TWI458729B - 作為ＴＲＫ激酶抑制劑之經取代吡唑并〔１，５－ａ〕嘧啶化合物 - Google Patents

Info

Publication number

TWI458729B

TWI458729B TW098135670A TW98135670A TWI458729B TW I458729 B TWI458729 B TW I458729B TW 098135670 A TW098135670 A TW 098135670A TW 98135670 A TW98135670 A TW 98135670A TW I458729 B TWI458729 B TW I458729B

Authority

TW

Taiwan

Prior art keywords

pyrrolidin

pyrazolo

pyrimidin

alkyl

difluorophenyl

Prior art date

2008-10-22

Links

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• -1 pyrazolo[1,5-a]pyrimidine compound Chemical class 0.000 title claims description 74
• 229940096912 Trk tyrosine kinase inhibitor Drugs 0.000 title 1
• 125000000217 alkyl group Chemical group 0.000 claims description 280
• 150000001875 compounds Chemical class 0.000 claims description 158
• 238000006243 chemical reaction Methods 0.000 claims description 101
• 238000002360 preparation method Methods 0.000 claims description 99
• 125000001424 substituent group Chemical group 0.000 claims description 95
• 229910052757 nitrogen Inorganic materials 0.000 claims description 74
• 229910052736 halogen Inorganic materials 0.000 claims description 65
• 150000002367 halogens Chemical class 0.000 claims description 59
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 57
• 125000005842 heteroatom Chemical group 0.000 claims description 55
• 125000003545 alkoxy group Chemical group 0.000 claims description 48
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 46
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
• 125000000623 heterocyclic group Chemical group 0.000 claims description 43
• 206010028980 Neoplasm Diseases 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 39
• 208000002193 Pain Diseases 0.000 claims description 38
• 238000000034 method Methods 0.000 claims description 38
• 238000011282 treatment Methods 0.000 claims description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 230000036407 pain Effects 0.000 claims description 32
• 125000005843 halogen group Chemical group 0.000 claims description 29
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 29
• 201000011510 cancer Diseases 0.000 claims description 26
• 150000003839 salts Chemical class 0.000 claims description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
• 239000002585 base Substances 0.000 claims description 21
• 201000010099 disease Diseases 0.000 claims description 21
• 229910052731 fluorine Inorganic materials 0.000 claims description 20
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 18
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 17
• 125000001072 heteroaryl group Chemical group 0.000 claims description 17
• 229910052717 sulfur Inorganic materials 0.000 claims description 17
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 14
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 241000124008 Mammalia Species 0.000 claims description 13
• 239000001257 hydrogen Substances 0.000 claims description 13
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 12
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 12
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 11
• 239000007822 coupling agent Substances 0.000 claims description 10
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 9
• 206010061218 Inflammation Diseases 0.000 claims description 8
• 230000004054 inflammatory process Effects 0.000 claims description 8
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 7
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 7
• 239000003814 drug Substances 0.000 claims description 7
• 229930182817 methionine Natural products 0.000 claims description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 230000004770 neurodegeneration Effects 0.000 claims description 6
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
• 238000006467 substitution reaction Methods 0.000 claims description 6
• 206010001935 American trypanosomiasis Diseases 0.000 claims description 5
• 208000024699 Chagas disease Diseases 0.000 claims description 5
• 239000004202 carbamide Substances 0.000 claims description 5
• 230000000010 osteolytic effect Effects 0.000 claims description 5
• KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 claims description 4
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
• 125000003118 aryl group Chemical group 0.000 claims description 4
• PKAHQJNJPDVTDP-UHFFFAOYSA-N methyl cyclopropanecarboxylate Chemical compound COC(=O)C1CC1 PKAHQJNJPDVTDP-UHFFFAOYSA-N 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• NYNZQNWKBKUAII-RDTXWAMCSA-N (3r)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-RDTXWAMCSA-N 0.000 claims description 3
• LYQALTAJYRLACT-KZNAEPCWSA-N (3r,4r)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3,4-dihydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)[C@H](O)CN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 LYQALTAJYRLACT-KZNAEPCWSA-N 0.000 claims description 3
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 3
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
• XEJCZVULEXZBII-LJQANCHMSA-N FC1=C(C=C(C=C1)F)[C@@H]1N(CCC1)C1=NC=2N(C=C1)N=CC2NC(COCC(=O)N2CC(C2)O)=O Chemical compound FC1=C(C=C(C=C1)F)[C@@H]1N(CCC1)C1=NC=2N(C=C1)N=CC2NC(COCC(=O)N2CC(C2)O)=O XEJCZVULEXZBII-LJQANCHMSA-N 0.000 claims description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
• 241000223109 Trypanosoma cruzi Species 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• HAPKHAXVBNALJN-MRXNPFEDSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-hydroxy-2-methylpropanamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(C)(O)C)=CC(F)=CC=C1F HAPKHAXVBNALJN-MRXNPFEDSA-N 0.000 claims description 3
• WMZOACWAPWJVJE-QGZVFWFLSA-N n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxy-3-methylazetidine-1-carboxamide Chemical compound C1C(C)(O)CN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 WMZOACWAPWJVJE-QGZVFWFLSA-N 0.000 claims description 3
• OHIHEIPCEBOBSX-LJQANCHMSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-2-carboxamide Chemical compound FC1=CC=CC([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4N=CC=CC=4)C=NN3C=C2)=C1 OHIHEIPCEBOBSX-LJQANCHMSA-N 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 230000008569 process Effects 0.000 claims description 3
• LIVISHFAOAESEN-RDTXWAMCSA-N (3r)-n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 LIVISHFAOAESEN-RDTXWAMCSA-N 0.000 claims description 2
• PIWHHONESBMIIR-NVXWUHKLSA-N (3r)-n-[5-[(2r)-2-(5-fluoropyridin-3-yl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C=C(F)C=NC=3)C=CN2N=C1 PIWHHONESBMIIR-NVXWUHKLSA-N 0.000 claims description 2
• NYNZQNWKBKUAII-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-KBXCAEBGSA-N 0.000 claims description 2
• LIVISHFAOAESEN-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 LIVISHFAOAESEN-KBXCAEBGSA-N 0.000 claims description 2
• LUIHHEKOUMPZBZ-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-[5-fluoro-2-(trifluoromethyl)phenyl]pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)C(F)(F)F)C=CN2N=C1 LUIHHEKOUMPZBZ-KBXCAEBGSA-N 0.000 claims description 2
• PAXBXCBVFOOXPP-UHFFFAOYSA-N 1H-pyridazin-6-one 1H-pyridin-2-one Chemical group N=1NC(C=CC1)=O.N1C(C=CC=C1)=O PAXBXCBVFOOXPP-UHFFFAOYSA-N 0.000 claims description 2
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• IPFJWILEQTTXKZ-LJQANCHMSA-N 5-chloro-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-2-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4N=CC(Cl)=CC=4)C=NN3C=C2)=C1 IPFJWILEQTTXKZ-LJQANCHMSA-N 0.000 claims description 2
• MMLKBUJDYTXDII-GOSISDBHSA-N 6-chloro-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-2-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4N=C(Cl)C=CC=4)C=NN3C=C2)=C1 MMLKBUJDYTXDII-GOSISDBHSA-N 0.000 claims description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 2
• 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
• 125000004122 cyclic group Chemical group 0.000 claims description 2
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 2
• 208000015181 infectious disease Diseases 0.000 claims description 2
• SXMHUKHEPKZDDA-QGZVFWFLSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-2,2-dimethylpropanamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(C)(C)C)=CC(F)=CC=C1F SXMHUKHEPKZDDA-QGZVFWFLSA-N 0.000 claims description 2
• YHBJBVSIEWTKMO-QGZVFWFLSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methyl-2-(methylamino)propanamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(C)(C)NC)=CC(F)=CC=C1F YHBJBVSIEWTKMO-QGZVFWFLSA-N 0.000 claims description 2
• HBFVIZODUVVXJR-NODKNVJMSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3,5-dimethylpiperazine-1-carboxamide Chemical compound C1C(C)NC(C)CN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 HBFVIZODUVVXJR-NODKNVJMSA-N 0.000 claims description 2
• FOBLAWQYOVPXHD-QGZVFWFLSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxyazetidine-1-carboxamide Chemical compound C1C(O)CN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 FOBLAWQYOVPXHD-QGZVFWFLSA-N 0.000 claims description 2
• BYOPZUKUWITKOE-LJQANCHMSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-methylpyridine-2-carboxamide Chemical compound CC1=CC=CN=C1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 BYOPZUKUWITKOE-LJQANCHMSA-N 0.000 claims description 2
• RKKFKBDFZXMCTJ-GOSISDBHSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyrazine-2-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4N=CC=NC=4)C=NN3C=C2)=C1 RKKFKBDFZXMCTJ-GOSISDBHSA-N 0.000 claims description 2
• WNDMOUJMYZPIGZ-LJQANCHMSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-2-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4N=CC=CC=4)C=NN3C=C2)=C1 WNDMOUJMYZPIGZ-LJQANCHMSA-N 0.000 claims description 2
• KYJUCBUFWGHCIR-QGZVFWFLSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyrimidine-2-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4N=CC=CN=4)C=NN3C=C2)=C1 KYJUCBUFWGHCIR-QGZVFWFLSA-N 0.000 claims description 2
• CIOUDHJPRJGNCX-QGZVFWFLSA-N n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxyazetidine-1-carboxamide Chemical compound C1C(O)CN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 CIOUDHJPRJGNCX-QGZVFWFLSA-N 0.000 claims description 2
• PDIREONSOPXOGN-GOSISDBHSA-N n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]morpholine-4-carboxamide Chemical compound FC1=CC=C(Cl)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)N4CCOCC4)C=NN3C=C2)=C1 PDIREONSOPXOGN-GOSISDBHSA-N 0.000 claims description 2
• GYYROWSUKDACLU-QGZVFWFLSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-1h-pyrazole-5-carboxamide Chemical compound FC1=CC=CC([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C4=NNC=C4)C=NN3C=C2)=C1 GYYROWSUKDACLU-QGZVFWFLSA-N 0.000 claims description 2
• DTPNACUCWLJPMK-LJQANCHMSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-methylpyridine-2-carboxamide Chemical compound CC1=CC=CN=C1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C=C(F)C=CC=3)C=CN2N=C1 DTPNACUCWLJPMK-LJQANCHMSA-N 0.000 claims description 2
• ONIGQJUEEKQPLR-LJQANCHMSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylpyrazine-2-carboxamide Chemical compound C1=NC(C)=CN=C1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C=C(F)C=CC=3)C=CN2N=C1 ONIGQJUEEKQPLR-LJQANCHMSA-N 0.000 claims description 2
• 125000006239 protecting group Chemical group 0.000 claims description 2
• ZKWFSTHEYLJLEL-UHFFFAOYSA-N morpholine-4-carboxamide Chemical compound NC(=O)N1CCOCC1 ZKWFSTHEYLJLEL-UHFFFAOYSA-N 0.000 claims 2
• GZYMBPFJMWHKLO-IFXJQAMLSA-N (3s)-n-[5-[(2r)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-methylpiperazine-1-carboxamide Chemical compound C1CN[C@@H](C)CN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)Cl)C=CN2N=C1 GZYMBPFJMWHKLO-IFXJQAMLSA-N 0.000 claims 1
• MANJIGKYCYWWBD-UHFFFAOYSA-N 2-chloro-2-oxoacetic acid Chemical compound OC(=O)C(Cl)=O MANJIGKYCYWWBD-UHFFFAOYSA-N 0.000 claims 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
• WWPIGFACMKDCHJ-LJQANCHMSA-N 4-chloro-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-2-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4N=CC=C(Cl)C=4)C=NN3C=C2)=C1 WWPIGFACMKDCHJ-LJQANCHMSA-N 0.000 claims 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 1
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