SK283162B6 - Karboxamid chinolínu ako inhibítor faktora nekrotizujúceho nádor, inhibítor fosfodiesterázy-IV a farmaceutický prostriedok s jeho obsahom - Google Patents
Karboxamid chinolínu ako inhibítor faktora nekrotizujúceho nádor, inhibítor fosfodiesterázy-IV a farmaceutický prostriedok s jeho obsahom Download PDFInfo
- Publication number
- SK283162B6 SK283162B6 SK1605-98A SK160598A SK283162B6 SK 283162 B6 SK283162 B6 SK 283162B6 SK 160598 A SK160598 A SK 160598A SK 283162 B6 SK283162 B6 SK 283162B6
- Authority
- SK
- Slovakia
- Prior art keywords
- carboxamide
- methoxyquinoline
- quinoline
- dichloropyridin
- disease
- Prior art date
Links
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 title description 7
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 title description 3
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 title description 2
- 201000010099 disease Diseases 0.000 claims abstract description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 27
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 claims abstract description 6
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 33
- -1 2,5-dichloropyridin-3-yl Chemical group 0.000 claims description 30
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 21
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 150000003857 carboxamides Chemical class 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 239000003981 vehicle Substances 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 6
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 5
- 206010015943 Eye inflammation Diseases 0.000 claims description 5
- 206010040070 Septic Shock Diseases 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 206010039966 Senile dementia Diseases 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000003367 polycyclic group Chemical group 0.000 claims description 4
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 3
- 206010017533 Fungal infection Diseases 0.000 claims description 3
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 201000010105 allergic rhinitis Diseases 0.000 claims description 3
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 230000002490 cerebral effect Effects 0.000 claims description 3
- 208000007451 chronic bronchitis Diseases 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000001848 dysentery Diseases 0.000 claims description 3
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 230000002685 pulmonary effect Effects 0.000 claims description 3
- 230000004044 response Effects 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 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 claims description 2
- 206010014824 Endotoxic shock Diseases 0.000 claims description 2
- 206010018367 Glomerulonephritis chronic Diseases 0.000 claims description 2
- 208000010496 Heart Arrest Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 208000031888 Mycoses Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 206010041591 Spinal osteoarthritis Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000024780 Urticaria Diseases 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 230000002917 arthritic effect Effects 0.000 claims description 2
- 229940124630 bronchodilator Drugs 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 230000007794 irritation Effects 0.000 claims description 2
- 201000008383 nephritis Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 230000000979 retarding effect Effects 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 208000005801 spondylosis Diseases 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims 4
- 230000001154 acute effect Effects 0.000 claims 3
- 102000003390 tumor necrosis factor Human genes 0.000 claims 3
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 208000030961 allergic reaction Diseases 0.000 claims 2
- 210000003979 eosinophil Anatomy 0.000 claims 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- 201000004792 malaria Diseases 0.000 claims 2
- 201000003651 pulmonary sarcoidosis Diseases 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 claims 1
- 208000030507 AIDS Diseases 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 208000014644 Brain disease Diseases 0.000 claims 1
- 206010006895 Cachexia Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 201000005569 Gout Diseases 0.000 claims 1
- 206010018691 Granuloma Diseases 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 206010020649 Hyperkeratosis Diseases 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 208000001126 Keratosis Diseases 0.000 claims 1
- 208000000112 Myalgia Diseases 0.000 claims 1
- 206010037549 Purpura Diseases 0.000 claims 1
- 241001672981 Purpura Species 0.000 claims 1
- 206010063837 Reperfusion injury Diseases 0.000 claims 1
- 206010044248 Toxic shock syndrome Diseases 0.000 claims 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 238000009825 accumulation Methods 0.000 claims 1
- 230000002052 anaphylactic effect Effects 0.000 claims 1
- 208000019664 bone resorption disease Diseases 0.000 claims 1
- 230000001066 destructive effect Effects 0.000 claims 1
- 230000002496 gastric effect Effects 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000007943 implant Substances 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 210000001503 joint Anatomy 0.000 claims 1
- 208000018937 joint inflammation Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 210000001165 lymph node Anatomy 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 230000001272 neurogenic effect Effects 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
- 208000023504 respiratory system disease Diseases 0.000 claims 1
- 150000003431 steroids Chemical class 0.000 claims 1
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims 1
- 230000008733 trauma Effects 0.000 claims 1
- 230000002485 urinary effect Effects 0.000 claims 1
- 201000005539 vernal conjunctivitis Diseases 0.000 claims 1
- 229940075420 xanthine Drugs 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 146
- 230000000694 effects Effects 0.000 abstract description 7
- 230000001413 cellular effect Effects 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- 102000004169 proteins and genes Human genes 0.000 abstract description 2
- 108090000623 proteins and genes Proteins 0.000 abstract description 2
- 102000018594 Tumour necrosis factor Human genes 0.000 abstract 1
- 108050007852 Tumour necrosis factor Proteins 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 237
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 153
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- 239000007787 solid Substances 0.000 description 85
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 81
- 239000000543 intermediate Substances 0.000 description 56
- 239000000243 solution Substances 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 239000011541 reaction mixture Substances 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 235000019341 magnesium sulphate Nutrition 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000003480 eluent Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- 239000000284 extract Substances 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 238000001819 mass spectrum Methods 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 150000003248 quinolines Chemical class 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- OWDKSNRCMYZGIM-UHFFFAOYSA-N 8-methoxyquinoline-5-carbonyl chloride;hydrochloride Chemical compound Cl.C1=CN=C2C(OC)=CC=C(C(Cl)=O)C2=C1 OWDKSNRCMYZGIM-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 4
- 239000004296 sodium metabisulphite Substances 0.000 description 4
- 235000010262 sodium metabisulphite Nutrition 0.000 description 4
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 230000006433 tumor necrosis factor production Effects 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- OQXVXPBDSJQYRR-UHFFFAOYSA-N 8-methoxy-2-methylquinoline Chemical compound C1=C(C)N=C2C(OC)=CC=CC2=C1 OQXVXPBDSJQYRR-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 3
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- OFGAJQZBICFUAC-UHFFFAOYSA-N 2-bromo-8-methoxyquinoline Chemical compound C1=C(Br)N=C2C(OC)=CC=CC2=C1 OFGAJQZBICFUAC-UHFFFAOYSA-N 0.000 description 2
- ISIQAMHROGZHOV-UHFFFAOYSA-N 3,5-dichloropyridin-4-amine Chemical compound NC1=C(Cl)C=NC=C1Cl ISIQAMHROGZHOV-UHFFFAOYSA-N 0.000 description 2
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 2
- QIPUCSNWEJQOKS-UHFFFAOYSA-N 5-bromo-2-ethyl-8-methoxyquinoline Chemical compound BrC1=CC=C(OC)C2=NC(CC)=CC=C21 QIPUCSNWEJQOKS-UHFFFAOYSA-N 0.000 description 2
- SDOVXVJPMNKLAP-UHFFFAOYSA-N 5-bromo-3-ethyl-8-methoxyquinoline Chemical compound COC1=CC=C(Br)C2=CC(CC)=CN=C21 SDOVXVJPMNKLAP-UHFFFAOYSA-N 0.000 description 2
- MCBRCJBMVOOJFX-UHFFFAOYSA-N 5-bromo-8-methoxy-2-methylquinoline Chemical compound C1=C(C)N=C2C(OC)=CC=C(Br)C2=C1 MCBRCJBMVOOJFX-UHFFFAOYSA-N 0.000 description 2
- SKDJMNAJJIQPST-UHFFFAOYSA-N 5-bromo-8-methoxyquinoline-2-carboxylic acid Chemical compound C1=C(C(O)=O)N=C2C(OC)=CC=C(Br)C2=C1 SKDJMNAJJIQPST-UHFFFAOYSA-N 0.000 description 2
- JNNGEAWILNVFFD-UHFFFAOYSA-N 6-hydroxy-7-methyl-1-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,4a,5,6,7,7a-hexahydrocyclopenta[c]pyran-4-carboxylic acid Chemical compound CC1C(O)CC(C(=CO2)C(O)=O)C1C2OC1OC(CO)C(O)C(O)C1O JNNGEAWILNVFFD-UHFFFAOYSA-N 0.000 description 2
- DBPXUETZRGVVJP-UHFFFAOYSA-N 7-fluoro-8-methoxyquinoline Chemical compound C1=CN=C2C(OC)=C(F)C=CC2=C1 DBPXUETZRGVVJP-UHFFFAOYSA-N 0.000 description 2
- UHBIKXOBLZWFKM-UHFFFAOYSA-N 8-hydroxy-2-quinolinecarboxylic acid Chemical compound C1=CC=C(O)C2=NC(C(=O)O)=CC=C21 UHBIKXOBLZWFKM-UHFFFAOYSA-N 0.000 description 2
- CUVZGMWTCWSHCM-UHFFFAOYSA-N 8-methoxy-2-methylquinoline-5-carbonyl chloride Chemical compound C1=C(C)N=C2C(OC)=CC=C(C(Cl)=O)C2=C1 CUVZGMWTCWSHCM-UHFFFAOYSA-N 0.000 description 2
- KIAUKLHNMBAIGX-UHFFFAOYSA-N 8-methoxy-2-pyridin-3-ylquinoline Chemical compound N1=C2C(OC)=CC=CC2=CC=C1C1=CC=CN=C1 KIAUKLHNMBAIGX-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- VROLVRUWWBDERI-UHFFFAOYSA-N CC(C)(C)C(=O)N(C)C1=NC2=C(C=CC(=C2C=C1)C(=O)O)OC Chemical compound CC(C)(C)C(=O)N(C)C1=NC2=C(C=CC(=C2C=C1)C(=O)O)OC VROLVRUWWBDERI-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 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 2
- 241001465754 Metazoa Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 238000005614 Skraup synthesis reaction Methods 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 229960004979 fampridine Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000003547 immunosorbent Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- UQQURTZDNGJSGA-UHFFFAOYSA-N methyl 5-bromo-8-methoxyquinoline-2-carboxylate Chemical compound BrC1=CC=C(OC)C2=NC(C(=O)OC)=CC=C21 UQQURTZDNGJSGA-UHFFFAOYSA-N 0.000 description 2
- DTYHRSIQPYNEJX-UHFFFAOYSA-N methyl 8-hydroxyquinoline-2-carboxylate Chemical compound C1=CC=C(O)C2=NC(C(=O)OC)=CC=C21 DTYHRSIQPYNEJX-UHFFFAOYSA-N 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 125000002524 organometallic group Chemical group 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000000552 rheumatic effect Effects 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- QMMDEILIWGCAJY-UHFFFAOYSA-N tert-butyl n-(5-bromo-8-methoxyquinolin-2-yl)-n-methylcarbamate Chemical compound C1=C(N(C)C(=O)OC(C)(C)C)N=C2C(OC)=CC=C(Br)C2=C1 QMMDEILIWGCAJY-UHFFFAOYSA-N 0.000 description 2
- WVYHWYJCJAGZNB-UHFFFAOYSA-N tert-butyl n-(5-bromo-8-methoxyquinolin-2-yl)carbamate Chemical compound C1=C(NC(=O)OC(C)(C)C)N=C2C(OC)=CC=C(Br)C2=C1 WVYHWYJCJAGZNB-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- 239000012049 topical pharmaceutical composition Substances 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- CHCOFDZSJYMQMX-NOQNJSOHSA-N (2s)-2-[[(2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-aminopropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1h-imidazol-5-yl)propanoyl]py Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C)N)C(C)C)C1=CC=C(O)C=C1 CHCOFDZSJYMQMX-NOQNJSOHSA-N 0.000 description 1
- XPYPOPCNLMRTBM-UHFFFAOYSA-N (4-nitrophenyl) 8-(difluoromethoxy)-2-methylquinoline-5-carboxylate Chemical compound C=1C=C(OC(F)F)C2=NC(C)=CC=C2C=1C(=O)OC1=CC=C([N+]([O-])=O)C=C1 XPYPOPCNLMRTBM-UHFFFAOYSA-N 0.000 description 1
- SVZVEHXGLZFKPZ-UHFFFAOYSA-N (4-nitrophenyl) 8-methoxy-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]quinoline-5-carboxylate Chemical compound C12=CC=C(N(C)C(=O)OC(C)(C)C)N=C2C(OC)=CC=C1C(=O)OC1=CC=C([N+]([O-])=O)C=C1 SVZVEHXGLZFKPZ-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OLZPJUVEGSNIJL-UHFFFAOYSA-N 2,5-dichloropyridin-3-amine Chemical compound NC1=CC(Cl)=CN=C1Cl OLZPJUVEGSNIJL-UHFFFAOYSA-N 0.000 description 1
- ZQABUULQVRIMPF-UHFFFAOYSA-N 2-(bromomethyl)quinolin-8-ol Chemical compound C1=C(CBr)N=C2C(O)=CC=CC2=C1 ZQABUULQVRIMPF-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 1
- NCZCTMVWCFBIMV-UHFFFAOYSA-N 2-cyano-8-methoxyquinoline-5-carbonyl chloride Chemical compound C1=C(C#N)N=C2C(OC)=CC=C(C(Cl)=O)C2=C1 NCZCTMVWCFBIMV-UHFFFAOYSA-N 0.000 description 1
- CQLMDWGCYABASW-UHFFFAOYSA-N 2-cyano-8-methoxyquinoline-5-carboxylic acid Chemical compound C1=C(C#N)N=C2C(OC)=CC=C(C(O)=O)C2=C1 CQLMDWGCYABASW-UHFFFAOYSA-N 0.000 description 1
- MZFNUHASPHZVRQ-UHFFFAOYSA-N 2-ethyl-8-methoxyquinoline Chemical compound C1=CC=C(OC)C2=NC(CC)=CC=C21 MZFNUHASPHZVRQ-UHFFFAOYSA-N 0.000 description 1
- ZEPSKDSWVKNJKR-UHFFFAOYSA-N 2-ethyl-8-methoxyquinoline-5-carbonyl chloride Chemical compound ClC(=O)C1=CC=C(OC)C2=NC(CC)=CC=C21 ZEPSKDSWVKNJKR-UHFFFAOYSA-N 0.000 description 1
- OIXIMCXKVWEXTR-UHFFFAOYSA-N 2-ethyl-8-methoxyquinoline-5-carboxylic acid Chemical compound OC(=O)C1=CC=C(OC)C2=NC(CC)=CC=C21 OIXIMCXKVWEXTR-UHFFFAOYSA-N 0.000 description 1
- GMLDCZYTIPCVMO-UHFFFAOYSA-N 2-methylidenebutanal Chemical compound CCC(=C)C=O GMLDCZYTIPCVMO-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- FDGAEAYZQQCBRN-UHFFFAOYSA-N 3-amino-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1N FDGAEAYZQQCBRN-UHFFFAOYSA-N 0.000 description 1
- KJBKPRMEMJKXDV-UHFFFAOYSA-N 3-chloropyridin-4-amine Chemical compound NC1=CC=NC=C1Cl KJBKPRMEMJKXDV-UHFFFAOYSA-N 0.000 description 1
- QBVUVMNSJBCGOL-UHFFFAOYSA-N 3-ethyl-8-methoxyquinoline Chemical compound COC1=CC=CC2=CC(CC)=CN=C21 QBVUVMNSJBCGOL-UHFFFAOYSA-N 0.000 description 1
- FQMJPELYPKOLPI-UHFFFAOYSA-N 3-ethyl-8-methoxyquinoline-5-carbonyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C2=CC(CC)=CN=C21 FQMJPELYPKOLPI-UHFFFAOYSA-N 0.000 description 1
- GEPKTUOODPRXCI-UHFFFAOYSA-N 3-ethyl-8-methoxyquinoline-5-carboxylic acid Chemical compound COC1=CC=C(C(O)=O)C2=CC(CC)=CN=C21 GEPKTUOODPRXCI-UHFFFAOYSA-N 0.000 description 1
- RCYMPYMITUEHOJ-UHFFFAOYSA-N 3-fluoro-2-methoxyaniline Chemical compound COC1=C(N)C=CC=C1F RCYMPYMITUEHOJ-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- MNENHUFMOQZAFF-UHFFFAOYSA-N 5-bromo-7-fluoro-8-methoxyquinoline Chemical compound C1=CN=C2C(OC)=C(F)C=C(Br)C2=C1 MNENHUFMOQZAFF-UHFFFAOYSA-N 0.000 description 1
- XOINTQKILDHQHQ-UHFFFAOYSA-N 5-bromo-8-(difluoromethoxy)quinoline Chemical compound C1=CN=C2C(OC(F)F)=CC=C(Br)C2=C1 XOINTQKILDHQHQ-UHFFFAOYSA-N 0.000 description 1
- VBVREYBPDNEEHO-UHFFFAOYSA-N 5-bromo-8-methoxy-2-(trifluoromethyl)quinoline Chemical compound C1=C(C(F)(F)F)N=C2C(OC)=CC=C(Br)C2=C1 VBVREYBPDNEEHO-UHFFFAOYSA-N 0.000 description 1
- ZTRASFSJIYYWTC-UHFFFAOYSA-N 5-bromo-8-methoxy-2-pyridin-3-ylquinoline Chemical compound N1=C2C(OC)=CC=C(Br)C2=CC=C1C1=CC=CN=C1 ZTRASFSJIYYWTC-UHFFFAOYSA-N 0.000 description 1
- VJUCHJLCCDUDPK-UHFFFAOYSA-N 5-bromo-8-methoxyquinoline-2-carbonitrile Chemical compound C1=C(C#N)N=C2C(OC)=CC=C(Br)C2=C1 VJUCHJLCCDUDPK-UHFFFAOYSA-N 0.000 description 1
- KQEISLAXONVLKE-UHFFFAOYSA-N 7-fluoro-8-methoxyquinoline-5-carbonyl chloride Chemical compound C1=CN=C2C(OC)=C(F)C=C(C(Cl)=O)C2=C1 KQEISLAXONVLKE-UHFFFAOYSA-N 0.000 description 1
- IBZGXWNYRJVFHX-UHFFFAOYSA-N 8-(difluoromethoxy)-2-methylquinoline-5-carboxylic acid Chemical compound OC(=O)C1=CC=C(OC(F)F)C2=NC(C)=CC=C21 IBZGXWNYRJVFHX-UHFFFAOYSA-N 0.000 description 1
- WGNAHKYSWAYSHH-UHFFFAOYSA-N 8-(difluoromethoxy)quinoline-5-carbonyl chloride Chemical compound C1=CN=C2C(OC(F)F)=CC=C(C(Cl)=O)C2=C1 WGNAHKYSWAYSHH-UHFFFAOYSA-N 0.000 description 1
- SYHDIKZRXDEFSN-UHFFFAOYSA-N 8-(difluoromethoxy)quinoline-5-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=C(OC(F)F)C2=N1 SYHDIKZRXDEFSN-UHFFFAOYSA-N 0.000 description 1
- UIEVJLCQJOBXDN-UHFFFAOYSA-N 8-methoxy-2-(trifluoromethyl)quinoline-5-carbonyl chloride Chemical compound C1=C(C(F)(F)F)N=C2C(OC)=CC=C(C(Cl)=O)C2=C1 UIEVJLCQJOBXDN-UHFFFAOYSA-N 0.000 description 1
- WSFPCQOJBVMWEE-UHFFFAOYSA-N 8-methoxy-2-(trifluoromethyl)quinoline-5-carboxylic acid Chemical compound C1=C(C(F)(F)F)N=C2C(OC)=CC=C(C(O)=O)C2=C1 WSFPCQOJBVMWEE-UHFFFAOYSA-N 0.000 description 1
- JAEFYFMAAPXHDG-UHFFFAOYSA-N 8-methoxy-2-methylquinoline-5-carbonyl chloride;hydrochloride Chemical compound Cl.C1=C(C)N=C2C(OC)=CC=C(C(Cl)=O)C2=C1 JAEFYFMAAPXHDG-UHFFFAOYSA-N 0.000 description 1
- PZHNHWCXHIOKLE-UHFFFAOYSA-N 8-methoxy-2-methylquinoline-5-carboxylic acid Chemical compound C1=C(C)N=C2C(OC)=CC=C(C(O)=O)C2=C1 PZHNHWCXHIOKLE-UHFFFAOYSA-N 0.000 description 1
- NYBGSGXDSZJQSJ-UHFFFAOYSA-N 8-methoxy-2-pyridin-3-ylquinoline-5-carbonyl chloride Chemical compound N1=C2C(OC)=CC=C(C(Cl)=O)C2=CC=C1C1=CC=CN=C1 NYBGSGXDSZJQSJ-UHFFFAOYSA-N 0.000 description 1
- NSFRAJZZSRUTOR-UHFFFAOYSA-N 8-methoxy-2-pyridin-3-ylquinoline-5-carboxylic acid Chemical compound N1=C2C(OC)=CC=C(C(O)=O)C2=CC=C1C1=CC=CN=C1 NSFRAJZZSRUTOR-UHFFFAOYSA-N 0.000 description 1
- GDSMTLWIGALEHM-UHFFFAOYSA-N 8-methoxyquinoline-2-carbonitrile Chemical compound C1=C(C#N)N=C2C(OC)=CC=CC2=C1 GDSMTLWIGALEHM-UHFFFAOYSA-N 0.000 description 1
- GLIRYBWADJHFOR-UHFFFAOYSA-N 8-methoxyquinoline-5-carbonyl chloride Chemical compound C1=CN=C2C(OC)=CC=C(C(Cl)=O)C2=C1 GLIRYBWADJHFOR-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- YNMKYRXSUZYGRU-UHFFFAOYSA-N CC(C)(C)OC(=O)COC(=O)C1=C2C=CC(=NC2=C(C=C1)OC)N Chemical compound CC(C)(C)OC(=O)COC(=O)C1=C2C=CC(=NC2=C(C=C1)OC)N YNMKYRXSUZYGRU-UHFFFAOYSA-N 0.000 description 1
- LZWDMXWQKAWRTL-UHFFFAOYSA-N CN1C(=NN=N1)C2C=CC3=C(N2C(=O)NC4=C(C=NC=C4Cl)Cl)C(=CC=C3)OC Chemical compound CN1C(=NN=N1)C2C=CC3=C(N2C(=O)NC4=C(C=NC=C4Cl)Cl)C(=CC=C3)OC LZWDMXWQKAWRTL-UHFFFAOYSA-N 0.000 description 1
- CJBFIUSGJHRPEM-UHFFFAOYSA-M COC1=CC=CC2=C1N(C(C=C2)C3=NN(N=N3)[Sn](C)(C)C)C(=O)NC4=C(C=NC=C4Cl)Cl Chemical compound COC1=CC=CC2=C1N(C(C=C2)C3=NN(N=N3)[Sn](C)(C)C)C(=O)NC4=C(C=NC=C4Cl)Cl CJBFIUSGJHRPEM-UHFFFAOYSA-M 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
- 238000006681 Combes synthesis reaction Methods 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010020164 HIV infection CDC Group III Diseases 0.000 description 1
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 208000031814 IgA Vasculitis Diseases 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- 206010069698 Langerhans' cell histiocytosis Diseases 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 206010027236 Meningitis fungal Diseases 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000005314 Multi-Infarct Dementia Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- BAUXAUBTSXKOSL-UHFFFAOYSA-N N-(3,5-dichloropyridin-4-yl)-8-methoxy-2-(2-methyltetrazol-5-yl)quinoline-5-carboxamide Chemical compound C12=CC=C(C3=NN(C)N=N3)N=C2C(OC)=CC=C1C(=O)NC1=C(Cl)C=NC=C1Cl BAUXAUBTSXKOSL-UHFFFAOYSA-N 0.000 description 1
- XDFOGDIBNCBIRK-UHFFFAOYSA-N N-(3,5-dichloropyridin-4-yl)formamide Chemical compound ClC1=CN=CC(Cl)=C1NC=O XDFOGDIBNCBIRK-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000713325 Visna/maedi virus Species 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 150000005415 aminobenzoic acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 108010083984 angiotensin A Proteins 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000003070 anti-hyperalgesia Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000005129 aryl carbonyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- OSJRGDBEYARHLX-UHFFFAOYSA-N azido(trimethyl)stannane Chemical compound [N-]=[N+]=[N-].C[Sn+](C)C OSJRGDBEYARHLX-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012050 conventional carrier Substances 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
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- 229960000258 corticotropin Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- UQHKFADEQIVWID-UHFFFAOYSA-N cytokinin Natural products C1=NC=2C(NCC=C(CO)C)=NC=NC=2N1C1CC(O)C(CO)O1 UQHKFADEQIVWID-UHFFFAOYSA-N 0.000 description 1
- 239000004062 cytokinin Substances 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- OJKBCQOJVMAHDX-UHFFFAOYSA-N diethyl(pyridin-3-yl)borane Chemical compound CCB(CC)C1=CC=CN=C1 OJKBCQOJVMAHDX-UHFFFAOYSA-N 0.000 description 1
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000003401 eosinophilic granuloma Diseases 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 201000010056 fungal meningitis Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005241 heteroarylamino group Chemical group 0.000 description 1
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 description 1
- 125000004470 heterocyclooxy group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 229960001317 isoprenaline Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- YNRMQTUOOLBRHW-UHFFFAOYSA-N methyl 8-methoxyquinoline-2-carboxylate Chemical compound C1=CC=C(OC)C2=NC(C(=O)OC)=CC=C21 YNRMQTUOOLBRHW-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- XAROOCXUVPWBFN-UHFFFAOYSA-N n-(3,5-dichloropyridin-2-yl)formamide Chemical compound ClC1=CN=C(NC=O)C(Cl)=C1 XAROOCXUVPWBFN-UHFFFAOYSA-N 0.000 description 1
- GBHRGRJICWEUSS-UHFFFAOYSA-N n-[2-(trifluoromethoxy)phenyl]formamide Chemical compound FC(F)(F)OC1=CC=CC=C1NC=O GBHRGRJICWEUSS-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- PAHJPOGEIAZYEN-UHFFFAOYSA-N quinoline-2-carbonyl chloride;hydrochloride Chemical compound Cl.C1=CC=CC2=NC(C(=O)Cl)=CC=C21 PAHJPOGEIAZYEN-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 239000011265 semifinished product Substances 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- TWRVYXVQOJCHIF-UHFFFAOYSA-N tert-butyl-chloro-methylsilane Chemical compound C[SiH](Cl)C(C)(C)C TWRVYXVQOJCHIF-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9610506.9A GB9610506D0 (en) | 1996-05-20 | 1996-05-20 | Novel compounds |
| GBGB9623234.3A GB9623234D0 (en) | 1996-11-07 | 1996-11-07 | Novel compounds |
| GBGB9626883.4A GB9626883D0 (en) | 1996-12-24 | 1996-12-24 | Compounds |
| GBGB9708072.5A GB9708072D0 (en) | 1997-04-22 | 1997-04-22 | Compounds |
| PCT/GB1997/001359 WO1997044036A1 (en) | 1996-05-20 | 1997-05-20 | Quinoline carboxamides as tnf inhibitors and as pde-iv inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK160598A3 SK160598A3 (en) | 1999-12-10 |
| SK283162B6 true SK283162B6 (sk) | 2003-03-04 |
Family
ID=27451451
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1605-98A SK283162B6 (sk) | 1996-05-20 | 1997-05-20 | Karboxamid chinolínu ako inhibítor faktora nekrotizujúceho nádor, inhibítor fosfodiesterázy-IV a farmaceutický prostriedok s jeho obsahom |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5804588A (cs) |
| EP (1) | EP0952832B1 (cs) |
| JP (1) | JP2000510865A (cs) |
| KR (1) | KR20000065219A (cs) |
| CN (1) | CN1148189C (cs) |
| AT (1) | ATE406163T1 (cs) |
| AU (1) | AU722472B2 (cs) |
| BR (1) | BR9709015A (cs) |
| CA (1) | CA2252531A1 (cs) |
| CZ (1) | CZ296163B6 (cs) |
| DE (1) | DE69738949D1 (cs) |
| IL (1) | IL126557A (cs) |
| NO (1) | NO312099B1 (cs) |
| NZ (1) | NZ332341A (cs) |
| PL (1) | PL329922A1 (cs) |
| RU (1) | RU2170730C2 (cs) |
| SK (1) | SK283162B6 (cs) |
| TR (1) | TR199802385T2 (cs) |
| WO (1) | WO1997044036A1 (cs) |
Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69633196D1 (de) * | 1995-10-16 | 2004-09-23 | Fujisawa Pharmaceutical Co | Heterocyclische verbindungen als h+-atpasen |
| GB9712761D0 (en) * | 1997-06-17 | 1997-08-20 | Chiroscience Ltd | Quinolines and their therapeutic use |
| GB9824160D0 (en) * | 1998-11-04 | 1998-12-30 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
| US6262070B1 (en) | 1998-11-04 | 2001-07-17 | Darwin Discovery Ltd. | Heterocyclic compounds and their therapeutic use |
| ATE320800T1 (de) * | 1999-08-21 | 2006-04-15 | Altana Pharma Ag | Synergistische kombination von roflumilast und salmeterol |
| AU1053501A (en) * | 1999-11-02 | 2001-05-14 | Ajinomoto Co., Inc. | Polyazanaphthalene compound and medicinal use thereof |
| JP4603646B2 (ja) * | 1999-11-15 | 2010-12-22 | 富士フイルムファインケミカルズ株式会社 | 新規なジピリジル誘導体 |
| US7217722B2 (en) * | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| GB0003256D0 (en) * | 2000-02-11 | 2000-04-05 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
| US6521618B2 (en) | 2000-03-28 | 2003-02-18 | Wyeth | 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors |
| DE10035928A1 (de) | 2000-07-21 | 2002-03-07 | Asta Medica Ag | Neue Heteroaryl-Derivate und deren Verwendung als Arzneimittel |
| US7112594B2 (en) | 2000-08-09 | 2006-09-26 | Mitsubishi Pharma Corporation | Fused bicyclic amide compounds and medicinal use thereof |
| US6953774B2 (en) | 2000-08-11 | 2005-10-11 | Applied Research Systems Ars Holding N.V. | Methods of inducing ovulation |
| JP2002300373A (ja) * | 2001-03-30 | 2002-10-11 | Minolta Co Ltd | 画像処理方法、画像処理装置、記録媒体及びプログラム |
| US20040180900A1 (en) * | 2001-05-23 | 2004-09-16 | Masaharu Takigawa | Therapeutic composition for repairing chondropathy |
| CN1520313A (zh) * | 2001-05-23 | 2004-08-11 | ������ҩ��ʽ���� | 一种加速骨折愈合的组合物 |
| WO2003008409A1 (en) | 2001-07-16 | 2003-01-30 | Astrazeneca Ab | Quinoline derivatives and their use as tyrosine kinase inhibitors |
| US7375232B2 (en) * | 2001-08-15 | 2008-05-20 | E.I. Du Pont De Nemours And Company | Ortho-heterocyclic substituted aryl amides for controlling invertebrate pests |
| MXPA04005782A (es) | 2001-12-14 | 2004-09-13 | Applied Research Systems | Metodos para inducir la ovulacion usando un modulador de nivel camp no polipeptido. |
| MY140561A (en) | 2002-02-20 | 2009-12-31 | Nycomed Gmbh | Dosage form containing pde 4 inhibitor as active ingredient |
| SE0200920D0 (sv) * | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Novel compounds |
| ES2195785B1 (es) * | 2002-05-16 | 2005-03-16 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| AU2002950217A0 (en) | 2002-07-16 | 2002-09-12 | Prana Biotechnology Limited | 8- Hydroxy Quinoline Derivatives |
| ES2211344B1 (es) * | 2002-12-26 | 2005-10-01 | Almirall Prodesfarma, S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| TWI324150B (en) * | 2003-02-28 | 2010-05-01 | Novartis Ag | Process for preparing 5-[(r)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1h)-quinolin-2-one salt |
| EA200501548A1 (ru) | 2003-04-01 | 2006-02-24 | Апплайд Резеч Системз Арс Холдинг Н.В. | Ингибиторы фосфодиэстераз при бесплодии |
| TWI324151B (en) * | 2003-04-02 | 2010-05-01 | Novartis Ag | Process for the preparation of 5-(haloacetyl)-8-substituted oxy-(1h)-quinolin-2-ones |
| US20070010497A1 (en) * | 2003-05-29 | 2007-01-11 | Nigel Boughton-Smith | Pharmaceutical composition comprising a p2x7 antagonist and sulfasalazine |
| EP1644042A1 (en) * | 2003-05-29 | 2006-04-12 | AstraZeneca AB | A pharmaceutical composition containing a p2x7 receptor antagonist and methotrexate |
| JP2007501270A (ja) * | 2003-05-29 | 2007-01-25 | アストラゼネカ・アクチエボラーグ | Ｐ２Ｘ７受容体アンタゴニストおよび腫瘍壊死因子αを含む医薬組成物 |
| GB0312609D0 (en) * | 2003-06-02 | 2003-07-09 | Astrazeneca Ab | Novel compounds |
| SE0302139D0 (sv) * | 2003-07-28 | 2003-07-28 | Astrazeneca Ab | Novel compounds |
| SE0302192D0 (sv) * | 2003-08-08 | 2003-08-08 | Astrazeneca Ab | Novel compounds |
| JP2007505834A (ja) * | 2003-09-15 | 2007-03-15 | シェーリング コーポレイション | Ｐｄｅｉｖインヒビターの調製のために有用なキノリン５−カルボキサミドの合成 |
| SE0302488D0 (sv) * | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | New combination |
| SV2005001973A (es) | 2003-12-12 | 2005-11-04 | Wyeth Corp | Quinolinas utiles en el tratamiento de enfermedades cardiovasculares ref. wyth0090-504 (am101500) |
| WO2005063293A1 (ja) | 2003-12-26 | 2005-07-14 | Masatoshi Hagiwara | Sr蛋白質のリン酸化制御方法、および、sr蛋白質の活性制御剤を有効成分とする抗ウイルス剤 |
| WO2005080373A1 (en) * | 2004-02-04 | 2005-09-01 | Pfizer Products Inc. | Substituted quinoline compounds |
| CN1950110B (zh) * | 2004-04-01 | 2012-11-21 | 列日大学 | 嘧啶-2,4,6-三酮的药物组合物 |
| CA2565599C (en) * | 2004-05-18 | 2012-07-31 | Schering Corporation | Substituted 2-quinolyl-oxazoles useful as pde4 inhibitors |
| ES2251866B1 (es) * | 2004-06-18 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| ES2251867B1 (es) * | 2004-06-21 | 2007-06-16 | Laboratorios Almirall S.A. | Nuevos derivados de piridazin-3(2h)-ona. |
| GB0413960D0 (en) * | 2004-06-22 | 2004-07-28 | Novartis Ag | Organic compounds |
| MX2007000095A (es) * | 2004-06-24 | 2007-03-21 | Vertex Pharma | Moduladores de transportadores con casete de union con atp. |
| US8354427B2 (en) * | 2004-06-24 | 2013-01-15 | Vertex Pharmaceutical Incorporated | Modulators of ATP-binding cassette transporters |
| SA05260265A (ar) * | 2004-08-30 | 2005-12-03 | استرازينيكا ايه بي | مركبات جديدة |
| WO2006040728A1 (en) * | 2004-10-12 | 2006-04-20 | Actelion Pharmaceuticals Ltd | 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea as crystalline sulfate salt |
| JP4660553B2 (ja) * | 2004-10-19 | 2011-03-30 | エフ．ホフマン−ラ ロシュ アーゲー | キノリン誘導体 |
| SE0402925D0 (sv) * | 2004-11-30 | 2004-11-30 | Astrazeneca Ab | Novel Compounds |
| EP1917245A1 (de) | 2005-08-21 | 2008-05-07 | Abbott GmbH & Co. KG | Heterocyclische verbindungen und ihre verwendung als bindungspartner für 5-ht5-rezeptoren |
| EP1928437A2 (en) | 2005-08-26 | 2008-06-11 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| JP2009512711A (ja) | 2005-10-21 | 2009-03-26 | ブレインセルス，インコーポレイティド | Ｐｄｅ阻害による神経新生の調節 |
| WO2007053596A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| JP2009521468A (ja) * | 2005-12-24 | 2009-06-04 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｂｃ輸送体の調節因子としてのキノリン−４−オン誘導体 |
| BRPI0620960A2 (pt) | 2005-12-28 | 2011-11-29 | Vertex Pharmaceuticals Incorporated | formas sólidas de n-[2,4-bis(1,1-dimetiletil)-5-hidroxifenil]-1,4-didro-4- oxiquinolina-3- carboxamida |
| KR100821649B1 (ko) | 2006-01-24 | 2008-04-11 | 서울시립대학교 산학협력단 | 클리오퀴놀을 유효성분으로 포함하는 ＨＩＦ-1α 활성제 |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| WO2007134136A2 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| MX2009000460A (es) * | 2006-07-11 | 2009-01-27 | Schering Corp | Sal xinafoato de un compuesto de 5-oxazol-2-il-quinolina sustituido. |
| JPWO2008026687A1 (ja) | 2006-09-01 | 2010-01-21 | 杏林製薬株式会社 | ピラゾロピリジンカルボキサミド誘導体及びそれらを含有するホスホジエステラーゼ（ｐｄｅ）阻害剤 |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| CL2007003874A1 (es) * | 2007-01-03 | 2008-05-16 | Boehringer Ingelheim Int | Compuestos derivados de benzamida; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar enfermedades cardiovasculares, hipertension, aterosclerosis, reestenosis, ictus, insuficiencia cardiaca, lesion isquemica, hipertensio |
| ES2306595B1 (es) * | 2007-02-09 | 2009-09-11 | Laboratorios Almirall S.A. | Sal de napadisilato de 5-(2-((6-(2,2-difluoro-2-feniletoxi)hexil)amino)-1-hidroxietil)-8-hidroxiquinolin-2(1h)-ona como agonista del receptor adrenergico beta2. |
| ES2320954B1 (es) * | 2007-03-02 | 2010-03-16 | Laboratorio Almirall S.A. | Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona. |
| WO2008114002A1 (en) * | 2007-03-22 | 2008-09-25 | Astrazeneca Ab | Quinoline derivatives for the treatment of inflammatory diseases |
| US9321730B2 (en) | 2007-08-21 | 2016-04-26 | The Hong Kong Polytechnic University | Method of making and administering quinoline derivatives as anti-cancer agents |
| US8106073B2 (en) | 2007-11-30 | 2012-01-31 | Astrazeneca Ab | Quinoline derivatives 057 |
| US12458635B2 (en) | 2008-08-13 | 2025-11-04 | Vertex Pharmaceuticals Incorporated | Pharmaceutical composition and administrations thereof |
| US20100074949A1 (en) | 2008-08-13 | 2010-03-25 | William Rowe | Pharmaceutical composition and administration thereof |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| PL2821400T3 (pl) | 2009-03-20 | 2018-04-30 | Vertex Pharmaceuticals Incorporated | Sposób wytwarzania modulatorów regulatora przewodności przezbłonowej zwłóknienia torbielowatego |
| JP2011042643A (ja) * | 2009-07-24 | 2011-03-03 | Bayer Cropscience Ag | 殺虫性カルボキサミド類 |
| UY33373A (es) | 2010-05-10 | 2011-12-30 | Gilead Sciences Inc | ?Compuestos de pirazolopiridina bifuncionales, su uso en terapia y composiciones que los comprenden?. |
| WO2011143105A1 (en) | 2010-05-10 | 2011-11-17 | Gilead Sciences, Inc. | Bifunctional quinoline derivatives |
| EP2635280A4 (en) * | 2010-11-05 | 2014-05-28 | Univ Minnesota | CYTOSINDEAMINASE MODULATORS TO IMPROVE DNA TRANSFECTION |
| US8802700B2 (en) | 2010-12-10 | 2014-08-12 | Vertex Pharmaceuticals Incorporated | Modulators of ATP-Binding Cassette transporters |
| CN102603628B (zh) | 2010-12-22 | 2016-08-17 | 香港理工大学 | 作为抗癌试剂的喹啉衍生物 |
| EP2804603A1 (en) | 2012-01-10 | 2014-11-26 | President and Fellows of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| IL311180A (en) | 2012-02-27 | 2024-04-01 | Vertex Pharma | Pharmaceutical preparations containing a solid dispersion of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and uses thereof |
| CN103254291B (zh) * | 2013-05-30 | 2014-06-25 | 常州亚当生物技术有限公司 | 肿瘤坏死因子-α多肽抑制剂及其应用 |
| CN103285373A (zh) * | 2013-05-30 | 2013-09-11 | 苏州普罗达生物科技有限公司 | 肿瘤坏死因子-α多肽抑制剂制备及其应用 |
| HUE048706T2 (hu) * | 2013-10-14 | 2020-08-28 | Eisai R&D Man Co Ltd | Szelektíven szubsztituált kinolin-vegyületek |
| MX370450B (es) | 2014-10-07 | 2019-12-13 | Vertex Pharma | Co-cristales de moduladores de regulador de conductancia de transmembrana en fibrosis quistica. |
| RU2624906C2 (ru) * | 2015-12-22 | 2017-07-10 | федеральное государственное бюджетное учреждение "Федеральный научно-исследовательский центр эпидемиологии и микробиологии имени почетного академика Н.Ф. Гамалеи" Министерства здравоохранения Российской Федерации | Производные 2-хинальдинкарбоновой кислоты и их противогриппозная активность |
| CN111050558B (zh) | 2017-09-13 | 2022-05-27 | 先正达参股股份有限公司 | 杀微生物的喹啉(硫代)羧酰胺衍生物 |
| CN107812006A (zh) * | 2017-11-13 | 2018-03-20 | 全椒先奇医药科技有限公司 | 一种治疗急性肾衰药物组合物及其应用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2517229A1 (de) * | 1975-04-18 | 1976-10-28 | Boehringer Mannheim Gmbh | Phenylalkylcarbonsaeure-derivate und verfahren zu ihrer herstellung |
| US4186201A (en) * | 1977-02-07 | 1980-01-29 | Riker Laboratories, Inc. | Methods of using 8(tetrazol-5-ylcarbamoyl)isoquinoline compounds |
| US4147694A (en) * | 1977-02-07 | 1979-04-03 | Riker Laboratories, Inc. | 8-(1H-Tetrazol-5-yl-carbamoyl)quinoline compounds |
| WO1986006721A1 (en) * | 1985-05-07 | 1986-11-20 | Alkaloida Vegyészeti Gyár | Triazolyl quinoline derivatives |
| ATE156120T1 (de) * | 1991-02-07 | 1997-08-15 | Roussel Uclaf | Bizyklische stickstoffverbindungen, ihre herstellung, erhaltene zwischenprodukte, ihre verwendung als arzneimittel und diese enthaltende pharmazeutische zusammensetzungen |
| US5455252A (en) * | 1993-03-31 | 1995-10-03 | Syntex (U.S.A.) Inc. | Optionally substituted 6,8-quinolines |
| SE9302490D0 (sv) * | 1993-07-26 | 1993-07-26 | Kabi Pharmacia Ab | New use of old drugs |
-
1997
- 1997-05-20 DE DE69738949T patent/DE69738949D1/de not_active Expired - Fee Related
- 1997-05-20 AT AT97923191T patent/ATE406163T1/de not_active IP Right Cessation
- 1997-05-20 CN CNB97194735XA patent/CN1148189C/zh not_active Expired - Fee Related
- 1997-05-20 AU AU29058/97A patent/AU722472B2/en not_active Ceased
- 1997-05-20 TR TR1998/02385T patent/TR199802385T2/xx unknown
- 1997-05-20 SK SK1605-98A patent/SK283162B6/sk unknown
- 1997-05-20 IL IL12655797A patent/IL126557A/en not_active IP Right Cessation
- 1997-05-20 RU RU98123074/04A patent/RU2170730C2/ru not_active IP Right Cessation
- 1997-05-20 WO PCT/GB1997/001359 patent/WO1997044036A1/en not_active Ceased
- 1997-05-20 PL PL97329922A patent/PL329922A1/xx unknown
- 1997-05-20 KR KR1019980709279A patent/KR20000065219A/ko not_active Ceased
- 1997-05-20 US US08/859,508 patent/US5804588A/en not_active Expired - Fee Related
- 1997-05-20 EP EP97923191A patent/EP0952832B1/en not_active Expired - Lifetime
- 1997-05-20 CA CA002252531A patent/CA2252531A1/en not_active Abandoned
- 1997-05-20 CZ CZ0365198A patent/CZ296163B6/cs not_active IP Right Cessation
- 1997-05-20 BR BR9709015A patent/BR9709015A/pt not_active IP Right Cessation
- 1997-05-20 NZ NZ332341A patent/NZ332341A/xx unknown
- 1997-05-20 JP JP09541788A patent/JP2000510865A/ja active Pending
-
1998
- 1998-11-19 NO NO19985376A patent/NO312099B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0952832B1 (en) | 2008-08-27 |
| BR9709015A (pt) | 1999-08-03 |
| DE69738949D1 (de) | 2008-10-09 |
| KR20000065219A (ko) | 2000-11-06 |
| AU2905897A (en) | 1997-12-09 |
| NO985376D0 (no) | 1998-11-19 |
| CN1219131A (zh) | 1999-06-09 |
| AU722472B2 (en) | 2000-08-03 |
| CA2252531A1 (en) | 1997-11-27 |
| US5804588A (en) | 1998-09-08 |
| NO312099B1 (no) | 2002-03-18 |
| JP2000510865A (ja) | 2000-08-22 |
| TR199802385T2 (xx) | 1999-04-21 |
| CN1148189C (zh) | 2004-05-05 |
| EP0952832A1 (en) | 1999-11-03 |
| RU2170730C2 (ru) | 2001-07-20 |
| CZ296163B6 (cs) | 2006-01-11 |
| NZ332341A (en) | 2000-05-26 |
| IL126557A (en) | 2002-09-12 |
| SK160598A3 (en) | 1999-12-10 |
| NO985376L (no) | 1998-11-19 |
| CZ365198A3 (cs) | 1999-03-17 |
| PL329922A1 (en) | 1999-04-26 |
| WO1997044036A1 (en) | 1997-11-27 |
| ATE406163T1 (de) | 2008-09-15 |
| IL126557A0 (en) | 1999-08-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SK283162B6 (sk) | Karboxamid chinolínu ako inhibítor faktora nekrotizujúceho nádor, inhibítor fosfodiesterázy-IV a farmaceutický prostriedok s jeho obsahom | |
| US5925636A (en) | Benzofuran carboxamides and their therapeutic use | |
| US6069151A (en) | Quinolines and their therapeutic use | |
| EP0946541B1 (en) | Quinolines and their therapeutic use | |
| US6353010B1 (en) | Bicyclic aryl carboxamides and their therapeutic use | |
| EP1263757B1 (en) | Benzthiazoles as tnf and pde-iv inhibitors | |
| US6403791B1 (en) | Heterocyclic compounds and their therapeutic use | |
| EP1086106B1 (en) | Furopyridine derivatives and their therapeutical use | |
| US6066657A (en) | Benzofuran-4-carboxamides and their therapeutic use | |
| JP2002528541A (ja) | Ｔｎｆおよびｐｄｅ−ｉｖ阻害活性を有する複素環式化合物のｎ−オキシド | |
| US6262070B1 (en) | Heterocyclic compounds and their therapeutic use | |
| MXPA98009740A (en) | Quinoline carboxamides as fnt inhibitors and as fde inhibitors | |
| MXPA00006346A (en) | N-oxides of heterocyclic compounds with tnf and pde-iv inhibiting activity |