JP2015505816A5 - - Google Patents

Info

Publication number

JP2015505816A5

JP2015505816A5 JP2014540146A JP2014540146A JP2015505816A5 JP 2015505816 A5 JP2015505816 A5 JP 2015505816A5 JP 2014540146 A JP2014540146 A JP 2014540146A JP 2014540146 A JP2014540146 A JP 2014540146A JP 2015505816 A5 JP2015505816 A5 JP 2015505816A5

Authority

JP

Japan

Prior art keywords

pharmaceutically acceptable

acceptable salt

hydroxycyclopentyl

inden

dihydro

Prior art date

2012-11-02

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.)

Granted

Links

• Espacenet
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• 150000003839 salts Chemical class 0.000 claims description 73
• 206010028980 Neoplasm Diseases 0.000 claims description 38
• 201000011510 cancer Diseases 0.000 claims description 38
• 102000038427 NEDD8-activating enzyme E1 Human genes 0.000 claims description 27
• 108091007790 NEDD8-activating enzyme E1 Proteins 0.000 claims description 27
• 239000003112 inhibitor Substances 0.000 claims description 27
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 25
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 24
• 229940075628 hypomethylating agent Drugs 0.000 claims description 22
• NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical group O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 15
• 229960002756 azacitidine Drugs 0.000 claims description 15
• MPUQHZXIXSTTDU-QXGSTGNESA-N sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7-pyrrolo[2,3-d]pyrimidinyl]-2-hydroxycyclopentyl]methyl ester Chemical group C1[C@H](O)[C@H](COS(=O)(=O)N)C[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2C=C1 MPUQHZXIXSTTDU-QXGSTGNESA-N 0.000 claims description 11
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 10
• 229940079593 drug Drugs 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• -1 {(1S, 2S, 4R) -4- [ (6-{[(1R, 2S) -5-chloro-2-methoxy-2,3-dihydro-1H-inden-1-yl] amino} pyrimidin-4-yl) oxy] -2-hydroxycyclopentyl} methyl Chemical group 0.000 claims description 10
• 208000009527 Refractory anemia Diseases 0.000 claims description 8
• 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 claims description 8
• 238000003745 diagnosis Methods 0.000 claims description 8
• XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 claims description 7
• 229960003603 decitabine Drugs 0.000 claims description 7
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 6
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 6
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 6
• 230000002071 myeloproliferative effect Effects 0.000 claims description 6
• 208000011580 syndromic disease Diseases 0.000 claims description 6
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
• 239000002552 dosage form Substances 0.000 claims description 4
• UVNSDOGOYDQGLY-ZDUSSCGKSA-N n-[(1s)-2,3-dihydro-1h-inden-1-yl]-7h-pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound N([C@@H]1C2=CC=CC=C2CC1)C1=NC=NC2=C1C=CN2 UVNSDOGOYDQGLY-ZDUSSCGKSA-N 0.000 claims description 3
• 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
• 229910052742 iron Inorganic materials 0.000 claims description 2
• 230000035755 proliferation Effects 0.000 claims description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 8
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 8
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 4
• 230000001684 chronic effect Effects 0.000 claims 4
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 4
• 208000032839 leukemia Diseases 0.000 claims 4
• 208000033833 Myelomonocytic Chronic Leukemia Diseases 0.000 claims 2
• 239000003795 chemical substances by application Substances 0.000 claims 2
• 201000010902 chronic myelomonocytic leukemia Diseases 0.000 claims 2
• 239000000203 mixture Substances 0.000 claims 2
• 210000001185 bone marrow Anatomy 0.000 claims 1
• FIYXUOWXHWJDAM-UHFFFAOYSA-N methyl sulfamate Chemical compound COS(N)(=O)=O FIYXUOWXHWJDAM-UHFFFAOYSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 description 31
• 208000017604 Hodgkin disease Diseases 0.000 description 2
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
• 150000001875 compounds Chemical class 0.000 description 2
• 206010066476 Haematological malignancy Diseases 0.000 description 1
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• HJKDNNXKYODZJI-BVMPOVDASA-N [(1s,2s,4r)-4-[4-[[(1s)-2,3-dihydro-1h-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate;hydrochloride Chemical compound Cl.C1[C@H](O)[C@H](COS(=O)(=O)N)C[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2C=C1 HJKDNNXKYODZJI-BVMPOVDASA-N 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 239000008194 pharmaceutical composition Substances 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1