BR112021010842A2 - Derivados de 2-oxoquinazolina como inibidores de metionina adenosiltransferase 2a - Google Patents
Derivados de 2-oxoquinazolina como inibidores de metionina adenosiltransferase 2a Download PDFInfo
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- BR112021010842A2 BR112021010842A2 BR112021010842-4A BR112021010842A BR112021010842A2 BR 112021010842 A2 BR112021010842 A2 BR 112021010842A2 BR 112021010842 A BR112021010842 A BR 112021010842A BR 112021010842 A2 BR112021010842 A2 BR 112021010842A2
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- Brazil
- Prior art keywords
- heterocyclyl
- cycloalkyl
- amino
- alkyl
- heteroaryl
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- 101000947881 Homo sapiens S-adenosylmethionine synthase isoform type-2 Proteins 0.000 title claims abstract description 26
- 102100035947 S-adenosylmethionine synthase isoform type-2 Human genes 0.000 title claims abstract description 25
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title abstract description 50
- 239000003112 inhibitor Substances 0.000 title abstract description 5
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- 102100034187 S-methyl-5'-thioadenosine phosphorylase Human genes 0.000 claims abstract description 44
- 238000000034 method Methods 0.000 claims abstract description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 24
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- -1 cyano, amino Chemical group 0.000 claims description 747
- 125000000623 heterocyclic group Chemical group 0.000 claims description 355
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 234
- 125000001072 heteroaryl group Chemical group 0.000 claims description 228
- 125000001188 haloalkyl group Chemical group 0.000 claims description 184
- 150000003839 salts Chemical class 0.000 claims description 177
- 125000005843 halogen group Chemical group 0.000 claims description 157
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 153
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 142
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 136
- 125000003545 alkoxy group Chemical group 0.000 claims description 135
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 129
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 126
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 125
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 121
- 125000003118 aryl group Chemical group 0.000 claims description 97
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 93
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 89
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 81
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- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 79
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 60
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 50
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 49
- 125000003342 alkenyl group Chemical group 0.000 claims description 47
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- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 37
- 239000011737 fluorine Chemical group 0.000 claims description 36
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 32
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 32
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 30
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 29
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 29
- 229910052794 bromium Inorganic materials 0.000 claims description 29
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 29
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 28
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- 125000005241 heteroarylamino group Chemical group 0.000 claims description 27
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 27
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- 125000005122 aminoalkylamino group Chemical group 0.000 claims description 26
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 26
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- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 25
- 229910052703 rhodium Inorganic materials 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 23
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 22
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- 125000005345 deuteroalkyl group Chemical group 0.000 claims description 21
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- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 19
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- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 18
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 18
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 18
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- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims description 17
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- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 13
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 13
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- 125000002098 pyridazinyl group Chemical group 0.000 claims description 13
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- 125000001544 thienyl group Chemical group 0.000 claims description 13
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
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- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
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- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 9
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000001246 bromo group Chemical group Br* 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 8
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- 101150102751 mtap gene Proteins 0.000 claims description 8
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 8
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 7
- 230000014509 gene expression Effects 0.000 claims description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 7
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Classifications
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
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- A61P35/02—Antineoplastic agents specific for leukemia
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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| PCT/US2019/065260 WO2020123395A1 (en) | 2018-12-10 | 2019-12-09 | 2-oxoquinazoline derivatives as methionine adenosyltransferase 2a inhibitors |
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| US12398140B2 (en) | 2019-02-13 | 2025-08-26 | Ptc Therapeutics, Inc. | Substituted pyrrolo [2,3-d]pyrimidines for treating familial dysautonomia |
| EA202192170A1 (ru) | 2019-02-13 | 2021-11-15 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | ТИЕНО[3,2-b]ПИРИДИН-7-АМИНОВЫЕ СОЕДИНЕНИЯ ДЛЯ ЛЕЧЕНИЯ СЕМЕЙНОЙ ВЕГЕТО-СОСУДИСТОЙ ДИСТОНИИ |
| CN115485025A (zh) * | 2020-02-28 | 2022-12-16 | 雷密克斯医疗公司 | 用于调节剪接的化合物和方法 |
| US20240208965A1 (en) * | 2020-06-10 | 2024-06-27 | Ideaya Biosciences, Inc. | Heteroaryl alkylene substituted 2-oxoquinazoline derivatives as methionine adenosyltransferase 2a inhibitors |
| CR20220644A (es) * | 2020-06-22 | 2023-02-17 | Hoffmann La Roche | Derivados de sulfona |
| WO2021259815A1 (en) * | 2020-06-22 | 2021-12-30 | F. Hoffmann-La Roche Ag | Amidopyrimidone derivatives |
| WO2021254529A1 (zh) * | 2020-07-14 | 2021-12-23 | 江苏先声药业有限公司 | 双环类化合物 |
| WO2022056307A1 (en) | 2020-09-11 | 2022-03-17 | Mirati Therapeutics, Inc. | Crystalline forms of a kras g12c inhibitor |
| CN115960099A (zh) * | 2020-09-24 | 2023-04-14 | 上海凌达生物医药有限公司 | 一类芳环或芳基杂环并吡啶酮类化合物、药物组合物及其应用 |
| CN116507624A (zh) | 2020-11-20 | 2023-07-28 | 美国安进公司 | 制备7-氯-6-氟-1-(2-异丙基-4-甲基吡啶-3-基)吡啶并f[2,3-d]嘧啶-2,4(1h,3h)-二酮的方法 |
| WO2022132200A1 (en) * | 2020-12-15 | 2022-06-23 | Mirati Therapeutics, Inc. | Azaquinazoline pan-kras inhibitors |
| EP4262803A4 (en) | 2020-12-16 | 2025-03-12 | Mirati Therapeutics, Inc. | Tetrahydropyridopyrimidine pan-kras inhibitors |
| WO2022143864A1 (zh) | 2020-12-31 | 2022-07-07 | 江苏先声药业有限公司 | 三环类化合物及用途 |
| CN115141202A (zh) * | 2021-03-29 | 2022-10-04 | 武汉人福创新药物研发中心有限公司 | 嘧啶并吡嗪酮化合物及其用途 |
| WO2022222911A1 (zh) * | 2021-04-19 | 2022-10-27 | 武汉人福创新药物研发中心有限公司 | 嘧啶酮化合物及其用途 |
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