HRP20220833T1 - Derivati n-(fenil)-2-(fenil)pirimidin-4-karboksamida i odgovarajući spojevi kao inhibitori hpk1 za liječenje raka - Google Patents
Derivati n-(fenil)-2-(fenil)pirimidin-4-karboksamida i odgovarajući spojevi kao inhibitori hpk1 za liječenje raka Download PDFInfo
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- HRP20220833T1 HRP20220833T1 HRP20220833TT HRP20220833T HRP20220833T1 HR P20220833 T1 HRP20220833 T1 HR P20220833T1 HR P20220833T T HRP20220833T T HR P20220833TT HR P20220833 T HRP20220833 T HR P20220833T HR P20220833 T1 HRP20220833 T1 HR P20220833T1
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- independently selected
- alkyl
- membered
- fluoro
- optionally substituted
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- 150000001875 compounds Chemical class 0.000 title claims 49
- 206010028980 Neoplasm Diseases 0.000 title claims 3
- 201000011510 cancer Diseases 0.000 title claims 3
- 101100177670 Caenorhabditis elegans hpk-1 gene Proteins 0.000 title 1
- 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 1
- 239000003112 inhibitor Substances 0.000 title 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 131
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 129
- 125000001424 substituent group Chemical group 0.000 claims 113
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 109
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 101
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 101
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 100
- -1 C6-10aryl Chemical group 0.000 claims 88
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 77
- 125000000217 alkyl group Chemical group 0.000 claims 64
- 229910020008 S(O) Inorganic materials 0.000 claims 63
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims 63
- 229910052799 carbon Inorganic materials 0.000 claims 60
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 59
- 150000003839 salts Chemical class 0.000 claims 56
- 229910052739 hydrogen Inorganic materials 0.000 claims 50
- 229910052736 halogen Inorganic materials 0.000 claims 48
- 150000002367 halogens Chemical class 0.000 claims 48
- 125000004432 carbon atom Chemical group C* 0.000 claims 29
- 125000004429 atom Chemical group 0.000 claims 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 22
- 229910052805 deuterium Inorganic materials 0.000 claims 20
- 229910052717 sulfur Inorganic materials 0.000 claims 19
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 16
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 15
- 125000005842 heteroatom Chemical group 0.000 claims 15
- 229910052760 oxygen Inorganic materials 0.000 claims 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 14
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 11
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 10
- 125000003545 alkoxy group Chemical group 0.000 claims 10
- 125000002947 alkylene group Chemical group 0.000 claims 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 9
- 125000003118 aryl group Chemical group 0.000 claims 9
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 8
- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims 8
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 229910052731 fluorine Inorganic materials 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 2
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 2
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 2
- 125000005983 2,5-diazabicyclo[2.2.1]heptan-2-yl group Chemical group 0.000 claims 2
- 101100310927 Caenorhabditis elegans sra-4 gene Proteins 0.000 claims 2
- 101000869592 Daucus carota Major allergen Dau c 1 Proteins 0.000 claims 2
- 101000650136 Homo sapiens WAS/WASL-interacting protein family member 3 Proteins 0.000 claims 2
- 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 2
- 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 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 2
- 102100027539 WAS/WASL-interacting protein family member 3 Human genes 0.000 claims 2
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims 2
- 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- HKSQZEGSMBFHGC-UHFFFAOYSA-N pyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=N1 HKSQZEGSMBFHGC-UHFFFAOYSA-N 0.000 claims 2
- 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 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 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 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 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 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- 101100310920 Caenorhabditis elegans sra-2 gene Proteins 0.000 claims 1
- 101100310926 Caenorhabditis elegans sra-3 gene Proteins 0.000 claims 1
- 101100310928 Caenorhabditis elegans sra-6 gene Proteins 0.000 claims 1
- 101100310929 Caenorhabditis elegans sra-7 gene Proteins 0.000 claims 1
- 101100310930 Caenorhabditis elegans sra-8 gene Proteins 0.000 claims 1
- 101100310931 Caenorhabditis elegans sra-9 gene Proteins 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 102100038417 Cytoplasmic FMR1-interacting protein 1 Human genes 0.000 claims 1
- 101710181791 Cytoplasmic FMR1-interacting protein 1 Proteins 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 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 1
- 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 1
- 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 1
- WTMHDVVBBKONHX-HZPDHXFCSA-N N-[2-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-(hydroxymethyl)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)CO)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F WTMHDVVBBKONHX-HZPDHXFCSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- VFYLBKWAGCOTCH-IAGOWNOFSA-N N-[2-[(1R,4R)-5-ethyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluorophenyl]-2-(2-fluoro-6-methoxyphenyl)pyrimidine-4-carboxamide Chemical compound C(C)N1[C@H]2CN([C@@H](C1)C2)C1=C(C=C(C=C1)F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F VFYLBKWAGCOTCH-IAGOWNOFSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 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 claims 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 claims 1
- DDNGJFFPOPCHAZ-IRXDYDNUSA-N N-[2-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-5-fluoro-4-morpholin-4-ylphenyl]-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)N1CCOCC1 DDNGJFFPOPCHAZ-IRXDYDNUSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- YLUXKRMQCFVPCP-ZIAGYGMSSA-N N-[3-bromo-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=C1Br)F)NC(=O)C1=NC(=NC=C1)C1=C(C=CC=C1OC)F YLUXKRMQCFVPCP-ZIAGYGMSSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
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- 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 1
- 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 1
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- 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 1
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- 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 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 claims 1
- 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 1
- 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 1
- PCYDUWDMJRORMQ-STQMWFEESA-N N-[4-bromo-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(Br)cc1N1C[C@@H]2C[C@H]1CN2 PCYDUWDMJRORMQ-STQMWFEESA-N 0.000 claims 1
- 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 1
- 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 1
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- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 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 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 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 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
- 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 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 101150081057 sra-10 gene Proteins 0.000 claims 1
- 101150019129 sra-11 gene Proteins 0.000 claims 1
- 101150075827 sra-12 gene Proteins 0.000 claims 1
- 101150028258 sra-13 gene Proteins 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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Claims (44)
1. Spoj, naznačen time, da je predstavljen Formulom (I’):
[image]
ili njegova farmaceutski prihvatljiva sol, gdje:
CyA je C3-12 cikloalkil ili 4-12-člani heterocikloalkil; pri čemu 4-12-člani heterocikloalkil ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji tvore prsten odabrana od N, O i S; gdje se N i S opcionalno oksidiraju; pri čemu se atom ugljika koji formira prsten od 4-12-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom se svaki od C3-12 cikloalkila i 4-12-članog heterocikloalkila opcionalno supstituira s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od RA;
A je N ili CR16;
R16 se bira od sljedećih: H, D, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halogen, CN, NO2, ORa16, SRa16, C(O)Rb16, C(O)NRc16Rd16, C(O)ORa16, OC(O)Rb16, OC(O)NRc16Rd16, NRc16Rd16, NRc16C(O)Rb16, NRc16C(O)Ra16, NRc16C(O)NRc16Rd16, NRc16S(O)Rb16, NRc16S(O)2Rb16, NRc16S(O)2NRc16Rd16, S(O)Rb16, S(O)NRc16Rd16, S(O)2Rb16, S(O)2NRc16Rd16, i BRh16Ri16; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od Rg;
R1 se bira od sljedećih: H, D, halogen, CN, C1-6 alkil, ORa15, i NRc15Rd15; pri čemu je C1-6 alkil opcionalno supstituiran s 1, 2, ili 3 supstituenta koji se neovisno biraju od Rg;
R2 se bira od sljedećih: H, D, Cy2, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halogen, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)Ra, NRcC(O)NRcRd, C(=NRe)Rb, C(=NORa)Rb, C(=NRe)NRcRd, NRcC(=NRe)NRcRd,
NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, S(O)2NRcRd, i BRhRi; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10;
Cy2 se bira od sljedećih: C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, i 5-10-člani heteroaril; pri čemu svaki 4-10-člani heterocikloalkil, i 5-10-člani-heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3, ili 4 heteroatoma koji formiraju prsten
neovisno odabrana od N, O, i S; gdje se N i S opcionalno oksidiraju; dok se atom ugljika koji formira prsten od 5-10-članog heteroarila i 4-10-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10-aril, i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10;
Z je N ili CR3;
R3 se bira od sljedećih: H, D, Cy3, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halogen, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)Ra4, NRc4C(O)NRc4Rd4, C(=NRe4)Rb4, C(=NORa4)Rb4, C(=NRe4)NRc4Rd4, NRc4C(=NRe4)NRc4Rd4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, i BRh4Ri4; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od R13;
Cy3 se bira od sljedećih: C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, i 5-10-člani-heteroaril; pri čemu svaki 4-10-člani heterocikloalkil, i 5-10-člani heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3, ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; gdje se N i S opcionalno oksidiraju; dok se atom ugljika koji formira prsten od 5-10-članog heteroarila i 4-10-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10-aril, i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R13;
svaki R4 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil,
C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3alkilen, halogen, D, CN, NO2, ORa8, SRa8, C(O)Rb8, C(O)NRc8Rd8, C(O)ORa8, OC(O)Rb8, OC(O)NRc8Rd8, NRc8Rd8, NRc8C(O)Rb8, NRc8C(O)ORa8, NRc8C(O)NRc8Rd8, C(=NRe8)Rb8, C(=NORa8)Rb8, C(=NRe8)NRc8Rd8, NRc8C(=NRe8)NRc8Rd8, NRc8S(O)Rb8, NRc8S(O)2Rb8, NRc8S(O)2NRc8Rd8, S(O)Rb8, S(O)NRc8Rd8, S(O)2Rb8, S(O)2NRc8Rd8, i BRh8Ri8; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani-heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen,
C6-10aril-C1-3alkilen, i 5-10-člani heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R5;
svaki R5 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani-heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3alkilen, halogen, D, CN, ORa9, SRa9, C(O)Rb9, C(O)NRc9Rd9, C(O)ORa9, NRc9Rd9, NRc9C(O)Rb9, NRc9C(O)ORa9, NRc9S(O)2Rb9, NRc9S(O)2NRc9Rd9, S(O)Rb9, S(O)NRc9Rd9, S(O)2Rb9, S(O)2NRc9Rd8, i BRh9Ri9; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen i 5-10-člani-heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od R6;
svaki R6 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil,
C3-6-cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, halogen, D, CN, ORa10, SRa10, C(O)Rb10, C(O)NRc10Rd10, C(O)ORa10, NRc10Rd10, NRc10C(O)Rb10, NRc10C(O)ORa10, NRc10S(O)Rb10, NRc10S(O)2Rb10, NRc10S(O)2NRc10Rd10, S(O)Rb10, S(O)NRc10Rd10, S(O)2Rb10, i S(O)2NRc10Rd10; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-6cikloalkil, fenil, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki RA se bira od sljedećih: H, D, Cy1, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halogen, CN, NO2, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11C(O)NRc11Rd11, C(=NRe11)Rb11, C(=NORa11)Rb11, C(=NRe11)NRc11Rd11, NRc11C(=NRe11)NRc11Rd11, NRc11S(O)Rb11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)Rb11, S(O)NRc11Rd11, S(O)2Rb11, S(O)2NRc11Rd11, i BRh11Ri11; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
Cy1 se bira od sljedećih: C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, i 5-10-člani heteroaril; pri čemu svaki 4-10-člani heterocikloalkil, i 5-10-člani-heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3, ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; gdje se N i S opcionalno oksidiraju; dok se atom ugljika koji formira prsten od 5-10-članog heteroarila i 4-10-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, i 5-10-člani heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
svaki R7 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10 cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3alkilen, halogen, D, CN, NO2, ORa12, SRa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12C(O)NRc12Rd12, C(=NRe12)Rb12, C(=NORa12)Rb12, C(=NRe12)NRc12Rd12, NRc12C(=NRe12)NRc12Rd12, NRc12S(O)Rb12, NRc12S(O)2Rb12, NRc12S(O)2NRc12Rd12, S(O)Rb12, S(O)NRc12Rd12, S(O)2Rb12, S(O)2NRc12Rd12, i BRh12Ri12; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, i 5-10-člani heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R8;
svaki R8 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3alkilen, halogen, D, CN, ORa13, SRa13, C(O)Rb13, C(O)NRc13Rd13, C(O)ORa13, NRc13Rd13, NRc13C(O)Rb13, NRc13C(O)ORa13, NRc13S(O)Rb13, NRc13S(O)2Rb13, NRc13S(O)2NRc13Rd13, S(O)Rb13, S(O)NRc13Rd13, S(O)2Rb13, S(O)2NRc13Rd13, i BRh13Ri13; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3 alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, i 5-10-člani heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R9;
svaki R9 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-6cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, halogen, D, CN, ORa14, SRa14, C(O)Rb14, C(O)NRc14Rd14, C(O)ORa14, NRc14Rd14, NRc14C(O)Rb14, NRc14C(O)ORa14, NRc14S(O)Rb14, NRc14S(O)2Rb14, NRc14S(O)2NRc14Rd14, S(O)Rb14, S(O)NRc14Rd14, S(O)2Rb14, i S(O)2NRc14Rd14; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-6cikloalkil, C6-10 aril, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki R10 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3 alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3alkilen, halogen, D, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, C(=NRe1)Rb1, C(=NORa1)Rb1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, S(O)2NRc1Ra1, i BRh1Ri1; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani-heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen i 5-10-člani heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11;
svaki R11 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3 alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3alkilen, halogen, D, CN, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, S(O)2NRc2Rd2, i BRh2Ri2; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen i 5-10-člani heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R12;
svaki R12 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-6cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, halogen, D, CN, ORa3, SRa3, C(O)ORb3, C(O)NRc3Rd3, C(O)ORa3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-6cikloalkil, C6-10 aril, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki R13 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10-aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3 alkilen, halogen, D, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, C(=NRe5)Rb5, C(=NORa5)Rb5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, S(O)2NRc5Rd5, i BRh5Ri5; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen i 5-10-člani heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R14;
svaki R14 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen, 5-10-člani heteroaril-C1-3alkilen, halogen, D, CN, ORa6, SRa6, C(O)Rb6, C(O)NRc6Rd6, C(O)ORa6, NRc6Rd6, NRc6C(O)Rb6, NRc6S(O)Rb6, NRc6S(O)2Rb6, NRc6S(O)2NRc6Rd6, S(O)Rb6, S(O)NRc6Rd6, S(O)2Rb6, S(O)2NRc6Rd6, i BRh6Ri6; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10aril, 5-10-člani heteroaril, C3-10cikloalkil-C1-3alkilen, 4-10-člani heterocikloalkil-C1-3alkilen, C6-10aril-C1-3alkilen i 5-10-člani heteroaril-C1-3alkilen, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R15;
svaki R15 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-6cikloalkil, fenil, 5-6-člani heteroaril, 4-7-člani heterocikloalkil, halogen, D, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)ORa7, NRc7S(O)Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, i S(O)2NRc7Rd7; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-6cikloalkil, fenil, 5-6-člani heteroaril, i 4-7-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Ra, Rc i Rd se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10;
ili bilo koji od Rc i Rd koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10;
svaki Rb se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10;
svaki Re se neovisno bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6alkiltio, C1-6alkilsulfonil, C1-6alkilkarbonil, C1-6alkilaminosulfonil, karbamil, C1-6alkilkarbamil, di(C1-6 alkil)karbamil, aminosulfonil, C1-6alkilaminosulfonil, i di(C1-6alkil)aminosulfonil;
svaki Rh i Ri se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh i Ri koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra1, Rc1 i Rd1 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od R11;
ili bilo koji od Rc1 i Rd1 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11;
svaki Rb1 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11;
svaki Re1 se neovisno bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6alkiltio, C1-6alkilsulfonil, C1-6alkilkarbonil, C1-6alkilaminosulfonil, karbamil, C1-6alkilkarbamil, di(C1-6 alkil)karbamil, aminosulfonil, C1-6 alkilaminosulfonil, i di(C1-6alkil)aminosulfonil;
svaki Rh1 i Ri1 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh1 i Ri1 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra2, Rc2 i Rd2 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R12;
ili bilo koji od Rc2 i Rd2 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R12;
svaki Rb2 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R12;
svaki Rh2 i Ri2 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh2 i Ri2 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra3, Rc3 i Rd3 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Rb3 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Ra4, Rc4 i Rd4 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R13;
ili bilo koji od Rc4 i Rd4 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R13;
svaki Rb4 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R13;
svaki Re4 se neovisno bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6alkiltio, C1-6 alkilsulfonil, C1-6alkilkarbonil, C1-6alkilaminosulfonil, karbamil, C1-6alkilkarbamil, di(C1-6 alkilkarbamil, aminosulfonil, C1-6alkilaminosulfonil, i di(C1-6alkil)aminosulfonil;
svaki Rh4 i Ri4 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh4 i Ri4 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra5, Rc5 i Rd5 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R14;
ili bilo koji od Rc5 i Rd5 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R14;
svaki Rb5 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R14;
svaki Re5 se neovisno bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6alkiltio, C1-6alkilsulfonil, C1-6alkilkarbonil, C1-6alkilaminosulfonil, karbamil, C1-6alkilkarbamil,
di(C1-6 alkil)karbamil, aminosulfonil, C1-6alkilaminosulfonil, i di(C1-6alkil)aminosulfonil;
svaki Rh5 i Ri5 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh5 i Ri5 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra6, Rc6 i Rd6 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R15;
ili bilo koji od Rc6 i Rd6 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R15;
svaki Rb6 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R15;
svaki Rh6 i Ri6 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh6 i Ri6 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra7, Rc7 i Rd7 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Rb7 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Ra8, Rc8 i Rd8 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R5;
ili bilo koji od Rc8 i Rd8 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R5;
svaki Rb8 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od R5;
svaki Re8 se neovisno bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6alkiltio, C1-6alkilsulfonil, C1-6alkilkarbonil, C1-6alkilaminosulfonil, karbamil, C1-6alkilkarbamil, di(C1-6 alkil)karbamil, aminosulfonil, C1-6alkilaminosulfonil, i di(C1-6-alkil)aminosulfonil;
svaki Rh8 i Ri8 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh8 i Ri8 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra9, Rc9 i Rd9 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R6;
ili bilo koji od Rc9 i Rd9 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R6;
svaki Rb9 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R6;
svaki Rh9 i Ri9 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh9 i Ri9koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra10, Rc10 i Rd10 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Rb10 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Ra11, Rc11 i Rd11 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
ili bilo koji od Rc11 i Rd11 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
svaki Rb11 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
svaki Re11 se neovisno bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6-alkiltio, C1-6alkilsulfonil, C1-6alkilkarbonil, C1-6alkilaminosulfonil, karbamil, C1-6alkilkarbamil,
di(C1-6 alkil)karbamil, aminosulfonil, C1-6alkilaminosulfonil, i di(C1-6alkil)aminosulfonil;
svaki Rh11 i Ri11 se neovisno bira od sljedećih: OH, i C1-6-alkoksi;
ili bilo koji od Rh11 i Ri11koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra12, Rc12 i Rd12 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R8;
ili bilo koji od Rc12 i Rd12 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R8;
svaki Rb12 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R8;
svaki Re12 se neovisno bira od sljedećih: H, CN, C1-6 alkil, C1-6 haloalkil, C1-6-alkiltio, C1-6alkilsulfonil, C1-6alkilkarbonil, C1-6alkilaminosulfonil, karbamil, C1-6alkilkarbamil,
di(C1-6-alkil)karbamil, aminosulfonil, C1-6alkilaminosulfonil, i di(C1-6-alkil)aminosulfonil;
svaki Rh12 i Ri12 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh12 i Ri12 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra13, Rc13 i Rd13 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R9;
ili bilo koji od Rc13 i Rd13 koji je vezan s istim N atomom, zajedno s N atomom s kojim je vezan, tvori 4-članu, 5-članu, 6-članu ili 7-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R9;
svaki Rb13 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-10 cikloalkil, 4-10-člani heterocikloalkil, C6-10 aril i 5-10-člani heteroaril, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R9;
svaki Rh13 i Ri13 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh13 i Ri13 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila;
svaki Ra14, Rc14 i Rd14 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Rb14 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Ra15, Rc15 i Rd15 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Ra16, Rc16 i Rd16 se neovisno bira od sljedećih: H, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Rb16 se neovisno bira od sljedećih: C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil; pri čemu je svaki navedeni C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Rh16 i Ri16 se neovisno bira od sljedećih: OH, i C1-6alkoksi;
ili bilo koji od Rh16 i Ri16 koji je vezan s istim B atomom, jest C2-3 dialkoksi i zajedno s B atomom s kojim je vezan, tvori 5-članu ili 6-članu heterocikloalkilnu skupinu opcionalno supstituiranu s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od C1-6alkila; i
svaki Rg se neovisno bira od sljedećih: OH, NO2, CN, halogen, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C3-6 cikloalkil, C3-6 cikloalkil-C1-2 alkilen, C1-6 alkoksi, C1-6 haloalkoksi, C1-3 alkoksi-C1-3 alkil, C1-3 alkoksi-C1-3 alkoksi, HO-C1-3 alkoksi, HO-C1-3 alkil, cijano-C1-3 alkil, H2N-C1-3 alkil, amino, C1-6 alkilamino, di(C1-6 alkil)amino, tio, C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkilsulfonil, karbamil, C1-6 alkilkarbamil, di(C1-6 alkil)karbamil, karboksi, C1-6 alkilkarbonil, C1-6 alkoksikarbonil, C1-6 alkilkarbonilamino, C1-6 alkilsulfonilamino, aminosulfonil, C1-6 alkilaminosulfonil, di(C1-6 alkil)aminosulfonil, aminosulfonilamino, C1-6 alkilaminosulfonilamino, di(C1-6 alkil)aminosulfonilamino, aminokarbonilamino, C1-6 alkilaminokarbonilamino, i di(C1-6 alkil)aminokarbonilamino; i
n je 0, 1, 2, 3 ili 4.
2. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da CyA je 4-12-člani heterocikloalkil; pri čemu 4-12-člani heterocikloalkil ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten a neovisno se biraju od N, O i S; pri čemu se atom ugljika koji formira prsten od 4-12-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom se 4-12-člani heterocikloalkil opcionalno supstituira s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od RA;
R16 se bira od sljedećih: H, D, C1-6 alkil, halogen, CN, ORa16;
R1 se bira od sljedećih: H, D, halogen, CN, C1-6 alkil, ORa15; pri čemu je C1-6 alkil opcionalno supstituiran s 1, 2, ili 3 supstituenta koji se neovisno biraju od Rg;
R2 se bira od sljedećih: H, D, Cy2, C1-6 alkil, C1-6 haloalkil, halogen, CN; pri čemu se navedeni C1-6 alkil, opcionalno supstituira s 1, 2, 3 ili 4 supstituenta koji se biraju od R10;
Cy2 se bira od sljedećih: 4-10-člani heterocikloalkil, C6-10-aril, i 5-10-člani-heteroaril; pri čemu svaki 4-10-člani heterocikloalkil, i 5-10-člani-heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; gdje se atom ugljika koji formira prsten od 5-10-članog heteroarila i 4-10-članog heterocikloalkila opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki 4-10-člani heterocikloalkil, i 5-10-člani-heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10;
R3 se bira od sljedećih: H, D, Cy3, halogen, i CN;
Cy3 je 6-10-člani heteroaril; pri čemu svaki 6-10-člani heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S;
svaki R4 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, halogen, D, CN, i ORa8;
RA se bira od sljedećih: H, D, Cy1, C1-6 alkil, C1-6 haloalkil, halogen, CN, ORa11, C(O)NRc11Rd11, i NRc11Ra11; pri čemu je spomenuti C1-6 alkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
Cy1 se bira od sljedećih: C3-10 cikloalkil, i 5-10-člani heteroaril; pri čemu svaki 5-10-člani heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; gdje se atom ugljika koji formira prsten od 5-10-članog heteroarila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki C3-10 cikloalkil, i 5-10-člani heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
svaki R7 se neovisno bira od sljedećih: C1-6 alkil, halogen, D, CN, NO2, ORa12, i NRc12Ra12;
svaki R10 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, 4-10-člani heterocikloalkil, halogen, D, CN, ORa1, C(O)NRc1Ra1, i NRc1Rd1; pri čemu je svaki spomenuti C1-6 alkil, i 4-10-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11;
svaki R11 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, halogen, D, CN, i ORa2;
svaki Ra1, Rc1 i Rd1 se neovisno bira od sljedećih: H, C1-6 alkil, C1-6 haloalkil, i C3-10 cikloalkil; pri čemu je svaki navedeni C1-6 alkil, i C3-10 cikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11;
svaki Ra2, Rc2 i Rd2 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil;
svaki Ra8, Rc8 i Rd8 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil;
svaki Ra11, Rc11 i Rd11 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil; pri čemu je navedeni C1-6 alkil opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od R7;
svaki Ra12, Rc12 i Rd12 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil;
svaki Ra15, Rc15 i Rd15 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil; pri čemu je navedeni C1-6 alkil opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od Rg;
Ra16 se neovisno bira od sljedećih: H, i C1-6 alkil;
svaki Rg se neovisno bira od sljedećih: OH, CN, halogen, C1-6 alkil, C1-6 haloalkil, C1-6-alkoksi, C1-6-haloalkoksi, amino, C1-6-alkiltio, C1-6-alkilsulfonil; i
n je 0, 1, 2 ili 3.
3. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da spoj Formule I’ je spoj Formule I:
[image]
ili njegova farmaceutski prihvatljiva sol, pri čemu:
A je N ili CF; i
R3 se bira od sljedećih: H, D, Cy3, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, halogen, CN, NO2, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)ORa4, NRc4C(O)NRc4Rd4, C(NRe4)Rb4, C(=NORa4)Rb4, C(=NRe4)NRc4Rd4, NRc4C(=NRe4)NRc4Rd4, NRc4S(O)Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, S(O)2NRc4Rd4, i BRh4Ri4; pri čemu je svaki spomenuti C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od R13.
4. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da spoj Formule I’ je spoj Formule I:
[image]
ili njegova farmaceutski prihvatljiva sol, pri čemu:
CyA je 4-12-člani heterocikloalkil; pri čemu 4-12-člani heterocikloalkil ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji tvore prsten neovisno odabrana od N, O i S; pri čemu se atom ugljika koji formira prsten od 4-12-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom se 4-12-člani heterocikloalkil opcionalno supstituira s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od RA;
A je N;
R1 se bira od sljedećih: H, D, halogen, CN, C1-6 alkil, i ORa15; pri čemu je C1-6 alkil opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od Rg;
R2 se bira od sljedećih: H, D, Cy2, C1-6 alkil, C1-6 haloalkil, halogen, CN; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od R10;
Cy2 se bira od sljedećih: 4-10-člani heterocikloalkil, i 5-10-člani heteroaril; pri čemu svaki 4-10-člani heterocikloalkil, i 5-10-člani heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; gdje se atom ugljika koji formira prsten od 5-10-članog heteroarila i 4-10-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki 4-10-člani heterocikloalkil, 5-10-člani heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10;
R3 se bira od sljedećih: H, D, Cy3, halogen, i CN;
Cy3 je 5-10-člani heteroaril; pri čemu 5-10-člani heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; gdje se atom ugljika koji formira prsten od 5-10-članog heteroarila opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je 5-10-člani heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R13;
svaki R4 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, halogen, D, CN, i ORa8; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1, 2, 3, ili 4 supstituenta koji se neovisno biraju od R5;
svaki R5 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, halogen, D, CN, ORa9, i NRc9Rd9;
RA se bira od sljedećih: H, D, Cy1, C1-6 alkil, C1-6 haloalkil, halogen, CN, ORa11, C(O)NRc11Rd11, i NRc11Rd11; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
Cy1 je 5-10 člani heteroaril; pri čemu svaki 5-10-člani-heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; gdje atom ugljika koji formira prsten od 5-10-članog heteroarila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki 5-10-člani heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
svaki R7 se neovisno bira od sljedećih: C1-6 alkil, halogen, D, CN, ORa12, i NRc12Rd12;
svaki R10 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, 4-10-člani heterocikloalkil, halogen, D, CN, ORa1, C(O)NRc1Rd1, i NRc1Rd1; pri čemu je svaki spomenuti C1-6 alkil, i 4-10-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11;
svaki R11 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, halogen, D, CN, i ORa2;
svaki R13 se neovisno bira od sljedećih: C1-6 alkil, i C1-6 haloalkil;
svaki Ra1, Rc1 i Rd1 se neovisno bira od sljedećih: H, C1-6 alkil, C1-6 haloalkil, i C3-10 cikloalkil; pri čemu je svaki navedeni C1-6 alkil, i C3-10 cikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11;
svaki Ra2, Rc2 i Rd2 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil;
svaki Ra8, Rc8 i Rd8 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil;
svaki Ra9, Rc9 i Rd9 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil;
svaki Ra11, Rc11 i Rd11 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil; pri čemu je navedeni C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7;
svaki Ra12, Rc12 i Rd12 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil;
svaki Ra15, Rc15 i Rd15 se neovisno bira od sljedećih: H, C1-6 alkil, i C1-6 haloalkil; pri čemu je navedeni C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od Rg;
svaki Rg se neovisno bira od sljedećih: OH, CN, halogen, C1-6 alkil, C1-6 haloalkil, C1-6 alkoksi, C1-6 haloalkoksi, amino, C1-6 alkilamino, di(C1-6 alkil)amino, tio,
C1-6 alkiltio, C1-6 alkilsulfinil, C1-6 alkiltio i C1-6 alkilsulfonil; i
n je 0, 1, 2 ili 3.
5. Spoj prema bilo kojem od patentnih zahtjeva 1 i 3, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) CyA je 4-12-člani heterocikloalkil; pri čemu 4-12-člani heterocikloalkil ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O i S; pri čemu se atom ugljika koji formira prsten od 4-12-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom se 4-12-člani heterocikloalkil opcionalno supstituira s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od RA; ili
(ii) CyA je C3-10 cikloalkil; pri čemu je C3-10 cikloalkil opcionalno supstituiran s 1, 2 ili 3 supstituenta koji se neovisno biraju od RA.
6. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se svaki RA neovisno bira od sljedećih: Cy1, C1-6 alkil, ORa11, C(O)NRc11Rd11, i NRc11Rd11; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7.
7. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) svaki RA je neovisno C1-6 alkil; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R7; ili
(ii) svaki RA se neovisno bira od metila i etila; pri čemu je svaki spomenuti metil i etil opcionalno supstituiran s 1, 2 ili 3 supstituenta koji se neovisno biraju od R7.
8. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se svaki RA neovisno bira od OH i NH2, aminometila, hidroksimetila, metoksimetila, piridinila, etila, hidroksietila, i propilkarbamoila.
9. Spoj prema bilo kojem od patentnih zahtjeva 1 do 4, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) CyA se bira od sljedećih: 2,5-diazabiciklo[2.2.1]heptan-2-il; 3-aminopirolidin-1-il; 2-(aminometil)pirolidin-1-il; 2-(hidroksimetil)pirolidin-1-il; 2-(metoksimetil)pirolidin-1-il; 4-amino-2-(hidroksimetil)pirolidin-1-il; 4-hidroksi-2-metilpirolidin-1-il; 2-(piridin-2-il)pirolidin-1-il; heksahidropirolo[3,4-b]pirol-1(2H)-il; 2-metilpiperazin-1-il; 2-(hidroksimetil)piperazin-1-il; 3-(hidroksimetil)morfolino; 5-etil-2,5-diazabiciklo[2.2.1]heptan-2-il; (2-hidroksietil)-2,5-diazabiciklo[2.2.1]heptan-2-il); 5-(propilkarbamoil)-2,5-diazabiciklo[2.2.1]heptan-2-il; 4-hidroksi-2-(hidroksimetil)pirolidin-1-il; 2-(hidroksimetil)-5-metilpiperazin-1-il; 6-(hidroksimetil)-4,7-diazaspiro[2.5]oktan-7-il; 4-amino-2-(1-hidroksiciklopropil)pirolidin-1-il; 4-amino-2-(2-hidroksipropan-2-il)pirolidin-1-il; 4-amino-2-(1-hidroksiciklopropil)pirolidin-1-il; 4-amino-2-(2-hidroksipropan-2-il)pirolidin-1-il; 4-amino-2-(hidroksimetil-d2)pirolidin-1-il; 3-(hidroksimetil)-2,5-diazabiciklo[2.2.1]heptan-2-il; 4-amino-2-metilpiperidin-1-il; piperidin-4-il; 4-(dimetilamino)-2-(hidroksimetil)pirolidin-1-il; 2-(hidroksimetil)-4-(izopropilamino)pirolidin-1-il; 4-(hidroksimetil)-5-metil-2,5-diazabiciklo[2.2.1]heptan-2-il; 2-(hidroksimetil)morfolino; 2-(2-((dimetilamino)metil)morfolino; 2-(cijanometil)morfolino; 3-oksotetrahidro-3H-oksazolo[3,4-a]pirazin-7(1H)-il; 3-(hidroksimetil)piperazin-1-il; 3-(metoksimetil)azetidin-1-il; 2-(hidroksimetil)azetidin-1-il; 2-((dimetilamino)metil)azetidin-1-il; 4-metilpiperazin-1-il; i 4-(2-hidroksietil)piperazin-1-il;
(ii) CyA se bira od sljedećih: 2,5-diazabiciklo[2.2.1]heptan-2-il; 3-aminopirolidin-1-il; 2-(aminometil)pirolidin-1-il; 2-(hidroksimetil)pirolidin-1-il; 2-(metoksimetil)pirolidin-1-il; 4-amino-2-(hidroksimetil)pirolidin-1-il; 4-hidroksi-2-metilpirolidin-1-il; 2-(piridin-2-il)pirolidin-1-il; heksahidropirolo[3,4-b]pirol-1(2H)-il; 2-metilpiperazin-1-il; 2-(hidroksimetil)piperazin-1-il; 3-(hidroksimetil)morfolino; 5-etil-2,5-diazabiciklo[2.2.1]heptan-2-il; (2-hidroksietil)-2,5-diazabiciklo[2.2.1]heptan-2-il; i 5-(propilkarbamoil)-2,5,diazabiciklo[2.2.1]heptan-2-il; ili
(iii) CyA jest 4-amino-2-(hidroksimetil)pirolidin-1-il.
10. Spoj prema bilo kojem od patentnih zahtjeva 1 do 9, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se R1 bira od sljedećih: H, D, halogen, CN, C1-6 alkil, i ORa15; pri čemu je C1-6 alkil opcionalno supstituiran s 1, 2 ili 3 supstituenta koji se neovisno biraju od Rg.
11. Spoj prema bilo kojem od patentnih zahtjeva 1 do 10, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) R1 se bira od sljedećih: H, D, F, CN, metil, hidroksimetil i metoksi;
(ii) R1 jest H; ili
(iii) R1 jest F.
12. Spoj prema bilo kojem od patentnih zahtjeva 1 do 11, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se R2 bira od sljedećih: H, D, Cy2, C1-6 alkil, halogen, i S(O)2Rb; pri čemu je navedeni C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10.
13. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se R2 bira od sljedećih: izopropil, F, Cl, Br, i S(O)2CH3.
14. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se R2 jest Cy2.
15. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12 i 14, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) Cy2 se bira od sljedećih: 4-10-člani heterocikloalkil, i 5-10-člani heteroaril; gdje svaki 4-10-člani heterocikloalkil, i 5-10-člani heteroaril, ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; pri čemu se atom ugljika koji formira prsten od 5-10-članog heteroarila i 4-10-članog heterocikloalkila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je svaki 4-10-člani heterocikloalkil i 5-10-člani heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10; ili
(ii) Cy2 je C6-10 aril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R10.
16. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12, 14 i 15, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se svaki R10 neovisno bira od sljedećih: C1-6 alkil, 4-10-člani heterocikloalkil, halogen, CN, OH, ORa1, C(O)NRc1Rd1 i NRc1Rd1; pri čemu svaki navedeni C1-6 alkil, i 4-10-člani heterocikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11.
17. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12, 14 i 15, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se svaki R10 neovisno bira od sljedećih: OH, F, CN, metil, hidroksimetil, metilkarbamoil, metoksi, morfolino, i ciklobutilamino.
18. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12, i 14 do 16, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) svaki Ra1, Rc1 i Rd1 se neovisno bira od sljedećih: H, C1-6 alkil, i C3-10 cikloalkil; pri čemu je svaki navedeni C1-6 alkil, i C3-10 cikloalkil, opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R11; i/ili
(ii) svaki R11 jest ORa2; ili svaki R11 jest OH.
19. Spoj prema bilo kojem od patentnih zahtjeva 1 do 11, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) Cy2 se bira od sljedećih: 1-metil-1H-pirazol-4-il; 6-(hidroksimetil)piridin-3-il; 6-(metilkarbamoil)piridin-3-il; 1-metil-6-okso-1,6-dihidropiridin-3-il; 2-metilpiridin-3-il; 4-metoksipiridin-3-il; 4-cijanopiridin-3-il; 1,3,5-trimetil-1H-pirazol-4-il; morfolino; azetidin-1-il; 2-(metoksimetil)azetidin-1-il); 3-cijanopiridin-4-il; 3-metoksipiridin-4-il; 2-cijano-6-fluorofenil; 3-cijanopiridin-2-il; 4-cijano-1-metil-1H-pirazol-5-il; tetrahidro-2H-piran-4-il; 5-cijano-2-(pirolidin-1-il)piridin-4-il; i 1-cijanociklopropil;
(ii) Cy2 se bira od sljedećih: 1-metil-1H-pirazol-4-il; 6-(hidroksimetil)piridin-3-il; 6-(metilkarbamoil)piridin-3-il; 1-metil-6-okso-1,6-dihidropiridin-3-il; 2-metilpiridin-3-il; 4-metoksipiridin-3-il; 4-cijanopiridin-3-il; 1,3,5-trimetil-1H-pirazol-4-il; morfolino; i azetidin-1-il; ili
(iii) Cy2 se bira od sljedećih: 3-cijanopiridin-4-il; 4-cijanopiridin-3-il; i 3-cijanopiridin-2-il.
20. Spoj prema bilo kojem od patentnih zahtjeva 1 i 2, ili njegova farmaceutski prihvatljiva sol, naznačen time, da Z jest CR3.
21. Spoj prema bilo kojem od patentnih zahtjeva 1 i 2, ili njegova farmaceutski prihvatljiva sol, naznačen time, da Z jest N.
22. Spoj prema bilo kojem od patentnih zahtjeva 1 do 20, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se R3 bira od sljedećih: H, D, Cy3, halogen i CN.
23. Spoj prema bilo kojem od patentnih zahtjeva 1 do 20, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) R3 se bira od sljedećih: H, D, F, Br i CN; ili
(ii) R3 jest H.
24. Spoj prema bilo kojem od patentnih zahtjeva 1 do 20, ili njegova farmaceutski prihvatljiva sol, naznačen time, da R3 jest Cy3.
25. Spoj prema bilo kojem od patentnih zahtjeva 1 do 20, 22 i 24, ili njegova farmaceutski prihvatljiva sol, naznačen time, da Cy3 jest 5-10-člani heteroaril; gdje svaki 5-10-člani heteroaril ima najmanje jedan atom ugljika koji formira prsten i 1, 2, 3 ili 4 heteroatoma koji formiraju prsten neovisno odabrana od N, O, i S; pri čemu se atom ugljika koji formira prsten od 5-10-članog heteroarila, opcionalno supstituira s okso u svrhu tvorbe karbonilne skupine; i pritom je 5-10-člani heteroaril opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R13.
26. Spoj prema bilo kojem od patentnih zahtjeva 1 do 20, 22, 24 i 25, ili njegova farmaceutski prihvatljiva sol, naznačen time, da R13 je neovisno C1-6 alkil.
27. Spoj prema bilo kojem od patentnih zahtjeva 1 do 20, 22, i 25, ili njegova farmaceutski prihvatljiva sol, naznačen time, da R13 jest metil.
28. Spoj prema bilo kojem od patentnih zahtjeva 1 do 20, i 22, ili njegova farmaceutski prihvatljiva sol, naznačen time, da Cy3 se bira od sljedećih: piridin-3-il, i 1-metil-1H-pirazol-4-il.
29. Spoj prema bilo kojem od patentnih zahtjeva 1 do 28, ili njegova farmaceutski prihvatljiva sol, naznačen time, da se svaki R4 neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, C3-10 cikloalkil, halogen, D, CN, i ORa8; pri čemu je spomenuti C1-6 alkil opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta koji se neovisno biraju od R5.
30. Spoj prema bilo kojem od patentnih zahtjeva 1 do 28, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) svaki R4 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, halogen, D, CN, i ORa8; ili
(ii) svaki R4 se neovisno bira od sljedećih: halogen, i ORa8.
31. Spoj prema bilo kojem od patentnih zahtjeva 1 do 28, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) svaki R4 se neovisno bira od halogena;
(ii) svaki R4 se neovisno bira od sljedećih: F i Cl;
(iii) svaki R4 se neovisno bira od sljedećih: F i metoksi;
(iv) svaki R4 se neovisno bira od sljedećih: F i metil; ili
(v) svaki R4 jest F.
32. Spoj prema bilo kojem od patentnih zahtjeva 1 do 30, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) svaki R5 se neovisno bira od sljedećih: C1-6 alkil, C1-6 haloalkil, halogen, D, CN, ORa9, i NRc9Rd9; ili
(ii) svaki R5 se neovisno bira od sljedećih: D i F.
33. Spoj prema bilo kojem od patentnih zahtjeva 1 do 32, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) svaki Rg jest OH; i/ili
(ii) n je 2.
34. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3 i 5 do 33, ili njegova farmaceutski prihvatljiva sol, naznačen time, da A jest N.
35. Spoj prema bilo kojem od patentnih zahtjeva 1, 2 i 5 do 33, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
(i) A jest CR16; i/ili
(ii) R16 je H, CN, ili ORa16; i/ili
(iii) Ra16 se bira od sljedećih: H i C1-6 alkil; ili Ra16 jest metil.
36. Spoj prema bilo kojem od patentnih zahtjeva 1 do 4, naznačen time, da ima:
(i)
[image]
ili njegova farmaceutski prihvatljiva sol;
(ii)
[image]
ili njegova farmaceutski prihvatljiva sol;
(iii)
Formula IIB:
[image]
ili njegova farmaceutski prihvatljiva sol;
(iv)
[image]
ili njegova farmaceutski prihvatljiva sol;
(v)
[image]
ili njegova farmaceutski prihvatljiva sol; ili
(vi)
[image]
ili njegova farmaceutski prihvatljiva sol.
37. Spoj prema bilo kojem od patentnih zahtjeva 1, 2 i 3, naznačen time, da ima Formulu IB:
[image]
ili njegova farmaceutski prihvatljiva sol.
38. Spoj prema bilo kojem od patentnih zahtjeva 1 i 2, naznačen time, da ima:
(i)
[image]
ili njegova farmaceutski prihvatljiva sol;
(ii)
[image]
ili njegova farmaceutski prihvatljiva sol;
(iii)
Formula V:
[image]
ili njegova farmaceutski prihvatljiva sol; ili
(vi)
[image]
ili njegova farmaceutski prihvatljiva sol.
39. Spoj prema patentnom zahtjevu 1, naznačen time, da se bira od sljedećih:
(i)
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(S)-N-(2-(3-aminopirolidin-1-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(2-(2-(aminometil)pirolidin-1-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(S-fluoro-2-(2-(hidroksimetil)pirolidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(5-fluoro-2-(2-(metoksimetil)pirolidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(5-fluoro-2-((2S,4S)-4-hidroksi-2-metilpirolidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(5-fluoro-2-(2-(piridin-2-il)pirolidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(5-fluoro-2-(heksahidropirolo[3,4-b]pirol-1(2H)-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(5-fluoro-2-(2-metilpiperazin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(5-fluoro-2-(2-(hidroksimetil)piperazin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(5-fluoro-2-(3-(hidroksimetil)morfolino)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-3-bromo-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-3-cijanofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-3-(piridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-3-(1-metil-1H-pirazol-4-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-(hidroksimetil)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-bromo-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-(1-metil-1H-pirazol-4-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-(6-(hidroksimetil)piridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-(6-(metilkarbamoil)piridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-(1-metil-6-okso-1,6-dihidropiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-(2-metilpiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-(2-metilpiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-(4-metoksipiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-(1,3,5-trimetil-1H-pirazol-4-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-morfolinofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N(4-(azetidin-1-il)-2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluoro-4-(morfolinometil)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-((ciklobutilamino)metil)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1R,4R)-5-etil-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(5-fluoro-2-((1R,4R)-5-(2-hidroksietil)-2,5-diazabiciklo[2.2.1]heptan-2-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(1R,4R)-5-(4-fluoro-2-(2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamido)fenil)-N-propil-2,5-diazabiciklo[2.2.1]heptan-2-karboksamid;
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-metoksifenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-(hidroksimetil)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid; i
N-(2-((1R,4R)-2,5-diazabiciklo[2.2.1]heptan-2-il)-5-cijanofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
ili njegova farmaceutski prihvatljiva sol;
(ii)
N-(4-(azetidin-1-il)-2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-((S)-2-(metoksimetil)azetidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-(3-cijanopiridin-4-il)-3-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(3-cijanopiridin-4-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6- metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(2-metilpiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(3-metoksipiridin-4-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(3-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-2'-cijano-6'-fluorobifenil-4-il)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(3-cijanopilidin-2-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijano-1-metil-1H-pirazol-5-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-izopropilfenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(3-cijanopiridin-4-il)-2-((2S,4S)-4-hidroksi-2-(hidroksimetil)piroIidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-((2S,5R)-2-(hidroksimetil)-5-metilpiperazin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-((2S,5S)-2-(hidroksimetil)-5-metilpiperazin-1-il)fenil)-2-(2-fluoro-6- metoksifenil) pirimidin-4- karboksamid;
(S)-N-(4-(4-cijanopiridin-3-il)-2-(6-(hidroksimetil)-4,7-diazaspiro[2.5]oktan-7-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(1-hidroksiciklopropil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(2-hidroksipropan-2-il)piroIidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil-d2)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-((1S,3R,4S)-3-(hidroksimetil)-2,5-diazabiciklo[2.2.1]heptan-2-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-((1S,4S)-1-(hidroksimetil)-2,5-diazabiciklo[2.2.1]heptan-2-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-metilpiperidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-6-(2-fluoro-6-metoksifenil)pikolinamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-5-cijano-6-(2-fluoro-6-metoksifenil)pikolinamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-6-(2-fluoro-6-metoksifenil)-5-metoksipikolinamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2,6-difluorofenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metilfenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-kloro-6-fluorofenil)pirimidin-4-karboksamid; i
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-6-(1,3,5-trimetil-1H-pirazol-4-il)piridin-3-il)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
ili njegova farmaceutski prihvatljiva sol.
(iii)
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-5-fluorofenil)-2-(2,6-difluorofenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-5-fluorofenil)-2-(3-cijano-2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-5-fluorofenil)-2-(2,3-difluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetiI)pirolidin-1-il)-5-fluorofenil)-2-(2-fluoro-6-(metoksi-d3)-3- metilfenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksi-4-metilfenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetiI)pirolidin-1-il)-4-(4-cijanopiridin-3-iI)fenil)-2-(3,6-difluoro-2-metilfenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)feniI)-2-(2,3-dilluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-iI)fenil)-2-(3,6-difluoro-2-metoksifeniI)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(3-cijano-2-fluoro-6-(metoksi-d3)fenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)piroIidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(3,6-difluoro-2-(metoksi-d3)feniI)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2,3-difluoro-6-(metoksi-d3)fenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-(metoksi-d3)fenil-5-d)pirimidin-4-karboksamid;
2-(2-fluoro-6-metoksifenil)-N-(2-(piperidin-4-il)fenil)pirimidin-4-karboksamid;
N-(2-(cis)4-aminocikloheksil)fenil)-2-(2-fluoro-6-metoksifenil) pirimidin-4-karboksamid;
N-(2-(trans)4-aminocikloheksil)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-(3-aminocikloheksil)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-(3-aminociklopentil)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((cis)-4-aminocikloheksil)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((trans)-4-aminocikloheksil)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((cis)-4-aminocikloheksil)-4-(4-cijano-1-metil-1H-pirazoI-5-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((trans)-4-aminocikloheksil)-4-(4-cijano-1-metil-1H-pirazol-5-il)fenil)-2-(2-fluoro-6-metoksifeniI)pirimidin-4-karboksamid;
N-(2-((cis)-4-aminocikloheksil)-4-(1,3,5-trimetil-1H-pirazol-4-iI)feniI)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(metilsulfonil)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-5-metilfenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-(dimetilamino)-2-(hidroksimetil)pirolidin-1-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(5-fIuoro-2-((2S,4S)-2-(hidroksimetil)-4-(izopropilamino)pirolidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(tetrahidro-2H-piran-4-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-klorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(5-cijano-2-(pirolidin-1-il)piridin-4-il)fenil)-2-(2,6-difluorofenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(1-cijanociklopropil)fenil)-2-(2,6-difluorofenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(1-cijanopiridin-3-il)fenil)-2-(2-difluorometoksi)-6-fluorofenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-(metoksi-d3)fenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-ciklopropil-6-fluorofenil)pirimidin-4-karboksamid;
N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-etoksi-6-fluorofenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-((1S,4S)-4-(hidroksimetil)-5-metil-2,5-diazabiciklo[2.2.1]heptan-2-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(S)-N-(4-(4-cijanopiridin-3-il)-2-(2-(hidroksimetil)morfolino)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(S)-N-(4-(4-cijanopiridin-3-il)-2-(2-((dimetilamino)metil)morfolino)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(2-(2-(cijanometil)morfolino)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(4-(4-cijanopiridin-3-il)-2-(3-oksotetrahidro-3H-oksazolo[3,4-a]pirazin-7(1H)-il)fenil)-2-(2-fluoro- 6-metoksifenil)pirimidin-4-karboksamid;
(S)-N-(5-fIuoro-2-(3-(hidroksimetil)piperazin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-(3-(metoksimetil)azetidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(S)-N-(4-(4-cijanopiridin-3-il)-2-(2-(hidroksimetil)azetidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
(R)-N-(4-(4-cijanopiridin-3-il)-2-(2-((dimetilamino)metil)azetidin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-(4-metilpiperazin-1-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
N-(4-(4-cijanopiridin-3-il)-2-(4-(2-hidroksietil)piperazin-1-iI)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid; i
(S)-N-(5-fIuoro-2-(3-(hidroksimetil)piperazin-1-il)-4-izopropilfenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid;
ili njegova farmaceutski prihvatljiva sol.
40. Spoj prema patentnom zahtjevu 1, naznačen time, da je N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-5-fluorofenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid, ili njegova farmaceutski prihvatljiva sol.
41. Spoj prema patentnom zahtjevu 1, naznačen time, da je N-(2-((1S,4S)-2,5-diazabiciklo[2.2.1]heptan-2-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid, ili njegova farmaceutski prihvatljiva sol.
42. Spoj prema patentnom zahtjevu 1, naznačen time, da je N-(2-((2S,4S)-4-amino-2-(hidroksimetil)pirolidin-1-il)-4-(4-cijanopiridin-3-il)fenil)-2-(2-fluoro-6-metoksifenil)pirimidin-4-karboksamid, ili njegova farmaceutski prihvatljiva sol.
43. Farmaceutski pripravak, naznačen time, da sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 42, ili njegovu farmaceutski prihvatljivu sol, i najmanje jedan farmaceutski prihvatljiv nosač ili pomoćno sredstvo.
44. Spoj prema bilo kojem od patentnih zahtjeva 1 do 42, ili njegova farmaceutski prihvatljiva sol, naznačen time, da je za uporabu u liječenju raka, opcionalno gdje se rak bira od raka dojke, kolorektalnog raka, raka pluća, raka jajnika i raka gušterače.
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WO2019051199A1 (en) | 2017-09-08 | 2019-03-14 | Incyte Corporation | 6-CYANO-INDAZOLE COMPOUNDS AS HEMATOPOIETIC PROGENITOR KINASE 1 (HPK1) MODULATORS |
WO2019164847A1 (en) | 2018-02-20 | 2019-08-29 | Incyte Corporation | Indazole compounds and uses thereof |
US10745388B2 (en) | 2018-02-20 | 2020-08-18 | Incyte Corporation | Indazole compounds and uses thereof |
LT3755703T (lt) | 2018-02-20 | 2022-10-10 | Incyte Corporation | N-(fenil)-2-(fenil)pirimidin-4-karboksamido dariniai ir susiję junginiai, kaip hpk1 inhibitoriai, skirti vėžio gydymui |
US11299473B2 (en) | 2018-04-13 | 2022-04-12 | Incyte Corporation | Benzimidazole and indole compounds and uses thereof |
KR102596598B1 (ko) | 2018-04-26 | 2023-11-03 | 화이자 인코포레이티드 | 사이클린 의존성 키나제 억제제로서 2-아미노-피리딘 또는 2-아미노-피리미딘 유도체 |
ES2961384T3 (es) | 2018-05-04 | 2024-03-11 | Novo Nordisk As | Derivados de GIP y usos de los mismos |
EA202092779A1 (ru) | 2018-05-17 | 2021-02-02 | Байер Акциенгезельшафт | Замещенные дигидропиразолопиразинкарбоксамидные производные |
US10899755B2 (en) | 2018-08-08 | 2021-01-26 | Incyte Corporation | Benzothiazole compounds and uses thereof |
PE20221419A1 (es) | 2019-08-06 | 2022-09-20 | Incyte Corp | Formas solidas de un inhibidor de hpk1 |
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