CA2596424C - Inhibitors of e1 activating enzymes - Google Patents
Inhibitors of e1 activating enzymes Download PDFInfo
- Publication number
- CA2596424C CA2596424C CA2596424A CA2596424A CA2596424C CA 2596424 C CA2596424 C CA 2596424C CA 2596424 A CA2596424 A CA 2596424A CA 2596424 A CA2596424 A CA 2596424A CA 2596424 C CA2596424 C CA 2596424C
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- CA
- Canada
- Prior art keywords
- purin
- compound
- pharmaceutically acceptable
- methyl
- acceptable salt
- Prior art date
- 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.)
- Expired - Fee Related
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- 102000004190 Enzymes Human genes 0.000 title claims abstract description 50
- 108090000790 Enzymes Proteins 0.000 title claims abstract description 50
- 230000003213 activating effect Effects 0.000 title abstract description 23
- 239000003112 inhibitor Substances 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 378
- 150000003839 salts Chemical class 0.000 claims abstract description 190
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 67
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
- 208000035475 disorder Diseases 0.000 claims abstract description 47
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 125000001931 aliphatic group Chemical group 0.000 claims description 269
- FIYXUOWXHWJDAM-UHFFFAOYSA-N methyl sulfamate Chemical compound COS(N)(=O)=O FIYXUOWXHWJDAM-UHFFFAOYSA-N 0.000 claims description 234
- 229910052739 hydrogen Inorganic materials 0.000 claims description 212
- 239000001257 hydrogen Substances 0.000 claims description 212
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 189
- -1 chloro, bromo, fluoro, iodo Chemical group 0.000 claims description 165
- 125000001072 heteroaryl group Chemical group 0.000 claims description 140
- 125000000623 heterocyclic group Chemical group 0.000 claims description 130
- 150000002431 hydrogen Chemical group 0.000 claims description 129
- 125000003118 aryl group Chemical group 0.000 claims description 114
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 77
- 229910052757 nitrogen Inorganic materials 0.000 claims description 71
- 125000001153 fluoro group Chemical group F* 0.000 claims description 70
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims description 63
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 60
- 125000001424 substituent group Chemical group 0.000 claims description 57
- 125000003107 substituted aryl group Chemical group 0.000 claims description 56
- 201000011510 cancer Diseases 0.000 claims description 55
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 51
- 125000002947 alkylene group Chemical group 0.000 claims description 49
- 125000004432 carbon atom Chemical group C* 0.000 claims description 45
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 43
- 230000000694 effects Effects 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 35
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 35
- 125000005843 halogen group Chemical group 0.000 claims description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 32
- 125000005842 heteroatom Chemical group 0.000 claims description 31
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 30
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 30
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 29
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 22
- 108091007790 NEDD8-activating enzyme E1 Proteins 0.000 claims description 17
- 102000038427 NEDD8-activating enzyme E1 Human genes 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000006413 ring segment Chemical group 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 11
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- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
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- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
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- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 9
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- 206010060862 Prostate cancer Diseases 0.000 claims description 9
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 9
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 8
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 201000005202 lung cancer Diseases 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 7
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 7
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 7
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 7
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 7
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 6
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 6
- 208000017604 Hodgkin disease Diseases 0.000 claims description 6
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 6
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 6
- 101150020251 NR13 gene Proteins 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
- 208000033501 Refractory anemia with excess blasts Diseases 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 208000016586 myelodysplastic syndrome with excess blasts Diseases 0.000 claims description 6
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 6
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 208000009527 Refractory anemia Diseases 0.000 claims description 5
- 206010072684 Refractory cytopenia with unilineage dysplasia Diseases 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 230000003247 decreasing effect Effects 0.000 claims description 5
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims description 4
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 claims description 4
- 206010058354 Bronchioloalveolar carcinoma Diseases 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 239000003098 androgen Substances 0.000 claims description 4
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 208000016992 lung adenocarcinoma in situ Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 208000024191 minimally invasive lung adenocarcinoma Diseases 0.000 claims description 4
- 201000002120 neuroendocrine carcinoma Diseases 0.000 claims description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
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- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
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- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
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- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
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- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
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- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
- RIQDBMCFMGPTOE-VUEMZVKRSA-N 2-[(2r,3s,4r,5r)-3,4-dihydroxy-5-[6-[(2-methoxy-2,3-dihydro-1h-inden-1-yl)amino]purin-9-yl]oxolan-2-yl]ethanesulfonamide Chemical compound COC1CC2=CC=CC=C2C1NC(C=1N=C2)=NC=NC=1N2[C@@H]1O[C@H](CCS(N)(=O)=O)[C@@H](O)[C@H]1O RIQDBMCFMGPTOE-VUEMZVKRSA-N 0.000 claims description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
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- YZHURPUGBIWJOP-IVZWLZJFSA-N [(2r,3s,5r)-3-hydroxy-5-(4-methoxypyrrolo[2,3-d]pyrimidin-7-yl)oxolan-2-yl]methyl sulfamate Chemical compound C1=CC=2C(OC)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COS(N)(=O)=O)O1 YZHURPUGBIWJOP-IVZWLZJFSA-N 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
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- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
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- RSOJSFYJLQADDM-UHFFFAOYSA-N ethanesulfonamide Chemical compound [CH2]CS(N)(=O)=O RSOJSFYJLQADDM-UHFFFAOYSA-N 0.000 claims 8
- MAFCPHXIMQXTTJ-SCRDCRAPSA-N 2-[(1r,2s,4r)-2-hydroxy-4-[6-(2-methylpropyl)purin-9-yl]cyclopentyl]ethanesulfonamide Chemical compound C1=NC=2C(CC(C)C)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](CCS(N)(=O)=O)C1 MAFCPHXIMQXTTJ-SCRDCRAPSA-N 0.000 claims 4
- JHNKHMOLMLBMDA-WLMAQUICSA-N 2-[(2r,3s,4r,5r)-5-[6-(3-bicyclo[2.2.1]heptanylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]ethanesulfonamide Chemical compound O[C@@H]1[C@H](O)[C@@H](CCS(=O)(=O)N)O[C@H]1N1C2=NC=NC(NC3C4CCC(C4)C3)=C2N=C1 JHNKHMOLMLBMDA-WLMAQUICSA-N 0.000 claims 2
- BCVKYQBJRGWHDF-SWQDORGXSA-N 2-[(2r,3s,4r,5r)-5-[6-[[(1s)-2,3-dihydro-1h-inden-1-yl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]ethanesulfonamide Chemical compound O[C@@H]1[C@H](O)[C@@H](CCS(=O)(=O)N)O[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2N=C1 BCVKYQBJRGWHDF-SWQDORGXSA-N 0.000 claims 2
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- HUMQZVVFANPAJL-BPAMBQHCSA-N 6-[[(1s)-2,3-dihydro-1h-inden-1-yl]amino]-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]purine Chemical compound O[C@@H]1[C@H](O)[C@@H](CNS(=O)(=O)N)O[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2N=C1 HUMQZVVFANPAJL-BPAMBQHCSA-N 0.000 claims 2
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- RRBDKNMCJCSIIS-GFOCRRMGSA-N 9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-6-(2-phenylethynyl)purine Chemical compound O[C@@H]1[C@H](O)[C@@H](CNS(=O)(=O)N)O[C@H]1N1C2=NC=NC(C#CC=3C=CC=CC=3)=C2N=C1 RRBDKNMCJCSIIS-GFOCRRMGSA-N 0.000 claims 2
- XUTKGHULPNVDHI-SCFUHWHPSA-N 9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-6-[(4-methoxyphenyl)methylsulfanyl]purine Chemical compound C1=CC(OC)=CC=C1CSC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CNS(N)(=O)=O)O1 XUTKGHULPNVDHI-SCFUHWHPSA-N 0.000 claims 2
- ZAXGTYGFFQBAHX-ZVWXDJDZSA-N 9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-6-[[(1r,2s)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]purine Chemical compound O[C@@H]1[C@H](O)[C@@H](CNS(=O)(=O)N)O[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4C[C@@H]3O)=C2N=C1 ZAXGTYGFFQBAHX-ZVWXDJDZSA-N 0.000 claims 2
- WTHVKASWJDJTSW-RKXAXZPRSA-N [(1r)-1-[(2s,3s,4r,5r)-5-[6-[[(1s)-2,3-dihydro-1h-inden-1-yl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]ethyl] sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H]([C@H](OS(N)(=O)=O)C)O[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2N=C1 WTHVKASWJDJTSW-RKXAXZPRSA-N 0.000 claims 2
- ZKHOXVPVIYXYOM-DXLKZPDWSA-N [(1r,2r,3s,4r)-2,3-dihydroxy-4-(6-propylpurin-9-yl)cyclopentyl]methyl sulfamate Chemical compound C1=NC=2C(CCC)=NC=NC=2N1[C@@H]1C[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O ZKHOXVPVIYXYOM-DXLKZPDWSA-N 0.000 claims 2
- BPYGEQGJGDQMEG-IMJCEVDSSA-N [(1r,2r,3s,4r)-2,3-dihydroxy-4-[6-(2-methylpropyl)purin-9-yl]cyclopentyl]methyl sulfamate Chemical compound C1=NC=2C(CC(C)C)=NC=NC=2N1[C@@H]1C[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O BPYGEQGJGDQMEG-IMJCEVDSSA-N 0.000 claims 2
- LWBQXUBIJDZDRO-UWIFEVILSA-N [(1r,2r,3s,4r)-2,3-dihydroxy-4-[6-(2-phenylethyl)purin-9-yl]cyclopentyl]methyl sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)N)C[C@H]1N1C2=NC=NC(CCC=3C=CC=CC=3)=C2N=C1 LWBQXUBIJDZDRO-UWIFEVILSA-N 0.000 claims 2
- VNCLEAFVQLFLEA-INMHGKMJSA-N [(1r,2s,4r)-2-hydroxy-4-[6-(2-phenylethynyl)purin-9-yl]cyclopentyl]methyl sulfamate Chemical compound C1[C@H](O)[C@@H](COS(=O)(=O)N)C[C@H]1N1C2=NC=NC(C#CC=3C=CC=CC=3)=C2N=C1 VNCLEAFVQLFLEA-INMHGKMJSA-N 0.000 claims 2
- AECBNNJCKMBMNP-WJWAHETDSA-N [(2R,3R,4S,5R)-5-[6-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]purin-9-yl]-4-fluoro-3-hydroxyoxolan-2-yl]methylsulfamic acid Chemical compound F[C@H]1[C@H](O)[C@@H](CNS(O)(=O)=O)O[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2N=C1 AECBNNJCKMBMNP-WJWAHETDSA-N 0.000 claims 2
- UBAIEGBPSJYGMJ-IKVITTDRSA-N [(2r,3r,4s,5r)-3-hydroxy-4-methoxy-5-[6-(2-methylpropyl)purin-9-yl]oxolan-2-yl]methyl sulfamate Chemical compound CO[C@H]1[C@H](O)[C@@H](COS(N)(=O)=O)O[C@H]1N1C2=NC=NC(CC(C)C)=C2N=C1 UBAIEGBPSJYGMJ-IKVITTDRSA-N 0.000 claims 2
- AQWCLIKCMXGYMQ-PNHWDRBUSA-N [(2r,3s,4r,5r)-3,4-dihydroxy-5-(6-methylpurin-9-yl)oxolan-2-yl]methyl sulfamate Chemical compound C1=NC=2C(C)=NC=NC=2N1[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O AQWCLIKCMXGYMQ-PNHWDRBUSA-N 0.000 claims 2
- KVOKLCBIHCGUAZ-VVHMCBODSA-N [(2r,3s,4r,5r)-3,4-dihydroxy-5-[6-(3-pyrazol-1-ylphenyl)purin-9-yl]oxolan-2-yl]methyl sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)N)O[C@H]1N1C2=NC=NC(C=3C=C(C=CC=3)N3N=CC=C3)=C2N=C1 KVOKLCBIHCGUAZ-VVHMCBODSA-N 0.000 claims 2
- BFWZJEZEXRXGGT-LSCFUAHRSA-N [(2r,3s,4r,5r)-3,4-dihydroxy-5-[6-[(pyridine-3-carbonylamino)methyl]purin-9-yl]oxolan-2-yl]methyl sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)N)O[C@H]1N1C2=NC=NC(CNC(=O)C=3C=NC=CC=3)=C2N=C1 BFWZJEZEXRXGGT-LSCFUAHRSA-N 0.000 claims 2
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- JKNADMJNGXJOCA-ZVWXDJDZSA-N [(2r,3s,4r,5r)-3,4-dihydroxy-5-[6-[[(1r,2s)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]purin-9-yl]oxolan-2-yl]methyl sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)N)O[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4C[C@@H]3O)=C2N=C1 JKNADMJNGXJOCA-ZVWXDJDZSA-N 0.000 claims 2
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- PGAMXUGSHMQFKD-BPAMBQHCSA-N [(2r,3s,4r,5r)-5-[6-[[(1s)-2,3-dihydro-1h-inden-1-yl]amino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl sulfamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COS(=O)(=O)N)O[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2N=C1 PGAMXUGSHMQFKD-BPAMBQHCSA-N 0.000 claims 2
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Classifications
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
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- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/048—Pyridine radicals
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/14—Pyrrolo-pyrimidine radicals
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- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/23—Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22
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- Pharmacology & Pharmacy (AREA)
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- Medicinal Chemistry (AREA)
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- Oncology (AREA)
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- Hematology (AREA)
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- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65043305P | 2005-02-04 | 2005-02-04 | |
| US60/650,433 | 2005-02-04 | ||
| PCT/US2006/004637 WO2006084281A1 (en) | 2005-02-04 | 2006-02-02 | Inhibitors of e1 activating enzymes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2596424A1 CA2596424A1 (en) | 2006-08-10 |
| CA2596424C true CA2596424C (en) | 2016-03-29 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2596424A Expired - Fee Related CA2596424C (en) | 2005-02-04 | 2006-02-02 | Inhibitors of e1 activating enzymes |
Country Status (15)
| Country | Link |
|---|---|
| US (6) | US7951810B2 (https=) |
| EP (1) | EP1848718B1 (https=) |
| JP (1) | JP5048520B2 (https=) |
| AU (1) | AU2006210422B2 (https=) |
| CA (1) | CA2596424C (https=) |
| CY (1) | CY1113166T1 (https=) |
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| HR (1) | HRP20120847T1 (https=) |
| ME (1) | ME02012B (https=) |
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| RS (1) | RS52458B (https=) |
| SI (1) | SI1848718T1 (https=) |
| WO (1) | WO2006084281A1 (https=) |
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- 2006-02-02 WO PCT/US2006/004637 patent/WO2006084281A1/en not_active Ceased
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- 2006-02-02 SI SI200631462T patent/SI1848718T1/sl unknown
- 2006-02-02 US US11/346,469 patent/US7951810B2/en active Active
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- 2006-02-02 EP EP06734691A patent/EP1848718B1/en not_active Expired - Lifetime
- 2006-02-02 JP JP2007554355A patent/JP5048520B2/ja not_active Expired - Fee Related
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- 2006-02-02 AU AU2006210422A patent/AU2006210422B2/en not_active Ceased
- 2006-02-02 PT PT06734691T patent/PT1848718E/pt unknown
- 2006-02-02 DK DK06734691.6T patent/DK1848718T3/da active
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| US20210070798A1 (en) | 2021-03-11 |
| PL1848718T3 (pl) | 2012-12-31 |
| US7951810B2 (en) | 2011-05-31 |
| EP1848718B1 (en) | 2012-08-01 |
| EP1848718A1 (en) | 2007-10-31 |
| PT1848718E (pt) | 2012-10-11 |
| US20060189636A1 (en) | 2006-08-24 |
| US20140256668A9 (en) | 2014-09-11 |
| US20180086785A1 (en) | 2018-03-29 |
| WO2006084281A1 (en) | 2006-08-10 |
| AU2006210422B2 (en) | 2012-09-13 |
| ES2390803T3 (es) | 2012-11-16 |
| US20160194348A1 (en) | 2016-07-07 |
| ME02012B (me) | 2013-02-28 |
| SI1848718T1 (sl) | 2012-12-31 |
| AU2006210422A1 (en) | 2006-08-10 |
| RS52458B (sr) | 2013-02-28 |
| US20110136834A1 (en) | 2011-06-09 |
| JP5048520B2 (ja) | 2012-10-17 |
| HRP20120847T1 (hr) | 2012-11-30 |
| JP2008530027A (ja) | 2008-08-07 |
| CY1113166T1 (el) | 2016-04-13 |
| CA2596424A1 (en) | 2006-08-10 |
| US20170073367A9 (en) | 2017-03-16 |
| US20130338094A1 (en) | 2013-12-19 |
| DK1848718T3 (da) | 2012-08-27 |
| HK1113363A1 (en) | 2008-10-03 |
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