KR20240009929A - Parp 억제제로서 치환된 융합 이환 화합물 및 이의 용도 - Google Patents

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Publication number

KR20240009929A

KR20240009929A KR1020237037924A KR20237037924A KR20240009929A KR 20240009929 A KR20240009929 A KR 20240009929A KR 1020237037924 A KR1020237037924 A KR 1020237037924A KR 20237037924 A KR20237037924 A KR 20237037924A KR 20240009929 A KR20240009929 A KR 20240009929A

Authority

KR

South Korea

Prior art keywords

methyl

ethyl

tetrahydroquinazolin

dioxo

piperazin

Prior art date

2021-04-12

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

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• 239000012661 PARP inhibitor Substances 0.000 title abstract description 20
• 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 title abstract description 20
• 125000002619 bicyclic group Chemical group 0.000 title abstract description 5
• 230000004927 fusion Effects 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 178
• 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims abstract description 29
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims abstract description 18
• 230000000694 effects Effects 0.000 claims abstract description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 238000011282 treatment Methods 0.000 claims abstract description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
• 201000011510 cancer Diseases 0.000 claims abstract description 13
• 230000005764 inhibitory process Effects 0.000 claims abstract description 13
• 239000003814 drug Substances 0.000 claims abstract description 12
• 201000010099 disease Diseases 0.000 claims abstract description 11
• 229940079593 drug Drugs 0.000 claims abstract description 11
• 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 claims abstract description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 207
• -1 alkoxy compound Chemical class 0.000 claims description 128
• 229910052736 halogen Inorganic materials 0.000 claims description 115
• 150000002367 halogens Chemical class 0.000 claims description 96
• 229910052739 hydrogen Inorganic materials 0.000 claims description 91
• 239000000203 mixture Substances 0.000 claims description 64
• 125000003545 alkoxy group Chemical group 0.000 claims description 59
• 125000001424 substituent group Chemical group 0.000 claims description 57
• 239000001257 hydrogen Substances 0.000 claims description 56
• 125000000623 heterocyclic group Chemical group 0.000 claims description 46
• 229910052799 carbon Inorganic materials 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 40
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 38
• 125000001072 heteroaryl group Chemical group 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 32
• IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 30
• 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 29
• 150000001204 N-oxides Chemical class 0.000 claims description 26
• 238000000034 method Methods 0.000 claims description 26
• 239000012453 solvate Substances 0.000 claims description 26
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
• 239000000651 prodrug Substances 0.000 claims description 23
• 229940002612 prodrug Drugs 0.000 claims description 23
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 18
• 125000002837 carbocyclic group Chemical group 0.000 claims description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
• 239000002246 antineoplastic agent Substances 0.000 claims description 16
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 14
• 125000004076 pyridyl group Chemical group 0.000 claims description 11
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 11
• 125000003107 substituted aryl group Chemical group 0.000 claims description 11
• 125000002947 alkylene group Chemical group 0.000 claims description 9
• 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 7
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 7
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• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 7
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• 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 6
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