumatoid arthritis Diseases 0.000 description 6
206010009900 Colitis ulcerative Diseases 0.000 description 5
201000006704 Ulcerative Colitis Diseases 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
239000013078 crystal Substances 0.000 description 5
201000010099 disease Diseases 0.000 description 5
230000000694 effects Effects 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
239000012071 phase Substances 0.000 description 5
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 5
GECHUMIMRBOMGK-UHFFFAOYSA-N sulfapyridine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CC=CC=N1 GECHUMIMRBOMGK-UHFFFAOYSA-N 0.000 description 5
229960002211 sulfapyridine Drugs 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
KJMVGCPQSGCFES-UHFFFAOYSA-N 2-methylpropyl 5-ethenyl-2-hydroxybenzoate Chemical compound CC(C)COC(=O)C1=CC(C=C)=CC=C1O KJMVGCPQSGCFES-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
238000002835 absorbance Methods 0.000 description 4
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
FWLIBCFNGXEMSR-UHFFFAOYSA-N ethyl 4-fluoro-2-hydroxy-5-iodobenzoate Chemical compound CCOC(=O)C1=CC(I)=C(F)C=C1O FWLIBCFNGXEMSR-UHFFFAOYSA-N 0.000 description 4
239000012065 filter cake Substances 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
230000020477 pH reduction Effects 0.000 description 4
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
230000009467 reduction Effects 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
238000001228 spectrum Methods 0.000 description 4
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
KPGJKGJAOSMINR-UHFFFAOYSA-N (4-methylphenyl) 4-iodobenzenesulfonate Chemical compound C1=CC(C)=CC=C1OS(=O)(=O)C1=CC=C(I)C=C1 KPGJKGJAOSMINR-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 3
JJNQWYPLIWCKRB-UHFFFAOYSA-N 2-hydroxy-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]ethynyl]benzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(C#CC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 JJNQWYPLIWCKRB-UHFFFAOYSA-N 0.000 description 3
SWDNKOFGNPGRPI-UHFFFAOYSA-N 2-hydroxy-5-iodobenzoic acid Chemical compound OC(=O)C1=CC(I)=CC=C1O SWDNKOFGNPGRPI-UHFFFAOYSA-N 0.000 description 3
JBDGRJKGTYVSCN-UHFFFAOYSA-N 2-methylpropyl 2-hydroxy-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]ethenyl]benzoate Chemical compound C1=C(O)C(C(=O)OCC(C)C)=CC(C=CC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 JBDGRJKGTYVSCN-UHFFFAOYSA-N 0.000 description 3
RGDQRXPEZUNWHX-UHFFFAOYSA-N 3-methylpyridin-2-amine Chemical compound CC1=CC=CN=C1N RGDQRXPEZUNWHX-UHFFFAOYSA-N 0.000 description 3
GJURZUDJCCSXDC-UHFFFAOYSA-N 4-ethenyl-n-(3-methylpyridin-2-yl)benzenesulfonamide Chemical compound CC1=CC=CN=C1NS(=O)(=O)C1=CC=C(C=C)C=C1 GJURZUDJCCSXDC-UHFFFAOYSA-N 0.000 description 3
HDBJXQPUVPCZND-UHFFFAOYSA-N 4-ethynyl-n-(3-methylpyridin-2-yl)benzenesulfonamide Chemical compound CC1=CC=CN=C1NS(=O)(=O)C1=CC=C(C#C)C=C1 HDBJXQPUVPCZND-UHFFFAOYSA-N 0.000 description 3
YAZFJXLIQSYTMS-UHFFFAOYSA-N 4-fluoro-2-hydroxy-5-[2-[4-[(3-methylpyridin-2-yl)sulfamoyl]phenyl]ethynyl]benzoic acid Chemical compound CC1=CC=CN=C1NS(=O)(=O)C1=CC=C(C#CC=2C(=CC(O)=C(C(O)=O)C=2)F)C=C1 YAZFJXLIQSYTMS-UHFFFAOYSA-N 0.000 description 3
OHAJZNBLNBPKEL-UHFFFAOYSA-N 4-iodo-n-(3-methylpyridin-2-yl)benzenesulfonamide Chemical compound CC1=CC=CN=C1NS(=O)(=O)C1=CC=C(I)C=C1 OHAJZNBLNBPKEL-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
239000005711 Benzoic acid Substances 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
230000004913 activation Effects 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
238000003556 assay Methods 0.000 description 3
235000010233 benzoic acid Nutrition 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 3
229940088679 drug related substance Drugs 0.000 description 3
239000003480 eluent Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
WDYQRLXOLXSMTC-UHFFFAOYSA-N ethyl 2-acetyloxy-5-[2-(4-chlorosulfonylphenyl)ethynyl]benzoate Chemical compound C1=C(OC(C)=O)C(C(=O)OCC)=CC(C#CC=2C=CC(=CC=2)S(Cl)(=O)=O)=C1 WDYQRLXOLXSMTC-UHFFFAOYSA-N 0.000 description 3
WKGNZGPAJWJRDO-UHFFFAOYSA-N ethyl 2-hydroxy-5-iodobenzoate Chemical compound CCOC(=O)C1=CC(I)=CC=C1O WKGNZGPAJWJRDO-UHFFFAOYSA-N 0.000 description 3
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230000002401 inhibitory effect Effects 0.000 description 3
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229910052740 iodine Inorganic materials 0.000 description 3
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239000011707 mineral Substances 0.000 description 3
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229910052757 nitrogen Inorganic materials 0.000 description 3
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239000001632 sodium acetate Substances 0.000 description 3
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235000017557 sodium bicarbonate Nutrition 0.000 description 3
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238000004809 thin layer chromatography Methods 0.000 description 3
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YNZOAEGJZNABCH-UHFFFAOYSA-N 2-hydroxy-5-[2-[4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]ethynyl]benzoic acid Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(=CC=2)C#CC=2C=C(C(O)=CC=2)C(O)=O)=N1 YNZOAEGJZNABCH-UHFFFAOYSA-N 0.000 description 2
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UJPUNLYVVLOSRU-UHFFFAOYSA-N 2-methylpropyl 2-hydroxy-5-[2-[4-[(3-methylpyridin-2-yl)sulfamoyl]phenyl]ethenyl]benzoate Chemical compound C1=C(O)C(C(=O)OCC(C)C)=CC(C=CC=2C=CC(=CC=2)S(=O)(=O)NC=2C(=CC=CN=2)C)=C1 UJPUNLYVVLOSRU-UHFFFAOYSA-N 0.000 description 2
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POXFXTSTVWDWIR-UHFFFAOYSA-N 4-iodobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(I)C=C1 POXFXTSTVWDWIR-UHFFFAOYSA-N 0.000 description 2
PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 2
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VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
108010062580 Concanavalin A Proteins 0.000 description 2
239000005749 Copper compound Substances 0.000 description 2
102000018832 Cytochromes Human genes 0.000 description 2
108010052832 Cytochromes Proteins 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
201000004681 Psoriasis Diseases 0.000 description 2
201000001263 Psoriatic Arthritis Diseases 0.000 description 2
208000036824 Psoriatic arthropathy Diseases 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-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
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FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
UKFWSNCTAHXBQN-UHFFFAOYSA-N ammonium iodide Chemical compound [NH4+].[I-] UKFWSNCTAHXBQN-UHFFFAOYSA-N 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
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229910052794 bromium Inorganic materials 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
238000006555 catalytic reaction Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
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238000010168 coupling process Methods 0.000 description 2
KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 2
238000004821 distillation Methods 0.000 description 2
WHXGVRZJCKTPKK-UHFFFAOYSA-N ethyl 2-hydroxy-5-[2-[4-(4-methylphenoxy)sulfonylphenyl]ethynyl]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(C#CC=2C=CC(=CC=2)S(=O)(=O)OC=2C=CC(C)=CC=2)=C1 WHXGVRZJCKTPKK-UHFFFAOYSA-N 0.000 description 2
XCDHHJALGUKAOQ-UHFFFAOYSA-N ethyl 2-hydroxy-5-[2-[4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]ethynyl]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(C#CC=2C=CC(=CC=2)S(=O)(=O)NC2=NOC(C)=C2)=C1 XCDHHJALGUKAOQ-UHFFFAOYSA-N 0.000 description 2
DTTCLTBLJULMQL-UHFFFAOYSA-N ethyl 4-fluoro-2-hydroxy-5-[2-[4-[(3-methylpyridin-2-yl)sulfamoyl]phenyl]ethynyl]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(C#CC=2C=CC(=CC=2)S(=O)(=O)NC=2C(=CC=CN=2)C)=C1F DTTCLTBLJULMQL-UHFFFAOYSA-N 0.000 description 2
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BVQSLHPKKBHKPI-UHFFFAOYSA-N ethyl 5-[2-(4-chlorosulfonylphenyl)ethynyl]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(C#CC=2C=CC(=CC=2)S(Cl)(=O)=O)=C1 BVQSLHPKKBHKPI-UHFFFAOYSA-N 0.000 description 2
238000000605 extraction Methods 0.000 description 2
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238000005984 hydrogenation reaction Methods 0.000 description 2
230000003301 hydrolyzing effect Effects 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
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208000004396 mastitis Diseases 0.000 description 2
BBZVZEIRSAJKBX-UHFFFAOYSA-N methyl 2-acetyloxy-5-[2-(4-chlorosulfonylphenyl)ethenyl]benzoate Chemical compound C1=C(OC(C)=O)C(C(=O)OC)=CC(C=CC=2C=CC(=CC=2)S(Cl)(=O)=O)=C1 BBZVZEIRSAJKBX-UHFFFAOYSA-N 0.000 description 2
SVSDOLBGZNROSZ-UHFFFAOYSA-N methyl 2-hydroxy-5-(2-trimethylsilylethynyl)benzoate Chemical compound COC(=O)C1=CC(C#C[Si](C)(C)C)=CC=C1O SVSDOLBGZNROSZ-UHFFFAOYSA-N 0.000 description 2
ITOCTEVTMRCLTO-UHFFFAOYSA-N methyl 2-hydroxy-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]ethenyl]benzoate Chemical compound C1=C(O)C(C(=O)OC)=CC(C=CC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 ITOCTEVTMRCLTO-UHFFFAOYSA-N 0.000 description 2
NRSWJTRJHPRZMH-UHFFFAOYSA-N methyl 2-hydroxy-5-iodobenzoate Chemical compound COC(=O)C1=CC(I)=CC=C1O NRSWJTRJHPRZMH-UHFFFAOYSA-N 0.000 description 2
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
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PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
235000011056 potassium acetate Nutrition 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
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VSWVMBDCAQHNLC-UHFFFAOYSA-N propan-2-yl 5-ethenyl-2-hydroxybenzoate Chemical compound CC(C)OC(=O)C1=CC(C=C)=CC=C1O VSWVMBDCAQHNLC-UHFFFAOYSA-N 0.000 description 2
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239000011734 sodium Substances 0.000 description 2
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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
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LZSFYFURKZAZOU-UHFFFAOYSA-N 2-acetylbenzenesulfonyl chloride Chemical compound CC(=O)C1=CC=CC=C1S(Cl)(=O)=O LZSFYFURKZAZOU-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- 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]
- 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
- A61P37/02—Immunomodulators
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-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
- C07D237/20—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
- C07D261/14—Nitrogen atoms
- C07D261/16—Benzene-sulfonamido isoxazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
- C07D277/82—Nitrogen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Immunology (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Transplantation (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyridine Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Thiazole And Isothizaole Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

SK547-94A 1991-11-18 1992-11-04 Substituované salicylové kyseliny a ich použitie SK282080B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9103397A SE9103397D0 (sv)	1991-11-18	1991-11-18	Nya substituerade salicylsyror
PCT/SE1992/000758 WO1993010094A1 (en)	1991-11-18	1992-11-04	Novel substituted salicyclic acids

Publications (2)

Publication Number	Publication Date
SK54794A3 SK54794A3 (en)	1995-02-08
SK282080B6 true SK282080B6 (sk)	2001-10-08

Family

ID=20384352

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK547-94A SK282080B6 (sk)	1991-11-18	1992-11-04	Substituované salicylové kyseliny a ich použitie

Country Status (29)

Country	Link
US (3)	US5302718A (pl)
EP (1)	EP0613468B1 (pl)
JP (1)	JP3259915B2 (pl)
KR (1)	KR100253748B1 (pl)
AT (1)	ATE194597T1 (pl)
AU (1)	AU668528B2 (pl)
CA (1)	CA2123697C (pl)
DE (1)	DE69231252T2 (pl)
DK (1)	DK0613468T3 (pl)
EE (1)	EE03026B1 (pl)
ES (1)	ES2149780T3 (pl)
FI (1)	FI106857B (pl)
GR (1)	GR3034585T3 (pl)
HU (2)	HU221476B (pl)
IL (1)	IL103665A (pl)
LT (1)	LT3182B (pl)
LV (1)	LV10246B (pl)
MX (1)	MX9206647A (pl)
MY (1)	MY130169A (pl)
NO (1)	NO300805B1 (pl)
NZ (1)	NZ244998A (pl)
PT (1)	PT101068B (pl)
RU (1)	RU2124501C1 (pl)
SE (1)	SE9103397D0 (pl)
SK (1)	SK282080B6 (pl)
TW (1)	TW304944B (pl)
UA (1)	UA42869C2 (pl)
WO (1)	WO1993010094A1 (pl)
ZA (1)	ZA928864B (pl)

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EP1093362A1 (en)	1998-06-12	2001-04-25	Ligand Pharmaceuticals Incorporated	Treatment of anti-estrogen resistant breast cancer using rxr modulators
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ATE344237T1 (de)	1999-09-04	2006-11-15	Astrazeneca Ab	Hydroxyacetamidobenzolsulfonamidderivate
ATE311189T1 (de) *	2000-04-28	2005-12-15	Univ British Columbia	N-heterosubstituierten salicylaten zur behandlung von krebs
CA2307278A1 (en) *	2000-04-28	2001-10-28	University Of British Columbia	Use of n-heterocyclic substituted salicylic acids for inhibition of cellular uptake of cystine
US6639082B2 (en)	2000-10-17	2003-10-28	Bristol-Myers Squibb Company	Methods for the preparation of biphenyl isoxazole sulfonamides
JPWO2005023771A1 (ja) *	2003-09-05	2006-11-02	小野薬品工業株式会社	ケモカインレセプターアンタゴニストおよびその医薬用途
WO2005060963A1 (en) *	2003-12-19	2005-07-07	Pfizer Inc.	Benzenesulfonylamino-pyridin-2-yl derivatives and related compounds as inhibitors of 11-beta-hydroxysteroid dehydrogenase type 1 (11-beta-hsd-1) for the treatment of diabetes and obesity
CA2572119A1 (en) *	2004-06-29	2006-01-12	Warner-Lambert Company Llc	Combination therapies utilizing benzamide inhibitors of the p2x7 receptor
GB2421947A (en) *	2005-01-07	2006-07-12	Univ Southampton	Sulphonamide compounds for use as inhibitors of NF-kB
CA2643963A1 (en) *	2006-02-21	2007-08-30	Amgen Inc.	Cinnoline derivatives as phosphodiesterase 10 inhibitors
KR20110027648A (ko) *	2008-06-23	2011-03-16	아스테라스 세이야쿠 가부시키가이샤	술폰아미드 화합물 또는 이의 염
AU2012220620A1 (en) *	2011-02-23	2013-10-03	Icahn School Of Medicine At Mount Sinai	Inhibitors of bromodomains as modulators of gene expression
HUE050317T2 (hu)	2015-05-20	2020-11-30	Amgen Inc	APJ receptor triazol agonistái
US20190016680A1 (en)	2016-01-14	2019-01-17	Beth Israel Deaconess Medical Center, Inc.	Mast-cell modulators and uses thereof
WO2017192485A1 (en)	2016-05-03	2017-11-09	Amgen Inc.	Heterocyclic triazole compounds as agonists of the apj receptor
EP3541805B1 (en)	2016-11-16	2020-10-14	Amgen Inc.	Heteroaryl-substituted triazoles as apj receptor agonists
WO2018097944A1 (en)	2016-11-16	2018-05-31	Amgen Inc.	Triazole furan compounds as agonists of the apj receptor
EP3541803B1 (en)	2016-11-16	2020-12-23	Amgen Inc.	Triazole pyridyl compounds as agonists of the apj receptor
EP3541802B1 (en)	2016-11-16	2025-01-01	Amgen Inc.	Alkyl substituted triazole compounds as agonists of the apj receptor
WO2018093579A1 (en)	2016-11-16	2018-05-24	Amgen Inc.	Triazole phenyl compounds as agonists of the apj receptor
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1991
- 1991-11-18 SE SE9103397A patent/SE9103397D0/xx unknown
1992
- 1992-11-03 NZ NZ244998A patent/NZ244998A/en not_active IP Right Cessation
- 1992-11-04 ES ES92924067T patent/ES2149780T3/es not_active Expired - Lifetime
- 1992-11-04 DE DE69231252T patent/DE69231252T2/de not_active Expired - Fee Related
- 1992-11-04 WO PCT/SE1992/000758 patent/WO1993010094A1/en active IP Right Grant
- 1992-11-04 UA UA94005499A patent/UA42869C2/uk unknown
- 1992-11-04 AT AT92924067T patent/ATE194597T1/de not_active IP Right Cessation
- 1992-11-04 EP EP92924067A patent/EP0613468B1/en not_active Expired - Lifetime
- 1992-11-04 SK SK547-94A patent/SK282080B6/sk unknown
- 1992-11-04 RU RU94028109A patent/RU2124501C1/ru not_active IP Right Cessation
- 1992-11-04 KR KR1019940701664A patent/KR100253748B1/ko not_active Expired - Fee Related
- 1992-11-04 AU AU29589/92A patent/AU668528B2/en not_active Ceased
- 1992-11-04 JP JP50919193A patent/JP3259915B2/ja not_active Expired - Fee Related
- 1992-11-04 CA CA002123697A patent/CA2123697C/en not_active Expired - Fee Related
- 1992-11-04 HU HU9401391A patent/HU221476B/hu not_active IP Right Cessation
- 1992-11-04 DK DK92924067T patent/DK0613468T3/da active
- 1992-11-06 IL IL10366592A patent/IL103665A/xx not_active IP Right Cessation
- 1992-11-09 US US07/973,753 patent/US5302718A/en not_active Expired - Lifetime
- 1992-11-13 LV LVP-92-202A patent/LV10246B/xx unknown
- 1992-11-17 MY MYPI92002100A patent/MY130169A/en unknown
- 1992-11-17 LT LTIP229A patent/LT3182B/lt not_active IP Right Cessation
- 1992-11-17 PT PT101068A patent/PT101068B/pt not_active IP Right Cessation
- 1992-11-17 ZA ZA928864A patent/ZA928864B/xx unknown
- 1992-11-18 MX MX9206647A patent/MX9206647A/es not_active IP Right Cessation
- 1992-11-27 TW TW081109532A patent/TW304944B/zh active
1993
- 1993-10-07 US US08/132,874 patent/US5403930A/en not_active Expired - Fee Related
1994
- 1994-05-13 NO NO941799A patent/NO300805B1/no unknown
- 1994-05-17 FI FI942289A patent/FI106857B/fi not_active IP Right Cessation
- 1994-11-02 EE EE9400111A patent/EE03026B1/xx not_active IP Right Cessation
- 1994-12-29 US US08/365,869 patent/US5556855A/en not_active Expired - Fee Related
1995
- 1995-06-28 HU HU95P/P00492P patent/HU211163A9/hu unknown
2000
- 2000-10-09 GR GR20000402274T patent/GR3034585T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
AU668528B2 (en)	1996-05-09
DE69231252T2 (de)	2001-03-01
AU2958992A (en)	1993-06-15
US5403930A (en)	1995-04-04
US5556855A (en)	1996-09-17
NO941799L (pl)	1994-06-22
FI942289L (fi)	1994-05-17
EP0613468B1 (en)	2000-07-12
JP3259915B2 (ja)	2002-02-25
MY130169A (en)	2007-06-29
LT3182B (en)	1995-03-27
CA2123697C (en)	2003-12-09
RU2124501C1 (ru)	1999-01-10
NZ244998A (en)	1995-09-26
CA2123697A1 (en)	1993-05-27
LTIP229A (en)	1994-09-25
EP0613468A1 (en)	1994-09-07
DK0613468T3 (da)	2000-10-23
PT101068A (pt)	1994-02-28
JPH07501330A (ja)	1995-02-09
NO300805B1 (no)	1997-07-28
MX9206647A (es)	1993-05-01
KR100253748B1 (ko)	2000-05-01
IL103665A (en)	1997-08-14
LV10246B (en)	1995-04-20
TW304944B (pl)	1997-05-11
HUT69723A (en)	1995-09-28
ATE194597T1 (de)	2000-07-15
PT101068B (pt)	1999-08-31
ZA928864B (en)	1993-05-13
LV10246A (lv)	1994-10-20
FI106857B (fi)	2001-04-30
SK54794A3 (en)	1995-02-08
IL103665A0 (en)	1993-04-04
HU9401391D0 (en)	1994-08-29
NO941799D0 (no)	1994-05-13
HU221476B (en)	2002-10-28
SE9103397D0 (sv)	1991-11-18
HU211163A9 (en)	1995-10-30
GR3034585T3 (en)	2001-01-31
ES2149780T3 (es)	2000-11-16
WO1993010094A1 (en)	1993-05-27
FI942289A0 (fi)	1994-05-17
EE03026B1 (et)	1997-08-15
DE69231252D1 (de)	2000-08-17
UA42869C2 (uk)	2001-11-15
US5302718A (en)	1994-04-12

Publication	Publication Date	Title
SK282080B6 (sk)	2001-10-08	Substituované salicylové kyseliny a ich použitie
US20070072914A1 (en)	2007-03-29	N-(pyridin-2-yl)-sulfonamide derivatives
EP0288973B1 (en)	1993-01-13	Benzothiazolinone derivatives, their production and pharmaceutical composition
WO1999062892A1 (en)	1999-12-09	Aminoazole compounds
JPH11269140A (ja)	1999-10-05	分化誘導剤
JP2003505367A (ja)	2003-02-12	マトリックスメタロプロテイナーゼ阻害剤としての３−アリールスルホニル−２−（置換メチル）プロパン酸誘導体
US6727266B2 (en)	2004-04-27	Substituted tryptophan derivatives
EP0315115B1 (en)	1994-06-15	1-acyl-2,3-dihydro-4(1H)-quinolinone-4-oxime derivatives, process for producing them and use thereof
EP0686631A1 (en)	1995-12-13	Pyrimidine derivatives and pharmaceutical composition
US5232922A (en)	1993-08-03	Imidazole compounds, processes for their preparation, pharmaceuticals based on these compounds and some intermediates
JP2860688B2 (ja)	1999-02-24	インドール誘導体
CZ287285B6 (cs)	2000-10-11	Nové substituované salicylové kyseliny
JPH09176165A (ja)	1997-07-08	イミダゾ［１，２−ａ］ピリジン誘導体、その製法およびその用途
JPH07101941A (ja)	1995-04-18	２−［２−（置換アミノ）ベンジルチオ］−５，６，７，８−テトラヒドロ−４（３ｈ）−キナゾリノン誘導体
JPH05112559A (ja)	1993-05-07	４−アミノ−５−ピリミジンカルボン酸誘導体
JPH05279336A (ja)	1993-10-26	フェノキシ酢酸誘導体
JPH05262736A (ja)	1993-10-12	フェノキシ酢酸誘導体
JPH068296B2 (ja)	1994-02-02	アミノクロマノール誘導体
JPH05262763A (ja)	1993-10-12	２−〔（１ｈ−ベンズイミダゾール−２−イル）スルフィニルメチル〕−４−置換アミノ−５−ピリミジンカルボン酸誘導体
JPH0641051A (ja)	1994-02-15	フェノキシ酢酸誘導体
JPS63250374A (ja)	1988-10-18	〔２−（１，３−ベンゾジオキソ−ル−５−イル）エチル〕チオ誘導体
JPH07330769A (ja)	1995-12-19	２−［２−（置換アミノ）ベンジルチオ］−５，６，７，８−テトラヒドロピリド［４，３−ｄ］ピリミジン−４（３Ｈ）−オン誘導体
JPH06100541A (ja)	1994-04-12	ピラゾリノン誘導体