AU2013315715A1 - Glucosylceramide synthase inhibitors - Google Patents
Glucosylceramide synthase inhibitors Download PDFInfo
- Publication number
- AU2013315715A1 AU2013315715A1 AU2013315715A AU2013315715A AU2013315715A1 AU 2013315715 A1 AU2013315715 A1 AU 2013315715A1 AU 2013315715 A AU2013315715 A AU 2013315715A AU 2013315715 A AU2013315715 A AU 2013315715A AU 2013315715 A1 AU2013315715 A1 AU 2013315715A1
- Authority
- AU
- Australia
- Prior art keywords
- cio
- methyl
- compound according
- spiro
- direct bond
- 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.)
- Abandoned
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- 239000003892 ceramide glucosyltransferase inhibitor Substances 0.000 title description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 61
- 201000010099 disease Diseases 0.000 claims abstract description 44
- 102000044956 Ceramide glucosyltransferases Human genes 0.000 claims abstract description 30
- 108091000114 ceramide glucosyltransferase Proteins 0.000 claims abstract description 30
- 208000015439 Lysosomal storage disease Diseases 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 238000002641 enzyme replacement therapy Methods 0.000 claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 6
- 201000011510 cancer Diseases 0.000 claims abstract description 5
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 863
- 150000001875 compounds Chemical class 0.000 claims description 837
- 125000003003 spiro group Chemical group 0.000 claims description 610
- 229910052739 hydrogen Inorganic materials 0.000 claims description 594
- 239000001257 hydrogen Substances 0.000 claims description 590
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 557
- 125000001072 heteroaryl group Chemical group 0.000 claims description 467
- 125000003118 aryl group Chemical group 0.000 claims description 456
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 419
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 345
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 339
- 229910052799 carbon Inorganic materials 0.000 claims description 318
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 316
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 175
- 125000003545 alkoxy group Chemical group 0.000 claims description 162
- -1 isopropenyl phenyl Chemical group 0.000 claims description 145
- 125000000217 alkyl group Chemical group 0.000 claims description 104
- 125000005843 halogen group Chemical group 0.000 claims description 72
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 65
- 125000001424 substituent group Chemical group 0.000 claims description 58
- 238000000034 method Methods 0.000 claims description 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
- 125000005605 benzo group Chemical group 0.000 claims description 26
- 239000000651 prodrug Substances 0.000 claims description 22
- 229940002612 prodrug Drugs 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 17
- 102000004190 Enzymes Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 12
- 238000002648 combination therapy Methods 0.000 claims description 12
- 230000002132 lysosomal effect Effects 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 239000000758 substrate Substances 0.000 claims description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 239000004202 carbamide Substances 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000005466 alkylenyl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 8
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 7
- 125000004069 aziridinyl group Chemical group 0.000 claims description 7
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 7
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 7
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 7
- 230000000694 effects Effects 0.000 claims description 7
- 150000002339 glycosphingolipids Chemical class 0.000 claims description 7
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 7
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 claims description 7
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 230000002981 neuropathic effect Effects 0.000 claims description 7
- 125000000466 oxiranyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 6
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 claims description 6
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004663 dialkyl amino group Chemical group 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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 5
- DGCOGZQDAXUUBY-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole Chemical compound C1=CC=C2OC(F)(F)OC2=C1 DGCOGZQDAXUUBY-UHFFFAOYSA-N 0.000 claims description 5
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 150000002305 glucosylceramides Chemical class 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 230000037361 pathway Effects 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 238000009825 accumulation Methods 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 3
- FGFRLPUTEXUVNL-UHFFFAOYSA-N 1-[1-[4-(4-fluorophenyl)phenyl]cyclopropyl]-1-methyl-3-(3-methyl-1-azabicyclo[2.2.2]octan-3-yl)urea Chemical compound C1N(CC2)CCC2C1(C)NC(=O)N(C)C1(C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)CC1 FGFRLPUTEXUVNL-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 3
- DDVRNOMZDQTUNS-UHFFFAOYSA-N 2,7-diazaspiro[4.4]nonane Chemical compound C1NCCC11CNCC1 DDVRNOMZDQTUNS-UHFFFAOYSA-N 0.000 claims description 3
- QPEJAHMNOVMSOZ-UHFFFAOYSA-N 2-azaspiro[3.3]heptane Chemical compound C1CCC21CNC2 QPEJAHMNOVMSOZ-UHFFFAOYSA-N 0.000 claims description 3
- YVHBSYTYLQYTOU-UHFFFAOYSA-N 3,6-diazabicyclo[3.1.1]heptane Chemical compound C1NCC2CC1N2 YVHBSYTYLQYTOU-UHFFFAOYSA-N 0.000 claims description 3
- PWVHZVWNAGLZFH-UHFFFAOYSA-N 3-azabicyclo[3.1.1]heptane Chemical compound C1C2CC1CNC2 PWVHZVWNAGLZFH-UHFFFAOYSA-N 0.000 claims description 3
- DENNCEQUAZKJGC-UHFFFAOYSA-N 6-azabicyclo[3.1.1]heptane Chemical compound C1CCC2CC1N2 DENNCEQUAZKJGC-UHFFFAOYSA-N 0.000 claims description 3
- 208000006515 AB Variant Tay-Sachs Disease Diseases 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 108010030291 alpha-Galactosidase Proteins 0.000 claims description 3
- 102000005840 alpha-Galactosidase Human genes 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 3
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 3
- 230000007547 defect Effects 0.000 claims description 3
- 125000005059 halophenyl group Chemical group 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 150000003852 triazoles Chemical class 0.000 claims description 3
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 2
- VZGGKFXPAHSTHX-UHFFFAOYSA-N 1-(3-butyl-1-azabicyclo[2.2.2]octan-3-yl)-3-[2-[1-(4-fluorophenyl)pyrazol-4-yl]propan-2-yl]urea Chemical compound C1N(CC2)CCC2C1(CCCC)NC(=O)NC(C)(C)C(=C1)C=NN1C1=CC=C(F)C=C1 VZGGKFXPAHSTHX-UHFFFAOYSA-N 0.000 claims description 2
- PASVOXGCIDVUKF-UHFFFAOYSA-N 1-(3-ethyl-1-azabicyclo[2.2.2]octan-3-yl)-3-[1-[4-(4-fluorophenyl)phenyl]cyclopropyl]urea Chemical compound C1N(CC2)CCC2C1(CC)NC(=O)NC1(C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)CC1 PASVOXGCIDVUKF-UHFFFAOYSA-N 0.000 claims description 2
- ZVFHVDNMPGRDDZ-UHFFFAOYSA-N 1-(4-methyl-1-azabicyclo[3.2.2]nonan-4-yl)-3-[1-(5-phenylpyridin-2-yl)cyclopropyl]urea Chemical compound C1CN(CC2)CCC2C1(C)NC(=O)NC1(C=2N=CC(=CC=2)C=2C=CC=CC=2)CC1 ZVFHVDNMPGRDDZ-UHFFFAOYSA-N 0.000 claims description 2
- FSWOXLOPKDRRRE-UHFFFAOYSA-N 1-[2-[4-(4-fluorophenyl)phenyl]propan-2-yl]-3-(3-methyl-1-azabicyclo[3.2.2]nonan-3-yl)urea Chemical compound C1C(CC2)CCN2CC1(C)NC(=O)NC(C)(C)C(C=C1)=CC=C1C1=CC=C(F)C=C1 FSWOXLOPKDRRRE-UHFFFAOYSA-N 0.000 claims description 2
- BHJQVTLWQHYLNT-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[1-[3-(4-fluorophenoxy)phenyl]cyclopropyl]carbamate Chemical compound C1=CC(F)=CC=C1OC1=CC=CC(C2(CC2)NC(=O)OC2C3CCN(CC3)C2)=C1 BHJQVTLWQHYLNT-UHFFFAOYSA-N 0.000 claims description 2
- ONKZHPRQDWJTOU-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[1-[4-(1,3-benzothiazol-5-yl)phenyl]cyclopropyl]carbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC1(C=2C=CC(=CC=2)C=2C=C3N=CSC3=CC=2)CC1 ONKZHPRQDWJTOU-UHFFFAOYSA-N 0.000 claims description 2
- YZIAQJHVEBCFGY-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[1-[4-(4-fluoro-3-methoxyphenyl)phenyl]cyclopropyl]carbamate Chemical compound C1=C(F)C(OC)=CC(C=2C=CC(=CC=2)C2(CC2)NC(=O)OC2C3CCN(CC3)C2)=C1 YZIAQJHVEBCFGY-UHFFFAOYSA-N 0.000 claims description 2
- SCDDHGVSCPEIQY-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[1-[6-(4-fluorophenoxy)pyridin-2-yl]cyclopropyl]carbamate Chemical compound C1=CC(F)=CC=C1OC1=CC=CC(C2(CC2)NC(=O)OC2C3CCN(CC3)C2)=N1 SCDDHGVSCPEIQY-UHFFFAOYSA-N 0.000 claims description 2
- SHJITOHUWKDRMO-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[2-(2-pyrrol-1-ylpyridin-4-yl)propan-2-yl]carbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC(C)(C)C(C=1)=CC=NC=1N1C=CC=C1 SHJITOHUWKDRMO-UHFFFAOYSA-N 0.000 claims description 2
- MMVDZVGPBITWFR-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[2-[3-fluoro-4-(4-fluorophenyl)phenyl]propan-2-yl]carbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC(C)(C)C(C=C1F)=CC=C1C1=CC=C(F)C=C1 MMVDZVGPBITWFR-UHFFFAOYSA-N 0.000 claims description 2
- KOVYXVXXJYWVKQ-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[2-[4-(1,3-benzothiazol-6-yl)phenyl]propan-2-yl]carbamate Chemical compound C1=C2N=CSC2=CC(C2=CC=C(C=C2)C(C)(NC(=O)OC2C3CCN(CC3)C2)C)=C1 KOVYXVXXJYWVKQ-UHFFFAOYSA-N 0.000 claims description 2
- JRALGKRLGSYVMC-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[3-[4-(4-fluorophenyl)phenyl]oxetan-3-yl]carbamate Chemical compound C1=CC(F)=CC=C1C1=CC=C(C2(COC2)NC(=O)OC2C3CCN(CC3)C2)C=C1 JRALGKRLGSYVMC-UHFFFAOYSA-N 0.000 claims description 2
- WKYLVNNRDQDAHM-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[3-[4-(4-fluorophenyl)phenyl]pentan-3-yl]carbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC(CC)(CC)C(C=C1)=CC=C1C1=CC=C(F)C=C1 WKYLVNNRDQDAHM-UHFFFAOYSA-N 0.000 claims description 2
- JFEYMBFKUPANIG-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-[4-(4-fluorophenyl)-2-methylbut-3-yn-2-yl]carbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC(C)(C)C#CC1=CC=C(F)C=C1 JFEYMBFKUPANIG-UHFFFAOYSA-N 0.000 claims description 2
- IZFZGAYDVYBYDL-UHFFFAOYSA-N 1-azabicyclo[3.2.2]nonan-4-yl n-[1-[5-(4-fluorophenyl)pyridin-2-yl]cyclopropyl]carbamate Chemical compound C1=CC(F)=CC=C1C1=CC=C(C2(CC2)NC(=O)OC2C3CCN(CC3)CC2)N=C1 IZFZGAYDVYBYDL-UHFFFAOYSA-N 0.000 claims description 2
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- HHTWDQMTAADGQQ-UHFFFAOYSA-N 3-methyl-n-[2-(4-phenylphenyl)propan-2-ylsulfamoyl]-1-azabicyclo[2.2.2]octan-3-amine Chemical compound C1N(CC2)CCC2C1(C)NS(=O)(=O)NC(C)(C)C(C=C1)=CC=C1C1=CC=CC=C1 HHTWDQMTAADGQQ-UHFFFAOYSA-N 0.000 claims description 2
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- 208000009796 Gangliosidoses Diseases 0.000 claims description 2
- 108010017544 Glucosylceramidase Proteins 0.000 claims description 2
- 108010053317 Hexosaminidase A Proteins 0.000 claims description 2
- 102000016871 Hexosaminidase A Human genes 0.000 claims description 2
- 102000016870 Hexosaminidase B Human genes 0.000 claims description 2
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- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
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- NLYHSWZIYAWLGU-UHFFFAOYSA-N n-(1-azabicyclo[2.2.2]octan-3-yl)-n'-[1-[4-(4-fluorophenyl)phenyl]cyclopropyl]oxamide Chemical compound C1=CC(F)=CC=C1C1=CC=C(C2(CC2)NC(=O)C(=O)NC2C3CCN(CC3)C2)C=C1 NLYHSWZIYAWLGU-UHFFFAOYSA-N 0.000 claims description 2
- HRIPRKAKDXNLPE-UHFFFAOYSA-N n-[1-[4-(4-fluorophenyl)phenyl]cyclopropyl]-1,4-diazabicyclo[3.2.2]nonane-4-carboxamide Chemical compound C1=CC(F)=CC=C1C1=CC=C(C2(CC2)NC(=O)N2C3CCN(CC3)CC2)C=C1 HRIPRKAKDXNLPE-UHFFFAOYSA-N 0.000 claims description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims description 2
- 210000002700 urine Anatomy 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 6
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 2
- 125000001422 pyrrolinyl group Chemical group 0.000 claims 2
- KPUSZZFAYGWAHZ-UHFFFAOYSA-N 3-azabicyclo[2.2.2]octane Chemical compound C1CC2CCC1NC2 KPUSZZFAYGWAHZ-UHFFFAOYSA-N 0.000 claims 1
- 102000004547 Glucosylceramidase Human genes 0.000 claims 1
- 101100082060 Xenopus laevis pou5f1.1 gene Proteins 0.000 claims 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 1
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- 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
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Landscapes
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261699714P | 2012-09-11 | 2012-09-11 | |
| US61/699,714 | 2012-09-11 | ||
| PCT/US2013/058896 WO2014043068A1 (en) | 2012-09-11 | 2013-09-10 | Glucosylceramide synthase inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| AU2018200675A Division AU2018200675A1 (en) | 2012-09-11 | 2018-01-30 | Glucosylceramide synthase inhibitors |
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| AU2013315715A1 true AU2013315715A1 (en) | 2015-04-09 |
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| AU2013315715A Abandoned AU2013315715A1 (en) | 2012-09-11 | 2013-09-10 | Glucosylceramide synthase inhibitors |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| MA37975B2 (fr) * | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
| MX365464B (es) * | 2013-03-15 | 2019-06-04 | Genzyme Corp | Prodecimiento para preparar inhibidores de la glucosilceramida sintasa. |
| EP3079695B1 (en) * | 2013-12-11 | 2021-03-17 | Genzyme Corporation | Glucosylceramide synthase inhibitors |
| FR3017867A1 (fr) * | 2014-02-21 | 2015-08-28 | Inventiva | Nouveaux composes de type phenylazetidine carboxylate ou carboxamide |
| RU2017106891A (ru) * | 2014-08-04 | 2018-09-06 | Джензим Корпорейшн | Биомаркеры поликистозной болезни почек и пути их применения |
| TW201642855A (zh) * | 2015-03-10 | 2016-12-16 | 健臻公司 | 用於治療蛋白質病變之方法 |
| WO2016141458A1 (en) | 2015-03-12 | 2016-09-15 | British Columbia Cancer Agency Branch | Bisphenol ether derivatives and methods for using the same |
| MX2018006250A (es) * | 2015-11-18 | 2018-09-05 | Genzyme Corp | Biomarcador de enfermedad poliquistica renal y usos del mismo. |
| EP3222292A1 (en) | 2016-03-03 | 2017-09-27 | Heidelberg Pharma GmbH | Amanitin conjugates |
| US20170298033A1 (en) | 2016-04-15 | 2017-10-19 | The University Of British Columbia | Bisphenol derivatives and their use as androgen receptor activity modulators |
| MX388576B (es) | 2016-06-07 | 2025-03-20 | Jacobio Pharmaceuticals Co Ltd | Derivados heterociclicos novedosos utiles como inhibidores de shp2. |
| TW201819376A (zh) | 2016-10-06 | 2018-06-01 | 比利時商健生藥品公司 | 經取代之１Ｈ－咪唑並［４，５－ｂ］吡啶－２（３Ｈ）－酮及其作為ＧＬＵＮ２Ｂ受體調節劑之用途 |
| EP3318277A1 (en) | 2016-11-04 | 2018-05-09 | Institut du Cerveau et de la Moelle Epiniere-ICM | Inhibitors of glucosylceramide synthase for the treatment of motor neuron diseases |
| EA202190196A1 (ru) | 2017-03-23 | 2021-08-31 | Джакобио Фармасьютикалс Ко., Лтд. | Новые гетероциклические производные, применимые в качестве ингибиторов shp2 |
| CN109111447A (zh) | 2017-06-23 | 2019-01-01 | 中国科学院上海药物研究所 | 7-位取代吡咯并三嗪类化合物或其药学上可用的盐，及其制备方法和用途 |
| JP2021506920A (ja) | 2017-12-21 | 2021-02-22 | リソソーマル・セラピューティクス・インコーポレイテッドＬｙｓｏｓｏｍａｌ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | 結晶性の置換シクロヘキシルピラゾロ［１，５−ａ］ピリミジニルカルボキサミド化合物およびその治療的使用 |
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| WO2020039088A2 (en) * | 2018-08-24 | 2020-02-27 | Xeniopro GmbH | Novel compounds |
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| WO2023177563A2 (en) * | 2022-03-14 | 2023-09-21 | Merck Sharp & Dohme Llc | Fused pyrazole amide analogs as glucosylceramide synthase inhibitors |
| JP2025541739A (ja) | 2022-12-01 | 2025-12-23 | ジェンザイム・コーポレーション | Ｃｙｐ３ａ４の強力な又は中程度の阻害剤と組み合わせたベングルスタット |
| KR20250117295A (ko) * | 2024-01-26 | 2025-08-04 | 주식회사유한양행 | 고셔병의 예방 또는 치료용 약제학적 조성물 |
| WO2025221055A1 (ko) * | 2024-04-18 | 2025-10-23 | 에스케이바이오팜 주식회사 | 유레아 화합물 및 이의 용도 |
| WO2025259779A1 (en) * | 2024-06-12 | 2025-12-18 | Insmed Incorporated | Uses of certain carboxamides as dpp1 inhibitors |
| WO2025262570A1 (en) | 2024-06-17 | 2025-12-26 | Genzyme Corporation | Venglustat as an inhibitor of glucosylceramide synthase in subjects having hepatic impairment |
Family Cites Families (80)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB725228A (en) | 1952-06-19 | 1955-03-02 | Roche Products Ltd | Substituted carbamic acid esters and process for the manufacture thereof |
| BE640616A (https=) | 1962-12-19 | |||
| NL130759C (https=) | 1965-10-07 | |||
| US3492397A (en) | 1967-04-07 | 1970-01-27 | Warner Lambert Pharmaceutical | Sustained release dosage in the pellet form and process thereof |
| US4060598A (en) | 1967-06-28 | 1977-11-29 | Boehringer Mannheim G.M.B.H. | Tablets coated with aqueous resin dispersions |
| US3538214A (en) | 1969-04-22 | 1970-11-03 | Merck & Co Inc | Controlled release medicinal tablets |
| US4173626A (en) | 1978-12-11 | 1979-11-06 | Merck & Co., Inc. | Sustained release indomethacin |
| US4593034A (en) * | 1984-04-06 | 1986-06-03 | A. H. Robins Company, Inc. | 2-alkoxy-N-(1-azabicyclo[2.2.2]oct-3-yl)benzamides and thiobenzamides |
| AU611976B2 (en) | 1987-12-24 | 1991-06-27 | John Wyeth & Brother Limited | Aroyl urea and carbamic acid derivatives of azabicyclo compounds |
| DE3878235T2 (de) * | 1988-08-04 | 1993-06-03 | Synthelabo | Antischizophren-wirksame s-n-(1-azabicyclo (2.2.2.)oct-3-yl)benzamide und thiobenzamide. |
| US5236838A (en) | 1988-12-23 | 1993-08-17 | Genzyme Corporation | Enzymatically active recombinant glucocerebrosidase |
| US5549892A (en) | 1988-12-23 | 1996-08-27 | Genzyme Corporation | Enhanced in vivo uptake of glucocerebrosidase |
| IT1228293B (it) | 1989-02-06 | 1991-06-07 | Angeli Inst Spa | Benzoderivati di composti eterociclici contenenti azoto. |
| DK443489D0 (da) | 1989-09-08 | 1989-09-08 | Ferrosan As | Substituerede urinstofforbindelser, deres fremstilling og anvendelse |
| US5272071A (en) | 1989-12-22 | 1993-12-21 | Applied Research Systems Ars Holding N.V. | Method for the modification of the expression characteristics of an endogenous gene of a given cell line |
| GB9106571D0 (en) | 1991-03-27 | 1991-05-15 | Erba Carlo Spa | Derivatives of substituted imidazol-2-one and process for their preparation |
| US5733761A (en) | 1991-11-05 | 1998-03-31 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
| AU685225B2 (en) | 1994-02-10 | 1998-01-15 | Yamanouchi Pharmaceutical Co., Ltd. | Novel carbamate derivative and medicinal composition containing the same |
| US5468875A (en) * | 1994-12-22 | 1995-11-21 | American Home Products Corporation | 1-azabicycloheptane derivatives |
| JPH08198751A (ja) * | 1995-01-19 | 1996-08-06 | Yamanouchi Pharmaceut Co Ltd | カルバメート誘導体 |
| KR19990067403A (ko) * | 1995-11-08 | 1999-08-16 | 이곤 이 버그 | 1-아자바이시클로헵탄 유도체 및 이의 약제학적용도 |
| SE9600683D0 (sv) | 1996-02-23 | 1996-02-23 | Astra Ab | Azabicyclic esters of carbamic acids useful in therapy |
| JP2000515881A (ja) * | 1996-07-29 | 2000-11-28 | フアーマシア・アンド・アツプジヨン・アー・ベー | アリールシクロアルカンカルボン酸エステル、その使用、薬剤組成物および調製 |
| IL135578A0 (en) | 1997-10-29 | 2001-05-20 | Genzyme Corp | Compositions and methods for treating lysosomal storage disease |
| US6468998B1 (en) | 1998-11-02 | 2002-10-22 | Mitsubishi Pharma Corporation | Pyrrolidine compounds and medicinal utilization thereof |
| US6953855B2 (en) * | 1998-12-11 | 2005-10-11 | Targacept, Inc. | 3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof |
| FR2791678B1 (fr) | 1999-03-30 | 2001-05-04 | Synthelabo | Derives de 1,4-diazabicyclo [3.2.2] nonane-4-carboxylates et -carboxamides, leur preparation et leur application en therapeutique |
| KR20020084116A (ko) | 2000-02-07 | 2002-11-04 | 애보트 게엠베하 운트 콤파니 카게 | 2-벤조티아졸릴 우레아 유도체 및 이의 단백질 키나제억제제로서의 용도 |
| GB0010955D0 (en) | 2000-05-05 | 2000-06-28 | Novartis Ag | Organic compounds |
| KR100751981B1 (ko) | 2000-06-27 | 2007-08-28 | 라보라토리오스 살바트, 에스.에이. | 아릴알킬아민으로부터 유도된 카바메이트 |
| AU2001284645A1 (en) | 2000-08-18 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| US6599916B2 (en) | 2000-08-21 | 2003-07-29 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| NZ526580A (en) | 2000-12-22 | 2005-04-29 | Almirall Prodesfarma Ag | Quinuclidine carbamate derivatives and their use as M3 antagonists |
| ATE348829T1 (de) | 2001-02-06 | 2007-01-15 | Pfizer Prod Inc | Pharmazeutische zusammensetzungen zur behandlung von störungen des zns oder anderen erkrankungen |
| JP2003267977A (ja) | 2002-03-14 | 2003-09-25 | Yamanouchi Pharmaceut Co Ltd | キヌクリジン誘導体 |
| DE10211415A1 (de) * | 2002-03-15 | 2003-09-25 | Bayer Ag | Bicyclische N-Biarylamide |
| ES2203327B1 (es) | 2002-06-21 | 2005-06-16 | Almirall Prodesfarma, S.A. | Nuevos carbamatos de quinuclidina y composiciones farmaceuticas que los contienen. |
| AU2003246942B2 (en) | 2002-07-17 | 2009-06-25 | Idorsia Pharmaceuticals Ltd | Piperidinetriol derivatives as inhibitors of glycosylceramide synthase |
| JPWO2004011430A1 (ja) | 2002-07-25 | 2005-11-24 | アステラス製薬株式会社 | ナトリウムチャネル阻害剤 |
| SE0202430D0 (sv) | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | New Compounds |
| JP4750421B2 (ja) * | 2002-12-06 | 2011-08-17 | ノース ショア−ロング アイランド ジュ−イッシュ リサ−チ インスティチュ−ト | α７受容体結合コリン作動性アゴニストを用いる炎症の阻害 |
| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| TW200529860A (en) | 2003-12-22 | 2005-09-16 | Astrazeneca Ab | Nicotinic acetylcholine receptor ligands |
| GB0400812D0 (en) | 2004-01-14 | 2004-02-18 | Celltech R&D Ltd | Novel compounds |
| JP2007186422A (ja) | 2004-01-28 | 2007-07-26 | Astellas Pharma Inc | アリールスルフィド誘導体 |
| JP2008504282A (ja) | 2004-06-23 | 2008-02-14 | ザ ファインスタイン インスティテュート フォー メディカル リサーチ | コリンレセプターの薬理活性により腸閉塞を処置する方法 |
| EP1811991B1 (en) | 2004-11-10 | 2018-11-07 | Genzyme Corporation | Treatment of type 2 diabetes using inhibitors of glycosphingolipid synthesis |
| JP2008545776A (ja) * | 2005-06-11 | 2008-12-18 | ヴァーナリス アールアンドディー リミテッド | 癌および自己免疫疾患の治療における使用のためのピラゾール−置換ベンズイミダゾール誘導体 |
| CN101312968A (zh) * | 2005-09-23 | 2008-11-26 | 记忆药物公司 | 吲唑、苯并噻唑、苯并异噻唑、苯并异噁唑、吡唑并吡啶、异噻唑并吡啶及其制备和用途 |
| SG131819A1 (en) | 2005-11-07 | 2007-05-28 | Chikka Pte Ltd | Buddy-based cross-carrier messaging system |
| WO2007083978A1 (en) * | 2006-01-23 | 2007-07-26 | Crystalgenomics, Inc. | Imidazopyridine derivatives inhibiting protein kinase activity, method for the preparation thereof and pharmaceutical composition containing same |
| CN101379065A (zh) * | 2006-01-23 | 2009-03-04 | 克里斯特尔吉诺密斯株式会社 | 抑制蛋白质激酶活性的咪唑并吡啶衍生物、其制备方法和包含它的药物组合物 |
| EP1976519A2 (en) | 2006-01-27 | 2008-10-08 | Yale University | Cytisine and acetylcholine analogs and methods of treating mood disorders |
| US7840109B2 (en) | 2006-08-14 | 2010-11-23 | Adc Telecommunications, Inc. | Factory spliced cable assembly |
| EP2119716A4 (en) * | 2007-02-09 | 2011-06-01 | Astellas Pharma Inc | AZA BRIDGE CYCLE COMPOUND |
| MX2009010557A (es) | 2007-03-30 | 2009-11-19 | Amicus Therapeutics Inc | Metodo para el tratamiento de la enfermedad de fabry que utiliza chaperonas farmacologicas. |
| EP2170065A4 (en) * | 2007-06-20 | 2011-11-23 | Merck Sharp & Dohme | DIPHENYL SUBSTITUTED ALKANES |
| CA2706727A1 (en) | 2007-11-29 | 2009-06-11 | Michael S. Mcgrath | Compositions and methods for treating lysosomal disorders |
| CA2731685A1 (en) | 2008-07-28 | 2010-02-04 | Genzyme Corporation | Glucosylceramide synthase inhibition for the treatment of collapsing glomerulopathy and other glomerular disease |
| EP2154136A1 (en) * | 2008-08-08 | 2010-02-17 | CHIESI FARMACEUTICI S.p.A. | Quinuclidine carbonate derivatives and medicinal compositions thereof |
| WO2010091104A1 (en) * | 2009-02-06 | 2010-08-12 | Exelixis, Inc. | Glucosylceramide synthase inhibitors |
| WO2010091164A1 (en) * | 2009-02-06 | 2010-08-12 | Exelixis, Inc. | Inhibitors of glucosylceramide synthase |
| WO2010121963A1 (en) * | 2009-04-21 | 2010-10-28 | Nerviano Medical Sciences S.R.L. | Resorcinol derivatives as hsp90 inhibitors |
| AR077468A1 (es) * | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| EP2959902A1 (en) | 2009-07-23 | 2015-12-30 | Novartis AG | Use of azabicycloalkyl derivatives for the treatment or prevention of ataxia |
| SI3998078T1 (sl) | 2009-08-28 | 2026-02-27 | Genzyme Corporation | Encimsko nadomestno zdravljenje z naraščajočim odmerkom za zdravljenje pomanjkanja kisle sfingomielinaze |
| US20110183938A1 (en) * | 2009-12-16 | 2011-07-28 | Genentech, Inc. | 1,7-diazacarbazoles and methods of use |
| KR101500915B1 (ko) | 2010-11-12 | 2015-03-10 | 시오노기세야쿠 가부시키가이샤 | 6,7-불포화-7-카르바모일 모르피난 유도체의 결정 및 그의 제조 방법 |
| KR101987736B1 (ko) * | 2011-03-18 | 2019-06-11 | 젠자임 코포레이션 | 글루코실세라마이드 합성효소 억제제 |
| US20140228575A1 (en) | 2011-06-22 | 2014-08-14 | Isochem | Process for the Preparation of Solifenacin and Salts Thereof |
| CA2840224C (en) | 2011-06-22 | 2019-08-13 | The General Hospital Corporation | Treatment of proteinopathies |
| US9655946B2 (en) | 2012-09-11 | 2017-05-23 | Hospira Australia Pty Ltd. | Daptomycin formulations and uses thereof |
| MA37975B2 (fr) | 2012-09-11 | 2021-03-31 | Genzyme Corp | Inhibiteurs de synthase de glucosylcéramide |
| JO3713B1 (ar) | 2013-03-15 | 2021-01-31 | Genzyme Corp | أشكال ملح (s)-كوينوكليدين-3-يل(2-(2-(4-فلوروفينيل)ثيازول-4-يل)بروبان-2-يل)كارباميت |
| MX365464B (es) | 2013-03-15 | 2019-06-04 | Genzyme Corp | Prodecimiento para preparar inhibidores de la glucosilceramida sintasa. |
| EP3079695B1 (en) | 2013-12-11 | 2021-03-17 | Genzyme Corporation | Glucosylceramide synthase inhibitors |
| TW201642855A (zh) | 2015-03-10 | 2016-12-16 | 健臻公司 | 用於治療蛋白質病變之方法 |
| CN114040762A (zh) | 2019-02-04 | 2022-02-11 | 建新公司 | 使用葡糖神经酰胺合酶(gcs)的抑制剂治疗纤毛疾病 |
| CN113645969A (zh) | 2019-02-04 | 2021-11-12 | 建新公司 | 用于治疗与溶酶体贮积症相关的症状和病症的方法 |
| JP2023512366A (ja) | 2020-02-03 | 2023-03-27 | ジェンザイム・コーポレーション | リソソーム蓄積性疾患と関連する神経学的症状を処置するための方法 |
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