ES2865483T3 - Pirazolo[1,5-a]pirazinas sustituidas en 4,6 como inhibidores de Janus cinasa - Google Patents
Pirazolo[1,5-a]pirazinas sustituidas en 4,6 como inhibidores de Janus cinasa Download PDFInfo
- Publication number
- ES2865483T3 ES2865483T3 ES15819933T ES15819933T ES2865483T3 ES 2865483 T3 ES2865483 T3 ES 2865483T3 ES 15819933 T ES15819933 T ES 15819933T ES 15819933 T ES15819933 T ES 15819933T ES 2865483 T3 ES2865483 T3 ES 2865483T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- pyrazol
- mmol
- formula
- compound
- 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
- 229940122245 Janus kinase inhibitor Drugs 0.000 title description 2
- 150000003216 pyrazines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 287
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 192
- -1 hetCyc4 Chemical group 0.000 claims abstract description 152
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 97
- 150000003839 salts Chemical class 0.000 claims abstract description 90
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 75
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 73
- 239000012453 solvate Substances 0.000 claims abstract description 70
- 125000001424 substituent group Chemical group 0.000 claims abstract description 54
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 43
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 40
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 40
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 38
- 150000002367 halogens Chemical class 0.000 claims abstract description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 31
- 125000004990 dihydroxyalkyl group Chemical group 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims abstract description 27
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 25
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 9
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 9
- 229910052705 radium Inorganic materials 0.000 claims abstract description 5
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 5
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 111
- 238000000034 method Methods 0.000 claims description 85
- 201000010099 disease Diseases 0.000 claims description 60
- 239000008194 pharmaceutical composition Substances 0.000 claims description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 52
- 208000035475 disorder Diseases 0.000 claims description 51
- 238000002360 preparation method Methods 0.000 claims description 41
- 208000023275 Autoimmune disease Diseases 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 20
- 239000002585 base Substances 0.000 claims description 19
- 239000003112 inhibitor Substances 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 210000000056 organ Anatomy 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 229940124597 therapeutic agent Drugs 0.000 claims description 15
- 206010052779 Transplant rejections Diseases 0.000 claims description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
- 208000014951 hematologic disease Diseases 0.000 claims description 12
- 206010025135 lupus erythematosus Diseases 0.000 claims description 12
- 238000002560 therapeutic procedure Methods 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 11
- 125000005228 aryl sulfonate group Chemical group 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 208000037979 autoimmune inflammatory disease Diseases 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 125000005227 alkyl sulfonate group Chemical group 0.000 claims description 8
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims description 8
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 7
- 108010036949 Cyclosporine Proteins 0.000 claims description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 7
- 230000019491 signal transduction Effects 0.000 claims description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 6
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 6
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 6
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims description 6
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 230000000968 intestinal effect Effects 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 4
- 108020004491 Antisense DNA Proteins 0.000 claims description 3
- 108020005544 Antisense RNA Proteins 0.000 claims description 3
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
- 229940123587 Cell cycle inhibitor Drugs 0.000 claims description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 3
- 229930105110 Cyclosporin A Natural products 0.000 claims description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 3
- 229940079156 Proteasome inhibitor Drugs 0.000 claims 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 claims description 3
- 229960003697 abatacept Drugs 0.000 claims description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 3
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 3
- 230000002280 anti-androgenic effect Effects 0.000 claims description 3
- 230000003388 anti-hormonal effect Effects 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 3
- 230000000340 anti-metabolite Effects 0.000 claims description 3
- 239000000051 antiandrogen Substances 0.000 claims description 3
- 229940100197 antimetabolite Drugs 0.000 claims description 3
- 239000002256 antimetabolite Substances 0.000 claims description 3
- 239000003816 antisense DNA Substances 0.000 claims description 3
- 229940092117 atgam Drugs 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 239000003184 complementary RNA Substances 0.000 claims description 3
- 229960004397 cyclophosphamide Drugs 0.000 claims description 3
- 239000000824 cytostatic agent Substances 0.000 claims description 3
- 229960002806 daclizumab Drugs 0.000 claims description 3
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 3
- 239000002532 enzyme inhibitor Substances 0.000 claims description 3
- 239000003102 growth factor Substances 0.000 claims description 3
- 229960004171 hydroxychloroquine Drugs 0.000 claims description 3
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 claims description 3
- 229960001680 ibuprofen Drugs 0.000 claims description 3
- 239000012444 intercalating antibiotic Substances 0.000 claims description 3
- 229960000681 leflunomide Drugs 0.000 claims description 3
- 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 claims description 3
- 239000003446 ligand Substances 0.000 claims description 3
- 229960003105 metformin Drugs 0.000 claims description 3
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 3
- 229960000485 methotrexate Drugs 0.000 claims description 3
- 230000000394 mitotic effect Effects 0.000 claims description 3
- 229940014456 mycophenolate Drugs 0.000 claims description 3
- 229960000951 mycophenolic acid Drugs 0.000 claims description 3
- 229960002009 naproxen Drugs 0.000 claims description 3
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 229960005489 paracetamol Drugs 0.000 claims description 3
- 229960002702 piroxicam Drugs 0.000 claims description 3
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 3
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 3
- 239000003207 proteasome inhibitor Substances 0.000 claims description 3
- 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 claims description 3
- 102000027483 retinoid hormone receptors Human genes 0.000 claims description 3
- 108091008679 retinoid hormone receptors Proteins 0.000 claims description 3
- 229960002930 sirolimus Drugs 0.000 claims 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 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims description 3
- 208000025705 Axial Spondyloarthritis Diseases 0.000 claims description 2
- 208000002633 Febrile Neutropenia Diseases 0.000 claims description 2
- 206010016654 Fibrosis Diseases 0.000 claims description 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 206010040047 Sepsis Diseases 0.000 claims description 2
- 201000002661 Spondylitis Diseases 0.000 claims description 2
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims description 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
- 238000011374 additional therapy Methods 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 229910021529 ammonia Inorganic materials 0.000 claims description 2
- 229960001265 ciclosporin Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 208000030533 eye disease Diseases 0.000 claims description 2
- 230000004761 fibrosis Effects 0.000 claims description 2
- 229960002706 gusperimus Drugs 0.000 claims description 2
- 239000000367 immunologic factor Substances 0.000 claims description 2
- IDINUJSAMVOPCM-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-INIZCTEOSA-N 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 208000013223 septicemia Diseases 0.000 claims description 2
- 239000003558 transferase inhibitor Substances 0.000 claims description 2
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 2
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 5
- 208000017520 skin disease Diseases 0.000 claims 2
- 102000014150 Interferons Human genes 0.000 claims 1
- 108010050904 Interferons Proteins 0.000 claims 1
- 208000018569 Respiratory Tract disease Diseases 0.000 claims 1
- 229940079322 interferon Drugs 0.000 claims 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims 1
- 229960001967 tacrolimus Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 393
- 239000011541 reaction mixture Substances 0.000 description 346
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 231
- 235000019439 ethyl acetate Nutrition 0.000 description 191
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 187
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 166
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 122
- 239000000203 mixture Substances 0.000 description 113
- 239000000741 silica gel Substances 0.000 description 112
- 229910002027 silica gel Inorganic materials 0.000 description 112
- 239000000243 solution Substances 0.000 description 106
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 102
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 94
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 82
- 239000012267 brine Substances 0.000 description 79
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 79
- 238000001819 mass spectrum Methods 0.000 description 72
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 60
- 108010024121 Janus Kinases Proteins 0.000 description 60
- 102000015617 Janus Kinases Human genes 0.000 description 60
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 60
- 229910052938 sodium sulfate Inorganic materials 0.000 description 60
- 235000011152 sodium sulphate Nutrition 0.000 description 60
- 239000012044 organic layer Substances 0.000 description 59
- 239000007787 solid Substances 0.000 description 57
- 238000005160 1H NMR spectroscopy Methods 0.000 description 55
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 49
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 48
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 47
- 235000019341 magnesium sulphate Nutrition 0.000 description 47
- 239000010410 layer Substances 0.000 description 43
- 239000012074 organic phase Substances 0.000 description 43
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 40
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 40
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
- 239000000284 extract Substances 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 229910000024 caesium carbonate Inorganic materials 0.000 description 33
- CGQVSZWMAXJEFB-UHFFFAOYSA-N 4-(1-pentan-3-ylpyrazol-4-yl)-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 CGQVSZWMAXJEFB-UHFFFAOYSA-N 0.000 description 32
- 239000003921 oil Substances 0.000 description 30
- 235000019198 oils Nutrition 0.000 description 30
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 26
- 239000007832 Na2SO4 Substances 0.000 description 24
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 23
- 238000003756 stirring Methods 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- 238000003556 assay Methods 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 101000997835 Homo sapiens Tyrosine-protein kinase JAK1 Proteins 0.000 description 18
- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 description 18
- 239000006260 foam Substances 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 101000997832 Homo sapiens Tyrosine-protein kinase JAK2 Proteins 0.000 description 17
- 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 description 17
- 102100033444 Tyrosine-protein kinase JAK2 Human genes 0.000 description 17
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 17
- 230000014759 maintenance of location Effects 0.000 description 17
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 17
- 108090000695 Cytokines Proteins 0.000 description 16
- 102000004127 Cytokines Human genes 0.000 description 16
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 16
- 208000027866 inflammatory disease Diseases 0.000 description 16
- CMGKRWOBNPTZBW-UHFFFAOYSA-N pyrazolo[1,5-a]pyrazine Chemical class C1=NC=CN2N=CC=C21 CMGKRWOBNPTZBW-UHFFFAOYSA-N 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 16
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 15
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 13
- 150000001721 carbon Chemical group 0.000 description 13
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 13
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 11
- 239000012230 colorless oil Substances 0.000 description 11
- 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 10
- BNPOTXLWPZOESZ-RXMQYKEDSA-N (4s)-4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OC[C@@H](CCl)O1 BNPOTXLWPZOESZ-RXMQYKEDSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 10
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 230000001363 autoimmune Effects 0.000 description 9
- 239000013058 crude material Substances 0.000 description 9
- 238000003821 enantio-separation Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 235000015320 potassium carbonate Nutrition 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- ONWJTTYWEKLZGO-UHFFFAOYSA-N 6-[1-(azetidin-3-yl)pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CNC1 ONWJTTYWEKLZGO-UHFFFAOYSA-N 0.000 description 8
- 241000282414 Homo sapiens Species 0.000 description 8
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 8
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000011521 glass Substances 0.000 description 8
- QISKQMKWYKAFDP-UHFFFAOYSA-N 4-chloro-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound ClC1=NC(=CN2N=CC=C12)C1=CNN=C1 QISKQMKWYKAFDP-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 230000000670 limiting effect Effects 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- KJMQZNQGRSHNBG-UHFFFAOYSA-N 4-chloro-6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine hydrochloride Chemical compound Cl.COc1ccc(Cn2cc(cn2)-c2cn3nccc3c(Cl)n2)cc1 KJMQZNQGRSHNBG-UHFFFAOYSA-N 0.000 description 6
- MYOBPAVMRNQYRS-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-4-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CN1C=C(C=N1)C1=CN2N=CC=C2C(=N1)C1=CNN=C1 MYOBPAVMRNQYRS-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 0 CC*1(C*NC)CC1 Chemical compound CC*1(C*NC)CC1 0.000 description 6
- 201000004624 Dermatitis Diseases 0.000 description 6
- 108091000080 Phosphotransferase Proteins 0.000 description 6
- 239000004146 Propane-1,2-diol Substances 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 208000037765 diseases and disorders Diseases 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 102000020233 phosphotransferase Human genes 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 235000013772 propylene glycol Nutrition 0.000 description 6
- 229960004063 propylene glycol Drugs 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- TVOJIBGZFYMWDT-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CNN=C1 TVOJIBGZFYMWDT-UHFFFAOYSA-N 0.000 description 5
- QKUDUXKQUNCZFN-UHFFFAOYSA-N 4-chloro-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine hydrochloride Chemical compound Cl.Cn1cc(cn1)-c1cn2nccc2c(Cl)n1 QKUDUXKQUNCZFN-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 5
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 239000012280 lithium aluminium hydride Substances 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 5
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 108010008165 Etanercept Proteins 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- 102000042838 JAK family Human genes 0.000 description 4
- 108091082332 JAK family Proteins 0.000 description 4
- 229910010084 LiAlH4 Inorganic materials 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 206010039710 Scleroderma Diseases 0.000 description 4
- 206010046851 Uveitis Diseases 0.000 description 4
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- TXWOGHSRPAYOML-UHFFFAOYSA-M cyclobutanecarboxylate Chemical compound [O-]C(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-M 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 230000002285 radioactive effect Effects 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- 238000003828 vacuum filtration Methods 0.000 description 4
- XSJHLFITRCFYLP-UHFFFAOYSA-N (2,2,4-trimethyl-1,3-dioxolan-4-yl)methyl methanesulfonate Chemical compound CC1(C)OCC(C)(COS(C)(=O)=O)O1 XSJHLFITRCFYLP-UHFFFAOYSA-N 0.000 description 3
- OIAGAWSCJMASIN-GOSISDBHSA-N (2R)-2-methoxy-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-1-amine Chemical compound CO[C@H](CN)CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(CC)CC OIAGAWSCJMASIN-GOSISDBHSA-N 0.000 description 3
- PRDYSVHWSCSUOP-VGAJERRHSA-N (3R)-4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]piperidin-3-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CCNC[C@H]1O PRDYSVHWSCSUOP-VGAJERRHSA-N 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- RHUKJQAHGGDNEQ-UHFFFAOYSA-N 1,3-oxazolidine-3-carboxylic acid Chemical compound OC(=O)N1CCOC1 RHUKJQAHGGDNEQ-UHFFFAOYSA-N 0.000 description 3
- IZKVGEWCELXYRI-UHFFFAOYSA-N 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C1=NN(C(C)OCC)C=C1B1OC(C)(C)C(C)(C)O1 IZKVGEWCELXYRI-UHFFFAOYSA-N 0.000 description 3
- KITCYDCXSZDXLF-UHFFFAOYSA-N 1-[2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]ethyl]piperazin-2-one Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CCN2CCNCC2=O)N=C1 KITCYDCXSZDXLF-UHFFFAOYSA-N 0.000 description 3
- SOXWEUBOXNGPLB-UHFFFAOYSA-N 2-(3-hydroxyazetidin-1-yl)-1-[3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]azetidin-1-yl]ethanone Chemical compound OC1CN(C1)CC(=O)N1CC(C1)N1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(CC)CC SOXWEUBOXNGPLB-UHFFFAOYSA-N 0.000 description 3
- LNIHJHKFYSROAO-UHFFFAOYSA-N 2-(methylamino)-1-[3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]azetidin-1-yl]ethanone Chemical compound CNCC(=O)N1CC(C1)N1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(CC)CC LNIHJHKFYSROAO-UHFFFAOYSA-N 0.000 description 3
- NLSOJIALIUJYIW-MRXNPFEDSA-N 4-[1-[(1R)-1-cyclopropylpropyl]pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CC[C@H](C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 NLSOJIALIUJYIW-MRXNPFEDSA-N 0.000 description 3
- BIQLFOVHGXFGRI-UHFFFAOYSA-N 4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]butane-1,3-diol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(O)CCO)N=C1 BIQLFOVHGXFGRI-UHFFFAOYSA-N 0.000 description 3
- XYCVFPRYIGXFPH-UHFFFAOYSA-N 4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclohexan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CCC(O)CC1 XYCVFPRYIGXFPH-UHFFFAOYSA-N 0.000 description 3
- LLNQWPTUJJYTTE-UHFFFAOYSA-N 4-iodopyrazole Chemical compound IC=1C=NNC=1 LLNQWPTUJJYTTE-UHFFFAOYSA-N 0.000 description 3
- DQSHWJOBNNVINQ-UHFFFAOYSA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-5H-pyrazolo[1,5-a]pyrazin-4-one Chemical compound COC1=CC=C(CN2C=C(C=N2)C2=CN3N=CC=C3C(O)=N2)C=C1 DQSHWJOBNNVINQ-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 3
- 206010003267 Arthritis reactive Diseases 0.000 description 3
- HIABHJAAHXXWGC-UHFFFAOYSA-N CCC(CC1CC1)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 Chemical compound CCC(CC1CC1)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 HIABHJAAHXXWGC-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- 208000015943 Coeliac disease Diseases 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 206010012438 Dermatitis atopic Diseases 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 208000003456 Juvenile Arthritis Diseases 0.000 description 3
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 3
- 208000005777 Lupus Nephritis Diseases 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 206010063663 Neuropsychiatric lupus Diseases 0.000 description 3
- 206010036774 Proctitis Diseases 0.000 description 3
- 208000003251 Pruritus Diseases 0.000 description 3
- 206010062164 Seronegative arthritis Diseases 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- PYHZXOYNICJOTG-UHFFFAOYSA-N [2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P PYHZXOYNICJOTG-UHFFFAOYSA-N 0.000 description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 description 3
- 208000004631 alopecia areata Diseases 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 201000008937 atopic dermatitis Diseases 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 description 3
- KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 3
- 230000002074 deregulated effect Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000002489 hematologic effect Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000155 isotopic effect Effects 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 208000008585 mastocytosis Diseases 0.000 description 3
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
- 229950010765 pivalate Drugs 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
- 229910000105 potassium hydride Inorganic materials 0.000 description 3
- 230000001823 pruritic effect Effects 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 208000002574 reactive arthritis Diseases 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000007789 sealing Methods 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 229940095064 tartrate Drugs 0.000 description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- GNLJBJNONOOOQC-UHFFFAOYSA-N $l^{3}-carbane;magnesium Chemical compound [Mg]C GNLJBJNONOOOQC-UHFFFAOYSA-N 0.000 description 2
- RGBAHPYNXOCIPY-UHFFFAOYSA-N (2,2,4-trimethyl-1,3-dioxolan-4-yl)methanol Chemical compound CC1(C)OCC(C)(CO)O1 RGBAHPYNXOCIPY-UHFFFAOYSA-N 0.000 description 2
- LJCWRJYVPJJTMB-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound CC(C)(C)OC(=O)NCC(=O)ON1C(=O)CCC1=O LJCWRJYVPJJTMB-UHFFFAOYSA-N 0.000 description 2
- QMHIQYFDHQKWPO-LJQANCHMSA-N (2R)-1-(dimethylamino)-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-2-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](O)CN(C)C)N=C1 QMHIQYFDHQKWPO-LJQANCHMSA-N 0.000 description 2
- ISWBZDSAQHLONO-GOSISDBHSA-N (2R)-1-methoxy-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-2-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](O)COC)N=C1 ISWBZDSAQHLONO-GOSISDBHSA-N 0.000 description 2
- VYIVPIOHJVLMDT-OAHLLOKOSA-N (2R)-2-hydroxy-1-[3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]azetidin-1-yl]propan-1-one Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CN(C1)C(=O)[C@@H](C)O VYIVPIOHJVLMDT-OAHLLOKOSA-N 0.000 description 2
- ACJCSGITKCJZNM-OAQYLSRUSA-N (2R)-2-methyl-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@](C)(O)CO)N=C1 ACJCSGITKCJZNM-OAQYLSRUSA-N 0.000 description 2
- JTBCMVGGBDUBFT-QGZVFWFLSA-N (2R)-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CCC(CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C[C@H](CO)O)N=CC=2 JTBCMVGGBDUBFT-QGZVFWFLSA-N 0.000 description 2
- BNGZGHJLRLYZLX-XPCCGILXSA-N (2R)-3-[4-[4-[1-(1,1,1-trifluorobutan-2-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CCC(N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](O)CO)N=C1)C(F)(F)F BNGZGHJLRLYZLX-XPCCGILXSA-N 0.000 description 2
- HQYCIYSQINFXHM-SOLBZPMBSA-N (2R)-3-[4-[4-[1-[(1R)-1-[(1S)-2,2-difluorocyclopropyl]propyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CC[C@H]([C@@H]1CC1(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](O)CO)N=C1 HQYCIYSQINFXHM-SOLBZPMBSA-N 0.000 description 2
- GVILQOVWHWVBRQ-XLIONFOSSA-N (2R)-3-[4-[4-[1-[(1S)-2,2-dimethylcyclopentyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CC1([C@H](CCC1)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C[C@H](CO)O)N=CC=2)C GVILQOVWHWVBRQ-XLIONFOSSA-N 0.000 description 2
- HGTQRXMBFVRIFR-QBIMZIAESA-N (2R)-3-[4-[4-[1-[(1S,2R)-2-methylcyclobutyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound C[C@@H]1CC[C@@H]1n1cc(cn1)-c1nc(cn2nccc12)-c1cnn(C[C@@H](O)CO)c1 HGTQRXMBFVRIFR-QBIMZIAESA-N 0.000 description 2
- SMROVSFEANQWIQ-IBGZPJMESA-N (2S)-2-[[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]methyl]morpholine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H]2CNCCO2)N=C1 SMROVSFEANQWIQ-IBGZPJMESA-N 0.000 description 2
- VYIVPIOHJVLMDT-HNNXBMFYSA-N (2S)-2-hydroxy-1-[3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]azetidin-1-yl]propan-1-one Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CN(C1)C(=O)[C@H](C)O VYIVPIOHJVLMDT-HNNXBMFYSA-N 0.000 description 2
- JTBCMVGGBDUBFT-KRWDZBQOSA-N (2S)-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](O)CO)N=C1 JTBCMVGGBDUBFT-KRWDZBQOSA-N 0.000 description 2
- AOWHHZSWFRKEHL-UHFFFAOYSA-N (3-hydroxycyclobutyl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1CC(O)C1 AOWHHZSWFRKEHL-UHFFFAOYSA-N 0.000 description 2
- BIQLFOVHGXFGRI-SFHVURJKSA-N (3S)-4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]butane-1,3-diol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](O)CCO)N=C1 BIQLFOVHGXFGRI-SFHVURJKSA-N 0.000 description 2
- KKLJYANZLRBCLU-UHFFFAOYSA-N 1,1,1-trifluorobutan-2-yl methanesulfonate Chemical compound CS(=O)(=O)OC(C(F)(F)F)CC KKLJYANZLRBCLU-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 2
- RBIYCKQPZCWGKL-UHFFFAOYSA-N 1-(1-cyclopropylpropyl)-4-iodopyrazole Chemical compound CCC(C1CC1)N1C=C(I)C=N1 RBIYCKQPZCWGKL-UHFFFAOYSA-N 0.000 description 2
- XPDWYXNGYUFNEG-UHFFFAOYSA-N 1-(1-ethoxyethyl)-4-iodopyrazole Chemical compound CCOC(C)N1C=C(I)C=N1 XPDWYXNGYUFNEG-UHFFFAOYSA-N 0.000 description 2
- OMNKUSFHMIQXPL-NXEZZACHSA-N 1-[(1R,2R)-2-methylcyclohexyl]pyrazole Chemical compound C[C@H]1[C@@H](CCCC1)N1N=CC=C1 OMNKUSFHMIQXPL-NXEZZACHSA-N 0.000 description 2
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 2
- SDNGLJCJUQMLCR-UHFFFAOYSA-N 1-amino-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-2-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(O)CN)N=C1 SDNGLJCJUQMLCR-UHFFFAOYSA-N 0.000 description 2
- CWBXRPMPOBUVMH-UHFFFAOYSA-N 1-cyclopropylbutan-2-one Chemical compound CCC(=O)CC1CC1 CWBXRPMPOBUVMH-UHFFFAOYSA-N 0.000 description 2
- ZVTCOQDWIJYYSQ-UHFFFAOYSA-N 1-cyclopropylpropan-1-ol Chemical compound CCC(O)C1CC1 ZVTCOQDWIJYYSQ-UHFFFAOYSA-N 0.000 description 2
- KCZANJXDZAFROI-UHFFFAOYSA-N 1-pentan-3-ylpyrazole Chemical compound CCC(CC)N1C=CC=N1 KCZANJXDZAFROI-UHFFFAOYSA-N 0.000 description 2
- QVZXJVILZBKCPS-UHFFFAOYSA-N 2,2-dimethyl-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(C)(C)CO)N=C1 QVZXJVILZBKCPS-UHFFFAOYSA-N 0.000 description 2
- MXGPPMXKCJUMCI-UHFFFAOYSA-N 2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]-N-propan-2-ylacetamide Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(=O)NC(C)C)N=C1 MXGPPMXKCJUMCI-UHFFFAOYSA-N 0.000 description 2
- RRUMNCYHIPZCJS-UHFFFAOYSA-N 2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C(C)CO RRUMNCYHIPZCJS-UHFFFAOYSA-N 0.000 description 2
- OANLOJFGMDFXLE-UHFFFAOYSA-N 2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,3-diol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C(CO)CO OANLOJFGMDFXLE-UHFFFAOYSA-N 0.000 description 2
- PFHQZHDUKYAXNC-AWEZNQCLSA-N 2-[4-[4-[1-[(2S)-pentan-2-yl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,3-diol Chemical compound CCC[C@H](C)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C(CO)CO PFHQZHDUKYAXNC-AWEZNQCLSA-N 0.000 description 2
- NGAAOEYVYQJXJR-UHFFFAOYSA-N 2-[4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]pyrazol-1-yl]butan-1-ol Chemical compound CCC(CO)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C)N=C1 NGAAOEYVYQJXJR-UHFFFAOYSA-N 0.000 description 2
- VHBISBSNGUVGTR-UHFFFAOYSA-N 2-[4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]pyrazol-1-yl]cyclopentan-1-ol Chemical compound CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C1C(CCC1)O VHBISBSNGUVGTR-UHFFFAOYSA-N 0.000 description 2
- NECGGEBCCVOZEZ-UHFFFAOYSA-N 2-[methyl(methylsulfonyl)amino]ethyl methanesulfonate Chemical compound CS(=O)(=O)N(C)CCOS(C)(=O)=O NECGGEBCCVOZEZ-UHFFFAOYSA-N 0.000 description 2
- ZFWHBPIQEJHLAR-UHFFFAOYSA-N 2-amino-1-[3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]azetidin-1-yl]ethanone Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CN(C1)C(=O)CN ZFWHBPIQEJHLAR-UHFFFAOYSA-N 0.000 description 2
- YCELUTLXURKQPL-UHFFFAOYSA-N 2-amino-1-[4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]piperidin-1-yl]ethanone Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CCN(CC1)C(=O)CN YCELUTLXURKQPL-UHFFFAOYSA-N 0.000 description 2
- QTOCMURLHLRIRU-UHFFFAOYSA-N 2-chloro-1-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]ethanone Chemical compound ClCC(=O)C=1C=NN(C=1)CC1=CC=C(C=C1)OC QTOCMURLHLRIRU-UHFFFAOYSA-N 0.000 description 2
- YZOGROCAAWYRBU-UHFFFAOYSA-N 2-cyclopropyl-n-methoxy-n-methylacetamide Chemical compound CON(C)C(=O)CC1CC1 YZOGROCAAWYRBU-UHFFFAOYSA-N 0.000 description 2
- KQHQNBIOGBNAOH-UHFFFAOYSA-N 2-methyl-1-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-2-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(C)(C)O)N=C1 KQHQNBIOGBNAOH-UHFFFAOYSA-N 0.000 description 2
- LIRSAFKJCZZQQI-UHFFFAOYSA-N 2-methyl-2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C(C)(C)CO LIRSAFKJCZZQQI-UHFFFAOYSA-N 0.000 description 2
- OFELUXOUVZRMPM-UHFFFAOYSA-N 3-[4-[6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-4-yl]pyrazol-1-yl]pentan-2-one Chemical compound COC1=CC=C(CN2N=CC(=C2)C=2N=C(C=3N(C=2)N=CC=3)C=2C=NN(C=2)C(C(C)=O)CC)C=C1 OFELUXOUVZRMPM-UHFFFAOYSA-N 0.000 description 2
- OKMJZZVJEXVNOK-UHFFFAOYSA-N 4-(1-pentan-3-ylpyrazol-4-yl)-6-[1-[(2,2,4-trimethyl-1,3-dioxolan-4-yl)methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2(C)COC(C)(C)O2)N=C1 OKMJZZVJEXVNOK-UHFFFAOYSA-N 0.000 description 2
- XENRQMHKPAIYOY-UHFFFAOYSA-N 4-[1-(1-ethoxyethyl)pyrazol-4-yl]-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCOC(C)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C)N=C1 XENRQMHKPAIYOY-UHFFFAOYSA-N 0.000 description 2
- MSKACUKRYNVIBO-LCQOSCCDSA-N 4-[1-(2,2-dimethylcyclopentyl)pyrazol-4-yl]-6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CC1(C)OC[C@@H](CN2C=C(C=N2)C2=CN3N=CC=C3C(=N2)C2=CN(N=C2)C2CCCC2(C)C)O1 MSKACUKRYNVIBO-LCQOSCCDSA-N 0.000 description 2
- HTJRLZZEMSIYIT-UHFFFAOYSA-N 4-[1-(2-ethylcyclopentyl)pyrazol-4-yl]-6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC1CCCC1N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2=CC=C(OC)C=C2)N=C1 HTJRLZZEMSIYIT-UHFFFAOYSA-N 0.000 description 2
- CIJCUJJBEHAVNW-UHFFFAOYSA-N 4-[1-(2-methylcycloheptyl)pyrazol-4-yl]-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C1C(CCCCC1)C CIJCUJJBEHAVNW-UHFFFAOYSA-N 0.000 description 2
- UTLNFRJIPFPDCE-UHFFFAOYSA-N 4-[1-(dicyclopropylmethyl)pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound C1CC1C(C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 UTLNFRJIPFPDCE-UHFFFAOYSA-N 0.000 description 2
- KRSQFNNUEKCRMU-TZIWHRDSSA-N 4-[1-[(1R)-1-cyclopropylpropyl]pyrazol-4-yl]-6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound C1(CC1)[C@@H](CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C[C@H]1OC(OC1)(C)C)N=CC=2 KRSQFNNUEKCRMU-TZIWHRDSSA-N 0.000 description 2
- OOWQPYBPYJTPMN-XHDPSFHLSA-N 4-[1-[(1R,2S)-2-methylcyclobutyl]pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound C[C@@H]1[C@@H](CC1)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NNC=1)N=CC=2 OOWQPYBPYJTPMN-XHDPSFHLSA-N 0.000 description 2
- ABRJSZPTHUTRIK-UHFFFAOYSA-N 4-[1-[1-(2,2-difluorocyclopropyl)propyl]pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(C1CC1(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 ABRJSZPTHUTRIK-UHFFFAOYSA-N 0.000 description 2
- AJAWHQDUZDCYMQ-UHFFFAOYSA-N 4-[2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]ethyl]morpholine Chemical compound CCC(CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)CCN1CCOCC1)N=CC=2 AJAWHQDUZDCYMQ-UHFFFAOYSA-N 0.000 description 2
- ZUXWPTUABRHWBA-UHFFFAOYSA-N 4-[[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]methyl]piperidin-4-ol Chemical compound CCC(CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)CC1(CCNCC1)O)N=CC=2 ZUXWPTUABRHWBA-UHFFFAOYSA-N 0.000 description 2
- SMUSRVWUPCHTDF-PSASIEDQSA-N 4-bromo-1-[(1R,2R)-2-methylcyclohexyl]pyrazole Chemical compound BrC=1C=NN(C=1)[C@H]1[C@@H](CCCC1)C SMUSRVWUPCHTDF-PSASIEDQSA-N 0.000 description 2
- GKTAAVSSNHFGGZ-UHFFFAOYSA-N 4-chloro-6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound COC1=CC=C(CN2C=C(C=N2)C2=CN3N=CC=C3C(Cl)=N2)C=C1 GKTAAVSSNHFGGZ-UHFFFAOYSA-N 0.000 description 2
- ZXNZREKRXQRZNP-UHFFFAOYSA-N 4-iodo-1-[(4-methoxyphenyl)methyl]pyrazole Chemical compound C1=CC(OC)=CC=C1CN1N=CC(I)=C1 ZXNZREKRXQRZNP-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- GWJXYJYIUILPON-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-4-oxo-5H-pyrazolo[1,5-a]pyrazine-2-carboxylic acid Chemical compound CN1C=C(C=N1)C1=CN2N=C(C=C2C(O)=N1)C(O)=O GWJXYJYIUILPON-UHFFFAOYSA-N 0.000 description 2
- GBHVDABDZIHIAX-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-5H-pyrazolo[1,5-a]pyrazin-4-one Chemical compound CN1C=C(C=N1)C1=CN2N=CC=C2C(=O)N1 GBHVDABDZIHIAX-UHFFFAOYSA-N 0.000 description 2
- LQUPJPMQEDAVNH-UHFFFAOYSA-N 6-(1H-pyrazol-4-yl)-4-[1-(1,1,1-trifluorobutan-2-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC(N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1)C(F)(F)F LQUPJPMQEDAVNH-UHFFFAOYSA-N 0.000 description 2
- HNPKKBMDNDMIGP-UHFFFAOYSA-N 6-[1-(1,3-dioxan-4-ylmethyl)pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2CCOCO2)N=C1 HNPKKBMDNDMIGP-UHFFFAOYSA-N 0.000 description 2
- MUXJGMIEWFFDGE-UHFFFAOYSA-N 6-[1-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CCC2(CC1)OCCO2 MUXJGMIEWFFDGE-UHFFFAOYSA-N 0.000 description 2
- BCGNYIDWPKUNKN-UHFFFAOYSA-N 6-[1-(2,2-dimethyl-1,3-dioxan-5-yl)pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1COC(C)(C)OC1 BCGNYIDWPKUNKN-UHFFFAOYSA-N 0.000 description 2
- YQBQXLRNAYEBCY-UHFFFAOYSA-N 6-[1-(2-methylsulfonylethyl)pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CS(=O)(=O)CCN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(CC)CC YQBQXLRNAYEBCY-UHFFFAOYSA-N 0.000 description 2
- JRZRWEBPWFKYBH-UHFFFAOYSA-N 6-[1-(3-methylidenecyclobutyl)pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC(=C)C1 JRZRWEBPWFKYBH-UHFFFAOYSA-N 0.000 description 2
- SUUUYFSQIYEYRT-UHFFFAOYSA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-4-[1-(1,1,1-trifluorobutan-2-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC(N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2=CC=C(OC)C=C2)N=C1)C(F)(F)F SUUUYFSQIYEYRT-UHFFFAOYSA-N 0.000 description 2
- KQLZIGJYMUWFLN-UHFFFAOYSA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-4-[1-(1,1,1-trifluoropentan-3-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC(F)(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2=CC=C(OC)C=C2)N=C1 KQLZIGJYMUWFLN-UHFFFAOYSA-N 0.000 description 2
- AEIFJVWDNFCUDZ-UHFFFAOYSA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-4-[1-(4,4,4-trifluorobutan-2-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound COC1=CC=C(CN2C=C(C=N2)C2=CN3N=CC=C3C(=N2)C2=CN(N=C2)C(C)CC(F)(F)F)C=C1 AEIFJVWDNFCUDZ-UHFFFAOYSA-N 0.000 description 2
- HLSORZHYKRRDMG-KBMIEXCESA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-4-[1-[(1R,2R)-2-methylcyclohexyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound COC1=CC=C(CN2N=CC(=C2)C=2N=C(C=3N(C=2)N=CC=3)C=2C=NN(C=2)[C@H]2[C@@H](CCCC2)C)C=C1 HLSORZHYKRRDMG-KBMIEXCESA-N 0.000 description 2
- SNPUUUZIQXBZSM-VTBWFHPJSA-N 6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]-4-[1-(1,1,1-trifluorobutan-2-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CC1(OC[C@H](O1)CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(C(F)(F)F)CC)C SNPUUUZIQXBZSM-VTBWFHPJSA-N 0.000 description 2
- ZLVGZRHYMHKEJB-QKYXUNIQSA-N 6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]-4-[1-[(1R,2S)-2-methylcyclobutyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CC1(OC[C@H](O1)CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)[C@H]1[C@H](CC1)C)C ZLVGZRHYMHKEJB-QKYXUNIQSA-N 0.000 description 2
- RTXZNLPQAVCPRU-IBGZPJMESA-N 6-[1-[[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H]2COC(C)(C)O2)N=C1 RTXZNLPQAVCPRU-IBGZPJMESA-N 0.000 description 2
- GJEZBVHHZQAEDB-UHFFFAOYSA-N 6-oxabicyclo[3.1.0]hexane Chemical compound C1CCC2OC21 GJEZBVHHZQAEDB-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- MGSVNUUDXIKGRR-TZMCWYRMSA-N C(C)[C@H]1[C@@H](CCC1)N1N=CC(=C1)B1OC(C(O1)(C)C)(C)C Chemical compound C(C)[C@H]1[C@@H](CCC1)N1N=CC(=C1)B1OC(C(O1)(C)C)(C)C MGSVNUUDXIKGRR-TZMCWYRMSA-N 0.000 description 2
- MOTGHCGCHYLZMI-LBPRGKRZSA-N CC(C)C[C@H](C)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 Chemical compound CC(C)C[C@H](C)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 MOTGHCGCHYLZMI-LBPRGKRZSA-N 0.000 description 2
- KFBQZBIZIJUYMN-UHFFFAOYSA-N CCC(C1CCC1)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 Chemical compound CCC(C1CCC1)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 KFBQZBIZIJUYMN-UHFFFAOYSA-N 0.000 description 2
- CFZKGLJHFXMZMG-UHFFFAOYSA-N CCC(CC)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 Chemical compound CCC(CC)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 CFZKGLJHFXMZMG-UHFFFAOYSA-N 0.000 description 2
- ZWNHDUPLKJBMEF-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](C(C4)CC4(CO)O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](C(C4)CC4(CO)O)nc3)c[n]3nccc23)c1 ZWNHDUPLKJBMEF-UHFFFAOYSA-N 0.000 description 2
- OUDUGVBXIJNWSG-YADARESESA-N CC[C@H](C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](C)O[Si](C)(C)C(C)(C)C)N=C1 Chemical compound CC[C@H](C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](C)O[Si](C)(C)C(C)(C)C)N=C1 OUDUGVBXIJNWSG-YADARESESA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 2
- 229940121730 Janus kinase 2 inhibitor Drugs 0.000 description 2
- 229940123241 Janus kinase 3 inhibitor Drugs 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 description 2
- 208000021908 Myocardial disease Diseases 0.000 description 2
- QLESZLJWQFXNGP-UHFFFAOYSA-N N,N-dimethyl-2-oxo-2-[3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]azetidin-1-yl]acetamide Chemical compound CN(C(C(N1CC(C1)N1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(CC)CC)=O)=O)C QLESZLJWQFXNGP-UHFFFAOYSA-N 0.000 description 2
- NZWKRMFCKXOQMF-UHFFFAOYSA-N N-(2-hydroxyethyl)-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclobutane-1-carboxamide Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC(C1)C(=O)NCCO NZWKRMFCKXOQMF-UHFFFAOYSA-N 0.000 description 2
- VXWDADMWHBDHHT-UHFFFAOYSA-N N-[2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]ethyl]cyclopropanamine Chemical compound CCC(CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)CCNC1CC1)N=CC=2 VXWDADMWHBDHHT-UHFFFAOYSA-N 0.000 description 2
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 2
- 229910002666 PdCl2 Inorganic materials 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- NZQZQJLZTDCMDP-SSDOTTSWSA-N [(2R)-4-methylpentan-2-yl] methanesulfonate Chemical compound CS(=O)(=O)O[C@H](C)CC(C)C NZQZQJLZTDCMDP-SSDOTTSWSA-N 0.000 description 2
- VWUQFWPEGNZUQV-PHDIDXHHSA-N [(4r,5r)-2,2,5-trimethyl-1,3-dioxolan-4-yl]methanol Chemical compound C[C@H]1OC(C)(C)O[C@@H]1CO VWUQFWPEGNZUQV-PHDIDXHHSA-N 0.000 description 2
- LTRACTCRKLEDCH-LURJTMIESA-N [(4s)-2,2,5,5-tetramethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)O[C@@H](CO)C(C)(C)O1 LTRACTCRKLEDCH-LURJTMIESA-N 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- OLPLCLUQAIDUNC-UHFFFAOYSA-N [2-[4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]pyrazol-1-yl]cyclopentyl]methanol Chemical compound CN1C=C(C=N1)C1=CN2N=CC=C2C(=N1)C1=CN(N=C1)C1CCCC1CO OLPLCLUQAIDUNC-UHFFFAOYSA-N 0.000 description 2
- IEVXFOVMPBXOPB-UHFFFAOYSA-N [3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclobutyl]methanol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC(CO)C1 IEVXFOVMPBXOPB-UHFFFAOYSA-N 0.000 description 2
- OXBWQUVGBOYGFN-UHFFFAOYSA-N [3-[[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]methyl]cyclobutyl]methanol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2CC(CO)C2)N=C1 OXBWQUVGBOYGFN-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 229960002964 adalimumab Drugs 0.000 description 2
- 125000006241 alcohol protecting group Chemical group 0.000 description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 125000006242 amine protecting group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 229960002170 azathioprine Drugs 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229940107810 cellcept Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 2
- LMKPHJYTFHAGHK-UHFFFAOYSA-N cyclodrine Chemical compound C1CCCC1(O)C(C(=O)OCCN(CC)CC)C1=CC=CC=C1 LMKPHJYTFHAGHK-UHFFFAOYSA-N 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 108010057085 cytokine receptors Proteins 0.000 description 2
- 102000003675 cytokine receptors Human genes 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 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 2
- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 2
- RXZZTAJADKQKMN-UHFFFAOYSA-N diethyl 1-[2-(1-methylpyrazol-4-yl)-2-oxoethyl]pyrazole-3,5-dicarboxylate Chemical compound CN1N=CC(=C1)C(CN1N=C(C=C1C(=O)OCC)C(=O)OCC)=O RXZZTAJADKQKMN-UHFFFAOYSA-N 0.000 description 2
- MBWXLICVQZUJOW-UHFFFAOYSA-N diethyl 1h-pyrazole-3,5-dicarboxylate Chemical compound CCOC(=O)C=1C=C(C(=O)OCC)NN=1 MBWXLICVQZUJOW-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 229940073621 enbrel Drugs 0.000 description 2
- 229960000403 etanercept Drugs 0.000 description 2
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 229940048921 humira Drugs 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 229940073062 imuran Drugs 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- XMBWDFGMSWQBCA-RNFDNDRNSA-M iodine-131(1-) Chemical compound [131I-] XMBWDFGMSWQBCA-RNFDNDRNSA-M 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- NFJPEKRRHIYYES-UHFFFAOYSA-N methylidenecyclopentane Chemical compound C=C1CCCC1 NFJPEKRRHIYYES-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- 229940063121 neoral Drugs 0.000 description 2
- 229940035567 orencia Drugs 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 208000003476 primary myelofibrosis Diseases 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N propane-1,3-diol Chemical compound OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- HCWPIIXVSYCSAN-OIOBTWANSA-N radium-223 Chemical compound [223Ra] HCWPIIXVSYCSAN-OIOBTWANSA-N 0.000 description 2
- 229960005562 radium-223 Drugs 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229940063122 sandimmune Drugs 0.000 description 2
- 201000000306 sarcoidosis Diseases 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- DYVSLMSAUAHWOH-UHFFFAOYSA-N tert-butyl 2,2,4-trimethyl-1,3-dioxolane-4-carboxylate Chemical compound CC(C)(C)OC(=O)C1(C)COC(C)(C)O1 DYVSLMSAUAHWOH-UHFFFAOYSA-N 0.000 description 2
- CJMWZUMIICXQCR-UHFFFAOYSA-N tert-butyl 2,3-dihydroxy-2-methylpropanoate Chemical compound OC(C(=O)OC(C)(C)C)(CO)C CJMWZUMIICXQCR-UHFFFAOYSA-N 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 2
- BRLQWZUYTZBJKN-GSVOUGTGSA-N (+)-Epichlorohydrin Chemical compound ClC[C@@H]1CO1 BRLQWZUYTZBJKN-GSVOUGTGSA-N 0.000 description 1
- ZWCOGBJQBIIEPG-UHFFFAOYSA-N (1,1-dioxothian-4-yl)methanol Chemical compound OCC1CCS(=O)(=O)CC1 ZWCOGBJQBIIEPG-UHFFFAOYSA-N 0.000 description 1
- DVXZLEHKUCHABK-TZIWHRDSSA-N (1R,2R)-2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclopentan-1-ol Chemical compound CCC(CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)[C@H]1[C@@H](CCC1)O)N=CC=2 DVXZLEHKUCHABK-TZIWHRDSSA-N 0.000 description 1
- DVXZLEHKUCHABK-QWAKEFERSA-N (1S)-2-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclopentan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C2=NC(=CN3C2=CC=N3)C4=CN(N=C4)C5CCC[C@@H]5O DVXZLEHKUCHABK-QWAKEFERSA-N 0.000 description 1
- JYSIPFBADBNFKR-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxan-5-yl) methanesulfonate Chemical compound CC1(C)OCC(OS(C)(=O)=O)CO1 JYSIPFBADBNFKR-UHFFFAOYSA-N 0.000 description 1
- BTAUZIVCHJIXAX-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxan-5-yl)methanol Chemical compound CC1(C)OCC(CO)CO1 BTAUZIVCHJIXAX-UHFFFAOYSA-N 0.000 description 1
- IUAJGXWNTGCAHA-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxan-5-yl)methyl methanesulfonate Chemical compound CC1(C)OCC(COS(C)(=O)=O)CO1 IUAJGXWNTGCAHA-UHFFFAOYSA-N 0.000 description 1
- BDNLKMOCJPCVQD-UHFFFAOYSA-N (2-phenyl-1,3-dioxan-5-yl) methanesulfonate Chemical compound O1CC(OS(=O)(=O)C)COC1C1=CC=CC=C1 BDNLKMOCJPCVQD-UHFFFAOYSA-N 0.000 description 1
- UYCFPNKTNWJDPG-OEMAIJDKSA-N (2R)-3-[4-[4-[1-(1,1,1-trifluoropentan-3-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CCC(CC(F)(F)F)N1C=C(C=N1)C2=NC(=CN3C2=CC=N3)C4=CN(N=C4)C[C@H](CO)O UYCFPNKTNWJDPG-OEMAIJDKSA-N 0.000 description 1
- JTYBFCFEYKYPMC-GOSISDBHSA-N (2R)-3-[4-[4-[1-(dicyclopropylmethyl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound OC[C@H](O)CN1C=C(C=N1)C1=CN2N=CC=C2C(=N1)C1=CN(N=C1)C(C1CC1)C1CC1 JTYBFCFEYKYPMC-GOSISDBHSA-N 0.000 description 1
- HGUMRBROBXBLAK-IEBWSBKVSA-N (2R)-3-[4-[4-[1-[(1R)-1-cyclopropylpropyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CC[C@H](C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](O)CO)N=C1 HGUMRBROBXBLAK-IEBWSBKVSA-N 0.000 description 1
- VELXQPPVCPGIEB-POZUXBRTSA-N (2R)-3-[4-[4-[1-[(1R,2S)-2-methylcyclopentyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound C[C@@H]1[C@@H](CCC1)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C[C@H](CO)O)N=CC=2 VELXQPPVCPGIEB-POZUXBRTSA-N 0.000 description 1
- KCFVSZJMFSMFCF-ZTNFWEORSA-N (2R)-3-[4-[4-[1-[(1S,2R)-2-ethylcyclopentyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound CC[C@@H]1CCC[C@@H]1N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](O)CO)N=C1 KCFVSZJMFSMFCF-ZTNFWEORSA-N 0.000 description 1
- YPBHFJWUPLVJAN-IUODEOHRSA-N (2R)-3-[4-[4-[1-[(2R)-4,4,4-trifluorobutan-2-yl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound FC(C[C@@H](C)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C[C@H](CO)O)N=CC=2)(F)F YPBHFJWUPLVJAN-IUODEOHRSA-N 0.000 description 1
- YPBHFJWUPLVJAN-SWLSCSKDSA-N (2R)-3-[4-[4-[1-[(2S)-4,4,4-trifluorobutan-2-yl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound FC(C[C@H](C)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C[C@H](CO)O)N=CC=2)(F)F YPBHFJWUPLVJAN-SWLSCSKDSA-N 0.000 description 1
- IHZCYGIKKXIIOQ-CRAIPNDOSA-N (2R)-3-[4-[4-[1-[(3R)-2,2-difluoropentan-3-yl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propane-1,2-diol Chemical compound FC(C)([C@@H](CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C[C@H](CO)O)N=CC=2)F IHZCYGIKKXIIOQ-CRAIPNDOSA-N 0.000 description 1
- LZEQHKULKROZGJ-KTQQKIMGSA-N (2S)-1-[4-[4-[1-(1-cyclopropylpropyl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-2-ol Chemical compound CCC(C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](C)O)N=C1 LZEQHKULKROZGJ-KTQQKIMGSA-N 0.000 description 1
- LZEQHKULKROZGJ-IFXJQAMLSA-N (2S)-1-[4-[4-[1-[(1R)-1-cyclopropylpropyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-2-ol Chemical compound CC[C@H](C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](C)O)N=C1 LZEQHKULKROZGJ-IFXJQAMLSA-N 0.000 description 1
- XLLHHLZZSBVTBI-IBGZPJMESA-N (2S)-2-(dimethylamino)-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](CO)N(C)C)N=C1 XLLHHLZZSBVTBI-IBGZPJMESA-N 0.000 description 1
- IPKHOCAMRZYLHH-INIZCTEOSA-N (2S)-2-amino-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](N)CO)N=C1 IPKHOCAMRZYLHH-INIZCTEOSA-N 0.000 description 1
- WDHNKTSCLXJOSV-VBKZILBWSA-N (2S,3S)-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]butane-1,2-diol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@@H](C)[C@H](O)CO WDHNKTSCLXJOSV-VBKZILBWSA-N 0.000 description 1
- LKMJVFRMDSNFRT-BYPYZUCNSA-N (2r)-2-(methoxymethyl)oxirane Chemical compound COC[C@H]1CO1 LKMJVFRMDSNFRT-BYPYZUCNSA-N 0.000 description 1
- WVYWICLMDOOCFB-ZCFIWIBFSA-N (2r)-4-methylpentan-2-ol Chemical compound CC(C)C[C@@H](C)O WVYWICLMDOOCFB-ZCFIWIBFSA-N 0.000 description 1
- QPYSQIQZVJMPGH-UHFFFAOYSA-N (3-oxocyclobutyl) 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1CC(=O)C1 QPYSQIQZVJMPGH-UHFFFAOYSA-N 0.000 description 1
- OLRNUXJNQGODGR-FQEVSTJZSA-N (3S)-3-amino-2-methyl-4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]butan-2-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@H](N)C(C)(C)O)N=C1 OLRNUXJNQGODGR-FQEVSTJZSA-N 0.000 description 1
- FFGZPNNLXMQFMO-QMMMGPOBSA-N (3r)-1,4-dioxaspiro[4.5]decane-3-carbaldehyde Chemical compound O1[C@@H](C=O)COC11CCCCC1 FFGZPNNLXMQFMO-QMMMGPOBSA-N 0.000 description 1
- BNPOTXLWPZOESZ-YFKPBYRVSA-N (4r)-4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OC[C@H](CCl)O1 BNPOTXLWPZOESZ-YFKPBYRVSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- XHTYQFMRBQUCPX-UHFFFAOYSA-N 1,1,3,3-tetramethoxypropane Chemical compound COC(OC)CC(OC)OC XHTYQFMRBQUCPX-UHFFFAOYSA-N 0.000 description 1
- OWOKCUXVMOFUSP-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-yl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1CCC2(OCCO2)CC1 OWOKCUXVMOFUSP-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- SMWRCGBHOWQACU-TZMCWYRMSA-N 1-[(1R,2R)-2-methylcyclohexyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound C[C@H]1[C@@H](CCCC1)N1N=CC(=C1)B1OC(C(O1)(C)C)(C)C SMWRCGBHOWQACU-TZMCWYRMSA-N 0.000 description 1
- SASZOMPJCVAWQU-YGPZHTELSA-N 1-[(3R)-1,4-dioxaspiro[4.5]decan-3-yl]ethanol Chemical compound CC(O)[C@H]1COC2(CCCCC2)O1 SASZOMPJCVAWQU-YGPZHTELSA-N 0.000 description 1
- IBNMAQFIGSSRFF-UHFFFAOYSA-N 1-[4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]piperidin-1-yl]ethanone Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CCN(CC1)C(C)=O IBNMAQFIGSSRFF-UHFFFAOYSA-N 0.000 description 1
- XDSZRCJOLWMRFZ-UHFFFAOYSA-N 1-cyclopropylbutan-2-ol Chemical compound CCC(O)CC1CC1 XDSZRCJOLWMRFZ-UHFFFAOYSA-N 0.000 description 1
- GQMPILIYOVYDCB-UHFFFAOYSA-N 1-methyl-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclobutan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC(C)(O)C1 GQMPILIYOVYDCB-UHFFFAOYSA-N 0.000 description 1
- WUIJTQZXUURFQU-UHFFFAOYSA-N 1-methylsulfonylethene Chemical compound CS(=O)(=O)C=C WUIJTQZXUURFQU-UHFFFAOYSA-N 0.000 description 1
- SJHNIRJBUIWPKT-UHFFFAOYSA-N 1-pentan-3-yl-4-(1H-pyrazol-4-yl)pyrazole Chemical compound CCC(CC)N1C=C(C=N1)C1=CNN=C1 SJHNIRJBUIWPKT-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- LCZASQOOGUQRIA-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane Chemical compound CCCP1OP(CCC)OP(CCC)O1 LCZASQOOGUQRIA-UHFFFAOYSA-N 0.000 description 1
- CNAVBWIAKVTYKS-UHFFFAOYSA-N 2-(3-bromo-2-methoxypropyl)isoindole-1,3-dione Chemical compound COC(CBr)CN1C(=O)C2=C(C=CC=C2)C1=O CNAVBWIAKVTYKS-UHFFFAOYSA-N 0.000 description 1
- YKFGLGXRUVEMNF-UHFFFAOYSA-N 2-(dimethylamino)-2-oxoacetic acid Chemical compound CN(C)C(=O)C(O)=O YKFGLGXRUVEMNF-UHFFFAOYSA-N 0.000 description 1
- GUHZIGLRPPALBJ-UHFFFAOYSA-N 2-(oxan-2-yloxy)ethanamine Chemical compound NCCOC1CCCCO1 GUHZIGLRPPALBJ-UHFFFAOYSA-N 0.000 description 1
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
- XIGIOMOZRZATTM-QFIPXVFZSA-N 2-[(2R)-2-methoxy-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propyl]isoindole-1,3-dione Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H](CN2C(=O)C3=C(C=CC=C3)C2=O)OC)N=C1 XIGIOMOZRZATTM-QFIPXVFZSA-N 0.000 description 1
- LDCYESWCZOFOEJ-LURJTMIESA-N 2-[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]propan-2-ol Chemical compound CC(C)(O)[C@@H]1COC(C)(C)O1 LDCYESWCZOFOEJ-LURJTMIESA-N 0.000 description 1
- XIGIOMOZRZATTM-UHFFFAOYSA-N 2-[2-methoxy-3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]propyl]isoindole-1,3-dione Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(CN2C(=O)C3=C(C=CC=C3)C2=O)OC)N=C1 XIGIOMOZRZATTM-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- LNWZSEFHRUUIPB-UHFFFAOYSA-N 2-[4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]pyrazol-1-yl]butanoic acid Chemical compound CCC(N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C)N=C1)C(O)=O LNWZSEFHRUUIPB-UHFFFAOYSA-N 0.000 description 1
- KOZYUMQITSCDRB-UHFFFAOYSA-N 2-[4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-4-yl]pyrazol-1-yl]cyclopentan-1-one Chemical compound CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C1C(CCC1)=O KOZYUMQITSCDRB-UHFFFAOYSA-N 0.000 description 1
- JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 1
- SCOJKGRNQDKFRP-UHFFFAOYSA-N 2-chloro-n-methoxy-n-methylacetamide Chemical compound CON(C)C(=O)CCl SCOJKGRNQDKFRP-UHFFFAOYSA-N 0.000 description 1
- AXDZFGRFZOQVBV-UHFFFAOYSA-N 2-chlorocyclopentan-1-one Chemical compound ClC1CCCC1=O AXDZFGRFZOQVBV-UHFFFAOYSA-N 0.000 description 1
- KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- LFSAPCRASZRSKS-UHFFFAOYSA-N 2-methylcyclohexan-1-one Chemical compound CC1CCCCC1=O LFSAPCRASZRSKS-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- HJUVFZGONSIZFY-UHFFFAOYSA-N 3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclobutan-1-ol Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC(O)C1 HJUVFZGONSIZFY-UHFFFAOYSA-N 0.000 description 1
- LWPZSJMSRTYMOY-UHFFFAOYSA-N 3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclobutan-1-one Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC(=O)C1 LWPZSJMSRTYMOY-UHFFFAOYSA-N 0.000 description 1
- QXNBQQFEJLEJRY-UHFFFAOYSA-N 3-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclobutane-1-carboxamide Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC(C1)C(N)=O QXNBQQFEJLEJRY-UHFFFAOYSA-N 0.000 description 1
- VTOQFOCYBTVOJZ-UHFFFAOYSA-N 3-bromopentane Chemical compound CCC(Br)CC VTOQFOCYBTVOJZ-UHFFFAOYSA-N 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
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 1
- MRWWWZLJWNIEEJ-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-propan-2-yloxy-1,3,2-dioxaborolane Chemical compound CC(C)OB1OC(C)(C)C(C)(C)O1 MRWWWZLJWNIEEJ-UHFFFAOYSA-N 0.000 description 1
- OUPNAKMUTDMSBJ-UHFFFAOYSA-N 4-(1-cycloheptylpyrazol-4-yl)-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CN1C=C(C=N1)C1=CN2N=CC=C2C(=N1)C1=CN(N=C1)C1CCCCCC1 OUPNAKMUTDMSBJ-UHFFFAOYSA-N 0.000 description 1
- IOFIUNRBSNSVEI-UHFFFAOYSA-N 4-(1-pentan-3-ylpyrazol-4-yl)-6-(1-piperidin-4-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1N=CC(=C1)C=1C=2N(C=C(N=1)C=1C=NN(C=1)C1CCNCC1)N=CC=2 IOFIUNRBSNSVEI-UHFFFAOYSA-N 0.000 description 1
- OKMJZZVJEXVNOK-XMMPIXPASA-N 4-(1-pentan-3-ylpyrazol-4-yl)-6-[1-[[(4R)-2,2,4-trimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@]2(C)COC(C)(C)O2)N=C1 OKMJZZVJEXVNOK-XMMPIXPASA-N 0.000 description 1
- NBJHDLKSWUDGJG-UHFFFAOYSA-N 4-(2-chloroethyl)morpholin-4-ium;chloride Chemical compound Cl.ClCCN1CCOCC1 NBJHDLKSWUDGJG-UHFFFAOYSA-N 0.000 description 1
- GKUCVLXFBHZZDE-UHFFFAOYSA-N 4-(chloromethyl)-1,3-dioxane Chemical compound ClCC1CCOCO1 GKUCVLXFBHZZDE-UHFFFAOYSA-N 0.000 description 1
- KRTPHJWJOAAJKP-UHFFFAOYSA-N 4-[1-(1-methylcyclopentyl)pyrazol-4-yl]-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CN1C=C(C=N1)C1=CN2N=CC=C2C(=N1)C1=CN(N=C1)C1(C)CCCC1 KRTPHJWJOAAJKP-UHFFFAOYSA-N 0.000 description 1
- KMFNQZDNXKQNCZ-UHFFFAOYSA-N 4-[1-(2,2-difluoropentan-3-yl)pyrazol-4-yl]-6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC(N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2=CC=C(OC)C=C2)N=C1)C(C)(F)F KMFNQZDNXKQNCZ-UHFFFAOYSA-N 0.000 description 1
- ZPAQLIMFKPKSTL-UHFFFAOYSA-N 4-[1-(2,2-dimethylcyclopentyl)pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CC1(C)CCCC1N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 ZPAQLIMFKPKSTL-UHFFFAOYSA-N 0.000 description 1
- CRUUABVVMVSMEI-UHFFFAOYSA-N 4-[1-(2-ethylcyclopentyl)pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC1CCCC1N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 CRUUABVVMVSMEI-UHFFFAOYSA-N 0.000 description 1
- WGLYKZWNJGLKTO-IMBCPYESSA-N 4-[1-[(1R)-1-(2,2-difluorocyclopropyl)propyl]pyrazol-4-yl]-6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CC[C@H](C1CC1(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H]2COC(C)(C)O2)N=C1 WGLYKZWNJGLKTO-IMBCPYESSA-N 0.000 description 1
- YKRDJBSVPYHBGQ-CXAGYDPISA-N 4-[1-[(1R,2R)-2-methylcyclohexyl]pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound C[C@@H]1CCCC[C@H]1N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 YKRDJBSVPYHBGQ-CXAGYDPISA-N 0.000 description 1
- NLSOJIALIUJYIW-INIZCTEOSA-N 4-[1-[(1S)-1-cyclopropylpropyl]pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CC[C@@H](C1CC1)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 NLSOJIALIUJYIW-INIZCTEOSA-N 0.000 description 1
- TYWQUKSIKDZVFJ-LBPRGKRZSA-N 4-[1-[(2S)-pentan-2-yl]pyrazol-4-yl]-6-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC[C@H](C)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 TYWQUKSIKDZVFJ-LBPRGKRZSA-N 0.000 description 1
- XXSNHPXLIDKIKK-VSRNOXKVSA-N 4-[1-[(2S)-pentan-2-yl]pyrazol-4-yl]-6-[1-(2-phenyl-1,3-dioxan-5-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC[C@H](C)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1COC(OC1)C1=CC=CC=C1 XXSNHPXLIDKIKK-VSRNOXKVSA-N 0.000 description 1
- NICFJHSFKDJWCZ-UHFFFAOYSA-N 4-[1-[3-ethyl-1-(trifluoromethylsulfonyl)azetidin-3-yl]pyrazol-4-yl]-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC1(CN(C1)S(=O)(=O)C(F)(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C)N=C1 NICFJHSFKDJWCZ-UHFFFAOYSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- RUHBXGUKYPQSFN-UHFFFAOYSA-N 4-[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]cyclohexan-1-one Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CCC(=O)CC1 RUHBXGUKYPQSFN-UHFFFAOYSA-N 0.000 description 1
- NDFBBDUBZDNHGS-UHFFFAOYSA-N 4-chloro-6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound ClC=1C=2N(C=C(N=1)C=1C=NN(C=1)C)N=CC=2 NDFBBDUBZDNHGS-UHFFFAOYSA-N 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- QRJCGVNDIQCAAA-UHFFFAOYSA-N 4-pyrazol-1-ylpiperidine;hydrochloride Chemical compound Cl.C1CNCCC1N1N=CC=C1 QRJCGVNDIQCAAA-UHFFFAOYSA-N 0.000 description 1
- XBNDSSWRAWNRLV-UHFFFAOYSA-N 5-[[4-[4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazin-6-yl]pyrazol-1-yl]methyl]-1,3-oxazolidin-2-one Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2CNC(=O)O2)N=C1 XBNDSSWRAWNRLV-UHFFFAOYSA-N 0.000 description 1
- DPWVAHISKMFXMY-UHFFFAOYSA-N 6-(1-cyclopent-3-en-1-ylpyrazol-4-yl)-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CC=CC1 DPWVAHISKMFXMY-UHFFFAOYSA-N 0.000 description 1
- FNTMPYDMWYLQKQ-UHFFFAOYSA-N 6-(1H-pyrazol-4-yl)-4-[1-(1,1,1-trifluoropentan-3-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC(F)(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 FNTMPYDMWYLQKQ-UHFFFAOYSA-N 0.000 description 1
- IIHWLGKWZKCOGF-UHFFFAOYSA-N 6-(1H-pyrazol-4-yl)-4-[1-(4,4,4-trifluorobutan-2-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CC(CC(F)(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CNN=C1 IIHWLGKWZKCOGF-UHFFFAOYSA-N 0.000 description 1
- KBKFIKWCFFXFIH-UHFFFAOYSA-N 6-[1-(1-methylsulfonylazetidin-3-yl)pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C1CN(C1)S(C)(=O)=O KBKFIKWCFFXFIH-UHFFFAOYSA-N 0.000 description 1
- NDWJROKGWYVBSL-KBMIEXCESA-N 6-[1-[(1R)-1-[(3S)-1,4-dioxaspiro[4.5]decan-3-yl]ethyl]pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@H](C)[C@H]1COC2(CCCCC2)O1 NDWJROKGWYVBSL-KBMIEXCESA-N 0.000 description 1
- NDWJROKGWYVBSL-UQBPGWFLSA-N 6-[1-[(1S)-1-[(3S)-1,4-dioxaspiro[4.5]decan-3-yl]ethyl]pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@@H](C)[C@H]1COC2(CCCCC2)O1 NDWJROKGWYVBSL-UQBPGWFLSA-N 0.000 description 1
- WLSGYOXRMIOHGE-UHFFFAOYSA-N 6-[1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]pyrazol-4-yl]-4-[1-(1,1,1-trifluoropentan-3-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CC1(OCC(O1)CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(CC(F)(F)F)CC)C WLSGYOXRMIOHGE-UHFFFAOYSA-N 0.000 description 1
- VMMFIJDQVMFKRJ-UHFFFAOYSA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC2=CC=C(OC)C=C2)N=C1 VMMFIJDQVMFKRJ-UHFFFAOYSA-N 0.000 description 1
- MZZISDJTGHLWLY-UHFFFAOYSA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-4-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound COC1=CC=C(CN2N=CC(=C2)C=2N=C(C=3N(C=2)N=CC=3)C=2C=NNC=2)C=C1 MZZISDJTGHLWLY-UHFFFAOYSA-N 0.000 description 1
- YPUPHBGJAQTLTR-UHFFFAOYSA-N 6-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-4-oxo-5H-pyrazolo[1,5-a]pyrazine-2-carboxylic acid Chemical compound COC1=CC=C(CN2C=C(C=N2)C2=CN3N=C(C=C3C(O)=N2)C(O)=O)C=C1 YPUPHBGJAQTLTR-UHFFFAOYSA-N 0.000 description 1
- NDWJROKGWYVBSL-OPEAARRCSA-N 6-[1-[1-[(3S)-1,4-dioxaspiro[4.5]decan-3-yl]ethyl]pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)C(C)[C@H]1COC2(CCCCC2)O1 NDWJROKGWYVBSL-OPEAARRCSA-N 0.000 description 1
- RWPLWVCEWWALKF-QGZVFWFLSA-N 6-[1-[[(2R)-oxiran-2-yl]methyl]pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H]2CO2)N=C1 RWPLWVCEWWALKF-QGZVFWFLSA-N 0.000 description 1
- RTXZNLPQAVCPRU-LJQANCHMSA-N 6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]-4-(1-pentan-3-ylpyrazol-4-yl)pyrazolo[1,5-a]pyrazine Chemical compound CC1(OC[C@H](O1)CN1N=CC(=C1)C=1N=C(C=2N(C=1)N=CC=2)C=1C=NN(C=1)C(CC)CC)C RTXZNLPQAVCPRU-LJQANCHMSA-N 0.000 description 1
- BJOWEAHDJUCAAS-FBMWCMRBSA-N 6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]-4-[1-(4,4,4-trifluorobutan-2-yl)pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound CC(CC(F)(F)F)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H]2COC(C)(C)O2)N=C1 BJOWEAHDJUCAAS-FBMWCMRBSA-N 0.000 description 1
- QZHTXMHQPZTQTP-LDQXTDLNSA-N 6-[1-[[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]pyrazol-4-yl]-4-[1-[(1R,2S)-2-methylcyclopentyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrazine Chemical compound C[C@H]1CCC[C@H]1N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(C[C@@H]2COC(C)(C)O2)N=C1 QZHTXMHQPZTQTP-LDQXTDLNSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000033237 Aicardi-Goutières syndrome Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000004300 Atrophic Gastritis Diseases 0.000 description 1
- 206010064539 Autoimmune myocarditis Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- CAJGDLFDBIRQQL-UHFFFAOYSA-N CC(C(OC(C)(C)C)=O)[n]1ncc(B2OC(C)(C)C(C)(C)O2)c1 Chemical compound CC(C(OC(C)(C)C)=O)[n]1ncc(B2OC(C)(C)C(C)(C)O2)c1 CAJGDLFDBIRQQL-UHFFFAOYSA-N 0.000 description 1
- GVILQOVWHWVBRQ-YLJYHZDGSA-N CC(C)(CCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C[C@H](CO)O)nc3)c[n]3nccc23)c1 Chemical compound CC(C)(CCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C[C@H](CO)O)nc3)c[n]3nccc23)c1 GVILQOVWHWVBRQ-YLJYHZDGSA-N 0.000 description 1
- FJVJTNUTSSIZDN-UHFFFAOYSA-N CC(CC(F)(F)F)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 Chemical compound CC(CC(F)(F)F)N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1 FJVJTNUTSSIZDN-UHFFFAOYSA-N 0.000 description 1
- WJSGOBUPZDROII-UHFFFAOYSA-N CC1(C)OB(OC1(C)C)C1=CN(N=C1)C(C1CC1)C1CC1 Chemical compound CC1(C)OB(OC1(C)C)C1=CN(N=C1)C(C1CC1)C1CC1 WJSGOBUPZDROII-UHFFFAOYSA-N 0.000 description 1
- TZSJIFBRHHOZKL-UHFFFAOYSA-N CC1(C)OB(OC1(C)C)C1=CN(N=C1)C1CCCCCC1 Chemical compound CC1(C)OB(OC1(C)C)C1=CN(N=C1)C1CCCCCC1 TZSJIFBRHHOZKL-UHFFFAOYSA-N 0.000 description 1
- TXYOKURZBHWTAH-UHFFFAOYSA-N CC1(OB(OC1(C)C)C=1C=NN(C=1)C(CC(F)(F)F)CC)C Chemical compound CC1(OB(OC1(C)C)C=1C=NN(C=1)C(CC(F)(F)F)CC)C TXYOKURZBHWTAH-UHFFFAOYSA-N 0.000 description 1
- IHZCYGIKKXIIOQ-UHFFFAOYSA-N CCC(C(C)(F)F)[n]1ncc(-c2nc(-c3c[n](CC(CO)O)nc3)c[n]3nccc23)c1 Chemical compound CCC(C(C)(F)F)[n]1ncc(-c2nc(-c3c[n](CC(CO)O)nc3)c[n]3nccc23)c1 IHZCYGIKKXIIOQ-UHFFFAOYSA-N 0.000 description 1
- PIWPDFFYEWNSGF-YCMKEVRSSA-N CCC(C1CC1)[n]1ncc(C(c2ccn[n]2C2)=NC2c2c[n](C[C@H](C)O)nc2)c1 Chemical compound CCC(C1CC1)[n]1ncc(C(c2ccn[n]2C2)=NC2c2c[n](C[C@H](C)O)nc2)c1 PIWPDFFYEWNSGF-YCMKEVRSSA-N 0.000 description 1
- NVDKIISFLSMRLH-UHFFFAOYSA-N CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(CCO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)N=C1 Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(CC(CCO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C)N=C1 NVDKIISFLSMRLH-UHFFFAOYSA-N 0.000 description 1
- BTEVYLQFUGHTDP-IBGZPJMESA-N CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@@H](C)CO[Si](C)(C)C(C)(C)C Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@@H](C)CO[Si](C)(C)C(C)(C)C BTEVYLQFUGHTDP-IBGZPJMESA-N 0.000 description 1
- VQHPVFQZSFEDED-AOYPEHQESA-N CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@@H]1CCC[C@H]1O[Si](C)(C)C(C)(C)C Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@@H]1CCC[C@H]1O[Si](C)(C)C(C)(C)C VQHPVFQZSFEDED-AOYPEHQESA-N 0.000 description 1
- VQHPVFQZSFEDED-AHWVRZQESA-N CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@H]1CCC[C@@H]1O[Si](C)(C)C(C)(C)C Chemical compound CCC(CC)N1C=C(C=N1)C1=NC(=CN2N=CC=C12)C1=CN(N=C1)[C@H]1CCC[C@@H]1O[Si](C)(C)C(C)(C)C VQHPVFQZSFEDED-AHWVRZQESA-N 0.000 description 1
- NMHJMLIJASQFTD-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](C(C4)CC4C(N)=O)nc3CCC(CC)[n]3ncc(-c4nc(-c5c[n](C(C6)CC6C(N(C)C)=O)nc5)c[n]5nccc45)c3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](C(C4)CC4C(N)=O)nc3CCC(CC)[n]3ncc(-c4nc(-c5c[n](C(C6)CC6C(N(C)C)=O)nc5)c[n]5nccc45)c3)c[n]3nccc23)c1 NMHJMLIJASQFTD-UHFFFAOYSA-N 0.000 description 1
- GMXOAGOSDAJBCC-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](C(C4)CN4C(C(C)(C)O)=O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](C(C4)CN4C(C(C)(C)O)=O)nc3)c[n]3nccc23)c1 GMXOAGOSDAJBCC-UHFFFAOYSA-N 0.000 description 1
- YVOPTXIQJFVIST-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](C4CC(CO)C4)nc3CCC(CC)[n]3ncc(-c4nc(-c5c[n](C(C6)CC6C(N(C)C)=O)nc5)c[n]5nccc45)c3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](C4CC(CO)C4)nc3CCC(CC)[n]3ncc(-c4nc(-c5c[n](C(C6)CC6C(N(C)C)=O)nc5)c[n]5nccc45)c3)c[n]3nccc23)c1 YVOPTXIQJFVIST-UHFFFAOYSA-N 0.000 description 1
- BUXTXUMSQJUUDR-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CC(CO)=O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CC(CO)=O)nc3)c[n]3nccc23)c1 BUXTXUMSQJUUDR-UHFFFAOYSA-N 0.000 description 1
- CCBGNZZUCHRKDG-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CC4(CO)COC4)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CC4(CO)COC4)nc3)c[n]3nccc23)c1 CCBGNZZUCHRKDG-UHFFFAOYSA-N 0.000 description 1
- FMWDSXYJPDRLET-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCC(CO)O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCC(CO)O)nc3)c[n]3nccc23)c1 FMWDSXYJPDRLET-UHFFFAOYSA-N 0.000 description 1
- GWFPRBLVHXNVTL-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCCN(C)C)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCCN(C)C)nc3)c[n]3nccc23)c1 GWFPRBLVHXNVTL-UHFFFAOYSA-N 0.000 description 1
- WKIYBLMNYFYECG-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(C)C)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(C)C)nc3)c[n]3nccc23)c1 WKIYBLMNYFYECG-UHFFFAOYSA-N 0.000 description 1
- APYUBZDPKVDVML-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(CC4)CC4(C)O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(CC4)CC4(C)O)nc3)c[n]3nccc23)c1 APYUBZDPKVDVML-UHFFFAOYSA-N 0.000 description 1
- XWEGZOWJKZVIPT-HXUWFJFHSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(CC4)C[C@@H]4O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(CC4)C[C@@H]4O)nc3)c[n]3nccc23)c1 XWEGZOWJKZVIPT-HXUWFJFHSA-N 0.000 description 1
- AQXLZXBTAYHUHU-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(CCN4)CC4=O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN(CCN4)CC4=O)nc3)c[n]3nccc23)c1 AQXLZXBTAYHUHU-UHFFFAOYSA-N 0.000 description 1
- KNAGBHSVICAWIT-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN4CCC(CO)CC4)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN4CCC(CO)CC4)nc3)c[n]3nccc23)c1 KNAGBHSVICAWIT-UHFFFAOYSA-N 0.000 description 1
- YMOTZDNJTZOVGM-UHFFFAOYSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCNC4CC(CO)C4)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCNC4CC(CO)C4)nc3)c[n]3nccc23)c1 YMOTZDNJTZOVGM-UHFFFAOYSA-N 0.000 description 1
- BDGZWYURCYSTKP-FQEVSTJZSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN[C@@H](CCN4C)C4=O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN[C@@H](CCN4C)C4=O)nc3)c[n]3nccc23)c1 BDGZWYURCYSTKP-FQEVSTJZSA-N 0.000 description 1
- BDGZWYURCYSTKP-HXUWFJFHSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN[C@H](CCN4C)C4=O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](CCN[C@H](CCN4C)C4=O)nc3)c[n]3nccc23)c1 BDGZWYURCYSTKP-HXUWFJFHSA-N 0.000 description 1
- LMRBMFGYPWUSQY-HXUWFJFHSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](C[C@@H](CN(C4)CC4OC)O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](C[C@@H](CN(C4)CC4OC)O)nc3)c[n]3nccc23)c1 LMRBMFGYPWUSQY-HXUWFJFHSA-N 0.000 description 1
- RLBJLTMGMDYGHH-XOBRGWDASA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](C[C@@H]([C@H](C)O)O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](C[C@@H]([C@H](C)O)O)nc3)c[n]3nccc23)c1 RLBJLTMGMDYGHH-XOBRGWDASA-N 0.000 description 1
- OIAGAWSCJMASIN-SFHVURJKSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n](C[C@H](CN)OC)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n](C[C@H](CN)OC)nc3)c[n]3nccc23)c1 OIAGAWSCJMASIN-SFHVURJKSA-N 0.000 description 1
- DVXZLEHKUCHABK-FPOVZHCZSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@@H](CCC4)[C@H]4O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@@H](CCC4)[C@H]4O)nc3)c[n]3nccc23)c1 DVXZLEHKUCHABK-FPOVZHCZSA-N 0.000 description 1
- ZWNHDUPLKJBMEF-CXGRPWHSSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@H](C4)C[C@@]4(CO)O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@H](C4)C[C@@]4(CO)O)nc3)c[n]3nccc23)c1 ZWNHDUPLKJBMEF-CXGRPWHSSA-N 0.000 description 1
- GAJCOKUXJVTBAP-LJQANCHMSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@H](CCC4)C4=O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@H](CCC4)C4=O)nc3)c[n]3nccc23)c1 GAJCOKUXJVTBAP-LJQANCHMSA-N 0.000 description 1
- DVXZLEHKUCHABK-CTNGQTDRSA-N CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@H](CCC4)[C@H]4O)nc3)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(-c3c[n]([C@H](CCC4)[C@H]4O)nc3)c[n]3nccc23)c1 DVXZLEHKUCHABK-CTNGQTDRSA-N 0.000 description 1
- RGCGLMRMLNRMIH-PCXBFCDLSA-N CCC(CC)[n]1ncc(-c2nc(/C(/C=N)=C/N[C@@H](CCC3)[C@@H]3O)c[n]3nccc23)c1 Chemical compound CCC(CC)[n]1ncc(-c2nc(/C(/C=N)=C/N[C@@H](CCC3)[C@@H]3O)c[n]3nccc23)c1 RGCGLMRMLNRMIH-PCXBFCDLSA-N 0.000 description 1
- ABSHOSPKDGNIJJ-UHFFFAOYSA-N CCC(N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1)C(C)=O Chemical compound CCC(N1C=C(C=N1)B1OC(C)(C)C(C)(C)O1)C(C)=O ABSHOSPKDGNIJJ-UHFFFAOYSA-N 0.000 description 1
- IHZCYGIKKXIIOQ-QAPCUYQASA-N CC[C@@H](C(C)(F)F)[n]1ncc(-c2nc(-c3c[n](C[C@H](CO)O)nc3)c[n]3nccc23)c1 Chemical compound CC[C@@H](C(C)(F)F)[n]1ncc(-c2nc(-c3c[n](C[C@H](CO)O)nc3)c[n]3nccc23)c1 IHZCYGIKKXIIOQ-QAPCUYQASA-N 0.000 description 1
- PVXMSOSQLLPNEY-XJKSGUPXSA-N CC[C@H](C)[n]1ncc(-c2nc(-c3c[n](C[C@H](CO)O)nc3)c[n]3nccc23)c1 Chemical compound CC[C@H](C)[n]1ncc(-c2nc(-c3c[n](C[C@H](CO)O)nc3)c[n]3nccc23)c1 PVXMSOSQLLPNEY-XJKSGUPXSA-N 0.000 description 1
- TWFBJJVTGYOJAH-CMPLNLGQSA-N C[C@@H]1[C@@H](CC1)N1N=CC(=C1)B1OC(C(O1)(C)C)(C)C Chemical compound C[C@@H]1[C@@H](CC1)N1N=CC(=C1)B1OC(C(O1)(C)C)(C)C TWFBJJVTGYOJAH-CMPLNLGQSA-N 0.000 description 1
- BGXDMZAQLSQTKH-FOIQADDNSA-N C[C@H](CCCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C(CO)CO)nc3)c[n]3nccc23)c1 Chemical compound C[C@H](CCCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C(CO)CO)nc3)c[n]3nccc23)c1 BGXDMZAQLSQTKH-FOIQADDNSA-N 0.000 description 1
- WDHJXPHWQBPKAW-MOXGXCLJSA-N C[C@H](CCCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C[C@@H](CO)O)nc3)c[n]3nccc23)c1 Chemical compound C[C@H](CCCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C[C@@H](CO)O)nc3)c[n]3nccc23)c1 WDHJXPHWQBPKAW-MOXGXCLJSA-N 0.000 description 1
- LMRDYJSPACVCJR-XFQXTVEOSA-N C[C@H](CCCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C[C@H](C=O)O)[n]c3)c[n]3nccc23)c1 Chemical compound C[C@H](CCCC1)[C@@H]1[n]1ncc(-c2nc(-c3c[n](C[C@H](C=O)O)[n]c3)c[n]3nccc23)c1 LMRDYJSPACVCJR-XFQXTVEOSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- TXEKLQOIVGTBPC-UHFFFAOYSA-N Cl.N1=CC=C2N1C=CN=C2 Chemical compound Cl.N1=CC=C2N1C=CN=C2 TXEKLQOIVGTBPC-UHFFFAOYSA-N 0.000 description 1
- 208000010007 Cogan syndrome Diseases 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 229930182843 D-Lactic acid Natural products 0.000 description 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010064212 Eosinophilic oesophagitis Diseases 0.000 description 1
- 208000032027 Essential Thrombocythemia Diseases 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- IJOCGMDUPGJPGN-UHFFFAOYSA-N FC1(C(C1)C(CC)N1N=CC(=C1)B1OC(C(O1)(C)C)(C)C)F Chemical compound FC1(C(C1)C(CC)N1N=CC(=C1)B1OC(C(O1)(C)C)(C)C)F IJOCGMDUPGJPGN-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000036495 Gastritis atrophic Diseases 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 102000018682 Interleukin Receptor Common gamma Subunit Human genes 0.000 description 1
- 108010066719 Interleukin Receptor Common gamma Subunit Proteins 0.000 description 1
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 1
- 230000004163 JAK-STAT signaling pathway Effects 0.000 description 1
- 229940116839 Janus kinase 1 inhibitor Drugs 0.000 description 1
- 238000000023 Kugelrohr distillation Methods 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000010635 Protein Inhibitors of Activated STAT Human genes 0.000 description 1
- 108010038241 Protein Inhibitors of Activated STAT Proteins 0.000 description 1
- 102000002727 Protein Tyrosine Phosphatase Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 206010041660 Splenomegaly Diseases 0.000 description 1
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 1
- 102000008036 Suppressor of Cytokine Signaling Proteins Human genes 0.000 description 1
- 108010075383 Suppressor of Cytokine Signaling Proteins Proteins 0.000 description 1
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 102000000887 Transcription factor STAT Human genes 0.000 description 1
- 108050007918 Transcription factor STAT Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 229940123371 Tyrosine kinase 2 inhibitor Drugs 0.000 description 1
- 206010052568 Urticaria chronic Diseases 0.000 description 1
- XAXXTYXMWOFKLW-UHFFFAOYSA-N [C-]1=CC=[NH+]1 Chemical compound [C-]1=CC=[NH+]1 XAXXTYXMWOFKLW-UHFFFAOYSA-N 0.000 description 1
- ISYOFZCEMBXHOL-UHFFFAOYSA-M [Li].CC(C)[Mg]Cl Chemical compound [Li].CC(C)[Mg]Cl ISYOFZCEMBXHOL-UHFFFAOYSA-M 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010936 aqueous wash Methods 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- UQUPQEUNHVVNKW-UHFFFAOYSA-N azetidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CNC1 UQUPQEUNHVVNKW-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 208000000594 bullous pemphigoid Diseases 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000023819 chronic asthma Diseases 0.000 description 1
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- FJWFZRXGXZLAGU-UHFFFAOYSA-N cyclopent-3-en-1-yl methanesulfonate Chemical compound CS(=O)(=O)OC1CC=CC1 FJWFZRXGXZLAGU-UHFFFAOYSA-N 0.000 description 1
- JBDSSBMEKXHSJF-UHFFFAOYSA-M cyclopentanecarboxylate Chemical compound [O-]C(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-M 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 1
- 229940022769 d- lactic acid Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- DXFXILXLXUQNSU-UHFFFAOYSA-N diethyl 1-[2-[1-[(4-methoxyphenyl)methyl]pyrazol-4-yl]-2-oxoethyl]pyrazole-3,5-dicarboxylate Chemical compound COC1=CC=C(CN2N=CC(=C2)C(CN2N=C(C=C2C(=O)OCC)C(=O)OCC)=O)C=C1 DXFXILXLXUQNSU-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 150000002012 dioxanes Chemical class 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 201000000708 eosinophilic esophagitis Diseases 0.000 description 1
- 201000001561 eosinophilic gastritis Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- PQWQQQGKMHENOC-UHFFFAOYSA-N imidazo[1,2-c]pyrimidine Chemical class C1=NC=CC2=NC=CN21 PQWQQQGKMHENOC-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000000302 ischemic effect Effects 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
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 201000008350 membranous glomerulonephritis Diseases 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- UGZBFCCHLUWCQI-LURJTMIESA-N methyl (2r)-3-iodo-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)[C@H](CI)NC(=O)OC(C)(C)C UGZBFCCHLUWCQI-LURJTMIESA-N 0.000 description 1
- DOWWCCDWPKGNGX-YFKPBYRVSA-N methyl (4s)-2,2-dimethyl-1,3-dioxolane-4-carboxylate Chemical compound COC(=O)[C@@H]1COC(C)(C)O1 DOWWCCDWPKGNGX-YFKPBYRVSA-N 0.000 description 1
- AELKYRWKHKGMAD-RITPCOANSA-N methyl (4s,5r)-2,2,5-trimethyl-1,3-dioxolane-4-carboxylate Chemical compound COC(=O)[C@H]1OC(C)(C)O[C@@H]1C AELKYRWKHKGMAD-RITPCOANSA-N 0.000 description 1
- MBAHGFJTIVZLFB-SNAWJCMRSA-N methyl (e)-pent-2-enoate Chemical compound CC\C=C\C(=O)OC MBAHGFJTIVZLFB-SNAWJCMRSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- PYLWYAGIWDJBMC-UHFFFAOYSA-N methyl 3-chlorocyclobutane-1-carboxylate Chemical compound COC(=O)C1CC(Cl)C1 PYLWYAGIWDJBMC-UHFFFAOYSA-N 0.000 description 1
- OCBOIQWPCVXVKT-UHFFFAOYSA-N methyl thiane-4-carboxylate Chemical compound COC(=O)C1CCSCC1 OCBOIQWPCVXVKT-UHFFFAOYSA-N 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 238000003032 molecular docking Methods 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 206010028537 myelofibrosis Diseases 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
- OWIUPIRUAQMTTK-UHFFFAOYSA-M n-aminocarbamate Chemical compound NNC([O-])=O OWIUPIRUAQMTTK-UHFFFAOYSA-M 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 201000005737 orchitis Diseases 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- XAMUDJHXFNRLCY-UHFFFAOYSA-N phenthoate Chemical compound CCOC(=O)C(SP(=S)(OC)OC)C1=CC=CC=C1 XAMUDJHXFNRLCY-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 201000006292 polyarteritis nodosa Diseases 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 108020000494 protein-tyrosine phosphatase Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 208000002491 severe combined immunodeficiency Diseases 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- ULSBMKGFFFMGOI-UHFFFAOYSA-N tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11OC1 ULSBMKGFFFMGOI-UHFFFAOYSA-N 0.000 description 1
- CVAWKJKISIPBOD-UHFFFAOYSA-N tert-butyl 2-bromopropanoate Chemical compound CC(Br)C(=O)OC(C)(C)C CVAWKJKISIPBOD-UHFFFAOYSA-N 0.000 description 1
- SJMYWORNLPSJQO-UHFFFAOYSA-N tert-butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC(C)(C)C SJMYWORNLPSJQO-UHFFFAOYSA-N 0.000 description 1
- XXBDTKYKFFIAEY-UHFFFAOYSA-N tert-butyl 3-methylsulfonyloxyazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(OS(C)(=O)=O)C1 XXBDTKYKFFIAEY-UHFFFAOYSA-N 0.000 description 1
- FCMLWBBLOASUSO-UHFFFAOYSA-N tert-butyl 3-oxopiperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(=O)C1 FCMLWBBLOASUSO-UHFFFAOYSA-N 0.000 description 1
- WOEQSXAIPTXOPY-UHFFFAOYSA-N tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1 WOEQSXAIPTXOPY-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- LRAGZDBHRDRNIK-QMMMGPOBSA-N tert-butyl-[(2S)-2-chloropropoxy]-dimethylsilane Chemical compound C(C)(C)(C)[Si](C)(C)OC[C@H](C)Cl LRAGZDBHRDRNIK-QMMMGPOBSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- LMVCLDAMMNHILO-UHFFFAOYSA-N thian-4-ylmethanol Chemical compound OCC1CCSCC1 LMVCLDAMMNHILO-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 102000042286 type I cytokine receptor family Human genes 0.000 description 1
- 108091052247 type I cytokine receptor family Proteins 0.000 description 1
- 102000042287 type II cytokine receptor family Human genes 0.000 description 1
- 108091052254 type II cytokine receptor family Proteins 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Communicable Diseases (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Emergency Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Hospice & Palliative Care (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462088068P | 2014-12-05 | 2014-12-05 | |
| PCT/US2015/064062 WO2016090285A1 (en) | 2014-12-05 | 2015-12-04 | 4,6-SUBSTITUTED-PYRAZOLO[1,5-a]PYRAZINES AS JANUS KINASE INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2865483T3 true ES2865483T3 (es) | 2021-10-15 |
Family
ID=55069089
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15819933T Active ES2865483T3 (es) | 2014-12-05 | 2015-12-04 | Pirazolo[1,5-a]pirazinas sustituidas en 4,6 como inhibidores de Janus cinasa |
Country Status (29)
| Country | Link |
|---|---|
| US (3) | US10189845B2 (enExample) |
| EP (2) | EP3227297B1 (enExample) |
| JP (2) | JP6641373B2 (enExample) |
| KR (1) | KR20170090476A (enExample) |
| CN (1) | CN107278203B (enExample) |
| AU (1) | AU2015357585B2 (enExample) |
| BR (1) | BR112017011798A2 (enExample) |
| CA (1) | CA2969709A1 (enExample) |
| CL (1) | CL2017001422A1 (enExample) |
| CO (1) | CO2017006674A2 (enExample) |
| CR (1) | CR20170309A (enExample) |
| DK (1) | DK3227297T3 (enExample) |
| ES (1) | ES2865483T3 (enExample) |
| HR (1) | HRP20210501T1 (enExample) |
| HU (1) | HUE054371T2 (enExample) |
| IL (1) | IL252656A0 (enExample) |
| MX (1) | MX386316B (enExample) |
| MY (1) | MY191016A (enExample) |
| PH (1) | PH12017501032A1 (enExample) |
| PL (1) | PL3227297T3 (enExample) |
| PT (1) | PT3227297T (enExample) |
| RS (1) | RS61693B1 (enExample) |
| RU (2) | RU2021102805A (enExample) |
| SG (1) | SG11201704542SA (enExample) |
| SI (1) | SI3227297T1 (enExample) |
| TW (1) | TWI725004B (enExample) |
| UA (1) | UA120065C2 (enExample) |
| WO (1) | WO2016090285A1 (enExample) |
| ZA (1) | ZA201704494B (enExample) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3227297B1 (en) | 2014-12-05 | 2021-01-20 | Array Biopharma, Inc. | 4,6-substituted-pyrazolo[1,5-a]pyrazines as janus kinase inhibitors |
| ES2794779T3 (es) | 2016-02-24 | 2020-11-19 | Pfizer | Derivados de pirazolo[1,5-a]pirazin-4-ilo como inhibidores de JAK |
| US11028080B2 (en) | 2016-03-11 | 2021-06-08 | Denali Therapeutics Inc. | Substituted pyrimidines as LRKK2 inhibitors |
| IL299415B2 (en) | 2016-06-16 | 2025-09-01 | Denali Therapeutics Inc | Pyrimidine-2-ylamino-1H-pyrazoles as LRRK2 inhibitors for use in the treatment of neurodegenerative disorders |
| GB201617758D0 (en) * | 2016-10-20 | 2016-12-07 | Almac Discovery Limited | Pharmaceutical compounds |
| US11168090B2 (en) | 2017-01-18 | 2021-11-09 | Array Biopharma Inc. | Substituted pyrazolo[1,5-a]pyrazines as RET kinase inhibitors |
| US20200157081A1 (en) * | 2017-05-24 | 2020-05-21 | Denali Therapeutics Inc. | Compounds, compositions and methods |
| EP3668858A1 (en) | 2017-08-14 | 2020-06-24 | Pfizer Inc | Pyrazolo[1,5-a]pyrazin-4-yl and related derivatives |
| CA3087972C (en) | 2018-01-18 | 2023-01-10 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| EP3740490A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| JP2022500383A (ja) | 2018-09-10 | 2022-01-04 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての縮合複素環式化合物 |
| PL3954689T3 (pl) * | 2019-04-12 | 2024-08-05 | Primegene (Beijing) Co., Ltd. | Związki pochodne pirazolopirazyny, kompozycja farmaceutyczna i ich zastosowanie |
| BR112021022682A2 (pt) | 2019-05-14 | 2022-02-22 | Provention Bio Inc | Métodos e composições para prevenir diabetes do tipo 1 |
| CN113150012B (zh) * | 2020-01-22 | 2023-03-24 | 浙江海正药业股份有限公司 | 吡唑并[1,5-a]吡嗪类衍生物及其制备方法和用途 |
| CA3177852A1 (en) | 2020-04-04 | 2021-10-07 | Pfizer Inc. | Methods of treating coronavirus disease 2019 |
| US12006366B2 (en) | 2020-06-11 | 2024-06-11 | Provention Bio, Inc. | Methods and compositions for preventing type 1 diabetes |
| WO2022251253A1 (en) | 2021-05-24 | 2022-12-01 | Provention Bio, Inc. | Methods for treating type 1 diabetes |
| MX2024005778A (es) * | 2021-11-12 | 2024-08-06 | Soter Biopharma Pte Ltd | Compuesto de anillo fusionado de pirazolo, y uso del mismo. |
| AU2024274086A1 (en) * | 2023-05-12 | 2026-01-08 | Cms Research & Development Pte. Ltd. | Pyrazolopyrazine compound and method for preparing crystal form thereof |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1105378B1 (en) | 1998-08-21 | 2005-03-30 | Parker Hughes Institute | Quinazoline derivatives |
| DE102007032349A1 (de) * | 2007-07-11 | 2009-01-15 | Bayer Healthcare Ag | Imidazo-, Pyrazolopyrazine und Imidazotriazine und ihre Verwendung |
| DK2516434T3 (en) * | 2009-12-23 | 2015-08-31 | Takeda Pharmaceutical | FUSED HETEROAROMATIC PYRROLIDINONS AS SICK INHIBITORS |
| WO2011089400A1 (en) * | 2010-01-22 | 2011-07-28 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Inhibitors of pi3 kinase |
| UY33213A (es) * | 2010-02-18 | 2011-09-30 | Almirall Sa | Derivados de pirazol como inhibidores de jak |
| US20110241987A1 (en) * | 2010-04-01 | 2011-10-06 | Smart Technologies Ulc | Interactive input system and information input method therefor |
| JP2013523884A (ja) * | 2010-04-14 | 2013-06-17 | アレイ バイオファーマ、インコーポレイテッド | ＪＡＫキナーゼの阻害剤としての５，７置換イミダゾ［１，２−ｃ］ピリミジン |
| WO2013055645A1 (en) * | 2011-10-12 | 2013-04-18 | Array Biopharma Inc. | 5,7-substituted-imidazo[1,2-c]pyrimidines |
| CN104169284B (zh) * | 2012-03-28 | 2017-03-29 | 默克专利股份公司 | 双环吡嗪酮衍生物 |
| EP3227297B1 (en) | 2014-12-05 | 2021-01-20 | Array Biopharma, Inc. | 4,6-substituted-pyrazolo[1,5-a]pyrazines as janus kinase inhibitors |
-
2015
- 2015-12-04 EP EP15819933.1A patent/EP3227297B1/en active Active
- 2015-12-04 RS RS20210415A patent/RS61693B1/sr unknown
- 2015-12-04 HU HUE15819933A patent/HUE054371T2/hu unknown
- 2015-12-04 ES ES15819933T patent/ES2865483T3/es active Active
- 2015-12-04 WO PCT/US2015/064062 patent/WO2016090285A1/en not_active Ceased
- 2015-12-04 JP JP2017529681A patent/JP6641373B2/ja not_active Expired - Fee Related
- 2015-12-04 AU AU2015357585A patent/AU2015357585B2/en not_active Ceased
- 2015-12-04 DK DK15819933.1T patent/DK3227297T3/da active
- 2015-12-04 UA UAA201707008A patent/UA120065C2/uk unknown
- 2015-12-04 EP EP21152373.3A patent/EP3878451A1/en not_active Withdrawn
- 2015-12-04 PT PT158199331T patent/PT3227297T/pt unknown
- 2015-12-04 SG SG11201704542SA patent/SG11201704542SA/en unknown
- 2015-12-04 BR BR112017011798A patent/BR112017011798A2/pt not_active IP Right Cessation
- 2015-12-04 RU RU2021102805A patent/RU2021102805A/ru unknown
- 2015-12-04 US US15/532,937 patent/US10189845B2/en active Active
- 2015-12-04 SI SI201531544T patent/SI3227297T1/sl unknown
- 2015-12-04 MY MYPI2017702034A patent/MY191016A/en unknown
- 2015-12-04 RU RU2017123387A patent/RU2742938C2/ru active
- 2015-12-04 CN CN201580066136.5A patent/CN107278203B/zh not_active Expired - Fee Related
- 2015-12-04 KR KR1020177018122A patent/KR20170090476A/ko not_active Withdrawn
- 2015-12-04 HR HRP20210501TT patent/HRP20210501T1/hr unknown
- 2015-12-04 PL PL15819933T patent/PL3227297T3/pl unknown
- 2015-12-04 CR CR20170309A patent/CR20170309A/es unknown
- 2015-12-04 MX MX2017007284A patent/MX386316B/es unknown
- 2015-12-04 CA CA2969709A patent/CA2969709A1/en not_active Abandoned
- 2015-12-04 TW TW104140878A patent/TWI725004B/zh not_active IP Right Cessation
-
2017
- 2017-06-02 PH PH12017501032A patent/PH12017501032A1/en unknown
- 2017-06-04 IL IL252656A patent/IL252656A0/en active IP Right Grant
- 2017-06-05 CL CL2017001422A patent/CL2017001422A1/es unknown
- 2017-06-30 CO CONC2017/0006674A patent/CO2017006674A2/es unknown
- 2017-07-03 ZA ZA2017/04494A patent/ZA201704494B/en unknown
-
2018
- 2018-12-06 US US16/212,493 patent/US10730880B2/en active Active
-
2019
- 2019-12-11 JP JP2019223760A patent/JP2020055859A/ja active Pending
-
2020
- 2020-06-02 US US16/890,663 patent/US11028093B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11028093B2 (en) | 4,6-substituted-pyrazolo[1,5-a]pyrazines as janus kinase inhibitors | |
| CA2846652C (en) | Heterocyclylamines as pi3k inhibitors | |
| ES2871524T3 (es) | Pirrolo[2,3-d]pirimidinilo, pirrolo[2,3-b]pirazinilo y pirrolo[2,3-d]piridinil acrilamidas | |
| ES2908412T3 (es) | Derivados de piperidin-4-IL azetidina como inhibidores de JAK1 | |
| ES2426407T3 (es) | Compuestos de pirrolo[2,3-d]pirimidina | |
| CA2907751C (en) | 3-(2-aminopyrimidin-4-yl)-5-(3-hydroxypropynyl)-1h-pyrrolo[2,3-c]pyridine derivatives as nik inhibitors for the treatment of cancer | |
| ES2654288T3 (es) | Moduladores de P2X7 | |
| ES2701516T3 (es) | Derivados de heterociclil-butanamida | |
| KR20160146778A (ko) | Ｊａｋ 및 ｐｉ3ｋ 억제제 조합에 의한 ｂ-세포 악성종양의 치료 | |
| WO2016060963A1 (en) | Substituted heteroaryl compounds and methods of use | |
| AU2012323399A1 (en) | 5,7-substituted-imidazo[1,2-c]pyrimidines | |
| JP2016503049A (ja) | 治療用に活性なピラゾロ−ピリミジン誘導体 | |
| WO2015178955A1 (en) | Substituted ethynyl heterobicyclic compounds as tyrosine kinase inhibitors | |
| WO2025194057A1 (en) | Macrocyclic compounds as modulators of kras and uses thereof | |
| AU2013318283A1 (en) | Dihydropyrrolidino-pyrimidines as kinase inhibitors | |
| HK1238236B (en) | 4,6-substituted-pyrazolo[1,5-a]pyrazines as janus kinase inhibitors | |
| KR20250169642A (ko) | 키나제 억제제로서의 이환식 우레아 | |
| CN117897159A (zh) | 杂环化合物及使用方法 | |
| NZ624366B2 (en) | Novel purine derivatives and their use in the treatment of disease |