BR112020013647A2

BR112020013647A2 - novo inibidor galactosídeo de galectinas

novo inibidor galactosídeo de galectinas Download PDF

Info

Publication number: BR112020013647A2
Authority: BR; Brazil
Prior art keywords: deoxy; galactopyranoside; thio; triazol; mmol
Prior art date: 2018-01-10

Application number

BR112020013647-6A

Other languages

English (en)

Portuguese (pt)

Inventor

Fredrik Zetterberg

Original Assignee

Galecto Biotech Ab

Priority date

2018-01-10

Filing date

2019-01-09

Publication date

2020-12-01

2019-01-09 Application filed by Galecto Biotech Ab filed Critical Galecto Biotech Ab

2020-12-01 Publication of BR112020013647A2 publication Critical patent/BR112020013647A2/pt

Links

102000007563 Galectins Human genes 0.000 title abstract description 44
108010046569 Galectins Proteins 0.000 title abstract description 44
239000003112 inhibitor Substances 0.000 title description 33
150000008195 galaktosides Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 250
108010001498 Galectin 1 Proteins 0.000 claims abstract description 56
238000000034 method Methods 0.000 claims abstract description 34
241000124008 Mammalia Species 0.000 claims abstract description 15
230000027455 binding Effects 0.000 claims abstract description 13
102000000795 Galectin 1 Human genes 0.000 claims abstract 3
-1 5-Chloro-6-cyano-pyridine-3-yl Chemical group 0.000 claims description 213
229910052736 halogen Inorganic materials 0.000 claims description 50
150000002367 halogens Chemical class 0.000 claims description 50
239000000460 chlorine Substances 0.000 claims description 43
206010028980 Neoplasm Diseases 0.000 claims description 40
229910052757 nitrogen Inorganic materials 0.000 claims description 32
201000011510 cancer Diseases 0.000 claims description 30
229910052801 chlorine Inorganic materials 0.000 claims description 27
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
238000011282 treatment Methods 0.000 claims description 25
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
229910052794 bromium Inorganic materials 0.000 claims description 22
206010016654 Fibrosis Diseases 0.000 claims description 20
230000004761 fibrosis Effects 0.000 claims description 20
239000003814 drug Substances 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
229910052731 fluorine Inorganic materials 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
239000008194 pharmaceutical composition Substances 0.000 claims description 16
125000001424 substituent group Chemical group 0.000 claims description 16
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 15
230000033115 angiogenesis Effects 0.000 claims description 15
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 14
208000035475 disorder Diseases 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 12
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
201000010099 disease Diseases 0.000 claims description 12
125000004076 pyridyl group Chemical group 0.000 claims description 12
231100000241 scar Toxicity 0.000 claims description 12
206010029113 Neovascularisation Diseases 0.000 claims description 10
208000030159 metabolic disease Diseases 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
230000015572 biosynthetic process Effects 0.000 claims description 9
239000000546 pharmaceutical excipient Substances 0.000 claims description 9
206010061218 Inflammation Diseases 0.000 claims description 8
230000004054 inflammatory process Effects 0.000 claims description 8
208000032839 leukemia Diseases 0.000 claims description 8
239000012453 solvate Substances 0.000 claims description 8
201000009030 Carcinoma Diseases 0.000 claims description 7
206010025323 Lymphomas Diseases 0.000 claims description 7
206010039491 Sarcoma Diseases 0.000 claims description 7
239000003446 ligand Substances 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
208000023275 Autoimmune disease Diseases 0.000 claims description 6
208000032544 Cicatrix Diseases 0.000 claims description 6
208000034038 Pathologic Neovascularization Diseases 0.000 claims description 6
208000031737 Tissue Adhesions Diseases 0.000 claims description 6
230000001594 aberrant effect Effects 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
208000030533 eye disease Diseases 0.000 claims description 6
208000011379 keloid formation Diseases 0.000 claims description 6
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 6
208000005069 pulmonary fibrosis Diseases 0.000 claims description 6
230000037387 scars Effects 0.000 claims description 6
206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 5
201000001320 Atherosclerosis Diseases 0.000 claims description 5
206010009900 Colitis ulcerative Diseases 0.000 claims description 5
206010055665 Corneal neovascularisation Diseases 0.000 claims description 5
208000011231 Crohn disease Diseases 0.000 claims description 5
206010019280 Heart failures Diseases 0.000 claims description 5
208000006933 Hermanski-Pudlak Syndrome Diseases 0.000 claims description 5
206010071775 Hermansky-Pudlak syndrome Diseases 0.000 claims description 5
208000029523 Interstitial Lung disease Diseases 0.000 claims description 5
206010027406 Mesothelioma Diseases 0.000 claims description 5
208000008589 Obesity Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
206010039710 Scleroderma Diseases 0.000 claims description 5
208000034189 Sclerosis Diseases 0.000 claims description 5
206010040070 Septic Shock Diseases 0.000 claims description 5
206010052779 Transplant rejections Diseases 0.000 claims description 5
201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
206010064930 age-related macular degeneration Diseases 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
208000019425 cirrhosis of liver Diseases 0.000 claims description 5
201000000159 corneal neovascularization Diseases 0.000 claims description 5
206010012601 diabetes mellitus Diseases 0.000 claims description 5
208000019622 heart disease Diseases 0.000 claims description 5
208000019423 liver disease Diseases 0.000 claims description 5
208000002780 macular degeneration Diseases 0.000 claims description 5
208000037819 metastatic cancer Diseases 0.000 claims description 5
208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 5
208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 5
206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 5
235000020824 obesity Nutrition 0.000 claims description 5
201000002793 renal fibrosis Diseases 0.000 claims description 5
206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
230000036303 septic shock Effects 0.000 claims description 5
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
KRFOHZKKGPUCCZ-AHXITHOBSA-N (2R,4S,5R)-2-(3,4-dichlorophenyl)sulfanyl-6-(hydroxymethyl)-4-[4-(4-hydroxy-1,3-thiazol-2-yl)triazol-1-yl]oxane-3,5-diol Chemical compound C1=CC(=C(C=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=NC(=CS4)O)O)Cl)Cl KRFOHZKKGPUCCZ-AHXITHOBSA-N 0.000 claims description 4
BWEZCWXAMQJAHD-BEBHXBEKSA-N 4-[1-[(2R,4S,5R)-2-(3,4-dichlorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=CC(=C(C=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)Cl)Cl BWEZCWXAMQJAHD-BEBHXBEKSA-N 0.000 claims description 4
GAHICCQTWURYKS-UKTBERIZSA-N 4-[1-[(2R,4S,5R)-2-(3,5-dichloro-4-fluorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=C(C(=C1Cl)F)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O GAHICCQTWURYKS-UKTBERIZSA-N 0.000 claims description 4
UCUUGPSLUNOFHQ-UNYRHXCVSA-N 4-[1-[(2R,4S,5R)-2-[5-bromo-6-(trifluoromethyl)pyridin-3-yl]sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=NC(=C1Br)C(F)(F)F)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O UCUUGPSLUNOFHQ-UNYRHXCVSA-N 0.000 claims description 4
QWGIRMCDGAQNHN-UKTBERIZSA-N 4-[1-[(3R,4S,6R)-3,5-dihydroxy-2-(hydroxymethyl)-6-(3,4,5-trichlorophenyl)sulfanyloxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=C(C(=C1Cl)Cl)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O QWGIRMCDGAQNHN-UKTBERIZSA-N 0.000 claims description 4
OXEBVPGLIMNUKG-MQRCVFDHSA-N 5-chloro-3-[(2R,4S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[4-(2-oxo-3H-1,3-thiazol-4-yl)triazol-1-yl]oxan-2-yl]sulfanyl-N,N-dimethylpyridine-2-carboxamide Chemical compound CN(C)C(=O)C1=C(C=C(C=N1)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O OXEBVPGLIMNUKG-MQRCVFDHSA-N 0.000 claims description 4
PRPUOSWXELEYOF-DMZMFVCCSA-N ClC=1N=C(SC=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Br)C(C)C)O[C@@H]([C@@H]1O)CO)O Chemical compound ClC=1N=C(SC=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Br)C(C)C)O[C@@H]([C@@H]1O)CO)O PRPUOSWXELEYOF-DMZMFVCCSA-N 0.000 claims description 4
DMKYSPPFUVMAFM-DZQJYWQESA-N OC=1SC=C(N=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]1O)CO)O Chemical compound OC=1SC=C(N=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]1O)CO)O DMKYSPPFUVMAFM-DZQJYWQESA-N 0.000 claims description 4
HZYYOOHDLIMLKQ-LYYZXLFJSA-N OC[C@H]1O[C@H](SC2=CC(Cl)=C(Cl)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(F)=N1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Cl)=C(Cl)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(F)=N1 HZYYOOHDLIMLKQ-LYYZXLFJSA-N 0.000 claims description 4
FEQAFWWDELXPQO-YNIRGQLTSA-N OC[C@H]1O[C@H](SC2=CC(Cl)=C(Cl)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(F)=CS1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Cl)=C(Cl)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(F)=CS1 FEQAFWWDELXPQO-YNIRGQLTSA-N 0.000 claims description 4
ANHHXIIEOYLBOB-LYYZXLFJSA-N OC[C@H]1O[C@H](SC2=CC(Cl)=C(F)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Cl)=C(F)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 ANHHXIIEOYLBOB-LYYZXLFJSA-N 0.000 claims description 4
WTMKWTUCQLAPLG-DZQJYWQESA-N OC[C@H]1O[C@H](SC2=CC(Cl)=C(SC(F)(F)F)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Cl)=C(SC(F)(F)F)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 WTMKWTUCQLAPLG-DZQJYWQESA-N 0.000 claims description 4
XDMSEZKGPZZNKV-DZQJYWQESA-N OC[C@H]1O[C@H](SC2=CC(Cl)=CN=C2C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Cl)=CN=C2C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 XDMSEZKGPZZNKV-DZQJYWQESA-N 0.000 claims description 4
206010042971 T-cell lymphoma Diseases 0.000 claims description 4
239000000654 additive Substances 0.000 claims description 4
230000000996 additive effect Effects 0.000 claims description 4
OXSNBWCOFLKQOE-DKYVEAMZSA-N (2R,4S,5R)-2-[5-bromo-6-(trifluoromethyl)pyridin-3-yl]sulfanyl-4-[4-(4-chloro-1,3-thiazol-2-yl)triazol-1-yl]-6-(hydroxymethyl)oxane-3,5-diol Chemical compound C1=C(C=NC(=C1Br)C(F)(F)F)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=NC(=CS4)Cl)O OXSNBWCOFLKQOE-DKYVEAMZSA-N 0.000 claims description 3
BZSCLIZOYQVCKE-DKYVEAMZSA-N (2R,4S,5R)-4-[4-(4-bromo-1,3-thiazol-2-yl)triazol-1-yl]-2-[5-bromo-6-(trifluoromethyl)pyridin-3-yl]sulfanyl-6-(hydroxymethyl)oxane-3,5-diol Chemical compound C1=C(C=NC(=C1Br)C(F)(F)F)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=NC(=CS4)Br)O BZSCLIZOYQVCKE-DKYVEAMZSA-N 0.000 claims description 3
BIXUJZWHKMBPPF-LAYQYYCJSA-N 2-bromo-4-[(2R,4S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[4-(2-oxo-3H-1,3-thiazol-4-yl)triazol-1-yl]oxan-2-yl]sulfanylbenzonitrile Chemical compound C1=CC(=C(C=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)Br)C#N BIXUJZWHKMBPPF-LAYQYYCJSA-N 0.000 claims description 3
RTGGHYKPRGSTFZ-AHXITHOBSA-N 3-chloro-5-[(2R,4S,5R)-4-[4-(4-chloro-1,3-thiazol-2-yl)triazol-1-yl]-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]sulfanylpyridine-2-carbonitrile Chemical compound C1=C(C=NC(=C1Cl)C#N)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=NC(=CS4)Cl)O RTGGHYKPRGSTFZ-AHXITHOBSA-N 0.000 claims description 3
DEZXUKFQGWEBPA-UKTBERIZSA-N 4-[1-[(2R,4S,5R)-2-(3,5-dibromo-4-fluorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=C(C(=C1Br)F)Br)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O DEZXUKFQGWEBPA-UKTBERIZSA-N 0.000 claims description 3
QFXZCDKRLMTLPM-LAYQYYCJSA-N 4-[1-[(2R,4S,5R)-2-(3-chloro-4-methylphenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound CC1=C(C=C(C=C1)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)Cl QFXZCDKRLMTLPM-LAYQYYCJSA-N 0.000 claims description 3
RMROEDKIZLORMI-UKTBERIZSA-N 4-[1-[(2R,4S,5R)-2-(4,5-dichloro-2-fluorophenyl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C(=CC(=C1Cl)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)F RMROEDKIZLORMI-UKTBERIZSA-N 0.000 claims description 3
WYESJSCHMLZEAD-OWKNBALPSA-N ClC=1N=C(SC=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]1O)CO)O Chemical compound ClC=1N=C(SC=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]1O)CO)O WYESJSCHMLZEAD-OWKNBALPSA-N 0.000 claims description 3
JYBNMFQGALVNGD-OWKNBALPSA-N ClC=1N=C(SC=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Cl)C#N)O[C@@H]([C@@H]1O)CO)O Chemical compound ClC=1N=C(SC=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Cl)C#N)O[C@@H]([C@@H]1O)CO)O JYBNMFQGALVNGD-OWKNBALPSA-N 0.000 claims description 3
CNDRVWDOHVXXCB-ZKPNFLFLSA-N OC[C@H]1O[C@H](SC2=CC(Cl)=C(Cl)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(F)=C(F)S1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Cl)=C(Cl)C=C2)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(F)=C(F)S1 CNDRVWDOHVXXCB-ZKPNFLFLSA-N 0.000 claims description 3
ANXOSUXMRNWBKV-NLRWUALESA-N OC[C@H]1O[C@H](SC2=CC(Cl)=C(N=C2)C(F)(F)F)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Cl)=C(N=C2)C(F)(F)F)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 ANXOSUXMRNWBKV-NLRWUALESA-N 0.000 claims description 2
NABQCTZBPFTOGB-LYYZXLFJSA-N OC[C@H]1O[C@H](SC2=CC(Br)=C(N=C2)C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Br)=C(N=C2)C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 NABQCTZBPFTOGB-LYYZXLFJSA-N 0.000 claims 1
CXCUPEGHBWIEBH-YNIRGQLTSA-N OC[C@H]1O[C@H](SC2=CC(Br)=C(N=C2)C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(Cl)=CS1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Br)=C(N=C2)C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(Cl)=CS1 CXCUPEGHBWIEBH-YNIRGQLTSA-N 0.000 claims 1
229960003082 galactose Drugs 0.000 abstract description 12
125000001425 triazolyl group Chemical group 0.000 abstract description 5
229910052799 carbon Inorganic materials 0.000 abstract description 4
150000003214 pyranose derivatives Chemical group 0.000 abstract description 3
239000000243 solution Substances 0.000 description 113
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 109
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 104
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 96
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
239000000203 mixture Substances 0.000 description 89
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 88
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 84
238000005160 1H NMR spectroscopy Methods 0.000 description 70
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 67
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
239000011541 reaction mixture Substances 0.000 description 56
239000002904 solvent Substances 0.000 description 54
102100021736 Galectin-1 Human genes 0.000 description 53
238000004440 column chromatography Methods 0.000 description 52
239000000543 intermediate Substances 0.000 description 42
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
239000012267 brine Substances 0.000 description 35
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
102000000802 Galectin 3 Human genes 0.000 description 34
108010001517 Galectin 3 Proteins 0.000 description 34
238000006243 chemical reaction Methods 0.000 description 34
235000019439 ethyl acetate Nutrition 0.000 description 32
229910021595 Copper(I) iodide Inorganic materials 0.000 description 31
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
239000012043 crude product Substances 0.000 description 29
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
239000012044 organic layer Substances 0.000 description 26
239000000741 silica gel Substances 0.000 description 25
229910002027 silica gel Inorganic materials 0.000 description 25
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 23
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 22
239000012074 organic phase Substances 0.000 description 22
230000008569 process Effects 0.000 description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 20
239000008346 aqueous phase Substances 0.000 description 19
238000002953 preparative HPLC Methods 0.000 description 19
239000007787 solid Substances 0.000 description 19
239000012442 inert solvent Substances 0.000 description 16
239000012299 nitrogen atmosphere Substances 0.000 description 16
229910052938 sodium sulfate Inorganic materials 0.000 description 16
235000011152 sodium sulphate Nutrition 0.000 description 16
CZWWCTHQXBMHDA-UHFFFAOYSA-N 3h-1,3-thiazol-2-one Chemical compound OC1=NC=CS1 CZWWCTHQXBMHDA-UHFFFAOYSA-N 0.000 description 15
239000007832 Na2SO4 Substances 0.000 description 15
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 15
239000012071 phase Substances 0.000 description 15
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 14
150000001720 carbohydrates Chemical class 0.000 description 14
239000012298 atmosphere Substances 0.000 description 13
230000000694 effects Effects 0.000 description 13
239000008101 lactose Substances 0.000 description 13
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
125000001072 heteroaryl group Chemical group 0.000 description 12
238000004519 manufacturing process Methods 0.000 description 12
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
229910000024 caesium carbonate Inorganic materials 0.000 description 10
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
210000004027 cell Anatomy 0.000 description 8
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
229930182830 galactose Natural products 0.000 description 8
230000005764 inhibitory process Effects 0.000 description 8
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
229940124597 therapeutic agent Drugs 0.000 description 8
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 8
WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 7
125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
239000003208 petroleum Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
229910052717 sulfur Inorganic materials 0.000 description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
210000001744 T-lymphocyte Anatomy 0.000 description 6
239000002671 adjuvant Substances 0.000 description 6
235000012538 ammonium bicarbonate Nutrition 0.000 description 6
239000003085 diluting agent Substances 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
108090000765 processed proteins & peptides Proteins 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
238000003756 stirring Methods 0.000 description 6
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 5
208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 5
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
229910052681 coesite Inorganic materials 0.000 description 5
229910052906 cristobalite Inorganic materials 0.000 description 5
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 5
230000004069 differentiation Effects 0.000 description 5
229940079593 drug Drugs 0.000 description 5
238000000605 extraction Methods 0.000 description 5
125000005842 heteroatom Chemical group 0.000 description 5
230000000670 limiting effect Effects 0.000 description 5
230000037361 pathway Effects 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
239000000843 powder Substances 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
108090000623 proteins and genes Proteins 0.000 description 5
238000001959 radiotherapy Methods 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
235000012239 silicon dioxide Nutrition 0.000 description 5
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 5
235000010288 sodium nitrite Nutrition 0.000 description 5
229910052682 stishovite Inorganic materials 0.000 description 5
229910052905 tridymite Inorganic materials 0.000 description 5
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 5
RRRFJEMWVAWRIX-UHFFFAOYSA-N 3-bromo-5-fluoro-2-(trifluoromethyl)pyridine Chemical compound FC1=CN=C(C(F)(F)F)C(Br)=C1 RRRFJEMWVAWRIX-UHFFFAOYSA-N 0.000 description 4
MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 4
208000031261 Acute myeloid leukaemia Diseases 0.000 description 4
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 4
KQEZTRQBXWHCFI-WHCFWRGISA-N C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O KQEZTRQBXWHCFI-WHCFWRGISA-N 0.000 description 4
RNMLIBJSDDXKBL-VUFOIJLHSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O RNMLIBJSDDXKBL-VUFOIJLHSA-N 0.000 description 4
YRDGLVVTACBOKH-WVXKDWSHSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O YRDGLVVTACBOKH-WVXKDWSHSA-N 0.000 description 4
102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 4
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 4
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 4
229910019213 POCl3 Inorganic materials 0.000 description 4
101710089372 Programmed cell death protein 1 Proteins 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
230000004913 activation Effects 0.000 description 4
150000001413 amino acids Chemical class 0.000 description 4
239000002246 antineoplastic agent Substances 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
229940127089 cytotoxic agent Drugs 0.000 description 4
150000002016 disaccharides Chemical class 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
229960002949 fluorouracil Drugs 0.000 description 4
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
230000014509 gene expression Effects 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
230000003308 immunostimulating effect Effects 0.000 description 4
230000001506 immunosuppresive effect Effects 0.000 description 4
230000003993 interaction Effects 0.000 description 4
210000002540 macrophage Anatomy 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000000047 product Substances 0.000 description 4
238000000746 purification Methods 0.000 description 4
235000009518 sodium iodide Nutrition 0.000 description 4
SYKYBMOFPMXDRQ-SOIZYFOBSA-N thiodigalactoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1S[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](CO)O1 SYKYBMOFPMXDRQ-SOIZYFOBSA-N 0.000 description 4
FPGQRMSFHPPXIU-BEBHXBEKSA-N (2R,4S,5R)-4-[4-(2-chloro-1,3-thiazol-4-yl)triazol-1-yl]-2-(3,4-dichlorophenyl)sulfanyl-6-(hydroxymethyl)oxane-3,5-diol Chemical compound C1=CC(=C(C=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=N4)Cl)O)Cl)Cl FPGQRMSFHPPXIU-BEBHXBEKSA-N 0.000 description 3
MKEJZKKVVUZXIS-UHFFFAOYSA-N 2,4-dibromo-1,3-thiazole Chemical compound BrC1=CSC(Br)=N1 MKEJZKKVVUZXIS-UHFFFAOYSA-N 0.000 description 3
INQKZAUXUDPPOX-UHFFFAOYSA-N 2-[2-[(4-methoxyphenyl)methoxy]-1,3-thiazol-4-yl]ethynyl-trimethylsilane Chemical compound COC1=CC=C(C=C1)COC=1SC=C(N=1)C#C[Si](C)(C)C INQKZAUXUDPPOX-UHFFFAOYSA-N 0.000 description 3
CXCUPEGHBWIEBH-AHXITHOBSA-N 3-bromo-5-[(2R,4S,5R)-4-[4-(4-chloro-1,3-thiazol-2-yl)triazol-1-yl]-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]sulfanylpyridine-2-carbonitrile Chemical compound C1=C(C=NC(=C1Br)C#N)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=NC(=CS4)Cl)O CXCUPEGHBWIEBH-AHXITHOBSA-N 0.000 description 3
AAGYWTCZOUXEDH-UHFFFAOYSA-N 3-bromo-5-chloropyridine-2-carbonitrile Chemical compound ClC1=CN=C(C#N)C(Br)=C1 AAGYWTCZOUXEDH-UHFFFAOYSA-N 0.000 description 3
CWWQFJQUFJTUGG-UHFFFAOYSA-N 3-bromo-5-fluoro-2-iodopyridine Chemical compound BrC=1C(=NC=C(C=1)F)I CWWQFJQUFJTUGG-UHFFFAOYSA-N 0.000 description 3
OZTRWWYTGPWGQL-BEBHXBEKSA-N 4-[1-[(2R,4S,5R)-2-[3-chloro-4-(trifluoromethyl)phenyl]sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=CC(=C(C=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)Cl)C(F)(F)F OZTRWWYTGPWGQL-BEBHXBEKSA-N 0.000 description 3
UWCSELZTEZZCFE-UHFFFAOYSA-N 4-bromo-2-[(4-methoxyphenyl)methoxy]-1,3-thiazole Chemical compound C1=CC(OC)=CC=C1COC1=NC(Br)=CS1 UWCSELZTEZZCFE-UHFFFAOYSA-N 0.000 description 3
RZULADBKEZCVKC-UHFFFAOYSA-N 5-bromo-6-(trifluoromethyl)pyridine-3-thiol Chemical compound BrC=1C=C(C=NC=1C(F)(F)F)S RZULADBKEZCVKC-UHFFFAOYSA-N 0.000 description 3
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 3
208000026310 Breast neoplasm Diseases 0.000 description 3
LREKHDPJIWGWMI-WHCFWRGISA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C(=C2)Br)F)Br)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C(=C2)Br)F)Br)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O LREKHDPJIWGWMI-WHCFWRGISA-N 0.000 description 3
KRGPVIVLJPLMOY-BMXMUORJSA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)C#N)Br)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)C#N)Br)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O KRGPVIVLJPLMOY-BMXMUORJSA-N 0.000 description 3
URZGMELZRUCWDC-WHCFWRGISA-N C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O URZGMELZRUCWDC-WHCFWRGISA-N 0.000 description 3
ROAQMDZYEQVIHG-VUFOIJLHSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C(=NC=C(C=2)Br)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O ROAQMDZYEQVIHG-VUFOIJLHSA-N 0.000 description 3
LVIWWBQBMPKMKS-CDJZJNNCSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O LVIWWBQBMPKMKS-CDJZJNNCSA-N 0.000 description 3
OJBDSHPWVOPXCW-XSEKTIEYSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O OJBDSHPWVOPXCW-XSEKTIEYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
208000033962 Fontaine progeroid syndrome Diseases 0.000 description 3
102100031351 Galectin-9 Human genes 0.000 description 3
101710121810 Galectin-9 Proteins 0.000 description 3
206010027476 Metastases Diseases 0.000 description 3
208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
KFEUJDWYNGMDBV-LODBTCKLSA-N N-acetyllactosamine Chemical compound O[C@@H]1[C@@H](NC(=O)C)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KFEUJDWYNGMDBV-LODBTCKLSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
230000001093 anti-cancer Effects 0.000 description 3
230000003510 anti-fibrotic effect Effects 0.000 description 3
230000006907 apoptotic process Effects 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
238000003556 assay Methods 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
239000000969 carrier Substances 0.000 description 3
230000021164 cell adhesion Effects 0.000 description 3
230000008859 change Effects 0.000 description 3
238000002648 combination therapy Methods 0.000 description 3
210000000172 cytosol Anatomy 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
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 3
235000008191 folinic acid Nutrition 0.000 description 3
239000011672 folinic acid Substances 0.000 description 3
230000006870 function Effects 0.000 description 3
125000000524 functional group Chemical group 0.000 description 3
230000002140 halogenating effect Effects 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
125000000592 heterocycloalkyl group Chemical group 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
230000001965 increasing effect Effects 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
239000010410 layer Substances 0.000 description 3
229960001691 leucovorin Drugs 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
210000000651 myofibroblast Anatomy 0.000 description 3
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
238000012552 review Methods 0.000 description 3
238000000926 separation method Methods 0.000 description 3
230000011664 signaling Effects 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
229910000342 sodium bisulfate Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910052979 sodium sulfide Inorganic materials 0.000 description 3
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 3
239000008107 starch Substances 0.000 description 3
239000011593 sulfur Substances 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
210000004881 tumor cell Anatomy 0.000 description 3
INGORPMDIARWLA-ZTBUYSOXSA-N (2R,4S,5R)-2-[5-bromo-6-(trifluoromethyl)pyridin-3-yl]sulfanyl-4-[4-(4,5-dichloro-1,3-thiazol-2-yl)triazol-1-yl]-6-(hydroxymethyl)oxane-3,5-diol Chemical compound C1=C(C=NC(=C1Br)C(F)(F)F)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=NC(=C(S4)Cl)Cl)O INGORPMDIARWLA-ZTBUYSOXSA-N 0.000 description 2
YXTKHLHCVFUPPT-YYFJYKOTSA-N (2s)-2-[[4-[(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid;(1r,2r)-1,2-dimethanidylcyclohexane;5-fluoro-1h-pyrimidine-2,4-dione;oxalic acid;platinum(2+) Chemical compound [Pt+2].OC(=O)C(O)=O.[CH2-][C@@H]1CCCC[C@H]1[CH2-].FC1=CNC(=O)NC1=O.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 YXTKHLHCVFUPPT-YYFJYKOTSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
ASHZMYYXNMJUDZ-UHFFFAOYSA-N 2,3-dibromo-5-fluoropyridine Chemical compound FC1=CN=C(Br)C(Br)=C1 ASHZMYYXNMJUDZ-UHFFFAOYSA-N 0.000 description 2
JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 2
AZCUZSLPTFALDX-UHFFFAOYSA-N 3,5-dibromo-4-fluorobenzenethiol Chemical compound Fc1c(Br)cc(S)cc1Br AZCUZSLPTFALDX-UHFFFAOYSA-N 0.000 description 2
YCKRLXQDUDACHI-UHFFFAOYSA-N 3,5-dichloro-4-fluorobenzenethiol Chemical compound FC1=C(Cl)C=C(S)C=C1Cl YCKRLXQDUDACHI-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
NABQCTZBPFTOGB-BEBHXBEKSA-N 3-bromo-5-[(2R,4S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[4-(2-oxo-3H-1,3-thiazol-4-yl)triazol-1-yl]oxan-2-yl]sulfanylpyridine-2-carbonitrile Chemical compound C1=C(C=NC(=C1Br)C#N)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O NABQCTZBPFTOGB-BEBHXBEKSA-N 0.000 description 2
KSNGNIUUZMMIOB-VFAFTYBQSA-N 4-chloro-2-[(2R,4S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[4-(2-oxo-3H-1,3-thiazol-4-yl)triazol-1-yl]oxan-2-yl]sulfanyl-N,N-dimethylbenzamide Chemical compound CN(C)C(=O)C1=C(C=C(C=C1)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O KSNGNIUUZMMIOB-VFAFTYBQSA-N 0.000 description 2
AAKSNUWBFNMWOT-CDZUSTAJSA-N 5-chloro-3-[(2R,4S,5R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[4-(2-oxo-3H-1,3-thiazol-4-yl)triazol-1-yl]oxan-2-yl]sulfanylpyridine-2-carboxylic acid Chemical compound C1=C(C=NC(=C1S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O)C(=O)O)Cl AAKSNUWBFNMWOT-CDZUSTAJSA-N 0.000 description 2
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
108010074708 B7-H1 Antigen Proteins 0.000 description 2
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
206010006187 Breast cancer Diseases 0.000 description 2
RYZUCJDBGQWDBP-WHCFWRGISA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C(=C2)Cl)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C(=C2)Cl)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O RYZUCJDBGQWDBP-WHCFWRGISA-N 0.000 description 2
PJFOGXKWERUIDK-CDJZJNNCSA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)C(F)(F)F)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)C(F)(F)F)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O PJFOGXKWERUIDK-CDJZJNNCSA-N 0.000 description 2
NJLQMGRSKNJJJU-BMXMUORJSA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)C)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)C)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O NJLQMGRSKNJJJU-BMXMUORJSA-N 0.000 description 2
CLLQMPREUHKPSL-HBMYTODVSA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)OCC1=CC=C(C=C1)OC)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)OCC1=CC=C(C=C1)OC)OC(C)=O)COC(C)=O CLLQMPREUHKPSL-HBMYTODVSA-N 0.000 description 2
BJIUBYCNEYPTJE-XSEKTIEYSA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)O)OC(C)=O)COC(C)=O BJIUBYCNEYPTJE-XSEKTIEYSA-N 0.000 description 2
YEVRZOCKXHBEKU-WHCFWRGISA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2F)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2F)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O YEVRZOCKXHBEKU-WHCFWRGISA-N 0.000 description 2
VFQSFWLHYKIWNL-XSEKTIEYSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O VFQSFWLHYKIWNL-XSEKTIEYSA-N 0.000 description 2
CSNCRMSDSLXESL-VUYAKXMISA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Br)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Br)OC(C)=O)COC(C)=O CSNCRMSDSLXESL-VUYAKXMISA-N 0.000 description 2
IBQPAJVRIIXLMD-VUYAKXMISA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Br)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1SC=C(N=1)Cl)OC(C)=O)COC(C)=O IBQPAJVRIIXLMD-VUYAKXMISA-N 0.000 description 2
DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
208000009798 Craniopharyngioma Diseases 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
229940076838 Immune checkpoint inhibitor Drugs 0.000 description 2
108010002350 Interleukin-2 Proteins 0.000 description 2
102000000588 Interleukin-2 Human genes 0.000 description 2
208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
HESSGHHCXGBPAJ-UHFFFAOYSA-N N-acetyllactosamine Natural products CC(=O)NC(C=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O HESSGHHCXGBPAJ-UHFFFAOYSA-N 0.000 description 2
101710195703 Oxygen-dependent coproporphyrinogen-III oxidase Proteins 0.000 description 2
102100036201 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Human genes 0.000 description 2
101710200437 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Proteins 0.000 description 2
229910019201 POBr3 Inorganic materials 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
208000005718 Stomach Neoplasms Diseases 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
208000024770 Thyroid neoplasm Diseases 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
108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 2
102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
229960001138 acetylsalicylic acid Drugs 0.000 description 2
239000002253 acid Substances 0.000 description 2
238000005903 acid hydrolysis reaction Methods 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
GZCGUPFRVQAUEE-UHFFFAOYSA-N alpha-D-galactose Natural products OCC(O)C(O)C(O)C(O)C=O GZCGUPFRVQAUEE-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-UHFFFAOYSA-N alpha-D-glucopyranose Natural products OCC1OC(O)C(O)C(O)C1O WQZGKKKJIJFFOK-UHFFFAOYSA-N 0.000 description 2
239000001099 ammonium carbonate Substances 0.000 description 2
230000001772 anti-angiogenic effect Effects 0.000 description 2
230000000118 anti-neoplastic effect Effects 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
125000006165 cyclic alkyl group Chemical group 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
230000001086 cytosolic effect Effects 0.000 description 2
230000006378 damage Effects 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
238000001212 derivatisation Methods 0.000 description 2
NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
230000003511 endothelial effect Effects 0.000 description 2
239000003623 enhancer Substances 0.000 description 2
206010017758 gastric cancer Diseases 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
229920000550 glycopolymer Polymers 0.000 description 2
230000003301 hydrolyzing effect Effects 0.000 description 2
210000002865 immune cell Anatomy 0.000 description 2
239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 2
230000036039 immunity Effects 0.000 description 2
230000001976 improved effect Effects 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
229960004768 irinotecan Drugs 0.000 description 2
UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
CSCZOWZTTGYYRE-UHFFFAOYSA-N methyl 5-chloro-3-fluoropyridine-2-carboxylate Chemical compound COC(=O)C1=NC=C(Cl)C=C1F CSCZOWZTTGYYRE-UHFFFAOYSA-N 0.000 description 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
239000000178 monomer Substances 0.000 description 2
238000010172 mouse model Methods 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 2
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
230000001737 promoting effect Effects 0.000 description 2
125000005494 pyridonyl group Chemical group 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
238000010992 reflux Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
125000006413 ring segment Chemical group 0.000 description 2
108010038196 saccharide-binding proteins Proteins 0.000 description 2
208000000587 small cell lung carcinoma Diseases 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
201000011549 stomach cancer Diseases 0.000 description 2
230000001629 suppression Effects 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
230000008685 targeting Effects 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
238000012360 testing method Methods 0.000 description 2
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 2
238000002560 therapeutic procedure Methods 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
201000002510 thyroid cancer Diseases 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 2
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 2
CXXYXDKJRAOBKX-UHFFFAOYSA-N (2,4-dimethoxyphenyl)methanethiol Chemical compound COC1=CC=C(CS)C(OC)=C1 CXXYXDKJRAOBKX-UHFFFAOYSA-N 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
GQBRZBHEPUQRPL-LJQANCHMSA-N 1-[4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 GQBRZBHEPUQRPL-LJQANCHMSA-N 0.000 description 1
125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
PYMYPHUHKUWMLA-UHFFFAOYSA-N 2,3,4,5-tetrahydroxypentanal Chemical compound OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
FDWSIACICRBLGW-UHFFFAOYSA-N 2,4,5-trichloro-1,3-thiazole Chemical compound ClC1=NC(Cl)=C(Cl)S1 FDWSIACICRBLGW-UHFFFAOYSA-N 0.000 description 1
MFBXAUUJBVLYJL-UHFFFAOYSA-N 2-(4,5-dichloro-1,3-thiazol-2-yl)ethynyl-trimethylsilane Chemical compound ClC=1N=C(SC=1Cl)C#C[Si](C)(C)C MFBXAUUJBVLYJL-UHFFFAOYSA-N 0.000 description 1
125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
ASETYIALRXDVDF-UHFFFAOYSA-N 2-Phenylethyl octanoate Chemical compound CCCCCCCC(=O)OCCC1=CC=CC=C1 ASETYIALRXDVDF-UHFFFAOYSA-N 0.000 description 1
WOUPIOIURYZNRU-UHFFFAOYSA-N 2-bromo-4-chloro-1,3-thiazole Chemical compound ClC1=CSC(Br)=N1 WOUPIOIURYZNRU-UHFFFAOYSA-N 0.000 description 1
ZUYRGLAEUQNRSZ-UHFFFAOYSA-N 2-bromo-4-sulfanylbenzonitrile Chemical compound BrC1=C(C#N)C=CC(=C1)S ZUYRGLAEUQNRSZ-UHFFFAOYSA-N 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
XOGYQVITULCUGU-UHFFFAOYSA-N 3,4,5-trichloroaniline Chemical compound NC1=CC(Cl)=C(Cl)C(Cl)=C1 XOGYQVITULCUGU-UHFFFAOYSA-N 0.000 description 1
VHUYFTLLFNDZPS-UHFFFAOYSA-N 3,4,5-trichlorobenzenethiol Chemical compound SC1=CC(Cl)=C(Cl)C(Cl)=C1 VHUYFTLLFNDZPS-UHFFFAOYSA-N 0.000 description 1
125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
VJKSFHMDFWEBEI-UHFFFAOYSA-N 3,5-dibromo-4-fluoroaniline Chemical compound NC1=CC(Br)=C(F)C(Br)=C1 VJKSFHMDFWEBEI-UHFFFAOYSA-N 0.000 description 1
FDHLQIBHWGBOBT-UHFFFAOYSA-N 3,5-dichloro-2-iodopyridine Chemical compound ClC=1C(=NC=C(C=1)Cl)I FDHLQIBHWGBOBT-UHFFFAOYSA-N 0.000 description 1
NKTZSKQMAITPBQ-UHFFFAOYSA-N 3,5-dichloro-4-fluoroaniline Chemical compound NC1=CC(Cl)=C(F)C(Cl)=C1 NKTZSKQMAITPBQ-UHFFFAOYSA-N 0.000 description 1
SMZAZDGFGOHROS-UHFFFAOYSA-N 3-bromo-2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=NC=CC=C1Br SMZAZDGFGOHROS-UHFFFAOYSA-N 0.000 description 1
HAWHARXIKMVJGR-UHFFFAOYSA-N 3-chloro-4-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=C(S)C=C1Cl HAWHARXIKMVJGR-UHFFFAOYSA-N 0.000 description 1
PXLHNIKIVRSZOO-UHFFFAOYSA-N 3-chloro-4-methylbenzenethiol Chemical compound CC1=CC=C(S)C=C1Cl PXLHNIKIVRSZOO-UHFFFAOYSA-N 0.000 description 1
AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
FHJVHVKVTUTGTA-UHFFFAOYSA-N 4,5-dichloro-2-fluoroaniline Chemical compound NC1=CC(Cl)=C(Cl)C=C1F FHJVHVKVTUTGTA-UHFFFAOYSA-N 0.000 description 1
UYBOCFWGSBKUEP-UHFFFAOYSA-N 4,5-dichloro-2-fluorobenzenethiol Chemical compound ClC1=CC(=C(C=C1Cl)S)F UYBOCFWGSBKUEP-UHFFFAOYSA-N 0.000 description 1
YKBLEWCBQGYSOX-UNYRHXCVSA-N 4-[1-[(2R,4S,5R)-2-(5,6-dichloropyridin-3-yl)sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=NC(=C1Cl)Cl)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O YKBLEWCBQGYSOX-UNYRHXCVSA-N 0.000 description 1
ANXOSUXMRNWBKV-UNYRHXCVSA-N 4-[1-[(2R,4S,5R)-2-[5-chloro-6-(trifluoromethyl)pyridin-3-yl]sulfanyl-3,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]triazol-4-yl]-3H-1,3-thiazol-2-one Chemical compound C1=C(C=NC(=C1Cl)C(F)(F)F)S[C@@H]2C([C@H]([C@H](C(O2)CO)O)N3C=C(N=N3)C4=CSC(=O)N4)O ANXOSUXMRNWBKV-UNYRHXCVSA-N 0.000 description 1
DLRXEPREUKUZQO-UHFFFAOYSA-N 4-chloro-1,3-thiazole Chemical compound ClC1=CSC=N1 DLRXEPREUKUZQO-UHFFFAOYSA-N 0.000 description 1
JRDMGVGCATYZPW-UHFFFAOYSA-N 4-chloro-2-fluorobenzonitrile Chemical compound FC1=CC(Cl)=CC=C1C#N JRDMGVGCATYZPW-UHFFFAOYSA-N 0.000 description 1
BVQCRCHSFBBKIM-UHFFFAOYSA-N 4-chloro-2-sulfanylbenzonitrile Chemical compound SC1=CC(Cl)=CC=C1C#N BVQCRCHSFBBKIM-UHFFFAOYSA-N 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
SIYPZKHSXDFDRA-UHFFFAOYSA-N 5-bromo-3-chloropyridine-2-carbonitrile Chemical compound ClC1=CC(Br)=CN=C1C#N SIYPZKHSXDFDRA-UHFFFAOYSA-N 0.000 description 1
AAKSNUWBFNMWOT-CXITWPJZSA-N 5-chloro-3-[(2R,3R,4S,5R,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-[4-(2-oxo-3H-1,3-thiazol-4-yl)triazol-1-yl]oxan-2-yl]sulfanylpyridine-2-carboxylic acid Chemical compound OC=1SC=C(N=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C(=NC=C(C=2)Cl)C(=O)O)O[C@@H]([C@@H]1O)CO)O AAKSNUWBFNMWOT-CXITWPJZSA-N 0.000 description 1
ISWYPIVHUPCJGU-UHFFFAOYSA-N 5-chloro-3-fluoropyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC=C(Cl)C=C1F ISWYPIVHUPCJGU-UHFFFAOYSA-N 0.000 description 1
102100023990 60S ribosomal protein L17 Human genes 0.000 description 1
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
206010067484 Adverse reaction Diseases 0.000 description 1
201000003076 Angiosarcoma Diseases 0.000 description 1
206010003571 Astrocytoma Diseases 0.000 description 1
102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
206010004146 Basal cell carcinoma Diseases 0.000 description 1
206010004593 Bile duct cancer Diseases 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
108010006654 Bleomycin Proteins 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
101100462138 Brassica napus OlnB1 gene Proteins 0.000 description 1
208000011691 Burkitt lymphomas Diseases 0.000 description 1
WENNNESZKBUYLY-CDJZJNNCSA-N C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC2=CC(=C(C=C2)Cl)Cl)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O WENNNESZKBUYLY-CDJZJNNCSA-N 0.000 description 1
VZTGDEUHJOKUFQ-IIIVKNBZSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C1(N=CSC1)Cl)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C1(N=CSC1)Cl)OC(C)=O)COC(C)=O VZTGDEUHJOKUFQ-IIIVKNBZSA-N 0.000 description 1
KLPDFLIRPRLFGR-WVXKDWSHSA-N C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O Chemical compound C(C)(=O)O[C@H]1[C@@H](SC=2C=NC(=C(C=2)Cl)C(F)(F)F)O[C@@H]([C@@H]([C@@H]1N1N=NC(=C1)C=1N=C(SC=1)O)OC(C)=O)COC(C)=O KLPDFLIRPRLFGR-WVXKDWSHSA-N 0.000 description 1
108091007381 CBL proteins Proteins 0.000 description 1
ZCUFTCUMEDALHC-UHFFFAOYSA-N CC[K] Chemical compound CC[K] ZCUFTCUMEDALHC-UHFFFAOYSA-N 0.000 description 1
102100024263 CD160 antigen Human genes 0.000 description 1
102100038077 CD226 antigen Human genes 0.000 description 1
101150013553 CD40 gene Proteins 0.000 description 1
108010062802 CD66 antigens Proteins 0.000 description 1
229940045513 CTLA4 antagonist Drugs 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 description 1
206010008342 Cervix carcinoma Diseases 0.000 description 1
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
208000005243 Chondrosarcoma Diseases 0.000 description 1
201000009047 Chordoma Diseases 0.000 description 1
208000006332 Choriocarcinoma Diseases 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
102100035813 E3 ubiquitin-protein ligase CBL Human genes 0.000 description 1
102100035273 E3 ubiquitin-protein ligase CBL-B Human genes 0.000 description 1
102100034214 E3 ubiquitin-protein ligase RNF128 Human genes 0.000 description 1
206010014733 Endometrial cancer Diseases 0.000 description 1
206010014759 Endometrial neoplasm Diseases 0.000 description 1
206010014967 Ependymoma Diseases 0.000 description 1
HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
208000000461 Esophageal Neoplasms Diseases 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
102000003973 Fibroblast growth factor 21 Human genes 0.000 description 1
108090000376 Fibroblast growth factor 21 Proteins 0.000 description 1
201000008808 Fibrosarcoma Diseases 0.000 description 1
108010001515 Galectin 4 Proteins 0.000 description 1
102000000805 Galectin 4 Human genes 0.000 description 1
102000044465 Galectin-7 Human genes 0.000 description 1
102000044445 Galectin-8 Human genes 0.000 description 1
102100025614 Galectin-related protein Human genes 0.000 description 1
208000032612 Glial tumor Diseases 0.000 description 1
206010018338 Glioma Diseases 0.000 description 1
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
101150012162 H-RAS gene Proteins 0.000 description 1
208000001258 Hemangiosarcoma Diseases 0.000 description 1
102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 1
101000884298 Homo sapiens CD226 antigen Proteins 0.000 description 1
101000737265 Homo sapiens E3 ubiquitin-protein ligase CBL-B Proteins 0.000 description 1
101000711673 Homo sapiens E3 ubiquitin-protein ligase RNF128 Proteins 0.000 description 1
101000608772 Homo sapiens Galectin-7 Proteins 0.000 description 1
101000608769 Homo sapiens Galectin-8 Proteins 0.000 description 1
101001004750 Homo sapiens Galectin-related protein Proteins 0.000 description 1
101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 1
101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 1
101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 1
101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 1
101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 1
241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
102000009438 IgE Receptors Human genes 0.000 description 1
108010073816 IgE Receptors Proteins 0.000 description 1
108010002352 Interleukin-1 Proteins 0.000 description 1
108010065805 Interleukin-12 Proteins 0.000 description 1
102000013462 Interleukin-12 Human genes 0.000 description 1
102000003812 Interleukin-15 Human genes 0.000 description 1
108090000172 Interleukin-15 Proteins 0.000 description 1
102100030704 Interleukin-21 Human genes 0.000 description 1
239000002211 L-ascorbic acid Substances 0.000 description 1
235000000069 L-ascorbic acid Nutrition 0.000 description 1
102000017578 LAG3 Human genes 0.000 description 1
102000007547 Laminin Human genes 0.000 description 1
108010085895 Laminin Proteins 0.000 description 1
206010023825 Laryngeal cancer Diseases 0.000 description 1
208000018142 Leiomyosarcoma Diseases 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
210000004322 M2 macrophage Anatomy 0.000 description 1
208000007054 Medullary Carcinoma Diseases 0.000 description 1
208000000172 Medulloblastoma Diseases 0.000 description 1
108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
101150097297 Nedd4 gene Proteins 0.000 description 1
208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
GIOMSDNHTBESOT-LYYZXLFJSA-N OC=1SC=C(N=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]1O)CO)O Chemical compound OC=1SC=C(N=1)C=1N=NN(C=1)[C@@H]1[C@H]([C@@H](SC=2C=NC(=C(C=2)Cl)C#N)O[C@@H]([C@@H]1O)CO)O GIOMSDNHTBESOT-LYYZXLFJSA-N 0.000 description 1
BIXUJZWHKMBPPF-DRRXZNNHSA-N OC[C@H]1O[C@H](SC2=CC(Br)=C(C=C2)C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Br)=C(C=C2)C#N)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=CSC(O)=N1 BIXUJZWHKMBPPF-DRRXZNNHSA-N 0.000 description 1
INGORPMDIARWLA-SKVYFBIASA-N OC[C@H]1O[C@H](SC2=CC(Br)=C(N=C2)C(F)(F)F)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(Cl)=C(Cl)S1 Chemical compound OC[C@H]1O[C@H](SC2=CC(Br)=C(N=C2)C(F)(F)F)[C@H](O)[C@H]([C@H]1O)N1C=C(N=N1)C1=NC(Cl)=C(Cl)S1 INGORPMDIARWLA-SKVYFBIASA-N 0.000 description 1
206010030155 Oesophageal carcinoma Diseases 0.000 description 1
201000010133 Oligodendroglioma Diseases 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
101150048735 POL3 gene Proteins 0.000 description 1
108010089484 PRM-151 Proteins 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
229910002666 PdCl2 Inorganic materials 0.000 description 1
241001494479 Pecora Species 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
208000007641 Pinealoma Diseases 0.000 description 1
241000139306 Platt Species 0.000 description 1
102100029740 Poliovirus receptor Human genes 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
108010076504 Protein Sorting Signals Proteins 0.000 description 1
208000003251 Pruritus Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
108030001238 RING-type E3 ubiquitin transferases Proteins 0.000 description 1
102000034442 RING-type E3 ubiquitin transferases Human genes 0.000 description 1
208000015634 Rectal Neoplasms Diseases 0.000 description 1
208000006265 Renal cell carcinoma Diseases 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
201000010208 Seminoma Diseases 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
241000282887 Suidae Species 0.000 description 1
230000005867 T cell response Effects 0.000 description 1
102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 1
208000000389 T-cell leukemia Diseases 0.000 description 1
208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
102100035268 T-cell surface protein tactile Human genes 0.000 description 1
102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
108091005735 TGF-beta receptors Proteins 0.000 description 1
208000024313 Testicular Neoplasms Diseases 0.000 description 1
210000000447 Th1 cell Anatomy 0.000 description 1
210000000068 Th17 cell Anatomy 0.000 description 1
102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 1
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
208000002495 Uterine Neoplasms Diseases 0.000 description 1
108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 description 1
102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 1
102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 1
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
208000008383 Wilms tumor Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
UOHUDFHWFDUDID-UHFFFAOYSA-N [Cl].C[SiH](C)C Chemical compound [Cl].C[SiH](C)C UOHUDFHWFDUDID-UHFFFAOYSA-N 0.000 description 1
WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
QQAGXJMLHRUMJF-UHFFFAOYSA-N acetylene trimethylsilane Chemical group C#C.C[SiH](C)C QQAGXJMLHRUMJF-UHFFFAOYSA-N 0.000 description 1
108010046470 acetylsalicylic acid hydrolase Proteins 0.000 description 1
150000008043 acidic salts Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
208000009956 adenocarcinoma Diseases 0.000 description 1
230000002411 adverse Effects 0.000 description 1
230000006838 adverse reaction Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
238000013019 agitation Methods 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
208000030961 allergic reaction Diseases 0.000 description 1
230000003281 allosteric effect Effects 0.000 description 1
230000002424 anti-apoptotic effect Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
238000011394 anticancer treatment Methods 0.000 description 1
150000008430 aromatic amides Chemical class 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
229960002756 azacitidine Drugs 0.000 description 1
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
229960002170 azathioprine Drugs 0.000 description 1
LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
201000007180 bile duct carcinoma Diseases 0.000 description 1
230000007321 biological mechanism Effects 0.000 description 1
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
201000001531 bladder carcinoma Diseases 0.000 description 1
229960001561 bleomycin Drugs 0.000 description 1
OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
238000009395 breeding Methods 0.000 description 1
230000001488 breeding effect Effects 0.000 description 1
208000003362 bronchogenic carcinoma Diseases 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229960004117 capecitabine Drugs 0.000 description 1
239000002775 capsule Substances 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
229960004562 carboplatin Drugs 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000000423 cell based assay Methods 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
230000022131 cell cycle Effects 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000003915 cell function Effects 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
238000002659 cell therapy Methods 0.000 description 1
208000030394 cerebellar neoplasm Diseases 0.000 description 1
201000010881 cervical cancer Diseases 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
229960004630 chlorambucil Drugs 0.000 description 1
239000012320 chlorinating reagent Substances 0.000 description 1
CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 1
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
208000006990 cholangiocarcinoma Diseases 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229940040387 citrus pectin Drugs 0.000 description 1
239000009194 citrus pectin Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
CZZBXGOYISFHRY-UHFFFAOYSA-N copper;hydroiodide Chemical compound [Cu].I CZZBXGOYISFHRY-UHFFFAOYSA-N 0.000 description 1
238000004132 cross linking Methods 0.000 description 1
239000013058 crude material Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
229960000684 cytarabine Drugs 0.000 description 1
229960000975 daunorubicin Drugs 0.000 description 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
230000007423 decrease Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
210000004443 dendritic cell Anatomy 0.000 description 1
230000000779 depleting effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000000539 dimer Substances 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
229960003668 docetaxel Drugs 0.000 description 1
ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
229950005454 doxifluridine Drugs 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
229940000406 drug candidate Drugs 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000007515 enzymatic degradation Effects 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
229960001904 epirubicin Drugs 0.000 description 1
208000037828 epithelial carcinoma Diseases 0.000 description 1
201000004101 esophageal cancer Diseases 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000010228 ex vivo assay Methods 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229960000390 fludarabine Drugs 0.000 description 1
GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
238000000198 fluorescence anisotropy Methods 0.000 description 1
238000002875 fluorescence polarization Methods 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 1
239000012634 fragment Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
108010065785 galectin 5 Proteins 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
229960005277 gemcitabine Drugs 0.000 description 1
230000013595 glycosylation Effects 0.000 description 1
238000006206 glycosylation reaction Methods 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
201000010536 head and neck cancer Diseases 0.000 description 1
208000014829 head and neck neoplasm Diseases 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
208000025750 heavy chain disease Diseases 0.000 description 1
210000002443 helper t lymphocyte Anatomy 0.000 description 1
201000002222 hemangioblastoma Diseases 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 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
230000001744 histochemical effect Effects 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
229960000908 idarubicin Drugs 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000001900 immune effect Effects 0.000 description 1
230000028993 immune response Effects 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000002055 immunohistochemical effect Effects 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000004968 inflammatory condition Effects 0.000 description 1
208000014674 injury Diseases 0.000 description 1
102000006495 integrins Human genes 0.000 description 1
108010044426 integrins Proteins 0.000 description 1
229940117681 interleukin-12 Drugs 0.000 description 1
108010074108 interleukin-21 Proteins 0.000 description 1
UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
150000002597 lactoses Chemical class 0.000 description 1
206010023841 laryngeal neoplasm Diseases 0.000 description 1
229960004942 lenalidomide Drugs 0.000 description 1
GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
206010024627 liposarcoma Diseases 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
201000007270 liver cancer Diseases 0.000 description 1
208000014018 liver neoplasm Diseases 0.000 description 1
201000005296 lung carcinoma Diseases 0.000 description 1
208000012804 lymphangiosarcoma Diseases 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
239000012528 membrane Substances 0.000 description 1
206010027191 meningioma Diseases 0.000 description 1
GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
229960001428 mercaptopurine Drugs 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
230000009456 molecular mechanism Effects 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
210000000663 muscle cell Anatomy 0.000 description 1
208000001611 myxosarcoma Diseases 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
239000002105 nanoparticle Substances 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229930014626 natural product Natural products 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
208000025189 neoplasm of testis Diseases 0.000 description 1
201000008026 nephroblastoma Diseases 0.000 description 1
208000007538 neurilemmoma Diseases 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
239000002547 new drug Substances 0.000 description 1
XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 1
229960004378 nintedanib Drugs 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
229920001542 oligosaccharide Polymers 0.000 description 1
150000002482 oligosaccharides Chemical class 0.000 description 1
CGBJSGAELGCMKE-UHFFFAOYSA-N omipalisib Chemical compound COC1=NC=C(C=2C=C3C(C=4C=NN=CC=4)=CC=NC3=CC=2)C=C1NS(=O)(=O)C1=CC=C(F)C=C1F CGBJSGAELGCMKE-UHFFFAOYSA-N 0.000 description 1
230000011164 ossification Effects 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
230000002018 overexpression Effects 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
229960001756 oxaliplatin Drugs 0.000 description 1
DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
201000002528 pancreatic cancer Diseases 0.000 description 1
208000008443 pancreatic carcinoma Diseases 0.000 description 1
208000004019 papillary adenocarcinoma Diseases 0.000 description 1
201000010198 papillary carcinoma Diseases 0.000 description 1
230000007110 pathogen host interaction Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
208000024724 pineal body neoplasm Diseases 0.000 description 1
201000004123 pineal gland cancer Diseases 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
125000004928 piperidonyl group Chemical group 0.000 description 1
229960003073 pirfenidone 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
108010048507 poliovirus receptor Proteins 0.000 description 1
229920000962 poly(amidoamine) Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000000861 pro-apoptotic effect Effects 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
230000002797 proteolythic effect Effects 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 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
230000005855 radiation Effects 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
206010038038 rectal cancer Diseases 0.000 description 1
201000001275 rectum cancer Diseases 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000021014 regulation of cell growth Effects 0.000 description 1
230000012121 regulation of immune response Effects 0.000 description 1
210000003289 regulatory T cell Anatomy 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000008844 regulatory mechanism Effects 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
229930002330 retinoic acid Natural products 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
201000009410 rhabdomyosarcoma Diseases 0.000 description 1
210000003705 ribosome Anatomy 0.000 description 1
229940121324 romilkimab Drugs 0.000 description 1
239000000523 sample Substances 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
201000008407 sebaceous adenocarcinoma Diseases 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
PEGQOIGYZLJMIB-UHFFFAOYSA-N setogepram Chemical compound CCCCCC1=CC=CC(CC(O)=O)=C1 PEGQOIGYZLJMIB-UHFFFAOYSA-N 0.000 description 1
229950009513 simtuzumab Drugs 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
241000894007 species Species 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
201000010965 sweat gland carcinoma Diseases 0.000 description 1
239000012622 synthetic inhibitor Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
201000003120 testicular cancer Diseases 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
150000003556 thioamides Chemical class 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
HHNQDLUNMOECFS-UHFFFAOYSA-N thiophene;2h-triazole Chemical group C=1C=CSC=1.C1=CNN=N1 HHNQDLUNMOECFS-UHFFFAOYSA-N 0.000 description 1
230000002992 thymic effect Effects 0.000 description 1
230000007838 tissue remodeling Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
WOFPTESETJKCBH-UHFFFAOYSA-N trimethyl(2-pyridin-2-ylethynyl)silane Chemical compound C[Si](C)(C)C#CC1=CC=CC=N1 WOFPTESETJKCBH-UHFFFAOYSA-N 0.000 description 1
230000005747 tumor angiogenesis Effects 0.000 description 1
230000004614 tumor growth Effects 0.000 description 1
125000004417 unsaturated alkyl group Chemical group 0.000 description 1
208000010570 urinary bladder carcinoma Diseases 0.000 description 1
230000002485 urinary effect Effects 0.000 description 1
206010046766 uterine cancer Diseases 0.000 description 1
229960005486 vaccine Drugs 0.000 description 1
229960000653 valrubicin Drugs 0.000 description 1
ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004355 vindesine Drugs 0.000 description 1
UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
229960002066 vinorelbine Drugs 0.000 description 1
GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
239000012991 xanthate Substances 0.000 description 1