JP2017503006A

JP2017503006A - プロテインキナーゼ阻害剤

プロテインキナーゼ阻害剤 Download PDF

Info

Publication number: JP2017503006A
Authority: JP; Japan
Prior art keywords: compound; mmol; inhibitors; treatment; diseases
Prior art date: 2013-11-26
Legal status : Withdrawn

Application number

JP2016554766A

Other languages

English (en)

Japanese (ja)

Other versions

JP2017503006A5 (OSRAM

Inventor

ローレント，アレイム

ローズ，ヤンニック

Current Assignee

Pharmascience Inc

Original Assignee

Pharmascience Inc

Priority date

2013-11-26

Filing date

2014-11-26

Publication date

2017-01-26

2014-11-26 Application filed by Pharmascience Inc filed Critical Pharmascience Inc

2017-01-26 Publication of JP2017503006A publication Critical patent/JP2017503006A/ja

2017-12-07 Publication of JP2017503006A5 publication Critical patent/JP2017503006A5/ja

Status Withdrawn legal-status Critical Current

Links

239000003909 protein kinase inhibitor Substances 0.000 title abstract description 4
229940043355 kinase inhibitor Drugs 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 142
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 78
238000011282 treatment Methods 0.000 claims abstract description 54
102000001253 Protein Kinase Human genes 0.000 claims abstract description 44
108060006633 protein kinase Proteins 0.000 claims abstract description 42
208000035475 disorder Diseases 0.000 claims abstract description 39
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 37
239000003112 inhibitor Substances 0.000 claims abstract description 34
230000000694 effects Effects 0.000 claims abstract description 31
230000002062 proliferating effect Effects 0.000 claims abstract description 24
208000023275 Autoimmune disease Diseases 0.000 claims abstract description 17
208000027866 inflammatory disease Diseases 0.000 claims abstract description 16
208000035473 Communicable disease Diseases 0.000 claims abstract description 12
208000015181 infectious disease Diseases 0.000 claims abstract description 5
230000002757 inflammatory effect Effects 0.000 claims abstract description 5
150000003839 salts Chemical class 0.000 claims description 70
239000003814 drug Substances 0.000 claims description 54
239000012453 solvate Substances 0.000 claims description 54
108091000080 Phosphotransferase Proteins 0.000 claims description 42
102000020233 phosphotransferase Human genes 0.000 claims description 42
201000010099 disease Diseases 0.000 claims description 39
239000000203 mixture Substances 0.000 claims description 32
229940079593 drug Drugs 0.000 claims description 31
-1 Fusion inhibitor Substances 0.000 claims description 28
206010028980 Neoplasm Diseases 0.000 claims description 27
125000000623 heterocyclic group Chemical group 0.000 claims description 26
125000000217 alkyl group Chemical group 0.000 claims description 25
125000003118 aryl group Chemical group 0.000 claims description 25
201000011510 cancer Diseases 0.000 claims description 24
125000001072 heteroaryl group Chemical group 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 19
239000003795 chemical substances by application Substances 0.000 claims description 18
230000005764 inhibitory process Effects 0.000 claims description 18
230000001404 mediated effect Effects 0.000 claims description 18
239000002207 metabolite Substances 0.000 claims description 17
239000000651 prodrug Substances 0.000 claims description 15
229940002612 prodrug Drugs 0.000 claims description 15
229940124597 therapeutic agent Drugs 0.000 claims description 13
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 12
125000004452 carbocyclyl group Chemical group 0.000 claims description 12
239000003246 corticosteroid Substances 0.000 claims description 12
208000024172 Cardiovascular disease Diseases 0.000 claims description 11
102000014150 Interferons Human genes 0.000 claims description 11
108010050904 Interferons Proteins 0.000 claims description 11
229960001334 corticosteroids Drugs 0.000 claims description 11
239000000546 pharmaceutical excipient Substances 0.000 claims description 11
125000004404 heteroalkyl group Chemical group 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 10
238000004519 manufacturing process Methods 0.000 claims description 10
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 9
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
229940079322 interferon Drugs 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
108090000623 proteins and genes Proteins 0.000 claims description 9
239000000523 sample Substances 0.000 claims description 9
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-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
229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 8
239000000556 agonist Substances 0.000 claims description 8
229960004397 cyclophosphamide Drugs 0.000 claims description 8
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 8
108010009978 Tec protein-tyrosine kinase Proteins 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
102000004169 proteins and genes Human genes 0.000 claims description 7
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 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
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
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
201000004792 malaria Diseases 0.000 claims description 6
230000002265 prevention Effects 0.000 claims description 6
229940044551 receptor antagonist Drugs 0.000 claims description 6
239000002464 receptor antagonist Substances 0.000 claims description 6
229960001940 sulfasalazine Drugs 0.000 claims description 6
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 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
102000004127 Cytokines Human genes 0.000 claims description 5
108090000695 Cytokines Proteins 0.000 claims description 5
206010020751 Hypersensitivity Diseases 0.000 claims description 5
206010061218 Inflammation Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
208000007536 Thrombosis Diseases 0.000 claims description 5
239000002260 anti-inflammatory agent Substances 0.000 claims description 5
239000002246 antineoplastic agent Substances 0.000 claims description 5
230000030833 cell death Effects 0.000 claims description 5
229940127089 cytotoxic agent Drugs 0.000 claims description 5
230000004054 inflammatory process Effects 0.000 claims description 5
239000003446 ligand Substances 0.000 claims description 5
208000030159 metabolic disease Diseases 0.000 claims description 5
230000001575 pathological effect 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
201000004384 Alopecia Diseases 0.000 claims description 4
102000038012 SFKs Human genes 0.000 claims description 4
108091008118 SFKs Proteins 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
231100000360 alopecia Toxicity 0.000 claims description 4
229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
206010003246 arthritis Diseases 0.000 claims description 4
239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
230000004927 fusion Effects 0.000 claims description 4
239000005556 hormone Substances 0.000 claims description 4
229940088597 hormone Drugs 0.000 claims description 4
239000003018 immunosuppressive agent Substances 0.000 claims description 4
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
210000001519 tissue Anatomy 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
102000035037 5-HT3 receptors Human genes 0.000 claims description 3
108091005477 5-HT3 receptors Proteins 0.000 claims description 3
239000005541 ACE inhibitor Substances 0.000 claims description 3
208000019838 Blood disease Diseases 0.000 claims description 3
229940127291 Calcium channel antagonist Drugs 0.000 claims description 3
208000031229 Cardiomyopathies Diseases 0.000 claims description 3
229940122444 Chemokine receptor antagonist Drugs 0.000 claims description 3
229920001268 Cholestyramine Polymers 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
206010014561 Emphysema Diseases 0.000 claims description 3
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 claims description 3
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 3
206010018364 Glomerulonephritis Diseases 0.000 claims description 3
229940122236 Histamine receptor antagonist Drugs 0.000 claims description 3
102000006992 Interferon-alpha Human genes 0.000 claims description 3
108010047761 Interferon-alpha Proteins 0.000 claims description 3
108010002352 Interleukin-1 Proteins 0.000 claims description 3
108010063738 Interleukins Proteins 0.000 claims description 3
102000015696 Interleukins Human genes 0.000 claims description 3
108090000862 Ion Channels Proteins 0.000 claims description 3
102000004310 Ion Channels Human genes 0.000 claims description 3
239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 3
239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 3
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 3
229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 3
208000031888 Mycoses Diseases 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
108010016731 PPAR gamma Proteins 0.000 claims description 3
229930012538 Paclitaxel Natural products 0.000 claims description 3
102100038825 Peroxisome proliferator-activated receptor gamma 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
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
229940123464 Thiazolidinedione Drugs 0.000 claims description 3
108010067390 Viral Proteins Proteins 0.000 claims description 3
229960002964 adalimumab Drugs 0.000 claims description 3
229940009456 adriamycin Drugs 0.000 claims description 3
208000026935 allergic disease Diseases 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
230000001078 anti-cholinergic effect Effects 0.000 claims description 3
230000003474 anti-emetic effect Effects 0.000 claims description 3
229940035678 anti-parkinson drug 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
229940125683 antiemetic agent Drugs 0.000 claims description 3
239000002111 antiemetic agent Substances 0.000 claims description 3
239000003443 antiviral agent Substances 0.000 claims description 3
244000052616 bacterial pathogen Species 0.000 claims description 3
229940049706 benzodiazepine Drugs 0.000 claims description 3
239000002876 beta blocker Substances 0.000 claims description 3
229940097320 beta blocking agent Drugs 0.000 claims description 3
239000000480 calcium channel blocker Substances 0.000 claims description 3
239000003557 cannabinoid Substances 0.000 claims description 3
229930003827 cannabinoid Natural products 0.000 claims description 3
229940065144 cannabinoids Drugs 0.000 claims description 3
239000003543 catechol methyltransferase inhibitor Substances 0.000 claims description 3
208000015114 central nervous system disease Diseases 0.000 claims description 3
239000002559 chemokine receptor antagonist Substances 0.000 claims description 3
239000000812 cholinergic antagonist Substances 0.000 claims description 3
230000037012 chymotrypsin-like activity Effects 0.000 claims description 3
229960001265 ciclosporin Drugs 0.000 claims description 3
229930182912 cyclosporin Natural products 0.000 claims description 3
229960003957 dexamethasone Drugs 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
239000002934 diuretic Substances 0.000 claims description 3
229940030606 diuretics Drugs 0.000 claims description 3
229960003638 dopamine Drugs 0.000 claims description 3
239000003210 dopamine receptor blocking agent Substances 0.000 claims description 3
230000010437 erythropoiesis Effects 0.000 claims description 3
229960005167 everolimus Drugs 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
208000014951 hematologic disease Diseases 0.000 claims description 3
208000018706 hematopoietic system disease Diseases 0.000 claims description 3
239000003276 histone deacetylase inhibitor Substances 0.000 claims description 3
210000000987 immune system Anatomy 0.000 claims description 3
239000002955 immunomodulating agent Substances 0.000 claims description 3
229940121354 immunomodulator Drugs 0.000 claims description 3
229960001438 immunostimulant agent Drugs 0.000 claims description 3
239000003022 immunostimulating agent Substances 0.000 claims description 3
230000003308 immunostimulating effect Effects 0.000 claims description 3
229960003444 immunosuppressant agent Drugs 0.000 claims description 3
239000002850 integrase inhibitor Substances 0.000 claims description 3
229940124524 integrase inhibitor Drugs 0.000 claims description 3
229940047122 interleukins Drugs 0.000 claims description 3
230000005865 ionizing radiation Effects 0.000 claims description 3
239000000436 ligase inhibitor Substances 0.000 claims description 3
208000019423 liver disease Diseases 0.000 claims description 3
229960004844 lovastatin Drugs 0.000 claims description 3
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 3
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 3
229950001869 mapatumumab Drugs 0.000 claims description 3
229910052751 metal Inorganic materials 0.000 claims description 3
239000002184 metal Substances 0.000 claims description 3
239000002899 monoamine oxidase inhibitor Substances 0.000 claims description 3
239000003900 neurotrophic factor Substances 0.000 claims description 3
208000004235 neutropenia Diseases 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
229960001592 paclitaxel Drugs 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
239000000137 peptide hydrolase inhibitor Substances 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
239000002243 precursor Substances 0.000 claims description 3
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 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
230000005855 radiation Effects 0.000 claims description 3
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 3
208000037803 restenosis Diseases 0.000 claims description 3
206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
229960004181 riluzole Drugs 0.000 claims description 3
229960000672 rosuvastatin Drugs 0.000 claims description 3
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 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
QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 3
229960002930 sirolimus Drugs 0.000 claims description 3
208000017520 skin disease Diseases 0.000 claims description 3
230000003637 steroidlike Effects 0.000 claims description 3
WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims description 3
229960001796 sunitinib Drugs 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
150000001467 thiazolidinediones Chemical class 0.000 claims description 3
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 claims description 3
229960000303 topotecan Drugs 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
230000003612 virological effect Effects 0.000 claims description 3
229940088594 vitamin Drugs 0.000 claims description 3
239000011782 vitamin Substances 0.000 claims description 3
235000013343 vitamin Nutrition 0.000 claims description 3
229930003231 vitamin Natural products 0.000 claims description 3
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims description 2
208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
229940086616 Monoamine oxidase B inhibitor Drugs 0.000 claims description 2
102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 claims description 2
229940123066 Polymerase inhibitor Drugs 0.000 claims description 2
229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 2
102100040247 Tumor necrosis factor Human genes 0.000 claims description 2
102000006275 Ubiquitin-Protein Ligases Human genes 0.000 claims description 2
108010083111 Ubiquitin-Protein Ligases Proteins 0.000 claims description 2
239000000063 antileukemic agent Substances 0.000 claims description 2
230000001363 autoimmune Effects 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
239000002872 contrast media Substances 0.000 claims description 2
239000002254 cytotoxic agent Substances 0.000 claims description 2
231100000599 cytotoxic agent Toxicity 0.000 claims description 2
229940042406 direct acting antivirals neuraminidase inhibitors Drugs 0.000 claims description 2
239000002834 estrogen receptor modulator Substances 0.000 claims description 2
229940125777 fusion inhibitor Drugs 0.000 claims description 2
239000004030 hiv protease inhibitor Substances 0.000 claims description 2
229960000598 infliximab Drugs 0.000 claims description 2
229910052742 iron Inorganic materials 0.000 claims description 2
230000036457 multidrug resistance Effects 0.000 claims description 2
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 2
229960004866 mycophenolate mofetil Drugs 0.000 claims description 2
208000010125 myocardial infarction Diseases 0.000 claims description 2
150000002823 nitrates Chemical class 0.000 claims description 2
230000005298 paramagnetic effect Effects 0.000 claims description 2
230000003071 parasitic effect Effects 0.000 claims description 2
108091008765 peroxisome proliferator-activated receptors β/δ Proteins 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
239000002911 sialidase inhibitor Substances 0.000 claims description 2
229940098778 Dopamine receptor agonist Drugs 0.000 claims 1
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims 1
210000004102 animal cell Anatomy 0.000 claims 1
230000001773 anti-convulsant effect Effects 0.000 claims 1
229960003965 antiepileptics Drugs 0.000 claims 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
239000013522 chelant Substances 0.000 claims 1
210000005260 human cell Anatomy 0.000 claims 1
230000009610 hypersensitivity Effects 0.000 claims 1
208000015891 sexual disease Diseases 0.000 claims 1
230000001568 sexual effect Effects 0.000 claims 1
239000000126 substance Substances 0.000 abstract description 4
230000002458 infectious effect Effects 0.000 abstract description 3
229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 abstract description 2
239000000543 intermediate Substances 0.000 description 204
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
239000000243 solution Substances 0.000 description 88
238000006243 chemical reaction Methods 0.000 description 70
230000002829 reductive effect Effects 0.000 description 57
238000000746 purification Methods 0.000 description 52
239000007787 solid Substances 0.000 description 52
238000010898 silica gel chromatography Methods 0.000 description 47
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
235000019439 ethyl acetate Nutrition 0.000 description 44
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
230000015572 biosynthetic process Effects 0.000 description 41
238000003786 synthesis reaction Methods 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 28
FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 28
238000000034 method Methods 0.000 description 28
239000003039 volatile agent Substances 0.000 description 28
210000004027 cell Anatomy 0.000 description 24
239000012267 brine Substances 0.000 description 23
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 23
229910000024 caesium carbonate Inorganic materials 0.000 description 23
239000012044 organic layer Substances 0.000 description 23
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
229910021595 Copper(I) iodide Inorganic materials 0.000 description 20
239000007864 aqueous solution Substances 0.000 description 19
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 19
229920006395 saturated elastomer Polymers 0.000 description 19
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 18
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
235000019270 ammonium chloride Nutrition 0.000 description 14
239000003921 oil Substances 0.000 description 14
235000019198 oils Nutrition 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
108700003601 dimethylglycine Proteins 0.000 description 13
229940078490 n,n-dimethylglycine Drugs 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
239000012730 sustained-release form Substances 0.000 description 12
238000003556 assay Methods 0.000 description 11
230000002401 inhibitory effect Effects 0.000 description 11
238000013268 sustained release Methods 0.000 description 11
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
XTHFKEDIFFGKHM-UHFFFAOYSA-N ethylene glycol dimethyl ether Natural products COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 10
238000001914 filtration Methods 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 10
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
101150003085 Pdcl gene Proteins 0.000 description 9
239000000908 ammonium hydroxide Substances 0.000 description 9
125000004429 atom Chemical group 0.000 description 9
239000002552 dosage form Substances 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
125000003342 alkenyl group Chemical group 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 8
238000013270 controlled release Methods 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
238000009472 formulation Methods 0.000 description 8
230000006870 function Effects 0.000 description 8
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
229910000041 hydrogen chloride Inorganic materials 0.000 description 8
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
230000004083 survival effect Effects 0.000 description 8
230000003111 delayed effect Effects 0.000 description 7
125000005842 heteroatom Chemical group 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
241000283690 Bos taurus Species 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
125000003545 alkoxy 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
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
244000052769 pathogen Species 0.000 description 6
HOBMGFDJYBEWLS-UHFFFAOYSA-N (2-methylpyrimidin-5-yl)methanol Chemical compound CC1=NC=C(CO)C=N1 HOBMGFDJYBEWLS-UHFFFAOYSA-N 0.000 description 5
BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
206010025323 Lymphomas Diseases 0.000 description 5
241000223105 Trypanosoma brucei Species 0.000 description 5
125000000304 alkynyl group Chemical group 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
230000004663 cell proliferation Effects 0.000 description 5
125000001183 hydrocarbyl group Chemical group 0.000 description 5
239000012729 immediate-release (IR) formulation Substances 0.000 description 5
125000003367 polycyclic group Polymers 0.000 description 5
108010087686 src-Family Kinases Proteins 0.000 description 5
OQUKJSVQMVBUBY-UHFFFAOYSA-N 1-bromo-3-fluoro-5-iodobenzene Chemical compound FC1=CC(Br)=CC(I)=C1 OQUKJSVQMVBUBY-UHFFFAOYSA-N 0.000 description 4
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 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
230000004913 activation Effects 0.000 description 4
239000008186 active pharmaceutical agent Substances 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
210000003719 b-lymphocyte Anatomy 0.000 description 4
201000008680 babesiosis Diseases 0.000 description 4
238000000576 coating method Methods 0.000 description 4
229940125773 compound 10 Drugs 0.000 description 4
230000001419 dependent effect Effects 0.000 description 4
238000013265 extended release Methods 0.000 description 4
239000006260 foam Substances 0.000 description 4
235000019253 formic acid Nutrition 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
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 4
239000000463 material Substances 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
ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 4
230000004044 response Effects 0.000 description 4
238000004366 reverse phase liquid chromatography Methods 0.000 description 4
230000011664 signaling Effects 0.000 description 4
239000002904 solvent Substances 0.000 description 4
102000009076 src-Family Kinases Human genes 0.000 description 4
239000007858 starting material Substances 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
238000010189 synthetic method Methods 0.000 description 4
239000003826 tablet Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 3
201000001320 Atherosclerosis Diseases 0.000 description 3
241000223836 Babesia Species 0.000 description 3
208000003495 Coccidiosis Diseases 0.000 description 3
RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
206010023076 Isosporiasis Diseases 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 3
241001494479 Pecora Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
206010052779 Transplant rejections Diseases 0.000 description 3
230000007815 allergy Effects 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
230000037396 body weight Effects 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
230000003915 cell function Effects 0.000 description 3
230000010261 cell growth Effects 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
229940125851 compound 27 Drugs 0.000 description 3
239000008187 granular material Substances 0.000 description 3
210000003630 histaminocyte Anatomy 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
206010025135 lupus erythematosus Diseases 0.000 description 3
201000006417 multiple sclerosis Diseases 0.000 description 3
239000006191 orally-disintegrating tablet Substances 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
239000010452 phosphate Substances 0.000 description 3
239000003757 phosphotransferase inhibitor Substances 0.000 description 3
230000008569 process Effects 0.000 description 3
239000000047 product Substances 0.000 description 3
230000019491 signal transduction Effects 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
210000004989 spleen cell Anatomy 0.000 description 3
210000004988 splenocyte Anatomy 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000758 substrate Substances 0.000 description 3
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 description 3
230000000699 topical effect Effects 0.000 description 3
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 3
GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-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
IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
JCPJGUPQZDEZQH-UHFFFAOYSA-N 3-bromo-5-fluorophenol Chemical compound OC1=CC(F)=CC(Br)=C1 JCPJGUPQZDEZQH-UHFFFAOYSA-N 0.000 description 2
208000000230 African Trypanosomiasis Diseases 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
206010059245 Angiopathy Diseases 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
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 description 2
206010006187 Breast cancer Diseases 0.000 description 2
208000026310 Breast neoplasm Diseases 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
208000008953 Cryptosporidiosis Diseases 0.000 description 2
206010011502 Cryptosporidiosis infection Diseases 0.000 description 2
241000223936 Cryptosporidium parvum Species 0.000 description 2
229920000858 Cyclodextrin Polymers 0.000 description 2
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 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
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
208000009329 Graft vs Host Disease Diseases 0.000 description 2
208000002250 Hematologic Neoplasms Diseases 0.000 description 2
101000864342 Homo sapiens Tyrosine-protein kinase BTK Proteins 0.000 description 2
239000005511 L01XE05 - Sorafenib Substances 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
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 2
OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
241000223960 Plasmodium falciparum Species 0.000 description 2
241001505293 Plasmodium ovale Species 0.000 description 2
108050002122 Protein kinase domains Proteins 0.000 description 2
102000012515 Protein kinase domains Human genes 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
206010037660 Pyrexia Diseases 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
241000224003 Sarcocystis Species 0.000 description 2
241000282887 Suidae Species 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical group OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
201000009594 Systemic Scleroderma Diseases 0.000 description 2
206010042953 Systemic sclerosis Diseases 0.000 description 2
210000001744 T-lymphocyte Anatomy 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
241000223104 Trypanosoma 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
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 2
230000001594 aberrant effect Effects 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
239000003146 anticoagulant agent Substances 0.000 description 2
229940125681 anticonvulsant agent Drugs 0.000 description 2
229940082992 antihypertensives mao inhibitors Drugs 0.000 description 2
229960004676 antithrombotic agent Drugs 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
239000002585 base Substances 0.000 description 2
230000008901 benefit Effects 0.000 description 2
150000001557 benzodiazepines Chemical class 0.000 description 2
KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
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 2
210000001185 bone marrow Anatomy 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
238000001516 cell proliferation assay Methods 0.000 description 2
230000005754 cellular signaling Effects 0.000 description 2
239000011248 coating agent Substances 0.000 description 2
206010009887 colitis Diseases 0.000 description 2
229940125904 compound 1 Drugs 0.000 description 2
229940125758 compound 15 Drugs 0.000 description 2
229940125810 compound 20 Drugs 0.000 description 2
229940126086 compound 21 Drugs 0.000 description 2
229940126208 compound 22 Drugs 0.000 description 2
229940125833 compound 23 Drugs 0.000 description 2
229940125961 compound 24 Drugs 0.000 description 2
229940125846 compound 25 Drugs 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
201000001981 dermatomyositis Diseases 0.000 description 2
229940052760 dopamine agonists 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
230000002255 enzymatic effect Effects 0.000 description 2
229940088598 enzyme Drugs 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
235000019441 ethanol Nutrition 0.000 description 2
MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 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
230000014509 gene expression Effects 0.000 description 2
208000024908 graft versus host disease Diseases 0.000 description 2
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
230000003394 haemopoietic effect Effects 0.000 description 2
208000014829 head and neck neoplasm Diseases 0.000 description 2
230000036541 health Effects 0.000 description 2
102000053446 human BTK Human genes 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
208000009326 ileitis Diseases 0.000 description 2
150000003949 imides Chemical class 0.000 description 2
230000036737 immune function Effects 0.000 description 2
230000001771 impaired effect Effects 0.000 description 2
229940047124 interferons Drugs 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
238000000021 kinase assay Methods 0.000 description 2
239000007788 liquid Substances 0.000 description 2
210000002540 macrophage Anatomy 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
230000004770 neurodegeneration Effects 0.000 description 2
210000000440 neutrophil Anatomy 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
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
239000008188 pellet Substances 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000035755 proliferation Effects 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
229960003787 sorafenib Drugs 0.000 description 2
239000000021 stimulant Substances 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
239000000725 suspension Substances 0.000 description 2
238000001308 synthesis method Methods 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
230000001960 triggered effect Effects 0.000 description 2
208000019553 vascular disease Diseases 0.000 description 2
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
XFQNWPYGEGCIMF-HCUGAJCMSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].[Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 XFQNWPYGEGCIMF-HCUGAJCMSA-N 0.000 description 1
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
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 description 1
DJCJOWDAAZEMCI-UHFFFAOYSA-N (6-methylpyridin-3-yl)methanol Chemical compound CC1=CC=C(CO)C=N1 DJCJOWDAAZEMCI-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
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
FXEGEEUPPGLIIC-UHFFFAOYSA-N 1-bromo-3-fluoro-2-iodobenzene Chemical compound FC1=CC=CC(Br)=C1I FXEGEEUPPGLIIC-UHFFFAOYSA-N 0.000 description 1
MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical class CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 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
LHRMBQARSBULRX-UHFFFAOYSA-N 2-bromo-1-fluoro-4-iodobenzene Chemical compound FC1=CC=C(I)C=C1Br LHRMBQARSBULRX-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
TYMBNRMIBWOQGH-UHFFFAOYSA-N 3,3-dimethoxypropanoic acid Chemical compound COC(OC)CC(O)=O TYMBNRMIBWOQGH-UHFFFAOYSA-N 0.000 description 1
MEZFCUMYQXLFOV-UHFFFAOYSA-N 3-bromo-2-fluorophenol Chemical compound OC1=CC=CC(Br)=C1F MEZFCUMYQXLFOV-UHFFFAOYSA-N 0.000 description 1
UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical class C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
GPPSQLLIFNWNSB-UHFFFAOYSA-N 3-phenylmethoxycyclobutan-1-one Chemical compound C1C(=O)CC1OCC1=CC=CC=C1 GPPSQLLIFNWNSB-UHFFFAOYSA-N 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
WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
208000031261 Acute myeloid leukaemia 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
206010002198 Anaphylactic reaction Diseases 0.000 description 1
241000224482 Apicomplexa Species 0.000 description 1
206010003210 Arteriosclerosis Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
108091008875 B cell receptors Proteins 0.000 description 1
208000010839 B-cell chronic lymphocytic leukemia Diseases 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
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical group OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
208000020084 Bone disease Diseases 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
BUMDCRZZIAWWSP-UHFFFAOYSA-N CC(CC1)=CC(C)=C1F Chemical compound CC(CC1)=CC(C)=C1F BUMDCRZZIAWWSP-UHFFFAOYSA-N 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
WSDGYKOIWLIUME-UHFFFAOYSA-N Cc1ccc(COc2cc(F)cc(Oc(cc3)ccc3-c3c[n](C4CCOCC4)c4ncnc(N)c34)c2)cn1 Chemical compound Cc1ccc(COc2cc(F)cc(Oc(cc3)ccc3-c3c[n](C4CCOCC4)c4ncnc(N)c34)c2)cn1 WSDGYKOIWLIUME-UHFFFAOYSA-N 0.000 description 1
VGGDACKISHLAEJ-UHFFFAOYSA-N Cc1ncc(COc2cc(Br)ccc2F)cn1 Chemical compound Cc1ncc(COc2cc(Br)ccc2F)cn1 VGGDACKISHLAEJ-UHFFFAOYSA-N 0.000 description 1
GNXLRNVOAFWANB-UHFFFAOYSA-N Cc1ncc(COc2cc(F)cc(Oc(cc3)ccc3-c3c[n](C4CCOCC4)c4ncnc(N)c34)c2)cn1 Chemical compound Cc1ncc(COc2cc(F)cc(Oc(cc3)ccc3-c3c[n](C4CCOCC4)c4ncnc(N)c34)c2)cn1 GNXLRNVOAFWANB-UHFFFAOYSA-N 0.000 description 1
YKYZTWFKHRJJRR-PLQXJYEYSA-N Cc1ncc(COc2cc(F)cc(Oc(cc3)ccc3-c3c[n]([C@H](C4)C[C@H]4N4CCOCC4)c4ncnc(N)c34)c2)cn1 Chemical compound Cc1ncc(COc2cc(F)cc(Oc(cc3)ccc3-c3c[n]([C@H](C4)C[C@H]4N4CCOCC4)c4ncnc(N)c34)c2)cn1 YKYZTWFKHRJJRR-PLQXJYEYSA-N 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
229940126657 Compound 17 Drugs 0.000 description 1
229920002261 Corn starch Polymers 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
102000015554 Dopamine receptor Human genes 0.000 description 1
108050004812 Dopamine receptor Proteins 0.000 description 1
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 1
241000223924 Eimeria Species 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
239000001116 FEMA 4028 Substances 0.000 description 1
108091008794 FGF receptors Proteins 0.000 description 1
208000002476 Falciparum Malaria Diseases 0.000 description 1
JNETZJWWXCLUKM-UHFFFAOYSA-N Fc(ccc(Br)c1)c1I Chemical compound Fc(ccc(Br)c1)c1I JNETZJWWXCLUKM-UHFFFAOYSA-N 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
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
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
241000282412 Homo Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
108060003951 Immunoglobulin Proteins 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
208000004554 Leishmaniasis Diseases 0.000 description 1
229940113306 Ligase inhibitor Drugs 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
208000014767 Myeloproliferative disease Diseases 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
229910002651 NO3 Inorganic materials 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
208000012902 Nervous system disease Diseases 0.000 description 1
102000005348 Neuraminidase Human genes 0.000 description 1
108010006232 Neuraminidase Proteins 0.000 description 1
208000025966 Neurological disease Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 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
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
208000030852 Parasitic disease Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241000721454 Pemphigus Species 0.000 description 1
229940122054 Peroxisome proliferator-activated receptor delta agonist Drugs 0.000 description 1
241000286209 Phasianidae Species 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
241000224016 Plasmodium Species 0.000 description 1
206010035500 Plasmodium falciparum infection Diseases 0.000 description 1
201000011336 Plasmodium falciparum malaria Diseases 0.000 description 1
241000223821 Plasmodium malariae Species 0.000 description 1
241000223810 Plasmodium vivax Species 0.000 description 1
241000233872 Pneumocystis carinii Species 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 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
102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
241001115903 Raphus cucullatus Species 0.000 description 1
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
235000019485 Safflower oil Nutrition 0.000 description 1
241001473628 Sarcocystis suihominis Species 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
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
108091008874 T cell receptors Proteins 0.000 description 1
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
201000008754 Tenosynovial giant cell tumor Diseases 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
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
241000223997 Toxoplasma gondii Species 0.000 description 1
201000005485 Toxoplasmosis Diseases 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
241001442399 Trypanosoma brucei gambiense Species 0.000 description 1
241001442397 Trypanosoma brucei rhodesiense Species 0.000 description 1
102100029823 Tyrosine-protein kinase BTK Human genes 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
230000002159 abnormal effect Effects 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
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
230000001464 adherent 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
150000001447 alkali salts 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
125000002947 alkylene 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
230000004075 alteration Effects 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
150000001409 amidines Chemical group 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
230000036783 anaphylactic response Effects 0.000 description 1
208000003455 anaphylaxis Diseases 0.000 description 1
230000001093 anti-cancer Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000719 anti-leukaemic effect Effects 0.000 description 1
239000003430 antimalarial agent Substances 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000005784 autoimmunity Effects 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
235000011175 beta-cyclodextrine Nutrition 0.000 description 1
229960004853 betadex Drugs 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000008827 biological function Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
230000036765 blood level Effects 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
229910052796 boron Inorganic materials 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
239000006172 buffering agent Substances 0.000 description 1
FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
230000009702 cancer cell proliferation Effects 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
229910002091 carbon monoxide Inorganic materials 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
238000000423 cell based assay Methods 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
238000012054 celltiter-glo Methods 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
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
229940125782 compound 2 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
238000013267 controlled drug release Methods 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 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
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000004122 cyclic group Chemical group 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
210000000172 cytosol Anatomy 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
238000002716 delivery method Methods 0.000 description 1
238000001514 detection method Methods 0.000 description 1
229910052805 deuterium Inorganic materials 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
TUGSJNQAIMFEDY-UHFFFAOYSA-N dimethyl pyridine-2,5-dicarboxylate Chemical compound COC(=O)C1=CC=C(C(=O)OC)N=C1 TUGSJNQAIMFEDY-UHFFFAOYSA-N 0.000 description 1
UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
231100000676 disease causative agent Toxicity 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
229940052764 dopaminergic anti-parkinson drug mao b inhibitors Drugs 0.000 description 1
230000003828 downregulation Effects 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
239000003844 drug implant Substances 0.000 description 1
208000001848 dysentery Diseases 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction 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
210000003743 erythrocyte Anatomy 0.000 description 1
201000004101 esophageal cancer Diseases 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
238000002474 experimental method Methods 0.000 description 1
239000003889 eye drop Substances 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
238000010579 first pass effect Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000012458 free base Substances 0.000 description 1
125000000524 functional group Chemical group 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
208000005017 glioblastoma Diseases 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
230000012010 growth Effects 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
125000001475 halogen functional group Chemical group 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
CHXARDKIHSVFDK-UHFFFAOYSA-N hexylphosphane Chemical compound CCCCCCP CHXARDKIHSVFDK-UHFFFAOYSA-N 0.000 description 1
208000029080 human African trypanosomiasis Diseases 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
150000002466 imines Chemical group 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
230000002584 immunomodulator Effects 0.000 description 1
229940125721 immunosuppressive agent 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
238000011065 in-situ storage Methods 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000009545 invasion Effects 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
SYJRVVFAAIUVDH-UHFFFAOYSA-N ipa isopropanol Chemical compound CC(C)O.CC(C)O SYJRVVFAAIUVDH-UHFFFAOYSA-N 0.000 description 1
235000000396 iron Nutrition 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
238000002955 isolation Methods 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
150000003951 lactams Chemical class 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000002386 leaching Methods 0.000 description 1
231100001231 less toxic Toxicity 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
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000000314 lubricant Substances 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
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
239000011654 magnesium acetate Substances 0.000 description 1
235000011285 magnesium acetate Nutrition 0.000 description 1
229940069446 magnesium acetate Drugs 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
159000000003 magnesium salts Chemical class 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
230000036210 malignancy Effects 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
208000026037 malignant tumor of neck Diseases 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 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
230000035772 mutation Effects 0.000 description 1
229940014456 mycophenolate 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
DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical group [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 description 1
WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000005487 naphthalate group Chemical group 0.000 description 1
230000008693 nausea Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
229940074355 nitric acid Drugs 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
210000004940 nucleus Anatomy 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
210000003463 organelle Anatomy 0.000 description 1
LMYJGUNNJIDROI-UHFFFAOYSA-N oxan-4-ol Chemical compound OC1CCOCC1 LMYJGUNNJIDROI-UHFFFAOYSA-N 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
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
230000036470 plasma concentration Effects 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
229920000573 polyethylene Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
108090000765 processed proteins & peptides Proteins 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
238000001959 radiotherapy Methods 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
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
230000007974 regulation of B cell activation Effects 0.000 description 1
230000027174 regulation of B cell differentiation Effects 0.000 description 1
230000020129 regulation of cell death Effects 0.000 description 1
230000024833 regulation of cytokine production Effects 0.000 description 1
230000012121 regulation of immune response Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 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
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 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
102000034285 signal transducing proteins Human genes 0.000 description 1
108091006024 signal transducing proteins Proteins 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
231100000245 skin permeability Toxicity 0.000 description 1
201000002612 sleeping sickness Diseases 0.000 description 1
150000003384 small molecules Chemical class 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
159000000000 sodium salts Chemical class 0.000 description 1
WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 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
206010041823 squamous cell carcinoma Diseases 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
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
201000004595 synovitis Diseases 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 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
150000003512 tertiary amines Chemical class 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
MHNHYTDAOYJUEZ-UHFFFAOYSA-N triphenylphosphane Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 MHNHYTDAOYJUEZ-UHFFFAOYSA-N 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
235000021081 unsaturated fats Nutrition 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
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000029812 viral genome replication Effects 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
230000009278 visceral effect Effects 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1