TW201713663A - 經雜芳基取代之胺基吡啶化合物 - Google Patents
經雜芳基取代之胺基吡啶化合物 Download PDFInfo
- Publication number
- TW201713663A TW201713663A TW105119779A TW105119779A TW201713663A TW 201713663 A TW201713663 A TW 201713663A TW 105119779 A TW105119779 A TW 105119779A TW 105119779 A TW105119779 A TW 105119779A TW 201713663 A TW201713663 A TW 201713663A
- Authority
- TW
- Taiwan
- Prior art keywords
- pyridin
- compound
- group
- alkyl
- carbonitrile
- Prior art date
Links
- -1 aminopyridine compounds Chemical class 0.000 title claims abstract description 50
- 125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 32
- 150000001875 compounds Chemical class 0.000 claims abstract description 194
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 27
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 19
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 18
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 9
- 125000001425 triazolyl group Chemical group 0.000 claims abstract description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 201000011510 cancer Diseases 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
- 201000010099 disease Diseases 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 18
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 16
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 16
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
- 239000003937 drug carrier Substances 0.000 claims description 13
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 claims description 12
- 201000005569 Gout Diseases 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 229960004979 fampridine Drugs 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- OAQFIXDKTZYDRL-UHFFFAOYSA-N imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound N=1C=CN2N=CC(=CC2=1)C#N OAQFIXDKTZYDRL-UHFFFAOYSA-N 0.000 claims description 9
- 125000003566 oxetanyl group Chemical group 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- CAJZIMCVNPNPSW-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound C1=C(C#N)C=NC2=CC=NN21 CAJZIMCVNPNPSW-UHFFFAOYSA-N 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- RENRCXJODALGTE-UHFFFAOYSA-N 2-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-5-[1-(oxan-4-yl)pyrazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=CC=2N(N=C1)C(=CN=2)C1=NC=C(C(=C1)NC(C)C)C=1C=NN(C=1)C1CCOCC1 RENRCXJODALGTE-UHFFFAOYSA-N 0.000 claims description 7
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
- XDESSKZUXMNMMO-UHFFFAOYSA-N 3-[4-(propan-2-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)C1=CN=C2N1N=CC(=C2)C#N XDESSKZUXMNMMO-UHFFFAOYSA-N 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
- 208000011231 Crohn disease Diseases 0.000 claims description 6
- 206010016207 Familial Mediterranean fever Diseases 0.000 claims description 6
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 6
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 208000024908 graft versus host disease Diseases 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 5
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
- TWOADEWSFFZZFG-UHFFFAOYSA-N 3-[4-(propan-2-ylamino)-5-(1-propylpyrazol-4-yl)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)CCC)C1=CN=C2N1N=CC(=C2)C#N TWOADEWSFFZZFG-UHFFFAOYSA-N 0.000 claims description 4
- SOVIOGDRQIIPMO-UHFFFAOYSA-N 3-[4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-5-(1-propylpyrazol-4-yl)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound FC(CN1N=CC(=C1)NC1=CC(=NC=C1C=1C=NN(C=1)CCC)C1=CN=C2N1N=CC(=C2)C#N)F SOVIOGDRQIIPMO-UHFFFAOYSA-N 0.000 claims description 4
- PYJGADHQKPQSHH-UHFFFAOYSA-N 3-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(oxetan-3-ylamino)pyridin-2-yl]pyrazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)C=1C=NN2C=1N=CC(=C2)C#N)NC1COC1)(C)C PYJGADHQKPQSHH-UHFFFAOYSA-N 0.000 claims description 4
- WOKMOGOUIVJJGR-UHFFFAOYSA-N 4-[1-[6-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-4-(propan-2-ylamino)pyridin-3-yl]triazol-4-yl]-2-methylbutan-2-ol Chemical compound ClC=1C=NC=2N(C=1)N=CC=2C1=CC(=C(C=N1)N1N=NC(=C1)CCC(C)(O)C)NC(C)C WOKMOGOUIVJJGR-UHFFFAOYSA-N 0.000 claims description 4
- 208000023328 Basedow disease Diseases 0.000 claims description 4
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000015023 Graves' disease Diseases 0.000 claims description 4
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 4
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 230000000737 periodic effect Effects 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 230000009885 systemic effect Effects 0.000 claims description 4
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 4
- FUCFDTKIFAGVLY-UHFFFAOYSA-N 2-(6-chloropyrazolo[1,5-a]pyrimidin-3-yl)-N-propan-2-yl-5-(4-propyltriazol-1-yl)pyridin-4-amine Chemical compound ClC=1C=NC=2N(C=1)N=CC=2C1=NC=C(C(=C1)NC(C)C)N1N=NC(=C1)CCC FUCFDTKIFAGVLY-UHFFFAOYSA-N 0.000 claims description 3
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- KFILYRVIDVXHNI-UHFFFAOYSA-N 2-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-N-propan-2-yl-5-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]pyridin-4-amine Chemical compound ClC1=CC=2N(N=C1)C(=CN=2)C1=NC=C(C(=C1)NC(C)C)C=1C=NN(C=1)CC(F)(F)F KFILYRVIDVXHNI-UHFFFAOYSA-N 0.000 claims 2
- JDHXZJLBUNAELN-UHFFFAOYSA-N 3-[4-(cyclopropylamino)-5-(1-propyltriazol-4-yl)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound C1(CC1)NC1=CC(=NC=C1C=1N=NN(C=1)CCC)C1=CN=C2N1N=CC(=C2)C#N JDHXZJLBUNAELN-UHFFFAOYSA-N 0.000 claims 2
- QSMXMQMCCMIAQQ-UHFFFAOYSA-N 3-[4-(propan-2-ylamino)-5-(4-propyltriazol-1-yl)pyridin-2-yl]pyrazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)C=1C=NN2C=1N=CC(=C2)C#N QSMXMQMCCMIAQQ-UHFFFAOYSA-N 0.000 claims 2
- KIFBHFOPKPWRAP-UHFFFAOYSA-N 3-[5-[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound OC(CN1N=CC(=C1)C=1C(=CC(=NC=1)C1=CN=C2N1N=CC(=C2)C#N)NC(C)C)(C)C KIFBHFOPKPWRAP-UHFFFAOYSA-N 0.000 claims 2
- VGDZIORKWAXUFJ-UHFFFAOYSA-N 3-[5-[1-(oxan-4-yl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)C1CCOCC1)C1=CN=C2N1N=CC(=C2)C#N VGDZIORKWAXUFJ-UHFFFAOYSA-N 0.000 claims 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims 2
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 47
- 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 abstract description 40
- 101000977771 Homo sapiens Interleukin-1 receptor-associated kinase 4 Proteins 0.000 abstract description 24
- 230000002757 inflammatory effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
- 239000000203 mixture Chemical class 0.000 description 73
- 235000019439 ethyl acetate Nutrition 0.000 description 69
- 239000011541 reaction mixture Substances 0.000 description 46
- 239000000243 solution Substances 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 239000000543 intermediate Substances 0.000 description 35
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 33
- 235000002639 sodium chloride Nutrition 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000012044 organic layer Substances 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 239000011734 sodium Substances 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
- 101710199010 Interleukin-1 receptor-associated kinase 4 Proteins 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 239000012453 solvate Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 102000002689 Toll-like receptor Human genes 0.000 description 12
- 108020000411 Toll-like receptor Proteins 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 12
- 229940002612 prodrug Drugs 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 11
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 241000124008 Mammalia Species 0.000 description 10
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 10
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102100036342 Interleukin-1 receptor-associated kinase 1 Human genes 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000002671 adjuvant Substances 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- 206010057190 Respiratory tract infections Diseases 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000003995 emulsifying agent Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000003755 preservative agent Substances 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 230000011664 signaling Effects 0.000 description 8
- 229940124597 therapeutic agent Drugs 0.000 description 8
- 229920000858 Cyclodextrin Polymers 0.000 description 7
- 108091000080 Phosphotransferase Proteins 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 150000004665 fatty acids Chemical class 0.000 description 7
- 239000000796 flavoring agent Substances 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 102000020233 phosphotransferase Human genes 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000035699 permeability Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 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 6
- 239000000080 wetting agent Substances 0.000 description 6
- XOYXADDAQJVPEI-UHFFFAOYSA-N 3-[5-[1-(3-hydroxy-3-methylbutyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound OC(CCN1N=CC(=C1)C=1C(=CC(=NC=1)C1=CN=C2N1N=CC(=C2)C#N)NC(C)C)(C)C XOYXADDAQJVPEI-UHFFFAOYSA-N 0.000 description 5
- QSRKCOCAYVQGSS-UHFFFAOYSA-N 3-[5-[4-(2-hydroxypropan-2-yl)pyrazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]pyrazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound OC(C)(C)C=1C=NN(C=1)C=1C(=CC(=NC=1)C=1C=NN2C=1N=CC(=C2)C#N)NC(C)C QSRKCOCAYVQGSS-UHFFFAOYSA-N 0.000 description 5
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
- 102000039996 IL-1 family Human genes 0.000 description 5
- 108091069196 IL-1 family Proteins 0.000 description 5
- 229940127590 IRAK4 inhibitor Drugs 0.000 description 5
- 102000000589 Interleukin-1 Human genes 0.000 description 5
- 108010002352 Interleukin-1 Proteins 0.000 description 5
- 101710199015 Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 5
- 206010037660 Pyrexia Diseases 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000007900 aqueous suspension Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- LAWGMJGGUZRERE-UHFFFAOYSA-N 2-chloro-N-propan-2-yl-5-(4-propyltriazol-1-yl)pyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)N1N=NC(=C1)CCC LAWGMJGGUZRERE-UHFFFAOYSA-N 0.000 description 4
- AWNOSZJJWBFBQD-UHFFFAOYSA-N 3-bromoimidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound BrC1=CN=C2N1N=CC(=C2)C#N AWNOSZJJWBFBQD-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 101000852483 Homo sapiens Interleukin-1 receptor-associated kinase 1 Proteins 0.000 description 4
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 4
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical class CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 4
- 208000034578 Multiple myelomas Diseases 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 235000019483 Peanut oil Nutrition 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 4
- 206010063837 Reperfusion injury Diseases 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 4
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 229910052796 boron Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000006880 cross-coupling reaction Methods 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 239000000312 peanut oil Substances 0.000 description 4
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- KZNUGOFCXKEALP-UHFFFAOYSA-N 1-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]ethanone Chemical compound ClC1=CC(=C(C=N1)C(C)=O)NC(C)C KZNUGOFCXKEALP-UHFFFAOYSA-N 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
- CLUIEZOGBBVHSO-UHFFFAOYSA-N 2-chloro-5-iodo-n-propan-2-ylpyridin-4-amine Chemical compound CC(C)NC1=CC(Cl)=NC=C1I CLUIEZOGBBVHSO-UHFFFAOYSA-N 0.000 description 3
- PMJAYULYKQKMBH-UHFFFAOYSA-N 3-[3-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]-1H-pyrazol-5-yl]propanoic acid Chemical compound ClC1=CC(=C(C=N1)C1=NNC(=C1)CCC(=O)O)NC(C)C PMJAYULYKQKMBH-UHFFFAOYSA-N 0.000 description 3
- 244000215068 Acacia senegal Species 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- 201000006474 Brain Ischemia Diseases 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 101000831567 Homo sapiens Toll-like receptor 2 Proteins 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
- 108010072621 Interleukin-1 Receptor-Associated Kinases Proteins 0.000 description 3
- 102000006940 Interleukin-1 Receptor-Associated Kinases Human genes 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 102000001253 Protein Kinase Human genes 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
- 102100024333 Toll-like receptor 2 Human genes 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 230000002491 angiogenic effect Effects 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000005587 bubbling Effects 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- NPTVZUXYHNHOJK-UHFFFAOYSA-N ethyl 6-chloro-4-(propan-2-ylamino)pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1NC(C)C NPTVZUXYHNHOJK-UHFFFAOYSA-N 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- ATBKVKDEMSGMTQ-UHFFFAOYSA-N hydrazine triphenylphosphane Chemical compound NN.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1 ATBKVKDEMSGMTQ-UHFFFAOYSA-N 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 208000030159 metabolic disease Diseases 0.000 description 3
- 239000004530 micro-emulsion Substances 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 239000000346 nonvolatile oil Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 239000000123 paper Substances 0.000 description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 108060006633 protein kinase Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 3
- 229910000080 stannane Inorganic materials 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- ZACIZZRZZPYFAZ-UHFFFAOYSA-N 1-[4-[6-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-4-(propan-2-ylamino)pyridin-3-yl]pyrazol-1-yl]-2-methylpropan-2-ol Chemical compound ClC1=CC=2N(N=C1)C(=CN=2)C1=CC(=C(C=N1)C=1C=NN(C=1)CC(C)(O)C)NC(C)C ZACIZZRZZPYFAZ-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 2
- DOTOFFAVTNZRLB-UHFFFAOYSA-N 2-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-N-cyclopropyl-5-(1-propyltriazol-4-yl)pyridin-4-amine Chemical compound ClC1=CC=2N(N=C1)C(=CN=2)C1=NC=C(C(=C1)NC1CC1)C=1N=NN(C=1)CCC DOTOFFAVTNZRLB-UHFFFAOYSA-N 0.000 description 2
- ZBRIPMUNBFXCSD-UHFFFAOYSA-N 2-(7-chloroimidazo[1,2-b]pyridazin-3-yl)-N-propan-2-yl-5-(1-propyltriazol-4-yl)pyridin-4-amine Chemical compound ClC1=CC=2N(N=C1)C(=CN=2)C1=NC=C(C(=C1)NC(C)C)C=1N=NN(C=1)CCC ZBRIPMUNBFXCSD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QSXYTAPZFDQJGR-UHFFFAOYSA-N 2-chloro-5-[1-(oxan-4-yl)pyrazol-4-yl]-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1C=NN(C=1)C1CCOCC1 QSXYTAPZFDQJGR-UHFFFAOYSA-N 0.000 description 2
- IMEAUUJJEBOVNT-UHFFFAOYSA-N 2-chloro-5-ethynyl-N-propan-2-ylpyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C#C IMEAUUJJEBOVNT-UHFFFAOYSA-N 0.000 description 2
- DEJUUKULVAIMNF-UHFFFAOYSA-N 2-chloro-5-iodopyridin-4-amine Chemical compound NC1=CC(Cl)=NC=C1I DEJUUKULVAIMNF-UHFFFAOYSA-N 0.000 description 2
- ZRJCNMYMCUBLAI-UHFFFAOYSA-N 2-chloro-N-propan-2-yl-5-(1H-pyrazol-4-yl)pyridin-4-amine Chemical compound ClC1=NC=C(C(=C1)NC(C)C)C=1C=NNC=1 ZRJCNMYMCUBLAI-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- NNNRRDCKNFXGMV-UHFFFAOYSA-N 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound CC1(C)OB(OC1(C)C)C1=C2N=CC(=CN2N=C1)C#N NNNRRDCKNFXGMV-UHFFFAOYSA-N 0.000 description 2
- PRAAEKYPJNFSSE-IRXDYDNUSA-N 3-[4-[[(1S,3S)-3-fluorocyclopentyl]amino]-5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]pyridin-2-yl]pyrazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound F[C@@H]1C[C@H](CC1)NC1=CC(=NC=C1N1N=NC(=C1)CCC(C)(C)O)C=1C=NN2C=1N=CC(=C2)C#N PRAAEKYPJNFSSE-IRXDYDNUSA-N 0.000 description 2
- BXPJRPWKDYCOMG-UHFFFAOYSA-N 3-[5-[4-(3-hydroxy-3-methylbutyl)triazol-1-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound OC(CCC=1N=NN(C=1)C=1C(=CC(=NC=1)C1=CN=C2N1N=CC(=C2)C#N)NC(C)C)(C)C BXPJRPWKDYCOMG-UHFFFAOYSA-N 0.000 description 2
- FYWMEWXIWGOWCJ-UHFFFAOYSA-N 3-bromo-6-chloropyrazolo[1,5-a]pyrimidine Chemical compound C1=C(Cl)C=NC2=C(Br)C=NN21 FYWMEWXIWGOWCJ-UHFFFAOYSA-N 0.000 description 2
- DVWYWNOKILBICA-UHFFFAOYSA-N 3-bromopyrazolo[1,5-a]pyrimidine-6-carbonitrile Chemical compound C1=C(C#N)C=NC2=C(Br)C=NN21 DVWYWNOKILBICA-UHFFFAOYSA-N 0.000 description 2
- YQUMLEDCOBPZNK-UHFFFAOYSA-N 5-bromo-2-chloro-N-propan-2-ylpyridin-4-amine Chemical compound BrC=1C(=CC(=NC=1)Cl)NC(C)C YQUMLEDCOBPZNK-UHFFFAOYSA-N 0.000 description 2
- VNNGLAHFEULQGK-UHFFFAOYSA-N 7-chloro-3-iodoimidazo[1,2-b]pyridazine Chemical compound C1=C(Cl)C=NN2C(I)=CN=C21 VNNGLAHFEULQGK-UHFFFAOYSA-N 0.000 description 2
- FLCAFSOTMLXPPX-UHFFFAOYSA-N 7-chloroimidazo[1,2-b]pyridazine Chemical compound C1=C(Cl)C=NN2C=CN=C21 FLCAFSOTMLXPPX-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- BSDGKDYHTSCUGR-UHFFFAOYSA-N C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)C1CCOCC1)[Sn](C)(C)C Chemical compound C(C)(C)NC1=CC(=NC=C1C=1C=NN(C=1)C1CCOCC1)[Sn](C)(C)C BSDGKDYHTSCUGR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000852255 Homo sapiens Interleukin-1 receptor-associated kinase-like 2 Proteins 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 102100036433 Interleukin-1 receptor-associated kinase-like 2 Human genes 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 201000011152 Pemphigus Diseases 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- 241000607768 Shigella Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 2
- DBDQQUWTCJIGTQ-UHFFFAOYSA-N [6-chloro-4-(propan-2-ylamino)pyridin-3-yl]methanol Chemical compound CC(C)NC1=CC(Cl)=NC=C1CO DBDQQUWTCJIGTQ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000012082 adaptor molecule Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229940127219 anticoagulant drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 201000004982 autoimmune uveitis Diseases 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004159 blood analysis Methods 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 208000001969 capillary hemangioma Diseases 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000011111 cardboard Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 208000001763 cytomegalovirus retinitis Diseases 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- LZWLLMFYVGUUAL-UHFFFAOYSA-L ditert-butyl(cyclopenta-1,3-dien-1-yl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1 LZWLLMFYVGUUAL-UHFFFAOYSA-L 0.000 description 2
- CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000007783 downstream signaling Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- SRZJTSWSJYVPKY-UHFFFAOYSA-N ethyl 3-[3-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]-1H-pyrazol-5-yl]propanoate Chemical compound ClC1=CC(=C(C=N1)C1=NNC(=C1)CCC(=O)OCC)NC(C)C SRZJTSWSJYVPKY-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 229960002706 gusperimus Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 208000031225 myocardial ischemia Diseases 0.000 description 2
- IDINUJSAMVOPCM-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-INIZCTEOSA-N 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 201000001976 pemphigus vulgaris Diseases 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 2
- 235000010378 sodium ascorbate Nutrition 0.000 description 2
- 229960005055 sodium ascorbate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 2
- 229960003676 tenidap Drugs 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 2
- 229960000984 tocofersolan Drugs 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 230000008736 traumatic injury Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000002076 α-tocopherol Substances 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- SQHSJJGGWYIFCD-UHFFFAOYSA-N (e)-1-diazonio-1-dimethoxyphosphorylprop-1-en-2-olate Chemical compound COP(=O)(OC)C(\[N+]#N)=C(\C)[O-] SQHSJJGGWYIFCD-UHFFFAOYSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- IBXNCJKFFQIKKY-UHFFFAOYSA-N 1-pentyne Chemical compound CCCC#C IBXNCJKFFQIKKY-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- KZDCMKVLEYCGQX-UDPGNSCCSA-N 2-(diethylamino)ethyl 4-aminobenzoate;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;hydrate Chemical compound O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 KZDCMKVLEYCGQX-UDPGNSCCSA-N 0.000 description 1
- JJAWKHLIZLJFFX-UHFFFAOYSA-N 2-[1-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]pyrazol-3-yl]propan-2-ol Chemical compound ClC1=CC(=C(C=N1)N1N=C(C=C1)C(C)(C)O)NC(C)C JJAWKHLIZLJFFX-UHFFFAOYSA-N 0.000 description 1
- CWWNZWXDPFYFQT-UHFFFAOYSA-N 2-[1-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]pyrazol-4-yl]propan-2-ol Chemical compound ClC1=CC(=C(C=N1)N1N=CC(=C1)C(C)(C)O)NC(C)C CWWNZWXDPFYFQT-UHFFFAOYSA-N 0.000 description 1
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
- NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 description 1
- BYVMKCHHWASQFN-UHFFFAOYSA-N 2-chloro-3-iodopyridin-4-amine Chemical compound NC1=CC=NC(Cl)=C1I BYVMKCHHWASQFN-UHFFFAOYSA-N 0.000 description 1
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
- JRYYVMDEUJQWRO-UHFFFAOYSA-N 2-methylnicotinamide Chemical compound CC1=NC=CC=C1C(N)=O JRYYVMDEUJQWRO-UHFFFAOYSA-N 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- XEMDFESAXKSEGI-UHFFFAOYSA-N 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CN=C1 XEMDFESAXKSEGI-UHFFFAOYSA-N 0.000 description 1
- XDSRHSZBMTXRBP-UHFFFAOYSA-N 3-[5-[1-(oxan-4-yl)triazol-4-yl]-4-(propan-2-ylamino)pyridin-2-yl]imidazo[1,2-b]pyridazine-7-carbonitrile Chemical compound C(C)(C)NC1=CC(=NC=C1C=1N=NN(C=1)C1CCOCC1)C1=CN=C2N1N=CC(=C2)C#N XDSRHSZBMTXRBP-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- BLBDTBCGPHPIJK-UHFFFAOYSA-N 4-Amino-2-chloropyridine Chemical compound NC1=CC=NC(Cl)=C1 BLBDTBCGPHPIJK-UHFFFAOYSA-N 0.000 description 1
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 1
- SUHBGSSMAYJXCS-UHFFFAOYSA-N 4-[3-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]-1H-pyrazol-5-yl]-2-methylbutan-2-ol Chemical compound ClC1=CC(=C(C=N1)C1=NNC(=C1)CCC(C)(O)C)NC(C)C SUHBGSSMAYJXCS-UHFFFAOYSA-N 0.000 description 1
- PIFJQRCPUURIFV-UHFFFAOYSA-N 4-azidooxane Chemical compound [N-]=[N+]=NC1CCOCC1 PIFJQRCPUURIFV-UHFFFAOYSA-N 0.000 description 1
- IVBVKTPDEWDNRW-UHFFFAOYSA-N 4-bromooxane Chemical compound BrC1CCOCC1 IVBVKTPDEWDNRW-UHFFFAOYSA-N 0.000 description 1
- IYGFIINCQJDWNJ-UHFFFAOYSA-N 4-chloro-2h-triazole Chemical compound ClC1=CNN=N1 IYGFIINCQJDWNJ-UHFFFAOYSA-N 0.000 description 1
- SGCSNJNPPSSPKZ-UHFFFAOYSA-N 5-bromo-2,4-dichloropyridine Chemical compound ClC1=CC(Cl)=C(Br)C=N1 SGCSNJNPPSSPKZ-UHFFFAOYSA-N 0.000 description 1
- FLLHRDDIQGNYLR-UHFFFAOYSA-N 5-chloropyridazin-3-amine Chemical compound NC1=CC(Cl)=CN=N1 FLLHRDDIQGNYLR-UHFFFAOYSA-N 0.000 description 1
- GYIVBXWFXLOPBO-UHFFFAOYSA-N 6-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]-4,6-dioxohexanoic acid Chemical compound ClC1=CC(=C(C=N1)C(CC(CCC(=O)O)=O)=O)NC(C)C GYIVBXWFXLOPBO-UHFFFAOYSA-N 0.000 description 1
- JNUURYOVLUZBPS-UHFFFAOYSA-N 6-chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidine Chemical compound ClC=1C=NC=2N(C=1)N=CC=2B1OC(C(O1)(C)C)(C)C JNUURYOVLUZBPS-UHFFFAOYSA-N 0.000 description 1
- MJFZDRIOIJLJRF-UHFFFAOYSA-N 6-chloro-4-(propan-2-ylamino)pyridine-3-carbaldehyde Chemical compound CC(C)NC1=CC(Cl)=NC=C1C=O MJFZDRIOIJLJRF-UHFFFAOYSA-N 0.000 description 1
- GALMKDSGRAUANF-UHFFFAOYSA-N 6-chloro-4-(propan-2-ylamino)pyridine-3-carboxylic acid Chemical compound CC(C)NC1=CC(Cl)=NC=C1C(O)=O GALMKDSGRAUANF-UHFFFAOYSA-N 0.000 description 1
- FQXQOIGAJJUUNH-UHFFFAOYSA-N 6-chloropyrazolo[1,5-a]pyrimidine Chemical compound C1=C(Cl)C=NC2=CC=NN21 FQXQOIGAJJUUNH-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010004053 Bacterial toxaemia Diseases 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- CDTDWZITKQFOLH-UHFFFAOYSA-N C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)[Sn](C)(C)C Chemical compound C(C)(C)NC1=CC(=NC=C1N1N=NC(=C1)CCC)[Sn](C)(C)C CDTDWZITKQFOLH-UHFFFAOYSA-N 0.000 description 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 102000004631 Calcineurin Human genes 0.000 description 1
- 108010042955 Calcineurin Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000713730 Equine infectious anemia virus Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 241000713800 Feline immunodeficiency virus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 239000001828 Gelatine Substances 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
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
- 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100039065 Interleukin-1 beta Human genes 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 102100026888 Mitogen-activated protein kinase kinase kinase 7 Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 102000042894 Pelle family Human genes 0.000 description 1
- 108091082316 Pelle family Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 208000004346 Smoldering Multiple Myeloma Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 102000003714 TNF receptor-associated factor 6 Human genes 0.000 description 1
- 108090000009 TNF receptor-associated factor 6 Proteins 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010043781 Thyroiditis chronic Diseases 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 208000013222 Toxemia Diseases 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DCUBASOTLJXLQS-UHFFFAOYSA-L [O-]C(=O)CCCCCCCCC.OC(=O)CCCCCCCCC.[O-]C(=O)CCCCCCCCC.[Mg+2] Chemical compound [O-]C(=O)CCCCCCCCC.OC(=O)CCCCCCCCC.[O-]C(=O)CCCCCCCCC.[Mg+2] DCUBASOTLJXLQS-UHFFFAOYSA-L 0.000 description 1
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
- 229960004748 abacavir Drugs 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 230000004721 adaptive immunity Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002390 adhesive tape Substances 0.000 description 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000012911 assay medium Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000005000 autoimmune gastritis Diseases 0.000 description 1
- 208000037979 autoimmune inflammatory disease Diseases 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 150000001638 boron Chemical class 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- CETPSERCERDGAM-UHFFFAOYSA-N ceric oxide Chemical compound O=[Ce]=O CETPSERCERDGAM-UHFFFAOYSA-N 0.000 description 1
- 229910000422 cerium(IV) oxide Inorganic materials 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940097362 cyclodextrins Drugs 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
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 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
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000005594 diketone group Chemical group 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- KZLUHGRPVSRSHI-UHFFFAOYSA-N dimethylmagnesium Chemical compound C[Mg]C KZLUHGRPVSRSHI-UHFFFAOYSA-N 0.000 description 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000003162 effector t lymphocyte Anatomy 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- KBAKNGCBTIDSCM-UHFFFAOYSA-N ethyl 1-[6-chloro-4-(propan-2-ylamino)pyridin-3-yl]pyrazole-4-carboxylate Chemical compound ClC1=CC(=C(C=N1)N1N=CC(=C1)C(=O)OCC)NC(C)C KBAKNGCBTIDSCM-UHFFFAOYSA-N 0.000 description 1
- AAUBVINEXCCXOK-UHFFFAOYSA-N ethyl 4,6-dichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1Cl AAUBVINEXCCXOK-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 1
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000003866 lung sarcoma Diseases 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000007721 medicinal effect Effects 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
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 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 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 238000006384 oligomerization reaction Methods 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-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
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
- 229940072288 prograf Drugs 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- XPPZAORQJNABAD-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=C=C[CH]N2N=CC=C21 XPPZAORQJNABAD-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 229940099538 rapamune Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
- 229950005741 rolipram Drugs 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 208000037921 secondary disease Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 208000010721 smoldering plasma cell myeloma Diseases 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical compound O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 108091008743 testicular receptors 4 Proteins 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001578 tight junction Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- OVCXRBARSPBVMC-UHFFFAOYSA-N triazolopyridine Chemical compound C=1N2C(C(C)C)=NN=C2C=CC=1C=1OC=NC=1C1=CC=C(F)C=C1 OVCXRBARSPBVMC-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- 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
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1880DE2015 | 2015-06-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW201713663A true TW201713663A (zh) | 2017-04-16 |
Family
ID=56345252
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW105119779A TW201713663A (zh) | 2015-06-24 | 2016-06-23 | 經雜芳基取代之胺基吡啶化合物 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US10202390B2 (enExample) |
| EP (1) | EP3313844B1 (enExample) |
| JP (1) | JP6720225B2 (enExample) |
| CN (1) | CN108026099B (enExample) |
| AR (1) | AR105114A1 (enExample) |
| ES (1) | ES2822956T3 (enExample) |
| TW (1) | TW201713663A (enExample) |
| UY (1) | UY36747A (enExample) |
| WO (1) | WO2016210037A1 (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10618903B2 (en) * | 2015-06-24 | 2020-04-14 | Bristol-Myers Squibb Company | Heteroaryl substituted aminopyridine compounds |
| EP3313840B1 (en) | 2015-06-24 | 2019-07-24 | Bristol-Myers Squibb Company | Heteroaryl substituted aminopyridine compounds |
| ES2822956T3 (es) | 2015-06-24 | 2021-05-05 | Bristol Myers Squibb Co | Compuestos de aminopiridina sustituidos con heteroarilo |
| TW202340194A (zh) | 2017-02-16 | 2023-10-16 | 美商基利科學股份有限公司 | 吡咯并[1,2-b]嗒𠯤衍生物 |
| PT3621960T (pt) | 2017-05-11 | 2021-09-16 | Bristol Myers Squibb Co | Tienopiridinas e benzotiofenos úteis como inibidores de irak4 |
| WO2019111218A1 (en) | 2017-12-08 | 2019-06-13 | Cadila Healthcare Limited | Novel heterocyclic compounds as irak4 inhibitors |
| TWI842978B (zh) | 2018-07-13 | 2024-05-21 | 美商基利科學股份有限公司 | 衍生物 |
| TWI727392B (zh) | 2018-08-13 | 2021-05-11 | 美商基利科學股份有限公司 | 噻二唑irak4抑制劑 |
| TWI797366B (zh) | 2018-08-13 | 2023-04-01 | 美商基利科學股份有限公司 | 吡咯并[1,2-b]嗒衍生物 |
| WO2020036830A1 (en) | 2018-08-13 | 2020-02-20 | Gilead Sciences, Inc. | Pyrrolo[1,2-b]pyridazine derivatives as irak4 inhibitors |
| EP3999508B1 (en) | 2019-07-18 | 2023-08-30 | Bristol-Myers Squibb Company | Tricyclic heteroaryl compounds useful as irak4 inhibitors |
| WO2021011727A1 (en) * | 2019-07-18 | 2021-01-21 | Bristol-Myers Squibb Company | PYRAZOLO[3,4-d]PYRROLO[1,2-b]PYRIDAZINYL COMPOUNDS USEFUL AS IRAK4 INHIBITORS |
| US12304916B2 (en) | 2019-07-23 | 2025-05-20 | Bristol-Myers Squibb Company | Thienopyridinyl and thiazolopyridinyl compounds useful as IRAK4 inhibitors |
| WO2021026181A1 (en) | 2019-08-06 | 2021-02-11 | Bristol-Myers Squibb Company | Bicyclic heterocyclic compounds useful as irak4 inhibitors |
| ES3059914T3 (en) | 2019-08-13 | 2026-03-24 | Bristol Myers Squibb Co | Bicyclic heteroaryl compounds useful as irak4 inhibitors |
| US12421230B2 (en) | 2020-02-03 | 2025-09-23 | Bristol-Myers Squibb Company | Tricyclic heteroaryl compounds useful as IRAK4 inhibitors |
| WO2021158495A1 (en) | 2020-02-03 | 2021-08-12 | Bristol-Myers Squibb Company | Benzo[5,6][1,4]dioxino[2,3-b]pyridine compounds useful as irak4 inhibitors |
| WO2021168197A1 (en) | 2020-02-19 | 2021-08-26 | Nurix Therapeutics, Inc. | Bifunctional degraders of interleukin-1 receptor-associated kinases and therapeutic use thereof |
| CN113149995A (zh) * | 2021-03-31 | 2021-07-23 | 安徽驱石医药科技有限公司 | 一种7-氟吡唑并[1,2-b]吡嗪-4-甲腈的合成方法及应用 |
| CN117813307A (zh) | 2021-08-18 | 2024-04-02 | 新锐思生物制药股份有限公司 | 白介素-1受体相关激酶的双官能降解物及其治疗用途 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2450769A1 (en) | 2001-06-15 | 2002-12-27 | Vertex Pharmaceuticals Incorporated | 5-(2-aminopyrimidin-4-yl) benzisoxazoles as protein kinase inhibitors |
| AUPR688101A0 (en) | 2001-08-08 | 2001-08-30 | Luminis Pty Limited | Protein domains and their ligands |
| GB0211019D0 (en) | 2002-05-14 | 2002-06-26 | Syngenta Ltd | Novel compounds |
| EP1518855B1 (en) | 2002-06-28 | 2011-10-26 | Astellas Pharma Inc. | Diaminopyrimidinecarboxa mide derivative |
| MXPA05007503A (es) | 2003-01-17 | 2005-09-21 | Warner Lambert Co | Heterociclicos 2-aminopiridina sustituidos como inhibidores de proliferacion celular. |
| WO2005007646A1 (en) | 2003-07-10 | 2005-01-27 | Neurogen Corporation | Substituted heterocyclic diarylamine analogues |
| GB0402653D0 (en) | 2004-02-06 | 2004-03-10 | Cyclacel Ltd | Compounds |
| US7521457B2 (en) | 2004-08-20 | 2009-04-21 | Boehringer Ingelheim International Gmbh | Pyrimidines as PLK inhibitors |
| FR2896503B1 (fr) | 2006-01-23 | 2012-07-13 | Aventis Pharma Sa | Nouveaux derives soufres d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases |
| CN101594909A (zh) * | 2006-09-07 | 2009-12-02 | 比奥根艾迪克Ma公司 | 用于治疗炎性病症、细胞增殖性失调、免疫失调的irak调节剂 |
| KR20100020454A (ko) | 2007-06-08 | 2010-02-22 | 바이엘 크롭사이언스 소시에떼아노님 | 살진균제 헤테로사이클릴-피리미디닐-아미노 유도체 |
| WO2009046416A1 (en) | 2007-10-05 | 2009-04-09 | Targegen Inc. | Anilinopyrimidines as jak kinase inhibitors |
| EP2361902A4 (en) | 2008-11-21 | 2012-04-25 | Astellas Pharma Inc | 4,6-DIAMINONICOTINSÄUREAMIDVERBINDUNG |
| WO2010061971A1 (ja) | 2008-11-28 | 2010-06-03 | 興和株式会社 | ピリジン－３－カルボキシアミド誘導体 |
| EP2440204B1 (en) | 2009-06-12 | 2013-12-18 | Bristol-Myers Squibb Company | Nicotinamide compounds useful as kinase modulators |
| EP2493863B1 (en) | 2009-10-30 | 2015-02-25 | Janssen Pharmaceutica NV | Phenoxy-substituted pyrimidines as opioid receptor modulators |
| KR20120130104A (ko) | 2010-02-01 | 2012-11-28 | 닛뽕 케미파 가부시키가이샤 | Ｇｐｒ119 작동약 |
| JP2014515029A (ja) | 2011-04-29 | 2014-06-26 | アイカーン・スクール・オブ・メディシン・アト・マウント・シナイ | キナーゼ阻害剤 |
| ES2575604T3 (es) * | 2012-01-13 | 2016-06-29 | Bristol-Myers Squibb Company | Compuestos de piridilo sustituidos con tiazolilo o tiadiazolilo útiles como inhibidores cinasa |
| CN104169275B (zh) | 2012-01-13 | 2017-06-09 | 百时美施贵宝公司 | 用作激酶抑制剂的三唑取代的吡啶化合物 |
| EP2802576B1 (en) | 2012-01-13 | 2018-06-27 | Bristol-Myers Squibb Company | Heterocyclic-substituted pyridyl compounds useful as kinase inhibitors |
| BR112015009850A2 (pt) | 2012-11-08 | 2017-07-11 | Bristol Myers Squibb Co | compostos de piridila substituídos por heteroarila úteis como moduladores de quinase |
| KR102233252B1 (ko) | 2012-11-08 | 2021-03-26 | 브리스톨-마이어스 스큅 컴퍼니 | ＩＬ-12, ＩＬ-23 및/또는 ＩＦＮα 반응의 조절제로서 유용한 알킬-아미드-치환된 피리딜 화합물 |
| JP6215338B2 (ja) | 2012-11-08 | 2017-10-18 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | キナーゼモジュレーターとして有用な二環式ヘテロ環置換ピリジル化合物 |
| TWI582077B (zh) | 2013-11-07 | 2017-05-11 | 必治妥美雅史谷比公司 | 作爲ＩＬ－１２、ＩＬ－２３及／或ＩＦＮα反應調節劑之經烷基－醯胺取代之吡啶化合物 |
| UY35935A (es) * | 2014-01-03 | 2015-06-30 | Bristol Myers Squibb Company Una Corporación Del Estado De Delaware | Compuestos de nicotinamida sustituida con heteroarilo como inhibidores de quinasa y moduladores de irak-4 |
| ES2822956T3 (es) | 2015-06-24 | 2021-05-05 | Bristol Myers Squibb Co | Compuestos de aminopiridina sustituidos con heteroarilo |
| EP3313840B1 (en) * | 2015-06-24 | 2019-07-24 | Bristol-Myers Squibb Company | Heteroaryl substituted aminopyridine compounds |
-
2016
- 2016-06-23 ES ES16734832T patent/ES2822956T3/es active Active
- 2016-06-23 AR ARP160101893A patent/AR105114A1/es unknown
- 2016-06-23 JP JP2017566812A patent/JP6720225B2/ja active Active
- 2016-06-23 UY UY0001036747A patent/UY36747A/es not_active Application Discontinuation
- 2016-06-23 US US15/738,435 patent/US10202390B2/en active Active
- 2016-06-23 EP EP16734832.5A patent/EP3313844B1/en active Active
- 2016-06-23 CN CN201680043479.4A patent/CN108026099B/zh active Active
- 2016-06-23 WO PCT/US2016/038862 patent/WO2016210037A1/en not_active Ceased
- 2016-06-23 TW TW105119779A patent/TW201713663A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP3313844B1 (en) | 2020-08-26 |
| ES2822956T3 (es) | 2021-05-05 |
| US10202390B2 (en) | 2019-02-12 |
| WO2016210037A1 (en) | 2016-12-29 |
| JP6720225B2 (ja) | 2020-07-08 |
| UY36747A (es) | 2016-12-30 |
| CN108026099A (zh) | 2018-05-11 |
| JP2018524331A (ja) | 2018-08-30 |
| AR105114A1 (es) | 2017-09-06 |
| US20180179213A1 (en) | 2018-06-28 |
| CN108026099B (zh) | 2020-07-10 |
| EP3313844A1 (en) | 2018-05-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108026099B (zh) | 经杂芳基取代的氨基吡啶化合物 | |
| CN107849039B (zh) | 经杂芳基取代的氨基吡啶化合物 | |
| CN110612298B (zh) | 用作irak4抑制剂的噻吩并吡啶及苯并噻吩化合物 | |
| CN107857755B (zh) | 作为trka激酶抑制剂的n-吡咯烷基、n′-吡唑基-脲、硫脲、胍和氰基胍化合物 | |
| JP7104775B2 (ja) | Ｔｌｒ７／８／９の阻害剤として有用な置換インドール化合物 | |
| CN103998042B (zh) | Pi3k的活性或功能的抑制剂的应用 | |
| JP2021506923A (ja) | Ｔｌｒ阻害剤として有用なアミド置換されたインドール化合物 | |
| AU2018386201A1 (en) | Substituted indole ether compounds | |
| TW201713655A (zh) | 經雜芳基取代之胺基吡啶化合物 | |
| JP7570399B2 (ja) | Ｉｒａｋ４阻害剤として有用な三環式ヘテロアリール化合物 | |
| JP2022545364A (ja) | Ｉｒａｋ４阻害剤として有用な二環ヘテロアリール化合物 | |
| CN110139862A (zh) | 可用作romk通道抑制剂的经取代的二环杂环衍生物 | |
| JP7620611B2 (ja) | ＩＲＡＫ４阻害剤として有用なピラゾロ［３，４－ｄ］ピロロ［１，２－ｂ］ピリダジニル化合物 | |
| JP7573596B2 (ja) | Ｉｒａｋ４阻害剤として有用なチエノピリジニルおよびチアゾロピリジニル化合物 | |
| KR20220136395A (ko) | Irak4 억제제로서 유용한 트리시클릭 헤테로아릴 화합물 | |
| JP7682154B2 (ja) | Ｉｒａｋ４阻害剤として有用な二環ヘテロ環式化合物 | |
| HK40074720B (zh) | [1,2,4]三唑并[1,5-c]喹唑啉-5-胺 | |
| HK40100302A (zh) | 作为激酶抑制剂的吲唑类化合物 |