ES2289124T3 - Derivados de pteridinona como moduladores de la actividad del receptor de quimioquinas. - Google Patents
Derivados de pteridinona como moduladores de la actividad del receptor de quimioquinas. Download PDFInfo
- Publication number
- ES2289124T3 ES2289124T3 ES02749129T ES02749129T ES2289124T3 ES 2289124 T3 ES2289124 T3 ES 2289124T3 ES 02749129 T ES02749129 T ES 02749129T ES 02749129 T ES02749129 T ES 02749129T ES 2289124 T3 ES2289124 T3 ES 2289124T3
- Authority
- ES
- Spain
- Prior art keywords
- amino
- methyl
- hydroxy
- thio
- difluorophenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- VWXIHLCLIOQWRA-UHFFFAOYSA-N 1h-pteridin-2-one Chemical class N1=CC=NC2=NC(O)=NC=C21 VWXIHLCLIOQWRA-UHFFFAOYSA-N 0.000 title abstract description 4
- 230000000694 effects Effects 0.000 title description 9
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 140
- -1 R 14 Chemical compound 0.000 claims description 83
- 125000001424 substituent group Chemical group 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 150000002148 esters Chemical class 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000004429 atom Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 238000001727 in vivo Methods 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000002837 carbocyclic group Chemical group 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 239000002671 adjuvant Substances 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 claims description 4
- 150000003573 thiols Chemical class 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- ZTFZCHNNRCXWAG-SSDOTTSWSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]pteridine-6,7-dione Chemical compound N=1C2=NC(=O)C(=O)N=C2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F ZTFZCHNNRCXWAG-SSDOTTSWSA-N 0.000 claims description 3
- GKLYYCIWVVQCGT-SSDOTTSWSA-N 6-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F GKLYYCIWVVQCGT-SSDOTTSWSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 150000002390 heteroarenes Chemical class 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 230000001012 protector Effects 0.000 claims description 3
- KKMVXGXYFFLOPQ-MRVPVSSYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-(1,3,4-thiadiazol-2-ylsulfanyl)-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(SC=3SC=NN=3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F KKMVXGXYFFLOPQ-MRVPVSSYSA-N 0.000 claims description 2
- MUDWPDAGHITARX-CQSZACIVSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-(3-morpholin-4-ylpropylamino)-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCCCN3CCOCC3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F MUDWPDAGHITARX-CQSZACIVSA-N 0.000 claims description 2
- MZFWXBLDIJWPCR-LLVKDONJSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[(3-methyl-1,2-oxazol-5-yl)methylamino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCC=3ON=C(C)C=3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F MZFWXBLDIJWPCR-LLVKDONJSA-N 0.000 claims description 2
- CHPJZELNRGVDLP-MRVPVSSYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[(4-methyl-5-oxo-1h-1,2,4-triazol-3-yl)sulfanyl]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(SC=3N(C(O)=NN=3)C)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F CHPJZELNRGVDLP-MRVPVSSYSA-N 0.000 claims description 2
- XGOWZCYPONHVKM-LLVKDONJSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[(5-methylfuran-2-yl)methylamino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCC=3OC(C)=CC=3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F XGOWZCYPONHVKM-LLVKDONJSA-N 0.000 claims description 2
- OIRZVBNJYAPRHE-GFCCVEGCSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[(5-methylpyrazin-2-yl)methylamino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCC=3N=CC(C)=NC=3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F OIRZVBNJYAPRHE-GFCCVEGCSA-N 0.000 claims description 2
- CQAQTXGPDRPWDH-GFCCVEGCSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[2-(pyrimidin-2-ylamino)ethylamino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCCNC=3N=CC=CN=3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F CQAQTXGPDRPWDH-GFCCVEGCSA-N 0.000 claims description 2
- SCJKIUVMYZARFJ-ZJUUUORDSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[[(2s)-2-hydroxypropyl]amino]-8h-pteridin-7-one Chemical compound N1=C2NC(=O)C(NC[C@@H](O)C)=NC2=C(N[C@H](C)CO)N=C1SCC1=CC=CC(F)=C1F SCJKIUVMYZARFJ-ZJUUUORDSA-N 0.000 claims description 2
- XXIIGXHZUBEGHE-LLVKDONJSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-morpholin-4-yl-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N3CCOCC3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F XXIIGXHZUBEGHE-LLVKDONJSA-N 0.000 claims description 2
- IBNATWDQRDENTJ-SNVBAGLBSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-6-(3-hydroxy-3-methylazetidin-1-yl)-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N3CC(C)(O)C3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F IBNATWDQRDENTJ-SNVBAGLBSA-N 0.000 claims description 2
- YXGWETQPTDXSGH-LLVKDONJSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-6-(furan-2-ylmethylamino)-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCC=3OC=CC=3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F YXGWETQPTDXSGH-LLVKDONJSA-N 0.000 claims description 2
- PVRSGKCTEXIMQU-FRRDWIJNSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-6-[(3r,5s)-3,5-dimethylpiperazin-1-yl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N3C[C@@H](C)N[C@@H](C)C3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F PVRSGKCTEXIMQU-FRRDWIJNSA-N 0.000 claims description 2
- GTHGGGWFVGCSEQ-RTXFEEFZSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-6-[[(1s,4r)-4-hydroxycyclopent-2-en-1-yl]amino]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N[C@@H]3C=C[C@H](O)C3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F GTHGGGWFVGCSEQ-RTXFEEFZSA-N 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims description 2
- YFLQCAXLEGLQJF-SECBINFHSA-N 6-(2-aminoethylsulfanyl)-2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(SCCN)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F YFLQCAXLEGLQJF-SECBINFHSA-N 0.000 claims description 2
- UKYVPZWPXDEYJV-SNVBAGLBSA-N 6-(azetidin-1-yl)-2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N3CCC3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F UKYVPZWPXDEYJV-SNVBAGLBSA-N 0.000 claims description 2
- AMRHSMUASGKNEG-CYBMUJFWSA-N 6-(benzylamino)-2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCC=3C=CC=CC=3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F AMRHSMUASGKNEG-CYBMUJFWSA-N 0.000 claims description 2
- ZQBXZTJWEMVRDP-PWSUYJOCSA-N 6-[(3s)-3-aminopyrrolidin-1-yl]-2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N3C[C@@H](N)CC3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F ZQBXZTJWEMVRDP-PWSUYJOCSA-N 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- 239000011800 void material Substances 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 86
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 201000010099 disease Diseases 0.000 description 21
- 238000004949 mass spectrometry Methods 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
- 102000019034 Chemokines Human genes 0.000 description 16
- 108010012236 Chemokines Proteins 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 229910052794 bromium Inorganic materials 0.000 description 11
- 206010039083 rhinitis Diseases 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 8
- 102000009410 Chemokine receptor Human genes 0.000 description 8
- 108050000299 Chemokine receptor Proteins 0.000 description 8
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 210000000440 neutrophil Anatomy 0.000 description 7
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 201000004681 Psoriasis Diseases 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 208000010668 atopic eczema Diseases 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 150000002431 hydrogen Chemical class 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 102000004890 Interleukin-8 Human genes 0.000 description 4
- 108090001007 Interleukin-8 Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- IFLVGRRVGPXYON-UHFFFAOYSA-N adci Chemical compound C12=CC=CC=C2C2(C(=O)N)C3=CC=CC=C3CC1N2 IFLVGRRVGPXYON-UHFFFAOYSA-N 0.000 description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 108010004073 cysteinylcysteine Proteins 0.000 description 4
- 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 4
- 229940096397 interleukin-8 Drugs 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000012266 salt solution Substances 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 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 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 108010001478 Bacitracin Proteins 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000007995 HEPES buffer Substances 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 229960003071 bacitracin Drugs 0.000 description 3
- 229930184125 bacitracin Natural products 0.000 description 3
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- BKMMTJMQCTUHRP-GSVOUGTGSA-N (2r)-2-aminopropan-1-ol Chemical compound C[C@@H](N)CO BKMMTJMQCTUHRP-GSVOUGTGSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 201000008283 Atrophic Rhinitis 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
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 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
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 241000721454 Pemphigus Species 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 206010039088 Rhinitis atrophic Diseases 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229950005228 bromoform Drugs 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 201000002491 encephalomyelitis Diseases 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
- 239000012160 loading buffer Substances 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- ULFIDBFKOXGOGD-UHFFFAOYSA-N methyl 2-methanimidoyloxyacetate;hydrochloride Chemical compound Cl.COC(=O)COC=N ULFIDBFKOXGOGD-UHFFFAOYSA-N 0.000 description 2
- 210000000274 microglia Anatomy 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 230000002969 morbid Effects 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000012536 storage buffer Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000009885 systemic effect Effects 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
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- ZUYAQWHOBKDCGB-SSDOTTSWSA-N (2r)-2-[[5,6-diamino-2-[(2,3-difluorophenyl)methylsulfanyl]pyrimidin-4-yl]amino]propan-1-ol Chemical compound NC1=C(N)C(N[C@@H](CO)C)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 ZUYAQWHOBKDCGB-SSDOTTSWSA-N 0.000 description 1
- OCVYJCWHULKKBX-SSDOTTSWSA-N (2r)-2-[[6-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-5-nitrosopyrimidin-4-yl]amino]propan-1-ol Chemical compound NC1=C(N=O)C(N[C@@H](CO)C)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 OCVYJCWHULKKBX-SSDOTTSWSA-N 0.000 description 1
- GIYHKZKPLCUONW-MRVPVSSYSA-N (2r)-2-[[6-amino-2-[(2,3-difluorophenyl)methylsulfanyl]pyrimidin-4-yl]amino]propan-1-ol Chemical compound OC[C@@H](C)NC1=CC(N)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 GIYHKZKPLCUONW-MRVPVSSYSA-N 0.000 description 1
- QUPFKBITVLIQNA-KPKJPENVSA-N (5e)-2-sulfanylidene-5-[[5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene]-1,3-thiazolidin-4-one Chemical compound FC(F)(F)C1=CC=CC(C=2OC(\C=C\3C(NC(=S)S/3)=O)=CC=2)=C1 QUPFKBITVLIQNA-KPKJPENVSA-N 0.000 description 1
- KZEVSDGEBAJOTK-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[5-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CC=1OC(=NN=1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O KZEVSDGEBAJOTK-UHFFFAOYSA-N 0.000 description 1
- FTBSGSZZESQDBM-UHFFFAOYSA-N 1-(bromomethyl)-2,3-difluorobenzene Chemical compound FC1=CC=CC(CBr)=C1F FTBSGSZZESQDBM-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- KUTWLEBOCQOIJI-SNVBAGLBSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-(2-methoxyethylamino)-8h-pteridin-7-one Chemical compound N1=C2NC(=O)C(NCCOC)=NC2=C(N[C@H](C)CO)N=C1SCC1=CC=CC(F)=C1F KUTWLEBOCQOIJI-SNVBAGLBSA-N 0.000 description 1
- CXIJOEKYFIEHRY-ZYHUDNBSSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[(3r)-3-hydroxypyrrolidin-1-yl]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N3C[C@H](O)CC3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F CXIJOEKYFIEHRY-ZYHUDNBSSA-N 0.000 description 1
- CXIJOEKYFIEHRY-PWSUYJOCSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-6-[(3s)-3-hydroxypyrrolidin-1-yl]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(N3C[C@@H](O)CC3)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F CXIJOEKYFIEHRY-PWSUYJOCSA-N 0.000 description 1
- LTHIETOWBQBYAF-MRVPVSSYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F LTHIETOWBQBYAF-MRVPVSSYSA-N 0.000 description 1
- UUSHWADNFWAUQP-UHFFFAOYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-5-nitrosopyrimidine-4,6-diamine Chemical compound NC1=C(N=O)C(N)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 UUSHWADNFWAUQP-UHFFFAOYSA-N 0.000 description 1
- QICOKHONKZYLDJ-SECBINFHSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]-6-(2-hydroxyethylamino)-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(NCCO)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F QICOKHONKZYLDJ-SECBINFHSA-N 0.000 description 1
- VMLNQOIISKHWST-UHFFFAOYSA-N 2-[(2,3-difluorophenyl)methylsulfanyl]pyrimidine-4,6-diamine Chemical compound NC1=CC(N)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 VMLNQOIISKHWST-UHFFFAOYSA-N 0.000 description 1
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- LCFFBTAVFPGIRI-UHFFFAOYSA-N 2-methanimidoyloxyacetic acid Chemical compound OC(=O)COC=N LCFFBTAVFPGIRI-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- LUBSJTIQAOZACI-UHFFFAOYSA-N 4-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C=NC=2C(N)=NC=1SCC1=CC=CC(F)=C1F LUBSJTIQAOZACI-UHFFFAOYSA-N 0.000 description 1
- QQYSUMFYUUZAML-UHFFFAOYSA-N 4-bromo-2-[(2,3-difluorophenyl)methylsulfanyl]-8h-pteridin-7-one Chemical compound FC1=CC=CC(CSC=2N=C3NC(=O)C=NC3=C(Br)N=2)=C1F QQYSUMFYUUZAML-UHFFFAOYSA-N 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- OIJAQCUSQDDCOY-UHFFFAOYSA-N 6-amino-2-[(2,3-difluorophenyl)methylsulfanyl]-1h-pyrimidin-4-one Chemical compound NC1=CC(=O)NC(SCC=2C(=C(F)C=CC=2)F)=N1 OIJAQCUSQDDCOY-UHFFFAOYSA-N 0.000 description 1
- BWYGMIYEADAIGW-UHFFFAOYSA-N 6-amino-2-sulfanylidene-1h-pyrimidin-4-one;hydrate Chemical compound O.NC1=CC(=O)NC(=S)N1 BWYGMIYEADAIGW-UHFFFAOYSA-N 0.000 description 1
- YWSPVVYDWQCLPK-SSDOTTSWSA-N 6-bromo-2-[(2,3-difluorophenyl)methylsulfanyl]-4-[[(2r)-1-hydroxypropan-2-yl]amino]-8h-pteridin-7-one Chemical compound N=1C=2NC(=O)C(Br)=NC=2C(N[C@@H](CO)C)=NC=1SCC1=CC=CC(F)=C1F YWSPVVYDWQCLPK-SSDOTTSWSA-N 0.000 description 1
- VQRYOXOOXNDQAU-UHFFFAOYSA-N 6-chloro-2-[(2,3-difluorophenyl)methylsulfanyl]pyrimidin-4-amine Chemical compound NC1=CC(Cl)=NC(SCC=2C(=C(F)C=CC=2)F)=N1 VQRYOXOOXNDQAU-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 208000035939 Alveolitis allergic Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 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
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100032367 C-C motif chemokine 5 Human genes 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
- 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
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 108700012434 CCL3 Proteins 0.000 description 1
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 1
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 1
- 102000000013 Chemokine CCL3 Human genes 0.000 description 1
- 102000001326 Chemokine CCL4 Human genes 0.000 description 1
- 108010055165 Chemokine CCL4 Proteins 0.000 description 1
- 108010055166 Chemokine CCL5 Proteins 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
- 108091026890 Coding region Proteins 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
- 102100023688 Eotaxin Human genes 0.000 description 1
- 101710139422 Eotaxin Proteins 0.000 description 1
- 206010053177 Epidermolysis Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 208000027445 Farmer Lung Diseases 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 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
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000798902 Homo sapiens Atypical chemokine receptor 4 Proteins 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
- 101000973997 Homo sapiens Nucleosome assembly protein 1-like 4 Proteins 0.000 description 1
- 101000947178 Homo sapiens Platelet basic protein Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia 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
- 208000009388 Job Syndrome Diseases 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-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
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 208000027771 Obstructive airways disease Diseases 0.000 description 1
- 208000011707 Ovulation disease 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
- 229910019213 POCl3 Inorganic materials 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102100036154 Platelet basic protein Human genes 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 206010060932 Postoperative adhesion Diseases 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 208000020307 Spinal disease Diseases 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 206010044696 Tropical spastic paresis Diseases 0.000 description 1
- 229940122618 Trypsin inhibitor Drugs 0.000 description 1
- 101710162629 Trypsin inhibitor Proteins 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000025865 Ulcer 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
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 125000002393 azetidinyl group Chemical group 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 class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 206010006451 bronchitis Diseases 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
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000001721 carboxyacetyl group Chemical group 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000025434 cerebellar degeneration Diseases 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000002113 chemopreventative effect Effects 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 201000009151 chronic rhinitis Diseases 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 150000001945 cysteines Chemical class 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 208000022195 farmer lung disease Diseases 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002008 hemorrhagic effect Effects 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
- 150000002391 heterocyclic compounds Chemical class 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
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 206010051040 hyper-IgE syndrome Diseases 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000002485 inorganic esters Chemical class 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 238000000670 ligand binding assay Methods 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 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
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 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
- 229960003194 meglumine Drugs 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 206010065579 multifocal motor neuropathy Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 208000020469 nerve plexus disease Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 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
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 208000012111 paraneoplastic syndrome Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 201000006380 plexopathy Diseases 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 208000000813 polyradiculoneuropathy Diseases 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
- 208000017443 reproductive system disease Diseases 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 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
- 229940095064 tartrate Drugs 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 150000008634 thiazolopyrimidines Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000006961 tropical spastic paraparesis Diseases 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61P17/06—Antipsoriatics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Virology (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Reproductive Health (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0102716 | 2001-08-14 | ||
| SE0102716A SE0102716D0 (sv) | 2001-08-14 | 2001-08-14 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2289124T3 true ES2289124T3 (es) | 2008-02-01 |
Family
ID=20285026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02749129T Expired - Lifetime ES2289124T3 (es) | 2001-08-14 | 2002-08-09 | Derivados de pteridinona como moduladores de la actividad del receptor de quimioquinas. |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US20050010047A1 (enExample) |
| EP (1) | EP1419158B1 (enExample) |
| JP (1) | JP2005507390A (enExample) |
| AT (1) | ATE368664T1 (enExample) |
| DE (1) | DE60221537T2 (enExample) |
| ES (1) | ES2289124T3 (enExample) |
| SE (1) | SE0102716D0 (enExample) |
| WO (1) | WO2003024966A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9903544D0 (sv) | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| GB2359081A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| GB2359078A (en) | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB2359551A (en) | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| SE0003828D0 (sv) | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
| SE0101322D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| GB0221828D0 (en) | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0221829D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| EP1520586A1 (en) * | 2003-09-30 | 2005-04-06 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Inhibition of fractalkine or of its receptor for the treatment of atopic allergic diseases |
| GB0328243D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
| WO2007014838A1 (en) * | 2005-08-03 | 2007-02-08 | Boehringer Ingelheim International Gmbh | Dihydropteridinones in the treatment of respiratory diseases |
| WO2009022185A2 (en) * | 2007-08-16 | 2009-02-19 | Astrazeneca Ab | 6, 6-fused heterocycles, their pharmaceutical compositions and methos of use |
| WO2014131741A1 (de) * | 2013-03-01 | 2014-09-04 | Bayer Pharma Aktiengesellschaft | Benzyl-substituierte pyrazolopyridine und ihre verwendung |
| HK1220974A1 (zh) * | 2013-03-01 | 2017-05-19 | Bayer Pharma Aktiengesellschaft | 三氟甲基取代的稠合嘧啶类及其用途 |
| ES2968371T3 (es) | 2013-10-10 | 2024-05-09 | Eastern Virginia Medical School | Derivados de 4-((2-hidroxi-3-metoxibencil)amino) bencenosulfonamida como inhibidores de la 12-lipoxigenasa |
| BR122020020657B1 (pt) * | 2014-04-14 | 2022-12-20 | Boehringer Ingelheim International Gmbh | Compostos, composição farmacêutica e seus usos como moduladores de ror gama |
| CN110540525B (zh) * | 2019-09-19 | 2022-11-22 | 广西师范大学 | 一种3-硫醚基喹喔啉酮化合物的合成方法 |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2924472A (en) * | 1957-06-27 | 1960-02-09 | Gen Motors Corp | Pipe joint seal |
| US3318900A (en) * | 1964-05-06 | 1967-05-09 | Janssen Pharmaceutica Nv | Derivatives of benzimidazolinyl piperidine |
| BE668603A (enExample) * | 1964-08-20 | |||
| US4120521A (en) * | 1975-08-28 | 1978-10-17 | Rieber & Son Plastic-Industri A/S | Combined mould element and sealing ring |
| EG12406A (en) * | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| GB1600293A (en) * | 1977-02-04 | 1981-10-14 | British Oceanics Ltd | Sealing arrangements |
| US4188040A (en) * | 1977-04-06 | 1980-02-12 | Firma WOCO Franz-Josef Wolf & Co. | Sealing ring |
| DE2726959A1 (de) * | 1977-06-15 | 1979-01-18 | Arlt Christian | Dichteinsatz zum dichten verbinden von zwei rohren |
| FR2421899A1 (fr) * | 1978-01-16 | 1979-11-02 | Roussel Uclaf | Nouveaux derives du tetrahydropyridinyl-indole et leurs sels, le procede de preparation et l'application a titre de medicaments de ces nouveaux produits |
| US4410528A (en) * | 1980-05-16 | 1983-10-18 | Kyowa Hakko Kogyo Co., Ltd. | Hypotensive piperidine derivatives |
| DE3219522A1 (de) * | 1981-10-28 | 1983-12-01 | Denso-Chemie Wedekind Kg, 5090 Leverkusen | Steckmuffendichtung fuer rohre |
| FR2547888B1 (fr) * | 1983-06-22 | 1985-12-13 | Sabla Sa | Bague d'etancheite a implants pour tuyaux a emboitement |
| SE8800348L (sv) * | 1988-02-03 | 1989-08-04 | Forsheda Ab | Taetningsring och verktyg foer framstaellning daerav |
| US5169161A (en) * | 1991-09-19 | 1992-12-08 | Hail Mary Rubber Co., Inc. | Symmetrical gasket for pipe joints |
| DE4134089C2 (de) * | 1991-10-15 | 1994-10-13 | Dueker Eisenwerk | Schubgesicherte Muffenverbindung |
| DE4229609C2 (de) * | 1992-09-04 | 2003-05-08 | Forsheda Stefa Gmbh | Abdichtung zwischen zwei ineinandersteckbaren Teilen |
| US5521197A (en) * | 1994-12-01 | 1996-05-28 | Eli Lilly And Company | 3-<1-alkylenearyl>-4-<1,2,3,6-tetrahydropyridinyl>-and 3-<1-alkylenearyl>-4-piperidinyl-1h-indoles: new 5-HT1F agonists |
| SE515033C2 (sv) * | 1995-12-27 | 2001-06-05 | Forsheda Ab | Tätningsanordning |
| JP4375901B2 (ja) * | 1997-11-28 | 2009-12-02 | 大日本住友製薬株式会社 | 新規な複素環化合物 |
| CA2324550A1 (en) * | 1998-03-19 | 1999-09-23 | Shigeyuki Chaki | Arylpiperidine derivatives and use thereof |
| MA26659A1 (fr) * | 1998-08-06 | 2004-12-20 | Pfizer | Dérivés de benzimidazole nouveaux, compositions pharmaceutiques les contenant et procédé pour leur préparation. |
| SE9802729D0 (sv) * | 1998-08-13 | 1998-08-13 | Astra Pharma Prod | Novel Compounds |
| US5988695A (en) * | 1998-08-26 | 1999-11-23 | S&B Technical Products, Inc. | Pipe gasket with embedded ring |
| US6248755B1 (en) * | 1999-04-06 | 2001-06-19 | Merck & Co., Inc. | Pyrrolidine modulators of chemokine receptor activity |
| US6142484A (en) * | 1999-04-15 | 2000-11-07 | Vassallo Research & Development Corporation | Composite multi-pressure gasket |
| AU5600100A (en) * | 1999-06-11 | 2001-01-02 | Merck & Co., Inc. | Cyclopentyl modulators of chemokine receptor activity |
| JP2003509425A (ja) * | 1999-09-15 | 2003-03-11 | ワーナー−ランバート・カンパニー | キナーゼ阻害剤としてのプテリジノン |
| SE9903544D0 (sv) * | 1999-10-01 | 1999-10-01 | Astra Pharma Prod | Novel compounds |
| DE60101372T2 (de) * | 2000-02-11 | 2004-10-14 | Astrazeneca Ab | Pyrimidinverbindungen und ihre verwendung als modulatoren der chemokin-rezeptor-aktivität |
| GB2359081A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active thiazolopyrimidines |
| GB2359078A (en) * | 2000-02-11 | 2001-08-15 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB2359551A (en) * | 2000-02-23 | 2001-08-29 | Astrazeneca Uk Ltd | Pharmaceutically active pyrimidine derivatives |
| GB0005642D0 (en) * | 2000-03-10 | 2000-05-03 | Astrazeneca Uk Ltd | Chemical compounds |
| AU2001242744B2 (en) * | 2000-03-24 | 2005-07-21 | Meiji Seika Kaisha Ltd | Diphenylalkylamine derivatives useful as opioid delta receptor ligands |
| SE0003828D0 (sv) * | 2000-10-20 | 2000-10-20 | Astrazeneca Ab | Novel compounds |
| SE0004110L (sv) * | 2000-11-10 | 2002-05-11 | Forsheda Ab | Tätningsring |
| SE0101322D0 (sv) * | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | Novel compounds |
| GB0221829D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0221828D0 (en) * | 2002-09-20 | 2002-10-30 | Astrazeneca Ab | Novel compound |
| GB0328243D0 (en) * | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Methods |
-
2001
- 2001-08-14 SE SE0102716A patent/SE0102716D0/xx unknown
-
2002
- 2002-08-09 EP EP02749129A patent/EP1419158B1/en not_active Expired - Lifetime
- 2002-08-09 JP JP2003528813A patent/JP2005507390A/ja active Pending
- 2002-08-09 US US10/486,503 patent/US20050010047A1/en not_active Abandoned
- 2002-08-09 WO PCT/GB2002/003684 patent/WO2003024966A1/en not_active Ceased
- 2002-08-09 DE DE60221537T patent/DE60221537T2/de not_active Expired - Fee Related
- 2002-08-09 AT AT02749129T patent/ATE368664T1/de not_active IP Right Cessation
- 2002-08-09 ES ES02749129T patent/ES2289124T3/es not_active Expired - Lifetime
-
2007
- 2007-02-08 US US11/672,708 patent/US20070142352A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1419158B1 (en) | 2007-08-01 |
| DE60221537T2 (de) | 2008-04-24 |
| SE0102716D0 (sv) | 2001-08-14 |
| JP2005507390A (ja) | 2005-03-17 |
| EP1419158A1 (en) | 2004-05-19 |
| WO2003024966A1 (en) | 2003-03-27 |
| ATE368664T1 (de) | 2007-08-15 |
| US20050010047A1 (en) | 2005-01-13 |
| DE60221537D1 (de) | 2007-09-13 |
| US20070142352A1 (en) | 2007-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2206402T3 (es) | Compuestos de pteridina para el tratamiento de soriasis. | |
| US20070142352A1 (en) | Pteridinone Derivatives as Modulators of Chemokine Receptor Activity | |
| ES2213043T3 (es) | Nuevos compuestos de tiazolo(4,5-d)pirimidina. | |
| ES2276836T3 (es) | 7-amino-2-alquiltiopteridin-4-il-aminas para el tratamiento de enfermedades relacionadas con las quimioquinas. | |
| US6806273B1 (en) | Compounds | |
| US6958344B2 (en) | Pyrimidine compounds and their use as modulators of chemokine receptor activity | |
| EP1257555B1 (en) | Pyrimidine compounds and their use as modulators of chemokine receptor activity | |
| JP2003522189A5 (enExample) | ||
| EP1385854B1 (en) | Thiazolopyrimidines and their use as modulators of chemokine receptor activity | |
| EP1257556B1 (en) | Thiazolopyrimidines and their use as modulators of chemokine receptor activity | |
| KR20140125389A (ko) | Mtor-저해제로서 피리미도옥사조신 유도체 | |
| GB2359079A (en) | Pharmaceutically active pyrimidine derivatives | |
| WO2010094721A1 (en) | Piperidin-pyrimidine derivatives as antagonists of histamine h4 receptor |