JP2014510122A - ｍＴＯＲ阻害剤としてのジヒドロピロロピリミジン誘導体 - Google Patents

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Publication number

JP2014510122A

JP2014510122A JP2014503105A JP2014503105A JP2014510122A JP 2014510122 A JP2014510122 A JP 2014510122A JP 2014503105 A JP2014503105 A JP 2014503105A JP 2014503105 A JP2014503105 A JP 2014503105A JP 2014510122 A JP2014510122 A JP 2014510122A

Authority

JP

Japan

Prior art keywords

phenyl

pyrrolo

dihydro

methylmorpholino

urea

Prior art date

2011-04-04

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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• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title abstract description 24
• 229940124302 mTOR inhibitor Drugs 0.000 title abstract description 21
• 150000001875 compounds Chemical class 0.000 claims abstract description 264
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims abstract description 73
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims abstract description 73
• 239000003814 drug Substances 0.000 claims abstract description 25
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
• 208000037765 diseases and disorders Diseases 0.000 claims abstract description 9
• 238000000034 method Methods 0.000 claims description 167
• 125000000217 alkyl group Chemical group 0.000 claims description 82
• 150000003839 salts Chemical class 0.000 claims description 65
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 63
• -1 8-oxa-3-azabicyclo [3.2.1] octane-3-yl residue Chemical group 0.000 claims description 56
• 201000010099 disease Diseases 0.000 claims description 43
• 229910052736 halogen Inorganic materials 0.000 claims description 40
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 35
• 229910052739 hydrogen Inorganic materials 0.000 claims description 27
• 150000002367 halogens Chemical class 0.000 claims description 23
• 208000035475 disorder Diseases 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 206010028980 Neoplasm Diseases 0.000 claims description 19
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 17
• 201000011510 cancer Diseases 0.000 claims description 17
• 125000005843 halogen group Chemical group 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• 230000008569 process Effects 0.000 claims description 16
• 125000001424 substituent group Chemical group 0.000 claims description 16
• POCXPTZODJTBLU-ZDUSSCGKSA-N 1-(2-hydroxyethyl)-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NCCO)=CC=2)=NC2=C1CNC2 POCXPTZODJTBLU-ZDUSSCGKSA-N 0.000 claims description 15
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
• 238000004519 manufacturing process Methods 0.000 claims description 13
• 229920006395 saturated elastomer Polymers 0.000 claims description 13
• 230000004900 autophagic degradation Effects 0.000 claims description 12
• 239000004202 carbamide Substances 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 230000004770 neurodegeneration Effects 0.000 claims description 11
• 230000002062 proliferating effect Effects 0.000 claims description 11
• 239000002207 metabolite Substances 0.000 claims description 10
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 10
• 206010052779 Transplant rejections Diseases 0.000 claims description 9
• 208000030159 metabolic disease Diseases 0.000 claims description 9
• 229940002612 prodrug Drugs 0.000 claims description 9
• 239000000651 prodrug Substances 0.000 claims description 9
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
• CZBUBLQDHOVGTL-ZDUSSCGKSA-N 1-cyclopropyl-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CNC2 CZBUBLQDHOVGTL-ZDUSSCGKSA-N 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
• 230000001363 autoimmune Effects 0.000 claims description 8
• 230000002757 inflammatory effect Effects 0.000 claims description 8
• 125000006239 protecting group Chemical group 0.000 claims description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
• 208000009329 Graft vs Host Disease Diseases 0.000 claims description 7
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
• 230000000172 allergic effect Effects 0.000 claims description 7
• 125000003277 amino group Chemical group 0.000 claims description 7
• 208000010668 atopic eczema Diseases 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 208000024908 graft versus host disease Diseases 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• YCARQKLKWBLJMR-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C=1C=C(C=2C=3CNCC=3N=C(N=2)N2CC3CCC(O3)C2)C=CC=1NC(=O)NC1CC1 YCARQKLKWBLJMR-UHFFFAOYSA-N 0.000 claims description 6
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
• 208000036142 Viral infection Diseases 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 230000009385 viral infection Effects 0.000 claims description 6
• FYYWCOPUFNOPHW-UHFFFAOYSA-N 1-ethyl-3-[4-[2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=NC2=C1CNC2 FYYWCOPUFNOPHW-UHFFFAOYSA-N 0.000 claims description 5
• 239000002253 acid Substances 0.000 claims description 5
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 5
• 208000016097 disease of metabolism Diseases 0.000 claims description 5
• FUDWUVIIZCZMPK-SFHVURJKSA-N 1-[4-[6-cyclohexyl-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NCCO)=CC=2)=NC2=C1CN(C1CCCCC1)C2 FUDWUVIIZCZMPK-SFHVURJKSA-N 0.000 claims description 4
• KPVMSZQAUKUFAF-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[6-(2-hydroxyacetyl)-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)CO)C2 KPVMSZQAUKUFAF-AWEZNQCLSA-N 0.000 claims description 4
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 4
• FFOJUOWHKSVEES-HNNXBMFYSA-N ethyl 4-[4-(ethylcarbamoylamino)phenyl]-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidine-6-carboxylate Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC2=C1CN(C(=O)OCC)C2 FFOJUOWHKSVEES-HNNXBMFYSA-N 0.000 claims description 4
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
• HENFKYHMWYZACJ-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[4-[2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCCO)=CC=C1C1=NC(N2CC3CCC(O3)C2)=NC2=C1CNC2 HENFKYHMWYZACJ-UHFFFAOYSA-N 0.000 claims description 3
• XWTRYXJRZVJUJF-AWEZNQCLSA-N 1-(2-hydroxyethyl)-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-methylsulfonyl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NCCO)=CC=2)=NC2=C1CN(S(C)(=O)=O)C2 XWTRYXJRZVJUJF-AWEZNQCLSA-N 0.000 claims description 3
• HBMSUNHRQYZPDV-BHWOMJMDSA-N 1-(2-hydroxypropyl)-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-propan-2-yl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC(O)C)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC2=C1CN(C(C)C)C2 HBMSUNHRQYZPDV-BHWOMJMDSA-N 0.000 claims description 3
• JZWOCGALZFONEV-AWEZNQCLSA-N 1-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]-3-(6-oxo-1h-pyridin-2-yl)urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC=3N=C(O)C=CC=3)=CC=2)=NC2=C1CNC2 JZWOCGALZFONEV-AWEZNQCLSA-N 0.000 claims description 3
• DGVWNHJXZRMMIP-HNNXBMFYSA-N 1-[4-[6-(2-cyanoacetyl)-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]-3-cyclopropylurea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)CC#N)C2 DGVWNHJXZRMMIP-HNNXBMFYSA-N 0.000 claims description 3
• HKZCXWUDQUIFNJ-INIZCTEOSA-N 1-[4-[6-(4-aminobutanoyl)-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]-3-cyclopropylurea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)CCCN)C2 HKZCXWUDQUIFNJ-INIZCTEOSA-N 0.000 claims description 3
• SOYPZZXVEBOXGA-AWEZNQCLSA-N 1-[4-[6-acetyl-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NCCO)=CC=2)=NC2=C1CN(C(C)=O)C2 SOYPZZXVEBOXGA-AWEZNQCLSA-N 0.000 claims description 3
• ZIVAOKMXNNFIAY-AWEZNQCLSA-N 1-[4-[6-acetyl-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]-3-cyclopropylurea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(C)=O)C2 ZIVAOKMXNNFIAY-AWEZNQCLSA-N 0.000 claims description 3
• OCFFAIAAVHCDBE-UHFFFAOYSA-N 1-cyclopropyl-3-[4-(2-morpholin-4-yl-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl)phenyl]urea Chemical compound C=1C=C(C=2C=3CNCC=3N=C(N=2)N2CCOCC2)C=CC=1NC(=O)NC1CC1 OCFFAIAAVHCDBE-UHFFFAOYSA-N 0.000 claims description 3
• CZBUBLQDHOVGTL-CYBMUJFWSA-N 1-cyclopropyl-3-[4-[2-[(3r)-3-methylmorpholin-4-yl]-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CNC2 CZBUBLQDHOVGTL-CYBMUJFWSA-N 0.000 claims description 3
• KRMYPJQWBWGIJJ-CISYCMJJSA-N 1-cyclopropyl-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-(oxolane-2-carbonyl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)C1OCCC1)C2 KRMYPJQWBWGIJJ-CISYCMJJSA-N 0.000 claims description 3
• DRECMKAOXUHZFE-ATNAJCNCSA-N 1-cyclopropyl-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-(oxolane-3-carbonyl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)C1COCC1)C2 DRECMKAOXUHZFE-ATNAJCNCSA-N 0.000 claims description 3
• GGQIVQXEQIKSBR-BJQOMGFOSA-N 1-cyclopropyl-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-(pyrrolidine-2-carbonyl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)C1NCCC1)C2 GGQIVQXEQIKSBR-BJQOMGFOSA-N 0.000 claims description 3
• ZWQJURMONLFUTR-INIZCTEOSA-N 1-cyclopropyl-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-propan-2-yl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C=12CN(C(C)C)CC2=NC(N2[C@H](COCC2)C)=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 ZWQJURMONLFUTR-INIZCTEOSA-N 0.000 claims description 3
• KNDMEOZHUDYXQB-HNNXBMFYSA-N 1-cyclopropyl-3-[4-[6-(2-methoxyacetyl)-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C=12CN(C(=O)COC)CC2=NC(N2[C@H](COCC2)C)=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 KNDMEOZHUDYXQB-HNNXBMFYSA-N 0.000 claims description 3
• IWYZKYJJXIFSBZ-INIZCTEOSA-N 1-cyclopropyl-3-[4-[6-(3-methoxypropanoyl)-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C=12CN(C(=O)CCOC)CC2=NC(N2[C@H](COCC2)C)=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 IWYZKYJJXIFSBZ-INIZCTEOSA-N 0.000 claims description 3
• KLPLSFUDFXYFFV-INIZCTEOSA-N 1-cyclopropyl-3-[4-[6-[2-(dimethylamino)acetyl]-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)CN(C)C)C2 KLPLSFUDFXYFFV-INIZCTEOSA-N 0.000 claims description 3
• IHWGACUWFRQZET-KRWDZBQOSA-N 1-cyclopropyl-3-[4-[6-[3-(dimethylamino)propanoyl]-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)CCN(C)C)C2 IHWGACUWFRQZET-KRWDZBQOSA-N 0.000 claims description 3
• OEVMVCVBCVCVJZ-SFHVURJKSA-N 1-cyclopropyl-3-[4-[6-[4-(dimethylamino)butanoyl]-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C(=O)CCCN(C)C)C2 OEVMVCVBCVCVJZ-SFHVURJKSA-N 0.000 claims description 3
• ZDKNPXREUPGCFX-HNNXBMFYSA-N 1-cyclopropyl-3-[4-[6-cyclopropyl-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C1CC1)C2 ZDKNPXREUPGCFX-HNNXBMFYSA-N 0.000 claims description 3
• SGHZFPHPAZAQIJ-HNNXBMFYSA-N 1-cyclopropyl-3-[4-[6-cyclopropylsulfonyl-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(S(=O)(=O)C1CC1)C2 SGHZFPHPAZAQIJ-HNNXBMFYSA-N 0.000 claims description 3
• DPKAJUHYNYDAQC-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[6-methyl-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C(N=C1C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CN(C)C2 DPKAJUHYNYDAQC-AWEZNQCLSA-N 0.000 claims description 3
• CSBZBORLJLMBKV-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[6-methylsulfonyl-2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C=12CN(S(=O)(=O)C)CC2=NC(N2CC3CCC(O3)C2)=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 CSBZBORLJLMBKV-UHFFFAOYSA-N 0.000 claims description 3
• ZYSALRMKCFMPJH-UHFFFAOYSA-N 1-ethyl-3-[4-(2-morpholin-4-yl-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl)phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CCOCC2)=NC2=C1CNC2 ZYSALRMKCFMPJH-UHFFFAOYSA-N 0.000 claims description 3
• QFKKPPIDPFZIJP-ZDUSSCGKSA-N 1-ethyl-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC2=C1CNC2 QFKKPPIDPFZIJP-ZDUSSCGKSA-N 0.000 claims description 3
• JYFUQTPIEMRCQF-AWEZNQCLSA-N 1-ethyl-3-[4-[6-formyl-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC2=C1CN(C=O)C2 JYFUQTPIEMRCQF-AWEZNQCLSA-N 0.000 claims description 3
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
• IGNMUKBJIDHYKE-UHFFFAOYSA-N [4-(2-morpholin-4-yl-6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yl)phenyl]urea Chemical compound C1=CC(NC(=O)N)=CC=C1C1=NC(N2CCOCC2)=NC2=C1CNC2 IGNMUKBJIDHYKE-UHFFFAOYSA-N 0.000 claims description 3
• WNDZPEWXAGALHH-HNNXBMFYSA-N ethyl 4-[4-(cyclopropylcarbamoylamino)phenyl]-2-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydropyrrolo[3,4-d]pyrimidine-6-carboxylate Chemical compound C=12CN(C(=O)OCC)CC2=NC(N2[C@H](COCC2)C)=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 WNDZPEWXAGALHH-HNNXBMFYSA-N 0.000 claims description 3
• GTGUCTGVJSSYDT-DJNXLDHESA-N 1-(1-hydroxypropan-2-yl)-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-propan-2-yl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC(CO)C)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC2=C1CN(C(C)C)C2 GTGUCTGVJSSYDT-DJNXLDHESA-N 0.000 claims description 2
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• UXFAIMJGYZYJAN-INIZCTEOSA-N 1-(2-hydroxyethyl)-3-[4-[2-[(3s)-3-methylmorpholin-4-yl]-6-propan-2-yl-5,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]phenyl]urea Chemical compound C=12CN(C(C)C)CC2=NC(N2[C@H](COCC2)C)=NC=1C1=CC=C(NC(=O)NCCO)C=C1 UXFAIMJGYZYJAN-INIZCTEOSA-N 0.000 claims description 2
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