DE60129445T2 - Quinolin-derivate als antientzündungsmittel - Google Patents
Quinolin-derivate als antientzündungsmittel Download PDFInfo
- Publication number
- DE60129445T2 DE60129445T2 DE60129445T DE60129445T DE60129445T2 DE 60129445 T2 DE60129445 T2 DE 60129445T2 DE 60129445 T DE60129445 T DE 60129445T DE 60129445 T DE60129445 T DE 60129445T DE 60129445 T2 DE60129445 T2 DE 60129445T2
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- compound
- methoxy
- phenyl
- methanesulfonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title description 26
- 239000002260 anti-inflammatory agent Substances 0.000 title description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 title description 2
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
- -1 4-substituted phenyl Chemical group 0.000 claims description 175
- 150000001875 compounds Chemical class 0.000 claims description 149
- 125000000217 alkyl group Chemical group 0.000 claims description 100
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 77
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 70
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 28
- 239000000460 chlorine Substances 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 230000003647 oxidation Effects 0.000 claims description 11
- 238000007254 oxidation reaction Methods 0.000 claims description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 7
- 239000007800 oxidant agent Substances 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000025978 Athletic injury Diseases 0.000 claims description 4
- 206010006811 Bursitis Diseases 0.000 claims description 4
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 4
- 201000005569 Gout Diseases 0.000 claims description 4
- 206010019233 Headaches Diseases 0.000 claims description 4
- 201000002481 Myositis Diseases 0.000 claims description 4
- 208000010040 Sprains and Strains Diseases 0.000 claims description 4
- 208000000491 Tendinopathy Diseases 0.000 claims description 4
- 206010043255 Tendonitis Diseases 0.000 claims description 4
- 231100000869 headache Toxicity 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 201000004595 synovitis Diseases 0.000 claims description 4
- 201000004415 tendinitis Diseases 0.000 claims description 4
- 208000004371 toothache Diseases 0.000 claims description 4
- 208000008035 Back Pain Diseases 0.000 claims description 3
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 3
- 125000005171 cycloalkylsulfanyl group Chemical group 0.000 claims description 3
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 208000005107 Premature Birth Diseases 0.000 claims 1
- 206010036590 Premature baby Diseases 0.000 claims 1
- 208000019804 backache Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 43
- 239000000243 solution Substances 0.000 description 42
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 22
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 238000012360 testing method Methods 0.000 description 21
- 241000700159 Rattus Species 0.000 description 19
- 239000000047 product Substances 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 230000003110 anti-inflammatory effect Effects 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 125000001153 fluoro group Chemical group F* 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 150000003180 prostaglandins Chemical class 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000004215 Carbon black (E152) Substances 0.000 description 8
- 230000000202 analgesic effect Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 229930195733 hydrocarbon Natural products 0.000 description 8
- 125000003884 phenylalkyl group Chemical group 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 7
- 239000000679 carrageenan Substances 0.000 description 7
- 235000010418 carrageenan Nutrition 0.000 description 7
- 229920001525 carrageenan Polymers 0.000 description 7
- 229940113118 carrageenan Drugs 0.000 description 7
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 7
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 7
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 6
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- AREWYRAETFMKAH-UHFFFAOYSA-N 1-sulfidoquinolin-1-ium Chemical compound C1=CC=C2[N+]([S-])=CC=CC2=C1 AREWYRAETFMKAH-UHFFFAOYSA-N 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 210000000548 hind-foot Anatomy 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- 238000010189 synthetic method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- ZFEJTYQUWRVCFW-UHFFFAOYSA-N 2-chloro-6-methoxyquinoline Chemical compound N1=C(Cl)C=CC2=CC(OC)=CC=C21 ZFEJTYQUWRVCFW-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 125000004104 aryloxy group Chemical group 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 125000004663 dialkyl amino group Chemical group 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000008282 halocarbons Chemical class 0.000 description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 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
- 239000004615 ingredient Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 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 4
- 239000003880 polar aprotic solvent Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000006177 thiolation reaction Methods 0.000 description 4
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- WPLABWLKEPFOSQ-UHFFFAOYSA-N 5-(2,4-difluorophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=C(F)C=C1F WPLABWLKEPFOSQ-UHFFFAOYSA-N 0.000 description 3
- OIYRFJFOTTZCJL-UHFFFAOYSA-N 5-(4-fluorophenyl)sulfanyl-2-methylsulfonylquinolin-6-ol Chemical compound OC=1C=CC2=NC(S(=O)(=O)C)=CC=C2C=1SC1=CC=C(F)C=C1 OIYRFJFOTTZCJL-UHFFFAOYSA-N 0.000 description 3
- XEMZUOZUYGPCSL-UHFFFAOYSA-N 6-methoxy-2-methylsulfonylquinoline Chemical compound N1=C(S(C)(=O)=O)C=CC2=CC(OC)=CC=C21 XEMZUOZUYGPCSL-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- OQHHSGRZCKGLCY-UHFFFAOYSA-N 8-nitroquinoline Chemical compound C1=CN=C2C([N+](=O)[O-])=CC=CC2=C1 OQHHSGRZCKGLCY-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 206010009944 Colon cancer Diseases 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 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
- 241001465754 Metazoa Species 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 239000012425 OXONE® Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical compound C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 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 3
- 239000002253 acid Substances 0.000 description 3
- 125000004442 acylamino group Chemical group 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 3
- 239000008135 aqueous vehicle Substances 0.000 description 3
- 125000005199 aryl carbonyloxy group Chemical group 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 3
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 3
- 210000000416 exudates and transudate Anatomy 0.000 description 3
- 210000002683 foot Anatomy 0.000 description 3
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229940124531 pharmaceutical excipient Drugs 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 3
- UZOLLAZNQYGQJJ-UHFFFAOYSA-N (6-methoxy-2-methylsulfonylquinolin-5-yl)-(4-methoxyphenyl)methanol Chemical compound C1=CC(OC)=CC=C1C(O)C1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 UZOLLAZNQYGQJJ-UHFFFAOYSA-N 0.000 description 2
- RGVSBESKUVTHKQ-UHFFFAOYSA-N (6-methoxy-2-methylsulfonylquinolin-5-yl)-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)C1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 RGVSBESKUVTHKQ-UHFFFAOYSA-N 0.000 description 2
- NHDODQWIKUYWMW-UHFFFAOYSA-N 1-bromo-4-chlorobenzene Chemical compound ClC1=CC=C(Br)C=C1 NHDODQWIKUYWMW-UHFFFAOYSA-N 0.000 description 2
- WVUYYXUATWMVIT-UHFFFAOYSA-N 1-bromo-4-ethoxybenzene Chemical compound CCOC1=CC=C(Br)C=C1 WVUYYXUATWMVIT-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- BICHBFCGCJNCAT-UHFFFAOYSA-N 2,4-difluorobenzenethiol Chemical compound FC1=CC=C(S)C(F)=C1 BICHBFCGCJNCAT-UHFFFAOYSA-N 0.000 description 2
- NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- DVCWPXUKHGBGMH-UHFFFAOYSA-N 2-bromo-1-sulfidoquinolin-1-ium Chemical compound C1=CC=C2[N+]([S-])=C(Br)C=CC2=C1 DVCWPXUKHGBGMH-UHFFFAOYSA-N 0.000 description 2
- LAHWVDUZLRNQDG-UHFFFAOYSA-N 2-chloro-5-(2,4-difluorophenoxy)-6-methoxyquinoline Chemical compound COC1=CC=C2N=C(Cl)C=CC2=C1OC1=CC=C(F)C=C1F LAHWVDUZLRNQDG-UHFFFAOYSA-N 0.000 description 2
- MLMQPDHYNJCQAO-UHFFFAOYSA-N 3,3-dimethylbutyric acid Chemical compound CC(C)(C)CC(O)=O MLMQPDHYNJCQAO-UHFFFAOYSA-N 0.000 description 2
- LKVFCSWBKOVHAH-UHFFFAOYSA-N 4-Ethoxyphenol Chemical compound CCOC1=CC=C(O)C=C1 LKVFCSWBKOVHAH-UHFFFAOYSA-N 0.000 description 2
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 2
- BQNCMAKOHJSBDH-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-methoxy-1-oxidoquinolin-1-ium Chemical compound COC1=CC=C2[N+]([O-])=CC=CC2=C1OC1=CC=C(F)C=C1F BQNCMAKOHJSBDH-UHFFFAOYSA-N 0.000 description 2
- YOWLQPNYLXHBBF-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-methoxy-1h-quinolin-2-one Chemical compound COC1=CC=C2NC(=O)C=CC2=C1OC1=CC=C(F)C=C1F YOWLQPNYLXHBBF-UHFFFAOYSA-N 0.000 description 2
- DNDQWFMQJTZDBK-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1OC1=CC=C(F)C=C1F DNDQWFMQJTZDBK-UHFFFAOYSA-N 0.000 description 2
- KUFMMTNIRHOQEH-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-methoxy-8-nitroquinoline Chemical compound COC1=CC([N+]([O-])=O)=C2N=CC=CC2=C1OC1=CC=C(F)C=C1F KUFMMTNIRHOQEH-UHFFFAOYSA-N 0.000 description 2
- BOOKSKOWMREWGZ-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-methoxyquinolin-8-amine Chemical compound COC1=CC(N)=C2N=CC=CC2=C1OC1=CC=C(F)C=C1F BOOKSKOWMREWGZ-UHFFFAOYSA-N 0.000 description 2
- QEXDEIXMNUBTTG-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-methoxyquinoline Chemical compound COC1=CC=C2N=CC=CC2=C1OC1=CC=C(F)C=C1F QEXDEIXMNUBTTG-UHFFFAOYSA-N 0.000 description 2
- PFZDNCWNMYTJLP-UHFFFAOYSA-N 5-(2,4-difluorophenyl)sulfinyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1S(=O)C1=CC=C(F)C=C1F PFZDNCWNMYTJLP-UHFFFAOYSA-N 0.000 description 2
- IATNJUAVOVWUFH-UHFFFAOYSA-N 5-(4-fluorophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=C(F)C=C1 IATNJUAVOVWUFH-UHFFFAOYSA-N 0.000 description 2
- JDCKYIARAZSFNM-UHFFFAOYSA-N 5-[(2,4-difluorophenyl)methyl]-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1CC1=CC=C(F)C=C1F JDCKYIARAZSFNM-UHFFFAOYSA-N 0.000 description 2
- ZYURLHXGBCKVLU-UHFFFAOYSA-N 5-bromo-2-chloro-6-methoxyquinoline Chemical compound N1=C(Cl)C=CC2=C(Br)C(OC)=CC=C21 ZYURLHXGBCKVLU-UHFFFAOYSA-N 0.000 description 2
- FWLKBJXOEUBXEB-UHFFFAOYSA-N 5-bromo-6-methoxy-2-methylsulfonylquinoline Chemical compound N1=C(S(C)(=O)=O)C=CC2=C(Br)C(OC)=CC=C21 FWLKBJXOEUBXEB-UHFFFAOYSA-N 0.000 description 2
- FELNBLNDYLAJLB-UHFFFAOYSA-N 5-bromo-8-nitroquinoline Chemical compound C1=CN=C2C([N+](=O)[O-])=CC=C(Br)C2=C1 FELNBLNDYLAJLB-UHFFFAOYSA-N 0.000 description 2
- WREVVZMUNPAPOV-UHFFFAOYSA-N 8-aminoquinoline Chemical compound C1=CN=C2C(N)=CC=CC2=C1 WREVVZMUNPAPOV-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 208000006399 Premature Obstetric Labor Diseases 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
- 150000005840 aryl radicals Chemical group 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000004768 bromobenzenes Chemical class 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 125000005518 carboxamido group Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 229960000616 diflunisal Drugs 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 2
- 150000002066 eicosanoids Chemical class 0.000 description 2
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- MSHFRERJPWKJFX-UHFFFAOYSA-N para-methoxybenzyl alcohol Natural products COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 229940127293 prostanoid Drugs 0.000 description 2
- 150000003814 prostanoids Chemical class 0.000 description 2
- WDXARTMCIRVMAE-UHFFFAOYSA-N quinoline-2-carbonitrile Chemical compound C1=CC=CC2=NC(C#N)=CC=C21 WDXARTMCIRVMAE-UHFFFAOYSA-N 0.000 description 2
- YHQSXWOXIHDVHQ-UHFFFAOYSA-N quinoline;hydrobromide Chemical compound [Br-].[NH+]1=CC=CC2=CC=CC=C21 YHQSXWOXIHDVHQ-UHFFFAOYSA-N 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- ZUHZGEOKBKGPSW-UHFFFAOYSA-N tetraglyme Chemical compound COCCOCCOCCOCCOC ZUHZGEOKBKGPSW-UHFFFAOYSA-N 0.000 description 2
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 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
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- WPJAHFYOACWPNA-UHFFFAOYSA-M zinc;2,4-difluoro-1-methanidylbenzene;bromide Chemical compound Br[Zn+].[CH2-]C1=CC=C(F)C=C1F WPJAHFYOACWPNA-UHFFFAOYSA-M 0.000 description 2
- GWEQGODFIGKZFJ-UHFFFAOYSA-N (2,4-difluorophenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=CC=C(F)C=C1F GWEQGODFIGKZFJ-UHFFFAOYSA-N 0.000 description 1
- ZMBXLYKOQIMIRD-UHFFFAOYSA-N (2,6-difluorophenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=C(F)C=CC=C1F ZMBXLYKOQIMIRD-UHFFFAOYSA-N 0.000 description 1
- ADZHQOWNKJUEOP-UHFFFAOYSA-N (2-chloro-4-methoxyphenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound ClC1=CC(OC)=CC=C1C(=O)C1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 ADZHQOWNKJUEOP-UHFFFAOYSA-N 0.000 description 1
- XEXVPWVHKWHTPK-UHFFFAOYSA-N (2-fluorophenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=CC=CC=C1F XEXVPWVHKWHTPK-UHFFFAOYSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- ZDWFHLMFDLTTNS-UHFFFAOYSA-N (3-bromo-2,6-difluorophenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=C(F)C=CC(Br)=C1F ZDWFHLMFDLTTNS-UHFFFAOYSA-N 0.000 description 1
- QVHKHIXIAJLNKE-UHFFFAOYSA-N (3-chloro-2-fluoro-6-methoxyphenyl)-(6-methoxy-2-methylsulfinylquinolin-5-yl)methanone Chemical compound COC1=CC=C(Cl)C(F)=C1C(=O)C1=C(OC)C=CC2=NC(S(C)=O)=CC=C12 QVHKHIXIAJLNKE-UHFFFAOYSA-N 0.000 description 1
- KLIRAUYQRSKMSX-UHFFFAOYSA-N (3-chloro-2-fluoro-6-methoxyphenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound COC1=CC=C(Cl)C(F)=C1C(=O)C1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 KLIRAUYQRSKMSX-UHFFFAOYSA-N 0.000 description 1
- DBDYPCDOHXSTBH-UHFFFAOYSA-N (4-chlorophenyl)-(6-methoxy-2-methylsulfinylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)=O)C=CC2=C1C(=O)C1=CC=C(Cl)C=C1 DBDYPCDOHXSTBH-UHFFFAOYSA-N 0.000 description 1
- JCIOMLCCLYSJTK-UHFFFAOYSA-N (4-chlorophenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=CC=C(Cl)C=C1 JCIOMLCCLYSJTK-UHFFFAOYSA-N 0.000 description 1
- GLYWXMPETYGAML-UHFFFAOYSA-N (4-ethoxyphenyl)-(6-methoxy-2-methylsulfinylquinolin-5-yl)methanone Chemical compound C1=CC(OCC)=CC=C1C(=O)C1=C(OC)C=CC2=NC(S(C)=O)=CC=C12 GLYWXMPETYGAML-UHFFFAOYSA-N 0.000 description 1
- FAOQQCLMOCEISC-UHFFFAOYSA-N (4-ethoxyphenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound C1=CC(OCC)=CC=C1C(=O)C1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 FAOQQCLMOCEISC-UHFFFAOYSA-N 0.000 description 1
- ODLBIFBFUSGGTO-UHFFFAOYSA-N (4-fluorophenyl)-(6-methoxy-2-methylsulfinylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)=O)C=CC2=C1C(=O)C1=CC=C(F)C=C1 ODLBIFBFUSGGTO-UHFFFAOYSA-N 0.000 description 1
- YOYKAJVWPHPEFI-UHFFFAOYSA-N (4-fluorophenyl)-(6-methoxy-2-methylsulfonylquinolin-5-yl)methanone Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1C(=O)C1=CC=C(F)C=C1 YOYKAJVWPHPEFI-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical class C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- MGHBDQZXPCTTIH-UHFFFAOYSA-N 1-bromo-2,4-difluorobenzene Chemical compound FC1=CC=C(Br)C(F)=C1 MGHBDQZXPCTTIH-UHFFFAOYSA-N 0.000 description 1
- IPWBFGUBXWMIPR-UHFFFAOYSA-N 1-bromo-2-fluorobenzene Chemical compound FC1=CC=CC=C1Br IPWBFGUBXWMIPR-UHFFFAOYSA-N 0.000 description 1
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
- FAVMSTGWFRDCRR-UHFFFAOYSA-N 1-chloro-2-fluoro-4-methoxybenzene Chemical compound COC1=CC=C(Cl)C(F)=C1 FAVMSTGWFRDCRR-UHFFFAOYSA-N 0.000 description 1
- AMMPLVWPWSYRDR-UHFFFAOYSA-N 1-methylbicyclo[2.2.2]oct-2-ene-4-carboxylic acid Chemical compound C1CC2(C(O)=O)CCC1(C)C=C2 AMMPLVWPWSYRDR-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- UVAMFBJPMUMURT-UHFFFAOYSA-N 2,3,4,5,6-pentafluorobenzenethiol Chemical compound FC1=C(F)C(F)=C(S)C(F)=C1F UVAMFBJPMUMURT-UHFFFAOYSA-N 0.000 description 1
- FGBVJFREPSJSNG-UHFFFAOYSA-N 2,4-dichlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1Cl FGBVJFREPSJSNG-UHFFFAOYSA-N 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- SOWRUJSGHKNOKN-UHFFFAOYSA-N 2,6-difluorobenzaldehyde Chemical compound FC1=CC=CC(F)=C1C=O SOWRUJSGHKNOKN-UHFFFAOYSA-N 0.000 description 1
- PALORHWWZVBSLZ-UHFFFAOYSA-N 2,6-difluorobenzenethiol Chemical compound FC1=CC=CC(F)=C1S PALORHWWZVBSLZ-UHFFFAOYSA-N 0.000 description 1
- CKKOVFGIBXCEIJ-UHFFFAOYSA-N 2,6-difluorophenol Chemical compound OC1=C(F)C=CC=C1F CKKOVFGIBXCEIJ-UHFFFAOYSA-N 0.000 description 1
- HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical class O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- KUAPPJSILOMQPC-UHFFFAOYSA-N 2-chloro-4-fluorobenzenethiol Chemical compound FC1=CC=C(S)C(Cl)=C1 KUAPPJSILOMQPC-UHFFFAOYSA-N 0.000 description 1
- YWGKOEQZKMSICW-UHFFFAOYSA-N 2-chloro-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C(Cl)=C1 YWGKOEQZKMSICW-UHFFFAOYSA-N 0.000 description 1
- MHEVJFMRUJDOHH-UHFFFAOYSA-N 2-chloro-4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C(Cl)=C1 MHEVJFMRUJDOHH-UHFFFAOYSA-N 0.000 description 1
- GNVRRKLFFYSLGT-UHFFFAOYSA-N 2-chloro-4-methoxyphenol Chemical compound COC1=CC=C(O)C(Cl)=C1 GNVRRKLFFYSLGT-UHFFFAOYSA-N 0.000 description 1
- PWOBDMNCYMQTCE-UHFFFAOYSA-N 2-chlorobenzenethiol Chemical compound SC1=CC=CC=C1Cl PWOBDMNCYMQTCE-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 229940093475 2-ethoxyethanol Drugs 0.000 description 1
- OBTRUKKHXQYRDD-UHFFFAOYSA-N 2-fluoro-4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C(F)=C1 OBTRUKKHXQYRDD-UHFFFAOYSA-N 0.000 description 1
- OVEMQCGVMRIIHW-UHFFFAOYSA-N 2-fluoro-4-methylsulfonylphenol Chemical compound CS(=O)(=O)C1=CC=C(O)C(F)=C1 OVEMQCGVMRIIHW-UHFFFAOYSA-N 0.000 description 1
- JGTRAUKVXOMUKV-UHFFFAOYSA-N 2-fluoro-6-methylsulfonylphenol Chemical compound CS(=O)(=O)C1=CC=CC(F)=C1O JGTRAUKVXOMUKV-UHFFFAOYSA-N 0.000 description 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
- BOJGOZZDGAVVCC-UHFFFAOYSA-N 3-[(2,4-difluorophenyl)methyl]-6-methoxy-2-methylsulfonylquinoline Chemical compound C=1C2=CC(OC)=CC=C2N=C(S(C)(=O)=O)C=1CC1=CC=C(F)C=C1F BOJGOZZDGAVVCC-UHFFFAOYSA-N 0.000 description 1
- BMUDPLZKKRQECS-UHFFFAOYSA-K 3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoic acid iron(3+) hydroxide Chemical compound [OH-].[Fe+3].[N-]1C2=C(C)C(CCC(O)=O)=C1C=C([N-]1)C(CCC(O)=O)=C(C)C1=CC(C(C)=C1C=C)=NC1=CC(C(C)=C1C=C)=NC1=C2 BMUDPLZKKRQECS-UHFFFAOYSA-K 0.000 description 1
- OXBHKEYDKAWFLS-UHFFFAOYSA-N 3-bromo-2,6-difluorobenzaldehyde Chemical compound FC1=CC=C(Br)C(F)=C1C=O OXBHKEYDKAWFLS-UHFFFAOYSA-N 0.000 description 1
- MNUYBJWIKBRXSA-UHFFFAOYSA-N 3-chloro-2-fluoro-6-methoxybenzaldehyde Chemical compound COC1=CC=C(Cl)C(F)=C1C=O MNUYBJWIKBRXSA-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- OKIHXNKYYGUVTE-UHFFFAOYSA-N 4-Fluorothiophenol Chemical compound FC1=CC=C(S)C=C1 OKIHXNKYYGUVTE-UHFFFAOYSA-N 0.000 description 1
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical compound SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 1
- ZQZQPQBXQIUSOT-UHFFFAOYSA-N 4-fluoro-2-methoxybenzenethiol Chemical compound COC1=CC(F)=CC=C1S ZQZQPQBXQIUSOT-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- ZNERZAJVUFOYOR-UHFFFAOYSA-N 5-(2,4-dichlorophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=C(Cl)C=C1Cl ZNERZAJVUFOYOR-UHFFFAOYSA-N 0.000 description 1
- GGDWYLNRZFWXPU-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-methoxy-2-methylsulfinylquinoline Chemical compound COC1=CC=C2N=C(S(C)=O)C=CC2=C1OC1=CC=C(F)C=C1F GGDWYLNRZFWXPU-UHFFFAOYSA-N 0.000 description 1
- OUKXLSKWQFNBPK-UHFFFAOYSA-N 5-(2,6-difluorophenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1OC1=C(F)C=CC=C1F OUKXLSKWQFNBPK-UHFFFAOYSA-N 0.000 description 1
- YMTAKDRUIABEGL-UHFFFAOYSA-N 5-(2,6-difluorophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=C(F)C=CC=C1F YMTAKDRUIABEGL-UHFFFAOYSA-N 0.000 description 1
- ZKJILGDAICTDHI-UHFFFAOYSA-N 5-(2-chloro-4-fluorophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=C(F)C=C1Cl ZKJILGDAICTDHI-UHFFFAOYSA-N 0.000 description 1
- PWYMWQRYZLBGJF-UHFFFAOYSA-N 5-(2-chloro-4-methoxyphenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound ClC1=CC(OC)=CC=C1OC1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 PWYMWQRYZLBGJF-UHFFFAOYSA-N 0.000 description 1
- NXYAPBXUQISTSV-UHFFFAOYSA-N 5-(2-chloro-4-methoxyphenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound ClC1=CC(OC)=CC=C1SC1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 NXYAPBXUQISTSV-UHFFFAOYSA-N 0.000 description 1
- ZNQRBELUULFDMX-UHFFFAOYSA-N 5-(2-chlorophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=CC=C1Cl ZNQRBELUULFDMX-UHFFFAOYSA-N 0.000 description 1
- ATYPBXKPVDROFY-UHFFFAOYSA-N 5-(2-fluoro-4-methoxyphenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound FC1=CC(OC)=CC=C1SC1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 ATYPBXKPVDROFY-UHFFFAOYSA-N 0.000 description 1
- GAOCXAQGUOCWEV-UHFFFAOYSA-N 5-(2-fluoro-4-methylsulfonylphenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1OC1=CC=C(S(C)(=O)=O)C=C1F GAOCXAQGUOCWEV-UHFFFAOYSA-N 0.000 description 1
- DRDLBOCKKMHTDA-UHFFFAOYSA-N 5-(2-fluoro-6-methylsulfonylphenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1OC1=C(F)C=CC=C1S(C)(=O)=O DRDLBOCKKMHTDA-UHFFFAOYSA-N 0.000 description 1
- CTLHMJFJXQXRNV-UHFFFAOYSA-N 5-(2-fluorophenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1OC1=CC=CC=C1F CTLHMJFJXQXRNV-UHFFFAOYSA-N 0.000 description 1
- FSVICHLSAGYYST-UHFFFAOYSA-N 5-(4-bromophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=C(Br)C=C1 FSVICHLSAGYYST-UHFFFAOYSA-N 0.000 description 1
- JPQJZAHXJIUCPM-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=C(Cl)C=C1 JPQJZAHXJIUCPM-UHFFFAOYSA-N 0.000 description 1
- ZSTACXOQVJGGFN-UHFFFAOYSA-N 5-(4-ethoxyphenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound C1=CC(OCC)=CC=C1OC1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 ZSTACXOQVJGGFN-UHFFFAOYSA-N 0.000 description 1
- WOYGMVHDVGBCPF-UHFFFAOYSA-N 5-(4-fluoro-2-methoxyphenyl)sulfanyl-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1SC1=CC=C(F)C=C1OC WOYGMVHDVGBCPF-UHFFFAOYSA-N 0.000 description 1
- KHIBCAVHIKFGAD-UHFFFAOYSA-N 5-(4-fluorophenoxy)-6-methoxy-2-methylsulfinylquinoline Chemical compound COC1=CC=C2N=C(S(C)=O)C=CC2=C1OC1=CC=C(F)C=C1 KHIBCAVHIKFGAD-UHFFFAOYSA-N 0.000 description 1
- WKGICZZZLMGSQE-UHFFFAOYSA-N 5-(4-fluorophenoxy)-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1OC1=CC=C(F)C=C1 WKGICZZZLMGSQE-UHFFFAOYSA-N 0.000 description 1
- WMNAZUNQOBNVLM-UHFFFAOYSA-N 5-[(2,4-difluorophenyl)methyl]-6-methoxy-2-methylsulfinylquinoline Chemical compound COC1=CC=C2N=C(S(C)=O)C=CC2=C1CC1=CC=C(F)C=C1F WMNAZUNQOBNVLM-UHFFFAOYSA-N 0.000 description 1
- VNISCBKKLGJOTR-UHFFFAOYSA-N 5-[(2-fluorophenyl)methyl]-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1CC1=CC=CC=C1F VNISCBKKLGJOTR-UHFFFAOYSA-N 0.000 description 1
- CWHCRWGEFOBNBP-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1CC1=CC=C(Cl)C=C1 CWHCRWGEFOBNBP-UHFFFAOYSA-N 0.000 description 1
- FAOWSMWOPLOPJK-UHFFFAOYSA-N 5-[(4-ethoxyphenyl)methyl]-6-methoxy-2-methylsulfonylquinoline Chemical compound C1=CC(OCC)=CC=C1CC1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 FAOWSMWOPLOPJK-UHFFFAOYSA-N 0.000 description 1
- LJESHKOZEUZDAJ-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-6-methoxy-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1CC1=CC=C(F)C=C1 LJESHKOZEUZDAJ-UHFFFAOYSA-N 0.000 description 1
- KWSLGOVYXMQPPX-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenyl]-2h-tetrazole Chemical compound FC(F)(F)C1=CC=CC(C2=NNN=N2)=C1 KWSLGOVYXMQPPX-UHFFFAOYSA-N 0.000 description 1
- NRBXCMIOQORNNX-UHFFFAOYSA-N 5-bromo-2-chloroquinoline Chemical compound BrC1=CC=CC2=NC(Cl)=CC=C21 NRBXCMIOQORNNX-UHFFFAOYSA-N 0.000 description 1
- SDMIYMJTQNOZRV-UHFFFAOYSA-N 5-bromo-6-methoxy-8-nitroquinoline Chemical compound N1=CC=CC2=C(Br)C(OC)=CC([N+]([O-])=O)=C21 SDMIYMJTQNOZRV-UHFFFAOYSA-N 0.000 description 1
- BWEGRKPOJXNZSK-UHFFFAOYSA-N 6-Methoxyquinoline N-oxide Chemical compound [O-][N+]1=CC=CC2=CC(OC)=CC=C21 BWEGRKPOJXNZSK-UHFFFAOYSA-N 0.000 description 1
- MLHXCMWXUMCLNK-UHFFFAOYSA-N 6-methoxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=CC(OC)=CC=C21 MLHXCMWXUMCLNK-UHFFFAOYSA-N 0.000 description 1
- KMVYQTJMBBYECW-UHFFFAOYSA-N 6-methoxy-2-methylsulfonyl-5-phenoxyquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1OC1=CC=CC=C1 KMVYQTJMBBYECW-UHFFFAOYSA-N 0.000 description 1
- WNMOWJIWPQIHEP-UHFFFAOYSA-N 6-methoxy-2-methylsulfonyl-5-phenylquinoline-3-thiol Chemical compound CS(=O)(=O)C1=NC2=CC=C(C(=C2C=C1S)C1=CC=CC=C1)OC WNMOWJIWPQIHEP-UHFFFAOYSA-N 0.000 description 1
- YROOEOJXIKZFRH-UHFFFAOYSA-N 6-methoxy-5-(4-methoxyphenyl)sulfanyl-2-methylsulfonylquinoline Chemical compound C1=CC(OC)=CC=C1SC1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 YROOEOJXIKZFRH-UHFFFAOYSA-N 0.000 description 1
- YRBYQLGEUNULES-UHFFFAOYSA-N 6-methoxy-5-[(4-methoxyphenyl)methyl]-2-methylsulfonylquinoline Chemical compound C1=CC(OC)=CC=C1CC1=C(OC)C=CC2=NC(S(C)(=O)=O)=CC=C12 YRBYQLGEUNULES-UHFFFAOYSA-N 0.000 description 1
- DIYPWGRIVONQAW-UHFFFAOYSA-N 6-methoxy-5-[(4-methylphenyl)methyl]-2-methylsulfonylquinoline Chemical compound COC1=CC=C2N=C(S(C)(=O)=O)C=CC2=C1CC1=CC=C(C)C=C1 DIYPWGRIVONQAW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- WEROLFNOZCOTQT-UHFFFAOYSA-N CC1=CC=C(C[Zn])C=C1 Chemical compound CC1=CC=C(C[Zn])C=C1 WEROLFNOZCOTQT-UHFFFAOYSA-N 0.000 description 1
- APFQSDVONZPBJX-UHFFFAOYSA-N CCOC1=CC=C(C[Zn])C=C1 Chemical compound CCOC1=CC=C(C[Zn])C=C1 APFQSDVONZPBJX-UHFFFAOYSA-N 0.000 description 1
- XEXOJFBWBSUMIK-UHFFFAOYSA-N COC1=CC=C(C[Zn])C=C1 Chemical compound COC1=CC=C(C[Zn])C=C1 XEXOJFBWBSUMIK-UHFFFAOYSA-N 0.000 description 1
- 0 COc(cc1)ccc1C(c(c1c(cc2)nc(*)cc1)c2OC)=O Chemical compound COc(cc1)ccc1C(c(c1c(cc2)nc(*)cc1)c2OC)=O 0.000 description 1
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- BFGFTMKOFFYBMU-UHFFFAOYSA-N ClC1=CC=C(C[Zn])C=C1 Chemical compound ClC1=CC=C(C[Zn])C=C1 BFGFTMKOFFYBMU-UHFFFAOYSA-N 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- AJFTZWGGHJXZOB-UHFFFAOYSA-N DuP 697 Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC(F)=CC=2)SC(Br)=C1 AJFTZWGGHJXZOB-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- IHYGMMRBIISIED-UHFFFAOYSA-N FC1=CC=C(C[Zn])C=C1 Chemical compound FC1=CC=C(C[Zn])C=C1 IHYGMMRBIISIED-UHFFFAOYSA-N 0.000 description 1
- RJXCCZCYRBFKOM-UHFFFAOYSA-N FC1=CC=CC=C1C[Zn] Chemical compound FC1=CC=CC=C1C[Zn] RJXCCZCYRBFKOM-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 208000004454 Hyperalgesia Diseases 0.000 description 1
- 208000035154 Hyperesthesia Diseases 0.000 description 1
- 101150062179 II gene Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 206010036600 Premature labour Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000006859 Swern oxidation reaction Methods 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- WSEYRYIQSMUYMG-UHFFFAOYSA-N [3-iodo-2-(2,2,2-trifluoroacetyl)oxyphenyl] 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OC1=CC=CC(I)=C1OC(=O)C(F)(F)F WSEYRYIQSMUYMG-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 125000004171 alkoxy aryl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- REDXJYDRNCIFBQ-UHFFFAOYSA-N aluminium(3+) Chemical compound [Al+3] REDXJYDRNCIFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 150000001504 aryl thiols Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 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
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940109738 hematin Drugs 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004476 heterocycloamino group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 150000007527 lewis bases Chemical class 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910001509 metal bromide Inorganic materials 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- KIWSYRHAAPLJFJ-DNZSEPECSA-N n-[(e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enyl]pyridine-3-carboxamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/CNC(=O)C1=CC=CN=C1 KIWSYRHAAPLJFJ-DNZSEPECSA-N 0.000 description 1
- YBSZEWLCECBDIP-UHFFFAOYSA-N n-[bis(dimethylamino)phosphoryl]-n-methylmethanamine Chemical compound CN(C)P(=O)(N(C)C)N(C)C.CN(C)P(=O)(N(C)C)N(C)C YBSZEWLCECBDIP-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000004351 phenylcyclohexyl group Chemical group C1(=CC=CC=C1)C1(CCCCC1)* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 208000026440 premature labor Diseases 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000003127 radioimmunoassay Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 229910001379 sodium hypophosphite Inorganic materials 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000001755 vocal effect Effects 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
- C07D215/36—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (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)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pregnancy & Childbirth (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22419600P | 2000-08-09 | 2000-08-09 | |
| US224196P | 2000-08-09 | ||
| PCT/EP2001/008880 WO2002012192A1 (en) | 2000-08-09 | 2001-08-01 | Quinolene derivatives as anti-inflammation agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60129445D1 DE60129445D1 (de) | 2007-08-30 |
| DE60129445T2 true DE60129445T2 (de) | 2008-04-24 |
Family
ID=22839655
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60129445T Expired - Fee Related DE60129445T2 (de) | 2000-08-09 | 2001-08-01 | Quinolin-derivate als antientzündungsmittel |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US7049325B2 (enExample) |
| EP (1) | EP1313707B1 (enExample) |
| JP (1) | JP3930428B2 (enExample) |
| KR (1) | KR20030027016A (enExample) |
| CN (1) | CN1199950C (enExample) |
| AR (1) | AR033554A1 (enExample) |
| AT (1) | ATE367379T1 (enExample) |
| AU (1) | AU2001277560A1 (enExample) |
| BR (1) | BR0113175A (enExample) |
| CA (1) | CA2418832A1 (enExample) |
| DE (1) | DE60129445T2 (enExample) |
| ES (1) | ES2290161T3 (enExample) |
| MX (1) | MXPA03001178A (enExample) |
| WO (1) | WO2002012192A1 (enExample) |
| ZA (1) | ZA200300847B (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW591089B (en) * | 2001-08-09 | 2004-06-11 | Cheil Ind Inc | Slurry composition for use in chemical mechanical polishing of metal wiring |
| GB0220953D0 (en) * | 2002-09-10 | 2002-10-23 | Novartis Ag | Organic compounds |
| US7132432B2 (en) * | 2003-06-05 | 2006-11-07 | Bristol-Myers Squibb Company | Hydantoin derivatives as inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) |
| PL1863833T3 (pl) * | 2005-03-08 | 2014-03-31 | Boehringer Ingelheim Int | Sposób otrzymywania związków makrocyklicznych |
| CN102159245B (zh) * | 2008-09-17 | 2013-07-24 | 贝林格尔.英格海姆国际有限公司 | Hcv ns3蛋白酶抑制剂与干扰素和利巴韦林的组合 |
| AU2010313497B2 (en) | 2009-10-30 | 2013-08-01 | Boehringer Ingelheim International Gmbh | Dosage regimens for HCV combination therapy comprising BI201335, interferon alpha and ribavirin |
| US9383448B2 (en) | 2012-07-05 | 2016-07-05 | Deca System Co., Ltd. | Golf GPS device with automatic hole recognition and playing hole selection |
| CN117924243B (zh) * | 2024-01-16 | 2025-09-12 | 沈阳药科大学 | 一种喹啉衍生物及其药用组合物和应用 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9018134D0 (en) * | 1989-09-29 | 1990-10-03 | Ici Plc | Heterocyclic derivatives |
| MX9200299A (es) | 1991-02-07 | 1992-12-01 | Roussel Uclaf | Nuevos derivados biciclicos nitrogenados, su procedimiento de preparacion los nuevos compuestos intermedios obtenidos su aplicacion como medicamentos y las composiciones farmaceuticas que los contienen. |
| EP0498722B1 (fr) | 1991-02-07 | 1997-07-30 | Roussel Uclaf | Dérivés bicycliques azotés, leur procédé de préparation, les intermédiaires obtenus, leur application comme médicaments et les compositions pharmaceutiques les renfermant |
| GB9311790D0 (en) * | 1993-06-08 | 1993-07-28 | Minnesota Mining & Mfg | Photothermographic materials |
| DK122693D0 (da) | 1993-10-29 | 1993-10-29 | Hempels Skibsfarve Fab J C | Marin struktur |
| HUP9801628A2 (hu) * | 1995-04-28 | 1999-01-28 | Takeda Chemical Industries, Ltd. | Artritisz elleni gyógyászati készítmények |
| DE19638484A1 (de) * | 1996-09-20 | 1998-03-26 | Basf Ag | Hetaroylderivate |
| DE19638486A1 (de) * | 1996-09-20 | 1998-03-26 | Basf Ag | Hetaroylderivate |
| US6069151A (en) | 1996-11-06 | 2000-05-30 | Darwin Discovery, Ltd. | Quinolines and their therapeutic use |
| IT1298159B1 (it) | 1997-01-28 | 1999-12-20 | Hoffmann La Roche | Derivati di un 5-aroilnaftalene |
| US6077850A (en) * | 1997-04-21 | 2000-06-20 | G.D. Searle & Co. | Substituted benzopyran analogs for the treatment of inflammation |
| US6034256A (en) * | 1997-04-21 | 2000-03-07 | G.D. Searle & Co. | Substituted benzopyran derivatives for the treatment of inflammation |
| US6479438B2 (en) * | 2001-01-04 | 2002-11-12 | Isp Investments Inc. | Gel inhibited liquid carrier for a biocide containing a carbodiimide and an emulsifier mixture |
-
2001
- 2001-08-01 CA CA002418832A patent/CA2418832A1/en not_active Abandoned
- 2001-08-01 AT AT01955382T patent/ATE367379T1/de not_active IP Right Cessation
- 2001-08-01 MX MXPA03001178A patent/MXPA03001178A/es unknown
- 2001-08-01 JP JP2002518170A patent/JP3930428B2/ja not_active Expired - Fee Related
- 2001-08-01 CN CNB018163513A patent/CN1199950C/zh not_active Expired - Fee Related
- 2001-08-01 AU AU2001277560A patent/AU2001277560A1/en not_active Abandoned
- 2001-08-01 WO PCT/EP2001/008880 patent/WO2002012192A1/en not_active Ceased
- 2001-08-01 EP EP01955382A patent/EP1313707B1/en not_active Expired - Lifetime
- 2001-08-01 BR BR0113175-3A patent/BR0113175A/pt not_active IP Right Cessation
- 2001-08-01 ES ES01955382T patent/ES2290161T3/es not_active Expired - Lifetime
- 2001-08-01 KR KR10-2003-7001942A patent/KR20030027016A/ko not_active Ceased
- 2001-08-01 DE DE60129445T patent/DE60129445T2/de not_active Expired - Fee Related
- 2001-08-07 US US09/925,883 patent/US7049325B2/en not_active Expired - Fee Related
- 2001-08-08 AR ARP010103784A patent/AR033554A1/es not_active Application Discontinuation
-
2003
- 2003-01-30 ZA ZA200300847A patent/ZA200300847B/en unknown
-
2005
- 2005-11-30 US US11/291,867 patent/US7186840B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE60129445D1 (de) | 2007-08-30 |
| ZA200300847B (en) | 2004-04-30 |
| AU2001277560A1 (en) | 2002-02-18 |
| CA2418832A1 (en) | 2002-02-14 |
| MXPA03001178A (es) | 2003-06-30 |
| KR20030027016A (ko) | 2003-04-03 |
| US20060084677A1 (en) | 2006-04-20 |
| JP3930428B2 (ja) | 2007-06-13 |
| US7049325B2 (en) | 2006-05-23 |
| BR0113175A (pt) | 2004-02-17 |
| JP2004505951A (ja) | 2004-02-26 |
| ATE367379T1 (de) | 2007-08-15 |
| US20020082276A1 (en) | 2002-06-27 |
| WO2002012192A1 (en) | 2002-02-14 |
| EP1313707B1 (en) | 2007-07-18 |
| CN1199950C (zh) | 2005-05-04 |
| US7186840B2 (en) | 2007-03-06 |
| ES2290161T3 (es) | 2008-02-16 |
| CN1466575A (zh) | 2004-01-07 |
| AR033554A1 (es) | 2003-12-26 |
| EP1313707A1 (en) | 2003-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE68929520T2 (de) | Chinolin-Derivate als Leukotrien-D4-Antagonisten, diese enthaltende Zusammensetzungen und Verfahren zu deren Herstellung | |
| EP0261539B1 (de) | Substituierte Phenylsulfonamide | |
| EP0134400B1 (de) | Anti-sekretorische, Fluoralkoxy-substituierte Pyridylmethylthio-(oder sulfinyl-)benzimidazole | |
| DE69413215T2 (de) | Chinoline als typ iv phosphodiesterase inhibitoren | |
| DE69118388T2 (de) | Substituierte bizyklische arylderivate mit selektiver leukotrien b4 antagonistischer wirkung | |
| DE60203529T2 (de) | Indolderivate als cox-ii-inhibitoren | |
| EP0612731B1 (de) | Neue Chinolon- und Naphthyridoncarbonsäurederivate | |
| EP0499926A1 (de) | 2-Substituierte Chinoline, Verfahren zu ihrer Herstellung sowie ihre Verwendung in Arzneimitteln | |
| DE3916663A1 (de) | Substituierte (chinolin-2-yl-methoxy)phenyl-acyl-sulfonamide und -cyanamide, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln | |
| DE60105195T2 (de) | Benzofuran- und benzothiophen-derivative als selektive cox-2 inhibitoren | |
| DE60129445T2 (de) | Quinolin-derivate als antientzündungsmittel | |
| EP0258729A2 (de) | Dihydropyridinverbindungen, Verfahren zu ihrer Herstellung und ihre Verwendung | |
| DE602004004378T2 (de) | Verbindungen mit einer 5-ht2c rezeptor-wirkung und ihre verwendung | |
| DE60113090T2 (de) | P-(sulfonyl)-aryl- und -heteroarylamine | |
| DE69805974T2 (de) | 5-aroylnaphthalin derivate | |
| EP0519291B1 (de) | Aminomethyl-substituierte 2,3-Dihydropyrano(2,3-b)pyridine, Verfahren zu ihrer Herstellung und ihre Verwendung in Arzneimitteln | |
| DE68924221T2 (de) | Imidazolderivate. | |
| EP0170861B1 (de) | 3-Aminocarbonylmethoxy-5-phenylpyrazol-Verbindungen sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| EP0072960B1 (de) | 1,5-Diphenylpyrazolin-3-on-Verbindungen sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE3320102C2 (enExample) | ||
| DE2142527A1 (de) | Neue Tetrazoldenvate und Verfahren zu deren Herstellung | |
| EP0549879A2 (de) | Thiazolyl-substituierte Chinolylmethoxyphenylessigsäurederivate | |
| EP0072961B1 (de) | 1-Phenylindazol-3-on-Verbindungen sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DD257430A5 (de) | Verfahren zur herstellung von pyrrolo(1,2-a)(4,1)benzoxarepinen | |
| DD201890A5 (de) | Verfahren zur herstellung neuartiger chinolonverbindungen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |