JP2019503337A5 - - Google Patents

Info

Publication number

JP2019503337A5

JP2019503337A5 JP2018522784A JP2018522784A JP2019503337A5 JP 2019503337 A5 JP2019503337 A5 JP 2019503337A5 JP 2018522784 A JP2018522784 A JP 2018522784A JP 2018522784 A JP2018522784 A JP 2018522784A JP 2019503337 A5 JP2019503337 A5 JP 2019503337A5

Authority

JP

Japan

Prior art keywords

methyl

compound

pharmaceutically acceptable

difluoromethyl

formula

Prior art date

2016-11-08

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
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 claims 24
• 238000006467 substitution reaction Methods 0.000 claims 9
• 125000004432 carbon atom Chemical group C* 0.000 claims 8
• -1 chloro, difluoromethyl Chemical group 0.000 claims 8
• 125000001424 substituent group Chemical group 0.000 claims 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 8
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 7
• 229910052739 hydrogen Inorganic materials 0.000 claims 6
• 239000001257 hydrogen Substances 0.000 claims 6
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 6
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 6
• 125000000217 alkyl group Chemical group 0.000 claims 5
• 229910052799 carbon Inorganic materials 0.000 claims 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims 4
• 239000008194 pharmaceutical composition Substances 0.000 claims 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
• 125000004076 pyridyl group Chemical group 0.000 claims 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims 3
• 239000002904 solvent Substances 0.000 claims 3
• 125000006509 3,4-difluorobenzyl group Chemical group [H]C1=C(F)C(F)=C([H])C(=C1[H])C([H])([H])* 0.000 claims 2
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 2
• 206010028980 Neoplasm Diseases 0.000 claims 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims 2
• 201000011510 cancer Diseases 0.000 claims 2
• 125000001153 fluoro group Chemical group F* 0.000 claims 2
• 238000000034 method Methods 0.000 claims 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
• 125000006239 protecting group Chemical group 0.000 claims 2
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 2
• HVIGNZUDBVLTLU-MRXNPFEDSA-N (6R)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one Chemical compound FC=1C=C(CN2C(C=3N(C[C@@H]2COC)C=C(N=3)C2=NC(=NC=C2C)NC2=CC=NN2C)=O)C=CC=1F HVIGNZUDBVLTLU-MRXNPFEDSA-N 0.000 claims 1
• SAVWHYNFWSMMCC-PKLMIRHRSA-N (6R)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one ethanesulfonic acid Chemical compound CCS(O)(=O)=O.COC[C@H]1Cn2cc(nc2C(=O)N1Cc1ccc(F)c(F)c1)-c1nc(Nc2ccnn2C)ncc1C SAVWHYNFWSMMCC-PKLMIRHRSA-N 0.000 claims 1
• MDDULEPFNKVNRJ-PKLMIRHRSA-N (6R)-7-[(3,4-difluorophenyl)methyl]-6-(methoxymethyl)-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one hexanedioic acid Chemical compound OC(=O)CCCCC(O)=O.COC[C@H]1Cn2cc(nc2C(=O)N1Cc1ccc(F)c(F)c1)-c1nc(Nc2ccnn2C)ncc1C MDDULEPFNKVNRJ-PKLMIRHRSA-N 0.000 claims 1
• FSSJOGPPVNJQGR-AWEZNQCLSA-N (6S)-7-[(3,5-difluorophenyl)methyl]-6-methyl-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one Chemical compound C[C@H]1CN2C=C(N=C2C(=O)N1CC1=CC(F)=CC(F)=C1)C1=C(C)C=NC(NC2=CC=NN2C)=N1 FSSJOGPPVNJQGR-AWEZNQCLSA-N 0.000 claims 1
• SGPPRSHLSJWWBC-AWEZNQCLSA-N (6S)-7-[(3-chlorophenyl)methyl]-6-methyl-2-[2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one Chemical compound ClC=1C=C(CN2C(C=3N(C[C@@H]2C)C=C(N=3)C2=NC(=NC=C2)NC2=CC=NN2C)=O)C=CC=1 SGPPRSHLSJWWBC-AWEZNQCLSA-N 0.000 claims 1
• NXDOCYPZIGXILP-AWEZNQCLSA-N (6S)-7-[[6-(difluoromethyl)pyridin-2-yl]methyl]-6-methyl-2-[5-methyl-2-[(2-methylpyrazol-3-yl)amino]pyrimidin-4-yl]-5,6-dihydroimidazo[1,2-a]pyrazin-8-one Chemical compound FC(C1=CC=CC(=N1)CN1C(C=2N(C[C@@H]1C)C=C(N=2)C1=NC(=NC=C1C)NC1=CC=NN1C)=O)F NXDOCYPZIGXILP-AWEZNQCLSA-N 0.000 claims 1
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
• 206010009944 Colon cancer Diseases 0.000 claims 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
• SCABJAMCNOWWAP-QGZVFWFLSA-N FC=1C=C(CN2C=C3N(C[C@@H]2COC)CC(=N3)C3=NC(=NC=C3C)NC3=CC=NN3C)C=CC1F Chemical compound FC=1C=C(CN2C=C3N(C[C@@H]2COC)CC(=N3)C3=NC(=NC=C3C)NC3=CC=NN3C)C=CC1F SCABJAMCNOWWAP-QGZVFWFLSA-N 0.000 claims 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
• 239000002253 acid Substances 0.000 claims 1
• 230000002378 acidificating effect Effects 0.000 claims 1
• 235000011037 adipic acid Nutrition 0.000 claims 1
• 239000001361 adipic acid Substances 0.000 claims 1
• 239000002246 antineoplastic agent Substances 0.000 claims 1
• 239000007864 aqueous solution Substances 0.000 claims 1
• 238000006243 chemical reaction Methods 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims 1
• 125000005843 halogen group Chemical group 0.000 claims 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims 1
• 239000000178 monomer Substances 0.000 claims 1
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 claims 1
• 201000002528 pancreatic cancer Diseases 0.000 claims 1
• 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
• 239000002243 precursor Substances 0.000 claims 1
• 230000002265 prevention Effects 0.000 claims 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1