MD3755703T2 - Derivați N-(fenil)-2-(fenil)pirimidin-4-carboxamidă și compuși înrudiți ca inhibitori HPK1 pentru tratarea cancerului - Google Patents

Info

Publication number

MD3755703T2

MD3755703T2 MDE20210010T MDE20210010T MD3755703T2 MD 3755703 T2 MD3755703 T2 MD 3755703T2 MD E20210010 T MDE20210010 T MD E20210010T MD E20210010 T MDE20210010 T MD E20210010T MD 3755703 T2 MD3755703 T2 MD 3755703T2

Authority

MD

Moldova

Prior art keywords

alkyl

independently selected

membered heterocycloalkyl

optionally substituted

cycloalkyl

Prior art date

2018-02-20

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 157
• 206010028980 Neoplasm Diseases 0.000 title claims abstract description 41
• 201000011510 cancer Diseases 0.000 title claims abstract description 11
• 102100028199 Mitogen-activated protein kinase kinase kinase kinase 1 Human genes 0.000 title abstract description 46
• 239000003112 inhibitor Substances 0.000 title abstract description 34
• XVLYIDSQDWSVHR-UHFFFAOYSA-N N,2-diphenylpyrimidine-4-carboxamide Chemical class C1(=CC=CC=C1)NC(=O)C1=NC(=NC=C1)C1=CC=CC=C1 XVLYIDSQDWSVHR-UHFFFAOYSA-N 0.000 title abstract 2
• 101001059991 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 1 Proteins 0.000 title description 2
• 206010006187 Breast cancer Diseases 0.000 claims abstract description 7
• 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 7
• 208000020816 lung neoplasm Diseases 0.000 claims abstract description 7
• 206010009944 Colon cancer Diseases 0.000 claims abstract description 5
• 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 5
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims abstract description 5
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims abstract description 4
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims abstract description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 4
• 201000005202 lung cancer Diseases 0.000 claims abstract description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims abstract description 4
• 201000002528 pancreatic cancer Diseases 0.000 claims abstract description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 claims abstract description 4
• NMDDKDJYFSZOAT-UHFFFAOYSA-N 2-(2-fluoro-6-methoxyphenyl)-N-[5-fluoro-2-(2-pyridin-2-ylpyrrolidin-1-yl)phenyl]pyrimidine-4-carboxamide Chemical compound FC=1C=CC(=C(C=1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1C(CCC1)C1=NC=CC=C1 NMDDKDJYFSZOAT-UHFFFAOYSA-N 0.000 claims abstract description 3
• CICYHHIRLJBKTE-UHFFFAOYSA-N N-[2-(3,3a,4,5,6,6a-hexahydro-2H-pyrrolo[2,3-c]pyrrol-1-yl)-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COC1=CC=CC(F)=C1C1=NC(=CC=N1)C(=O)NC1=C(C=CC(F)=C1)N1CCC2CNCC12 CICYHHIRLJBKTE-UHFFFAOYSA-N 0.000 claims abstract description 3
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 452
• 125000001424 substituent group Chemical group 0.000 claims description 431
• 125000000217 alkyl group Chemical group 0.000 claims description 413
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 410
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 409
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 385
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 384
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 332
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 304
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 265
• 229910020008 S(O) Inorganic materials 0.000 claims description 264
• -1 aminosulfonylamino Chemical group 0.000 claims description 263
• 229910052799 carbon Inorganic materials 0.000 claims description 250
• 125000002947 alkylene group Chemical group 0.000 claims description 242
• 229910052739 hydrogen Inorganic materials 0.000 claims description 212
• 125000005843 halogen group Chemical group 0.000 claims description 177
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 170
• 125000003118 aryl group Chemical group 0.000 claims description 138
• 125000004429 atom Chemical group 0.000 claims description 108
• 150000003839 salts Chemical class 0.000 claims description 101
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 90
• 229910052717 sulfur Inorganic materials 0.000 claims description 81
• 229910052805 deuterium Inorganic materials 0.000 claims description 71
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 64
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 64
• 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 60
• 125000005842 heteroatom Chemical group 0.000 claims description 60
• 229910052760 oxygen Inorganic materials 0.000 claims description 59
• 125000004432 carbon atom Chemical group C* 0.000 claims description 57
• 125000003545 alkoxy group Chemical group 0.000 claims description 51
• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 47
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 47
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 39
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 39
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 36
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 32
• 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims description 32
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 32
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 229910052701 rubidium Inorganic materials 0.000 claims description 18
• 229910052731 fluorine Inorganic materials 0.000 claims description 13
• 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
• HKSQZEGSMBFHGC-UHFFFAOYSA-N pyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=N1 HKSQZEGSMBFHGC-UHFFFAOYSA-N 0.000 claims description 9
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 7
• 101100310927 Caenorhabditis elegans sra-4 gene Proteins 0.000 claims description 7
• 101000869592 Daucus carota Major allergen Dau c 1 Proteins 0.000 claims description 7
• 101000650136 Homo sapiens WAS/WASL-interacting protein family member 3 Proteins 0.000 claims description 7
• 102100027539 WAS/WASL-interacting protein family member 3 Human genes 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 101100310930 Caenorhabditis elegans sra-8 gene Proteins 0.000 claims description 6
• 102100038417 Cytoplasmic FMR1-interacting protein 1 Human genes 0.000 claims description 5
• 101710181791 Cytoplasmic FMR1-interacting protein 1 Proteins 0.000 claims description 5
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 5
• 229910052794 bromium Inorganic materials 0.000 claims description 5
• 101150019129 sra-11 gene Proteins 0.000 claims description 5
• 101150075827 sra-12 gene Proteins 0.000 claims description 5
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 4
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 4
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 4
• 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 4
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 4
• 101100310920 Caenorhabditis elegans sra-2 gene Proteins 0.000 claims description 4
• 101100310926 Caenorhabditis elegans sra-3 gene Proteins 0.000 claims description 4
• 101100310928 Caenorhabditis elegans sra-6 gene Proteins 0.000 claims description 4
• 101100310929 Caenorhabditis elegans sra-7 gene Proteins 0.000 claims description 4
• 101100310931 Caenorhabditis elegans sra-9 gene Proteins 0.000 claims description 4
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims description 4
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• BYKKKWRJTQLOBH-PXAMGESCSA-N nrc-15 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(C)=O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)CN)C1=CN=CN1 BYKKKWRJTQLOBH-PXAMGESCSA-N 0.000 claims description 4
• 101150081057 sra-10 gene Proteins 0.000 claims description 4
• 101150028258 sra-13 gene Proteins 0.000 claims description 4
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
• XCAXLCSQKKQKHA-PMACEKPBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)CO XCAXLCSQKKQKHA-PMACEKPBSA-N 0.000 claims description 3
• SUBYPZBREZXPCW-GJZGRUSLSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=C(C=C1)F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)CO SUBYPZBREZXPCW-GJZGRUSLSA-N 0.000 claims description 3
• 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• ABTDMVCVUKSZKX-QZTJIDSGSA-N (1R,4R)-5-[4-fluoro-2-[[2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carbonyl]amino]phenyl]-N-propyl-2,5-diazabicyclo[2.2.1]heptane-2-carboxamide Chemical compound FC1=CC(=C(C=C1)N1[C@H]2CN([C@@H](C1)C2)C(=O)NCCC)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F ABTDMVCVUKSZKX-QZTJIDSGSA-N 0.000 claims description 2
• AASCKKABVVRGPP-UHFFFAOYSA-N 2-(2-fluoro-6-methoxyphenyl)-N-(2-piperidin-4-ylphenyl)pyrimidine-4-carboxamide Chemical compound FC1=C(C(=CC=C1)OC)C1=NC=CC(=N1)C(=O)NC1=C(C=CC=C1)C1CCNCC1 AASCKKABVVRGPP-UHFFFAOYSA-N 0.000 claims description 2
• LEIMWMGQPLLTEJ-CQSZACIVSA-N 2-(2-fluoro-6-methoxyphenyl)-N-[5-fluoro-2-[(2R)-2-methylpiperazin-1-yl]phenyl]pyrimidine-4-carboxamide Chemical compound C1=C(F)C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1[C@@H](CNCC1)C LEIMWMGQPLLTEJ-CQSZACIVSA-N 0.000 claims description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
• RNXDYGITDFPZQI-TYKWCNGQSA-N C=1(C(=NN(C=1C)C)C)C1=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(OC)C=CC=C2F)C([C@H]2CC[C@@H](N)CC2)=C1 Chemical compound C=1(C(=NN(C=1C)C)C)C1=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(OC)C=CC=C2F)C([C@H]2CC[C@@H](N)CC2)=C1 RNXDYGITDFPZQI-TYKWCNGQSA-N 0.000 claims description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
• GQAGJQNVOPGUCQ-UHFFFAOYSA-N N-[2-(3-aminocyclohexyl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N(C1=C(C2CC(CCC2)N)C=CC=C1)C(=O)C1=CC=NC(=N1)C1=C(OC)C=CC=C1F GQAGJQNVOPGUCQ-UHFFFAOYSA-N 0.000 claims description 2
• LLFCXYBVJBKXHH-UHFFFAOYSA-N N-[2-(3-aminocyclopentyl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N(C1=C(C2CCC(N)C2)C=CC=C1)C(=O)C1=CC=NC(=N1)C1=C(OC)C=CC=C1F LLFCXYBVJBKXHH-UHFFFAOYSA-N 0.000 claims description 2
• KDAAWCZNTXBHPP-QZTJIDSGSA-N N-[2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-3-(1-methylpyrazol-4-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound [C@H]12N(C[C@H](NC1)C2)C1=C(C=C(C=C1C=1C=NN(C=1)C)F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F KDAAWCZNTXBHPP-QZTJIDSGSA-N 0.000 claims description 2
• YOVUFANMIRCCQZ-RTBURBONSA-N N-[2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-3-pyridin-3-ylphenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound [C@H]12N(C[C@H](NC1)C2)C1=C(C=C(C=C1C=1C=NC=CC=1)F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F YOVUFANMIRCCQZ-RTBURBONSA-N 0.000 claims description 2
• JKHBVOCOHYSWTQ-HUUCEWRRSA-N N-[2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound [C@H]12N(C[C@H](NC1)C2)C1=C(C=C(C=C1)F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F JKHBVOCOHYSWTQ-HUUCEWRRSA-N 0.000 claims description 2
• UTYUODSGWVOIFI-HUUCEWRRSA-N N-[2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-methoxyphenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound [C@H]12N(C[C@H](NC1)C2)C1=C(C=C(C=C1)OC)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F UTYUODSGWVOIFI-HUUCEWRRSA-N 0.000 claims description 2
• QIDMUDUZDJKNEX-PMACEKPBSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-(1,3,5-trimethylpyrazol-4-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1ccc(cc1N1C[C@@H]2C[C@H]1CN2)-c1c(C)nn(C)c1C QIDMUDUZDJKNEX-PMACEKPBSA-N 0.000 claims description 2
• VCZPJHYQIPIKSV-PMACEKPBSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-(2-methylpyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1ccc(cc1N1C[C@@H]2C[C@H]1CN2)-c1cccnc1C VCZPJHYQIPIKSV-PMACEKPBSA-N 0.000 claims description 2
• DSDYWUYEEWMDFK-OALUTQOASA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-(4-methoxypyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1ccncc1-c1ccc(NC(=O)c2ccnc(n2)-c2c(F)cccc2OC)c(c1)N1C[C@@H]2C[C@H]1CN2 DSDYWUYEEWMDFK-OALUTQOASA-N 0.000 claims description 2
• JEHNXRAWWCPZSM-IHPCNDPISA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-[(2S)-2-(methoxymethyl)azetidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COC[C@@H]1CCN1c1ccc(NC(=O)c2ccnc(n2)-c2c(F)cccc2OC)c(c1)N1C[C@@H]2C[C@H]1CN2 JEHNXRAWWCPZSM-IHPCNDPISA-N 0.000 claims description 2
• UZLJNVXUUAUUCL-ROUUACIJSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-(1-methyl-6-oxopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1cc(F)c(cc1N1C[C@@H]2C[C@H]1CN2)-c1ccc(=O)n(C)c1 UZLJNVXUUAUUCL-ROUUACIJSA-N 0.000 claims description 2
• IVCZPZNMHCJCCD-IRXDYDNUSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-(1-methylpyrazol-4-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1cc(F)c(cc1N1C[C@@H]2C[C@H]1CN2)-c1cnn(C)c1 IVCZPZNMHCJCCD-IRXDYDNUSA-N 0.000 claims description 2
• JBFWLYUTIKICBY-ROUUACIJSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-(2-methylpyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1cc(F)c(cc1N1C[C@@H]2C[C@H]1CN2)-c1cccnc1C JBFWLYUTIKICBY-ROUUACIJSA-N 0.000 claims description 2
• UIXZBVNKVGAKSX-GJZGRUSLSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-(hydroxymethyl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1cc(F)c(CO)cc1N1C[C@@H]2C[C@H]1CN2 UIXZBVNKVGAKSX-GJZGRUSLSA-N 0.000 claims description 2
• YVDUQPDPKGEWFB-OALUTQOASA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-(morpholin-4-ylmethyl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1cc(F)c(CN2CCOCC2)cc1N1C[C@@H]2C[C@H]1CN2 YVDUQPDPKGEWFB-OALUTQOASA-N 0.000 claims description 2
• JJXNJDIRWJNGBX-OAHLLOKOSA-N N-[2-[(2R)-2-(aminomethyl)pyrrolidin-1-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N(C1=C(N2CCC[C@@H]2CN)C=CC(F)=C1)C(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC JJXNJDIRWJNGBX-OAHLLOKOSA-N 0.000 claims description 2
• HGFPJAGQCIFATM-OAQYLSRUSA-N N-[2-[(2R)-2-(cyanomethyl)morpholin-4-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(C=2C=NC=CC=2C#N)=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)C(N2C[C@@H](CC#N)OCC2)=C1 HGFPJAGQCIFATM-OAQYLSRUSA-N 0.000 claims description 2
• NRYRSQRRSBLVER-IRXDYDNUSA-N N-[2-[(2S,4S)-4-(dimethylamino)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(F)C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1C[C@@H](N(C)C)C[C@H]1CO NRYRSQRRSBLVER-IRXDYDNUSA-N 0.000 claims description 2
• WXKLVVXNBFIYSG-DCFHFQCYSA-N N-[2-[(2S,4S)-4-amino-2-(1-hydroxycyclopropyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)C1(CC1)O WXKLVVXNBFIYSG-DCFHFQCYSA-N 0.000 claims description 2
• YTYIKQGGIQKXKW-DCFHFQCYSA-N N-[2-[(2S,4S)-4-amino-2-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)C(C)(C)O YTYIKQGGIQKXKW-DCFHFQCYSA-N 0.000 claims description 2
• WJEPQBUJWFNXPG-IRXDYDNUSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(1-cyanocyclopropyl)phenyl]-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C1(CC1)C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1F)F)CO WJEPQBUJWFNXPG-IRXDYDNUSA-N 0.000 claims description 2
• SXTCCWXLNUBUGV-PMACEKPBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(2-cyano-6-fluorophenyl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound FC1=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(F)C=CC=C3OC)C(N3C[C@@H](N)C[C@H]3CO)=C2)C(C#N)=CC=C1 SXTCCWXLNUBUGV-PMACEKPBSA-N 0.000 claims description 2
• BLLJUCXNHUVEHL-PMACEKPBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(2-methylpyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C=1(C=CC=NC=1C)C1=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)C(N2C[C@@H](N)C[C@H]2CO)=C1 BLLJUCXNHUVEHL-PMACEKPBSA-N 0.000 claims description 2
• MRLPZQXQFOPDDQ-PMACEKPBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(3-cyanopyridin-4-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C1=C(C=NC=C1)C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)CO MRLPZQXQFOPDDQ-PMACEKPBSA-N 0.000 claims description 2
• ZMSBSUWREUXWEU-OALUTQOASA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(3-methoxypyridin-4-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(C=2C(OC)=CN=CC=2)=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)C(N2[C@@H](C[C@H](N)C2)CO)=C1 ZMSBSUWREUXWEU-OALUTQOASA-N 0.000 claims description 2
• WAWDCCVZPCGIJC-OALUTQOASA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyano-2-methylpyrazol-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(=C(C=NN1C)C#N)C1=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)C(N2[C@@H](C[C@H](N)C2)CO)=C1 WAWDCCVZPCGIJC-OALUTQOASA-N 0.000 claims description 2
• SEKQICVALVTKMV-OALUTQOASA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2,3-difluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(C#N)=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(OC)C=CC(F)=C3F)C(N3C[C@@H](N)C[C@H]3CO)=C2)C=NC=C1 SEKQICVALVTKMV-OALUTQOASA-N 0.000 claims description 2
• PJPVNRZDRDNSLL-OALUTQOASA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-chloro-6-fluorophenyl)pyrimidine-4-carboxamide Chemical compound C1(C#N)=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(Cl)C=CC=C3F)C(N3C[C@@H](N)C[C@H]3CO)=C2)C=NC=C1 PJPVNRZDRDNSLL-OALUTQOASA-N 0.000 claims description 2
• KZPWAZPBJQZJGY-VXKWHMMOSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-cyclopropyl-6-fluorophenyl)pyrimidine-4-carboxamide Chemical compound C=1(C=NC=CC=1C#N)C1=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(C3CC3)C=CC=C2F)C(N2C[C@@H](N)C[C@H]2CO)=C1 KZPWAZPBJQZJGY-VXKWHMMOSA-N 0.000 claims description 2
• RQXLMBLSWQYUNA-SFTDATJTSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-ethoxy-6-fluorophenyl)pyrimidine-4-carboxamide Chemical compound C=1(C=NC=CC=1C#N)C1=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(OCC)C=CC=C2F)C(N2[C@H](CO)C[C@H](N)C2)=C1 RQXLMBLSWQYUNA-SFTDATJTSA-N 0.000 claims description 2
• BZUQIMZNTIMOAJ-SFTDATJTSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxy-4-methylphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=C(C=C1OC)C)F)CO BZUQIMZNTIMOAJ-SFTDATJTSA-N 0.000 claims description 2
• SOVOQANEIZCLPU-SFTDATJTSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methylphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(C)C=CC=C3F)C(N3[C@@H](C[C@H](N)C3)CO)=C2)C=NC=C1 SOVOQANEIZCLPU-SFTDATJTSA-N 0.000 claims description 2
• YAOFYZWYGQFFGQ-OALUTQOASA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(3,6-difluoro-2-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(C#N)=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(OC)C(F)=CC=C3F)C(N3C[C@@H](N)C[C@H]3CO)=C2)C=NC=C1 YAOFYZWYGQFFGQ-OALUTQOASA-N 0.000 claims description 2
• GNAQOVDYXBQJML-PMACEKPBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(3,6-difluoro-2-methylphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(C)C(F)=CC=C3F)C(N3[C@@H](C[C@H](N)C3)CO)=C2)C=NC=C1 GNAQOVDYXBQJML-PMACEKPBSA-N 0.000 claims description 2
• SEKQICVALVTKMV-LAYNNCTGSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-[2,3-difluoro-6-(trideuteriomethoxy)phenyl]pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C(=CC=C1OC([2H])([2H])[2H])F)F)CO SEKQICVALVTKMV-LAYNNCTGSA-N 0.000 claims description 2
• FMVORWLTJBNIRP-OALUTQOASA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-[2-(difluoromethoxy)-6-fluorophenyl]pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1F)OC(F)F)CO FMVORWLTJBNIRP-OALUTQOASA-N 0.000 claims description 2
• XCAXLCSQKKQKHA-HIXAKMJBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-[2-fluoro-6-(trideuteriomethoxy)phenyl]pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC([2H])([2H])[2H])F)CO XCAXLCSQKKQKHA-HIXAKMJBSA-N 0.000 claims description 2
• YAOFYZWYGQFFGQ-LAYNNCTGSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-[3,6-difluoro-2-(trideuteriomethoxy)phenyl]pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C(=CC=C1F)F)OC([2H])([2H])[2H])CO YAOFYZWYGQFFGQ-LAYNNCTGSA-N 0.000 claims description 2
• OBXZCGSMSIDKGN-JDNSAJSRSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-[3-cyano-2-fluoro-6-(trideuteriomethoxy)phenyl]pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C(=CC=C1OC([2H])([2H])[2H])C#N)F)CO OBXZCGSMSIDKGN-JDNSAJSRSA-N 0.000 claims description 2
• XCAXLCSQKKQKHA-QJPPTZNUSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-[3-deuterio-6-fluoro-2-(trideuteriomethoxy)phenyl]pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC(=C1OC([2H])([2H])[2H])[2H])F)CO XCAXLCSQKKQKHA-QJPPTZNUSA-N 0.000 claims description 2
• XBYPJFSNPXFDIH-VXKWHMMOSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-5-cyano-6-(2-fluoro-6-methoxyphenyl)pyridine-2-carboxamide Chemical compound C1(C#N)=C(C2=CC=C(NC(=O)C3=CC=C(C#N)C(C4=C(F)C=CC=C4OC)=N3)C(N3C[C@@H](N)C[C@H]3CO)=C2)C=NC=C1 XBYPJFSNPXFDIH-VXKWHMMOSA-N 0.000 claims description 2
• CHVFUQSUXYNPPR-VXKWHMMOSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(5-cyano-2-pyrrolidin-1-ylpyridin-4-yl)phenyl]-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C1=CC(=NC=C1C#N)N1CCCC1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1F)F)CO CHVFUQSUXYNPPR-VXKWHMMOSA-N 0.000 claims description 2
• UBLUXQFTLMTYLO-PMACEKPBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(oxan-4-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1C(C2=CC(=C(C=C2)NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)N2C[C@@H](N)C[C@H]2CO)CCOC1 UBLUXQFTLMTYLO-PMACEKPBSA-N 0.000 claims description 2
• LYYVVXSDOBKXQQ-GJZGRUSLSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-chlorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(=CC=C(C=C1N1[C@@H](C[C@H](N)C1)CO)Cl)NC(=O)C1=CC=NC(=N1)C1=C(OC)C=CC=C1F LYYVVXSDOBKXQQ-GJZGRUSLSA-N 0.000 claims description 2
• ATUJAUVLSRXUKR-GJZGRUSLSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(=CC=C(C=C1N1[C@@H](C[C@H](N)C1)CO)F)NC(=O)C1=CC=NC(=N1)C1=C(OC)C=CC=C1F ATUJAUVLSRXUKR-GJZGRUSLSA-N 0.000 claims description 2
• IOHPKJPPERILGU-GJZGRUSLSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-methylsulfonylphenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)S(=O)(=O)C)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)CO IOHPKJPPERILGU-GJZGRUSLSA-N 0.000 claims description 2
• BJCGXALNCRGPBG-ROUUACIJSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-propan-2-ylphenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C(C)C)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)CO BJCGXALNCRGPBG-ROUUACIJSA-N 0.000 claims description 2
• NDNBINPLTHGVKS-KBPBESRZSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-5-fluorophenyl]-2-(2,3-difluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(OC)C=CC(F)=C1F)N1C[C@@H](N)C[C@H]1CO)F NDNBINPLTHGVKS-KBPBESRZSA-N 0.000 claims description 2
• AJBJISUUCJXQBM-KBPBESRZSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-5-fluorophenyl]-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=C(C=C1)F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1F)F)CO AJBJISUUCJXQBM-KBPBESRZSA-N 0.000 claims description 2
• VCJUDPLLCXBMCM-HOTGVXAUSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-5-fluorophenyl]-2-(3-cyano-2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=C(C=C1)F)NC(=O)C1=NC(=NC=C1)C1=C(C(=CC=C1OC)C#N)F)CO VCJUDPLLCXBMCM-HOTGVXAUSA-N 0.000 claims description 2
• NQUIPSPVQHBWOM-LYDMTYCISA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-5-fluorophenyl]-2-[2-fluoro-3-methyl-6-(trideuteriomethoxy)phenyl]pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=C(C=C1)F)NC(=O)C1=NC(=NC=C1)C1=C(C(=CC=C1OC([2H])([2H])[2H])C)F)CO NQUIPSPVQHBWOM-LYDMTYCISA-N 0.000 claims description 2
• ADUXEIHMPHRMBP-HOTGVXAUSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylphenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(=CC(=CC=C1N1C[C@@H](N)C[C@H]1CO)C)NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC ADUXEIHMPHRMBP-HOTGVXAUSA-N 0.000 claims description 2
• NSYCWQABINWBNU-ROUUACIJSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-6-(1,3,5-trimethylpyrazol-4-yl)pyridin-3-yl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=NC(=CC=C1NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)C=1C(=NN(C=1C)C)C)CO NSYCWQABINWBNU-ROUUACIJSA-N 0.000 claims description 2
• FEHHLVAMJBTESK-GJZGRUSLSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)CO FEHHLVAMJBTESK-GJZGRUSLSA-N 0.000 claims description 2
• XCAXLCSQKKQKHA-PVPQDCENSA-N N-[2-[(2S,4S)-4-amino-2-[dideuterio(hydroxy)methyl]pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)C([2H])([2H])O XCAXLCSQKKQKHA-PVPQDCENSA-N 0.000 claims description 2
• ZXFVDANYDFDDRY-RXVVDRJESA-N N-[2-[(2S,4S)-4-amino-2-methylpiperidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@@H]1C[C@@H](N(CC1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)C ZXFVDANYDFDDRY-RXVVDRJESA-N 0.000 claims description 2
• PZWKQEQSYRXWEJ-AWEZNQCLSA-N N-[2-[(3S)-3-aminopyrrolidin-1-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1C[C@@H](N)CC1)F PZWKQEQSYRXWEJ-AWEZNQCLSA-N 0.000 claims description 2
• JZPWBAMLOBMQQB-HXUWFJFHSA-N N-[2-[(8aR)-3-oxo-5,6,8,8a-tetrahydro-1H-[1,3]oxazolo[3,4-a]pyrazin-7-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C=NC=C1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1C[C@H]2N(CC1)C(OC2)=O JZPWBAMLOBMQQB-HXUWFJFHSA-N 0.000 claims description 2
• LABQLLVGLJUGKJ-HZPDHXFCSA-N N-[3-cyano-2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound [C@H]12N(C[C@H](NC1)C2)C1=C(C=CC=C1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F LABQLLVGLJUGKJ-HZPDHXFCSA-N 0.000 claims description 2
• XYVBNQKFSKHJQS-ROUUACIJSA-N N-[4-(3-cyanopyridin-4-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1ccc(c(F)c1N1C[C@@H]2C[C@H]1CN2)-c1ccncc1C#N XYVBNQKFSKHJQS-ROUUACIJSA-N 0.000 claims description 2
• IPHYANNUDKBFBD-PMACEKPBSA-N N-[4-(3-cyanopyridin-4-yl)-2-[(2S,4S)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C=1(C=CN=CC=1C#N)C1=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)C(N2C[C@@H](O)C[C@H]2CO)=C1 IPHYANNUDKBFBD-PMACEKPBSA-N 0.000 claims description 2
• XDLMFXYMCXJTLV-UHFFFAOYSA-N N-[4-(4-cyanopyridin-3-yl)-2-(4-methylpiperazin-1-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C=NC=C1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1CCN(CC1)C XDLMFXYMCXJTLV-UHFFFAOYSA-N 0.000 claims description 2
• IKKRRLFINVYTBM-YLORPAJWSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(1S,3R,4S)-3-(hydroxymethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C=NC=C1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1[C@@H]2CN[C@H]([C@@H]1CO)C2 IKKRRLFINVYTBM-YLORPAJWSA-N 0.000 claims description 2
• QLSPHCRQKIJNFU-WRGVRERRSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(1S,4S)-1-(hydroxymethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C=NC=C1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1[C@@]2(CN[C@H](C1)C2)CO QLSPHCRQKIJNFU-WRGVRERRSA-N 0.000 claims description 2
• XRORCPXIZILXNC-PMACEKPBSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1ccc(cc1N1C[C@@H]2C[C@H]1CN2)-c1cnccc1C#N XRORCPXIZILXNC-PMACEKPBSA-N 0.000 claims description 2
• YQXNONOLWITCCE-BGOLNKOXSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(1S,4S)-4-(hydroxymethyl)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C=NC=C1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1[C@@H]2CN([C@](C1)(C2)CO)C YQXNONOLWITCCE-BGOLNKOXSA-N 0.000 claims description 2
• NFWXCTFEDOTPOS-IBGZPJMESA-N N-[4-(4-cyanopyridin-3-yl)-2-[(2S)-2-(hydroxymethyl)azetidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(C=2C=NC=CC=2C#N)=CC=C(NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)C(N2CC[C@H]2CO)=C1 NFWXCTFEDOTPOS-IBGZPJMESA-N 0.000 claims description 2
• GIJBICQSKQXRAY-FQEVSTJZSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(2S)-2-(hydroxymethyl)morpholin-4-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N#CC1=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(F)C=CC=C3OC)C(N3C[C@@H](CO)OCC3)=C2)C=NC=C1 GIJBICQSKQXRAY-FQEVSTJZSA-N 0.000 claims description 2
• QXYFMKJAPDFZAL-QFIPXVFZSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(2S)-2-[(dimethylamino)methyl]morpholin-4-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C=NC=C1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1C[C@@H](OCC1)CN(C)C QXYFMKJAPDFZAL-QFIPXVFZSA-N 0.000 claims description 2
• QWYZASZVCSXDCB-NQIIRXRSSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(2S,5R)-2-(hydroxymethyl)-5-methylpiperazin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C=NC=C1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1[C@@H](CN[C@@H](C1)C)CO QWYZASZVCSXDCB-NQIIRXRSSA-N 0.000 claims description 2
• QWYZASZVCSXDCB-RXVVDRJESA-N N-[4-(4-cyanopyridin-3-yl)-2-[(2S,5S)-2-(hydroxymethyl)-5-methylpiperazin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(#N)C1=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(F)C=CC=C3OC)C(N3[C@@H](CN[C@H](C3)C)CO)=C2)C=NC=C1 QWYZASZVCSXDCB-RXVVDRJESA-N 0.000 claims description 2
• AEUIHHIOWGKVTM-NRFANRHFSA-N N-[4-(4-cyanopyridin-3-yl)-2-[(6S)-6-(hydroxymethyl)-4,7-diazaspiro[2.5]octan-7-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(C#N)=C(C2=CC=C(NC(=O)C3=CC=NC(=N3)C3=C(F)C=CC=C3OC)C(N3[C@@H](CNC4(C3)CC4)CO)=C2)C=NC=C1 AEUIHHIOWGKVTM-NRFANRHFSA-N 0.000 claims description 2
• SMOFRAIZAKBEKX-UHFFFAOYSA-N N-[4-(4-cyanopyridin-3-yl)-2-[3-(methoxymethyl)azetidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(C=C(C(NC(=O)C2=CC=NC(=N2)C2=C(F)C=CC=C2OC)=C1)N1CC(COC)C1)C1=CN=CC=C1C#N SMOFRAIZAKBEKX-UHFFFAOYSA-N 0.000 claims description 2
• RFRULRQBRDHJSB-UHFFFAOYSA-N N-[4-(4-cyanopyridin-3-yl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(C=C(C(=C1)NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1CCN(CC1)CCO)C1=CN=CC=C1C#N RFRULRQBRDHJSB-UHFFFAOYSA-N 0.000 claims description 2
• ASQRDBRAOIOVCV-WMZOPIPTSA-N N-[4-(azetidin-1-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N1(CCC1)C1=CC(=C(C=C1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1[C@@H]2CN[C@H](C1)C2 ASQRDBRAOIOVCV-WMZOPIPTSA-N 0.000 claims description 2
• QBKVMDTUGKFMFU-OALUTQOASA-N N-[4-[(cyclobutylamino)methyl]-2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1cc(F)c(CNC2CCC2)cc1N1C[C@@H]2C[C@H]1CN2 QBKVMDTUGKFMFU-OALUTQOASA-N 0.000 claims description 2
• GCSAIPWEYFAKIV-HZPDHXFCSA-N N-[5-cyano-2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound [C@H]12N(C[C@H](NC1)C2)C1=C(C=C(C=C1)C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F GCSAIPWEYFAKIV-HZPDHXFCSA-N 0.000 claims description 2
• KHDDAKVJAWLZOV-IAGOWNOFSA-N N-[5-fluoro-2-[(1R,4R)-5-(2-hydroxyethyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound FC=1C=CC(=C(C=1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1[C@H]2CN([C@@H](C1)C2)CCO KHDDAKVJAWLZOV-IAGOWNOFSA-N 0.000 claims description 2
• KWFNRFXZHFURGM-OAHLLOKOSA-N N-[5-fluoro-2-[(2R)-2-(hydroxymethyl)piperazin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(F)C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1CCNC[C@@H]1CO KWFNRFXZHFURGM-OAHLLOKOSA-N 0.000 claims description 2
• QKZQZKCJWCHGHH-OAHLLOKOSA-N N-[5-fluoro-2-[(2R)-2-(hydroxymethyl)pyrrolidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(F)C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1[C@H](CCC1)CO QKZQZKCJWCHGHH-OAHLLOKOSA-N 0.000 claims description 2
• PBRXEKAVOHWRAQ-MRXNPFEDSA-N N-[5-fluoro-2-[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(F)C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1[C@H](CCC1)COC PBRXEKAVOHWRAQ-MRXNPFEDSA-N 0.000 claims description 2
• KAHMPNUNDKTEOW-ROUUACIJSA-N N-[5-fluoro-2-[(2S,4S)-2-(hydroxymethyl)-4-(propan-2-ylamino)pyrrolidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(F)C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1C[C@@H](NC(C)C)C[C@H]1CO KAHMPNUNDKTEOW-ROUUACIJSA-N 0.000 claims description 2
• JOXBUECBAXTYRH-ZFWWWQNUSA-N N-[5-fluoro-2-[(2S,4S)-4-hydroxy-2-methylpyrrolidin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1C[C@@H](O)C[C@@H]1C)F JOXBUECBAXTYRH-ZFWWWQNUSA-N 0.000 claims description 2
• BMOHPMIYUFXSQJ-INIZCTEOSA-N N-[5-fluoro-2-[(3S)-3-(hydroxymethyl)piperazin-1-yl]-4-propan-2-ylphenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound FC=1C(=CC(=C(C=1)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1C[C@H](NCC1)CO)C(C)C BMOHPMIYUFXSQJ-INIZCTEOSA-N 0.000 claims description 2
• YBFBZHKVFCRAFM-HNNXBMFYSA-N N-[5-fluoro-2-[(3S)-3-(hydroxymethyl)piperazin-1-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1=C(C=CC(=C1NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC)N1C[C@@H](CO)NCC1)F YBFBZHKVFCRAFM-HNNXBMFYSA-N 0.000 claims description 2
• OOBNMPQXQXCPBF-UHFFFAOYSA-N N-[5-fluoro-2-[3-(hydroxymethyl)morpholin-4-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C1(=CC(=CC=C1N1C(COCC1)CO)F)NC(=O)C1=CC=NC(=N1)C1=C(F)C=CC=C1OC OOBNMPQXQXCPBF-UHFFFAOYSA-N 0.000 claims description 2
• NAXWLXJDZBNCQG-IRJFHVNHSA-N N[C@@H]1CC[C@H](CC1)C1=C(C=CC(=C1)C1=C(C=NN1C)C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F Chemical compound N[C@@H]1CC[C@H](CC1)C1=C(C=CC(=C1)C1=C(C=NN1C)C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F NAXWLXJDZBNCQG-IRJFHVNHSA-N 0.000 claims description 2
• PRBXACPKTPJDIW-XGAFWQRZSA-N N[C@@H]1CC[C@H](CC1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F Chemical compound N[C@@H]1CC[C@H](CC1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F PRBXACPKTPJDIW-XGAFWQRZSA-N 0.000 claims description 2
• PRBXACPKTPJDIW-RVWIWJKTSA-N N[C@H]1CC[C@H](CC1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F Chemical compound N[C@H]1CC[C@H](CC1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F PRBXACPKTPJDIW-RVWIWJKTSA-N 0.000 claims description 2
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
• 239000008194 pharmaceutical composition Substances 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
• SAERCLLLTAZHHL-SFTDATJTSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-6-(2-fluoro-6-methoxyphenyl)-5-methoxypyridine-2-carboxamide Chemical compound C1(C#N)=C(C2=CC=C(NC(=O)C3=CC=C(OC)C(C4=C(F)C=CC=C4OC)=N3)C(N3[C@@H](C[C@H](N)C3)CO)=C2)C=NC=C1 SAERCLLLTAZHHL-SFTDATJTSA-N 0.000 claims 1
• WWTQVAUFPQCPKO-SFTDATJTSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-6-(2-fluoro-6-methoxyphenyl)pyridine-2-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(C1=NC(=CC=C1)C1=C(C=CC=C1OC)F)=O)CO WWTQVAUFPQCPKO-SFTDATJTSA-N 0.000 claims 1
• HFZNPKDYLSOGBE-SCEMAYBHSA-N nrc-12 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(C)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C1=CC=C(O)C=C1 HFZNPKDYLSOGBE-SCEMAYBHSA-N 0.000 claims 1
• 108010002838 hematopoietic progenitor kinase 1 Proteins 0.000 abstract description 44
• 150000001721 carbon Chemical group 0.000 description 67
• 125000004043 oxo group Chemical group O=* 0.000 description 36
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
• 125000000753 cycloalkyl group Chemical group 0.000 description 19
• 201000010099 disease Diseases 0.000 description 17
• 238000000034 method Methods 0.000 description 17
• 102000037982 Immune checkpoint proteins Human genes 0.000 description 16
• 108091008036 Immune checkpoint proteins Proteins 0.000 description 16
• 229940126546 immune checkpoint molecule Drugs 0.000 description 15
• 210000001744 T-lymphocyte Anatomy 0.000 description 14
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
• 238000006243 chemical reaction Methods 0.000 description 11
• 239000000203 mixture Substances 0.000 description 11
• 230000000694 effects Effects 0.000 description 10
• 125000001188 haloalkyl group Chemical group 0.000 description 10
• 208000009956 adenocarcinoma Diseases 0.000 description 9
• 208000035475 disorder Diseases 0.000 description 9
• 125000002950 monocyclic group Chemical group 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• 206010025323 Lymphomas Diseases 0.000 description 8
• 230000001404 mediated effect Effects 0.000 description 8
• 238000006467 substitution reaction Methods 0.000 description 8
• 229940045513 CTLA4 antagonist Drugs 0.000 description 7
• 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 7
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 7
• 206010039491 Sarcoma Diseases 0.000 description 7
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
• 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
• 239000001301 oxygen Substances 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 125000006413 ring segment Chemical group 0.000 description 7
• 206010041823 squamous cell carcinoma Diseases 0.000 description 7
• 239000011593 sulfur Substances 0.000 description 7
• 108010074708 B7-H1 Antigen Proteins 0.000 description 6
• 201000009030 Carcinoma Diseases 0.000 description 6
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 6
• 108091008874 T cell receptors Proteins 0.000 description 6
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 125000003342 alkenyl group Chemical group 0.000 description 6
• XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 6
• 229960002986 dinoprostone Drugs 0.000 description 6
• XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 6
• 150000003254 radicals Chemical class 0.000 description 6
• 230000011664 signaling Effects 0.000 description 6
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 5
• 108091008875 B cell receptors Proteins 0.000 description 5
• 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 5
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 5
• 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 5
• 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 5
• 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 5
• 125000000304 alkynyl group Chemical group 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
• 230000002950 deficient Effects 0.000 description 5
• 125000005647 linker group Chemical group 0.000 description 5
• 201000001441 melanoma Diseases 0.000 description 5
• 230000007170 pathology Effects 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 238000011282 treatment Methods 0.000 description 5
• 102100022464 5'-nucleotidase Human genes 0.000 description 4
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
• 102100035634 B-cell linker protein Human genes 0.000 description 4
• 108010021064 CTLA-4 Antigen Proteins 0.000 description 4
• 102000008203 CTLA-4 Antigen Human genes 0.000 description 4
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
• 206010014733 Endometrial cancer Diseases 0.000 description 4
• 206010014759 Endometrial neoplasm Diseases 0.000 description 4
• 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 4
• 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 4
• 101000803266 Homo sapiens B-cell linker protein Proteins 0.000 description 4
• 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 4
• 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 4
• 101001090688 Homo sapiens Lymphocyte cytosolic protein 2 Proteins 0.000 description 4
• 102000017578 LAG3 Human genes 0.000 description 4
• 206010024612 Lipoma Diseases 0.000 description 4
• 102100034709 Lymphocyte cytosolic protein 2 Human genes 0.000 description 4
• 241000699670 Mus sp. Species 0.000 description 4
• 102100040678 Programmed cell death protein 1 Human genes 0.000 description 4
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 4
• 208000000453 Skin Neoplasms Diseases 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 210000003719 b-lymphocyte Anatomy 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 238000006880 cross-coupling reaction Methods 0.000 description 4
• 229950009791 durvalumab Drugs 0.000 description 4
• 230000006870 function Effects 0.000 description 4
• 230000014509 gene expression Effects 0.000 description 4
• 208000005017 glioblastoma Diseases 0.000 description 4
• 208000014829 head and neck neoplasm Diseases 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• 230000036039 immunity Effects 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 238000011813 knockout mouse model Methods 0.000 description 4
• 201000008968 osteosarcoma Diseases 0.000 description 4
• 229960002621 pembrolizumab Drugs 0.000 description 4
• 238000002360 preparation method Methods 0.000 description 4
• 238000002560 therapeutic procedure Methods 0.000 description 4
• 125000001544 thienyl group Chemical group 0.000 description 4
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 3
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 3
• 206010005949 Bone cancer Diseases 0.000 description 3
• 208000018084 Bone neoplasm Diseases 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 201000008808 Fibrosarcoma Diseases 0.000 description 3
• 208000017604 Hodgkin disease Diseases 0.000 description 3
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 3
• 241000282414 Homo sapiens Species 0.000 description 3
• 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
• 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 3
• 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 description 3
• 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 description 3
• 208000007766 Kaposi sarcoma Diseases 0.000 description 3
• 208000008839 Kidney Neoplasms Diseases 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
• 208000034578 Multiple myelomas Diseases 0.000 description 3
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• 150000001204 N-oxides Chemical class 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• 206010038389 Renal cancer Diseases 0.000 description 3
• 230000006044 T cell activation Effects 0.000 description 3
• 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 3
• 206010043276 Teratoma Diseases 0.000 description 3
• 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 3
• 208000002495 Uterine Neoplasms Diseases 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 239000000556 agonist Substances 0.000 description 3
• 230000005809 anti-tumor immunity Effects 0.000 description 3
• 125000002393 azetidinyl group Chemical group 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• 210000004443 dendritic cell Anatomy 0.000 description 3
• 206010016629 fibroma Diseases 0.000 description 3
• 201000011066 hemangioma Diseases 0.000 description 3
• 210000003958 hematopoietic stem cell Anatomy 0.000 description 3
• 125000000623 heterocyclic group Chemical group 0.000 description 3
• 150000002430 hydrocarbons Chemical group 0.000 description 3
• 210000002865 immune cell Anatomy 0.000 description 3
• 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 238000001727 in vivo Methods 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 201000010982 kidney cancer Diseases 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 208000014018 liver neoplasm Diseases 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 239000012041 precatalyst Substances 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 125000003226 pyrazolyl group Chemical group 0.000 description 3
• 230000000306 recurrent effect Effects 0.000 description 3
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 239000012453 solvate Substances 0.000 description 3
• 125000004089 sulfido group Chemical group [S-]* 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 125000000335 thiazolyl group Chemical group 0.000 description 3
• 208000022679 triple-negative breast carcinoma Diseases 0.000 description 3
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
• 206010046766 uterine cancer Diseases 0.000 description 3
• KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
• 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 2
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 201000003076 Angiosarcoma Diseases 0.000 description 2
• 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 2
• 230000003844 B-cell-activation Effects 0.000 description 2
• 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 206010005003 Bladder cancer Diseases 0.000 description 2
• 208000011691 Burkitt lymphomas Diseases 0.000 description 2
• 102100027207 CD27 antigen Human genes 0.000 description 2
• 102100038078 CD276 antigen Human genes 0.000 description 2
• 101710185679 CD276 antigen Proteins 0.000 description 2
• 101150013553 CD40 gene Proteins 0.000 description 2
• 101150071146 COX2 gene Proteins 0.000 description 2
• 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 2
• 208000005243 Chondrosarcoma Diseases 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 102100029722 Ectonucleoside triphosphate diphosphohydrolase 1 Human genes 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
• 208000032027 Essential Thrombocythemia Diseases 0.000 description 2
• 208000006168 Ewing Sarcoma Diseases 0.000 description 2
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 206010018338 Glioma Diseases 0.000 description 2
• 208000002927 Hamartoma Diseases 0.000 description 2
• 208000001258 Hemangiosarcoma Diseases 0.000 description 2
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 2
• 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 2
• 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
• 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 2
• 101001012447 Homo sapiens Ectonucleoside triphosphate diphosphohydrolase 1 Proteins 0.000 description 2
• 101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
• 101000573441 Homo sapiens Misshapen-like kinase 1 Proteins 0.000 description 2
• 101001059984 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 4 Proteins 0.000 description 2
• 101001059982 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 5 Proteins 0.000 description 2
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
• 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• 208000018142 Leiomyosarcoma Diseases 0.000 description 2
• 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 2
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
• 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 2
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• 102100026287 Misshapen-like kinase 1 Human genes 0.000 description 2
• 102100028192 Mitogen-activated protein kinase kinase kinase kinase 2 Human genes 0.000 description 2
• 102100028193 Mitogen-activated protein kinase kinase kinase kinase 3 Human genes 0.000 description 2
• 102100028194 Mitogen-activated protein kinase kinase kinase kinase 4 Human genes 0.000 description 2
• 102100028195 Mitogen-activated protein kinase kinase kinase kinase 5 Human genes 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• 125000000815 N-oxide group Chemical group 0.000 description 2
• 238000005481 NMR spectroscopy Methods 0.000 description 2
• 201000004404 Neurofibroma Diseases 0.000 description 2
• 102000004473 OX40 Ligand Human genes 0.000 description 2
• 108010042215 OX40 Ligand Proteins 0.000 description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
• 108091007960 PI3Ks Proteins 0.000 description 2
• 101150000187 PTGS2 gene Proteins 0.000 description 2
• 108091000080 Phosphotransferase Proteins 0.000 description 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
• 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 2
• 206010060862 Prostate cancer Diseases 0.000 description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
• 206010041067 Small cell lung cancer Diseases 0.000 description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 description 2
• 230000006052 T cell proliferation Effects 0.000 description 2
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
• 208000024313 Testicular Neoplasms Diseases 0.000 description 2
• 206010057644 Testis cancer Diseases 0.000 description 2
• 208000024770 Thyroid neoplasm Diseases 0.000 description 2
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
• 206010046431 Urethral cancer Diseases 0.000 description 2
• 206010046458 Urethral neoplasms Diseases 0.000 description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
• 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 description 2
• 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 2
• 208000008383 Wilms tumor Diseases 0.000 description 2
• 208000017733 acquired polycythemia vera Diseases 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 150000001335 aliphatic alkanes Chemical class 0.000 description 2
• 150000001336 alkenes Chemical class 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 125000005605 benzo group Chemical group 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 208000002458 carcinoid tumor Diseases 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 238000006555 catalytic reaction Methods 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 208000019065 cervical carcinoma Diseases 0.000 description 2
• 125000003636 chemical group Chemical group 0.000 description 2
• 208000006990 cholangiocarcinoma Diseases 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 208000024207 chronic leukemia Diseases 0.000 description 2
• 208000009060 clear cell adenocarcinoma Diseases 0.000 description 2
• 208000029742 colonic neoplasm Diseases 0.000 description 2
• 239000000470 constituent Substances 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 125000004431 deuterium atom Chemical group 0.000 description 2
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
• 230000003828 downregulation Effects 0.000 description 2
• 201000003914 endometrial carcinoma Diseases 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• 201000004101 esophageal cancer Diseases 0.000 description 2
• 210000003238 esophagus Anatomy 0.000 description 2
• 230000001747 exhibiting effect Effects 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 230000003325 follicular Effects 0.000 description 2
• 238000010575 fractional recrystallization Methods 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 201000010536 head and neck cancer Diseases 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 230000002489 hematologic effect Effects 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 239000000543 intermediate Substances 0.000 description 2
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 201000010260 leiomyoma Diseases 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 206010027191 meningioma Diseases 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 206010028537 myelofibrosis Diseases 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 201000008026 nephroblastoma Diseases 0.000 description 2
• 201000011682 nervous system cancer Diseases 0.000 description 2
• 229960003301 nivolumab Drugs 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• HTDJMMGADYFBCS-GMHXGFMTSA-N nrc-11 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(C)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CN)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 HTDJMMGADYFBCS-GMHXGFMTSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• 125000002971 oxazolyl group Chemical group 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 102000020233 phosphotransferase Human genes 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• 208000037244 polycythemia vera Diseases 0.000 description 2
• 208000003476 primary myelofibrosis Diseases 0.000 description 2
• 239000000047 product Substances 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 210000003289 regulatory T cell Anatomy 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 208000007056 sickle cell anemia Diseases 0.000 description 2
• 201000000849 skin cancer Diseases 0.000 description 2
• 208000000587 small cell lung carcinoma Diseases 0.000 description 2
• 229950007213 spartalizumab Drugs 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 201000011549 stomach cancer Diseases 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• 201000003120 testicular cancer Diseases 0.000 description 2
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 201000002510 thyroid cancer Diseases 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 206010044412 transitional cell carcinoma Diseases 0.000 description 2
• 201000005112 urinary bladder cancer Diseases 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 2
• FMCGSUUBYTWNDP-ONGXEEELSA-N (1R,2S)-2-(dimethylamino)-1-phenyl-1-propanol Chemical compound CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 FMCGSUUBYTWNDP-ONGXEEELSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• LFHLEABTNIQIQO-UHFFFAOYSA-N 1H-isoindole Chemical compound C1=CC=C2CN=CC2=C1 LFHLEABTNIQIQO-UHFFFAOYSA-N 0.000 description 1
• SSNMISUJOQAFRR-UHFFFAOYSA-N 2,6-naphthyridine Chemical compound N1=CC=C2C=NC=CC2=C1 SSNMISUJOQAFRR-UHFFFAOYSA-N 0.000 description 1
• UZYQSNQJLWTICD-UHFFFAOYSA-N 2-(n-benzoylanilino)-2,2-dinitroacetic acid Chemical compound C=1C=CC=CC=1N(C(C(=O)O)([N+]([O-])=O)[N+]([O-])=O)C(=O)C1=CC=CC=C1 UZYQSNQJLWTICD-UHFFFAOYSA-N 0.000 description 1
• IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical compound OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• 206010000830 Acute leukaemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 206010001233 Adenoma benign Diseases 0.000 description 1
• 206010061424 Anal cancer Diseases 0.000 description 1
• 208000007860 Anus Neoplasms Diseases 0.000 description 1
• 102000004452 Arginase Human genes 0.000 description 1
• 108700024123 Arginases Proteins 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 229940125565 BMS-986016 Drugs 0.000 description 1
• 101000840545 Bacillus thuringiensis L-isoleucine-4-hydroxylase Proteins 0.000 description 1
• 206010004146 Basal cell carcinoma Diseases 0.000 description 1
• 206010004593 Bile duct cancer Diseases 0.000 description 1
• 206010073106 Bone giant cell tumour malignant Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 206010006143 Brain stem glioma Diseases 0.000 description 1
• 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• 101100177670 Caenorhabditis elegans hpk-1 gene Proteins 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 208000009458 Carcinoma in Situ Diseases 0.000 description 1
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
• 206010008263 Cervical dysplasia Diseases 0.000 description 1
• 201000005262 Chondroma Diseases 0.000 description 1
• 201000009047 Chordoma Diseases 0.000 description 1
• 208000006332 Choriocarcinoma Diseases 0.000 description 1
• 125000006605 Cn-m alkenyl group Chemical group 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 201000002847 Cowden syndrome Diseases 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 208000007033 Dysgerminoma Diseases 0.000 description 1
• 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 208000007659 Fibroadenoma Diseases 0.000 description 1
• 206010053717 Fibrous histiocytoma Diseases 0.000 description 1
• 201000003741 Gastrointestinal carcinoma Diseases 0.000 description 1
• 208000000527 Germinoma Diseases 0.000 description 1
• 208000007569 Giant Cell Tumors Diseases 0.000 description 1
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
• 201000005409 Gliomatosis cerebri Diseases 0.000 description 1
• 206010018404 Glucagonoma Diseases 0.000 description 1
• 101710155270 Glycerate 2-kinase Proteins 0.000 description 1
• 206010018691 Granuloma Diseases 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 206010019629 Hepatic adenoma Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 1
• 101001055145 Homo sapiens Interleukin-2 receptor subunit beta Proteins 0.000 description 1
• 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 1
• 101001138062 Homo sapiens Leukocyte-associated immunoglobulin-like receptor 1 Proteins 0.000 description 1
• 101001059990 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 2 Proteins 0.000 description 1
• 101001059989 Homo sapiens Mitogen-activated protein kinase kinase kinase kinase 3 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
• 101000818543 Homo sapiens Tyrosine-protein kinase ZAP-70 Proteins 0.000 description 1
• 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• 102000000588 Interleukin-2 Human genes 0.000 description 1
• 102100026879 Interleukin-2 receptor subunit beta Human genes 0.000 description 1
• 102000042838 JAK family Human genes 0.000 description 1
• 108091082332 JAK family Proteins 0.000 description 1
• 102000002698 KIR Receptors Human genes 0.000 description 1
• 108010043610 KIR Receptors Proteins 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
• 206010023825 Laryngeal cancer Diseases 0.000 description 1
• 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 1
• 102100020943 Leukocyte-associated immunoglobulin-like receptor 1 Human genes 0.000 description 1
• 208000022010 Lhermitte-Duclos disease Diseases 0.000 description 1
• 208000002404 Liver Cell Adenoma Diseases 0.000 description 1
• 206010052178 Lymphocytic lymphoma Diseases 0.000 description 1
• 208000032271 Malignant tumor of penis Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
• 101710144533 Mitogen-activated protein kinase kinase kinase kinase 2 Proteins 0.000 description 1
• 101710144521 Mitogen-activated protein kinase kinase kinase kinase 3 Proteins 0.000 description 1
• 208000003445 Mouth Neoplasms Diseases 0.000 description 1
• 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 description 1
• 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• FMCGSUUBYTWNDP-UHFFFAOYSA-N N-Methylephedrine Natural products CN(C)C(C)C(O)C1=CC=CC=C1 FMCGSUUBYTWNDP-UHFFFAOYSA-N 0.000 description 1
• YVSYOIRMGSWDKV-OALUTQOASA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-[6-(hydroxymethyl)pyridin-3-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound COc1cccc(F)c1-c1nccc(n1)C(=O)Nc1cc(F)c(cc1N1C[C@@H]2C[C@H]1CN2)-c1ccc(CO)nc1 YVSYOIRMGSWDKV-OALUTQOASA-N 0.000 description 1
• CDXQAYIDSWLSDP-ROUUACIJSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-[6-(methylcarbamoyl)pyridin-3-yl]phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound CNC(=O)c1ccc(cn1)-c1cc(N2C[C@@H]3C[C@H]2CN3)c(NC(=O)c2ccnc(n2)-c2c(F)cccc2OC)cc1F CDXQAYIDSWLSDP-ROUUACIJSA-N 0.000 description 1
• HENRITOGWFFGGA-PMACEKPBSA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(3-cyanopyridin-2-yl)phenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C1=NC=CC=C1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)CO HENRITOGWFFGGA-PMACEKPBSA-N 0.000 description 1
• LDCDYMPNMGJUDB-OALUTQOASA-N N-[2-[(2S,4S)-4-amino-2-(hydroxymethyl)pyrrolidin-1-yl]-4-(4-cyanopyridin-3-yl)phenyl]-2-(2,6-difluorophenyl)pyrimidine-4-carboxamide Chemical compound N[C@H]1C[C@H](N(C1)C1=C(C=CC(=C1)C=1C=NC=CC=1C#N)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1F)F)CO LDCDYMPNMGJUDB-OALUTQOASA-N 0.000 description 1
• NBISRCWVBMUOCS-HOTGVXAUSA-N N-[4-(azetidin-1-yl)-2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound N1(CCC1)C1=CC(=C(C=C1F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F)N1[C@@H]2CN[C@H](C1)C2 NBISRCWVBMUOCS-HOTGVXAUSA-N 0.000 description 1
• 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 1
• 206010061306 Nasopharyngeal cancer Diseases 0.000 description 1
• 238000006411 Negishi coupling reaction Methods 0.000 description 1
• 206010029113 Neovascularisation Diseases 0.000 description 1
• 241000772415 Neovison vison Species 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 208000007256 Nevus Diseases 0.000 description 1
• 201000010133 Oligodendroglioma Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000010191 Osteitis Deformans Diseases 0.000 description 1
• 208000000035 Osteochondroma Diseases 0.000 description 1
• 239000012270 PD-1 inhibitor Substances 0.000 description 1
• 239000012668 PD-1-inhibitor Substances 0.000 description 1
• 208000027067 Paget disease of bone Diseases 0.000 description 1
• 208000000821 Parathyroid Neoplasms Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 206010034299 Penile cancer Diseases 0.000 description 1
• 102000004422 Phospholipase C gamma Human genes 0.000 description 1
• 108010056751 Phospholipase C gamma Proteins 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 208000007641 Pinealoma Diseases 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 201000005746 Pituitary adenoma Diseases 0.000 description 1
• 206010061538 Pituitary tumour benign Diseases 0.000 description 1
• 241000288906 Primates Species 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
• 102000008866 Prostaglandin E receptors Human genes 0.000 description 1
• 108010088540 Prostaglandin E receptors Proteins 0.000 description 1
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
• 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 208000005678 Rhabdomyoma Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 101001037255 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Indoleamine 2,3-dioxygenase Proteins 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 101100215487 Sus scrofa ADRA2A gene Proteins 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 230000005867 T cell response Effects 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin 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
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 102100021125 Tyrosine-protein kinase ZAP-70 Human genes 0.000 description 1
• 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 1
• 208000009311 VIPoma Diseases 0.000 description 1
• 201000003761 Vaginal carcinoma Diseases 0.000 description 1
• 206010047741 Vulval cancer Diseases 0.000 description 1
• 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• 206010048214 Xanthoma Diseases 0.000 description 1
• 206010048215 Xanthomatosis Diseases 0.000 description 1
• 102000035181 adaptor proteins Human genes 0.000 description 1
• 108091005764 adaptor proteins Proteins 0.000 description 1
• 208000002718 adenomatoid tumor Diseases 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 201000005188 adrenal gland cancer Diseases 0.000 description 1
• 208000024447 adrenal gland neoplasm Diseases 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 125000004450 alkenylene group Chemical group 0.000 description 1
• 150000001345 alkine derivatives Chemical class 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 238000010976 amide bond formation reaction Methods 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 230000002491 angiogenic effect Effects 0.000 description 1
• 201000011165 anus cancer Diseases 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 125000000732 arylene group Chemical group 0.000 description 1
• 239000010425 asbestos Substances 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 230000005784 autoimmunity Effects 0.000 description 1
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
• 125000003943 azolyl group Chemical group 0.000 description 1
• 208000001119 benign fibrous histiocytoma Diseases 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 208000026900 bile duct neoplasm Diseases 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 210000003969 blast cell Anatomy 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 208000016738 bone Paget disease Diseases 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 201000009480 botryoid rhabdomyosarcoma Diseases 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 201000003149 breast fibroadenoma Diseases 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
• 201000002143 bronchus adenoma Diseases 0.000 description 1
• 230000003185 calcium uptake Effects 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 208000035269 cancer or benign tumor Diseases 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000011712 cell development Effects 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 201000005217 chondroblastoma Diseases 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 230000000139 costimulatory effect Effects 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 201000010305 cutaneous fibrous histiocytoma Diseases 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
• SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 150000001975 deuterium Chemical group 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000003814 drug Substances 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 210000003162 effector t lymphocyte Anatomy 0.000 description 1
• 229940056913 eftilagimod alfa Drugs 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000012156 elution solvent Substances 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 201000002491 encephalomyelitis Diseases 0.000 description 1
• 210000000750 endocrine system Anatomy 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 239000002532 enzyme inhibitor Substances 0.000 description 1
• 229960002179 ephedrine Drugs 0.000 description 1
• 235000019439 ethyl acetate Nutrition 0.000 description 1
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 201000001343 fallopian tube carcinoma Diseases 0.000 description 1
• 230000008713 feedback mechanism Effects 0.000 description 1
• 125000003709 fluoroalkyl group Chemical group 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
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
• 201000000052 gastrinoma Diseases 0.000 description 1
• 201000003115 germ cell cancer Diseases 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 208000006359 hepatoblastoma Diseases 0.000 description 1
• 201000002735 hepatocellular adenoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 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
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 229940121569 ieramilimab Drugs 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 238000002649 immunization Methods 0.000 description 1
• 230000003053 immunization Effects 0.000 description 1
• 201000004933 in situ carcinoma Diseases 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 206010022498 insulinoma Diseases 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000004073 interleukin-2 production Effects 0.000 description 1
• 210000002570 interstitial cell Anatomy 0.000 description 1
• 201000002313 intestinal cancer Diseases 0.000 description 1
• 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 229960005386 ipilimumab Drugs 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 229960004592 isopropanol Drugs 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 230000000155 isotopic effect Effects 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 208000022013 kidney Wilms tumor Diseases 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 206010023841 laryngeal neoplasm Diseases 0.000 description 1
• 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
• 208000025036 lymphosarcoma Diseases 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 201000004593 malignant giant cell tumor Diseases 0.000 description 1
• 201000000289 malignant teratoma Diseases 0.000 description 1
• 208000026037 malignant tumor of neck Diseases 0.000 description 1
• 208000026045 malignant tumor of parathyroid gland Diseases 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 210000000716 merkel cell Anatomy 0.000 description 1
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
• 208000021039 metastatic melanoma Diseases 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• 208000009091 myxoma Diseases 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• AGVKXDPPPSLISR-UHFFFAOYSA-N n-ethylcyclohexanamine Chemical compound CCNC1CCCCC1 AGVKXDPPPSLISR-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 229940073569 n-methylephedrine Drugs 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 125000005482 norpinyl group Chemical group 0.000 description 1
• 239000012038 nucleophile Substances 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 229960003347 obinutuzumab Drugs 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 208000003388 osteoid osteoma Diseases 0.000 description 1
• 208000008798 osteoma Diseases 0.000 description 1
• 229940127084 other anti-cancer agent Drugs 0.000 description 1
• 230000002611 ovarian Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 210000003101 oviduct Anatomy 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 208000021255 pancreatic insulinoma Diseases 0.000 description 1
• 201000003913 parathyroid carcinoma Diseases 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 229940121655 pd-1 inhibitor Drugs 0.000 description 1
• RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
• 229960000395 phenylpropanolamine Drugs 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
• 229950010773 pidilizumab Drugs 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
• 208000021310 pituitary gland adenoma Diseases 0.000 description 1
• 238000010837 poor prognosis Methods 0.000 description 1
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 201000005825 prostate adenocarcinoma Diseases 0.000 description 1
• 230000005588 protonation Effects 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 201000007444 renal pelvis carcinoma Diseases 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
• 229910052895 riebeckite Inorganic materials 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
• 230000007727 signaling mechanism Effects 0.000 description 1
• 210000003625 skull Anatomy 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 238000002798 spectrophotometry method Methods 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 206010062261 spinal cord neoplasm Diseases 0.000 description 1
• 208000017572 squamous cell neoplasm Diseases 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 125000001174 sulfone group Chemical group 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 229940126625 tavolimab Drugs 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 208000013066 thyroid gland cancer Diseases 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 229950007217 tremelimumab Drugs 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 208000022271 tubular adenoma Diseases 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 230000001173 tumoral effect Effects 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 230000034512 ubiquitination Effects 0.000 description 1
• 229950005972 urelumab Drugs 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 208000023747 urothelial carcinoma Diseases 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 229950003520 utomilumab Drugs 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 208000009540 villous adenoma Diseases 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 210000003905 vulva Anatomy 0.000 description 1
• 201000004916 vulva carcinoma Diseases 0.000 description 1
• 208000013013 vulvar carcinoma Diseases 0.000 description 1