CA3007993C - Inhibitors of bruton's tyrosine kinase and methods of their use - Google Patents

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Publication number

CA3007993C

CA3007993C CA3007993A CA3007993A CA3007993C CA 3007993 C CA3007993 C CA 3007993C CA 3007993 A CA3007993 A CA 3007993A CA 3007993 A CA3007993 A CA 3007993A CA 3007993 C CA3007993 C CA 3007993C

Authority

CA

Canada

Prior art keywords

oxo

dihydro

carboxamide

thia

triazaacenaphthylene

Prior art date

2015-12-10

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 title claims description 8
• 102000001714 Agammaglobulinaemia Tyrosine Kinase Human genes 0.000 title claims 3
• 238000000034 method Methods 0.000 title abstract description 160
• 239000003112 inhibitor Substances 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 623
• 125000001424 substituent group Chemical group 0.000 claims description 210
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 156
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 118
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 100
• 229910052736 halogen Inorganic materials 0.000 claims description 90
• 150000002367 halogens Chemical class 0.000 claims description 90
• 125000004076 pyridyl group Chemical group 0.000 claims description 76
• -1 CH2CH2-piperidinyl Chemical group 0.000 claims description 71
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 49
• 238000011282 treatment Methods 0.000 claims description 47
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 46
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 43
• 229910052731 fluorine Inorganic materials 0.000 claims description 42
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 40
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 39
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 37
• 229910052801 chlorine Inorganic materials 0.000 claims description 36
• 150000003839 salts Chemical class 0.000 claims description 36
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 30
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 26
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 24
• 125000001544 thienyl group Chemical group 0.000 claims description 24
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 23
• 208000035475 disorder Diseases 0.000 claims description 23
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 21
• 125000005605 benzo group Chemical group 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 19
• 230000000155 isotopic effect Effects 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 17
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 16
• 229960002685 biotin Drugs 0.000 claims description 16
• 239000011616 biotin Substances 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 16
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 16
• 125000003566 oxetanyl group Chemical group 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 15
• 206010028980 Neoplasm Diseases 0.000 claims description 14
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
• 125000003386 piperidinyl group Chemical group 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 13
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 12
• 201000011510 cancer Diseases 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• CXWQAPHDSYDHBR-UHFFFAOYSA-N piperidine-4-carboxamide Chemical compound NC(=O)C1CCNCC1.NC(=O)C1CCNCC1 CXWQAPHDSYDHBR-UHFFFAOYSA-N 0.000 claims description 11
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 10
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 10
• 125000003725 azepanyl group Chemical group 0.000 claims description 9
• 125000002393 azetidinyl group Chemical group 0.000 claims description 9
• 125000005961 oxazepanyl group Chemical group 0.000 claims description 9
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
• ILUDPPGBUXWYAU-UHFFFAOYSA-N piperidine-3-carboxamide Chemical compound NC(=O)C1CCCNC1.NC(=O)C1CCCNC1 ILUDPPGBUXWYAU-UHFFFAOYSA-N 0.000 claims description 8
• 239000012453 solvate Substances 0.000 claims description 8
• XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical group N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 7
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
• 235000019256 formaldehyde Nutrition 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 6
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 5
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 5
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 5
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 5
• 239000004305 biphenyl Substances 0.000 claims description 5
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 0.000 claims description 5
• 208000034578 Multiple myelomas Diseases 0.000 claims description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 4
• VMWJCFLUSKZZDX-UHFFFAOYSA-N n,n-dimethylmethanamine Chemical compound [CH2]N(C)C VMWJCFLUSKZZDX-UHFFFAOYSA-N 0.000 claims description 4
• 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
• 206010034277 Pemphigoid Diseases 0.000 claims description 3
• 241000721454 Pemphigus Species 0.000 claims description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
• 230000000694 effects Effects 0.000 claims description 3
• 201000000564 macroglobulinemia Diseases 0.000 claims description 3
• 230000001404 mediated effect Effects 0.000 claims description 3
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 3
• RCCYSVYHULFYHE-UHFFFAOYSA-N pentanediamide Chemical compound NC(=O)CCCC(N)=O RCCYSVYHULFYHE-UHFFFAOYSA-N 0.000 claims description 3
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
• ISBHMJZRKAFTGE-ONEGZZNKSA-N (e)-pent-2-enenitrile Chemical compound CC\C=C\C#N ISBHMJZRKAFTGE-ONEGZZNKSA-N 0.000 claims description 2
• 150000001204 N-oxides Chemical class 0.000 claims description 2
• AQIAIZBHFAKICS-UHFFFAOYSA-N methylaminomethyl Chemical compound [CH2]NC AQIAIZBHFAKICS-UHFFFAOYSA-N 0.000 claims description 2
• 229940055764 triaz Drugs 0.000 claims 41
• 150000001408 amides Chemical class 0.000 claims 19
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 16
• QKDCLUARMDUUKN-XMMPIXPASA-N 6-ethyl-3-[4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]anilino]-5-[(3r)-1-prop-2-enoylpyrrolidin-3-yl]oxypyrazine-2-carboxamide Chemical compound N1=C(O[C@H]2CN(CC2)C(=O)C=C)C(CC)=NC(C(N)=O)=C1NC(C=C1)=CC=C1N(CC1)CCC1N1CCN(C)CC1 QKDCLUARMDUUKN-XMMPIXPASA-N 0.000 claims 7
• 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims 7
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 5
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 4
• 101100063435 Caenorhabditis elegans din-1 gene Proteins 0.000 claims 3
• 235000010290 biphenyl Nutrition 0.000 claims 2
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 2
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims 1
• MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical compound C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 claims 1
• MBDUIEKYVPVZJH-UHFFFAOYSA-N 1-ethylsulfonylethane Chemical compound CCS(=O)(=O)CC MBDUIEKYVPVZJH-UHFFFAOYSA-N 0.000 claims 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• ATAOWUKBUWDMLL-UQHTVBEOSA-N 6-oxo-7-(3-phenoxyphenyl)-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound C=CC(=O)N1CCC[C@H](C1)NC(=O)C2=C3C4C(CCNC4S2)N(C(=O)N3)C5=CC(=CC=C5)OC6=CC=CC=C6 ATAOWUKBUWDMLL-UQHTVBEOSA-N 0.000 claims 1
• USLVGSJQYZZRKM-LJQANCHMSA-N 6-oxo-7-(3-phenylphenyl)-N-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene-3-carboxamide Chemical compound C1(=CC(=CC=C1)N1C(NC2=C(SC=3N=CC=C1C=32)C(=O)N[C@H]1CN(CC1)C(C=C)=O)=O)C1=CC=CC=C1 USLVGSJQYZZRKM-LJQANCHMSA-N 0.000 claims 1
• SKJMOWRWVPGHCQ-JHCJGPRDSA-N 6-oxo-7-(3-propan-2-ylphenyl)-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC(C)C1=CC(=CC=C1)N2C3CCNC4C3C(=C(S4)C(=O)N[C@@H]5CCCN(C5)C(=O)C=C)NC2=O SKJMOWRWVPGHCQ-JHCJGPRDSA-N 0.000 claims 1
• XUFCIFVQJBBVJA-YHWPXVMFSA-N 6-oxo-7-(4-phenylpyridin-2-yl)-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound C=CC(=O)N1CCC[C@H](C1)NC(=O)C2=C3C4C(CCNC4S2)N(C(=O)N3)C5=NC=CC(=C5)C6=CC=CC=C6 XUFCIFVQJBBVJA-YHWPXVMFSA-N 0.000 claims 1
• SCHTZBWDXPXBCN-MXRZHXBVSA-N 6-oxo-7-(5-phenoxypyrazin-2-yl)-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound C=CC(=O)N1CCC[C@H](C1)NC(=O)C2=C3C4C(CCNC4S2)N(C(=O)N3)C5=CN=C(C=N5)OC6=CC=CC=C6 SCHTZBWDXPXBCN-MXRZHXBVSA-N 0.000 claims 1
• GRYUVQJFLGNJQA-JLGTUDDPSA-N 6-oxo-7-(6-phenylpyridazin-4-yl)-N-[(3R)-piperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound C1C[C@H](CNC1)NC(=O)C2=C3C4C(CCNC4S2)N(C(=O)N3)C5=CC(=NN=C5)C6=CC=CC=C6 GRYUVQJFLGNJQA-JLGTUDDPSA-N 0.000 claims 1
• UMUBBNGQWATINQ-JHCJGPRDSA-N 6-oxo-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-7-(3-propylphenyl)-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CCCC1=CC(=CC=C1)N2C3CCNC4C3C(=C(S4)C(=O)N[C@@H]5CCCN(C5)C(=O)C=C)NC2=O UMUBBNGQWATINQ-JHCJGPRDSA-N 0.000 claims 1
• BBPUOJHHUPXODX-QSVYXZOGSA-N 6-oxo-N-[(3R)-piperidin-3-yl]-7-(2-propan-2-ylpyridin-4-yl)-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC(C)C1=NC=CC(=C1)N2C3CCNC4C3C(=C(S4)C(=O)N[C@@H]5CCCNC5)NC2=O BBPUOJHHUPXODX-QSVYXZOGSA-N 0.000 claims 1
• AKDDFUXQOLXECO-QLDSGSDYSA-N 7-(2-cyclohexylpyridin-4-yl)-6-oxo-N-[(3R)-piperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound C1CCC(CC1)C2=NC=CC(=C2)N3C4CCNC5C4C(=C(S5)C(=O)N[C@@H]6CCCNC6)NC3=O AKDDFUXQOLXECO-QLDSGSDYSA-N 0.000 claims 1
• TZUSLBKUWBJERQ-WGEGCMKZSA-N 7-(2-methyl-6-phenylpyridin-4-yl)-6-oxo-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=CC(=CC(=N1)C2=CC=CC=C2)N3C4CCNC5C4C(=C(S5)C(=O)N[C@@H]6CCCN(C6)C(=O)C=C)NC3=O TZUSLBKUWBJERQ-WGEGCMKZSA-N 0.000 claims 1
• DNTNDSQIKFXJEE-UHFFFAOYSA-N 7-(2-methyl-6-phenylpyridin-4-yl)-6-oxo-N-piperidin-3-yl-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=CC(=CC(=N1)C2=CC=CC=C2)N3C4CCNC5C4C(=C(S5)C(=O)NC6CCCNC6)NC3=O DNTNDSQIKFXJEE-UHFFFAOYSA-N 0.000 claims 1
• IQCQORMDRTVJCU-MIOXTJDRSA-N 7-(2-methyl-6-propan-2-yloxypyridin-3-yl)-6-oxo-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=C(C=CC(=N1)OC(C)C)N2C3CCNC4C3C(=C(S4)C(=O)N[C@@H]5CCCN(C5)C(=O)C=C)NC2=O IQCQORMDRTVJCU-MIOXTJDRSA-N 0.000 claims 1
• DJVMJEJUNOJHDO-WIQGMUCESA-N 7-(3-cyclobutylphenyl)-6-oxo-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound C=CC(=O)N1CCC[C@H](C1)NC(=O)C2=C3C4C(CCNC4S2)N(C(=O)N3)C5=CC=CC(=C5)C6CCC6 DJVMJEJUNOJHDO-WIQGMUCESA-N 0.000 claims 1
• PUBSSKZYSYISDZ-RQILOKFUSA-N 7-(3-methyl-2-phenylpyridin-4-yl)-6-oxo-N-[(3R)-piperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=C(C=CN=C1C2=CC=CC=C2)N3C4CCNC5C4C(=C(S5)C(=O)N[C@@H]6CCCNC6)NC3=O PUBSSKZYSYISDZ-RQILOKFUSA-N 0.000 claims 1
• IOHDALZLVIIQCR-JHCJGPRDSA-N 7-(5-methyl-2-phenylpyridin-4-yl)-6-oxo-N-[(3R)-piperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=CN=C(C=C1N2C3CCNC4C3C(=C(S4)C(=O)N[C@@H]5CCCNC5)NC2=O)C6=CC=CC=C6 IOHDALZLVIIQCR-JHCJGPRDSA-N 0.000 claims 1
• IVIFSYUYRRWYQR-MXRZHXBVSA-N 7-(6-cyclobutyloxy-4-methylpyridin-3-yl)-6-oxo-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=CC(=NC=C1N2C3CCNC4C3C(=C(S4)C(=O)N[C@@H]5CCCN(C5)C(=O)C=C)NC2=O)OC6CCC6 IVIFSYUYRRWYQR-MXRZHXBVSA-N 0.000 claims 1
• BFMKUBONPNEKHS-UHFFFAOYSA-N 7-[2-methyl-4-(2-propan-2-yloxyethoxy)phenyl]-6-oxo-N-piperidin-3-yl-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=C(C=CC(=C1)OCCOC(C)C)N2C3CCNC4C3C(=C(S4)C(=O)NC5CCCNC5)NC2=O BFMKUBONPNEKHS-UHFFFAOYSA-N 0.000 claims 1
• ZFVBWTUZQQYTFL-OAQYLSRUSA-N 7-[3-(4-methylphenyl)phenyl]-6-oxo-N-[(3R)-1-prop-2-enoylpiperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene-3-carboxamide Chemical compound C(C=C)(=O)N1C[C@@H](CCC1)NC(=O)C=1SC=2N=CC=C3N(C(NC=1C=23)=O)C=1C=C(C=CC=1)C1=CC=C(C=C1)C ZFVBWTUZQQYTFL-OAQYLSRUSA-N 0.000 claims 1
• VVPVVHQCFWZVIL-MQKVROSBSA-N 7-[3-(oxan-4-yl)phenyl]-6-oxo-N-[(3R)-piperidin-3-yl]-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound C1C[C@H](CNC1)NC(=O)C2=C3C4C(CCNC4S2)N(C(=O)N3)C5=CC=CC(=C5)C6CCOCC6 VVPVVHQCFWZVIL-MQKVROSBSA-N 0.000 claims 1
• ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims 1
• UREXMVKIIYMXOJ-NOQJQSDCSA-N N-[(3R)-1-[(2S)-2-(methylamino)propanoyl]piperidin-3-yl]-7-(2-methyl-4-phenoxyphenyl)-6-oxo-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=C(C=CC(=C1)OC2=CC=CC=C2)N3C4CCNC5C4C(=C(S5)C(=O)N[C@@H]6CCCN(C6)C(=O)[C@H](C)NC)NC3=O UREXMVKIIYMXOJ-NOQJQSDCSA-N 0.000 claims 1
• KIJRGBRZMWSKIQ-OMJKCUTDSA-N N-[(3R)-1-[(E)-4-(methanesulfonamido)but-2-enoyl]piperidin-3-yl]-7-(2-methyl-4-phenoxyphenyl)-6-oxo-2-thia-5,11-diazatricyclo[6.3.1.04,12]dodeca-1(11),3,8(12),9-tetraene-3-carboxamide Chemical compound Cc1cc(Oc2ccccc2)ccc1C1C(=O)Nc2c(sc3nccc1c23)C(=O)N[C@@H]1CCCN(C1)C(=O)\C=C\CNS(C)(=O)=O KIJRGBRZMWSKIQ-OMJKCUTDSA-N 0.000 claims 1
• NQAAFDKFVSZGBQ-COPDTSMESA-N N-[(3R)-1-[(E)-4-aminobut-2-enoyl]pyrrolidin-3-yl]-7-(2-methyl-4-phenoxyphenyl)-6-oxo-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=C(C=CC(=C1)OC2=CC=CC=C2)N3C4CCNC5C4C(=C(S5)C(=O)N[C@@H]6CCN(C6)C(=O)/C=C/CN)NC3=O NQAAFDKFVSZGBQ-COPDTSMESA-N 0.000 claims 1
• BTYXWSOVGKLEAC-COPDTSMESA-N N-[(3R)-1-[(E)-4-hydroxybut-2-enoyl]pyrrolidin-3-yl]-7-(2-methyl-4-phenoxyphenyl)-6-oxo-2-thia-5,7,11-triazatricyclo[6.3.1.04,12]dodec-3-ene-3-carboxamide Chemical compound CC1=C(C=CC(=C1)OC2=CC=CC=C2)N3C4CCNC5C4C(=C(S5)C(=O)N[C@@H]6CCN(C6)C(=O)/C=C/CO)NC3=O BTYXWSOVGKLEAC-COPDTSMESA-N 0.000 claims 1
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