ZA200006190B - PDE IV inhibiting pyridine derivatives. - Google Patents
PDE IV inhibiting pyridine derivatives. Download PDFInfo
- Publication number
- ZA200006190B ZA200006190B ZA200006190A ZA200006190A ZA200006190B ZA 200006190 B ZA200006190 B ZA 200006190B ZA 200006190 A ZA200006190 A ZA 200006190A ZA 200006190 A ZA200006190 A ZA 200006190A ZA 200006190 B ZA200006190 B ZA 200006190B
- Authority
- ZA
- South Africa
- Prior art keywords
- substituted
- 4alkyl
- formula
- hydrogen
- compound
- Prior art date
Links
- 230000002401 inhibitory effect Effects 0.000 title description 12
- 150000003222 pyridines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 101
- -1 cyano, amino, hydroxy Chemical group 0.000 claims description 65
- 239000000203 mixture Substances 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 150000002431 hydrogen Chemical group 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 125000005936 piperidyl group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 229920006395 saturated elastomer Polymers 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000002541 furyl group Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000000815 N-oxide group Chemical group 0.000 claims description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 8
- 239000012442 inert solvent Substances 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 125000005973 6,7-dihydro-5H-cyclopentapyridyl group Chemical group 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 206010003645 Atopy Diseases 0.000 claims description 3
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 238000000844 transformation Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 39
- 239000002904 solvent Substances 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 26
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 20
- 230000000694 effects Effects 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- 208000026935 allergic disease Diseases 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 208000012657 Atopic disease Diseases 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 7
- 230000000172 allergic effect Effects 0.000 description 7
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000027866 inflammatory disease Diseases 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- 102000011017 Type 4 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 3
- 108010037584 Type 4 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 210000003651 basophil Anatomy 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- SLIKWVTWIGHFJE-UHFFFAOYSA-N diphenoxymethylidenecyanamide Chemical compound C=1C=CC=CC=1OC(=NC#N)OC1=CC=CC=C1 SLIKWVTWIGHFJE-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 3
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 241000701447 unidentified baculovirus Species 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 206010001513 AIDS related complex Diseases 0.000 description 2
- 102000014654 Aromatase Human genes 0.000 description 2
- 108010078554 Aromatase Proteins 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 description 2
- 206010006895 Cachexia Diseases 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010012442 Dermatitis contact Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000013967 Monokines Human genes 0.000 description 2
- 108010050619 Monokines Proteins 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- IULFXBLVJIPESI-UHFFFAOYSA-N bis(methylsulfanyl)methylidenecyanamide Chemical compound CSC(SC)=NC#N IULFXBLVJIPESI-UHFFFAOYSA-N 0.000 description 2
- 230000007885 bronchoconstriction Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 208000010247 contact dermatitis Diseases 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- AEJUHWYEBDQKPN-UHFFFAOYSA-N ethane-1,1-diol;dihydrochloride Chemical compound Cl.Cl.CC(O)O AEJUHWYEBDQKPN-UHFFFAOYSA-N 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 2
- 229940096397 interleukin-8 Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical group OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium superoxide Chemical compound [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 238000010956 selective crystallization Methods 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229960001407 sodium bicarbonate Drugs 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 1
- OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
- MKHGVMIXRPGHOO-UHFFFAOYSA-N 2-(benzenesulfonyl)-3-phenyloxaziridine Chemical compound C=1C=CC=CC=1S(=O)(=O)N1OC1C1=CC=CC=C1 MKHGVMIXRPGHOO-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- GLOZBUONZNVBJP-UHFFFAOYSA-N 3-[2-(6-cyclopentyloxy-5-methoxypyridin-2-yl)propyl]-1h-imidazol-2-one Chemical compound COC1=CC=C(C(C)CN2C(NC=C2)=O)N=C1OC1CCCC1 GLOZBUONZNVBJP-UHFFFAOYSA-N 0.000 description 1
- KRYKNWYVOUPUIS-UHFFFAOYSA-N 3-[2-hydroxy-2-[5-methoxy-4-(5-phenylpentoxy)pyridin-2-yl]propyl]-1h-imidazol-2-one Chemical compound COC1=CN=C(C(C)(O)CN2C(NC=C2)=O)C=C1OCCCCCC1=CC=CC=C1 KRYKNWYVOUPUIS-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- RZVOGWQTTXJDAB-UHFFFAOYSA-N 5-methoxy-4-(oxolan-3-yloxy)pyridine-2-carbaldehyde Chemical compound COC1=CN=C(C=O)C=C1OC1COCC1 RZVOGWQTTXJDAB-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical group N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012435 Dermatitis and eczema Diseases 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- GNDJOCGXGLNCKY-ACZMJKKPSA-N Gln-Cys-Cys Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(O)=O GNDJOCGXGLNCKY-ACZMJKKPSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010018634 Gouty Arthritis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 230000006181 N-acylation Effects 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 206010050661 Platelet aggregation inhibition Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- MXZNUGFCDVAXLG-CHWSQXEVSA-N [(2S)-1-[(2R)-3-methyl-2-(pyridine-4-carbonylamino)butanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@@H](NC(=O)c1ccncc1)C(=O)N1CCC[C@@H]1B(O)O MXZNUGFCDVAXLG-CHWSQXEVSA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- DCQLZTSRKLWEAB-UHFFFAOYSA-N ac1ndudu Chemical compound O1C(C(C2OCC(C)O)OCC(C)O)C(COCC(C)O)OC2OC(C(C2OCC(C)O)OCC(C)O)C(COCC(C)O)OC2OC(C(C2OCC(C)O)OCC(C)O)C(COCC(C)O)OC2OC(C(C2OCC(C)O)OCC(C)O)C(COCC(C)O)OC2OC(C(OCC(C)O)C2OCC(C)O)C(COCC(O)C)OC2OC(C(C2OCC(C)O)OCC(C)O)C(COCC(C)O)OC2OC2C(OCC(C)O)C(OCC(C)O)C1OC2COCC(C)O DCQLZTSRKLWEAB-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- ZPNFWUPYTFPOJU-MPSLMFKFSA-N aprotinin Chemical compound CC[C@H](C)[C@@H]1NC(=O)[C@@H](CCCNC(N)=N)NC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CSSC[C@H]3NC(=O)CNC(=O)CNC(=O)[C@H](Cc4ccc(O)cc4)NC(=O)[C@H](NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CSSC[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc4ccccc4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC3=O)C(=O)N[C@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](CSSC[C@@H](NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@@H](CC(O)=O)NC(=O)[C@H]3CCCN3C(=O)[C@H](N)CCCNC(N)=N)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N3CCC[C@@H]3C(=O)N3CCC[C@H]3C(=O)N[C@H](Cc3ccc(O)cc3)C(=O)N[C@H]([C@H](C)O)C(=O)NCC(=O)N3CCC[C@H]3C(=O)N2)C(=O)NCC(=O)NCC(=O)N[C@H](C)C(O)=O)NC(=O)[C@@H](CC(C)C)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](NC1=O)[C@H](C)CC)[C@@H](C)O)C(C)C ZPNFWUPYTFPOJU-MPSLMFKFSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009640 blood culture Methods 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000007883 bronchodilation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-M carbamimidate Chemical compound NC([NH-])=O XSQUKJJJFZCRTK-UHFFFAOYSA-M 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 208000007287 cheilitis Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000006167 equilibration buffer Substances 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical class C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- CLIDMUTWHLMPMN-UHFFFAOYSA-N imidazole-1-carboxamide Chemical compound NC(=O)N1C=CN=C1 CLIDMUTWHLMPMN-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000004972 metal peroxides Chemical class 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- DUUZHMLQQPSTJY-UHFFFAOYSA-N n-(2,2-dimethoxyethyl)imidazole-1-carboxamide Chemical compound COC(OC)CNC(=O)N1C=CN=C1 DUUZHMLQQPSTJY-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229910052754 neon Inorganic materials 0.000 description 1
- GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002923 oximes Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical group 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- 125000004346 phenylpentyl group Chemical group C1(=CC=CC=C1)CCCCC* 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 239000004544 spot-on Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 208000002003 vulvitis Diseases 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98201020 | 1998-04-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200006190B true ZA200006190B (en) | 2001-10-31 |
Family
ID=8233543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200006190A ZA200006190B (en) | 1998-04-01 | 2000-10-31 | PDE IV inhibiting pyridine derivatives. |
Country Status (34)
| Country | Link |
|---|---|
| US (1) | US6656959B1 (ja) |
| EP (1) | EP1068194B1 (ja) |
| JP (1) | JP4778612B2 (ja) |
| KR (1) | KR100596664B1 (ja) |
| CN (1) | CN1172930C (ja) |
| AR (1) | AR014972A1 (ja) |
| AT (1) | ATE253569T1 (ja) |
| AU (1) | AU760771B2 (ja) |
| BG (1) | BG64705B1 (ja) |
| BR (1) | BR9909326A (ja) |
| CA (1) | CA2326045C (ja) |
| CZ (1) | CZ298747B6 (ja) |
| DE (1) | DE69912590T2 (ja) |
| DK (1) | DK1068194T3 (ja) |
| EA (1) | EA004207B1 (ja) |
| EE (1) | EE04718B1 (ja) |
| ES (1) | ES2211061T3 (ja) |
| HK (1) | HK1033579A1 (ja) |
| HR (1) | HRP20000619B1 (ja) |
| HU (1) | HU229412B1 (ja) |
| ID (1) | ID27207A (ja) |
| IL (2) | IL138745A0 (ja) |
| MY (1) | MY124696A (ja) |
| NO (1) | NO319531B1 (ja) |
| NZ (1) | NZ507022A (ja) |
| PL (1) | PL196026B1 (ja) |
| PT (1) | PT1068194E (ja) |
| SI (1) | SI1068194T1 (ja) |
| SK (1) | SK284468B6 (ja) |
| TR (1) | TR200002801T2 (ja) |
| TW (1) | TWI242558B (ja) |
| UA (1) | UA66842C2 (ja) |
| WO (1) | WO1999050262A1 (ja) |
| ZA (1) | ZA200006190B (ja) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY123585A (en) | 2000-03-23 | 2006-05-31 | Merck Canada Inc | Tri-aryl-substituted-ethane pde4 inhibitors. |
| US6639077B2 (en) | 2000-03-23 | 2003-10-28 | Merck Frosst Canada & Co. | Tri-aryl-substituted-ethane PDE4 inhibitors |
| DE10130397A1 (de) * | 2001-06-23 | 2003-01-09 | Bayer Cropscience Gmbh | Herbizide substituierte Pyridine, Verfahren zu ihrer Herstellung und ihre Verwendung als Herbzide und Pflanzenwachstumsregulatoren |
| DE10318610A1 (de) * | 2003-04-24 | 2004-11-11 | Elbion Ag | 7-Azaindole und deren Verwendung als Therapeutika |
| MXPA06012505A (es) | 2004-04-30 | 2006-12-15 | Warner Lambert Co | Compuestos de morfolina sustituida para el tratamiento de trastornos del sistema nervioso central. |
| US7863446B2 (en) | 2006-01-19 | 2011-01-04 | Orchid Research Laboratories Limited | Heterocycles |
| JP2009525269A (ja) | 2006-01-30 | 2009-07-09 | ユーロ−セルティーク エス．エイ． | カルシウムチャネルブロッカーとしての環状尿素化合物 |
| PL2076508T3 (pl) | 2006-10-18 | 2011-05-31 | Pfizer Prod Inc | Związki biaryloeteru mocznika |
| RU2572616C2 (ru) | 2008-02-01 | 2016-01-20 | Оркид Рисерч Лабораториз Лимитед | Новые гетероциклы |
| JOP20190060A1 (ar) | 2016-09-26 | 2019-03-26 | Chugai Pharmaceutical Co Ltd | مشتق بيرازولو بيريدين له تأثير مساعد لمستقبل glp-1 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3876657A (en) * | 1971-06-03 | 1975-04-08 | Ashland Oil Inc | Preparation of 1-substituted-2-imidazolidinones |
| US4600430A (en) | 1985-02-22 | 1986-07-15 | Eli Lilly And Company | Pyridinylimidazolidinone compounds |
| EP0711282B1 (en) * | 1993-07-28 | 2002-06-05 | Aventis Pharma Limited | Compounds as pde iv and tnf inhibitors |
| GB9401460D0 (en) * | 1994-01-26 | 1994-03-23 | Rhone Poulenc Rorer Ltd | Compositions of matter |
| WO1996004186A1 (en) * | 1994-08-03 | 1996-02-15 | Gics & Vermee, L.P. | Ovenable food package |
| TW332201B (en) * | 1995-04-06 | 1998-05-21 | Janssen Pharmaceutica Nv | 1,3-Dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatives |
| TW375612B (en) * | 1995-04-06 | 1999-12-01 | Janssen Pharmaceutica Nv | 1,3-dihydro-2H-imidazol-2-one derivatives for the treatment of disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase type IV, preparation thereof and pharmaceutical composition containing the same |
| TW424087B (en) * | 1995-04-06 | 2001-03-01 | Janssen Pharmaceutica Nv | 1,3-dihydro-1-(phenylalkenyl)-2H-imidazol-2-one derivatives |
| WO1997003967A1 (en) * | 1995-07-22 | 1997-02-06 | Rhone-Poulenc Rorer Limited | Substituted aromatic compounds and their pharmaceutical use |
| BR9612378A (pt) * | 1995-12-29 | 1999-07-13 | Smithkline Beecham Corp | Antagonistas receptores de vitronectina |
| SK285878B6 (sk) * | 1996-10-02 | 2007-10-04 | Janssen Pharmaceutica N. V. | Derivát 2-kyaniminoimidazolu, prostriedok obsahujúci tento derivát, spôsob prípravy tohto prostriedku, uvedený derivát na použitie ako liečivo, použitie tohto derivátu na prípravu liečiva a spôsob prípravy tohto derivátu |
-
1999
- 1999-03-24 SK SK1387-2000A patent/SK284468B6/sk not_active IP Right Cessation
- 1999-03-24 ES ES99913302T patent/ES2211061T3/es not_active Expired - Lifetime
- 1999-03-24 KR KR1020007008557A patent/KR100596664B1/ko not_active IP Right Cessation
- 1999-03-24 EP EP99913302A patent/EP1068194B1/en not_active Expired - Lifetime
- 1999-03-24 AT AT99913302T patent/ATE253569T1/de active
- 1999-03-24 WO PCT/EP1999/002045 patent/WO1999050262A1/en active IP Right Grant
- 1999-03-24 JP JP2000541166A patent/JP4778612B2/ja not_active Expired - Lifetime
- 1999-03-24 IL IL13874599A patent/IL138745A0/xx active IP Right Grant
- 1999-03-24 CN CNB998047376A patent/CN1172930C/zh not_active Expired - Lifetime
- 1999-03-24 ID IDW20001941A patent/ID27207A/id unknown
- 1999-03-24 CA CA002326045A patent/CA2326045C/en not_active Expired - Lifetime
- 1999-03-24 HU HU0101239A patent/HU229412B1/hu unknown
- 1999-03-24 DK DK99913302T patent/DK1068194T3/da active
- 1999-03-24 EE EEP200000569A patent/EE04718B1/xx unknown
- 1999-03-24 SI SI9930470T patent/SI1068194T1/xx unknown
- 1999-03-24 CZ CZ20003338A patent/CZ298747B6/cs not_active IP Right Cessation
- 1999-03-24 PL PL99343194A patent/PL196026B1/pl unknown
- 1999-03-24 NZ NZ507022A patent/NZ507022A/en not_active IP Right Cessation
- 1999-03-24 UA UA2000105769A patent/UA66842C2/uk unknown
- 1999-03-24 BR BR9909326-0A patent/BR9909326A/pt not_active Application Discontinuation
- 1999-03-24 AU AU31474/99A patent/AU760771B2/en not_active Expired
- 1999-03-24 DE DE69912590T patent/DE69912590T2/de not_active Expired - Lifetime
- 1999-03-24 PT PT99913302T patent/PT1068194E/pt unknown
- 1999-03-24 EA EA200001009A patent/EA004207B1/ru not_active IP Right Cessation
- 1999-03-24 TR TR2000/02801T patent/TR200002801T2/xx unknown
- 1999-03-24 US US09/647,668 patent/US6656959B1/en not_active Expired - Lifetime
- 1999-03-26 MY MYPI99001169A patent/MY124696A/en unknown
- 1999-03-29 TW TW088104881A patent/TWI242558B/zh not_active IP Right Cessation
- 1999-03-31 AR ARP990101489A patent/AR014972A1/es not_active Application Discontinuation
-
2000
- 2000-08-28 BG BG104718A patent/BG64705B1/bg unknown
- 2000-09-19 HR HR20000619A patent/HRP20000619B1/xx not_active IP Right Cessation
- 2000-09-28 IL IL138745A patent/IL138745A/en not_active IP Right Cessation
- 2000-09-29 NO NO20004906A patent/NO319531B1/no not_active IP Right Cessation
- 2000-10-31 ZA ZA200006190A patent/ZA200006190B/en unknown
-
2001
- 2001-05-19 HK HK01103462A patent/HK1033579A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100406628B1 (ko) | Pdeiv및사이토킨억제활성을가진1,3-디하이드로-1-(페닐알킬)-2h-이미다졸-2-온유도체 | |
| EP0934280B1 (en) | Pde iv inhibiting 2-cyanoiminoimidazole derivatives | |
| ZA200006190B (en) | PDE IV inhibiting pyridine derivatives. | |
| KR100400159B1 (ko) | Pdeiv및사이토킨억제활성을가진1,3-디하이드로-2h-이미다졸-2-온유도체 | |
| MXPA00009632A (en) | Pde iv inhibiting pyridine derivatives |