TW201542554A - 蛋白質激酶抑制劑 - Google Patents

Info

Publication number

TW201542554A

TW201542554A TW103139934A TW103139934A TW201542554A TW 201542554 A TW201542554 A TW 201542554A TW 103139934 A TW103139934 A TW 103139934A TW 103139934 A TW103139934 A TW 103139934A TW 201542554 A TW201542554 A TW 201542554A

Authority

TW

Taiwan

Prior art keywords

disease

compound

group

disorder

inhibitor

Prior art date

2013-11-19

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003909 protein kinase inhibitor Substances 0.000 title abstract description 5
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 154
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 101
• 238000011282 treatment Methods 0.000 claims abstract description 53
• 208000035475 disorder Diseases 0.000 claims abstract description 49
• 102000001253 Protein Kinase Human genes 0.000 claims abstract description 46
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 46
• 108060006633 protein kinase Proteins 0.000 claims abstract description 46
• 230000000694 effects Effects 0.000 claims abstract description 38
• 238000000034 method Methods 0.000 claims abstract description 37
• 239000003112 inhibitor Substances 0.000 claims abstract description 36
• 230000002062 proliferating effect Effects 0.000 claims abstract description 20
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 16
• 208000027866 inflammatory disease Diseases 0.000 claims abstract description 15
• 208000035473 Communicable disease Diseases 0.000 claims abstract description 10
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 8
• 238000002360 preparation method Methods 0.000 claims abstract description 7
• 150000003839 salts Chemical class 0.000 claims description 68
• 239000012453 solvate Substances 0.000 claims description 55
• 201000010099 disease Diseases 0.000 claims description 52
• 239000003814 drug Substances 0.000 claims description 43
• 108091000080 Phosphotransferase Proteins 0.000 claims description 41
• 102000020233 phosphotransferase Human genes 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 32
• 206010028980 Neoplasm Diseases 0.000 claims description 30
• -1 carbopredil Chemical compound 0.000 claims description 30
• 239000000126 substance Substances 0.000 claims description 30
• 239000003795 chemical substances by application Substances 0.000 claims description 28
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 201000011510 cancer Diseases 0.000 claims description 25
• 125000001072 heteroaryl group Chemical group 0.000 claims description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• 239000001257 hydrogen Substances 0.000 claims description 24
• 125000000217 alkyl group Chemical group 0.000 claims description 21
• 239000002207 metabolite Substances 0.000 claims description 19
• 230000005764 inhibitory process Effects 0.000 claims description 16
• 229940002612 prodrug Drugs 0.000 claims description 16
• 239000000651 prodrug Substances 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
• 125000004122 cyclic group Chemical group 0.000 claims description 14
• 230000002401 inhibitory effect Effects 0.000 claims description 13
• 125000002837 carbocyclic group Chemical group 0.000 claims description 12
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 12
• 229940124597 therapeutic agent Drugs 0.000 claims description 12
• 102000014150 Interferons Human genes 0.000 claims description 11
• 108010050904 Interferons Proteins 0.000 claims description 11
• 239000003246 corticosteroid Substances 0.000 claims description 11
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 10
• 229940079322 interferon Drugs 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 108010009978 Tec protein-tyrosine kinase Proteins 0.000 claims description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 150000002431 hydrogen Chemical class 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 102000009058 Death Domain Receptors Human genes 0.000 claims description 8
• 108010049207 Death Domain Receptors Proteins 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 230000004663 cell proliferation Effects 0.000 claims description 8
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 7
• 102000015696 Interleukins Human genes 0.000 claims description 7
• 108010063738 Interleukins Proteins 0.000 claims description 7
• 241001465754 Metazoa Species 0.000 claims description 7
• 229960004397 cyclophosphamide Drugs 0.000 claims description 7
• 208000015181 infectious disease Diseases 0.000 claims description 7
• 229940047122 interleukins Drugs 0.000 claims description 7
• 239000000523 sample Substances 0.000 claims description 7
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 6
• 206010020751 Hypersensitivity Diseases 0.000 claims description 6
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 claims description 6
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 6
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 6
• 208000007536 Thrombosis Diseases 0.000 claims description 6
• 239000000556 agonist Substances 0.000 claims description 6
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 6
• 229960002170 azathioprine Drugs 0.000 claims description 6
• 125000004452 carbocyclyl group Chemical group 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 6
• 229910052736 halogen Inorganic materials 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 229960001940 sulfasalazine Drugs 0.000 claims description 6
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 claims description 6
• 108020002739 Catechol O-methyltransferase Proteins 0.000 claims description 5
• 102000006378 Catechol O-methyltransferase Human genes 0.000 claims description 5
• 206010061218 Inflammation Diseases 0.000 claims description 5
• 102000038012 SFKs Human genes 0.000 claims description 5
• 108091008118 SFKs Proteins 0.000 claims description 5
• 208000026935 allergic disease Diseases 0.000 claims description 5
• 230000007815 allergy Effects 0.000 claims description 5
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 5
• 239000002246 antineoplastic agent Substances 0.000 claims description 5
• 206010003246 arthritis Diseases 0.000 claims description 5
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 239000003446 ligand Substances 0.000 claims description 5
• 230000005855 radiation Effects 0.000 claims description 5
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 5
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 4
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 4
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 4
• 210000004556 brain Anatomy 0.000 claims description 4
• 229940127089 cytotoxic agent Drugs 0.000 claims description 4
• 239000002804 dopamine agent Substances 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 230000004927 fusion Effects 0.000 claims description 4
• 210000000987 immune system Anatomy 0.000 claims description 4
• 229940125721 immunosuppressive agent Drugs 0.000 claims description 4
• 239000003018 immunosuppressive agent Substances 0.000 claims description 4
• 230000002458 infectious effect Effects 0.000 claims description 4
• 229960004844 lovastatin Drugs 0.000 claims description 4
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 4
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 4
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 4
• 239000002243 precursor Substances 0.000 claims description 4
• 229940044551 receptor antagonist Drugs 0.000 claims description 4
• 239000002464 receptor antagonist Substances 0.000 claims description 4
• 150000003431 steroids Chemical class 0.000 claims description 4
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
• ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 3
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 3
• 229940127291 Calcium channel antagonist Drugs 0.000 claims description 3
• 229940122444 Chemokine receptor antagonist Drugs 0.000 claims description 3
• 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 3
• 108010036949 Cyclosporine Proteins 0.000 claims description 3
• 229940098778 Dopamine receptor agonist Drugs 0.000 claims description 3
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
• 241000725303 Human immunodeficiency virus Species 0.000 claims description 3
• 208000029462 Immunodeficiency disease Diseases 0.000 claims description 3
• 102000006992 Interferon-alpha Human genes 0.000 claims description 3
• 108010047761 Interferon-alpha Proteins 0.000 claims description 3
• 108090000862 Ion Channels Proteins 0.000 claims description 3
• 102000004310 Ion Channels Human genes 0.000 claims description 3
• 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 3
• 239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 3
• 229940113306 Ligase inhibitor Drugs 0.000 claims description 3
• 108010025020 Nerve Growth Factor Proteins 0.000 claims description 3
• 102000007072 Nerve Growth Factors Human genes 0.000 claims description 3
• 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 3
• 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 3
• 102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 claims description 3
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 3
• 229940079156 Proteasome inhibitor Drugs 0.000 claims description 3
• 229940123573 Protein synthesis inhibitor Drugs 0.000 claims description 3
• FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 claims description 3
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 3
• 208000006011 Stroke Diseases 0.000 claims description 3
• 102100037346 Substance-P receptor Human genes 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
• 229940123468 Transferase inhibitor Drugs 0.000 claims description 3
• 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 claims description 3
• 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 claims description 3
• 108010067390 Viral Proteins Proteins 0.000 claims description 3
• 229960002964 adalimumab Drugs 0.000 claims description 3
• 208000007502 anemia Diseases 0.000 claims description 3
• 239000004037 angiogenesis inhibitor Substances 0.000 claims description 3
• 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 3
• 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 3
• 230000001773 anti-convulsant effect Effects 0.000 claims description 3
• 230000003474 anti-emetic effect Effects 0.000 claims description 3
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
• 230000001028 anti-proliverative effect Effects 0.000 claims description 3
• 239000001961 anticonvulsive agent Substances 0.000 claims description 3
• 239000002111 antiemetic agent Substances 0.000 claims description 3
• 229960003965 antiepileptics Drugs 0.000 claims description 3
• 239000000063 antileukemic agent Substances 0.000 claims description 3
• 239000000939 antiparkinson agent Substances 0.000 claims description 3
• 239000003443 antiviral agent Substances 0.000 claims description 3
• 229940049706 benzodiazepine Drugs 0.000 claims description 3
• 239000000480 calcium channel blocker Substances 0.000 claims description 3
• 239000002559 chemokine receptor antagonist Substances 0.000 claims description 3
• 229960001265 ciclosporin Drugs 0.000 claims description 3
• 229930182912 cyclosporin Natural products 0.000 claims description 3
• 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 claims description 3
• 229960003957 dexamethasone Drugs 0.000 claims description 3
• 239000002934 diuretic Substances 0.000 claims description 3
• 229960003638 dopamine Drugs 0.000 claims description 3
• 239000003210 dopamine receptor blocking agent Substances 0.000 claims description 3
• 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 3
• 229960002949 fluorouracil Drugs 0.000 claims description 3
• 229960003765 fluvastatin Drugs 0.000 claims description 3
• 108010074605 gamma-Globulins Proteins 0.000 claims description 3
• 239000003102 growth factor Substances 0.000 claims description 3
• 230000002519 immonomodulatory effect Effects 0.000 claims description 3
• 230000002434 immunopotentiative effect Effects 0.000 claims description 3
• 229960000598 infliximab Drugs 0.000 claims description 3
• 229910052742 iron Inorganic materials 0.000 claims description 3
• 239000000436 ligase inhibitor Substances 0.000 claims description 3
• 208000019423 liver disease Diseases 0.000 claims description 3
• 229910052751 metal Inorganic materials 0.000 claims description 3
• 239000002184 metal Substances 0.000 claims description 3
• 230000036457 multidrug resistance Effects 0.000 claims description 3
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 3
• 229960004866 mycophenolate mofetil Drugs 0.000 claims description 3
• 239000003900 neurotrophic factor Substances 0.000 claims description 3
• 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 claims description 3
• 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 claims description 3
• 239000000734 parasympathomimetic agent Substances 0.000 claims description 3
• CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 3
• 229960000639 pazopanib Drugs 0.000 claims description 3
• 108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 claims description 3
• 229960002797 pitavastatin Drugs 0.000 claims description 3
• VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 claims description 3
• 150000003057 platinum Chemical class 0.000 claims description 3
• 229960002965 pravastatin Drugs 0.000 claims description 3
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 3
• 239000003207 proteasome inhibitor Substances 0.000 claims description 3
• 230000009145 protein modification Effects 0.000 claims description 3
• 239000000007 protein synthesis inhibitor Substances 0.000 claims description 3
• 229960004181 riluzole Drugs 0.000 claims description 3
• 239000002911 sialidase inhibitor Substances 0.000 claims description 3
• 229960002855 simvastatin Drugs 0.000 claims description 3
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 3
• 229960003787 sorafenib Drugs 0.000 claims description 3
• 239000013589 supplement Substances 0.000 claims description 3
• 229960001967 tacrolimus Drugs 0.000 claims description 3
• 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 description 3
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 210000001519 tissue Anatomy 0.000 claims description 3
• 239000003558 transferase inhibitor Substances 0.000 claims description 3
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 3
• 229960004528 vincristine Drugs 0.000 claims description 3
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
• 230000006656 viral protein synthesis Effects 0.000 claims description 3
• 239000011782 vitamin Substances 0.000 claims description 3
• 229940088594 vitamin Drugs 0.000 claims description 3
• 229930003231 vitamin Natural products 0.000 claims description 3
• 235000013343 vitamin Nutrition 0.000 claims description 3
• VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims description 2
• 229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 claims description 2
• 239000005541 ACE inhibitor Substances 0.000 claims description 2
• 208000019838 Blood disease Diseases 0.000 claims description 2
• 108010008165 Etanercept Proteins 0.000 claims description 2
• 229940122355 Insulin sensitizer Drugs 0.000 claims description 2
• 108010002352 Interleukin-1 Proteins 0.000 claims description 2
• 229940086616 Monoamine oxidase B inhibitor Drugs 0.000 claims description 2
• 229940123685 Monoamine oxidase inhibitor Drugs 0.000 claims description 2
• 229940123424 Neuraminidase inhibitor Drugs 0.000 claims description 2
• 229930012538 Paclitaxel Natural products 0.000 claims description 2
• 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 claims description 2
• 229940123066 Polymerase inhibitor Drugs 0.000 claims description 2
• 206010036790 Productive cough Diseases 0.000 claims description 2
• 102000001400 Tryptase Human genes 0.000 claims description 2
• 108060005989 Tryptase Proteins 0.000 claims description 2
• 239000007801 affinity label Substances 0.000 claims description 2
• 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
• 239000002876 beta blocker Substances 0.000 claims description 2
• 229940097320 beta blocking agent Drugs 0.000 claims description 2
• 229960002685 biotin Drugs 0.000 claims description 2
• 235000020958 biotin Nutrition 0.000 claims description 2
• 239000011616 biotin Substances 0.000 claims description 2
• CJFCGSLFEZPBNJ-UHFFFAOYSA-N carbamimidoylazanium;phosphate Chemical compound NC([NH3+])=N.NC([NH3+])=N.NC([NH3+])=N.[O-]P([O-])([O-])=O CJFCGSLFEZPBNJ-UHFFFAOYSA-N 0.000 claims description 2
• 239000002738 chelating agent Substances 0.000 claims description 2
• 239000002532 enzyme inhibitor Substances 0.000 claims description 2
• 229960000403 etanercept Drugs 0.000 claims description 2
• 229940125777 fusion inhibitor Drugs 0.000 claims description 2
• 208000019622 heart disease Diseases 0.000 claims description 2
• 208000014951 hematologic disease Diseases 0.000 claims description 2
• 208000018706 hematopoietic system disease Diseases 0.000 claims description 2
• 239000003276 histone deacetylase inhibitor Substances 0.000 claims description 2
• 229940124524 integrase inhibitor Drugs 0.000 claims description 2
• 239000002850 integrase inhibitor Substances 0.000 claims description 2
• 229950001869 mapatumumab Drugs 0.000 claims description 2
• 239000002899 monoamine oxidase inhibitor Substances 0.000 claims description 2
• 229960001592 paclitaxel Drugs 0.000 claims description 2
• 230000005298 paramagnetic effect Effects 0.000 claims description 2
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 2
• 229940044601 receptor agonist Drugs 0.000 claims description 2
• 239000000018 receptor agonist Substances 0.000 claims description 2
• 229940075993 receptor modulator Drugs 0.000 claims description 2
• 102000027483 retinoid hormone receptors Human genes 0.000 claims description 2
• 108091008679 retinoid hormone receptors Proteins 0.000 claims description 2
• 239000000849 selective androgen receptor modulator Substances 0.000 claims description 2
• 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 claims description 2
• 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 2
• 229960002930 sirolimus Drugs 0.000 claims description 2
• 208000024794 sputum Diseases 0.000 claims description 2
• 210000003802 sputum Anatomy 0.000 claims description 2
• 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims 7
• ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims 2
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims 2
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims 2
• 102100040247 Tumor necrosis factor Human genes 0.000 claims 2
• NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 claims 2
• 101710129690 Angiotensin-converting enzyme inhibitor Proteins 0.000 claims 1
• 101710086378 Bradykinin-potentiating and C-type natriuretic peptides Proteins 0.000 claims 1
• 102100038595 Estrogen receptor Human genes 0.000 claims 1
• 229910002651 NO3 Inorganic materials 0.000 claims 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
• 108091005804 Peptidases Proteins 0.000 claims 1
• 239000004365 Protease Substances 0.000 claims 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
• 229960004373 acetylcholine Drugs 0.000 claims 1
• 210000004102 animal cell Anatomy 0.000 claims 1
• 239000005557 antagonist Substances 0.000 claims 1
• 239000002254 cytotoxic agent Substances 0.000 claims 1
• 230000001882 diuretic effect Effects 0.000 claims 1
• 229940125532 enzyme inhibitor Drugs 0.000 claims 1
• 229960003276 erythromycin Drugs 0.000 claims 1
• 108010038795 estrogen receptors Proteins 0.000 claims 1
• 229960001340 histamine Drugs 0.000 claims 1
• 210000005260 human cell Anatomy 0.000 claims 1
• 108091005629 prenylated proteins Proteins 0.000 claims 1
• 125000006239 protecting group Chemical group 0.000 claims 1
• 239000000543 intermediate Substances 0.000 abstract description 168
• 230000008569 process Effects 0.000 abstract description 2
• 230000001363 autoimmune Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 196
• 239000000243 solution Substances 0.000 description 84
• 235000019439 ethyl acetate Nutrition 0.000 description 70
• 238000006243 chemical reaction Methods 0.000 description 69
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• 230000002829 reductive effect Effects 0.000 description 41
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• 238000000746 purification Methods 0.000 description 36
• 239000000203 mixture Substances 0.000 description 32
• 239000007787 solid Substances 0.000 description 29
• 210000004027 cell Anatomy 0.000 description 27
• 229940079593 drug Drugs 0.000 description 25
• 230000015572 biosynthetic process Effects 0.000 description 24
• 239000003039 volatile agent Substances 0.000 description 24
• 239000012267 brine Substances 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
• 238000003786 synthesis reaction Methods 0.000 description 22
• 238000004440 column chromatography Methods 0.000 description 21
• 239000000499 gel Substances 0.000 description 21
• 239000012044 organic layer Substances 0.000 description 21
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 239000000284 extract Substances 0.000 description 15
• 229920006395 saturated elastomer Polymers 0.000 description 14
• 239000006260 foam Substances 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• 239000007864 aqueous solution Substances 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• 125000000524 functional group Chemical group 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• BWLBGMIXKSTLSX-UHFFFAOYSA-N 2-hydroxyisobutyric acid Chemical compound CC(C)(O)C(O)=O BWLBGMIXKSTLSX-UHFFFAOYSA-N 0.000 description 10
• 239000002552 dosage form Substances 0.000 description 10
• 108090000623 proteins and genes Proteins 0.000 description 10
• 239000011541 reaction mixture Substances 0.000 description 10
• 125000001424 substituent group Chemical group 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• 235000019270 ammonium chloride Nutrition 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• 102000004169 proteins and genes Human genes 0.000 description 9
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 9
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 125000004429 atom Chemical group 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 125000005842 heteroatom Chemical group 0.000 description 7
• 201000004792 malaria Diseases 0.000 description 7
• 238000004519 manufacturing process Methods 0.000 description 7
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
• 108010087686 src-Family Kinases Proteins 0.000 description 7
• 230000004083 survival effect Effects 0.000 description 7
• 239000012730 sustained-release form Substances 0.000 description 7
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
• 125000003342 alkenyl group Chemical group 0.000 description 6
• 239000012230 colorless oil Substances 0.000 description 6
• 125000000392 cycloalkenyl group Chemical group 0.000 description 6
• 125000000753 cycloalkyl group Chemical group 0.000 description 6
• 230000003111 delayed effect Effects 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 238000010898 silica gel chromatography Methods 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000013268 sustained release Methods 0.000 description 6
• 102000003390 tumor necrosis factor Human genes 0.000 description 6
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
• 241000283690 Bos taurus Species 0.000 description 5
• 206010025323 Lymphomas Diseases 0.000 description 5
• 229910019142 PO4 Inorganic materials 0.000 description 5
• 125000003545 alkoxy group Chemical group 0.000 description 5
• 125000000304 alkynyl group Chemical group 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 210000003719 b-lymphocyte Anatomy 0.000 description 5
• 238000013270 controlled release Methods 0.000 description 5
• 230000006870 function Effects 0.000 description 5
• 239000012729 immediate-release (IR) formulation Substances 0.000 description 5
• 238000000338 in vitro Methods 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 244000052769 pathogen Species 0.000 description 5
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
• 239000010452 phosphate Substances 0.000 description 5
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
• 210000004989 spleen cell Anatomy 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 4
• OQUKJSVQMVBUBY-UHFFFAOYSA-N 1-bromo-3-fluoro-5-iodobenzene Chemical compound FC1=CC(Br)=CC(I)=C1 OQUKJSVQMVBUBY-UHFFFAOYSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 4
• 201000004384 Alopecia Diseases 0.000 description 4
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 206010023076 Isosporiasis Diseases 0.000 description 4
• 241001467552 Mycobacterium bovis BCG Species 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 201000004681 Psoriasis Diseases 0.000 description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
• 241000224003 Sarcocystis Species 0.000 description 4
• 231100000360 alopecia Toxicity 0.000 description 4
• 208000006673 asthma Diseases 0.000 description 4
• 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 238000013265 extended release Methods 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 229940043355 kinase inhibitor Drugs 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• 208000030159 metabolic disease Diseases 0.000 description 4
• 150000002894 organic compounds Chemical class 0.000 description 4
• 230000001717 pathogenic effect Effects 0.000 description 4
• YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 4
• 210000003491 skin Anatomy 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 102000009076 src-Family Kinases Human genes 0.000 description 4
• 238000010189 synthetic method Methods 0.000 description 4
• 208000019553 vascular disease Diseases 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 208000003495 Coccidiosis Diseases 0.000 description 3
• RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 102000010909 Monoamine Oxidase Human genes 0.000 description 3
• 108010062431 Monoamine oxidase Proteins 0.000 description 3
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 102000001332 SRC Human genes 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
• 201000008754 Tenosynovial giant cell tumor Diseases 0.000 description 3
• 206010052779 Transplant rejections Diseases 0.000 description 3
• 241000223105 Trypanosoma brucei Species 0.000 description 3
• 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 230000033228 biological regulation Effects 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 230000003915 cell function Effects 0.000 description 3
• 230000010261 cell growth Effects 0.000 description 3
• 229940125904 compound 1 Drugs 0.000 description 3
• 229940125773 compound 10 Drugs 0.000 description 3
• 229940125898 compound 5 Drugs 0.000 description 3
• IGMWDYQIKLLYQH-UHFFFAOYSA-N cyanomethyl diethyl phosphate Chemical compound CCOP(=O)(OCC)OCC#N IGMWDYQIKLLYQH-UHFFFAOYSA-N 0.000 description 3
• 229940088598 enzyme Drugs 0.000 description 3
• 210000003743 erythrocyte Anatomy 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 210000003630 histaminocyte Anatomy 0.000 description 3
• 239000005556 hormone Substances 0.000 description 3
• 229940088597 hormone Drugs 0.000 description 3
• 125000001183 hydrocarbyl group Chemical group 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
• 206010025135 lupus erythematosus Diseases 0.000 description 3
• 201000006417 multiple sclerosis Diseases 0.000 description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 230000035755 proliferation Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 230000011664 signaling Effects 0.000 description 3
• HOBMGFDJYBEWLS-UHFFFAOYSA-N (2-methylpyrimidin-5-yl)methanol Chemical compound CC1=NC=C(CO)C=N1 HOBMGFDJYBEWLS-UHFFFAOYSA-N 0.000 description 2
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
• DJCJOWDAAZEMCI-UHFFFAOYSA-N (6-methylpyridin-3-yl)methanol Chemical compound CC1=CC=C(CO)C=N1 DJCJOWDAAZEMCI-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 2
• IENOFRJPUPTEMI-UHFFFAOYSA-N 3-oxocyclobutane-1-carboxylic acid Chemical compound OC(=O)C1CC(=O)C1 IENOFRJPUPTEMI-UHFFFAOYSA-N 0.000 description 2
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
• 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• 241000271566 Aves Species 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• 208000031229 Cardiomyopathies Diseases 0.000 description 2
• 229920001268 Cholestyramine Polymers 0.000 description 2
• 208000008953 Cryptosporidiosis Diseases 0.000 description 2
• 206010011502 Cryptosporidiosis infection Diseases 0.000 description 2
• 229920000858 Cyclodextrin Polymers 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 206010014561 Emphysema Diseases 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
• 229940122236 Histamine receptor antagonist Drugs 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
• FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 208000030852 Parasitic disease Diseases 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• 201000009594 Systemic Scleroderma Diseases 0.000 description 2
• 206010042953 Systemic sclerosis Diseases 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 241000223109 Trypanosoma cruzi Species 0.000 description 2
• 102100039079 Tyrosine-protein kinase TXK Human genes 0.000 description 2
• 101710101516 Tyrosine-protein kinase TXK Proteins 0.000 description 2
• 206010046851 Uveitis Diseases 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 229940009456 adriamycin Drugs 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 125000000539 amino acid group Chemical group 0.000 description 2
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 239000003146 anticoagulant agent Substances 0.000 description 2
• 229960004676 antithrombotic agent Drugs 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 230000005540 biological transmission Effects 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 230000020411 cell activation Effects 0.000 description 2
• 230000005754 cellular signaling Effects 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 239000000812 cholinergic antagonist Substances 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 206010009887 colitis Diseases 0.000 description 2
• 229940125782 compound 2 Drugs 0.000 description 2
• 229940126214 compound 3 Drugs 0.000 description 2
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• YGXMYKTZDMYISM-IDIVVRGQSA-J dimagnesium;[[[(2r,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate Chemical compound [Mg+2].[Mg+2].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O YGXMYKTZDMYISM-IDIVVRGQSA-J 0.000 description 2
• 208000037765 diseases and disorders Diseases 0.000 description 2
• 229940030606 diuretics Drugs 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 108010075324 emt protein-tyrosine kinase Proteins 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 238000002875 fluorescence polarization Methods 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 206010020718 hyperplasia Diseases 0.000 description 2
• 208000009326 ileitis Diseases 0.000 description 2
• 230000036737 immune function Effects 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 230000001965 increasing effect Effects 0.000 description 2
• 230000004968 inflammatory condition Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• QHDRKFYEGYYIIK-UHFFFAOYSA-N isovaleronitrile Chemical compound CC(C)CC#N QHDRKFYEGYYIIK-UHFFFAOYSA-N 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 244000144972 livestock Species 0.000 description 2
• 230000007774 longterm Effects 0.000 description 2
• 210000002540 macrophage Anatomy 0.000 description 2
• UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 2
• 239000011654 magnesium acetate Substances 0.000 description 2
• 235000011285 magnesium acetate Nutrition 0.000 description 2
• 229940069446 magnesium acetate Drugs 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 230000003211 malignant effect Effects 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 208000004235 neutropenia Diseases 0.000 description 2
• 210000000440 neutrophil Anatomy 0.000 description 2
• 150000002823 nitrates Chemical class 0.000 description 2
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 2
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 2
• FJDUDHYHRVPMJZ-UHFFFAOYSA-N nonan-1-amine Chemical compound CCCCCCCCCN FJDUDHYHRVPMJZ-UHFFFAOYSA-N 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000008203 oral pharmaceutical composition Substances 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 230000004962 physiological condition Effects 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 208000037803 restenosis Diseases 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• 229960000672 rosuvastatin Drugs 0.000 description 2
• BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• UGNOVENEUBRGNI-UHFFFAOYSA-N (2-methyl-1,3-thiazol-5-yl)methanol Chemical compound CC1=NC=C(CO)S1 UGNOVENEUBRGNI-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 1
• KQBDLOVXZHOAJI-UHFFFAOYSA-N (4-phenylmethoxyphenyl)azanium;chloride Chemical compound Cl.C1=CC(N)=CC=C1OCC1=CC=CC=C1 KQBDLOVXZHOAJI-UHFFFAOYSA-N 0.000 description 1
• UVNPEUJXKZFWSJ-LMTQTHQJSA-N (R)-N-[(4S)-8-[6-amino-5-[(3,3-difluoro-2-oxo-1H-pyrrolo[2,3-b]pyridin-4-yl)sulfanyl]pyrazin-2-yl]-2-oxa-8-azaspiro[4.5]decan-4-yl]-2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](=O)N[C@@H]1COCC11CCN(CC1)c1cnc(Sc2ccnc3NC(=O)C(F)(F)c23)c(N)n1 UVNPEUJXKZFWSJ-LMTQTHQJSA-N 0.000 description 1
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 1
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
• ZCSOJXHICDKYJO-UHFFFAOYSA-N 2,3-dihydropyran-4-one Chemical compound O=C1CCOC=C1 ZCSOJXHICDKYJO-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
• KWMBADTWRIGGGG-UHFFFAOYSA-N 2-diethoxyphosphorylacetonitrile Chemical compound CCOP(=O)(CC#N)OCC KWMBADTWRIGGGG-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
• BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 1
• FIIDVVUUWRJXLF-UHFFFAOYSA-N 4-phenylmethoxyaniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CC=C1 FIIDVVUUWRJXLF-UHFFFAOYSA-N 0.000 description 1
• 102000035037 5-HT3 receptors Human genes 0.000 description 1
• 108091005477 5-HT3 receptors Proteins 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 208000000230 African Trypanosomiasis Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 206010001935 American trypanosomiasis Diseases 0.000 description 1
• 241000224489 Amoeba Species 0.000 description 1
• 241000224482 Apicomplexa Species 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• 108091008875 B cell receptors Proteins 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 241000223836 Babesia Species 0.000 description 1
• 241000223840 Babesia bigemina Species 0.000 description 1
• 241000223838 Babesia bovis Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 201000010717 Bruton-type agammaglobulinemia Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 244000025254 Cannabis sativa Species 0.000 description 1
• 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
• 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 208000010711 Cattle disease Diseases 0.000 description 1
• 208000024699 Chagas disease Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 241000224483 Coccidia Species 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 229940126062 Compound A Drugs 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000223936 Cryptosporidium parvum Species 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• 241000205707 Cystoisospora belli Species 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 241000224432 Entamoeba histolytica Species 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[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 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
• 239000001116 FEMA 4028 Substances 0.000 description 1
• 108091008794 FGF receptors Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 208000007990 Giant Cell Tumor of Tendon Sheath Diseases 0.000 description 1
• 206010018255 Giant cell tumour of tendon sheath Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• 208000009329 Graft vs Host Disease Diseases 0.000 description 1
• 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
• 101100058683 Homo sapiens BTK gene Proteins 0.000 description 1
• 101000579425 Homo sapiens Proto-oncogene tyrosine-protein kinase receptor Ret Proteins 0.000 description 1
• 101000864342 Homo sapiens Tyrosine-protein kinase BTK Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 206010061217 Infestation Diseases 0.000 description 1
• 102000004877 Insulin Human genes 0.000 description 1
• 108090001061 Insulin Proteins 0.000 description 1
• 229940119178 Interleukin 1 receptor antagonist Drugs 0.000 description 1
• 102000000589 Interleukin-1 Human genes 0.000 description 1
• 241000567229 Isospora Species 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 241000222722 Leishmania <genus> Species 0.000 description 1
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027452 Metastases to bone Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• NUGPIZCTELGDOS-QHCPKHFHSA-N N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclopentanecarboxamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CC[C@@H](C=1C=NC=CC=1)NC(=O)C1CCCC1)C NUGPIZCTELGDOS-QHCPKHFHSA-N 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 108010016731 PPAR gamma Proteins 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
• 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
• 241000286209 Phasianidae Species 0.000 description 1
• 241000223960 Plasmodium falciparum Species 0.000 description 1
• 241000223821 Plasmodium malariae Species 0.000 description 1
• 206010035501 Plasmodium malariae infection Diseases 0.000 description 1
• 241001505293 Plasmodium ovale Species 0.000 description 1
• 241000223810 Plasmodium vivax Species 0.000 description 1
• 241000233872 Pneumocystis carinii Species 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
• 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 102000012515 Protein kinase domains Human genes 0.000 description 1
• 108050002122 Protein kinase domains Proteins 0.000 description 1
• 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 241001506137 Rapa Species 0.000 description 1
• 229940123934 Reductase inhibitor Drugs 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• 206010039484 Sarcocystis infections Diseases 0.000 description 1
• 208000006775 Sarcocystosis Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 108091008874 T cell receptors Proteins 0.000 description 1
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• 241000223777 Theileria Species 0.000 description 1
• 241000223779 Theileria parva Species 0.000 description 1
• 208000001117 Theileriasis Diseases 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 229940123464 Thiazolidinedione Drugs 0.000 description 1
• 206010043647 Thrombotic Stroke Diseases 0.000 description 1
• 241000223997 Toxoplasma gondii Species 0.000 description 1
• 201000005485 Toxoplasmosis Diseases 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 241000223104 Trypanosoma Species 0.000 description 1
• 241001442399 Trypanosoma brucei gambiense Species 0.000 description 1
• 241001442397 Trypanosoma brucei rhodesiense Species 0.000 description 1
• 241000223107 Trypanosoma congolense Species 0.000 description 1
• 241000223099 Trypanosoma vivax Species 0.000 description 1
• 101710086214 Tyrosine-protein kinase BTK Proteins 0.000 description 1
• 108091008605 VEGF receptors Proteins 0.000 description 1
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 208000016349 X-linked agammaglobulinemia Diseases 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• RGJOLSWGURYBNM-UHFFFAOYSA-N [Cl-].C[NH3+].C1=CC=CC=C1 Chemical compound [Cl-].C[NH3+].C1=CC=CC=C1 RGJOLSWGURYBNM-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 229940022663 acetate Drugs 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
• XMGZWGBXVLJOKE-UHFFFAOYSA-N acetic acid;toluene Chemical compound CC(O)=O.CC1=CC=CC=C1 XMGZWGBXVLJOKE-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• TTWYZDPBDWHJOR-IDIVVRGQSA-L adenosine triphosphate disodium Chemical compound [Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O TTWYZDPBDWHJOR-IDIVVRGQSA-L 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001345 alkine derivatives Chemical class 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 230000003444 anaesthetic effect Effects 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000000648 anti-parkinson Effects 0.000 description 1
• 239000003173 antianemic agent Substances 0.000 description 1
• 229940125683 antiemetic agent Drugs 0.000 description 1
• 239000000739 antihistaminic agent Substances 0.000 description 1
• 239000003430 antimalarial agent Substances 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 230000002238 attenuated effect Effects 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• 201000008680 babesiosis Diseases 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
• 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
• 229960004853 betadex Drugs 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 230000009702 cancer cell proliferation Effects 0.000 description 1
• 229930003827 cannabinoid Natural products 0.000 description 1
• 239000003557 cannabinoid Substances 0.000 description 1
• 229940065144 cannabinoids Drugs 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 201000011529 cardiovascular cancer Diseases 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000011748 cell maturation Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 238000012054 celltiter-glo Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000019522 cellular metabolic process Effects 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 208000015114 central nervous system disease Diseases 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 239000000544 cholinesterase inhibitor Substances 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000002131 composite material Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 125000004093 cyano group Chemical group *C#N 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 238000002716 delivery method Methods 0.000 description 1
• 239000000841 delta opiate receptor agonist Substances 0.000 description 1
• 201000001981 dermatomyositis Diseases 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 208000035647 diffuse type tenosynovial giant cell tumor Diseases 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 108700003601 dimethylglycine Proteins 0.000 description 1
• 229940042406 direct acting antivirals neuraminidase inhibitors Drugs 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 230000007783 downstream signaling Effects 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 208000001848 dysentery Diseases 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 229940007078 entamoeba histolytica Drugs 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
• 229940125367 erythropoiesis stimulating agent Drugs 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• 239000003797 essential amino acid Substances 0.000 description 1
• 235000020776 essential amino acid Nutrition 0.000 description 1
• 239000002834 estrogen receptor modulator Substances 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 229960005167 everolimus Drugs 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000007888 film coating Substances 0.000 description 1
• 238000009501 film coating Methods 0.000 description 1
• 239000010419 fine particle Substances 0.000 description 1
• 238000010579 first pass effect Methods 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
• 125000004475 heteroaralkyl group Chemical group 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
• 230000006197 histone deacetylation Effects 0.000 description 1
• 102000053446 human BTK Human genes 0.000 description 1
• 244000052637 human pathogen Species 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 230000002637 immunotoxin Effects 0.000 description 1
• 229940051026 immunotoxin Drugs 0.000 description 1
• 239000002596 immunotoxin Substances 0.000 description 1
• 231100000608 immunotoxin Toxicity 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229940125396 insulin Drugs 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 230000007794 irritation 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
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000008263 liquid aerosol Substances 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 238000007422 luminescence assay Methods 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• AWIJRPNMLHPLNC-UHFFFAOYSA-N methanethioic s-acid Chemical compound SC=O AWIJRPNMLHPLNC-UHFFFAOYSA-N 0.000 description 1
• 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 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• APNPVBXEWGCCLU-QNRZBPGKSA-N mycomycin Chemical compound OC(=O)C\C=C\C=C/C=C=CC#CC#C APNPVBXEWGCCLU-QNRZBPGKSA-N 0.000 description 1
• 229940014456 mycophenolate Drugs 0.000 description 1
• 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 description 1
• 229940078490 n,n-dimethylglycine Drugs 0.000 description 1
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000011017 operating method Methods 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 210000003463 organelle Anatomy 0.000 description 1
• JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 210000002824 peroxisome Anatomy 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
• 208000007420 pigmented villonodular synovitis Diseases 0.000 description 1
• 229940118768 plasmodium malariae Drugs 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000035409 positive regulation of cell proliferation Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 239000002510 pyrogen Substances 0.000 description 1
• 150000004060 quinone imines Chemical class 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000020129 regulation of cell death Effects 0.000 description 1
• 230000012121 regulation of immune response Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 208000019116 sleep disease Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 210000004988 splenocyte Anatomy 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 210000000130 stem cell Anatomy 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical group 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 201000004595 synovitis Diseases 0.000 description 1
• 239000000057 synthetic resin Substances 0.000 description 1
• 229920003002 synthetic resin Polymers 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• 150000001467 thiazolidinediones Chemical class 0.000 description 1
• 150000007970 thio esters Chemical class 0.000 description 1
• DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 231100000588 tumorigenic Toxicity 0.000 description 1
• 230000000381 tumorigenic effect Effects 0.000 description 1
• 108010002164 tyrosine receptor Proteins 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 229940070710 valerate Drugs 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 229940075420 xanthine Drugs 0.000 description 1
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1