HUE028999T2 - Bicyclic heterocyclic compounds as protein tyrosine kinase inhibitors - Google Patents

Info

Publication number

HUE028999T2

HUE028999T2 HUE08806575A HUE08806575A HUE028999T2 HU E028999 T2 HUE028999 T2 HU E028999T2 HU E08806575 A HUE08806575 A HU E08806575A HU E08806575 A HUE08806575 A HU E08806575A HU E028999 T2 HUE028999 T2 HU E028999T2

Authority

HU

Hungary

Prior art keywords

compound

group

compounds

ring

groups

Prior art date

2007-10-12

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002618 bicyclic heterocycle group Chemical group 0.000 title description 3
• 239000005483 tyrosine kinase inhibitor Substances 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 395
• 206010028980 Neoplasm Diseases 0.000 claims description 123
• 125000000623 heterocyclic group Chemical group 0.000 claims description 112
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 102
• 125000000217 alkyl group Chemical group 0.000 claims description 93
• 229910052757 nitrogen Inorganic materials 0.000 claims description 93
• 238000011282 treatment Methods 0.000 claims description 86
• 125000003118 aryl group Chemical group 0.000 claims description 63
• 229910052739 hydrogen Inorganic materials 0.000 claims description 51
• 201000011510 cancer Diseases 0.000 claims description 49
• 239000001257 hydrogen Substances 0.000 claims description 48
• 125000004122 cyclic group Chemical group 0.000 claims description 47
• 150000003839 salts Chemical class 0.000 claims description 47
• 239000003112 inhibitor Substances 0.000 claims description 37
• 150000002367 halogens Chemical class 0.000 claims description 32
• 229910052736 halogen Inorganic materials 0.000 claims description 31
• 125000002837 carbocyclic group Chemical group 0.000 claims description 29
• 239000002253 acid Substances 0.000 claims description 27
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 27
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
• 239000008194 pharmaceutical composition Substances 0.000 claims description 24
• 108090000623 proteins and genes Proteins 0.000 claims description 24
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
• 150000002431 hydrogen Chemical class 0.000 claims description 21
• 125000003342 alkenyl group Chemical group 0.000 claims description 17
• 125000002950 monocyclic group Chemical group 0.000 claims description 14
• 102000004169 proteins and genes Human genes 0.000 claims description 14
• 125000001425 triazolyl group Chemical group 0.000 claims description 10
• 239000000126 substance Substances 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
• 230000002265 prevention Effects 0.000 claims description 6
• 238000002560 therapeutic procedure Methods 0.000 claims description 6
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 5
• 150000002391 heterocyclic compounds Chemical class 0.000 claims description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid group Chemical group C(CCCCCCC\C=C/CCCCCCCC)(=O)O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
• 125000001475 halogen functional group Chemical group 0.000 claims 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
• 125000002252 acyl group Chemical group 0.000 claims 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
• 238000000034 method Methods 0.000 description 120
• -1 - C=N Chemical group 0.000 description 85
• 108091008794 FGF receptors Proteins 0.000 description 81
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 75
• 238000006243 chemical reaction Methods 0.000 description 70
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 69
• 201000010099 disease Diseases 0.000 description 63
• 239000000203 mixture Substances 0.000 description 54
• 230000035772 mutation Effects 0.000 description 51
• 230000000694 effects Effects 0.000 description 49
• 125000003545 alkoxy group Chemical group 0.000 description 48
• 108091008606 PDGF receptors Proteins 0.000 description 42
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 42
• 210000004027 cell Anatomy 0.000 description 41
• 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 39
• 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 39
• 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 39
• 108091008605 VEGF receptors Proteins 0.000 description 38
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 37
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 37
• 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 37
• 230000033115 angiogenesis Effects 0.000 description 35
• 239000003814 drug Substances 0.000 description 35
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
• ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 31
• 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 31
• 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 31
• 239000012453 solvate Substances 0.000 description 29
• 108091000080 Phosphotransferase Proteins 0.000 description 28
• 102000020233 phosphotransferase Human genes 0.000 description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
• 150000001408 amides Chemical class 0.000 description 27
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 26
• 125000000392 cycloalkenyl group Chemical group 0.000 description 26
• 230000002401 inhibitory effect Effects 0.000 description 26
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
• 125000004433 nitrogen atom Chemical group N* 0.000 description 25
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
• 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 23
• 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 23
• 238000011321 prophylaxis Methods 0.000 description 23
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
• 125000005842 heteroatom Chemical group 0.000 description 22
• 230000003827 upregulation Effects 0.000 description 22
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 21
• 229910052799 carbon Inorganic materials 0.000 description 21
• 239000003795 chemical substances by application Substances 0.000 description 21
• 125000001072 heteroaryl group Chemical group 0.000 description 21
• 230000001404 mediated effect Effects 0.000 description 21
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 21
• 239000002904 solvent Substances 0.000 description 21
• 210000001519 tissue Anatomy 0.000 description 21
• 230000004913 activation Effects 0.000 description 19
• 150000002148 esters Chemical class 0.000 description 19
• 230000014509 gene expression Effects 0.000 description 19
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 18
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 18
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 18
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 18
• 125000004093 cyano group Chemical group *C#N 0.000 description 18
• 238000003786 synthesis reaction Methods 0.000 description 18
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 17
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 17
• 208000034578 Multiple myelomas Diseases 0.000 description 17
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 17
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 17
• 230000015572 biosynthetic process Effects 0.000 description 17
• 239000003446 ligand Substances 0.000 description 17
• 230000008569 process Effects 0.000 description 17
• 239000000047 product Substances 0.000 description 17
• 239000000243 solution Substances 0.000 description 17
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
• 102000018233 Fibroblast Growth Factor Human genes 0.000 description 16
• 108050007372 Fibroblast Growth Factor Proteins 0.000 description 16
• 238000009472 formulation Methods 0.000 description 16
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
• 206010035226 Plasma cell myeloma Diseases 0.000 description 15
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
• 125000000304 alkynyl group Chemical group 0.000 description 15
• 239000002585 base Substances 0.000 description 15
• 229940079593 drug Drugs 0.000 description 15
• 230000005764 inhibitory process Effects 0.000 description 15
• 230000002018 overexpression Effects 0.000 description 15
• 229910052763 palladium Inorganic materials 0.000 description 15
• 102000004190 Enzymes Human genes 0.000 description 14
• 108090000790 Enzymes Proteins 0.000 description 14
• 230000002159 abnormal effect Effects 0.000 description 14
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 14
• 238000001802 infusion Methods 0.000 description 14
• 150000001204 N-oxides Chemical class 0.000 description 13
• 238000003556 assay Methods 0.000 description 13
• 125000002619 bicyclic group Chemical group 0.000 description 13
• 229940126864 fibroblast growth factor Drugs 0.000 description 13
• 230000001965 increasing effect Effects 0.000 description 13
• 125000004076 pyridyl group Chemical group 0.000 description 13
• 102000005962 receptors Human genes 0.000 description 13
• 108020003175 receptors Proteins 0.000 description 13
• 239000003054 catalyst Substances 0.000 description 12
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 125000003373 pyrazinyl group Chemical group 0.000 description 12
• 239000003826 tablet Substances 0.000 description 12
• 125000001113 thiadiazolyl group Chemical group 0.000 description 12
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 12
• 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 11
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 11
• 230000003213 activating effect Effects 0.000 description 11
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
• 238000005859 coupling reaction Methods 0.000 description 11
• 150000004820 halides Chemical class 0.000 description 11
• 238000010438 heat treatment Methods 0.000 description 11
• 238000004519 manufacturing process Methods 0.000 description 11
• 230000003287 optical effect Effects 0.000 description 11
• 229910052760 oxygen Inorganic materials 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 150000001299 aldehydes Chemical class 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 230000008901 benefit Effects 0.000 description 10
• 239000003153 chemical reaction reagent Substances 0.000 description 10
• 238000002347 injection Methods 0.000 description 10
• 239000007924 injection Substances 0.000 description 10
• 239000000758 substrate Substances 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 9
• 206010006187 Breast cancer Diseases 0.000 description 9
• 208000026310 Breast neoplasm Diseases 0.000 description 9
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
• 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 9
• 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 9
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 238000006069 Suzuki reaction reaction Methods 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 9
• 230000027455 binding Effects 0.000 description 9
• 239000000872 buffer Substances 0.000 description 9
• 230000010261 cell growth Effects 0.000 description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 230000035755 proliferation Effects 0.000 description 9
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 9
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 9
• 230000002829 reductive effect Effects 0.000 description 9
• 230000019491 signal transduction Effects 0.000 description 9
• 208000011580 syndromic disease Diseases 0.000 description 9
• 206010005003 Bladder cancer Diseases 0.000 description 8
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 8
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
• 206010060862 Prostate cancer Diseases 0.000 description 8
• 102000001253 Protein Kinase Human genes 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 239000002775 capsule Substances 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 230000007423 decrease Effects 0.000 description 8
• 238000001514 detection method Methods 0.000 description 8
• 239000003102 growth factor Substances 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• 239000000314 lubricant Substances 0.000 description 8
• 238000004949 mass spectrometry Methods 0.000 description 8
• 150000007523 nucleic acids Chemical class 0.000 description 8
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
• 239000000546 pharmaceutical excipient Substances 0.000 description 8
• 108060006633 protein kinase Proteins 0.000 description 8
• 229910052702 rhenium Inorganic materials 0.000 description 8
• 239000007787 solid Substances 0.000 description 8
• 229910052717 sulfur Inorganic materials 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• 201000010028 Acrocephalosyndactylia Diseases 0.000 description 7
• 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 7
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 7
• 230000005856 abnormality Effects 0.000 description 7
• 150000001733 carboxylic acid esters Chemical class 0.000 description 7
• 239000011248 coating agent Substances 0.000 description 7
• 238000000576 coating method Methods 0.000 description 7
• 230000000875 corresponding effect Effects 0.000 description 7
• 238000011161 development Methods 0.000 description 7
• 230000018109 developmental process Effects 0.000 description 7
• 238000003745 diagnosis Methods 0.000 description 7
• 239000002552 dosage form Substances 0.000 description 7
• 125000002883 imidazolyl group Chemical group 0.000 description 7
• 238000004811 liquid chromatography Methods 0.000 description 7
• 230000003211 malignant effect Effects 0.000 description 7
• 229910052751 metal Inorganic materials 0.000 description 7
• 239000002184 metal Substances 0.000 description 7
• 239000000651 prodrug Substances 0.000 description 7
• 229940002612 prodrug Drugs 0.000 description 7
• 230000011664 signaling Effects 0.000 description 7
• 238000010561 standard procedure Methods 0.000 description 7
• 229940124597 therapeutic agent Drugs 0.000 description 7
• BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 6
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 6
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
• 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 6
• 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 6
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
• 201000004014 Pfeiffer syndrome Diseases 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 6
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 6
• 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 6
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 6
• 125000003277 amino group Chemical group 0.000 description 6
• 230000002491 angiogenic effect Effects 0.000 description 6
• 230000009286 beneficial effect Effects 0.000 description 6
• 238000010168 coupling process Methods 0.000 description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
• 230000001419 dependent effect Effects 0.000 description 6
• 230000004069 differentiation Effects 0.000 description 6
• 208000035475 disorder Diseases 0.000 description 6
• 235000019439 ethyl acetate Nutrition 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 238000004108 freeze drying Methods 0.000 description 6
• 230000004077 genetic alteration Effects 0.000 description 6
• 230000012010 growth Effects 0.000 description 6
• 238000009396 hybridization Methods 0.000 description 6
• 239000002502 liposome Substances 0.000 description 6
• 210000004072 lung Anatomy 0.000 description 6
• 238000002595 magnetic resonance imaging Methods 0.000 description 6
• 230000007246 mechanism Effects 0.000 description 6
• 108020004707 nucleic acids Proteins 0.000 description 6
• 102000039446 nucleic acids Human genes 0.000 description 6
• 229920000642 polymer Polymers 0.000 description 6
• 229910000160 potassium phosphate Inorganic materials 0.000 description 6
• 235000011009 potassium phosphates Nutrition 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 230000002062 proliferating effect Effects 0.000 description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• 238000011160 research Methods 0.000 description 6
• 239000000523 sample Substances 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 238000012216 screening Methods 0.000 description 6
• 239000006104 solid solution Substances 0.000 description 6
• 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 6
• 210000005166 vasculature Anatomy 0.000 description 6
• HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 5
• 102100031126 6-phosphogluconolactonase Human genes 0.000 description 5
• 108010029731 6-phosphogluconolactonase Proteins 0.000 description 5
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 5
• 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 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 5
• 238000002965 ELISA Methods 0.000 description 5
• VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 5
• 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 5
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 5
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
• 238000010240 RT-PCR analysis Methods 0.000 description 5
• 208000024770 Thyroid neoplasm Diseases 0.000 description 5
• 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 5
• 230000006907 apoptotic process Effects 0.000 description 5
• 150000001502 aryl halides Chemical class 0.000 description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
• 230000004071 biological effect Effects 0.000 description 5
• 238000006555 catalytic reaction Methods 0.000 description 5
• 230000004663 cell proliferation Effects 0.000 description 5
• 208000019065 cervical carcinoma Diseases 0.000 description 5
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 5
• 230000008878 coupling Effects 0.000 description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 238000002405 diagnostic procedure Methods 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
• 239000007884 disintegrant Substances 0.000 description 5
• 210000002889 endothelial cell Anatomy 0.000 description 5
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
• 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 5
• 229910052731 fluorine Inorganic materials 0.000 description 5
• 239000011737 fluorine Substances 0.000 description 5
• 210000001035 gastrointestinal tract Anatomy 0.000 description 5
• 208000005017 glioblastoma Diseases 0.000 description 5
• 230000007062 hydrolysis Effects 0.000 description 5
• 238000006460 hydrolysis reaction Methods 0.000 description 5
• 238000000338 in vitro Methods 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 239000007972 injectable composition Substances 0.000 description 5
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• 150000002576 ketones Chemical class 0.000 description 5
• 208000032839 leukemia Diseases 0.000 description 5
• 208000020816 lung neoplasm Diseases 0.000 description 5
• 238000005259 measurement Methods 0.000 description 5
• 108020004999 messenger RNA Proteins 0.000 description 5
• 238000010606 normalization Methods 0.000 description 5
• 125000001715 oxadiazolyl group Chemical group 0.000 description 5
• 239000001301 oxygen Substances 0.000 description 5
• 235000015108 pies Nutrition 0.000 description 5
• 230000001023 pro-angiogenic effect Effects 0.000 description 5
• 210000002307 prostate Anatomy 0.000 description 5
• LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 238000006722 reduction reaction Methods 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 230000002441 reversible effect Effects 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 125000001424 substituent group Chemical group 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• 210000001685 thyroid gland Anatomy 0.000 description 5
• 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 5
• 230000004614 tumor growth Effects 0.000 description 5
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 5
• 230000029663 wound healing Effects 0.000 description 5
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• 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 4
• MORDDYJPVSRHAG-UHFFFAOYSA-N 7-chloro-6h-imidazo[1,2-c]pyrimidin-5-one Chemical compound O=C1NC(Cl)=CC2=NC=CN21 MORDDYJPVSRHAG-UHFFFAOYSA-N 0.000 description 4
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 4
• 208000009283 Craniosynostoses Diseases 0.000 description 4
• 230000004544 DNA amplification Effects 0.000 description 4
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
• 206010014759 Endometrial neoplasm Diseases 0.000 description 4
• 101150021185 FGF gene Proteins 0.000 description 4
• 206010016654 Fibrosis Diseases 0.000 description 4
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• 206010018364 Glomerulonephritis Diseases 0.000 description 4
• 239000007995 HEPES buffer Substances 0.000 description 4
• 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 4
• 206010021143 Hypoxia Diseases 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 208000000265 Lobular Carcinoma Diseases 0.000 description 4
• 239000007993 MOPS buffer Substances 0.000 description 4
• 238000005481 NMR spectroscopy Methods 0.000 description 4
• 206010033128 Ovarian cancer Diseases 0.000 description 4
• 108010029485 Protein Isoforms Proteins 0.000 description 4
• 102000001708 Protein Isoforms Human genes 0.000 description 4
• 208000005718 Stomach Neoplasms Diseases 0.000 description 4
• 230000001594 aberrant effect Effects 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 230000003321 amplification Effects 0.000 description 4
• 125000002393 azetidinyl group Chemical group 0.000 description 4
• 238000001574 biopsy Methods 0.000 description 4
• 201000001531 bladder carcinoma Diseases 0.000 description 4
• 210000004369 blood Anatomy 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 208000029742 colonic neoplasm Diseases 0.000 description 4
• 238000002648 combination therapy Methods 0.000 description 4
• 239000002299 complementary DNA Substances 0.000 description 4
• 210000004714 cranial suture Anatomy 0.000 description 4
• 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 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
• 230000002354 daily effect Effects 0.000 description 4
• 125000004185 ester group Chemical group 0.000 description 4
• 230000004761 fibrosis Effects 0.000 description 4
• 230000003176 fibrotic effect Effects 0.000 description 4
• 238000005755 formation reaction Methods 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 239000008273 gelatin Substances 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 description 4
• 229940088597 hormone Drugs 0.000 description 4
• 239000005556 hormone Substances 0.000 description 4
• 150000002430 hydrocarbons Chemical group 0.000 description 4
• 230000007954 hypoxia Effects 0.000 description 4
• 238000007901 in situ hybridization Methods 0.000 description 4
• 230000003834 intracellular effect Effects 0.000 description 4
• 238000002955 isolation Methods 0.000 description 4
• 239000008101 lactose Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 239000003550 marker Substances 0.000 description 4
• KYHRVKMXYXBEQN-UHFFFAOYSA-N methyl imidazo[1,2-a]pyridine-7-carboxylate Chemical compound C1=C(C(=O)OC)C=CN2C=CN=C21 KYHRVKMXYXBEQN-UHFFFAOYSA-N 0.000 description 4
• RXLCKDMEKFNFSF-UHFFFAOYSA-N n-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,3,4-thiadiazol-2-amine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(NC=2SC=NN=2)=C1 RXLCKDMEKFNFSF-UHFFFAOYSA-N 0.000 description 4
• 208000015122 neurodegenerative disease Diseases 0.000 description 4
• 125000006574 non-aromatic ring group Chemical group 0.000 description 4
• 238000003199 nucleic acid amplification method Methods 0.000 description 4
• 239000003960 organic solvent Substances 0.000 description 4
• 230000011164 ossification Effects 0.000 description 4
• 239000007800 oxidant agent Substances 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• 239000002798 polar solvent Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 201000001514 prostate carcinoma Diseases 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 208000005069 pulmonary fibrosis Diseases 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 4
• 230000004044 response Effects 0.000 description 4
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 description 4
• 102200143304 rs351855 Human genes 0.000 description 4
• 230000012488 skeletal system development Effects 0.000 description 4
• 150000003384 small molecules Chemical class 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 238000007920 subcutaneous administration Methods 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 201000003896 thanatophoric dysplasia Diseases 0.000 description 4
• 229910052720 vanadium Inorganic materials 0.000 description 4
• 239000003643 water by type Substances 0.000 description 4
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 3
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 3
• QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 3
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
• MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 description 3
• XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 3
• 125000002373 5 membered heterocyclic group Chemical group 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
• 229930024421 Adenine Natural products 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
• 201000001320 Atherosclerosis Diseases 0.000 description 3
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• 206010066946 Craniofacial dysostosis Diseases 0.000 description 3
• 206010049889 Craniosynostosis Diseases 0.000 description 3
• 201000006526 Crouzon syndrome Diseases 0.000 description 3
• 102000004127 Cytokines Human genes 0.000 description 3
• 108090000695 Cytokines Proteins 0.000 description 3
• 108020004414 DNA Proteins 0.000 description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
• 206010014733 Endometrial cancer Diseases 0.000 description 3
• 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 3
• 208000034951 Genetic Translocation Diseases 0.000 description 3
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
• 101000617130 Homo sapiens Stromal cell-derived factor 1 Proteins 0.000 description 3
• 206010020772 Hypertension Diseases 0.000 description 3
• 208000009289 Jackson-Weiss syndrome Diseases 0.000 description 3
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 3
• 239000000232 Lipid Bilayer Substances 0.000 description 3
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
• WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical class O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
• 208000014767 Myeloproliferative disease Diseases 0.000 description 3
• 102000043276 Oncogene Human genes 0.000 description 3
• 108700020796 Oncogene Proteins 0.000 description 3
• 206010061535 Ovarian neoplasm Diseases 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 3
• 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 239000005864 Sulphur Substances 0.000 description 3
• 239000012317 TBTU Substances 0.000 description 3
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 3
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
• 229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 0.000 description 3
• 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 3
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
• 229960000583 acetic acid Drugs 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 125000004423 acyloxy group Chemical group 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 150000008064 anhydrides Chemical class 0.000 description 3
• 239000003963 antioxidant agent Substances 0.000 description 3
• 235000006708 antioxidants Nutrition 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• 239000012131 assay buffer Substances 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 239000012472 biological sample Substances 0.000 description 3
• 230000036772 blood pressure Effects 0.000 description 3
• 210000004204 blood vessel Anatomy 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 125000005621 boronate group Chemical class 0.000 description 3
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical class OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
• 210000000481 breast Anatomy 0.000 description 3
• 239000007963 capsule composition Substances 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 229910002091 carbon monoxide Inorganic materials 0.000 description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
• 125000002843 carboxylic acid group Chemical group 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 229960002412 cediranib Drugs 0.000 description 3
• 230000032823 cell division Effects 0.000 description 3
• 230000033077 cellular process Effects 0.000 description 3
• 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 3
• 210000001072 colon Anatomy 0.000 description 3
• 230000002596 correlated effect Effects 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 230000008021 deposition Effects 0.000 description 3
• 238000001212 derivatisation Methods 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 238000006073 displacement reaction Methods 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• 230000002357 endometrial effect Effects 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 239000012634 fragment Substances 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 206010017758 gastric cancer Diseases 0.000 description 3
• 230000002496 gastric effect Effects 0.000 description 3
• 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 3
• 229960002897 heparin Drugs 0.000 description 3
• 229920000669 heparin Polymers 0.000 description 3
• 230000002209 hydrophobic effect Effects 0.000 description 3
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 3
• 229960002411 imatinib Drugs 0.000 description 3
• YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 3
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 230000000977 initiatory effect Effects 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 125000000468 ketone group Chemical group 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• 201000005202 lung cancer Diseases 0.000 description 3
• 230000009401 metastasis Effects 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• SVWWNEYBEFASMP-UHFFFAOYSA-N methyl 2-aminopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(N)=C1 SVWWNEYBEFASMP-UHFFFAOYSA-N 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 239000003607 modifier Substances 0.000 description 3
• 201000002740 oral squamous cell carcinoma Diseases 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 230000007170 pathology Effects 0.000 description 3
• 230000002085 persistent effect Effects 0.000 description 3
• 230000026731 phosphorylation Effects 0.000 description 3
• 238000006366 phosphorylation reaction Methods 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
• 125000002577 pseudohalo group Chemical group 0.000 description 3
• DVUBDHRTVYLIPA-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine Chemical group C1=CC=CN2N=CC=C21 DVUBDHRTVYLIPA-UHFFFAOYSA-N 0.000 description 3
• 125000003226 pyrazolyl group Chemical group 0.000 description 3
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
• 230000002285 radioactive effect Effects 0.000 description 3
• 230000001105 regulatory effect Effects 0.000 description 3
• 150000003335 secondary amines Chemical class 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 239000004017 serum-free culture medium Substances 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 239000007962 solid dispersion Substances 0.000 description 3
• 239000007909 solid dosage form Substances 0.000 description 3
• 210000002784 stomach Anatomy 0.000 description 3
• 201000011549 stomach cancer Diseases 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 239000004094 surface-active agent Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 238000010189 synthetic method Methods 0.000 description 3
• 239000007916 tablet composition Substances 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 238000013518 transcription Methods 0.000 description 3
• 230000035897 transcription Effects 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 230000005945 translocation Effects 0.000 description 3
• 238000011269 treatment regimen Methods 0.000 description 3
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• 201000005112 urinary bladder cancer Diseases 0.000 description 3
• 239000008215 water for injection Substances 0.000 description 3
• 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 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
• UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 2
• KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 2
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 2
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• OYJGEOAXBALSMM-UHFFFAOYSA-N 2,3-dihydro-1,3-thiazole Chemical compound C1NC=CS1 OYJGEOAXBALSMM-UHFFFAOYSA-N 0.000 description 2
• KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 2
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 2
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• UBOOKRVGOBKDMM-UHFFFAOYSA-N 3h-imidazo[4,5-c]pyridine Chemical compound C1=NC=C2NC=NC2=C1 UBOOKRVGOBKDMM-UHFFFAOYSA-N 0.000 description 2
• YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 2
• 125000004008 6 membered carbocyclic group Chemical group 0.000 description 2
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
• VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 208000003950 B-cell lymphoma Diseases 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
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 206010008723 Chondrodystrophy Diseases 0.000 description 2
• 229920000858 Cyclodextrin Polymers 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• 208000008334 Dermatofibrosarcoma Diseases 0.000 description 2
• 206010057070 Dermatofibrosarcoma protuberans Diseases 0.000 description 2
• 102000003951 Erythropoietin Human genes 0.000 description 2
• 108090000394 Erythropoietin Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 2
• 206010018338 Glioma Diseases 0.000 description 2
• 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
• 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
• 206010053759 Growth retardation Diseases 0.000 description 2
• 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 2
• 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 229930194542 Keto Natural products 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• 238000005004 MAS NMR spectroscopy Methods 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
• 206010029098 Neoplasm skin Diseases 0.000 description 2
• 208000022873 Ocular disease Diseases 0.000 description 2
• 206010030113 Oedema Diseases 0.000 description 2
• 208000007571 Ovarian Epithelial Carcinoma Diseases 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 2
• 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 239000012979 RPMI medium Substances 0.000 description 2
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
• 206010038389 Renal cancer Diseases 0.000 description 2
• 208000006265 Renal cell carcinoma Diseases 0.000 description 2
• 206010038933 Retinopathy of prematurity Diseases 0.000 description 2
• 229940124639 Selective inhibitor Drugs 0.000 description 2
• 206010070834 Sensitisation Diseases 0.000 description 2
• 108020004459 Small interfering RNA Proteins 0.000 description 2
• 102000005157 Somatostatin Human genes 0.000 description 2
• 108010056088 Somatostatin Proteins 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• 206010049808 Thanatophoric dwarfism Diseases 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 2
• 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 2
• 150000001241 acetals Chemical class 0.000 description 2
• 208000008919 achondroplasia Diseases 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
• 229960000643 adenine Drugs 0.000 description 2
• 206010064930 age-related macular degeneration Diseases 0.000 description 2
• 125000005907 alkyl ester group Chemical group 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 150000001409 amidines Chemical class 0.000 description 2
• 125000000539 amino acid group Chemical group 0.000 description 2
• 239000002870 angiogenesis inducing agent Substances 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 125000000129 anionic group Chemical group 0.000 description 2
• 230000003466 anti-cipated effect Effects 0.000 description 2
• 238000010913 antigen-directed enzyme pro-drug therapy Methods 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• 239000003125 aqueous solvent Substances 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 230000003305 autocrine Effects 0.000 description 2
• AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
• BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• LUFPJJNWMYZRQE-UHFFFAOYSA-N benzylsulfanylmethylbenzene Chemical compound C=1C=CC=CC=1CSCC1=CC=CC=C1 LUFPJJNWMYZRQE-UHFFFAOYSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 239000000090 biomarker Substances 0.000 description 2
• MURHTRJNCNWAQQ-UHFFFAOYSA-N bis(1-bicyclo[2.2.1]heptanyl)phosphane hydrochloride Chemical compound Cl.C1CC(C2)CCC12PC1(C2)CCC2CC1 MURHTRJNCNWAQQ-UHFFFAOYSA-N 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 125000005620 boronic acid group Chemical class 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 229940040544 bromides Drugs 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 239000004067 bulking agent Substances 0.000 description 2
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
• 238000010804 cDNA synthesis Methods 0.000 description 2
• 238000002045 capillary electrochromatography Methods 0.000 description 2
• 230000006315 carbonylation Effects 0.000 description 2
• 238000005810 carbonylation reaction Methods 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• 208000015636 celiac disease-epilepsy-cerebral calcification syndrome Diseases 0.000 description 2
• 230000003915 cell function Effects 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 230000036755 cellular response Effects 0.000 description 2
• OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical compound C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 239000007910 chewable tablet Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 2
• 208000019425 cirrhosis of liver Diseases 0.000 description 2
• 230000001276 controlling effect Effects 0.000 description 2
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
• 150000003950 cyclic amides Chemical group 0.000 description 2
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 2
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 230000002074 deregulated effect Effects 0.000 description 2
• 239000008298 dragée Substances 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 150000002081 enamines Chemical class 0.000 description 2
• 238000003821 enantio-separation Methods 0.000 description 2
• JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 2
• 229940105423 erythropoietin Drugs 0.000 description 2
• 238000010931 ester hydrolysis Methods 0.000 description 2
• 230000005284 excitation Effects 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 210000002950 fibroblast Anatomy 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 238000011049 filling Methods 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
• VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 2
• 235000008191 folinic acid Nutrition 0.000 description 2
• 239000011672 folinic acid Substances 0.000 description 2
• 230000003325 follicular Effects 0.000 description 2
• 238000007710 freezing Methods 0.000 description 2
• 230000008014 freezing Effects 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 210000004602 germ cell Anatomy 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 208000035474 group of disease Diseases 0.000 description 2
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• 201000011066 hemangioma Diseases 0.000 description 2
• 208000014951 hematologic disease Diseases 0.000 description 2
• 208000016356 hereditary diffuse gastric adenocarcinoma Diseases 0.000 description 2
• 102000058223 human VEGFA Human genes 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• 230000001631 hypertensive effect Effects 0.000 description 2
• 229960003685 imatinib mesylate Drugs 0.000 description 2
• UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical group C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 description 2
• 150000002460 imidazoles Chemical class 0.000 description 2
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 230000001939 inductive effect Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• 201000010982 kidney cancer Diseases 0.000 description 2
• 238000000021 kinase assay Methods 0.000 description 2
• 229940043355 kinase inhibitor Drugs 0.000 description 2
• 229960001691 leucovorin Drugs 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 201000007270 liver cancer Diseases 0.000 description 2
• 208000014018 liver neoplasm Diseases 0.000 description 2
• 239000012139 lysis buffer Substances 0.000 description 2
• 208000002780 macular degeneration Diseases 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 150000002825 nitriles Chemical class 0.000 description 2
• 150000002828 nitro derivatives Chemical class 0.000 description 2
• 239000012457 nonaqueous media Substances 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 125000003729 nucleotide group Chemical group 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 230000003204 osmotic effect Effects 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 239000013610 patient sample Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
• 239000000049 pigment Substances 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
• 238000010837 poor prognosis Methods 0.000 description 2
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
• OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 2
• 150000003217 pyrazoles Chemical class 0.000 description 2
• USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 238000010791 quenching Methods 0.000 description 2
• 230000000171 quenching effect Effects 0.000 description 2
• 238000001959 radiotherapy Methods 0.000 description 2
• 230000007420 reactivation Effects 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 230000000250 revascularization Effects 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 102200126674 rs121913478 Human genes 0.000 description 2
• 238000003345 scintillation counting Methods 0.000 description 2
• 238000012163 sequencing technique Methods 0.000 description 2
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 2
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
• 229960000553 somatostatin Drugs 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000003381 stabilizer Substances 0.000 description 2
• 210000000130 stem cell Anatomy 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• 150000003512 tertiary amines Chemical class 0.000 description 2
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 2
• 238000002411 thermogravimetry Methods 0.000 description 2
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 230000002103 transcriptional effect Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 206010044412 transitional cell carcinoma Diseases 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 2
• BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
• 230000005747 tumor angiogenesis Effects 0.000 description 2
• 102000003390 tumor necrosis factor Human genes 0.000 description 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
• 208000023747 urothelial carcinoma Diseases 0.000 description 2
• 230000008728 vascular permeability Effects 0.000 description 2
• 238000001262 western blot Methods 0.000 description 2
• SYSFTTYJTWPOOR-UHFFFAOYSA-N (2-diphenylphosphanyl-1-naphthalen-1-yl-3h-naphthalen-2-yl)-diphenylphosphane Chemical group C1C=C2C=CC=CC2=C(C=2C3=CC=CC=C3C=CC=2)C1(P(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)C1=CC=CC=C1 SYSFTTYJTWPOOR-UHFFFAOYSA-N 0.000 description 1
• WMJNKBXKYHXOHC-PMACEKPBSA-N (2S,3S)-2,3-dihydroxy-2,3-bis(2-methylbenzoyl)butanedioic acid Chemical compound C=1(C(=CC=CC1)C(=O)[C@]([C@](C(=O)O)(O)C(=O)C=1C(=CC=CC1)C)(O)C(=O)O)C WMJNKBXKYHXOHC-PMACEKPBSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
• RPXFFIVUGGIKCZ-UHFFFAOYSA-N (6-bromopyrazolo[1,5-a]pyrazin-2-yl)-trimethylsilane Chemical compound C1=NC(Br)=CN2N=C([Si](C)(C)C)C=C21 RPXFFIVUGGIKCZ-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
• CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
• XGYCWCIGCYGQFU-UHFFFAOYSA-N 1,2-thiazolidine 1,1-dioxide Chemical compound O=S1(=O)CCCN1 XGYCWCIGCYGQFU-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
• VMLKTERJLVWEJJ-UHFFFAOYSA-N 1,5-naphthyridine Chemical compound C1=CC=NC2=CC=CN=C21 VMLKTERJLVWEJJ-UHFFFAOYSA-N 0.000 description 1
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
• DDZGQYREBDXECY-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyrazine Chemical group C1=CN=C2C=NNC2=N1 DDZGQYREBDXECY-UHFFFAOYSA-N 0.000 description 1
• AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 1
• MXILHVKNAYIRPJ-UHFFFAOYSA-N 2,3,7,7a-tetrahydro-1h-triazolo[4,5-b]pyrazine Chemical compound N1C=CN=C2NNNC21 MXILHVKNAYIRPJ-UHFFFAOYSA-N 0.000 description 1
• OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
• JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
• ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical group CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 1
• LETNIFKIIPQERI-UHFFFAOYSA-N 2-(5-bromopyrazin-2-yl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CN=C(Br)C=N1 LETNIFKIIPQERI-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
• LDHYTBAFXANWKM-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one Chemical compound O=C1NC(N)=NC2=C1NC=N2.O=C1NC(N)=NC2=C1N=CN2 LDHYTBAFXANWKM-UHFFFAOYSA-N 0.000 description 1
• 150000005768 2-amino-5-bromopyridine Chemical class 0.000 description 1
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
• AGSDASDGMNDAIE-UHFFFAOYSA-N 2-aminopyridine-4-carboxamide Chemical group NC(=O)C1=CC=NC(N)=C1 AGSDASDGMNDAIE-UHFFFAOYSA-N 0.000 description 1
• UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
• PHPYXVIHDRDPDI-UHFFFAOYSA-N 2-bromo-1h-benzimidazole Chemical compound C1=CC=C2NC(Br)=NC2=C1 PHPYXVIHDRDPDI-UHFFFAOYSA-N 0.000 description 1
• OHTQHZVNZWWYFD-UHFFFAOYSA-N 2-bromo-5-iodopyrazine Chemical compound BrC1=CN=C(I)C=N1 OHTQHZVNZWWYFD-UHFFFAOYSA-N 0.000 description 1
• SURMYNZXHKLDFO-UHFFFAOYSA-N 2-bromopropanedial Chemical compound O=CC(Br)C=O SURMYNZXHKLDFO-UHFFFAOYSA-N 0.000 description 1
• MEQBJJUWDCYIAB-UHFFFAOYSA-N 2-chloropyridin-3-amine Chemical compound NC1=CC=CN=C1Cl MEQBJJUWDCYIAB-UHFFFAOYSA-N 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• CMRFJAMFEWYMKE-UHFFFAOYSA-N 2-oxaadamantane Chemical compound C1C(O2)CC3CC1CC2C3 CMRFJAMFEWYMKE-UHFFFAOYSA-N 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 1
• UMZCLZPXPCNKML-UHFFFAOYSA-N 2h-imidazo[4,5-d][1,3]thiazole Chemical compound C1=NC2=NCSC2=N1 UMZCLZPXPCNKML-UHFFFAOYSA-N 0.000 description 1
• FDHRGQIRBRQMPF-UHFFFAOYSA-N 2h-pyridin-1-amine Chemical compound NN1CC=CC=C1 FDHRGQIRBRQMPF-UHFFFAOYSA-N 0.000 description 1
• WPWNEKFMGCWNPR-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromene Chemical compound C1=CC=C2CCCSC2=C1 WPWNEKFMGCWNPR-UHFFFAOYSA-N 0.000 description 1
• WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• YCVAGNVTZICLNM-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzofuran Chemical compound C1CCCC2=C1C=CO2 YCVAGNVTZICLNM-UHFFFAOYSA-N 0.000 description 1
• UQEANKGXXSENNF-UHFFFAOYSA-N 4-bromo-1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Br)=CC=C1F UQEANKGXXSENNF-UHFFFAOYSA-N 0.000 description 1
• BAQKUNMKVAPWGU-UHFFFAOYSA-N 4-bromopyridin-2-amine Chemical compound NC1=CC(Br)=CC=N1 BAQKUNMKVAPWGU-UHFFFAOYSA-N 0.000 description 1
• RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• ORLGLBZRQYOWNA-UHFFFAOYSA-N 4-methylpyridin-2-amine Chemical compound CC1=CC=NC(N)=C1 ORLGLBZRQYOWNA-UHFFFAOYSA-N 0.000 description 1
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 1
• GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
• BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 description 1
• UMEIYBJBGZKZOS-UHFFFAOYSA-N 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine Chemical compound C1NCCN2C=NN=C21 UMEIYBJBGZKZOS-UHFFFAOYSA-N 0.000 description 1
• VNHBYKHXBCYPBJ-UHFFFAOYSA-N 5-ethynylimidazo[1,2-a]pyridine Chemical group C#CC1=CC=CC2=NC=CN12 VNHBYKHXBCYPBJ-UHFFFAOYSA-N 0.000 description 1
• ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
• KXPKWHNZKVLCRR-UHFFFAOYSA-N 6-aminopyrimidine-4-carboxylic acid Chemical compound NC1=CC(C(O)=O)=NC=N1 KXPKWHNZKVLCRR-UHFFFAOYSA-N 0.000 description 1
• GDXABUJCXZZPBI-UHFFFAOYSA-N 6-chloro-3h-imidazo[4,5-c]pyridine Chemical compound C1=NC(Cl)=CC2=C1N=CN2 GDXABUJCXZZPBI-UHFFFAOYSA-N 0.000 description 1
• DUKKRSPKJMHASP-UHFFFAOYSA-N 6-chloropyrimidin-4-amine Chemical compound NC1=CC(Cl)=NC=N1 DUKKRSPKJMHASP-UHFFFAOYSA-N 0.000 description 1
• BMZKZBWPMWEQAY-UHFFFAOYSA-N 6h-1,2,5-thiadiazine Chemical compound C1SN=CC=N1 BMZKZBWPMWEQAY-UHFFFAOYSA-N 0.000 description 1
• KMTAQISQHMXAQG-UHFFFAOYSA-N 7-chloroimidazo[1,2-c]pyrimidine Chemical compound C1=NC(Cl)=CC2=NC=CN21 KMTAQISQHMXAQG-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• USVZHTBPMMSRHY-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-chlorophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Cl USVZHTBPMMSRHY-UHFFFAOYSA-N 0.000 description 1
• 230000035495 ADMET Effects 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
• 206010000599 Acromegaly Diseases 0.000 description 1
• 206010000830 Acute leukaemia Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
• 102100022987 Angiogenin Human genes 0.000 description 1
• 102000009088 Angiopoietin-1 Human genes 0.000 description 1
• 108010048154 Angiopoietin-1 Proteins 0.000 description 1
• 102400000068 Angiostatin Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• 208000025490 Apert syndrome Diseases 0.000 description 1
• 208000032467 Aplastic anaemia Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 201000007791 Beare-Stevenson cutis gyrata syndrome Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 229940122361 Bisphosphonate Drugs 0.000 description 1
• 201000004569 Blindness Diseases 0.000 description 1
• 238000005696 Bodroux-Chichibabin Aldehyde synthesis reaction Methods 0.000 description 1
• 208000006386 Bone Resorption Diseases 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 1
• 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 1
• 101100243951 Caenorhabditis elegans pie-1 gene Proteins 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 206010008479 Chest Pain Diseases 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• 108010077544 Chromatin Proteins 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 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
• 102000008186 Collagen Human genes 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241001137251 Corvidae Species 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• 108091029523 CpG island Proteins 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 208000037461 Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome Diseases 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 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-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
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
• 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
• 201000004624 Dermatitis Diseases 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
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102100037241 Endoglin Human genes 0.000 description 1
• 102400001047 Endostatin Human genes 0.000 description 1
• 108010079505 Endostatins Proteins 0.000 description 1
• 208000032027 Essential Thrombocythemia 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
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 229920003134 Eudragit® polymer Polymers 0.000 description 1
• 208000006168 Ewing Sarcoma Diseases 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 101150081124 FGFR gene Proteins 0.000 description 1
• 101150025764 FGFR3 gene Proteins 0.000 description 1
• 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
• 102100028412 Fibroblast growth factor 10 Human genes 0.000 description 1
• 102100028043 Fibroblast growth factor 3 Human genes 0.000 description 1
• 102100028071 Fibroblast growth factor 7 Human genes 0.000 description 1
• 102100037362 Fibronectin Human genes 0.000 description 1
• 108010067306 Fibronectins Proteins 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 1
• 201000011240 Frontotemporal dementia Diseases 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 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
• 238000003747 Grignard reaction Methods 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 108010051696 Growth Hormone Proteins 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• IVDFJHOHABJVEH-UHFFFAOYSA-N HOCMe2CMe2OH Natural products CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 1
• 208000023661 Haematological disease Diseases 0.000 description 1
• 206010019196 Head injury Diseases 0.000 description 1
• 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101000762379 Homo sapiens Bone morphogenetic protein 4 Proteins 0.000 description 1
• 101000917237 Homo sapiens Fibroblast growth factor 10 Proteins 0.000 description 1
• 101001060280 Homo sapiens Fibroblast growth factor 3 Proteins 0.000 description 1
• 101001060261 Homo sapiens Fibroblast growth factor 7 Proteins 0.000 description 1
• 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
• 101000604123 Homo sapiens Noggin Proteins 0.000 description 1
• 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010048643 Hypereosinophilic syndrome Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 241000692870 Inachis io Species 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
• 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
• 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
• 241001435619 Lile Species 0.000 description 1
• 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 206010025421 Macule Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
• 108060004795 Methyltransferase Proteins 0.000 description 1
• 102000016397 Methyltransferase Human genes 0.000 description 1
• 208000026072 Motor neurone disease Diseases 0.000 description 1
• 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
• 101001033276 Mus musculus Interleukin-3 Proteins 0.000 description 1
• 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
• OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 206010029113 Neovascularisation Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 102100038454 Noggin Human genes 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• VYEAHXRPWKOEMY-UHFFFAOYSA-N O-(9H-fluoren-9-ylmethyl)hydroxylamine Chemical compound C1=CC=C2C(CON)C3=CC=CC=C3C2=C1 VYEAHXRPWKOEMY-UHFFFAOYSA-N 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• BHVRCUAHXVLSNX-UHFFFAOYSA-N O-[(4,5-dimethoxy-2-nitrophenyl)methyl]hydroxylamine Chemical compound COC1=CC(CON)=C([N+]([O-])=O)C=C1OC BHVRCUAHXVLSNX-UHFFFAOYSA-N 0.000 description 1
• 108010016076 Octreotide Proteins 0.000 description 1
• 108091034117 Oligonucleotide Proteins 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 102000004316 Oxidoreductases Human genes 0.000 description 1
• 108090000854 Oxidoreductases Proteins 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 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
• 239000005922 Phosphane Substances 0.000 description 1
• 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
• 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 206010035104 Pituitary tumour Diseases 0.000 description 1
• 102100024616 Platelet endothelial cell adhesion molecule Human genes 0.000 description 1
• 102100030485 Platelet-derived growth factor receptor alpha Human genes 0.000 description 1
• 101710148465 Platelet-derived growth factor receptor alpha Proteins 0.000 description 1
• 241000276498 Pollachius virens Species 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940079156 Proteasome inhibitor Drugs 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 206010038934 Retinopathy proliferative Diseases 0.000 description 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
• 108091028664 Ribonucleotide Proteins 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 102100038803 Somatotropin Human genes 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 238000005668 Stille Carbonyl synthesis reaction Methods 0.000 description 1
• 238000006619 Stille reaction Methods 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
• 108700025695 Suppressor Genes Proteins 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• 102000002938 Thrombospondin Human genes 0.000 description 1
• 108060008245 Thrombospondin Proteins 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
• 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 102000004243 Tubulin Human genes 0.000 description 1
• 108090000704 Tubulin Proteins 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
• 102000016663 Vascular Endothelial Growth Factor Receptor-3 Human genes 0.000 description 1
• 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
• SRNKZYRMFBGSGE-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=CC=CN2N=CN=C21 SRNKZYRMFBGSGE-UHFFFAOYSA-N 0.000 description 1
• XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 1
• 208000017733 acquired polycythemia vera Diseases 0.000 description 1
• 238000010535 acyclic diene metathesis reaction Methods 0.000 description 1
• 125000005042 acyloxymethyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 210000004712 air sac Anatomy 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 229910001413 alkali metal ion Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 150000001345 alkine derivatives Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 125000003275 alpha amino acid group Chemical group 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 238000010976 amide bond formation reaction Methods 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 230000006427 angiogenic response Effects 0.000 description 1
• 108010072788 angiogenin Proteins 0.000 description 1
• 150000001448 anilines Chemical group 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000001772 anti-angiogenic effect Effects 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 230000003388 anti-hormonal effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 239000000729 antidote Substances 0.000 description 1
• 239000002111 antiemetic agent Substances 0.000 description 1
• 229940125683 antiemetic agent Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 210000000436 anus Anatomy 0.000 description 1
• 230000005775 apoptotic pathway Effects 0.000 description 1
• 230000004596 appetite loss Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 150000003934 aromatic aldehydes Chemical class 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 238000003491 array Methods 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 239000008122 artificial sweetener Substances 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• 150000001503 aryl iodides Chemical class 0.000 description 1
• 210000003567 ascitic fluid Anatomy 0.000 description 1
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 229940120638 avastin Drugs 0.000 description 1
• JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 1
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
• JPNZKPRONVOMLL-UHFFFAOYSA-N azane;octadecanoic acid Chemical class [NH4+].CCCCCCCCCCCCCCCCCC([O-])=O JPNZKPRONVOMLL-UHFFFAOYSA-N 0.000 description 1
• OJCKJHHYVUPUSJ-UHFFFAOYSA-N benzamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.NC(=O)C1=CC=CC=C1 OJCKJHHYVUPUSJ-UHFFFAOYSA-N 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 210000003445 biliary tract Anatomy 0.000 description 1
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000008238 biochemical pathway Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• VQYOKDLEFVOVEV-UHFFFAOYSA-L bis(2,6-diphenylphenoxy)-methylalumane Chemical compound [Al+2]C.[O-]C1=C(C=2C=CC=CC=2)C=CC=C1C1=CC=CC=C1.[O-]C1=C(C=2C=CC=CC=2)C=CC=C1C1=CC=CC=C1 VQYOKDLEFVOVEV-UHFFFAOYSA-L 0.000 description 1
• 150000004663 bisphosphonates Chemical class 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 230000024279 bone resorption Effects 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
• 229960001467 bortezomib Drugs 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 201000003714 breast lobular carcinoma Diseases 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 1
• 229930188620 butyrolactone Natural products 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 239000003560 cancer drug Substances 0.000 description 1
• 239000007894 caplet Substances 0.000 description 1
• 235000013877 carbamide Nutrition 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 210000000845 cartilage Anatomy 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 239000003729 cation exchange resin Substances 0.000 description 1
• 229940023913 cation exchange resins Drugs 0.000 description 1
• 150000001767 cationic compounds Chemical class 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 238000002701 cell growth assay Methods 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 208000025434 cerebellar degeneration Diseases 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 229940068682 chewable tablet Drugs 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 150000005753 chloropyridines Chemical class 0.000 description 1
• 201000003478 cholangiolocellular carcinoma Diseases 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 210000003483 chromatin Anatomy 0.000 description 1
• QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
• KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
• AHXGRMIPHCAXFP-UHFFFAOYSA-L chromyl dichloride Chemical compound Cl[Cr](Cl)(=O)=O AHXGRMIPHCAXFP-UHFFFAOYSA-L 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 239000007979 citrate buffer Substances 0.000 description 1
• 230000007012 clinical effect Effects 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 201000010897 colon adenocarcinoma Diseases 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 230000006552 constitutive activation Effects 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 208000013044 corticobasal degeneration disease Diseases 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229920006037 cross link polymer Polymers 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• GTGIXCPOLMWQTC-UHFFFAOYSA-N cyanomethylazanium;hydrogen sulfate Chemical compound NCC#N.OS(O)(=O)=O GTGIXCPOLMWQTC-UHFFFAOYSA-N 0.000 description 1
• 150000004292 cyclic ethers Chemical group 0.000 description 1
• 150000004294 cyclic thioethers Chemical group 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 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
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
• KDUIUFJBNGTBMD-VXMYFEMYSA-N cyclooctatetraene Chemical compound C1=C\C=C/C=C\C=C1 KDUIUFJBNGTBMD-VXMYFEMYSA-N 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 230000003413 degradative effect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 230000003831 deregulation Effects 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
• LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical group C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 238000000113 differential scanning calorimetry Methods 0.000 description 1
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 1
• SACNIGZYDTUHKB-UHFFFAOYSA-N ditert-butyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C SACNIGZYDTUHKB-UHFFFAOYSA-N 0.000 description 1
• LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
• 230000000857 drug effect Effects 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 125000006575 electron-withdrawing group Chemical group 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 210000004696 endometrium Anatomy 0.000 description 1
• 230000010595 endothelial cell migration Effects 0.000 description 1
• 125000002587 enol group Chemical group 0.000 description 1
• 150000002085 enols Chemical class 0.000 description 1
• 238000001952 enzyme assay 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
• 210000002615 epidermis Anatomy 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 210000003743 erythrocyte Anatomy 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• UWYWNAGXCZHLLM-UHFFFAOYSA-N ethyl imidazo[1,2-a]pyridine-7-carboxylate Chemical compound C1=C(C(=O)OCC)C=CN2C=CN=C21 UWYWNAGXCZHLLM-UHFFFAOYSA-N 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
• 230000003203 everyday effect Effects 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 206010016256 fatigue Diseases 0.000 description 1
• 230000003352 fibrogenic effect Effects 0.000 description 1
• 239000007888 film coating Substances 0.000 description 1
• 238000009501 film coating Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 235000019152 folic acid Nutrition 0.000 description 1
• 239000011724 folic acid Substances 0.000 description 1
• 229960000304 folic acid Drugs 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 238000011223 gene expression profiling Methods 0.000 description 1
• 238000001415 gene therapy Methods 0.000 description 1
• 231100000118 genetic alteration Toxicity 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 239000000122 growth hormone Substances 0.000 description 1
• 125000004438 haloalkoxy group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 235000013828 hydroxypropyl starch Nutrition 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 229940015872 ibandronate Drugs 0.000 description 1
• 210000003405 ileum Anatomy 0.000 description 1
• YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 1
• ZQLZNGUJOGWVCB-UHFFFAOYSA-N imidazo[1,2-a]pyridine-7-carboxamide Chemical compound C1=C(C(=O)N)C=CN2C=CN=C21 ZQLZNGUJOGWVCB-UHFFFAOYSA-N 0.000 description 1
• TUKDVVKJZVLVTD-UHFFFAOYSA-N imidazo[1,2-a]pyridine-7-carboxylic acid Chemical compound C1=C(C(=O)O)C=CN2C=CN=C21 TUKDVVKJZVLVTD-UHFFFAOYSA-N 0.000 description 1
• 150000005238 imidazo[1,2-a]pyrimidines Chemical class 0.000 description 1
• PQWQQQGKMHENOC-UHFFFAOYSA-N imidazo[1,2-c]pyrimidine Chemical class C1=NC=CC2=NC=CN21 PQWQQQGKMHENOC-UHFFFAOYSA-N 0.000 description 1
• UFBBWLWUIISIPW-UHFFFAOYSA-N imidazo[2,1-b][1,3]thiazole Chemical compound C1=CSC2=NC=CN21 UFBBWLWUIISIPW-UHFFFAOYSA-N 0.000 description 1
• CQQJSOXDEFZGFG-UHFFFAOYSA-N imidazo[4,5-d]imidazole Chemical compound C1=NC2=NC=NC2=N1 CQQJSOXDEFZGFG-UHFFFAOYSA-N 0.000 description 1
• 150000005232 imidazopyridines Chemical class 0.000 description 1
• 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 238000003018 immunoassay Methods 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229910001411 inorganic cation Inorganic materials 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000002452 interceptive effect Effects 0.000 description 1
• 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
• 230000032631 intramembranous ossification Effects 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 230000002601 intratumoral effect Effects 0.000 description 1
• 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 230000026045 iodination Effects 0.000 description 1
• 238000006192 iodination reaction Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical compound C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• 150000002513 isocyanates Chemical class 0.000 description 1
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 230000000155 isotopic effect Effects 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 208000019017 loss of appetite Diseases 0.000 description 1
• 235000021266 loss of appetite Nutrition 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000001165 lymph node Anatomy 0.000 description 1
• 208000003747 lymphoid leukemia Diseases 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 238000007726 management method Methods 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 229960004296 megestrol acetate Drugs 0.000 description 1
• RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 210000004914 menses Anatomy 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• WNTQMFVAHQHLSK-UHFFFAOYSA-N methyl 2-(benzenesulfonyl)-3-(dimethylamino)prop-2-enoate Chemical compound COC(=O)C(=CN(C)C)S(=O)(=O)C1=CC=CC=C1 WNTQMFVAHQHLSK-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 238000010208 microarray analysis Methods 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 210000004088 microvessel Anatomy 0.000 description 1
• 238000010369 molecular cloning Methods 0.000 description 1
• 239000002062 molecular scaffold Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 208000005264 motor neuron disease Diseases 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 210000002346 musculoskeletal system Anatomy 0.000 description 1
• 239000003471 mutagenic agent Substances 0.000 description 1
• 231100000707 mutagenic chemical Toxicity 0.000 description 1
• 230000003505 mutagenic effect Effects 0.000 description 1
• 206010028537 myelofibrosis Diseases 0.000 description 1
• 230000002071 myeloproliferative effect Effects 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• MRHQBBSKCLIMRH-UHFFFAOYSA-N n-(acetamidomethoxymethyl)acetamide Chemical compound CC(=O)NCOCNC(C)=O MRHQBBSKCLIMRH-UHFFFAOYSA-N 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
• GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-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
• VLSFITLAADJYOS-UHFFFAOYSA-N n-methyl-1-trimethylsilylmethanamine Chemical compound CNC[Si](C)(C)C VLSFITLAADJYOS-UHFFFAOYSA-N 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
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 210000000822 natural killer cell Anatomy 0.000 description 1
• 230000009707 neogenesis Effects 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• 208000004235 neutropenia Diseases 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• GWCBVFMHGHMALR-UHFFFAOYSA-N o-(2-trimethylsilylethyl)hydroxylamine Chemical compound C[Si](C)(C)CCON GWCBVFMHGHMALR-UHFFFAOYSA-N 0.000 description 1
• XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
• KKVUFSINQFSJNK-UHFFFAOYSA-N o-tert-butylhydroxylamine Chemical compound CC(C)(C)ON KKVUFSINQFSJNK-UHFFFAOYSA-N 0.000 description 1
• WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
• 229960001494 octreotide acetate Drugs 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 108091008819 oncoproteins Proteins 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002892 organic cations Chemical class 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 210000000963 osteoblast Anatomy 0.000 description 1
• 230000002188 osteogenic effect Effects 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 229940127084 other anti-cancer agent Drugs 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000016087 ovulation Effects 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• CQDAMYNQINDRQC-UHFFFAOYSA-N oxatriazole Chemical compound C1=NN=NO1 CQDAMYNQINDRQC-UHFFFAOYSA-N 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 238000006213 oxygenation reaction Methods 0.000 description 1
• OTYPIDNRISCWQY-UHFFFAOYSA-L palladium(2+);tris(2-methylphenyl)phosphane;dichloride Chemical compound Cl[Pd]Cl.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C.CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C OTYPIDNRISCWQY-UHFFFAOYSA-L 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
• MXQOYLRVSVOCQT-UHFFFAOYSA-N palladium;tritert-butylphosphane Chemical compound [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
• 229940046231 pamidronate Drugs 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 230000003076 paracrine Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000001991 pathophysiological effect Effects 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• MVDYEFQVZNBPPH-UHFFFAOYSA-N pentane-2,3,4-trione Chemical compound CC(=O)C(=O)C(C)=O MVDYEFQVZNBPPH-UHFFFAOYSA-N 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N pentanoic acid group Chemical class C(CCCC)(=O)O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 230000010412 perfusion Effects 0.000 description 1
• 210000003668 pericyte Anatomy 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 230000035699 permeability Effects 0.000 description 1
• 150000004965 peroxy acids Chemical class 0.000 description 1
• 229910000064 phosphane Inorganic materials 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
• 238000002428 photodynamic therapy Methods 0.000 description 1
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229960005235 piperonyl butoxide Drugs 0.000 description 1
• ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
• 229960003073 pirfenidone Drugs 0.000 description 1
• 230000036470 plasma concentration Effects 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 210000004910 pleural fluid Anatomy 0.000 description 1
• 239000003880 polar aprotic solvent Substances 0.000 description 1
• 108010056274 polo-like kinase 1 Chemical class 0.000 description 1
• 208000037244 polycythemia vera Diseases 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920005596 polymer binder Polymers 0.000 description 1
• 239000002491 polymer binding agent Substances 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229920000137 polyphosphoric acid Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 229910001414 potassium ion Inorganic materials 0.000 description 1
• 238000000634 powder X-ray diffraction Methods 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 229960005205 prednisolone Drugs 0.000 description 1
• OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 238000004237 preparative chromatography Methods 0.000 description 1
• 238000004262 preparative liquid chromatography Methods 0.000 description 1
• 150000003138 primary alcohols Chemical class 0.000 description 1
• 208000003476 primary myelofibrosis Diseases 0.000 description 1
• 230000037452 priming Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 239000003207 proteasome inhibitor Substances 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 150000003219 pyrazolines Chemical class 0.000 description 1
• GDASVOXREDJRGF-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine-6-carboxylic acid Chemical compound C1=C(C(=O)O)C=NC2=CC=NN21 GDASVOXREDJRGF-UHFFFAOYSA-N 0.000 description 1
• LETVJWLLIMJADE-UHFFFAOYSA-N pyridazin-3-amine Chemical class NC1=CC=CN=N1 LETVJWLLIMJADE-UHFFFAOYSA-N 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 229910052705 radium Inorganic materials 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 238000009877 rendering Methods 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000000979 retarding effect Effects 0.000 description 1
• 210000001525 retina Anatomy 0.000 description 1
• 206010039083 rhinitis Diseases 0.000 description 1
• 239000002336 ribonucleotide Substances 0.000 description 1
• 125000002652 ribonucleotide group Chemical group 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 102200126698 rs1057519045 Human genes 0.000 description 1
• 102200158153 rs11057353 Human genes 0.000 description 1
• 102200126858 rs121918488 Human genes 0.000 description 1
• 102200126859 rs121918488 Human genes 0.000 description 1
• 102200126856 rs121918496 Human genes 0.000 description 1
• 102200126968 rs121918499 Human genes 0.000 description 1
• 102200126971 rs121918510 Human genes 0.000 description 1
• 102200126834 rs1554928884 Human genes 0.000 description 1
• 229910052701 rubidium Inorganic materials 0.000 description 1
• 239000012723 sample buffer Substances 0.000 description 1
• 238000005070 sampling Methods 0.000 description 1
• 238000007127 saponification reaction Methods 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 230000037390 scarring Effects 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 206010039667 schwannoma Diseases 0.000 description 1
• 238000007423 screening assay 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
• 230000028327 secretion Effects 0.000 description 1
• 238000003375 selectivity assay Methods 0.000 description 1
• 230000009919 sequestration Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 208000013220 shortness of breath Diseases 0.000 description 1
• 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
• 201000009890 sinusitis Diseases 0.000 description 1
• 230000022379 skeletal muscle tissue development Effects 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 229960003787 sorafenib Drugs 0.000 description 1
• IVDHYUQIDRJSTI-UHFFFAOYSA-N sorafenib tosylate Chemical compound [H+].CC1=CC=C(S([O-])(=O)=O)C=C1.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 IVDHYUQIDRJSTI-UHFFFAOYSA-N 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 1
• 230000037436 splice-site mutation Effects 0.000 description 1
• 208000024794 sputum Diseases 0.000 description 1
• 210000003802 sputum Anatomy 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 230000003019 stabilising effect Effects 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical class [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 239000003270 steroid hormone Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 239000006190 sub-lingual tablet Substances 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 235000011044 succinic acid Nutrition 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000005846 sugar alcohols Chemical class 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
• MBDNRNMVTZADMQ-UHFFFAOYSA-N sulfolene Chemical compound O=S1(=O)CC=CC1 MBDNRNMVTZADMQ-UHFFFAOYSA-N 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 230000008093 supporting effect Effects 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 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
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 238000002626 targeted therapy Methods 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
• 150000003536 tetrazoles Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
• CUWHXIJMTMMRTI-UHFFFAOYSA-N thiadiazol-4-amine Chemical class NC1=CSN=N1 CUWHXIJMTMMRTI-UHFFFAOYSA-N 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• NFRGCMIFZVPLSJ-UHFFFAOYSA-N thiazepane 1,1-dioxide Chemical compound O=S1(=O)CCCCCN1 NFRGCMIFZVPLSJ-UHFFFAOYSA-N 0.000 description 1
• DNGMYXZLJGHHOM-UHFFFAOYSA-N thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCCCN1 DNGMYXZLJGHHOM-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 150000003568 thioethers Chemical class 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
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 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
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 231100000440 toxicity profile Toxicity 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 102000027257 transmembrane receptors Human genes 0.000 description 1
• 108091008578 transmembrane receptors Proteins 0.000 description 1
• 238000006478 transmetalation reaction Methods 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical compound BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
• 150000008648 triflates Chemical class 0.000 description 1
• PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• YOIAWAIKYVEKMF-UHFFFAOYSA-N trifluoromethanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)F.OS(=O)(=O)C(F)(F)F YOIAWAIKYVEKMF-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
• DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 210000005239 tubule Anatomy 0.000 description 1
• 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
• 230000009452 underexpressoin Effects 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 208000011479 upper respiratory tract disease Diseases 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 125000005500 uronium group Chemical group 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 239000002966 varnish Substances 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000007998 vessel formation Effects 0.000 description 1
• 235000012431 wafers Nutrition 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 238000002424 x-ray crystallography Methods 0.000 description 1
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 1
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1