JP6928005B2 - 新規なピペリジニル誘導体、それらの調製方法及びそれらを含有する医薬組成物 - Google Patents

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Publication number

JP6928005B2

JP6928005B2 JP2018564356A JP2018564356A JP6928005B2 JP 6928005 B2 JP6928005 B2 JP 6928005B2 JP 2018564356 A JP2018564356 A JP 2018564356A JP 2018564356 A JP2018564356 A JP 2018564356A JP 6928005 B2 JP6928005 B2 JP 6928005B2

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JP

Japan

Prior art keywords

methyl

carbonyl

pyrrolo

hydroxy

piperidine

Prior art date

2016-06-10

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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• 239000008194 pharmaceutical composition Substances 0.000 title claims description 18
• 238000002360 preparation method Methods 0.000 title description 369
• 125000003386 piperidinyl group Chemical group 0.000 title description 4
• 239000003153 chemical reaction reagent Substances 0.000 claims description 266
• 238000000034 method Methods 0.000 claims description 199
• 150000001875 compounds Chemical class 0.000 claims description 94
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 82
• -1 4-fluoro-3-methoxyphenyl Chemical group 0.000 claims description 57
• 125000000217 alkyl group Chemical group 0.000 claims description 35
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 30
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
• 238000011282 treatment Methods 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 19
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• 125000005843 halogen group Chemical group 0.000 claims description 17
• 238000006243 chemical reaction Methods 0.000 claims description 15
• 201000011510 cancer Diseases 0.000 claims description 14
• 125000001072 heteroaryl group Chemical group 0.000 claims description 13
• 229910052757 nitrogen Chemical group 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 11
• 239000002253 acid Substances 0.000 claims description 10
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
• 150000003839 salts Chemical class 0.000 claims description 7
• 206010009944 Colon cancer Diseases 0.000 claims description 6
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 6
• 206010060862 Prostate cancer Diseases 0.000 claims description 6
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 125000002619 bicyclic group Chemical group 0.000 claims description 6
• 208000029742 colonic neoplasm Diseases 0.000 claims description 6
• 238000005859 coupling reaction Methods 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 229910052740 iodine Inorganic materials 0.000 claims description 6
• 229910052760 oxygen Inorganic materials 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 5
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 5
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 5
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 5
• 206010025323 Lymphomas Diseases 0.000 claims description 5
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 5
• 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 5
• 206010033128 Ovarian cancer Diseases 0.000 claims description 5
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 5
• 206010041067 Small cell lung cancer Diseases 0.000 claims description 5
• 208000002495 Uterine Neoplasms Diseases 0.000 claims description 5
• 150000007513 acids Chemical class 0.000 claims description 5
• 230000006907 apoptotic process Effects 0.000 claims description 5
• 210000004556 brain Anatomy 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
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• 201000004101 esophageal cancer Diseases 0.000 claims description 5
• 239000003112 inhibitor Substances 0.000 claims description 5
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• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 5
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• ICBQESRGJNANIL-RPWUZVMVSA-N 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-[[4-hydroxy-1-[(3R,4R)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound OC1(CN2C=NC3=C(C=NN3C3=CC=C4OCCOC4=C3)C2=O)CCN(CC1)C(=O)[C@@H]1CCNC[C@H]1C1=CC=CC=C1 ICBQESRGJNANIL-RPWUZVMVSA-N 0.000 claims description 4
• PCYKNOLYCOERKA-IAPPQJPRSA-N 3-[[1-[(3R,4R)-1-acetyl-3-phenylpiperidine-4-carbonyl]-4-hydroxypiperidin-4-yl]methyl]-7-(3-chlorophenyl)pyrrolo[2,3-d]pyrimidin-4-one Chemical compound CC(=O)N1CC[C@H]([C@@H](C1)C1=CC=CC=C1)C(=O)N1CCC(O)(CN2C=NC3=C(C=CN3C3=CC(Cl)=CC=C3)C2=O)CC1 PCYKNOLYCOERKA-IAPPQJPRSA-N 0.000 claims description 4
• AZXXVPVIZIVIAU-IAPPQJPRSA-N 3-[[1-[(3R,4R)-1-acetyl-3-phenylpiperidine-4-carbonyl]-4-hydroxypiperidin-4-yl]methyl]-7-(4-chlorophenyl)pyrrolo[2,3-d]pyrimidin-4-one Chemical compound CC(=O)N1CC[C@H]([C@@H](C1)C1=CC=CC=C1)C(=O)N1CCC(O)(CN2C=NC3=C(C=CN3C3=CC=C(Cl)C=C3)C2=O)CC1 AZXXVPVIZIVIAU-IAPPQJPRSA-N 0.000 claims description 4
• XQSUEBDSRGCZSO-IAPPQJPRSA-N 3-[[1-[(3R,4R)-1-acetyl-3-phenylpiperidine-4-carbonyl]-4-hydroxypiperidin-4-yl]methyl]-7-phenylpyrrolo[2,3-d]pyrimidin-4-one Chemical compound CC(=O)N1CC[C@H]([C@@H](C1)C1=CC=CC=C1)C(=O)N1CCC(O)(CN2C=NC3=C(C=CN3C3=CC=CC=C3)C2=O)CC1 XQSUEBDSRGCZSO-IAPPQJPRSA-N 0.000 claims description 4
• MKVPUEAFZBZZDF-PXJZQJOASA-N 3-[[4-hydroxy-1-[(3R,4R)-1-(2-methylpropanoyl)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]-7-phenylpyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(C(C)C)=O)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC=CC=C1 MKVPUEAFZBZZDF-PXJZQJOASA-N 0.000 claims description 4
• SCIREYXUHUICRN-VPUSJEBWSA-N 3-[[4-hydroxy-1-[(3R,4R)-1-methyl-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]-7-phenylpyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC=CC=C1 SCIREYXUHUICRN-VPUSJEBWSA-N 0.000 claims description 4
• QFHRCEAMGLYUCA-CTNGQTDRSA-N 3-[[4-hydroxy-1-[(3R,4R)-3-phenyl-1-(2,2,2-trifluoroethyl)piperidine-4-carbonyl]piperidin-4-yl]methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)CC(F)(F)F)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2 QFHRCEAMGLYUCA-CTNGQTDRSA-N 0.000 claims description 4
• RBLAHBIYRKJXLL-VPUSJEBWSA-N 3-[[4-hydroxy-1-[(3R,4R)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]-7-(4-methoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC=C(C=C1)OC RBLAHBIYRKJXLL-VPUSJEBWSA-N 0.000 claims description 4
• RDFJHEFCCUGDIY-RSXGOPAZSA-N 3-[[4-hydroxy-1-[(3R,4R)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]-7-phenylpyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC=CC=C1 RDFJHEFCCUGDIY-RSXGOPAZSA-N 0.000 claims description 4
• OFODESCIVZQIAY-VWNXMTODSA-N 3-[[4-hydroxy-1-[(3R,4R)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]-7-pyridin-2-ylpyrrolo[2,3-d]pyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=NC=CC=C1 OFODESCIVZQIAY-VWNXMTODSA-N 0.000 claims description 4
• DCSOHSVOGJZKCY-RPWUZVMVSA-N 5-[[4-hydroxy-1-[(3R,4R)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]-1-phenylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CNCC1)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=NN2C1=CC=CC=C1 DCSOHSVOGJZKCY-RPWUZVMVSA-N 0.000 claims description 4
• KTQPACWKBOEIMZ-RSXGOPAZSA-N 7-(3-chlorophenyl)-3-[[4-hydroxy-1-[(3R,4R)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]pyrrolo[2,3-d]pyrimidin-4-one Chemical compound ClC=1C=C(C=CC=1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CNCC1)C1=CC=CC=C1)O KTQPACWKBOEIMZ-RSXGOPAZSA-N 0.000 claims description 4
• WRIUEQTZANEUQC-VPUSJEBWSA-N 7-(4-fluorophenyl)-3-[[4-hydroxy-1-[(3R,4R)-1-methyl-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]pyrrolo[2,3-d]pyrimidin-4-one Chemical compound FC1=CC=C(C=C1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C)C1=CC=CC=C1)O WRIUEQTZANEUQC-VPUSJEBWSA-N 0.000 claims description 4
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 230000001028 anti-proliverative effect Effects 0.000 claims description 4
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• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
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• 208000026278 immune system disease Diseases 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
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• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 239000011593 sulfur Chemical group 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• NLQHOVKWTFJHJI-PXJZQJOASA-N 3-[[1-[(3R,4R)-1-(2,2-dimethylpropanoyl)-3-phenylpiperidine-4-carbonyl]-4-hydroxypiperidin-4-yl]methyl]-7-phenylpyrrolo[2,3-d]pyrimidin-4-one Chemical compound CC(C(=O)N1C[C@H]([C@@H](CC1)C(=O)N1CCC(CC1)(O)CN1C=NC2=C(C1=O)C=CN2C1=CC=CC=C1)C1=CC=CC=C1)(C)C NLQHOVKWTFJHJI-PXJZQJOASA-N 0.000 claims description 3
• KPXGJUXNLJXVKL-IAPPQJPRSA-N 3-[[1-[(3R,4R)-1-acetyl-3-phenylpiperidine-4-carbonyl]-4-hydroxypiperidin-4-yl]methyl]-7-(4-fluorophenyl)pyrrolo[2,3-d]pyrimidin-4-one Chemical compound CC(=O)N1CC[C@H]([C@@H](C1)C1=CC=CC=C1)C(=O)N1CCC(O)(CN2C=NC3=C(C=CN3C3=CC=C(F)C=C3)C2=O)CC1 KPXGJUXNLJXVKL-IAPPQJPRSA-N 0.000 claims description 3
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• IJTNMTLJEUKTRS-RSXGOPAZSA-N 7-(4-fluorophenyl)-3-[[4-hydroxy-1-[(3R,4R)-3-phenylpiperidine-4-carbonyl]piperidin-4-yl]methyl]pyrrolo[2,3-d]pyrimidin-4-one Chemical compound FC1=CC=C(C=C1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CNCC1)C1=CC=CC=C1)O IJTNMTLJEUKTRS-RSXGOPAZSA-N 0.000 claims description 3
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• HLAMMMLDPOBAGL-PXJZQJOASA-N tert-butyl (3R,4R)-4-[4-[[7-(4-fluorophenyl)-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound FC1=CC=C(C=C1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O HLAMMMLDPOBAGL-PXJZQJOASA-N 0.000 description 2
• AZUNZHFNRZXHQQ-NOZRDPDXSA-N tert-butyl (3R,4R)-4-[4-[[7-(5-chlorothiophen-2-yl)-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound ClC1=CC=C(S1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O AZUNZHFNRZXHQQ-NOZRDPDXSA-N 0.000 description 2
• DNYFAZUDBLNTNP-PXJZQJOASA-N tert-butyl (3R,4R)-4-[4-[[7-[(2-chlorophenyl)methyl]-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound ClC1=C(C=CC=C1)CN1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O DNYFAZUDBLNTNP-PXJZQJOASA-N 0.000 description 2
• AZLBJCNLKRJSHU-DGPALRBDSA-N tert-butyl (3R,4R)-4-[4-[[7-[(3-chlorophenyl)methyl]-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound ClC=1C=C(C=CC=1)CN1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O AZLBJCNLKRJSHU-DGPALRBDSA-N 0.000 description 2
• ZQZCKLJSJFMCSG-DGPALRBDSA-N tert-butyl (3R,4R)-4-[4-[[7-[(4-chlorophenyl)methyl]-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound ClC1=CC=C(C=C1)CN1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O ZQZCKLJSJFMCSG-DGPALRBDSA-N 0.000 description 2
• LGHALKWEBUYJEY-RSXGOPAZSA-N tert-butyl (3R,4R)-4-[4-[[7-[1-(difluoromethyl)pyrazol-4-yl]-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound FC(N1N=CC(=C1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O)F LGHALKWEBUYJEY-RSXGOPAZSA-N 0.000 description 2
• CLUDUCRMOJAXNY-VEEOACQBSA-N tert-butyl (3R,4R)-4-[4-[[7-[3-(dimethylamino)phenyl]-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound CN(C=1C=C(C=CC=1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O)C CLUDUCRMOJAXNY-VEEOACQBSA-N 0.000 description 2
• OAXQKDUXWJKXES-IAPPQJPRSA-N tert-butyl (3R,4R)-4-[4-[[7-[3-(dimethylamino)propyl]-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound CN(CCCN1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O)C OAXQKDUXWJKXES-IAPPQJPRSA-N 0.000 description 2
• MWVHSSJWTXEHNG-VEEOACQBSA-N tert-butyl (3R,4R)-4-[4-[[7-[4-(dimethylamino)phenyl]-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]-4-hydroxypiperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound CN(C1=CC=C(C=C1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O)C MWVHSSJWTXEHNG-VEEOACQBSA-N 0.000 description 2
• YBAFTRGPZBVCEM-IAPPQJPRSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-1-phenylpyrazolo[3,4-d]pyrimidin-5-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=NN2C1=CC=CC=C1 YBAFTRGPZBVCEM-IAPPQJPRSA-N 0.000 description 2
• ILWHULJSZZTNGF-IAPPQJPRSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-phenyl-5H-pyrrolo[3,2-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)NC=C2C1=CC=CC=C1 ILWHULJSZZTNGF-IAPPQJPRSA-N 0.000 description 2
• UFVLSEZIZBWRCM-PXJZQJOASA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-phenylpyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC=CC=C1 UFVLSEZIZBWRCM-PXJZQJOASA-N 0.000 description 2
• VGMSYOAECWLWED-SXOMAYOGSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-phenylthieno[3,4-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC=2C(C1=O)=CSC=2C1=CC=CC=C1 VGMSYOAECWLWED-SXOMAYOGSA-N 0.000 description 2
• WTVCKBDRBYQHNI-RSXGOPAZSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-prop-2-ynylpyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2CC#C WTVCKBDRBYQHNI-RSXGOPAZSA-N 0.000 description 2
• KXMJVJWEZVXBLH-VPUSJEBWSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-pyridin-2-ylpyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=NC=CC=C1 KXMJVJWEZVXBLH-VPUSJEBWSA-N 0.000 description 2
• DCUHDBNUIWKURF-RSXGOPAZSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-pyrimidin-2-ylpyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=NC=CC=N1 DCUHDBNUIWKURF-RSXGOPAZSA-N 0.000 description 2
• ARXMIQHGMXTCRQ-RSXGOPAZSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-thiophen-2-ylpyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C=1SC=CC=1 ARXMIQHGMXTCRQ-RSXGOPAZSA-N 0.000 description 2
• MFLYIFPARGPDBE-VPUSJEBWSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxo-7-thiophen-3-ylpyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CSC=C1 MFLYIFPARGPDBE-VPUSJEBWSA-N 0.000 description 2
• PFBFFMXALUDGQE-PKTZIBPZSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(4-oxopyrido[3,2-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)N=CC=C2 PFBFFMXALUDGQE-PKTZIBPZSA-N 0.000 description 2
• VETAOWINMIDAKW-GGAORHGYSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(6-iodo-7-methyl-4-oxopyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=C(N2C)I VETAOWINMIDAKW-GGAORHGYSA-N 0.000 description 2
• OPMZJUCORBQMHT-PKTZIBPZSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(6-methoxy-4-oxopyrido[3,2-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)N=C(C=C2)OC OPMZJUCORBQMHT-PKTZIBPZSA-N 0.000 description 2
• LQOATZMFAFCPJJ-DGPALRBDSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(6-methyl-4-oxo-7-phenylpyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=C(N2C1=CC=CC=C1)C LQOATZMFAFCPJJ-DGPALRBDSA-N 0.000 description 2
• UZPDEFFNUXJERF-SXOMAYOGSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(6-oxo-9-phenylpurin-1-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC=2N(C=NC=2C1=O)C1=CC=CC=C1 UZPDEFFNUXJERF-SXOMAYOGSA-N 0.000 description 2
• DWIWMCAKAJAUFA-VWNXMTODSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(7-methyl-4-oxopyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C DWIWMCAKAJAUFA-VWNXMTODSA-N 0.000 description 2
• NRLIXNLQBATUKQ-BHYZAODMSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(7-naphthalen-1-yl-4-oxopyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC=CC2=CC=CC=C12 NRLIXNLQBATUKQ-BHYZAODMSA-N 0.000 description 2
• MDRKLPHUWRQIIU-VTIYRKAUSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(7-naphthalen-2-yl-4-oxopyrrolo[2,3-d]pyrimidin-3-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC2=CC=CC=C2C=C1 MDRKLPHUWRQIIU-VTIYRKAUSA-N 0.000 description 2
• FKCYVNKPDFADEF-FTJBHMTQSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(7-oxo-3-phenyl-[1,2]oxazolo[4,5-d]pyrimidin-6-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)ON=C2C1=CC=CC=C1 FKCYVNKPDFADEF-FTJBHMTQSA-N 0.000 description 2
• ZTJXJFOSXRPNOD-FTJBHMTQSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(7-oxo-3-phenyl-[1,2]thiazolo[4,5-d]pyrimidin-6-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)SN=C2C1=CC=CC=C1 ZTJXJFOSXRPNOD-FTJBHMTQSA-N 0.000 description 2
• GKOXVXPYVHAIHJ-FTJBHMTQSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[(7-oxo-3-phenyltriazolo[4,5-d]pyrimidin-6-yl)methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)N=NN2C1=CC=CC=C1 GKOXVXPYVHAIHJ-FTJBHMTQSA-N 0.000 description 2
• GRMILLCOZFEBKA-PXJZQJOASA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[1-(4-methoxyphenyl)-4-oxopyrazolo[3,4-d]pyrimidin-5-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound COC1=CC=C(C=C1)N1N=CC2=C1N=CN(CC1(O)CCN(CC1)C(=O)[C@@H]1CCN(C[C@H]1C1=CC=CC=C1)C(=O)OC(C)(C)C)C2=O GRMILLCOZFEBKA-PXJZQJOASA-N 0.000 description 2
• CFWSDIOYRQSYKY-NOZRDPDXSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[4-oxo-7-(1,3-thiazol-2-yl)pyrrolo[2,3-d]pyrimidin-3-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C=1SC=CN=1 CFWSDIOYRQSYKY-NOZRDPDXSA-N 0.000 description 2
• ATQJRBQJLRZOGW-VHFKIGOXSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[4-oxo-7-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-3-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound C(C1=CC=CC=C1)OC=1C=C(C=CC=1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O ATQJRBQJLRZOGW-VHFKIGOXSA-N 0.000 description 2
• IDMQIYLPKBQPHN-VHFKIGOXSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[4-oxo-7-(4-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-3-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound C(C1=CC=CC=C1)OC1=CC=C(C=C1)N1C=CC2=C1N=CN(C2=O)CC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)O IDMQIYLPKBQPHN-VHFKIGOXSA-N 0.000 description 2
• FTZTXJYOSJXXKB-PXJZQJOASA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[7-(1-methylpiperidin-4-yl)-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1CCN(CC1)C FTZTXJYOSJXXKB-PXJZQJOASA-N 0.000 description 2
• KWNHZMHVDWEHOM-VPUSJEBWSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[7-(2-methylpropyl)-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2CC(C)C KWNHZMHVDWEHOM-VPUSJEBWSA-N 0.000 description 2
• PDGQWLSDMFMKKT-DGPALRBDSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[7-(3-methoxyphenyl)-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C1=CC(=CC=C1)OC PDGQWLSDMFMKKT-DGPALRBDSA-N 0.000 description 2
• RODIODRBPUBQGV-DGPALRBDSA-N tert-butyl (3R,4R)-4-[4-hydroxy-4-[[7-(3-methylphenyl)-4-oxopyrrolo[2,3-d]pyrimidin-3-yl]methyl]piperidine-1-carbonyl]-3-phenylpiperidine-1-carboxylate Chemical compound OC1(CCN(CC1)C(=O)[C@H]1[C@@H](CN(CC1)C(=O)OC(C)(C)C)C1=CC=CC=C1)CN1C=NC2=C(C1=O)C=CN2C=1C=C(C=CC=1)C RODIODRBPUBQGV-DGPALRBDSA-N 0.000 description 2
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