AU2012320465B2 - Morpholino substituted bicyclic pyrimidine urea or carbamate derivatives as mTOR inhibitors - Google Patents

Info

Publication number

AU2012320465B2

AU2012320465B2 AU2012320465A AU2012320465A AU2012320465B2 AU 2012320465 B2 AU2012320465 B2 AU 2012320465B2 AU 2012320465 A AU2012320465 A AU 2012320465A AU 2012320465 A AU2012320465 A AU 2012320465A AU 2012320465 B2 AU2012320465 B2 AU 2012320465B2

Authority

AU

Australia

Prior art keywords

pyrimidin

phenyl

dioxido

dihydrothieno

urea

Prior art date

2011-10-07

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.)

Ceased

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• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title description 30
• 229940124302 mTOR inhibitor Drugs 0.000 title description 25
• 150000004657 carbamic acid derivatives Chemical class 0.000 title description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 title description 2
• ZENDWEPAVHORFD-UHFFFAOYSA-N pyrimidine;urea Chemical compound NC(N)=O.C1=CN=CN=C1 ZENDWEPAVHORFD-UHFFFAOYSA-N 0.000 title description 2
• 125000002619 bicyclic group Chemical group 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 143
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 174
• 238000000034 method Methods 0.000 claims description 101
• 239000004202 carbamide Substances 0.000 claims description 97
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 95
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 93
• 125000000217 alkyl group Chemical group 0.000 claims description 79
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 72
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 70
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 70
• 201000010099 disease Diseases 0.000 claims description 49
• 150000003839 salts Chemical class 0.000 claims description 46
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 229910052736 halogen Inorganic materials 0.000 claims description 41
• 229910052757 nitrogen Inorganic materials 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
• -1 8-oxa-3-azabicyclo[3.2.1]octan-3-yl Chemical group 0.000 claims description 30
• 125000005843 halogen group Chemical group 0.000 claims description 28
• 239000003814 drug Substances 0.000 claims description 25
• 208000035475 disorder Diseases 0.000 claims description 23
• 238000011282 treatment Methods 0.000 claims description 20
• 230000004900 autophagic degradation Effects 0.000 claims description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims description 18
• 229920006395 saturated elastomer Polymers 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 125000000623 heterocyclic group Chemical group 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 13
• 230000004770 neurodegeneration Effects 0.000 claims description 13
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 13
• 230000002757 inflammatory effect Effects 0.000 claims description 12
• 230000002062 proliferating effect Effects 0.000 claims description 12
• 206010052779 Transplant rejections Diseases 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 208000030159 metabolic disease Diseases 0.000 claims description 11
• 230000001900 immune effect Effects 0.000 claims description 10
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
• 230000000172 allergic effect Effects 0.000 claims description 9
• 208000010668 atopic eczema Diseases 0.000 claims description 9
• 208000023275 Autoimmune disease Diseases 0.000 claims description 8
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 8
• 208000036142 Viral infection Diseases 0.000 claims description 8
• 208000016097 disease of metabolism Diseases 0.000 claims description 8
• 208000037765 diseases and disorders Diseases 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 8
• 208000024908 graft versus host disease Diseases 0.000 claims description 8
• 230000009385 viral infection Effects 0.000 claims description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
• 125000004043 oxo group Chemical group O=* 0.000 claims description 7
• 208000027866 inflammatory disease Diseases 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• PTZJHIUMDDFCMD-LSLKUGRBSA-N 1-cyclopropyl-3-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NC3CC3)=CC=1)N=C2N1CCOC[C@@H]1C PTZJHIUMDDFCMD-LSLKUGRBSA-N 0.000 claims description 4
• 208000026278 immune system disease Diseases 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• PTZJHIUMDDFCMD-UONOGXRCSA-N 1-cyclopropyl-3-[4-[(5r)-5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1([C@H](S(C2)(=O)=O)C)=C2N=C(C=2C=CC(NC(=O)NC3CC3)=CC=2)N=C1N1CCOC[C@@H]1C PTZJHIUMDDFCMD-UONOGXRCSA-N 0.000 claims description 3
• CBOPGLRBWYFSAV-ZDUSSCGKSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CSC2 CBOPGLRBWYFSAV-ZDUSSCGKSA-N 0.000 claims description 3
• LPSHTXQPFSXJOB-ZDUSSCGKSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2 LPSHTXQPFSXJOB-ZDUSSCGKSA-N 0.000 claims description 3
• WKRMKFLEXUWZBH-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)CC2 WKRMKFLEXUWZBH-AWEZNQCLSA-N 0.000 claims description 3
• ZDQYTKONHYFZQR-NFOMZHRRSA-N 1-cyclopropyl-3-[4-[5,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C=12C(C)S(=O)(=O)C(C)C2=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC=1N1CCOC[C@@H]1C ZDQYTKONHYFZQR-NFOMZHRRSA-N 0.000 claims description 3
• NXJSNBXHECGNMG-LSLKUGRBSA-N 1-cyclopropyl-3-[4-[7-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C=12CS(=O)(=O)C(C)C2=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC=1N1CCOC[C@@H]1C NXJSNBXHECGNMG-LSLKUGRBSA-N 0.000 claims description 3
• SLYBINBFUIDZMB-MLCCFXAWSA-N 1-ethyl-3-[4-[5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2(C)C SLYBINBFUIDZMB-MLCCFXAWSA-N 0.000 claims description 3
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
• 125000003566 oxetanyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 229910052705 radium Inorganic materials 0.000 claims description 3
• 229910052701 rubidium Inorganic materials 0.000 claims description 3
• DSEPRWCGCACJDI-MLCCFXAWSA-N 1-(cyclopropylmethyl)-3-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NCC3CC3)=CC=1)N=C2N1CCOC[C@@H]1C DSEPRWCGCACJDI-MLCCFXAWSA-N 0.000 claims description 2
• ZVRSXMXKIYBKHA-UEWDXFNNSA-N 1-[3-fluoro-4-[5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-methylurea Chemical compound FC1=CC(NC(=O)NC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2(C)C ZVRSXMXKIYBKHA-UEWDXFNNSA-N 0.000 claims description 2
• DPPZUXQNNUIBRE-UHFFFAOYSA-N 1-[4-(7,7-dimethyl-4-morpholin-4-yl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl)phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2CCOCC2)=NC2=C1CS(=O)(=O)C2(C)C DPPZUXQNNUIBRE-UHFFFAOYSA-N 0.000 claims description 2
• SRKUSFHOYIWTOR-HNNXBMFYSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC=3C=NC=CC=3)=CC=2)=NC2=C1CS(=O)(=O)C2 SRKUSFHOYIWTOR-HNNXBMFYSA-N 0.000 claims description 2
• IZLPVLBNRGPOHA-AWEZNQCLSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C2(C)C IZLPVLBNRGPOHA-AWEZNQCLSA-N 0.000 claims description 2
• PTZJHIUMDDFCMD-KGLIPLIRSA-N 1-cyclopropyl-3-[4-[(5s)-5-methyl-4-[(3r)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1([C@@H](S(C2)(=O)=O)C)=C2N=C(C=2C=CC(NC(=O)NC3CC3)=CC=2)N=C1N1CCOC[C@H]1C PTZJHIUMDDFCMD-KGLIPLIRSA-N 0.000 claims description 2
• SIBSISWCPBOCCQ-SFHVURJKSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-7,7-dimethyl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound CC[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2(C)C SIBSISWCPBOCCQ-SFHVURJKSA-N 0.000 claims description 2
• XYUAGXOXDFFZRI-FHERZECASA-N 1-cyclopropyl-3-[4-[5,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1C(C)S(=O)(=O)C(C)C2 XYUAGXOXDFFZRI-FHERZECASA-N 0.000 claims description 2
• SASGGXUCBYHSDM-MLCCFXAWSA-N 1-cyclopropyl-3-[4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1C(C)S(=O)(=O)CC2 SASGGXUCBYHSDM-MLCCFXAWSA-N 0.000 claims description 2
• IJFVQKCBLRLTQJ-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[6,6-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-5,5-dioxo-7h-thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1S(=O)(=O)C(C)(C)C2 IJFVQKCBLRLTQJ-AWEZNQCLSA-N 0.000 claims description 2
• NRGBYJVUETZWNN-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[7,7-dimethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound N=1C(N2C3CCC2COC3)=C2CS(=O)(=O)C(C)(C)C2=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 NRGBYJVUETZWNN-UHFFFAOYSA-N 0.000 claims description 2
• ITKFZXHURONRPX-CQSZACIVSA-N 1-cyclopropyl-3-[4-[7,7-dimethyl-4-[(3r)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2(C)C ITKFZXHURONRPX-CQSZACIVSA-N 0.000 claims description 2
• ITKFZXHURONRPX-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2(C)C ITKFZXHURONRPX-AWEZNQCLSA-N 0.000 claims description 2
• HQADXOKORBKKGD-MLCCFXAWSA-N 1-cyclopropyl-3-[4-[7-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C(C)C2 HQADXOKORBKKGD-MLCCFXAWSA-N 0.000 claims description 2
• MWVPVSMZQXQKFK-UEWDXFNNSA-N 1-ethyl-3-[2-fluoro-4-[5-methyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=C(F)C(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1C(C)S(=O)(=O)C2 MWVPVSMZQXQKFK-UEWDXFNNSA-N 0.000 claims description 2
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
• 125000006001 difluoroethyl group Chemical group 0.000 claims description 2
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
• 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 238000011321 prophylaxis Methods 0.000 claims description 2
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 3
• 230000002526 effect on cardiovascular system Effects 0.000 claims 3
• 230000002503 metabolic effect Effects 0.000 claims 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• XHHSHSSMZWHEGZ-LBPRGKRZSA-N 1-(2,2-difluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(F)F)=CC=2)=NC2=C1CS(=O)(=O)C2 XHHSHSSMZWHEGZ-LBPRGKRZSA-N 0.000 claims 1
• LGLAILBRUKQLGF-UHFFFAOYSA-N 1-(2-fluoroethyl)-3-[4-(5,7,7-trimethyl-4-morpholin-4-yl-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl)phenyl]urea Chemical compound CC1(C)S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NCCF)=CC=1)N=C2N1CCOCC1 LGLAILBRUKQLGF-UHFFFAOYSA-N 0.000 claims 1
• GKMBYWKXCDKMRS-ZDUSSCGKSA-N 1-(2-fluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=NC2=C1CS(=O)(=O)C2 GKMBYWKXCDKMRS-ZDUSSCGKSA-N 0.000 claims 1
• OBOYUQKGYQANBL-MLCCFXAWSA-N 1-(2-fluoroethyl)-3-[4-[5,7,7-trimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5h-thieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound CC1(C)S(=O)(=O)C(C)C2=C1N=C(C=1C=CC(NC(=O)NCCF)=CC=1)N=C2N1CCOC[C@@H]1C OBOYUQKGYQANBL-MLCCFXAWSA-N 0.000 claims 1
• SDUIYXKCZZSAEF-ZDUSSCGKSA-N 1-(2-hydroxyethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=NC2=C1CS(=O)(=O)C2 SDUIYXKCZZSAEF-ZDUSSCGKSA-N 0.000 claims 1
• JSOHXGJSEVULKJ-AWEZNQCLSA-N 1-(3-fluoropropyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCCF)=CC=2)=NC2=C1CS(=O)(=O)C2 JSOHXGJSEVULKJ-AWEZNQCLSA-N 0.000 claims 1
• KJAYNLZEOIBUQM-HNNXBMFYSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC=3C=CN=CC=3)=CC=2)=NC2=C1CS(=O)(=O)C2 KJAYNLZEOIBUQM-HNNXBMFYSA-N 0.000 claims 1
• HCGQDQOTVMEVFV-HNNXBMFYSA-N 1-[4-[7,7-dimethyl-4-[(3s)-3-methylmorpholin-4-yl]-6,6-dioxo-5,8-dihydrothiopyrano[4,3-d]pyrimidin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CS(=O)(=O)C(C)(C)C2 HCGQDQOTVMEVFV-HNNXBMFYSA-N 0.000 claims 1
• XZUZIENJVIHTTD-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(3-ethylmorpholin-4-yl)-5-methyl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound CCC1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1C(C)S(=O)(=O)C2 XZUZIENJVIHTTD-UHFFFAOYSA-N 0.000 claims 1
• MTHDMBXVDMTBNP-OKILXGFUSA-N 1-cyclopropyl-3-[4-[4-[(2s,6r)-2,6-dimethylmorpholin-4-yl]-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1[C@@H](C)O[C@@H](C)CN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CS(=O)(=O)C2 MTHDMBXVDMTBNP-OKILXGFUSA-N 0.000 claims 1
• XZUZIENJVIHTTD-IBYPIGCZSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-ethylmorpholin-4-yl]-5-methyl-6,6-dioxo-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound CC[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1C(C)S(=O)(=O)C2 XZUZIENJVIHTTD-IBYPIGCZSA-N 0.000 claims 1
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