DK2350071T3 - SUBSTITUTED PYRAZOLO [1,5-a] PYRIMIDINE COMPOUNDS AS TRK-KINASE INHIBITORS - Google Patents

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Publication number

DK2350071T3

DK2350071T3 DK09740245.7T DK09740245T DK2350071T3 DK 2350071 T3 DK2350071 T3 DK 2350071T3 DK 09740245 T DK09740245 T DK 09740245T DK 2350071 T3 DK2350071 T3 DK 2350071T3

Authority

DK

Denmark

Prior art keywords

pyrrolidin

pyrazolo

pyrimidin

alkyl

difluorophenyl

Prior art date

2008-10-22

Links

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• Global Dossier
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• LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title description 8
• 229940043355 kinase inhibitor Drugs 0.000 title description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
• 125000000217 alkyl group Chemical group 0.000 claims description 256
• 150000001875 compounds Chemical class 0.000 claims description 134
• -1 hetAr3 Chemical group 0.000 claims description 132
• 238000002360 preparation method Methods 0.000 claims description 86
• 125000001424 substituent group Chemical group 0.000 claims description 84
• 238000000034 method Methods 0.000 claims description 77
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 64
• 229910052736 halogen Inorganic materials 0.000 claims description 55
• 150000002367 halogens Chemical class 0.000 claims description 54
• 125000005842 heteroatom Chemical group 0.000 claims description 46
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
• 229910052757 nitrogen Inorganic materials 0.000 claims description 42
• 125000000623 heterocyclic group Chemical group 0.000 claims description 36
• 125000003545 alkoxy group Chemical group 0.000 claims description 35
• 208000002193 Pain Diseases 0.000 claims description 34
• 206010028980 Neoplasm Diseases 0.000 claims description 29
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 24
• 238000011282 treatment Methods 0.000 claims description 22
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
• 201000011510 cancer Diseases 0.000 claims description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 19
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
• 150000003839 salts Chemical class 0.000 claims description 18
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 17
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 16
• 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 16
• 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 201000010099 disease Diseases 0.000 claims description 15
• 239000003153 chemical reaction reagent Substances 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 239000002585 base Substances 0.000 claims description 12
• 230000008878 coupling Effects 0.000 claims description 12
• 238000010168 coupling process Methods 0.000 claims description 12
• 238000005859 coupling reaction Methods 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 12
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 11
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 10
• AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical group OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims description 6
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 6
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 6
• 206010061218 Inflammation Diseases 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• 230000004054 inflammatory process Effects 0.000 claims description 5
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
• 150000003857 carboxamides Chemical class 0.000 claims description 4
• ZKWFSTHEYLJLEL-UHFFFAOYSA-N morpholine-4-carboxamide Chemical compound NC(=O)N1CCOCC1 ZKWFSTHEYLJLEL-UHFFFAOYSA-N 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 4
• CDIBLDMRAYKSQO-HXUWFJFHSA-N 1-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-phenylurea Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)NC=4C=CC=CC=4)C=NN3C=C2)=C1 CDIBLDMRAYKSQO-HXUWFJFHSA-N 0.000 claims description 3
• 150000007942 carboxylates Chemical class 0.000 claims description 3
• FNVBJPOUCSMKSD-OAHLLOKOSA-N methyl 2-[[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]amino]-2-oxoacetate Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(=O)OC)=CC(F)=CC=C1F FNVBJPOUCSMKSD-OAHLLOKOSA-N 0.000 claims description 3
• ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 claims description 3
• FJCFOBAIIMESRH-ZBQZNYHESA-N (1s,3r)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxycyclopentane-1-carboxamide Chemical compound C1[C@H](O)CC[C@@H]1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 FJCFOBAIIMESRH-ZBQZNYHESA-N 0.000 claims description 2
• CFTQSUXKDYMQPE-YZVOILCLSA-N (1s,4s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-oxa-5-azabicyclo[2.2.1]heptane-5-carboxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)N2C[C@]3(OC[C@]2([H])C3)[H])=CC(F)=CC=C1F CFTQSUXKDYMQPE-YZVOILCLSA-N 0.000 claims description 2
• 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
• GMWUABQJDWHYLA-RDTXWAMCSA-N (3r)-n-[5-[(2r)-2-[2-(difluoromethyl)-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)C(F)F)C=CN2N=C1 GMWUABQJDWHYLA-RDTXWAMCSA-N 0.000 claims description 2
• GMWUABQJDWHYLA-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-[2-(difluoromethyl)-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)C(F)F)C=CN2N=C1 GMWUABQJDWHYLA-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
• PYBWSZQDXHRTIN-HXUWFJFHSA-N 1-(4-chlorophenyl)-3-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]urea Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)NC=4C=CC(Cl)=CC=4)C=NN3C=C2)=C1 PYBWSZQDXHRTIN-HXUWFJFHSA-N 0.000 claims description 2
• JUDAJZGKKWTDNT-HXUWFJFHSA-N 1-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-(4-fluorophenyl)urea Chemical compound C1=CC(F)=CC=C1NC(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 JUDAJZGKKWTDNT-HXUWFJFHSA-N 0.000 claims description 2
• CODLSAASTUQBHU-OAQYLSRUSA-N 1-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-(4-methoxyphenyl)urea Chemical compound C1=CC(OC)=CC=C1NC(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 CODLSAASTUQBHU-OAQYLSRUSA-N 0.000 claims description 2
• NMAVVRBCLSUDSN-CQSZACIVSA-N 2-[[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]amino]-2-oxoacetic acid Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(=O)O)=CC(F)=CC=C1F NMAVVRBCLSUDSN-CQSZACIVSA-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
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
• 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 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
• YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 2
• 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 2
• 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 208000015181 infectious disease Diseases 0.000 claims description 2
• NATYJNDZWKBODH-OAHLLOKOSA-N n'-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-n-methyloxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(=O)NC)=CC(F)=CC=C1F NATYJNDZWKBODH-OAHLLOKOSA-N 0.000 claims description 2
• SSULIMRGZQKFMY-QGZVFWFLSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-2-methylpropanamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(C)C)=CC(F)=CC=C1F SSULIMRGZQKFMY-QGZVFWFLSA-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
• JPMLMYWOHXSCPD-OOKWDQIISA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxycyclobutane-1-carboxamide Chemical compound C1C(O)CC1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 JPMLMYWOHXSCPD-OOKWDQIISA-N 0.000 claims description 2
• XMQORYSYMMCYTB-HXUWFJFHSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-4-ethylpiperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 XMQORYSYMMCYTB-HXUWFJFHSA-N 0.000 claims description 2
• ASNCBWCDJMZVSE-MRXNPFEDSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-n',n'-dimethyloxamide Chemical compound C1([C@H]2CCCN2C=2C=CN3N=CC(=C3N=2)NC(=O)C(=O)N(C)C)=CC(F)=CC=C1F ASNCBWCDJMZVSE-MRXNPFEDSA-N 0.000 claims description 2
• NBXJYYGLFILKIE-GOSISDBHSA-N n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]morpholine-4-carboxamide Chemical compound FC1=CC=C(F)C([C@@H]2N(CCC2)C2=NC3=C(NC(=O)N4CCOCC4)C=NN3C=C2)=C1 NBXJYYGLFILKIE-GOSISDBHSA-N 0.000 claims description 2
• OXNMHSYUFCUDSC-QGZVFWFLSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-1-methylimidazole-2-carboxamide Chemical compound CN1C=CN=C1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C=C(F)C=CC=3)C=CN2N=C1 OXNMHSYUFCUDSC-QGZVFWFLSA-N 0.000 claims description 2
• XMJIQDRPYVNBGS-QGZVFWFLSA-N n-[5-[(2r)-2-(3-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=C(F)C=CC=3)C=CN2N=C1 XMJIQDRPYVNBGS-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
• VSSOJTPOJHCKOA-HXUWFJFHSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-methylpyridine-4-carboxamide Chemical compound CC1=CN=CC=C1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C=C(F)C=CC=3)C=CN2N=C1 VSSOJTPOJHCKOA-HXUWFJFHSA-N 0.000 claims description 2
• 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 2
• PYEVULUZURCWQW-LJQANCHMSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-3-carboxamide Chemical compound FC1=CC=CC([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4C=NC=CC=4)C=NN3C=C2)=C1 PYEVULUZURCWQW-LJQANCHMSA-N 0.000 claims description 2
• ITARCDAWCMUQPF-LJQANCHMSA-N n-[5-[(2r)-2-(3-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyridine-4-carboxamide Chemical compound FC1=CC=CC([C@@H]2N(CCC2)C2=NC3=C(NC(=O)C=4C=CN=CC=4)C=NN3C=C2)=C1 ITARCDAWCMUQPF-LJQANCHMSA-N 0.000 claims description 2
• WPFWKUYRUAHZEG-QGZVFWFLSA-N n-[5-[(2r)-2-[2-(difluoromethyl)-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)C(F)F)C=CN2N=C1 WPFWKUYRUAHZEG-QGZVFWFLSA-N 0.000 claims description 2
• XJFZMEWLTKRUAV-LJQANCHMSA-N n-[5-[(2r)-2-[2-(difluoromethyl)-5-fluorophenyl]pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-4-hydroxypiperidine-1-carboxamide Chemical compound C1CC(O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)C(F)F)C=CN2N=C1 XJFZMEWLTKRUAV-LJQANCHMSA-N 0.000 claims description 2
• VDXGZMWESOKUJV-UHFFFAOYSA-N n-[5-[2-(3-fluorophenyl)-2-methylpyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxyazetidine-1-carboxamide Chemical compound C=1C=CC(F)=CC=1C1(C)CCCN1C(=NC1=2)C=CN1N=CC=2NC(=O)N1CC(O)C1 VDXGZMWESOKUJV-UHFFFAOYSA-N 0.000 claims description 2
• 230000000010 osteolytic effect Effects 0.000 claims description 2
• XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 claims description 2
• 125000006239 protecting group Chemical group 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 7
• FJCFOBAIIMESRH-ZUEVXXBESA-N (1s,3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxycyclopentane-1-carboxamide Chemical compound C1[C@@H](O)CC[C@@H]1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 FJCFOBAIIMESRH-ZUEVXXBESA-N 0.000 claims 1
• ANOOLCKSSQEQMQ-WMLDXEAASA-N (3S)-1-[5-[(2R)-2-(2-chloro-5-fluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]pyrrolidin-3-ol Chemical compound ClC1=C(C=C(C=C1)F)[C@@H]1N(CCC1)C1=NC=2N(C=C1)N=CC=2N1C[C@H](CC1)O ANOOLCKSSQEQMQ-WMLDXEAASA-N 0.000 claims 1
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