JPWO2021257532A5 - - Google Patents

Info

Publication number

JPWO2021257532A5

JPWO2021257532A5 JP2022577319A JP2022577319A JPWO2021257532A5 JP WO2021257532 A5 JPWO2021257532 A5 JP WO2021257532A5 JP 2022577319 A JP2022577319 A JP 2022577319A JP 2022577319 A JP2022577319 A JP 2022577319A JP WO2021257532 A5 JPWO2021257532 A5 JP WO2021257532A5

Authority

JP

Japan

Prior art keywords

compound

mds

pharma

acceptable salt

ceutically acceptable

Prior art date

2024-06-28

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

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 claims description 93
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 36
• 150000003839 salts Chemical class 0.000 claims description 36
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
• 208000007502 anemia Diseases 0.000 claims description 15
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
• 208000020832 chronic kidney disease Diseases 0.000 claims description 9
• 206010058314 Dysplasia Diseases 0.000 claims description 8
• 208000020075 IRIDA syndrome Diseases 0.000 claims description 8
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 8
• 230000001419 dependent effect Effects 0.000 claims description 8
• 206010028537 myelofibrosis Diseases 0.000 claims description 8
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 6
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 6
• KPRPFTOLWQQUAV-OCVAFRRMSA-N 2-amino-N-(4-hydroxy-1-bicyclo[2.2.2]octanyl)-5-[4-[(1R,5S)-3-(oxan-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]phenyl]pyridine-3-carboxamide Chemical compound NC1=C(C(=O)NC23CCC(CC2)(CC3)O)C=C(C=N1)C1=CC=C(C=C1)[C@@]12CN(C[C@H]2C1)C1CCOCC1 KPRPFTOLWQQUAV-OCVAFRRMSA-N 0.000 claims description 6
• KPRPFTOLWQQUAV-UHFFFAOYSA-N 2-amino-N-(4-hydroxy-1-bicyclo[2.2.2]octanyl)-5-[4-[3-(oxan-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]phenyl]pyridine-3-carboxamide Chemical compound NC1=C(C(=O)NC23CCC(CC2)(CC3)O)C=C(C=N1)C1=CC=C(C=C1)C12CN(CC2C1)C1CCOCC1 KPRPFTOLWQQUAV-UHFFFAOYSA-N 0.000 claims description 6
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 6
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000001475 halogen functional group Chemical group 0.000 claims description 6
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
• 238000009097 single-agent therapy Methods 0.000 claims description 6
• KPRPFTOLWQQUAV-GXLPGVSKSA-N 2-amino-N-(4-hydroxy-1-bicyclo[2.2.2]octanyl)-5-[4-[(1S,5R)-3-(oxan-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]phenyl]pyridine-3-carboxamide Chemical compound Nc1ncc(cc1C(=O)NC12CCC(O)(CC1)CC2)-c1ccc(cc1)[C@]12C[C@H]1CN(C2)C1CCOCC1 KPRPFTOLWQQUAV-GXLPGVSKSA-N 0.000 claims description 5
• 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 compound 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 4
• 208000034578 Multiple myelomas Diseases 0.000 claims description 4
• 102000018511 hepcidin Human genes 0.000 claims description 4
• 229940066919 hepcidin Drugs 0.000 claims description 4
• 108060003558 hepcidin Proteins 0.000 claims description 4
• 201000000050 myeloid neoplasm Diseases 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims 19
• 238000000034 method Methods 0.000 claims 16
• 239000008177 pharmaceutical agent Substances 0.000 claims 7
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims 2
• 239000003814 drug Substances 0.000 claims 2
• 229960003966 nicotinamide Drugs 0.000 claims 1
• 235000005152 nicotinamide Nutrition 0.000 claims 1
• 239000011570 nicotinamide Substances 0.000 claims 1
• 125000003545 alkoxy group Chemical group 0.000 description 6
• 125000000217 alkyl group Chemical group 0.000 description 6