ES2849974T3 - Moduladores de imidazopiridazina de IL-12, IL-23 y/o IFNalfa - Google Patents
Moduladores de imidazopiridazina de IL-12, IL-23 y/o IFNalfa Download PDFInfo
- Publication number
- ES2849974T3 ES2849974T3 ES17812112T ES17812112T ES2849974T3 ES 2849974 T3 ES2849974 T3 ES 2849974T3 ES 17812112 T ES17812112 T ES 17812112T ES 17812112 T ES17812112 T ES 17812112T ES 2849974 T3 ES2849974 T3 ES 2849974T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- mmol
- compounds
- pharmaceutically acceptable
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108010065637 Interleukin-23 Proteins 0.000 title description 46
- 102000013264 Interleukin-23 Human genes 0.000 title description 46
- 108010065805 Interleukin-12 Proteins 0.000 title description 40
- 102000013462 Interleukin-12 Human genes 0.000 title description 40
- MJQSRSOTRPMVKB-UHFFFAOYSA-N 5h-imidazo[4,5-c]pyridazine Chemical compound C1=NNC2=NC=NC2=C1 MJQSRSOTRPMVKB-UHFFFAOYSA-N 0.000 title description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 83
- 150000003839 salts Chemical class 0.000 claims abstract description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 47
- 125000003118 aryl group Chemical group 0.000 claims abstract description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 38
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 28
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 20
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 10
- 125000005843 halogen group Chemical group 0.000 claims abstract description 8
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 143
- 208000023275 Autoimmune disease Diseases 0.000 claims description 15
- 239000003937 drug carrier Substances 0.000 claims description 10
- 208000027866 inflammatory disease Diseases 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000002757 inflammatory effect Effects 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- -1 3-pentenyl Chemical group 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- 201000010099 disease Diseases 0.000 description 33
- 239000000203 mixture Substances 0.000 description 33
- 201000006417 multiple sclerosis Diseases 0.000 description 32
- 238000000034 method Methods 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 238000006243 chemical reaction Methods 0.000 description 25
- 125000001424 substituent group Chemical group 0.000 description 25
- 239000000047 product Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- 230000014759 maintenance of location Effects 0.000 description 21
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 21
- 239000002904 solvent Substances 0.000 description 19
- 239000002253 acid Chemical group 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 125000004429 atom Chemical group 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical class N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 125000000217 alkyl group Chemical group 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- 125000002619 bicyclic group Chemical group 0.000 description 14
- 125000001072 heteroaryl group Chemical group 0.000 description 14
- 206010025135 lupus erythematosus Diseases 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 201000004681 Psoriasis Diseases 0.000 description 13
- 150000001412 amines Chemical class 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 208000011231 Crohn disease Diseases 0.000 description 11
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- 102000014150 Interferons Human genes 0.000 description 11
- 108010050904 Interferons Proteins 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 125000005842 heteroatom Chemical group 0.000 description 11
- 125000002950 monocyclic group Chemical group 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 206010039073 rheumatoid arthritis Diseases 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 description 9
- 230000001363 autoimmune Effects 0.000 description 9
- 230000005784 autoimmunity Effects 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- YCLUMBJQKREDFM-UHFFFAOYSA-N imidazo[1,2-b]pyridazine-3-carboxamide Chemical compound C1=CC=NN2C(C(=O)N)=CN=C21 YCLUMBJQKREDFM-UHFFFAOYSA-N 0.000 description 9
- 239000000651 prodrug Substances 0.000 description 9
- 229940002612 prodrug Drugs 0.000 description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 125000000547 substituted alkyl group Chemical group 0.000 description 8
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 7
- 208000005777 Lupus Nephritis Diseases 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 208000035475 disorder Diseases 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000014509 gene expression Effects 0.000 description 7
- 229940047124 interferons Drugs 0.000 description 7
- 229940124829 interleukin-23 Drugs 0.000 description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 201000005569 Gout Diseases 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 108010010057 TYK2 Kinase Proteins 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 231100000252 nontoxic Toxicity 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 230000007170 pathology Effects 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 6
- 0 *C(c1cnc2[n]1nc(*)cc2*)=O Chemical compound *C(c1cnc2[n]1nc(*)cc2*)=O 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 206010009900 Colitis ulcerative Diseases 0.000 description 5
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 5
- 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 description 5
- 108010014726 Interferon Type I Proteins 0.000 description 5
- 102000002227 Interferon Type I Human genes 0.000 description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- 208000034578 Multiple myelomas Diseases 0.000 description 5
- 206010035226 Plasma cell myeloma Diseases 0.000 description 5
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 description 5
- 206010003246 arthritis Diseases 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 210000004698 lymphocyte Anatomy 0.000 description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 230000019491 signal transduction Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- MJZJYWCQPMNPRM-UHFFFAOYSA-N 6,6-dimethyl-1-[3-(2,4,5-trichlorophenoxy)propoxy]-1,6-dihydro-1,3,5-triazine-2,4-diamine Chemical compound CC1(C)N=C(N)N=C(N)N1OCCCOC1=CC(Cl)=C(Cl)C=C1Cl MJZJYWCQPMNPRM-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 102100036672 Interleukin-23 receptor Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 201000011152 Pemphigus Diseases 0.000 description 4
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 206010063837 Reperfusion injury Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000004450 alkenylene group Chemical group 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 229940079322 interferon Drugs 0.000 description 4
- 229940117681 interleukin-12 Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 201000001976 pemphigus vulgaris Diseases 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000006168 tricyclic group Chemical group 0.000 description 4
- 229960003824 ustekinumab Drugs 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 3
- 208000004429 Bacillary Dysentery Diseases 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 3
- 206010018634 Gouty Arthritis Diseases 0.000 description 3
- 208000003807 Graves Disease Diseases 0.000 description 3
- 208000015023 Graves' disease Diseases 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 102100030698 Interleukin-12 subunit alpha Human genes 0.000 description 3
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 3
- 208000007766 Kaposi sarcoma Diseases 0.000 description 3
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 206010033645 Pancreatitis Diseases 0.000 description 3
- 206010039710 Scleroderma Diseases 0.000 description 3
- 206010040047 Sepsis Diseases 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- 206010040550 Shigella infections Diseases 0.000 description 3
- 208000021386 Sjogren Syndrome Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke 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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 150000001447 alkali salts Chemical class 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000002491 angiogenic effect Effects 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 208000001969 capillary hemangioma Diseases 0.000 description 3
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 229940040731 human interleukin-12 Drugs 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 208000030159 metabolic disease Diseases 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 208000021039 metastatic melanoma Diseases 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 206010028417 myasthenia gravis Diseases 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 230000004770 neurodegeneration Effects 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- 230000036303 septic shock Effects 0.000 description 3
- 201000005113 shigellosis Diseases 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
- 208000020408 systemic-onset juvenile idiopathic arthritis Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- WZKYQXHOGZRHKQ-UHFFFAOYSA-N 1-[3-(cyclopropylcarbamoyl)-8-(methylamino)imidazo[1,2-b]pyridazin-6-yl]indazole-3-carboxylic acid Chemical compound CNC1=CC(=NN2C(=CN=C12)C(=O)NC1CC1)N1N=C(C(O)=O)C2=C1C=CC=C2 WZKYQXHOGZRHKQ-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000026326 Adult-onset Still disease Diseases 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000020084 Bone disease Diseases 0.000 description 2
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- 206010006895 Cachexia Diseases 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 2
- 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 description 2
- 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 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 206010018364 Glomerulonephritis Diseases 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 2
- 101100508538 Homo sapiens IKBKE gene Proteins 0.000 description 2
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 2
- 102100021857 Inhibitor of nuclear factor kappa-B kinase subunit epsilon Human genes 0.000 description 2
- 102000007438 Interferon alpha-beta Receptor Human genes 0.000 description 2
- 108010086140 Interferon alpha-beta Receptor Proteins 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 102000013691 Interleukin-17 Human genes 0.000 description 2
- 108050003558 Interleukin-17 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 241000233805 Phoenix Species 0.000 description 2
- 241000219061 Rheum Species 0.000 description 2
- 108010019992 STAT4 Transcription Factor Proteins 0.000 description 2
- 102000005886 STAT4 Transcription Factor Human genes 0.000 description 2
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 2
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
- 201000007023 Thrombotic Thrombocytopenic Purpura Diseases 0.000 description 2
- 102000000887 Transcription factor STAT Human genes 0.000 description 2
- 108050007918 Transcription factor STAT Proteins 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 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 2
- 150000008043 acidic salts Chemical class 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 125000004419 alkynylene group Chemical group 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 201000005000 autoimmune gastritis Diseases 0.000 description 2
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 208000019664 bone resorption disease Diseases 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 208000001763 cytomegalovirus retinitis Diseases 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 230000009266 disease activity Effects 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000013265 extended release Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 2
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 108040001844 interleukin-23 receptor activity proteins Proteins 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- 208000037906 ischaemic injury Diseases 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000003902 lesion 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
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- UHNSRFWQBVXBSK-UHFFFAOYSA-N methanol;2,2,2-trifluoroacetic acid Chemical compound OC.OC(=O)C(F)(F)F UHNSRFWQBVXBSK-UHFFFAOYSA-N 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 125000002757 morpholinyl group Chemical group 0.000 description 2
- 230000011234 negative regulation of signal transduction Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000001185 psoriatic effect Effects 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl 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
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 150000003873 salicylate salts Chemical class 0.000 description 2
- 238000011894 semi-preparative HPLC Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 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 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000008736 traumatic injury Effects 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- AIJFPNKGGAPZFJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)-n-methylmethanamine Chemical compound CNCC1=CC=C(OC)C=C1 AIJFPNKGGAPZFJ-UHFFFAOYSA-N 0.000 description 1
- DQYHJPFGVUFHHG-UHFFFAOYSA-N 1-[3-(cyclopropylcarbamoyl)-8-[(4-methoxyphenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-6-yl]indazole-3-carboxylic acid Chemical compound COc1ccc(CN(C)c2cc(nn3c(cnc23)C(=O)NC2CC2)-n2nc(C(O)=O)c3ccccc23)cc1 DQYHJPFGVUFHHG-UHFFFAOYSA-N 0.000 description 1
- LXQMHOKEXZETKB-UHFFFAOYSA-N 1-amino-2-methylpropan-2-ol Chemical compound CC(C)(O)CN LXQMHOKEXZETKB-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical class OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical class OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- FGOWNGCSUSKHQI-UHFFFAOYSA-N 4-bromo-6-chloropyridazin-3-amine Chemical compound NC1=NN=C(Cl)C=C1Br FGOWNGCSUSKHQI-UHFFFAOYSA-N 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- WAZPLXZGZWWXDQ-UHFFFAOYSA-N 4-methyl-4-oxidomorpholin-4-ium;hydrate Chemical compound O.C[N+]1([O-])CCOCC1 WAZPLXZGZWWXDQ-UHFFFAOYSA-N 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- HODXZMLAMQJTGR-UHFFFAOYSA-N 6-chloro-8-[(4-methoxyphenyl)methyl-methylamino]imidazo[1,2-b]pyridazine-3-carboxylic acid Chemical compound COC1=CC=C(CN(C)C2=CC(Cl)=NN3C(=CN=C23)C(O)=O)C=C1 HODXZMLAMQJTGR-UHFFFAOYSA-N 0.000 description 1
- FQXGFJBFUHDYIJ-UHFFFAOYSA-N 6-indazol-1-yl-8-(methylamino)imidazo[1,2-b]pyridazine-3-carbonyl fluoride Chemical compound CNC1=CC(=NN2C(=CN=C12)C(F)=O)N1N=CC2=C1C=CC=C2 FQXGFJBFUHDYIJ-UHFFFAOYSA-N 0.000 description 1
- UYKVIOYQOGSSBJ-UHFFFAOYSA-N 6-indazol-1-yl-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxylic acid Chemical compound CNC1=CC(=NN2C(=CN=C12)C(O)=O)N1N=CC2=C1C=CC=C2 UYKVIOYQOGSSBJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 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 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
- 208000011594 Autoinflammatory disease Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- WVNMLOGVAVGQIT-UHFFFAOYSA-N CC[n]1c(cccc2)c2nc1 Chemical compound CC[n]1c(cccc2)c2nc1 WVNMLOGVAVGQIT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 208000029713 Catastrophic antiphospholipid syndrome Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010063094 Cerebral malaria Diseases 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
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 208000004332 Evans syndrome Diseases 0.000 description 1
- 206010016207 Familial Mediterranean fever Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 108091006054 His-tagged proteins Proteins 0.000 description 1
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
- 101001011442 Homo sapiens Interferon regulatory factor 5 Proteins 0.000 description 1
- 101001003142 Homo sapiens Interleukin-12 receptor subunit beta-1 Proteins 0.000 description 1
- 101001003138 Homo sapiens Interleukin-12 receptor subunit beta-2 Proteins 0.000 description 1
- 101001010600 Homo sapiens Interleukin-12 subunit alpha Proteins 0.000 description 1
- 101000852992 Homo sapiens Interleukin-12 subunit beta Proteins 0.000 description 1
- 101000853012 Homo sapiens Interleukin-23 receptor Proteins 0.000 description 1
- 101000852980 Homo sapiens Interleukin-23 subunit alpha Proteins 0.000 description 1
- 101100371344 Homo sapiens TYK2 gene Proteins 0.000 description 1
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity 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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 102100030131 Interferon regulatory factor 5 Human genes 0.000 description 1
- 102000003814 Interleukin-10 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 102100020790 Interleukin-12 receptor subunit beta-1 Human genes 0.000 description 1
- 102100020792 Interleukin-12 receptor subunit beta-2 Human genes 0.000 description 1
- 102100036701 Interleukin-12 subunit beta Human genes 0.000 description 1
- 101710195550 Interleukin-23 receptor Proteins 0.000 description 1
- 102100036705 Interleukin-23 subunit alpha Human genes 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- 206010050551 Lupus-like syndrome Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100508438 Mus musculus Ifnk gene Proteins 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 208000007027 Oral Candidiasis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 208000034943 Primary Sjögren syndrome Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 108010017324 STAT3 Transcription Factor Proteins 0.000 description 1
- 102100024040 Signal transducer and activator of transcription 3 Human genes 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 102000015774 TYK2 Kinase Human genes 0.000 description 1
- 101150033562 TYK2 gene Proteins 0.000 description 1
- 210000000068 Th17 cell Anatomy 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
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010048873 Traumatic arthritis Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
- 241000287411 Turdidae Species 0.000 description 1
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
- GRPOFAKYHPAXNP-QMMMGPOBSA-N [(2s)-2,3-dihydro-1h-indol-2-yl]methanol Chemical compound C1=CC=C2N[C@H](CO)CC2=C1 GRPOFAKYHPAXNP-QMMMGPOBSA-N 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
- 230000001594 aberrant effect Effects 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 150000001265 acyl fluorides Chemical class 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
- 125000006177 alkyl benzyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229950010117 anifrolumab Drugs 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001064 anti-interferon Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000798 anti-retroviral effect Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
- 201000003308 autosomal dominant familial periodic fever Diseases 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 125000005870 benzindolyl group Chemical group 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229930194791 calphostin Natural products 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000004452 carbocyclyl group Chemical group 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical group 0.000 description 1
- 150000001768 cations Chemical class 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
- 229960000590 celecoxib Drugs 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000470 constituent Substances 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
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- VMKJWLXVLHBJNK-UHFFFAOYSA-N cyanuric fluoride Chemical compound FC1=NC(F)=NC(F)=N1 VMKJWLXVLHBJNK-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 206010061811 demyelinating polyneuropathy Diseases 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 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
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000000890 drug combination Substances 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
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000017214 establishment of T cell polarity Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- DWXKSCKBUSAOKS-UHFFFAOYSA-N ethyl 2-chloro-3-oxopropanoate Chemical compound CCOC(=O)C(Cl)C=O DWXKSCKBUSAOKS-UHFFFAOYSA-N 0.000 description 1
- PFVAGCVRRYYJLB-UHFFFAOYSA-N ethyl 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylate Chemical compound ClC1=CC(Cl)=NN2C(C(=O)OCC)=CN=C21 PFVAGCVRRYYJLB-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 150000002315 glycerophosphates Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036541 health Effects 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
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 102000047536 human TYK2 Human genes 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 150000004680 hydrogen peroxides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 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
- 206010020718 hyperplasia Diseases 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- SGRMUAZFOWNSGE-UHFFFAOYSA-N imidazo[1,2-b]pyridazine-3-carboxylic acid Chemical compound C1=CC=NN2C(C(=O)O)=CN=C21 SGRMUAZFOWNSGE-UHFFFAOYSA-N 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 150000005233 imidazopyridazines Chemical class 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 208000018615 immunodeficiency 35 Diseases 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- QNRXNRGSOJZINA-UHFFFAOYSA-N indoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CC2=C1 QNRXNRGSOJZINA-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 229940076144 interleukin-10 Drugs 0.000 description 1
- 230000024949 interleukin-17 production Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 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
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 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
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 201000004990 juvenile ankylosing spondylitis Diseases 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 150000003893 lactate salts Chemical class 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
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000002794 lymphocyte assay Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- BZZIFKOZWPMWHB-UHFFFAOYSA-N methyl 1-[3-(cyclobutylcarbamoyl)-8-[(4-methoxyphenyl)methyl-methylamino]imidazo[1,2-b]pyridazin-6-yl]indole-3-carboxylate Chemical compound COC(=O)c1cn(-c2cc(N(C)Cc3ccc(OC)cc3)c3ncc(C(=O)NC4CCC4)n3n2)c2ccccc12 BZZIFKOZWPMWHB-UHFFFAOYSA-N 0.000 description 1
- QLMBVRCJGIGWBV-UHFFFAOYSA-N methyl 2,3-dihydro-1h-indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)CNC2=C1 QLMBVRCJGIGWBV-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000004784 molecular pathogenesis Effects 0.000 description 1
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 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
- 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
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 239000007922 nasal spray Substances 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
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 150000002814 niacins Chemical class 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940046781 other immunosuppressants in atc Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 150000002926 oxygen Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 208000027232 peripheral nervous system disease Diseases 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 125000005547 pivalate group Chemical group 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 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
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 229940072288 prograf Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 229940099538 rapamune Drugs 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 125000006413 ring segment Chemical group 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
- 102200157260 rs34536443 Human genes 0.000 description 1
- 201000005404 rubella Diseases 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 201000004595 synovitis Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 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 1
- 229960003676 tenidap Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical compound OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 230000010472 type I IFN response Effects 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662423409P | 2016-11-17 | 2016-11-17 | |
| PCT/US2017/061895 WO2018093968A1 (en) | 2016-11-17 | 2017-11-16 | Imidazopyridazine modulators of il-12, il-23 and/or ifn-alpha |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2849974T3 true ES2849974T3 (es) | 2021-08-24 |
Family
ID=60655055
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES17812112T Active ES2849974T3 (es) | 2016-11-17 | 2017-11-16 | Moduladores de imidazopiridazina de IL-12, IL-23 y/o IFNalfa |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US11299494B2 (https=) |
| EP (1) | EP3541817B1 (https=) |
| JP (1) | JP7012082B2 (https=) |
| KR (1) | KR102611856B1 (https=) |
| CN (1) | CN110191887B (https=) |
| ES (1) | ES2849974T3 (https=) |
| WO (1) | WO2018093968A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR117398A1 (es) | 2018-03-12 | 2021-08-04 | Abbvie Inc | Inhibidores de la señalización mediada por tirosina cinasa 2 |
| JP7179161B2 (ja) | 2018-09-10 | 2022-11-28 | イーライ リリー アンド カンパニー | 乾癬および全身性エリテマトーデスの処置に有用なピラゾロ［１，５－ａ］ピリミジン－３－カルボキサミド誘導体 |
| AR117177A1 (es) | 2018-12-10 | 2021-07-14 | Lilly Co Eli | DERIVADOS DE 7-(METILAMINO)PIRAZOLO[1,5-A]PIRIMIDIN-3-CARBOXAMIDA COMO INHIBIDORES DE IL-23 E INFa |
| CN113348021B (zh) * | 2019-01-23 | 2025-07-11 | 武田药品工业株式会社 | Tyk2抑制剂和其用途 |
| SG11202112043PA (en) | 2019-04-30 | 2021-11-29 | Celgene Corp | Combination therapies comprising apremilast and tyk2 inhibitors |
| CN115052660B (zh) | 2020-02-12 | 2024-01-09 | 伊莱利利公司 | 取代的7-(甲氨基)吡唑并[1,5-a]嘧啶-3-甲酰胺衍生物 |
| TWI810520B (zh) | 2020-02-12 | 2023-08-01 | 美商美國禮來大藥廠 | 7-(甲基胺基)吡唑并[1,5-a]嘧啶-3-甲醯胺化合物 |
| EP3944859A1 (en) | 2020-07-30 | 2022-02-02 | Assistance Publique Hôpitaux de Paris | Method for treating immune toxicities induced by immune checkpoint inhibitors |
| CA3213816A1 (en) | 2021-03-16 | 2022-09-22 | Anrui Biomedical Technology (Guangzhou) Co., Ltd. | Amino heteroaryl compounds and compositions |
| EP4423086A1 (en) | 2021-10-25 | 2024-09-04 | Kymera Therapeutics, Inc. | Tyk2 degraders and uses thereof |
| CN119156388A (zh) * | 2022-04-15 | 2024-12-17 | 海南先声再明医药股份有限公司 | 膜缔合酪氨酸和苏氨酸激酶抑制剂 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004041285A1 (en) * | 2002-10-31 | 2004-05-21 | Amgen Inc. | Antiinflammation agents |
| US7176214B2 (en) | 2003-05-21 | 2007-02-13 | Bristol-Myers Squibb Company | Imidazo-fused oxazolo[4,5-β]pyridine and imidazo-fused thiazolo[4,5-β]pyridine based tricyclic compounds and pharmaceutical compositions comprising same |
| US20070078136A1 (en) * | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| WO2009100375A1 (en) * | 2008-02-06 | 2009-08-13 | Bristol-Myers Squibb Company | Substituted imidazopyridazines useful as kinase inhibitors |
| TWI491610B (zh) | 2008-10-09 | 2015-07-11 | 必治妥美雅史谷比公司 | 作為激酶抑制劑之咪唑并嗒腈 |
| PA8851101A1 (es) * | 2008-12-16 | 2010-07-27 | Lilly Co Eli | Compuesto amino pirazol |
| 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 |
| ES2702126T3 (es) * | 2013-12-10 | 2019-02-27 | Bristol Myers Squibb Co | Compuestos de imidazopiridazina útiles como moduladores de respuestas a IL-12, IL-23 y/o IFN alfa |
| US10479793B2 (en) * | 2015-11-18 | 2019-11-19 | Bristol-Myers Squibb Company | Imidazopyridazine compounds useful as modulators of IL-12, IL-23 and/or IFN alpha responses |
-
2017
- 2017-11-16 EP EP17812112.5A patent/EP3541817B1/en active Active
- 2017-11-16 WO PCT/US2017/061895 patent/WO2018093968A1/en not_active Ceased
- 2017-11-16 US US16/461,479 patent/US11299494B2/en active Active
- 2017-11-16 JP JP2019526262A patent/JP7012082B2/ja active Active
- 2017-11-16 ES ES17812112T patent/ES2849974T3/es active Active
- 2017-11-16 KR KR1020197016792A patent/KR102611856B1/ko active Active
- 2017-11-16 CN CN201780083328.6A patent/CN110191887B/zh active Active
Also Published As
| Publication number | Publication date |
|---|---|
| KR102611856B1 (ko) | 2023-12-07 |
| KR20190077530A (ko) | 2019-07-03 |
| US11299494B2 (en) | 2022-04-12 |
| WO2018093968A1 (en) | 2018-05-24 |
| EP3541817B1 (en) | 2020-12-23 |
| JP2019535723A (ja) | 2019-12-12 |
| EP3541817A1 (en) | 2019-09-25 |
| CN110191887B (zh) | 2022-02-18 |
| CN110191887A (zh) | 2019-08-30 |
| JP7012082B2 (ja) | 2022-01-27 |
| US20210323966A1 (en) | 2021-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2849974T3 (es) | Moduladores de imidazopiridazina de IL-12, IL-23 y/o IFNalfa | |
| ES2828733T3 (es) | Compuestos de imidazopiridazina útiles como moduladores de respuestas a IL-12, IL-23 y/o IFN alfa | |
| ES2902995T3 (es) | Compuestos de imidazopiridazina útiles como moduladores de respuestas a IL-12, IL-23 y/o IFN alfa | |
| ES2702126T3 (es) | Compuestos de imidazopiridazina útiles como moduladores de respuestas a IL-12, IL-23 y/o IFN alfa | |
| ES2648226T3 (es) | Compuestos de pirimidina sustituidos con alquilamida útiles en la modulación de IL-12, IL-23 y/o IFN | |
| ES2738826T3 (es) | Compuestos de piridilo sustituidos con alquilamida útiles como moduladores de respuestas de IL-12, IL-23 y/o IFNalfa | |
| ES3035735T3 (en) | Amide-disubstituted pyridine or pyridazine compounds | |
| ES2895107T3 (es) | Compuestos heterobicíclicos útiles como moduladores de las respuestas de IL-12, IL-23 y/o IFN alfa | |
| ES2907008T3 (es) | Compuestos de heteroarilo sustituidos con fosfinóxido alquilamida como moduladores de respuestas de IL-12, IL-23 y/o IFN alfa | |
| ES2987809T3 (es) | Compuestos de imidazopiridazina útiles como moduladores de las respuestas de IL-12, IL-23 y/o IFN alfa |