AU2001274763B2 - Novel compounds - Google Patents
Novel compounds Download PDFInfo
- Publication number
- AU2001274763B2 AU2001274763B2 AU2001274763A AU2001274763A AU2001274763B2 AU 2001274763 B2 AU2001274763 B2 AU 2001274763B2 AU 2001274763 A AU2001274763 A AU 2001274763A AU 2001274763 A AU2001274763 A AU 2001274763A AU 2001274763 B2 AU2001274763 B2 AU 2001274763B2
- Authority
- AU
- Australia
- Prior art keywords
- phenyl
- amino
- acetamide
- alkoxycarbonyl
- hydrogen atom
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims description 113
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 114
- -1 nitro, carboxyl Chemical group 0.000 claims description 96
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 94
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 79
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 64
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 32
- 239000012453 solvate Substances 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 27
- 229920006395 saturated elastomer Polymers 0.000 claims description 26
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 25
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 239000005864 Sulphur Chemical group 0.000 claims description 9
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 7
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 102000009410 Chemokine receptor Human genes 0.000 claims description 3
- 108050000299 Chemokine receptor Proteins 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 235000015429 Mirabilis expansa Nutrition 0.000 claims description 2
- 244000294411 Mirabilis expansa Species 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 229940047889 isobutyramide Drugs 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 235000013536 miso Nutrition 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 9
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- GTKIGDZXPDCIKR-UHFFFAOYSA-N 2-phenylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=CC=C1 GTKIGDZXPDCIKR-UHFFFAOYSA-N 0.000 claims 1
- 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- RKWKLTLIBREDHD-DEOSSOPVSA-N n-[2-[(2s)-3-[[1-[(4-chlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]-4-hydroxyphenyl]acetamide Chemical compound CC(=O)NC1=CC=C(O)C=C1OC[C@@](C)(O)CNC1CCN(CC=2C=CC(Cl)=CC=2)CC1 RKWKLTLIBREDHD-DEOSSOPVSA-N 0.000 claims 1
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 83
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 239000000203 mixture Substances 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 19
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 18
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 18
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 18
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 150000002118 epoxides Chemical class 0.000 description 17
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- 229940093499 ethyl acetate Drugs 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000003545 alkoxy group Chemical group 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 206010039083 rhinitis Diseases 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- XQGVQRPSTODODM-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrrole-2-carboxylic acid Chemical compound CC1=CC(C)=C(C(O)=O)N1 XQGVQRPSTODODM-UHFFFAOYSA-N 0.000 description 6
- 102000019034 Chemokines Human genes 0.000 description 6
- 108010012236 Chemokines Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000035605 chemotaxis Effects 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 5
- 125000004414 alkyl thio group Chemical group 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 4
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 102000004257 Potassium Channel Human genes 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 210000003050 axon Anatomy 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 description 4
- 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 4
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 4
- 125000004438 haloalkoxy group Chemical group 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- 125000006606 n-butoxy group Chemical group 0.000 description 4
- 125000006252 n-propylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 108020001213 potassium channel Proteins 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- QOZLOYKAFDTQNU-UHFFFAOYSA-N 2-amino-3-fluorophenol Chemical compound NC1=C(O)C=CC=C1F QOZLOYKAFDTQNU-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 101150041968 CDC13 gene Proteins 0.000 description 3
- 201000004624 Dermatitis Diseases 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 229960004132 diethyl ether Drugs 0.000 description 3
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- MCGIQVVVGVAMEI-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(Cl)C(Cl)=C1 MCGIQVVVGVAMEI-UHFFFAOYSA-N 0.000 description 2
- ADVGKWPZRIDURE-UHFFFAOYSA-N 2'-Hydroxyacetanilide Chemical compound CC(=O)NC1=CC=CC=C1O ADVGKWPZRIDURE-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- OABOXRPGTFRBFZ-IMJSIDKUSA-N Cys-Cys Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(O)=O OABOXRPGTFRBFZ-IMJSIDKUSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 206010014950 Eosinophilia Diseases 0.000 description 2
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 2
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 2
- 241000721454 Pemphigus Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-O Piperidinium(1+) Chemical compound C1CC[NH2+]CC1 NQRYJNQNLNOLGT-UHFFFAOYSA-O 0.000 description 2
- 102100036154 Platelet basic protein Human genes 0.000 description 2
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 229910021607 Silver chloride Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 125000004803 chlorobenzyl group Chemical group 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 108010035886 connective tissue-activating peptide Proteins 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 108010004073 cysteinylcysteine Proteins 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 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
- 210000003734 kidney Anatomy 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- PHOAIOPTKPVQOB-UHFFFAOYSA-N n-(2-hydroxy-4-methoxyphenyl)acetamide Chemical compound COC1=CC=C(NC(C)=O)C(O)=C1 PHOAIOPTKPVQOB-UHFFFAOYSA-N 0.000 description 2
- UYKVWAQEMQDRGG-UHFFFAOYSA-N n-(2-hydroxyphenyl)benzamide Chemical compound OC1=CC=CC=C1NC(=O)C1=CC=CC=C1 UYKVWAQEMQDRGG-UHFFFAOYSA-N 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical class [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 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 2
- 238000005406 washing Methods 0.000 description 2
- AAVHHYWBSVSPPN-UHFFFAOYSA-N (2-methyloxiran-2-yl)methanol Chemical compound OCC1(C)CO1 AAVHHYWBSVSPPN-UHFFFAOYSA-N 0.000 description 1
- SMKKEOQDQNCTGL-ZETCQYMHSA-N (2s)-2-[(2-nitrophenoxy)methyl]oxirane Chemical compound [O-][N+](=O)C1=CC=CC=C1OC[C@H]1OC1 SMKKEOQDQNCTGL-ZETCQYMHSA-N 0.000 description 1
- AYFOLFULJIWELF-ZETCQYMHSA-N (2s)-2-[(5-fluoro-2-nitrophenoxy)methyl]oxirane Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OC[C@H]1OC1 AYFOLFULJIWELF-ZETCQYMHSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- NBIOUVFLTIZZER-UHFFFAOYSA-N 1,2-dichloro-4-(chloromethyl)benzene;1-[(3,4-dichlorophenyl)methyl]piperidin-4-amine Chemical compound ClCC1=CC=C(Cl)C(Cl)=C1.C1CC(N)CCN1CC1=CC=C(Cl)C(Cl)=C1 NBIOUVFLTIZZER-UHFFFAOYSA-N 0.000 description 1
- SSNCMIDZGFCTST-UHFFFAOYSA-N 1,3-difluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(F)C=CC=C1F SSNCMIDZGFCTST-UHFFFAOYSA-N 0.000 description 1
- DDPNUBVUABSUEG-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(Br)C=C1 DDPNUBVUABSUEG-UHFFFAOYSA-N 0.000 description 1
- BIMZLZOTBSPLRM-UHFFFAOYSA-N 1-[(4-chlorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(Cl)C=C1 BIMZLZOTBSPLRM-UHFFFAOYSA-N 0.000 description 1
- KRIHULMCWJRKQE-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=C(F)C=C1 KRIHULMCWJRKQE-UHFFFAOYSA-N 0.000 description 1
- YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 1
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- VVHFXJOCUKBZFS-UHFFFAOYSA-N 2-(chloromethyl)-2-methyloxirane Chemical compound ClCC1(C)CO1 VVHFXJOCUKBZFS-UHFFFAOYSA-N 0.000 description 1
- PTHRRXYZMDTTOA-UHFFFAOYSA-N 2-[2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound NC(=O)CC1=CC=CC=C1OCC1OC1 PTHRRXYZMDTTOA-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- BCKXMQIYWWTZDP-UHFFFAOYSA-N 2-hydroxy-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1O BCKXMQIYWWTZDP-UHFFFAOYSA-N 0.000 description 1
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 1
- FRIBMENBGGCKPD-UHFFFAOYSA-N 3-(2,3-dimethoxyphenyl)prop-2-enal Chemical compound COC1=CC=CC(C=CC=O)=C1OC FRIBMENBGGCKPD-UHFFFAOYSA-N 0.000 description 1
- MWWNNNAOGWPTQY-UHFFFAOYSA-N 3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(S(Cl)(=O)=O)=C1 MWWNNNAOGWPTQY-UHFFFAOYSA-N 0.000 description 1
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 208000035939 Alveolitis allergic Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 201000008283 Atrophic Rhinitis Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- UBYIKLZCJXKABO-UHFFFAOYSA-N C(C)(C)(C)OC(=O)OC(=O)OC(C)(C)C.N1CCC(CC1)NC(OC(C)(C)C)=O Chemical compound C(C)(C)(C)OC(=O)OC(=O)OC(C)(C)C.N1CCC(CC1)NC(OC(C)(C)C)=O UBYIKLZCJXKABO-UHFFFAOYSA-N 0.000 description 1
- GUDPJHONHNSJBI-PMMFOGROSA-N C([ClH]([2H])([2H])([2H])([2H])[2H])(Cl)(Cl)[2H] Chemical compound C([ClH]([2H])([2H])([2H])([2H])[2H])(Cl)(Cl)[2H] GUDPJHONHNSJBI-PMMFOGROSA-N 0.000 description 1
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 1
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 1
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 1
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 102100034871 C-C motif chemokine 8 Human genes 0.000 description 1
- 101710155833 C-C motif chemokine 8 Proteins 0.000 description 1
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 1
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 101710139422 Eotaxin Proteins 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 208000027445 Farmer Lung Diseases 0.000 description 1
- 206010016228 Fasciitis Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 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 1
- 239000007821 HATU Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 101000777558 Homo sapiens C-C chemokine receptor type 10 Proteins 0.000 description 1
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 1
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 1
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura 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
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 1
- 208000009388 Job Syndrome Diseases 0.000 description 1
- 229920006063 Lamide® Polymers 0.000 description 1
- 206010024227 Lepromatous leprosy Diseases 0.000 description 1
- 102000009571 Macrophage Inflammatory Proteins Human genes 0.000 description 1
- 108010009474 Macrophage Inflammatory Proteins Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 229920005439 Perspex® Polymers 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010039088 Rhinitis atrophic Diseases 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- 101100095563 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SEO1 gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047112 Vasculitides Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HDTDGVNYXDYKSO-JTQLQIEISA-N [(2s)-2-methyloxiran-2-yl]methyl 3-nitrobenzenesulfonate Chemical compound C=1C=CC([N+]([O-])=O)=CC=1S(=O)(=O)OC[C@]1(C)CO1 HDTDGVNYXDYKSO-JTQLQIEISA-N 0.000 description 1
- 108010076089 accutase Proteins 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 125000000656 azaniumyl group Chemical group [H][N+]([H])([H])[*] 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- VBQDSLGFSUGBBE-UHFFFAOYSA-N benzyl(triethyl)azanium Chemical compound CC[N+](CC)(CC)CC1=CC=CC=C1 VBQDSLGFSUGBBE-UHFFFAOYSA-N 0.000 description 1
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- BQRGNLJZBFXNCZ-UHFFFAOYSA-N calcein am Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)=C(OC(C)=O)C=C1OC1=C2C=C(CN(CC(=O)OCOC(C)=O)CC(=O)OCOC(=O)C)C(OC(C)=O)=C1 BQRGNLJZBFXNCZ-UHFFFAOYSA-N 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000017760 chronic graft versus host disease Diseases 0.000 description 1
- 201000009151 chronic rhinitis Diseases 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- XEBCWEDRGPSHQH-YUMQZZPRSA-N dipropan-2-yl (2s,3s)-2,3-dihydroxybutanedioate Chemical compound CC(C)OC(=O)[C@@H](O)[C@H](O)C(=O)OC(C)C XEBCWEDRGPSHQH-YUMQZZPRSA-N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- IZSBSZYFPYIJDI-UHFFFAOYSA-N ethyl 3,5-dimethyl-1h-pyrrole-2-carboxylate Chemical compound CCOC(=O)C=1NC(C)=CC=1C IZSBSZYFPYIJDI-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 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
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 208000022195 farmer lung disease Diseases 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 206010051040 hyper-IgE syndrome Diseases 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 230000004047 hyperresponsiveness Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- AEUKDPKXTPNBNY-XEYRWQBLSA-N mcp 2 Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)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(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C1=CC=CC=C1 AEUKDPKXTPNBNY-XEYRWQBLSA-N 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 201000005962 mycosis fungoides Diseases 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
- NEOWELJZRVSZFJ-UHFFFAOYSA-N n-(2-hydroxy-6-methylphenyl)acetamide Chemical compound CC(=O)NC1=C(C)C=CC=C1O NEOWELJZRVSZFJ-UHFFFAOYSA-N 0.000 description 1
- SENIMHNFLVMDJV-UHFFFAOYSA-N n-[2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC1OC1 SENIMHNFLVMDJV-UHFFFAOYSA-N 0.000 description 1
- XPODWBQYZVBKMF-UHFFFAOYSA-N n-[2-(oxiran-2-ylmethoxy)phenyl]benzamide Chemical compound C=1C=CC=CC=1C(=O)NC1=CC=CC=C1OCC1CO1 XPODWBQYZVBKMF-UHFFFAOYSA-N 0.000 description 1
- ASMACUZVQOCUAE-UHFFFAOYSA-N n-[2-[(2-methyloxiran-2-yl)methoxy]phenyl]benzamide Chemical compound C=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1OCC1(C)CO1 ASMACUZVQOCUAE-UHFFFAOYSA-N 0.000 description 1
- OVJRIIXZEYSYCL-UHFFFAOYSA-N n-[2-[3-[[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]amino]-2-hydroxy-2-methylpropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OCC(C)(O)CNC1CCN(CC=2C=C(Cl)C(Cl)=CC=2)CC1 OVJRIIXZEYSYCL-UHFFFAOYSA-N 0.000 description 1
- FLLVVOSLUFQJDH-GFCCVEGCSA-N n-[2-[[(2s)-2-methyloxiran-2-yl]methoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC=C1OC[C@@]1(C)OC1 FLLVVOSLUFQJDH-GFCCVEGCSA-N 0.000 description 1
- ZTJOGPJQQWHVRL-UHFFFAOYSA-N n-[2-methyl-6-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=C(C)C=CC=C1OCC1OC1 ZTJOGPJQQWHVRL-UHFFFAOYSA-N 0.000 description 1
- TZZHHYPBZAQPHS-VIFPVBQESA-N n-[4-fluoro-2-[[(2s)-oxiran-2-yl]methoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(F)C=C1OC[C@H]1OC1 TZZHHYPBZAQPHS-VIFPVBQESA-N 0.000 description 1
- ATQSLKHGSWFGIB-UHFFFAOYSA-N n-[4-methoxy-2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound COC1=CC=C(NC(C)=O)C(OCC2OC2)=C1 ATQSLKHGSWFGIB-UHFFFAOYSA-N 0.000 description 1
- IYQNZAROPVZDKE-UHFFFAOYSA-N n-[4-methyl-2-(oxiran-2-ylmethoxy)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C)C=C1OCC1OC1 IYQNZAROPVZDKE-UHFFFAOYSA-N 0.000 description 1
- XYNZOQAPGUNBDC-UHFFFAOYSA-N n-methyl-2-(oxiran-2-ylmethoxy)benzamide Chemical compound CNC(=O)C1=CC=CC=C1OCC1OC1 XYNZOQAPGUNBDC-UHFFFAOYSA-N 0.000 description 1
- NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000012402 patch clamp technique Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000018102 proteins Nutrition 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
- 238000000746 purification Methods 0.000 description 1
- ODNFVADIRXKBCY-UHFFFAOYSA-N pyrrolidin-1-yl carbamate Chemical compound NC(=O)ON1CCCC1 ODNFVADIRXKBCY-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 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
- 239000003826 tablet Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- JHYOUOHNCPGQOS-UHFFFAOYSA-N tert-butyl 3-hydroxypiperidine-1-carboxylate;3-(4-chlorophenoxy)piperidine Chemical compound CC(C)(C)OC(=O)N1CCCC(O)C1.C1=CC(Cl)=CC=C1OC1CNCCC1 JHYOUOHNCPGQOS-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 201000005539 vernal conjunctivitis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0002331A SE0002331D0 (sv) | 2000-06-20 | 2000-06-20 | Novel compounds |
| SE0002331 | 2000-06-20 | ||
| SE0004480 | 2000-12-05 | ||
| SE0004480A SE0004480D0 (sv) | 2000-12-05 | 2000-12-05 | Novel compounds |
| PCT/SE2001/001377 WO2001098273A1 (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2001274763A1 AU2001274763A1 (en) | 2002-03-21 |
| AU2001274763B2 true AU2001274763B2 (en) | 2006-10-05 |
Family
ID=26655154
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2001274763A Ceased AU2001274763B2 (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
| AU7476301A Pending AU7476301A (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU7476301A Pending AU7476301A (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
Country Status (22)
| Country | Link |
|---|---|
| US (3) | US6911458B2 (enExample) |
| EP (1) | EP1299357A1 (enExample) |
| JP (1) | JP4022142B2 (enExample) |
| KR (1) | KR100799061B1 (enExample) |
| CN (1) | CN1307157C (enExample) |
| AR (1) | AR028948A1 (enExample) |
| AU (2) | AU2001274763B2 (enExample) |
| BR (1) | BR0111667A (enExample) |
| CA (1) | CA2414095C (enExample) |
| CZ (1) | CZ20024146A3 (enExample) |
| EE (1) | EE05157B1 (enExample) |
| HU (1) | HUP0301187A3 (enExample) |
| IL (2) | IL153167A0 (enExample) |
| IS (1) | IS6658A (enExample) |
| MX (1) | MXPA02012425A (enExample) |
| MY (1) | MY136520A (enExample) |
| NO (1) | NO324698B1 (enExample) |
| NZ (1) | NZ523047A (enExample) |
| PL (1) | PL203936B1 (enExample) |
| RU (2) | RU2298550C2 (enExample) |
| SK (1) | SK17932002A3 (enExample) |
| WO (1) | WO2001098273A1 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CO5300399A1 (es) | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | Heterocicliocs que contienen nitrogeno, proceso para su preparacion y composiciones farmaceuticas que los contienen |
| US7005439B2 (en) * | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
| AR028948A1 (es) * | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
| AR035230A1 (es) * | 2001-03-19 | 2004-05-05 | Astrazeneca Ab | Compuestos de bencimidazol, proceso para su preparacion, composicion farmaceutica, proceso para la preparacion de dicha composicion farmaceutica, y usos de estos compuestos para la elaboracion de medicamentos |
| SE0202133D0 (sv) | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Novel compounds |
| CN100372838C (zh) * | 2003-02-17 | 2008-03-05 | 弗·哈夫曼-拉罗切有限公司 | 哌啶-苯磺酰胺衍生物 |
| US8017762B2 (en) | 2003-04-17 | 2011-09-13 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| US8796436B2 (en) | 2003-04-17 | 2014-08-05 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| JP4597976B2 (ja) | 2003-04-17 | 2010-12-15 | アルナイラム ファーマシューティカルズ インコーポレイテッド | 修飾ｉＲＮＡ剤 |
| US7723509B2 (en) | 2003-04-17 | 2010-05-25 | Alnylam Pharmaceuticals | IRNA agents with biocleavable tethers |
| US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
| WO2005023771A1 (ja) * | 2003-09-05 | 2005-03-17 | Ono Pharmaceutical Co., Ltd. | ケモカインレセプターアンタゴニストおよびその医薬用途 |
| SE0303090D0 (sv) | 2003-11-20 | 2003-11-20 | Astrazeneca Ab | Novel compounds |
| SE0303541D0 (sv) | 2003-12-22 | 2003-12-22 | Astrazeneca Ab | New compounds |
| EP1912942A1 (en) * | 2005-08-01 | 2008-04-23 | AstraZeneca AB | Novel piperidine derivatives as chemokine receptor modulators useful for the treatment of respiratory diseases. |
| TW200738635A (en) * | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
| TW200738634A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
| TW200734305A (en) * | 2005-08-02 | 2007-09-16 | Astrazeneca Ab | New salt III |
| TW200744612A (en) * | 2005-08-26 | 2007-12-16 | Astrazeneca Ab | New combination |
| JO2769B1 (en) | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
| TW200800895A (en) * | 2005-11-02 | 2008-01-01 | Astrazeneca Ab | Novel compounds |
| CN101437797A (zh) * | 2006-03-07 | 2009-05-20 | 阿斯利康(瑞典)有限公司 | 哌啶衍生物，制备它们的方法，它们作为治疗剂的用途和含有它们的药物组合物 |
| CN101437795A (zh) * | 2006-03-07 | 2009-05-20 | 阿斯利康(瑞典)有限公司 | 哌啶衍生物，制备它们的方法，它们作为治疗剂的用途和含有它们的药物组合物 |
| US20080064884A1 (en) * | 2006-05-10 | 2008-03-13 | Astrazeneca Ab | Novel Process 1 |
| CN101516863A (zh) * | 2006-07-18 | 2009-08-26 | 阿斯利康(瑞典)有限公司 | 制备取代的2-乙酰基氨基-烷氧基苯的方法 |
| JO2642B1 (en) | 2006-12-08 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| GB0702456D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | New combination |
| JO2849B1 (en) | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| EP2125728A4 (en) * | 2007-02-23 | 2011-06-22 | Astrazeneca Ab | NOVEL COMBINATION OF COMPOUNDS FOR THE TREATMENT OF AIRWAY DISEASES, IN PARTICULAR CHRONIC OBSTRUCTIVE BRONCHOPNEUMOPATHY (COPD) AND ASTHMA |
| WO2008121065A1 (en) * | 2007-03-30 | 2008-10-09 | Astrazeneca Ab | Novel pyrrolidine derivatives as antagonists of the chemokine receptor |
| WO2008128996A1 (en) | 2007-04-23 | 2008-10-30 | Janssen Pharmaceutica N.V. | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
| CA2683111A1 (en) | 2007-04-23 | 2008-10-30 | Janssen Pharmaceutica N.V. | 4-alkoxypyridazine derivatives as fast dissociating dopamine 2 receptor antagonists |
| MX2011000043A (es) | 2008-07-03 | 2011-02-22 | Janssen Pharmaceutica Nv | 6-(1-piperazinil)-piridazinas sustituidas como antagonistas del receptor 5-ht6. |
| DK2307374T3 (en) | 2008-07-31 | 2017-05-01 | Janssen Pharmaceutica Nv | PIPERAZIN-1-YLTRIFLUORMETHYL-SUBSTITUTED PYRIDINES AS QUICK DISSOCATING DOPAMIN-2 RECEPTOR ANTAGONISTS |
| GB0913345D0 (en) | 2009-07-31 | 2009-09-16 | Astrazeneca Ab | New combination 802 |
| WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
| WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
| GB201021979D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | New compound |
| GB201021992D0 (en) | 2010-12-23 | 2011-02-02 | Astrazeneca Ab | Compound |
| WO2012163848A1 (en) | 2011-05-27 | 2012-12-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of crohn's disease |
| EP3083609B1 (en) | 2013-12-19 | 2018-08-15 | Merck Sharp & Dohme Corp. | Hiv protease inhibitors |
| CN113767095A (zh) * | 2019-05-01 | 2021-12-07 | 勃林格殷格翰国际有限公司 | (r)-4-溴苯磺酸(2-甲基环氧乙烷-2-基)甲酯 |
| EP4115885A1 (en) | 2021-07-05 | 2023-01-11 | Charité - Universitätsmedizin Berlin | A pharmaceutical composition comprising bay 86-5277 and salts thereof for use in the treatment of viral infections and hyperinflammation |
| JP2025500826A (ja) | 2021-12-14 | 2025-01-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 慢性腎疾患を処置するためのアルドステロンシンターゼ阻害薬 |
Family Cites Families (106)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1220440B (de) | 1962-02-14 | 1966-07-07 | Sanol Arznei Schwarz Gmbh | Verfahren zur Herstellung von Derivaten des 1-(o-Bromphenoxy)-2-hydroxy-3-amino-propans und deren Saeureadditionssalzen |
| US3577432A (en) * | 1968-12-23 | 1971-05-04 | Robins Co Inc A H | 1-substituted-3-phenoxypyrrolidines |
| US4029801A (en) | 1970-09-03 | 1977-06-14 | John Wyeth & Brother Limited | Pharmaceutical compositions and methods of treating hypertension |
| JPS5511670B1 (enExample) | 1971-07-13 | 1980-03-26 | ||
| US4080328A (en) * | 1971-07-13 | 1978-03-21 | Sumitomo Chemical Company, Limited | N-substituted heterocyclic derivatives and preparation thereof |
| US3994974A (en) * | 1972-02-05 | 1976-11-30 | Yamanouchi Pharmaceutical Co., Ltd. | α-Aminomethylbenzyl alcohol derivatives |
| US3755584A (en) * | 1972-04-03 | 1973-08-28 | Abbott Lab | Tranquilizers |
| SE378109B (enExample) | 1972-05-19 | 1975-08-18 | Bofors Ab | |
| FR2190430A1 (en) | 1972-06-29 | 1974-02-01 | Ferlux | N-aminomethylhydroxamic acids - with antiinflammatory activity pre-pared by Mannich reaction |
| US3818017A (en) | 1973-01-04 | 1974-06-18 | Janssen Pharmaceutica Nv | 1-{8 1-(2-hydroxy-3-aryloxypropyl)-4-piperidyl{9 -2-benzimidazolinones and related compounds |
| US3894030A (en) | 1973-01-04 | 1975-07-08 | Janssen Pharmaceutica Nv | 1-{8 1-(2-Hydroxy-3-aryloxypropyl)-4-piperidyl{9 -2-benzimidazolinones and related compounds |
| US4166119A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing spiro[dihydrobenzofuran]piperidines and pyrrolidines |
| WO1980000152A1 (fr) * | 1978-07-03 | 1980-02-07 | Sandoz Ag | Derives d'un 3-aminopropoxy-aryle, leur preparation et utilisation |
| US4264613A (en) | 1979-08-01 | 1981-04-28 | Science Union Et Cie, Societe Francaise De Recherche Medicale | Piperidylbenzimidazolinone compounds |
| FR2469411A1 (fr) | 1979-11-15 | 1981-05-22 | Science Union & Cie | Nouveaux derives de la piperidylbenzimidazolinone, leurs procedes de preparation et les compositions pharmaceutiques les renfermant |
| EP0095454A3 (de) | 1982-05-13 | 1985-04-03 | Gerot-Pharmazeutika Gesellschaft m.b.H. | Neue kernsubstituierte Pyrogallol-Derivate |
| JPS59222484A (ja) | 1983-06-02 | 1984-12-14 | Kowa Co | テトラヒドロナフチルカルボン酸フエニルエステル誘導体 |
| GB8334494D0 (en) * | 1983-12-24 | 1984-02-01 | Tanabe Seiyaku Co | Carbostyril derivatives |
| US5614533A (en) * | 1987-03-13 | 1997-03-25 | Bio-Mega/Boehringer Ingelheim Research, Inc. | Substituted pipecolinic acid derivatives as HIV protease inhibitors |
| DE3723568C2 (de) | 1987-07-16 | 1994-01-27 | Siemens Ag | Differenzstromschutzschalter |
| DE3723648A1 (de) | 1987-07-17 | 1989-01-26 | Sandoz Ag | Indol-derivate, ihre herstellung und sie enthaltende arzneimittel |
| US4791121A (en) * | 1987-11-02 | 1988-12-13 | The Boc Group, Inc. | 4-phenyl-4-(N-(phenyl)amido) piperidine derivatives and pharmaceutical compositions and method employing such compounds |
| AU4414289A (en) * | 1988-09-30 | 1990-04-18 | Mallinckrodt, Inc. | A process for the production of granular metal soaps |
| GR1001529B (el) | 1990-09-07 | 1994-03-31 | Elmuquimica Farm Sl | Μέ?οδος για την λήψη νέων 21-εστέρων της 16-17-ακετάλης της πρ να-1,4-διενο-3,20-διόνης. |
| SE9003057D0 (sv) | 1990-09-26 | 1990-09-26 | Astra Ab | New process |
| ES2027897A6 (es) | 1991-01-24 | 1992-06-16 | Espanola Prod Quimicos | Procedimiento de preparacion de nuevos derivados de la difenilmetilpiperacina. |
| FR2676054B1 (fr) * | 1991-05-03 | 1993-09-03 | Sanofi Elf | Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| IL105716A0 (en) | 1992-06-08 | 1993-09-22 | Richter Gedeon Vegyeszet | Aminopropanol derivatives,their preparation and pharmaceutical compositions containing them |
| IL106600A (en) | 1992-08-07 | 1997-09-30 | Sankyo Co | Peptides, pharmaceutical compositions containing the same and processes for the preparation thereof |
| US5614523A (en) * | 1995-01-17 | 1997-03-25 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| US5627196A (en) * | 1995-01-17 | 1997-05-06 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| US5789402A (en) * | 1995-01-17 | 1998-08-04 | Eli Lilly Company | Compounds having effects on serotonin-related systems |
| US5741789A (en) * | 1995-01-17 | 1998-04-21 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| US5576321A (en) * | 1995-01-17 | 1996-11-19 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| ZA9610738B (en) | 1995-12-22 | 1997-06-24 | Warner Lambert Co | Subtype selective nmda receptor ligands and the use thereof |
| AU719434B2 (en) | 1996-02-13 | 2000-05-11 | Astrazeneca Ab | Quinazoline derivatives as VEGF inhibitors |
| AU719327B2 (en) | 1996-03-05 | 2000-05-04 | Astrazeneca Ab | 4-anilinoquinazoline derivatives |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| DE19703131A1 (de) | 1997-01-29 | 1998-07-30 | Bayer Ag | Verwendung von Chinoxalin in Dreier-Kombination mit Protease-Inhibitoren und Reverse Transkriptaseinhibitoren als Arzneimittel zur Behandlung von AIDS und/oder HIV-Infektionen |
| GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
| IL125658A0 (en) | 1997-08-18 | 1999-04-11 | Hoffmann La Roche | Ccr-3 receptor antagonists |
| NZ503782A (en) * | 1997-11-18 | 2002-03-28 | Dupont Pharmaceuticals Res Lab | Cyclic amine derivatives and chemokine receptor antagonists that are effective in treating disease caused by infiltration of the tissue by blood leukocytes |
| DE19755268A1 (de) | 1997-12-12 | 1999-06-17 | Merck Patent Gmbh | Benzamidinderivate |
| FR2780057B1 (fr) | 1998-06-18 | 2002-09-13 | Sanofi Sa | Phenoxypropanolamines, procede pour leur preparation et compositions pharmaceutiques les contenant |
| BR9915735A (pt) | 1998-11-20 | 2001-09-04 | Hoffmann La Roche | Antagonistas receptores de ccr-3 de piperidina |
| CA2346933A1 (en) | 1998-12-18 | 2000-06-22 | Dupont Pharmaceuticals Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| AU2057200A (en) | 1998-12-18 | 2000-07-03 | Du Pont Pharmaceuticals Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| GB9900334D0 (en) | 1999-01-07 | 1999-02-24 | Angiogene Pharm Ltd | Tricylic vascular damaging agents |
| GB9900752D0 (en) | 1999-01-15 | 1999-03-03 | Angiogene Pharm Ltd | Benzimidazole vascular damaging agents |
| SE9900833D0 (sv) | 1999-03-09 | 1999-03-09 | Astra Ab | Novel combination |
| AU2942000A (en) | 1999-03-11 | 2000-09-28 | Banyu Pharmaceutical Co., Ltd. | Novel piperidine derivatives |
| JP3495955B2 (ja) * | 1999-03-26 | 2004-02-09 | シャープ株式会社 | 半導体メモリ装置及びその製造方法 |
| KR20010108394A (ko) * | 1999-03-26 | 2001-12-07 | 다비드 에 질레스 | 신규 화합물 |
| GB9913083D0 (en) | 1999-06-04 | 1999-08-04 | Novartis Ag | Organic compounds |
| AU5011300A (en) | 1999-05-14 | 2000-12-05 | Combichem, Inc. | Cyclic amine derivatives and their uses |
| ES2165768B1 (es) * | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | Nuevos derivados de quinuclidina y composiciones farmaceuticas que los contienen. |
| AUPQ165599A0 (en) | 1999-07-15 | 1999-08-05 | University Of Sydney, The | Optical processing method and apparatus and products thereof |
| SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| FR2802533B1 (fr) | 1999-12-17 | 2002-02-15 | Sanofi Synthelabo | Phenoxypropanolamines, leur preparation et leur application en therapeutique |
| ATE356624T1 (de) | 1999-12-17 | 2007-04-15 | Sanofi Aventis | Phenoxypropanolamin-derivate, ihre herstellung und therapeutische verwendung |
| CO5300399A1 (es) * | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | Heterocicliocs que contienen nitrogeno, proceso para su preparacion y composiciones farmaceuticas que los contienen |
| GB0011838D0 (en) | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
| GB0012260D0 (en) | 2000-05-19 | 2000-07-12 | Astrazeneca Ab | Novel composition |
| CA2406979A1 (en) | 2000-05-31 | 2001-12-06 | Astrazeneca Ab | Indole derivatives with vascular damaging activity |
| AR028948A1 (es) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
| US7005439B2 (en) * | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
| AR028947A1 (es) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
| EP1294690A2 (en) | 2000-06-21 | 2003-03-26 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| GB0015876D0 (en) | 2000-06-28 | 2000-08-23 | Novartis Ag | Organic compounds |
| AU2001266233B2 (en) | 2000-07-07 | 2006-06-29 | Angiogene Pharmaceuticals Limited | Colchinol derivatives as vascular damaging agents |
| MXPA02012903A (es) | 2000-07-07 | 2004-07-30 | Angiogene Pharm Ltd | Derivados de colquinol como inhibidores de angiogenesis. |
| AU7649701A (en) | 2000-08-05 | 2002-02-18 | Glaxo Group Ltd | 17.beta.-carbothioate 17.alpha.-arylcarbonyloxyloxy androstane derivative as anti-inflammatory agents |
| GB0021670D0 (en) | 2000-09-04 | 2000-10-18 | Astrazeneca Ab | Chemical compounds |
| GB0029562D0 (en) | 2000-12-04 | 2001-01-17 | Novartis Ag | Organic compounds |
| GB2373186A (en) | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
| AR035230A1 (es) * | 2001-03-19 | 2004-05-05 | Astrazeneca Ab | Compuestos de bencimidazol, proceso para su preparacion, composicion farmaceutica, proceso para la preparacion de dicha composicion farmaceutica, y usos de estos compuestos para la elaboracion de medicamentos |
| GB0107228D0 (en) | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
| DE60224172T2 (de) | 2001-03-22 | 2008-12-04 | Glaxo Group Ltd., Greenford | Formanilid-derivative als beta2-adrenorezeptor-agonisten |
| SE0101038D0 (sv) * | 2001-03-23 | 2001-03-23 | Astrazeneca Ab | Novel compounds |
| KR100406536B1 (ko) * | 2001-03-28 | 2003-11-20 | 주식회사 하이닉스반도체 | 산소확산방지막으로서 알루미늄 산화막을 구비하는강유전체 메모리 소자 및 그 제조 방법 |
| GB0108046D0 (en) | 2001-03-30 | 2001-05-23 | Astrazeneca Ab | Chemical compounds |
| CA2445348A1 (en) | 2001-04-27 | 2002-11-07 | Mitsubishi Pharma Corporation | Novel benzylpiperidine compound |
| CN1302007C (zh) | 2001-04-30 | 2007-02-28 | 葛兰素集团有限公司 | 具有抗炎性的在17.α位上具有环酯基的雄甾烷的17.β.－硫代羧酸酯衍生物 |
| CN1290194C (zh) * | 2001-06-25 | 2006-12-13 | 松下电器产业株式会社 | 电容元件、半导体存储器及其制备方法 |
| JP4467229B2 (ja) * | 2001-09-12 | 2010-05-26 | 株式会社ハイニックスセミコンダクター | 半導体素子の製造方法 |
| TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
| US20030229058A1 (en) | 2001-11-13 | 2003-12-11 | Moran Edmund J. | Aryl aniline beta2 adrenergic receptor agonists |
| GB0127547D0 (en) | 2001-11-16 | 2002-01-09 | Astrazeneca Ab | Chemical compounds |
| SE0104251D0 (sv) | 2001-12-14 | 2001-12-14 | Astrazeneca Ab | Novel compounds |
| TW200303304A (en) | 2002-02-18 | 2003-09-01 | Astrazeneca Ab | Chemical compounds |
| SE0200919D0 (sv) | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Chemical compounds |
| GB0207436D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
| US6583507B1 (en) * | 2002-04-26 | 2003-06-24 | Bum Ki Moon | Barrier for capacitor over plug structures |
| EA200500618A1 (ru) | 2002-10-11 | 2005-12-29 | Пфайзер Инк. | Производные индола в качестве бета-2 агонистов |
| KR100578212B1 (ko) * | 2003-06-30 | 2006-05-11 | 주식회사 하이닉스반도체 | 엠티피 구조의 강유전체 캐패시터 및 그 제조 방법 |
| US20060183731A1 (en) | 2003-07-15 | 2006-08-17 | Min Ge | 7 and 8 membered heterocyclic cyclopentyl benzylamide modulators of chemokine receptor activity |
| US20090246281A1 (en) | 2003-11-03 | 2009-10-01 | Norton Healthcare Ltd. | Soft steroid compositions for use in dry powder inhalers |
| US7180141B2 (en) * | 2004-12-03 | 2007-02-20 | Texas Instruments Incorporated | Ferroelectric capacitor with parallel resistance for ferroelectric memory |
| EP1912942A1 (en) | 2005-08-01 | 2008-04-23 | AstraZeneca AB | Novel piperidine derivatives as chemokine receptor modulators useful for the treatment of respiratory diseases. |
| TW200738635A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
| TW200734305A (en) | 2005-08-02 | 2007-09-16 | Astrazeneca Ab | New salt III |
| TW200738634A (en) * | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
| TW200744612A (en) | 2005-08-26 | 2007-12-16 | Astrazeneca Ab | New combination |
| AU2006282122A1 (en) | 2005-08-26 | 2007-03-01 | Astrazeneca Ab | A combination of compounds, which can be used in the treatment of respiratory diseases, especially chronic obstructive pulmonary disease (COPD) and asthma |
| TW200800895A (en) | 2005-11-02 | 2008-01-01 | Astrazeneca Ab | Novel compounds |
-
2001
- 2001-06-11 AR ARP010102758A patent/AR028948A1/es unknown
- 2001-06-14 JP JP2002504229A patent/JP4022142B2/ja not_active Expired - Lifetime
- 2001-06-14 SK SK1793-2002A patent/SK17932002A3/sk not_active Application Discontinuation
- 2001-06-14 BR BR0111667-3A patent/BR0111667A/pt not_active Application Discontinuation
- 2001-06-14 WO PCT/SE2001/001377 patent/WO2001098273A1/en not_active Ceased
- 2001-06-14 HU HU0301187A patent/HUP0301187A3/hu unknown
- 2001-06-14 CA CA002414095A patent/CA2414095C/en not_active Expired - Fee Related
- 2001-06-14 CN CNB018142141A patent/CN1307157C/zh not_active Expired - Fee Related
- 2001-06-14 AU AU2001274763A patent/AU2001274763B2/en not_active Ceased
- 2001-06-14 US US10/311,841 patent/US6911458B2/en not_active Expired - Fee Related
- 2001-06-14 RU RU2002132385/04A patent/RU2298550C2/ru not_active IP Right Cessation
- 2001-06-14 AU AU7476301A patent/AU7476301A/xx active Pending
- 2001-06-14 EE EEP200200704A patent/EE05157B1/xx not_active IP Right Cessation
- 2001-06-14 CZ CZ20024146A patent/CZ20024146A3/cs unknown
- 2001-06-14 PL PL366198A patent/PL203936B1/pl not_active IP Right Cessation
- 2001-06-14 EP EP01941406A patent/EP1299357A1/en not_active Withdrawn
- 2001-06-14 NZ NZ523047A patent/NZ523047A/en unknown
- 2001-06-14 IL IL15316701A patent/IL153167A0/xx unknown
- 2001-06-14 RU RU2006141320/04A patent/RU2419608C2/ru not_active IP Right Cessation
- 2001-06-14 KR KR1020027017281A patent/KR100799061B1/ko not_active Expired - Fee Related
- 2001-06-14 MX MXPA02012425A patent/MXPA02012425A/es active IP Right Grant
- 2001-06-18 MY MYPI20012866A patent/MY136520A/en unknown
-
2002
- 2002-11-28 IL IL153167A patent/IL153167A/en not_active IP Right Cessation
- 2002-12-17 NO NO20026064A patent/NO324698B1/no not_active IP Right Cessation
- 2002-12-17 IS IS6658A patent/IS6658A/is unknown
-
2004
- 2004-11-22 US US10/994,683 patent/US7528156B2/en not_active Expired - Fee Related
-
2009
- 2009-05-04 US US12/434,955 patent/US20090306141A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2001274763B2 (en) | Novel compounds | |
| AU2001274763A1 (en) | Novel compounds | |
| EP1499590B1 (en) | Piperidine derivatives as potassium channel blockers | |
| EP1263725B1 (en) | Novel compounds | |
| US7345063B2 (en) | Amides, preparation and therapeutic use as modulators of CCR-receptor activity | |
| EP1421082B1 (en) | piperidinyl-morpholinyl derivatives as modulators of chemokine receptor activity | |
| EP1299356B1 (en) | Novel compounds | |
| EP1421070B1 (en) | New piperidinyl derivates as modulators of chemokine receptor activity | |
| US7005439B2 (en) | Compounds | |
| AU2001274764B2 (en) | Novel compounds | |
| AU2001274764A1 (en) | Novel compounds | |
| AU2002243154A1 (en) | Novel amides, preparation and therapeutic use as modulators of CCR-receptor activity | |
| HK1071134B (en) | Piperidine derivatives as potassium channel blockers | |
| HK1051372B (en) | Novel compounds | |
| ZA200209904B (en) | Novel compounds. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |