BR112020019111A2 - Derivados de imidazolidin-2-ona substituída como inibidores de prmt5 - Google Patents

Info

Publication number

BR112020019111A2

BR112020019111A2 BR112020019111-6A BR112020019111A BR112020019111A2 BR 112020019111 A2 BR112020019111 A2 BR 112020019111A2 BR 112020019111 A BR112020019111 A BR 112020019111A BR 112020019111 A2 BR112020019111 A2 BR 112020019111A2

Authority

BR

Brazil

Prior art keywords

methyl

hydroxypropyl

dihydroisoquinolin

imidazolidin

pyridin

Prior art date

2018-03-22

Links

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• 102100034607 Protein arginine N-methyltransferase 5 Human genes 0.000 title claims description 74
• 239000003112 inhibitor Substances 0.000 title abstract description 60
• 101710084427 Protein arginine N-methyltransferase 5 Proteins 0.000 title 1
• YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical class O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims abstract description 180
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• -1 -NReRf Chemical group 0.000 claims description 394
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 157
• 125000000217 alkyl group Chemical group 0.000 claims description 128
• 239000001257 hydrogen Substances 0.000 claims description 85
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 82
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• 125000005843 halogen group Chemical group 0.000 claims description 57
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 48
• 125000003545 alkoxy group Chemical group 0.000 claims description 46
• 125000001072 heteroaryl group Chemical group 0.000 claims description 46
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 39
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 33
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
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• 125000001188 haloalkyl group Chemical group 0.000 claims description 29
• 125000003118 aryl group Chemical group 0.000 claims description 28
• 125000005842 heteroatom Chemical group 0.000 claims description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
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• 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
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• 125000001424 substituent group Chemical group 0.000 claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
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• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 19
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• 125000000304 alkynyl group Chemical group 0.000 claims description 17
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• IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 claims description 13
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• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
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• VLQUMXQISVRXIY-AREMUKBSSA-N 1-[[6-(1-acetylpiperidin-4-yl)pyridin-3-yl]methyl]-3-[(2R)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]imidazolidin-2-one Chemical compound C(C)(=O)N1CCC(CC1)C1=CC=C(C=N1)CN1C(N(CC1)C[C@@H](CN1CC2=CC=CC=C2CC1)O)=O VLQUMXQISVRXIY-AREMUKBSSA-N 0.000 claims description 3
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• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
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• ASDSUYBUNFWGDS-MUUNZHRXSA-N 1-[(2R)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-3-[[5-[1-(2H-triazol-4-ylmethyl)piperidin-4-yl]pyridin-2-yl]methyl]imidazolidin-2-one Chemical compound O[C@@H](CN1CCN(CC2=NC=C(C=C2)C2CCN(CC3=CNN=N3)CC2)C1=O)CN1CCC2=C(C1)C=CC=C2 ASDSUYBUNFWGDS-MUUNZHRXSA-N 0.000 claims description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
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• AVSAARZNYRHBBA-RUZDIDTESA-N 4-[6-[[3-[(2R)-3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropyl]-2-oxoimidazolidin-1-yl]methyl]pyridin-3-yl]-1-methylpyridin-2-one Chemical compound Cn1ccc(cc1=O)-c1ccc(CN2CCN(C[C@H](O)CN3CCc4ccccc4C3)C2=O)nc1 AVSAARZNYRHBBA-RUZDIDTESA-N 0.000 claims 1
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