JPWO2022026629A5 - - Google Patents

Info

Publication number

JPWO2022026629A5

JPWO2022026629A5 JP2023505923A JP2023505923A JPWO2022026629A5 JP WO2022026629 A5 JPWO2022026629 A5 JP WO2022026629A5 JP 2023505923 A JP2023505923 A JP 2023505923A JP 2023505923 A JP2023505923 A JP 2023505923A JP WO2022026629 A5 JPWO2022026629 A5 JP WO2022026629A5

Authority

JP

Japan

Prior art keywords

lys

substituted

pharma

solvate

acceptable salt

Prior art date

2024-07-16

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.)

Pending

Links

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• 150000003839 salts Chemical class 0.000 claims description 188
• 239000012453 solvate Substances 0.000 claims description 188
• XJOTXKZIRSHZQV-RXHOOSIZSA-N (3S)-3-amino-4-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S,3S)-1-[[(1R,6R,12R,17R,20S,23S,26R,31R,34R,39R,42S,45S,48S,51S,59S)-51-(4-aminobutyl)-31-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]-20-benzyl-23-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-48-(hydroxymethyl)-42-(1H-imidazol-4-ylmethyl)-59-(2-methylsulfanylethyl)-7,10,19,22,25,33,40,43,46,49,52,54,57,60,63,64-hexadecaoxo-3,4,14,15,28,29,36,37-octathia-8,11,18,21,24,32,41,44,47,50,53,55,58,61,62,65-hexadecazatetracyclo[32.19.8.26,17.212,39]pentahexacontan-26-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical class CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1cnc[nH]1)NC3=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N2)C(=O)NCC(=O)N4)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJOTXKZIRSHZQV-RXHOOSIZSA-N 0.000 claims description 179
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 57
• -1 pentafluoro Chemical group 0.000 claims description 20
• 150000001413 amino acids Chemical class 0.000 claims description 18
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 16
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 8
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 8
• 125000005336 allyloxy group Chemical group 0.000 claims description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
• 125000003963 dichloro group Chemical group Cl* 0.000 claims description 8
• 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 8
• PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 150000003852 triazoles Chemical class 0.000 claims description 7
• 150000003951 lactams Chemical class 0.000 claims description 6
• 125000003118 aryl group Chemical group 0.000 claims description 5
• 125000001589 carboacyl group Chemical group 0.000 claims description 5
• IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 claims description 4
• RWLSBXBFZHDHHX-VIFPVBQESA-N (2s)-2-(naphthalen-2-ylamino)propanoic acid Chemical compound C1=CC=CC2=CC(N[C@@H](C)C(O)=O)=CC=C21 RWLSBXBFZHDHHX-VIFPVBQESA-N 0.000 claims description 4
• CNMAQBJBWQQZFZ-LURJTMIESA-N (2s)-2-(pyridin-2-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CC=N1 CNMAQBJBWQQZFZ-LURJTMIESA-N 0.000 claims description 4
• PECGVEGMRUZOML-AWEZNQCLSA-N (2s)-2-amino-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C([C@H](N)C(O)=O)C1=CC=CC=C1 PECGVEGMRUZOML-AWEZNQCLSA-N 0.000 claims description 4
• XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims description 4
• HIDODKLFTVMWQL-ZCFIWIBFSA-N 3-[(2r)-pyrrolidin-1-ium-2-yl]propanoate Chemical compound OC(=O)CC[C@H]1CCCN1 HIDODKLFTVMWQL-ZCFIWIBFSA-N 0.000 claims description 4
• PECYZEOJVXMISF-REOHCLBHSA-N 3-amino-L-alanine Chemical compound [NH3+]C[C@H](N)C([O-])=O PECYZEOJVXMISF-REOHCLBHSA-N 0.000 claims description 4
• HIDODKLFTVMWQL-UHFFFAOYSA-N 3-pyrrolidin-1-ium-2-ylpropanoate Chemical compound OC(=O)CCC1CCCN1 HIDODKLFTVMWQL-UHFFFAOYSA-N 0.000 claims description 4
• UMSXVMNFSBMABN-SSDOTTSWSA-N 4-[(2r)-pyrrolidin-2-yl]butanoic acid Chemical compound OC(=O)CCC[C@@H]1CCCN1 UMSXVMNFSBMABN-SSDOTTSWSA-N 0.000 claims description 4
• UMSXVMNFSBMABN-UHFFFAOYSA-N 4-pyrrolidin-2-ylbutanoic acid Chemical compound OC(=O)CCCC1CCCN1 UMSXVMNFSBMABN-UHFFFAOYSA-N 0.000 claims description 4
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 4
• XUJNEKJLAYXESH-UHFFFAOYSA-N Cysteine Chemical compound SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 4
• ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical group OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 claims description 4
• COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 claims description 4
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical group CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 claims description 4
• 244000137850 Marrubium vulgare Species 0.000 claims description 4
• CZCIKBSVHDNIDH-NSHDSACASA-N N(alpha)-methyl-L-tryptophan Chemical group C1=CC=C2C(C[C@H]([NH2+]C)C([O-])=O)=CNC2=C1 CZCIKBSVHDNIDH-NSHDSACASA-N 0.000 claims description 4
• CZCIKBSVHDNIDH-UHFFFAOYSA-N Nalpha-methyl-DL-tryptophan Natural products C1=CC=C2C(CC(NC)C(O)=O)=CNC2=C1 CZCIKBSVHDNIDH-UHFFFAOYSA-N 0.000 claims description 4
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 4
• JCZLABDVDPYLRZ-AWEZNQCLSA-N biphenylalanine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1C1=CC=CC=C1 JCZLABDVDPYLRZ-AWEZNQCLSA-N 0.000 claims description 4
• 229910052739 hydrogen Inorganic materials 0.000 claims description 4
• 239000001257 hydrogen Substances 0.000 claims description 4
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• SEWIYICDCVPBEW-UHFFFAOYSA-N methyl glutamate Chemical compound COC(=O)C(N)CCC(O)=O SEWIYICDCVPBEW-UHFFFAOYSA-N 0.000 claims description 4
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 4
• COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 4
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 4
• 229960004799 tryptophan Drugs 0.000 claims description 4
• 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 4
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 2
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 2
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 2
• 229960003104 ornithine Drugs 0.000 claims description 2
• 238000000034 method Methods 0.000 description 11
• 125000000217 alkyl group Chemical group 0.000 description 10
• 239000008194 pharmaceutical composition Substances 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• DTERQYGMUDWYAZ-UHFFFAOYSA-N N-acetyl-N-thioacetyl-Lysine Natural products CC(=O)NCCCCC(N)C(O)=O DTERQYGMUDWYAZ-UHFFFAOYSA-N 0.000 description 8
• 201000010099 disease Diseases 0.000 description 6
• 239000002253 acid Substances 0.000 description 5
• 108060003558 hepcidin Proteins 0.000 description 5
• 102000018511 hepcidin Human genes 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 3
• 229940066919 hepcidin Drugs 0.000 description 3
• 230000010438 iron metabolism Effects 0.000 description 3
• 102000040430 polynucleotide Human genes 0.000 description 3
• 108091033319 polynucleotide Proteins 0.000 description 3
• 239000002157 polynucleotide Substances 0.000 description 3
• 108091006976 SLC40A1 Proteins 0.000 description 2
• 125000003282 alkyl amino group Chemical group 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
• 208000018565 Hemochromatosis Diseases 0.000 description 1
• 101000999322 Homo sapiens Putative insulin-like growth factor 2 antisense gene protein Proteins 0.000 description 1
• 206010065973 Iron Overload Diseases 0.000 description 1
• 102100036485 Putative insulin-like growth factor 2 antisense gene protein Human genes 0.000 description 1
• 208000002903 Thalassemia Diseases 0.000 description 1
• 208000017733 acquired polycythemia vera Diseases 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 230000008482 dysregulation Effects 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 125000001072 heteroaryl group Chemical group 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• BBJIPMIXTXKYLZ-UHFFFAOYSA-N isoglutamic acid Chemical group OC(=O)CC(N)CC(O)=O BBJIPMIXTXKYLZ-UHFFFAOYSA-N 0.000 description 1
• GLZWNFNQMJAZGY-UHFFFAOYSA-N octaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCOCCOCCO GLZWNFNQMJAZGY-UHFFFAOYSA-N 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 208000037244 polycythemia vera Diseases 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• PSVXZQVXSXSQRO-UHFFFAOYSA-N undecaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO PSVXZQVXSXSQRO-UHFFFAOYSA-N 0.000 description 1
• 230000008016 vaporization Effects 0.000 description 1
• 238000009834 vaporization Methods 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1