JPWO2019233941A5 - - Google Patents
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- JPWO2019233941A5 JPWO2019233941A5 JP2020567772A JP2020567772A JPWO2019233941A5 JP WO2019233941 A5 JPWO2019233941 A5 JP WO2019233941A5 JP 2020567772 A JP2020567772 A JP 2020567772A JP 2020567772 A JP2020567772 A JP 2020567772A JP WO2019233941 A5 JPWO2019233941 A5 JP WO2019233941A5
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- JP
- Japan
- Prior art keywords
- methyl
- amino
- pyrazino
- tetrahydro
- carbonitrile
- Prior art date
- 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
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- 150000001875 compounds Chemical class 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 10
- IODLXTMPCJEECR-RSGGTXFJSA-N 5-[(4R,10bS)-8-[(3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@H]2N1CC3=C2C=CC(=C3)N4C[C@H]([C@@H](C4)O)N)C5=C6C=CC=NC6=C(C=C5)C#N IODLXTMPCJEECR-RSGGTXFJSA-N 0.000 claims description 4
- IZNJCGCCGDJMIO-RUQDXMQKSA-N 5-[(4R,10bS)-8-[(3R,4R)-3-amino-4-methoxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(C[C@H]([C@@H](C1)OC)N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 IZNJCGCCGDJMIO-RUQDXMQKSA-N 0.000 claims description 4
- CIIFKVFOVFJZDM-UHFFFAOYSA-N quinoline-8-carbonitrile Chemical compound C1=CN=C2C(C#N)=CC=CC2=C1 CIIFKVFOVFJZDM-UHFFFAOYSA-N 0.000 claims description 3
- XCJJRXBASIIHNX-FMHBECPCSA-N (4R,10bS)-2-(8-chloroquinolin-5-yl)-N-[(3S,4R)-4-fluoropyrrolidin-3-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-8-amine Chemical compound [C@H]1(F)[C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=C3C(=C(C=C2)Cl)N=CC=C3)CNC1 XCJJRXBASIIHNX-FMHBECPCSA-N 0.000 claims description 2
- VUYAUAUTWXXEBF-FLNQWHAFSA-N (4R,10bS)-N-[(3S,4R)-4-fluoropyrrolidin-3-yl]-4-methyl-2-(8-methylquinolin-5-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-8-amine Chemical compound [C@H]1(F)[C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C)C3=NC=CC=C23)CNC1 VUYAUAUTWXXEBF-FLNQWHAFSA-N 0.000 claims description 2
- BMQNJIOLKPNBOB-BMWHPICZSA-N (4R,10bS)-N-[(3S,4R)-4-fluoropyrrolidin-3-yl]-4-methyl-2-(8-methylquinoxalin-5-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-8-amine Chemical compound [C@H]1(F)[C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=C3C(=C(C)C=C2)N=CC=N3)CNC1 BMQNJIOLKPNBOB-BMWHPICZSA-N 0.000 claims description 2
- WXKZCGQJPLRPBD-POHZVDBMSA-N (4R,10bS)-N-[(3S,4R)-4-fluoropyrrolidin-3-yl]-4-methyl-2-[8-(trifluoromethyl)quinoxalin-5-yl]-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-8-amine Chemical compound [C@H]1(F)[C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C(F)(F)F)C3=NC=CN=C23)CNC1 WXKZCGQJPLRPBD-POHZVDBMSA-N 0.000 claims description 2
- KGBZFVXVBATRNF-IQGLISFBSA-N 4-[(4R,10bS)-4-methyl-8-(5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound C1NCC2(OC1)CN(C2)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2 KGBZFVXVBATRNF-IQGLISFBSA-N 0.000 claims description 2
- WXIBHIPEEQNYNY-PIXOLUOSSA-N 4-[(4R,10bS)-4-methyl-8-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound C12OC(CN(C1)C1=CC=C3[C@H]4CN(C[C@H](N4CC3=C1)C)C1=CC=C(C#N)N3C1=CC=N3)CNC2 WXIBHIPEEQNYNY-PIXOLUOSSA-N 0.000 claims description 2
- VCYJITKLZWIEFD-QJMRKGMQSA-N 4-[(4R,10bS)-4-methyl-8-[(3R)-3-methylpiperazin-1-yl]-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound C[C@@H]1CN(C[C@H]2N1CC1=CC(=CC=C21)N2C[C@H](NCC2)C)C=2C=1N(C(=CC2)C#N)N=CC1 VCYJITKLZWIEFD-QJMRKGMQSA-N 0.000 claims description 2
- GJOKQLBCRDCZMU-MZNJEOGPSA-N 4-[(4R,10bS)-4-methyl-8-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N1(CCNCC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2 GJOKQLBCRDCZMU-MZNJEOGPSA-N 0.000 claims description 2
- ZWRUTSVWAXRQGY-IQGLISFBSA-N 4-[(4R,10bS)-8-(4-amino-4-methylpiperidin-1-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound C1(N)(CCN(CC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2)C ZWRUTSVWAXRQGY-IQGLISFBSA-N 0.000 claims description 2
- YBYMWPQXDFQOIC-LJXNEXSDSA-N 4-[(4R,10bS)-8-[(3R)-3-amino-3-methylpyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound [C@]1(N)(C)CN(CC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2 YBYMWPQXDFQOIC-LJXNEXSDSA-N 0.000 claims description 2
- WJBYTTQLYNYMLF-BUKPSGGLSA-N 4-[(4R,10bS)-8-[(3R)-3-aminopyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound C1CN(C[C@@H]1N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2 WJBYTTQLYNYMLF-BUKPSGGLSA-N 0.000 claims description 2
- WQXYVFNOBDDWNB-LGZMKHIYSA-N 4-[(4R,10bS)-8-[(3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1CN(C[C@H]1O)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1 WQXYVFNOBDDWNB-LGZMKHIYSA-N 0.000 claims description 2
- HJIBOJRSGWDLFJ-SDXDBNRQSA-N 4-[(4R,10bS)-8-[(3R,4R)-3-amino-4-methoxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-3-fluoropyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1CN(C[C@H]1OC)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1F HJIBOJRSGWDLFJ-SDXDBNRQSA-N 0.000 claims description 2
- MNWQYMQUKDJVHS-CYFQLWIMSA-N 4-[(4R,10bS)-8-[(3R,4R)-3-amino-4-methoxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1CN(C[C@H]1OC)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1 MNWQYMQUKDJVHS-CYFQLWIMSA-N 0.000 claims description 2
- FINOZXRXSNAVLA-YIVRPQLRSA-N 4-[(4R,10bS)-8-[(3R,4R)-4-amino-3-hydroxy-3-methylpyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@H]1[C@](CN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1)(C)O FINOZXRXSNAVLA-YIVRPQLRSA-N 0.000 claims description 2
- VFGSOXDITYVSLP-AACVKEQHSA-N 4-[(4R,10bS)-8-[(3R,4R)-4-amino-3-methoxypiperidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound C1CN(C[C@H]([C@@H]1N)OC)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2 VFGSOXDITYVSLP-AACVKEQHSA-N 0.000 claims description 2
- FYHREBOKFLBRAX-DINKTKQASA-N 4-[(4R,10bS)-8-[(3R,4S)-3-amino-4-fluoropyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1CN(C[C@@H]1F)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1 FYHREBOKFLBRAX-DINKTKQASA-N 0.000 claims description 2
- VFGSOXDITYVSLP-RDGSPMQLSA-N 4-[(4R,10bS)-8-[(3R,4S)-4-amino-3-methoxypiperidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1[C@@H](CN(CC1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1)OC VFGSOXDITYVSLP-RDGSPMQLSA-N 0.000 claims description 2
- WQXYVFNOBDDWNB-RIJOHQFPSA-N 4-[(4R,10bS)-8-[(3S,4S)-3-amino-4-hydroxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound [C@H]1(O)CN(C[C@@H]1N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2 WQXYVFNOBDDWNB-RIJOHQFPSA-N 0.000 claims description 2
- MNWQYMQUKDJVHS-JQRXQXTESA-N 4-[(4R,10bS)-8-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound CO[C@H]1CN(C[C@@H]1N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)N2C1=CC=N2 MNWQYMQUKDJVHS-JQRXQXTESA-N 0.000 claims description 2
- MSENQUSJLMKPFQ-SBEIQJPNSA-N 4-[(4R,10bS)-8-[(3S,4S)-4-amino-3-hydroxy-3-methylpyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-3-fluoropyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1[C@@](CN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1F)(C)O MSENQUSJLMKPFQ-SBEIQJPNSA-N 0.000 claims description 2
- FINOZXRXSNAVLA-AMKSYCFISA-N 4-[(4R,10bS)-8-[(3S,4S)-4-amino-3-hydroxy-3-methylpyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1[C@@](CN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1)(C)O FINOZXRXSNAVLA-AMKSYCFISA-N 0.000 claims description 2
- KEYIRIVAOVZYTK-RAWGQGSESA-N 4-[(4R,10bS)-8-[(6R)-6-amino-1,4-oxazepan-4-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N[C@@H]1CN(CCOC1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C=3C=1N(C(=CC3)C#N)N=CC1 KEYIRIVAOVZYTK-RAWGQGSESA-N 0.000 claims description 2
- YEOLVMMEBPKULH-CIIINLIZSA-N 4-[(4R,10bS)-8-[[(3S,4R)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound [C@H]1(F)[C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)N3C2=CC=N3)CNC1 YEOLVMMEBPKULH-CIIINLIZSA-N 0.000 claims description 2
- GJFFVYGPVOUSJN-UHFFFAOYSA-N 5-(8-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl)quinoline-8-carbonitrile Chemical compound C1N(CCNC1)C1=CC=C2C3CN(CCN3CC2=C1)C1=CC=C(C#N)C2=NC=CC=C12 GJFFVYGPVOUSJN-UHFFFAOYSA-N 0.000 claims description 2
- FUGQVIKQJHFXAJ-IQGLISFBSA-N 5-[(4R,10bS)-4-methyl-7-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1CN(CCN1)C1=C2C(=CC=C1)[C@H]1CN(C[C@H](N1C2)C)C1=CC=C(C#N)C2=NC=CC=C12 FUGQVIKQJHFXAJ-IQGLISFBSA-N 0.000 claims description 2
- KFYWKQVOYOLNSX-UVWOLYCHSA-N 5-[(4R,10bS)-4-methyl-8-(1,4-oxazepan-6-ylamino)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1COCC(NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)C3=NC=CC=C23)CN1 KFYWKQVOYOLNSX-UVWOLYCHSA-N 0.000 claims description 2
- FDIVMIYSWNDEGF-NFQMXDRXSA-N 5-[(4R,10bS)-4-methyl-8-(2-morpholin-4-ylethylamino)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@H]2N1CC1=CC(=CC=C21)NCCN2CCOCC2)C2=C1C=CC=NC1=C(C=C2)C#N FDIVMIYSWNDEGF-NFQMXDRXSA-N 0.000 claims description 2
- MCNPETFOZCFSER-GRHAOBRKSA-N 5-[(4R,10bS)-4-methyl-8-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@H]2N1CC1=CC(=CC=C21)N2CC1COCC(C2)N1)C1=C2C=CC=NC2=C(C=C1)C#N MCNPETFOZCFSER-GRHAOBRKSA-N 0.000 claims description 2
- YUSSXJOISVXBCD-XCFYXVKUSA-N 5-[(4R,10bS)-4-methyl-8-(5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-2-deuterioquinoline-8-carbonitrile Chemical compound [2H]C1=NC2=C(C=CC(=C2C=C1)N3C[C@H](N4CC5=C([C@H]4C3)C=CC(=C5)N6CC7(C6)CNCCO7)C)C#N YUSSXJOISVXBCD-XCFYXVKUSA-N 0.000 claims description 2
- YUSSXJOISVXBCD-NIYFSFCBSA-N 5-[(4R,10bS)-4-methyl-8-(5-oxa-2,8-diazaspiro[3.5]nonan-2-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1COC2(CN(C2)C2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)C3=NC=CC=C23)CN1 YUSSXJOISVXBCD-NIYFSFCBSA-N 0.000 claims description 2
- IHNRRPXBYJZHDT-NIYFSFCBSA-N 5-[(4R,10bS)-4-methyl-8-(5-oxa-2,8-diazaspiro[3.5]nonan-8-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N(CC2(OC1)CNC2)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(=C(C=C1)C#N)N=CC=C2 IHNRRPXBYJZHDT-NIYFSFCBSA-N 0.000 claims description 2
- WODFHOAQDJLMTC-NIYFSFCBSA-N 5-[(4R,10bS)-4-methyl-8-(6-methyl-2,6-diazaspiro[3.3]heptan-2-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(CC2(C1)CN(C2)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12)C WODFHOAQDJLMTC-NIYFSFCBSA-N 0.000 claims description 2
- ZGYPXHAHIWLLAW-FUDSMUEISA-N 5-[(4R,10bS)-4-methyl-8-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-2-deuterioquinoline-8-carbonitrile Chemical compound [2H]C1=NC2=C(C=CC(=C2C=C1)N3C[C@H](N4CC5=C([C@H]4C3)C=CC(=C5)N6CC7CNCC(C6)O7)C)C#N ZGYPXHAHIWLLAW-FUDSMUEISA-N 0.000 claims description 2
- ZGYPXHAHIWLLAW-ATAZYPGZSA-N 5-[(4R,10bS)-4-methyl-8-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O1C2CN(CC1CNC2)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 ZGYPXHAHIWLLAW-ATAZYPGZSA-N 0.000 claims description 2
- ZBUAVGQJZANEJQ-UVWOLYCHSA-N 5-[(4R,10bS)-4-methyl-8-(morpholin-3-ylmethylamino)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@H]2N1CC1=CC(=CC=C21)NCC2NCCOC2)C2=C1C=CC=NC1=C(C=C2)C#N ZBUAVGQJZANEJQ-UVWOLYCHSA-N 0.000 claims description 2
- DCYVKDHFBSFDBY-IQGLISFBSA-N 5-[(4R,10bS)-4-methyl-8-(piperazine-1-carbonyl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(C(=O)C2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)C3=NC=CC=C23)CCNCC1 DCYVKDHFBSFDBY-IQGLISFBSA-N 0.000 claims description 2
- WMPBXWPBPBSNLK-NDKUEENFSA-N 5-[(4R,10bS)-4-methyl-8-[[(2R)-morpholin-2-yl]methylamino]-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1NC[C@@H](OC1)CNC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 WMPBXWPBPBSNLK-NDKUEENFSA-N 0.000 claims description 2
- WMPBXWPBPBSNLK-QGUBCYKSSA-N 5-[(4R,10bS)-4-methyl-8-[[(2S)-morpholin-2-yl]methylamino]-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CCO[C@@H](C1)CNC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 WMPBXWPBPBSNLK-QGUBCYKSSA-N 0.000 claims description 2
- IGODMOIOXXMMNE-NDKUEENFSA-N 5-[(4R,10bS)-4-methyl-8-[[(3R)-piperidin-3-yl]amino]-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1C[C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)C3=NC=CC=C23)CNC1 IGODMOIOXXMMNE-NDKUEENFSA-N 0.000 claims description 2
- KFYWKQVOYOLNSX-NDKUEENFSA-N 5-[(4R,10bS)-4-methyl-8-[[(6R)-1,4-oxazepan-6-yl]amino]-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CCOC[C@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)C3=NC=CC=C23)C1 KFYWKQVOYOLNSX-NDKUEENFSA-N 0.000 claims description 2
- KFYWKQVOYOLNSX-QGUBCYKSSA-N 5-[(4R,10bS)-4-methyl-8-[[(6S)-1,4-oxazepan-6-yl]amino]-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CCOC[C@H](C1)NC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 KFYWKQVOYOLNSX-QGUBCYKSSA-N 0.000 claims description 2
- NQLIADGFQLAFRR-IQGLISFBSA-N 5-[(4R,10bS)-4-methyl-8-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(CCNCC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 NQLIADGFQLAFRR-IQGLISFBSA-N 0.000 claims description 2
- UJSRRFUJIISXHE-WXTAPIANSA-N 5-[(4R,10bS)-4-methyl-8-piperidin-4-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1(CCNCC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 UJSRRFUJIISXHE-WXTAPIANSA-N 0.000 claims description 2
- HDLRJAKJTMAZIT-WXJXEWBDSA-N 5-[(4R,10bS)-7-[2-[(3S)-3-hydroxypyrrolidin-1-yl]ethylamino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(CN(CC1)CCNC1=C2CN3[C@H](CN(C[C@H]3C)C3=CC=C(C#N)C4=NC=CC=C34)C2=CC=C1)O HDLRJAKJTMAZIT-WXJXEWBDSA-N 0.000 claims description 2
- YEWDPAICCGZGOE-BPFDRDFASA-N 5-[(4R,10bS)-7-[[(3S,4R)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound F[C@H]1[C@H](CNC1)NC1=C2CN3[C@@H](C2=CC=C1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N YEWDPAICCGZGOE-BPFDRDFASA-N 0.000 claims description 2
- BWAVJEPJPMFIKI-IQGLISFBSA-N 5-[(4R,10bS)-8-(1,6-diazaspiro[3.3]heptan-6-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CCC12CN(C2)C=2C=C1CN3[C@@H](C1=CC2)CN(C[C@H]3C)C3=C2C=CC=NC2=C(C=C3)C#N BWAVJEPJPMFIKI-IQGLISFBSA-N 0.000 claims description 2
- DSKHUNJNZPMWPY-IQGLISFBSA-N 5-[(4R,10bS)-8-(2,6-diazaspiro[3.3]heptan-2-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N(CC12CNC2)C=2C=C1CN3[C@@H](C1=CC2)CN(C[C@H]3C)C3=C2C=CC=NC2=C(C=C3)C#N DSKHUNJNZPMWPY-IQGLISFBSA-N 0.000 claims description 2
- PGHDESCWVDSOOA-CRICUBBOSA-N 5-[(4R,10bS)-8-(2,6-diazaspiro[3.3]heptan-2-yl)-9-fluoro-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N(CC12CNC2)C=2C=C1CN3[C@@H](C1=CC2F)CN(C[C@H]3C)C3=C2C=CC=NC2=C(C=C3)C#N PGHDESCWVDSOOA-CRICUBBOSA-N 0.000 claims description 2
- FMKLASALOBGCFV-PDQLQIGBSA-N 5-[(4R,10bS)-8-(3,4a,5,6,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazin-4-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O1C2C(N(CC1)C1=CC=C3[C@H]4CN(C[C@H](N4CC3=C1)C)C1=CC=C(C#N)C3=NC=CC=C13)CNC2 FMKLASALOBGCFV-PDQLQIGBSA-N 0.000 claims description 2
- ZFDFLPBUWCAUSH-ATAZYPGZSA-N 5-[(4R,10bS)-8-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(C(=O)C2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=C3C(=C(C=C2)C#N)N=CC=C3)CC2CCC(N2)C1 ZFDFLPBUWCAUSH-ATAZYPGZSA-N 0.000 claims description 2
- UUZRMUCIPQFCHX-FTLMHOBCSA-N 5-[(4R,10bS)-8-(3-amino-3-methylazetidin-1-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-2-deuterioquinoline-8-carbonitrile Chemical compound [2H]C1=NC2=C(C=CC(=C2C=C1)N3C[C@H](N4CC5=C([C@H]4C3)C=CC(=C5)N6CC(C6)(C)N)C)C#N UUZRMUCIPQFCHX-FTLMHOBCSA-N 0.000 claims description 2
- UUZRMUCIPQFCHX-MZNJEOGPSA-N 5-[(4R,10bS)-8-(3-amino-3-methylazetidin-1-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound NC1(CN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)C UUZRMUCIPQFCHX-MZNJEOGPSA-N 0.000 claims description 2
- GCTLDHVCMCVXLH-VOIUYBSRSA-N 5-[(4R,10bS)-8-(3-aminoazetidin-1-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(CC(C1)N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(=C(C=C1)C#N)N=CC=C2 GCTLDHVCMCVXLH-VOIUYBSRSA-N 0.000 claims description 2
- STWJRRQLEOCSIF-LJWPGGNMSA-N 5-[(4R,10bS)-8-(3a-methoxy-1,2,3,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CC2CN(CC2(OC)C1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 STWJRRQLEOCSIF-LJWPGGNMSA-N 0.000 claims description 2
- UGXKIKNPBWJCSR-NIYFSFCBSA-N 5-[(4R,10bS)-8-(4-amino-4-methylpiperidin-1-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1(C)(CCN(CC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(N=CC=C2)=C(C#N)C=C1)N UGXKIKNPBWJCSR-NIYFSFCBSA-N 0.000 claims description 2
- LFEFENQRIMJHAO-NIYFSFCBSA-N 5-[(4R,10bS)-8-(4-amino-4-methylpiperidine-1-carbonyl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(C(=O)C2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=C3C(=C(C=C2)C#N)N=CC=C3)CCC(C)(N)CC1 LFEFENQRIMJHAO-NIYFSFCBSA-N 0.000 claims description 2
- DWWIMSCULKQDMB-BGDRAHPGSA-N 5-[(4R,10bS)-8-(5-amino-2-oxa-7-azaspiro[3.4]octan-7-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1OCC21CN(CC2N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(N=CC=C2)=C(C#N)C=C1 DWWIMSCULKQDMB-BGDRAHPGSA-N 0.000 claims description 2
- ZGCGVSFDKHYMAR-QYXRORFCSA-N 5-[(4R,10bS)-8-(6-amino-1,4-oxazepan-4-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1OCCN(CC1N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(=C(C=C1)C#N)N=CC=C2 ZGCGVSFDKHYMAR-QYXRORFCSA-N 0.000 claims description 2
- RIJJJVIFAIEUPI-UVWOLYCHSA-N 5-[(4R,10bS)-8-(6-hydroxy-1,4-diazepan-1-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N(CC(O)CNC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 RIJJJVIFAIEUPI-UVWOLYCHSA-N 0.000 claims description 2
- OXNSUQUKUVJATB-GPGZCZDWSA-N 5-[(4R,10bS)-8-(6-hydroxy-6-methyl-1,4-diazepan-1-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1NCCN(CC1(C)O)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 OXNSUQUKUVJATB-GPGZCZDWSA-N 0.000 claims description 2
- PZQRPNMBTICEBQ-VOIUYBSRSA-N 5-[(4R,10bS)-8-(azetidin-3-yl)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CC(C1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 PZQRPNMBTICEBQ-VOIUYBSRSA-N 0.000 claims description 2
- XCLLBSFSZAOMFX-VOIUYBSRSA-N 5-[(4R,10bS)-8-(azetidin-3-ylamino)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1C(CN1)NC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 XCLLBSFSZAOMFX-VOIUYBSRSA-N 0.000 claims description 2
- XQZGIEIZVANHLM-VOIUYBSRSA-N 5-[(4R,10bS)-8-(azetidin-3-yloxy)-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CC(C1)OC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N XQZGIEIZVANHLM-VOIUYBSRSA-N 0.000 claims description 2
- ALMUMLFGDBCSAM-PLEUHSGWSA-N 5-[(4R,10bS)-8-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carbonyl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@@H]12N(C[C@@H](NC1)C2)C(=O)C=2C=C1CN3[C@@H](C1=CC2)CN(C[C@H]3C)C3=C2C=CC=NC2=C(C=C3)C#N ALMUMLFGDBCSAM-PLEUHSGWSA-N 0.000 claims description 2
- YRMGRJXCUVNFTI-NDKUEENFSA-N 5-[(4R,10bS)-8-[(2R)-2-(hydroxymethyl)piperazin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(CCNC[C@@H]1CO)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(=C(C=C1)C#N)N=CC=C2 YRMGRJXCUVNFTI-NDKUEENFSA-N 0.000 claims description 2
- YRMGRJXCUVNFTI-QGUBCYKSSA-N 5-[(4R,10bS)-8-[(2S)-2-(hydroxymethyl)piperazin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1CCN([C@@H](C1)CO)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 YRMGRJXCUVNFTI-QGUBCYKSSA-N 0.000 claims description 2
- IYFORPLQFVIIJV-MZNJEOGPSA-N 5-[(4R,10bS)-8-[(3-fluoroazetidin-3-yl)methylamino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound FC1(CNC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=C3C(=C(C=C2)C#N)N=CC=C3)CNC1 IYFORPLQFVIIJV-MZNJEOGPSA-N 0.000 claims description 2
- UOBSUMRIORRZQK-RAKYAITLSA-N 5-[(4R,10bS)-8-[(3R)-3-(methoxymethyl)piperazin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N(C[C@@H](NC1)COC)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 UOBSUMRIORRZQK-RAKYAITLSA-N 0.000 claims description 2
- FMUPCLHMFYHEOG-FLPMJASOSA-N 5-[(4R,10bS)-8-[(3R)-3-aminopyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1CN(C[C@@H]1N)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 FMUPCLHMFYHEOG-FLPMJASOSA-N 0.000 claims description 2
- ZEJVZMSPGGTZRZ-KHRGITBJSA-N 5-[(4R,10bS)-8-[(3R,4R)-3-amino-4-fluoropyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(CN(C[C@H]1F)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12)N ZEJVZMSPGGTZRZ-KHRGITBJSA-N 0.000 claims description 2
- NCDGOROIOUEVHZ-RUQDXMQKSA-N 5-[(4R,10bS)-8-[(3R,4R)-3-hydroxy-4-(methylamino)pyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@H]2N1CC1=CC(=CC=C21)N2C[C@H]([C@@H](C2)NC)O)C2=C1C=CC=NC1=C(C=C2)C#N NCDGOROIOUEVHZ-RUQDXMQKSA-N 0.000 claims description 2
- JWUMZZJGIPNRGA-YGHZRGPQSA-N 5-[(4R,10bS)-8-[(3R,4R)-4-amino-3-hydroxy-3-methylpyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N[C@H]1[C@](CN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)(C)O JWUMZZJGIPNRGA-YGHZRGPQSA-N 0.000 claims description 2
- JFSVAISMOVUTDY-ZGBKXNSBSA-N 5-[(4R,10bS)-8-[(3R,4R)-4-amino-3-hydroxy-3-methylpyrrolidin-1-yl]-9-fluoro-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N[C@H]1[C@](CN(C1)C=1C=C2CN3[C@@H](C2=CC1F)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)(C)O JFSVAISMOVUTDY-ZGBKXNSBSA-N 0.000 claims description 2
- ZEJVZMSPGGTZRZ-KIOVBMKUSA-N 5-[(4R,10bS)-8-[(3R,4S)-3-amino-4-fluoropyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N(C[C@@H]([C@@H]1N)F)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 ZEJVZMSPGGTZRZ-KIOVBMKUSA-N 0.000 claims description 2
- IZNJCGCCGDJMIO-KJNDHEABSA-N 5-[(4R,10bS)-8-[(3R,4S)-3-amino-4-methoxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N[C@@H]1CN(C[C@@H]1OC)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N IZNJCGCCGDJMIO-KJNDHEABSA-N 0.000 claims description 2
- INPWGJCZPLTLFH-JJHGTGHCSA-N 5-[(4R,10bS)-8-[(3S)-3-(hydroxymethyl)piperazin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(CO)NCCN(C1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 INPWGJCZPLTLFH-JJHGTGHCSA-N 0.000 claims description 2
- ZEJVZMSPGGTZRZ-YARGXFNKSA-N 5-[(4R,10bS)-8-[(3S,4R)-3-amino-4-fluoropyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N[C@H]1CN(C[C@H]1F)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N ZEJVZMSPGGTZRZ-YARGXFNKSA-N 0.000 claims description 2
- ZEJVZMSPGGTZRZ-BCZIVGSGSA-N 5-[(4R,10bS)-8-[(3S,4S)-3-amino-4-fluoropyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1([C@@H](N)CN(C1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12)F ZEJVZMSPGGTZRZ-BCZIVGSGSA-N 0.000 claims description 2
- IODLXTMPCJEECR-MZGXNLLNSA-N 5-[(4R,10bS)-8-[(3S,4S)-3-amino-4-hydroxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(N)CN(C[C@@H]1O)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 IODLXTMPCJEECR-MZGXNLLNSA-N 0.000 claims description 2
- IZNJCGCCGDJMIO-ZTNKVBRBSA-N 5-[(4R,10bS)-8-[(3S,4S)-3-amino-4-methoxypyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O(C)[C@@H]1[C@@H](N)CN(C1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(=C(C#N)C=C1)N=CC=C2 IZNJCGCCGDJMIO-ZTNKVBRBSA-N 0.000 claims description 2
- NCDGOROIOUEVHZ-ZTNKVBRBSA-N 5-[(4R,10bS)-8-[(3S,4S)-3-hydroxy-4-(methylamino)pyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(O)CN(C[C@@H]1NC)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 NCDGOROIOUEVHZ-ZTNKVBRBSA-N 0.000 claims description 2
- JWUMZZJGIPNRGA-YZAQAPLFSA-N 5-[(4R,10bS)-8-[(3S,4S)-4-amino-3-hydroxy-3-methylpyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N[C@@H]1[C@@](CN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)(C)O JWUMZZJGIPNRGA-YZAQAPLFSA-N 0.000 claims description 2
- JFSVAISMOVUTDY-AUROACQKSA-N 5-[(4R,10bS)-8-[(3S,4S)-4-amino-3-hydroxy-3-methylpyrrolidin-1-yl]-9-fluoro-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N[C@@H]1[C@@](CN(C1)C=1C=C2CN3[C@@H](C2=CC1F)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)(C)O JFSVAISMOVUTDY-AUROACQKSA-N 0.000 claims description 2
- ZIKLHKYXYUEXNX-MZGXNLLNSA-N 5-[(4R,10bS)-8-[(3S,4S)-4-fluoropyrrolidin-3-yl]oxy-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound F[C@@H]1[C@H](CNC1)OC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N ZIKLHKYXYUEXNX-MZGXNLLNSA-N 0.000 claims description 2
- GHBMRNDTFJEJFB-IDYIBUKASA-N 5-[(4R,10bS)-8-[(4aR,7aR)-3,4,4a,5,7,7a-hexahydro-2H-pyrrolo[3,4-b][1,4]oxazin-6-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N[C@@H]2CN(C[C@H]2OC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 GHBMRNDTFJEJFB-IDYIBUKASA-N 0.000 claims description 2
- ZGCGVSFDKHYMAR-KAWPREARSA-N 5-[(4R,10bS)-8-[(6R)-6-amino-1,4-oxazepan-4-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1[C@@H](CN(CCO1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(=C(C=C1)C#N)N=CC=C2)N ZGCGVSFDKHYMAR-KAWPREARSA-N 0.000 claims description 2
- RIJJJVIFAIEUPI-NDKUEENFSA-N 5-[(4R,10bS)-8-[(6R)-6-hydroxy-1,4-diazepan-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O[C@@H]1CNCCN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N RIJJJVIFAIEUPI-NDKUEENFSA-N 0.000 claims description 2
- OXNSUQUKUVJATB-WHPKCEERSA-N 5-[(4R,10bS)-8-[(6R)-6-hydroxy-6-methyl-1,4-diazepan-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@]1(O)(CNCCN(C1)C1=CC2=C(C=C1)[C@H]1CN(C[C@H](N1C2)C)C1=CC=C(C#N)C2=NC=CC=C12)C OXNSUQUKUVJATB-WHPKCEERSA-N 0.000 claims description 2
- ZGCGVSFDKHYMAR-JJHGTGHCSA-N 5-[(4R,10bS)-8-[(6S)-6-amino-1,4-oxazepan-4-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1[C@H](CN(CCO1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12)N ZGCGVSFDKHYMAR-JJHGTGHCSA-N 0.000 claims description 2
- RIJJJVIFAIEUPI-QGUBCYKSSA-N 5-[(4R,10bS)-8-[(6S)-6-hydroxy-1,4-diazepan-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O[C@H]1CNCCN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N RIJJJVIFAIEUPI-QGUBCYKSSA-N 0.000 claims description 2
- OXNSUQUKUVJATB-YPLOMLCWSA-N 5-[(4R,10bS)-8-[(6S)-6-hydroxy-6-methyl-1,4-diazepan-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O[C@]1(CNCCN(C1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)C OXNSUQUKUVJATB-YPLOMLCWSA-N 0.000 claims description 2
- CCCDSOYAGIVCTL-NDKUEENFSA-N 5-[(4R,10bS)-8-[(8aR)-3-oxo-1,5,6,7,8,8a-hexahydroimidazo[1,5-a]pyrazin-2-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1N2[C@H](CNC1)CN(C2=O)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 CCCDSOYAGIVCTL-NDKUEENFSA-N 0.000 claims description 2
- CCCDSOYAGIVCTL-QGUBCYKSSA-N 5-[(4R,10bS)-8-[(8aS)-3-oxo-1,5,6,7,8,8a-hexahydroimidazo[1,5-a]pyrazin-2-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound C1CN2[C@@H](CN1)CN(C2=O)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 CCCDSOYAGIVCTL-QGUBCYKSSA-N 0.000 claims description 2
- WRPRDHGWPUYOGK-IQGLISFBSA-N 5-[(4R,10bS)-8-[2-(dimethylamino)ethoxy]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N(C)(CCOC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12)C WRPRDHGWPUYOGK-IQGLISFBSA-N 0.000 claims description 2
- JFEHETRXVVCYRB-IQGLISFBSA-N 5-[(4R,10bS)-8-[2-(dimethylamino)ethylamino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N(C)(CCNC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12)C JFEHETRXVVCYRB-IQGLISFBSA-N 0.000 claims description 2
- GYGAEXAYPLDHNR-VQEMNGCCSA-N 5-[(4R,10bS)-8-[2-[(3S)-3-hydroxypyrrolidin-1-yl]ethylamino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O[C@@H]1CN(CC1)CCNC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N GYGAEXAYPLDHNR-VQEMNGCCSA-N 0.000 claims description 2
- LEISOXCKBFWOMM-QNQPXHJKSA-N 5-[(4R,10bS)-8-[3-amino-3-(hydroxymethyl)pyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound NC1(CN(CC1)C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)CO LEISOXCKBFWOMM-QNQPXHJKSA-N 0.000 claims description 2
- XTOLQGLYWVWXJK-SXFZBGDPSA-N 5-[(4R,10bS)-8-[[(2S,4S)-4-fluoropyrrolidin-2-yl]methoxy]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound F[C@H]1C[C@H](NC1)COC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N XTOLQGLYWVWXJK-SXFZBGDPSA-N 0.000 claims description 2
- BBBAOFQXWOYKQC-QLQMMUPBSA-N 5-[(4R,10bS)-8-[[(2S,4S)-4-fluoropyrrolidin-2-yl]methylamino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound F[C@H]1C[C@H](NC1)CNC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N BBBAOFQXWOYKQC-QLQMMUPBSA-N 0.000 claims description 2
- SGWZDBKSFDZSOM-KHRGITBJSA-N 5-[(4R,10bS)-8-[[(3R,4R)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(F)[C@@H](CNC1)NC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 SGWZDBKSFDZSOM-KHRGITBJSA-N 0.000 claims description 2
- XYVNBHDETOTRPB-IDYIBUKASA-N 5-[(4R,10bS)-8-[[(3R,4R)-4-methoxypyrrolidin-3-yl]amino]-4,9-dimethyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O(C)[C@H]1[C@@H](CNC1)NC1=C(C)C=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 XYVNBHDETOTRPB-IDYIBUKASA-N 0.000 claims description 2
- ABGKUCIYNDVTGH-RUQDXMQKSA-N 5-[(4R,10bS)-8-[[(3R,4R)-4-methoxypyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound CO[C@H]1[C@@H](CNC1)NC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N ABGKUCIYNDVTGH-RUQDXMQKSA-N 0.000 claims description 2
- SGWZDBKSFDZSOM-KIOVBMKUSA-N 5-[(4R,10bS)-8-[[(3R,4S)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1([C@@H](CNC1)NC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12)F SGWZDBKSFDZSOM-KIOVBMKUSA-N 0.000 claims description 2
- ABGKUCIYNDVTGH-KJNDHEABSA-N 5-[(4R,10bS)-8-[[(3R,4S)-4-methoxypyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(CNC[C@@H]1OC)NC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 ABGKUCIYNDVTGH-KJNDHEABSA-N 0.000 claims description 2
- DSHVDOFOLAGTOG-YLMCOQJISA-N 5-[(4R,10bS)-8-[[(3S,4R)-3-methoxypiperidin-4-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound O(C)[C@H]1CNCC[C@H]1NC1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C2=NC=CC=C12 DSHVDOFOLAGTOG-YLMCOQJISA-N 0.000 claims description 2
- SGWZDBKSFDZSOM-COUFWFNFSA-N 5-[(4R,10bS)-8-[[(3S,4R)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-2-deuterioquinoline-8-carbonitrile Chemical compound [2H]C1=NC2=C(C=CC(=C2C=C1)N3C[C@H](N4CC5=C([C@H]4C3)C=CC(=C5)N[C@H]6CNC[C@H]6F)C)C#N SGWZDBKSFDZSOM-COUFWFNFSA-N 0.000 claims description 2
- SGWZDBKSFDZSOM-YARGXFNKSA-N 5-[(4R,10bS)-8-[[(3S,4R)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound F[C@H]1[C@H](CNC1)NC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N SGWZDBKSFDZSOM-YARGXFNKSA-N 0.000 claims description 2
- ABGKUCIYNDVTGH-WWSLDTRNSA-N 5-[(4R,10bS)-8-[[(3S,4R)-4-methoxypyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound CO[C@H]1[C@H](CNC1)NC=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N ABGKUCIYNDVTGH-WWSLDTRNSA-N 0.000 claims description 2
- SGWZDBKSFDZSOM-BCZIVGSGSA-N 5-[(4R,10bS)-8-[[(3S,4S)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1([C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)C3=NC=CC=C23)CNC1)F SGWZDBKSFDZSOM-BCZIVGSGSA-N 0.000 claims description 2
- NSVQEBGSTFNDFI-ODOWTIOMSA-N 5-[(4R,10bS)-8-[[(3S,4S)-4-methoxypyrrolidin-3-yl]-methylamino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound CO[C@@H]1[C@H](CNC1)N(C=1C=C2CN3[C@@H](C2=CC1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)C NSVQEBGSTFNDFI-ODOWTIOMSA-N 0.000 claims description 2
- ABGKUCIYNDVTGH-ZTNKVBRBSA-N 5-[(4R,10bS)-8-[[(3S,4S)-4-methoxypyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound [C@H]1(NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=CC=C(C#N)C3=NC=CC=C23)CNC[C@@H]1OC ABGKUCIYNDVTGH-ZTNKVBRBSA-N 0.000 claims description 2
- BHZXDZPKIXZZJZ-XBXZGVGYSA-N 5-[(4R,10bS)-9-fluoro-4-methyl-8-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound FC1=C(C=C2CN3[C@@H](C2=C1)CN(C[C@H]3C)C3=C1C=CC=NC1=C(C=C3)C#N)N3CC1CNCC(C3)O1 BHZXDZPKIXZZJZ-XBXZGVGYSA-N 0.000 claims description 2
- NQLIADGFQLAFRR-BVZFJXPGSA-N 5-[(4S,10bR)-4-methyl-8-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N1(CCNCC1)C1=CC2=C(C=C1)[C@H]1N(C2)[C@H](CN(C1)C1=CC=C(C#N)C2=NC=CC=C12)C NQLIADGFQLAFRR-BVZFJXPGSA-N 0.000 claims description 2
- LQZJUWWESWCREX-UHFFFAOYSA-N 7-(8-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl)-1,3-benzothiazole-4-carbonitrile Chemical compound C1CN(CCN1)C1=CC=C2C3CN(CCN3CC2=C1)C1=CC=C(C#N)C=2N=CSC1=2 LQZJUWWESWCREX-UHFFFAOYSA-N 0.000 claims description 2
- LYGGEQNHUXHWCK-POHZVDBMSA-N 7-[(4R,10bS)-8-[[(3S,4R)-4-fluoropyrrolidin-3-yl]amino]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-1,3-benzothiazole-4-carbonitrile Chemical compound [C@H]1(F)[C@@H](NC2=CC=C3[C@H]4CN(C[C@H](N4CC3=C2)C)C2=C3C(=C(C#N)C=C2)N=CS3)CNC1 LYGGEQNHUXHWCK-POHZVDBMSA-N 0.000 claims description 2
- LTJVVXUANVJFKG-UZUQRXQVSA-N 8-[(4R,10bS)-4-methyl-8-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoxaline-5-carbonitrile Chemical compound N1(CCNCC1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=C2C(=C(C=C1)C#N)N=CC=N2 LTJVVXUANVJFKG-UZUQRXQVSA-N 0.000 claims description 2
- -1 1,2,3,4,6,6a-hexahydropyrrolo[3,4-c]pyrrolyl Chemical group 0.000 claims 143
- 125000000217 alkyl group Chemical group 0.000 claims 79
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 42
- 125000003545 alkoxy group Chemical group 0.000 claims 25
- 125000003282 alkyl amino group Chemical group 0.000 claims 14
- 229910052736 halogen Inorganic materials 0.000 claims 14
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 14
- 125000001424 substituent group Chemical group 0.000 claims 14
- 150000002367 halogens Chemical class 0.000 claims 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 13
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 11
- 229910052805 deuterium Inorganic materials 0.000 claims 11
- 125000002393 azetidinyl group Chemical group 0.000 claims 9
- 125000004193 piperazinyl group Chemical group 0.000 claims 9
- 239000003054 catalyst Substances 0.000 claims 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 6
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- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 125000003386 piperidinyl group Chemical group 0.000 claims 6
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- 208000005777 Lupus Nephritis Diseases 0.000 claims 4
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 claims 4
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- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 4
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- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 claims 3
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 claims 3
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- 108010060818 Toll-Like Receptor 9 Proteins 0.000 claims 3
- 102100039390 Toll-like receptor 7 Human genes 0.000 claims 3
- 102100033110 Toll-like receptor 8 Human genes 0.000 claims 3
- 239000005557 antagonist Substances 0.000 claims 3
- 229910052739 hydrogen Inorganic materials 0.000 claims 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 150000004820 halides Chemical class 0.000 claims 2
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- KSMXPVOPWPDGKM-TYSKNPMGSA-N 5-[(4R,10bS)-8-[(3S,4S)-3-methoxy-4-(methylamino)pyrrolidin-1-yl]-4-methyl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]quinoline-8-carbonitrile Chemical compound N(C)[C@@H]1[C@@H](OC)CN(C1)C1=CC2=C(C=C1)[C@H]1CN(C[C@H](N1C2)C)C1=CC=C(C#N)C2=NC=CC=C12 KSMXPVOPWPDGKM-TYSKNPMGSA-N 0.000 claims 1
- 238000006443 Buchwald-Hartwig cross coupling reaction Methods 0.000 claims 1
- 238000006411 Negishi coupling reaction Methods 0.000 claims 1
- 238000006619 Stille reaction Methods 0.000 claims 1
- 238000006069 Suzuki reaction reaction Methods 0.000 claims 1
- 239000012445 acidic reagent Substances 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000005103 alkyl silyl group Chemical group 0.000 claims 1
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims 1
- 229910000024 caesium carbonate Inorganic materials 0.000 claims 1
- MXFYYFVVIIWKFE-UHFFFAOYSA-N dicyclohexyl-[2-[2,6-di(propan-2-yloxy)phenyl]phenyl]phosphane Chemical compound CC(C)OC1=CC=CC(OC(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 MXFYYFVVIIWKFE-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 1
- 125000000168 pyrrolyl group Chemical group 0.000 claims 1
- UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 claims 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- OKKXOCBVMQGWJJ-OPAMFIHVSA-N 7-[(4R,10bS)-4-methyl-8-piperazin-1-yl-3,4,6,10b-tetrahydro-1H-pyrazino[2,1-a]isoindol-2-yl]-1,3-benzothiazole-4-carbonitrile Chemical compound C1CN(CCN1)C1=CC=C2[C@H]3CN(C[C@H](N3CC2=C1)C)C1=CC=C(C#N)C=2N=CSC1=2 OKKXOCBVMQGWJJ-OPAMFIHVSA-N 0.000 description 1
- KIDIJBYYGAEULX-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine-7-carbonitrile Chemical compound N#CC1=CC=CC2=CC=NN12 KIDIJBYYGAEULX-UHFFFAOYSA-N 0.000 description 1
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| WO2021084022A1 (en) | 2019-10-31 | 2021-05-06 | F. Hoffmann-La Roche Ag | Hydropyrazino[1,2-d][1,4]diazepine compounds for the treatment of autoimmune disease |
| CN114728959B (zh) * | 2019-11-12 | 2024-11-12 | 豪夫迈·罗氏有限公司 | 用于治疗自身免疫性疾病的氢吡嗪并[1,2-b]异喹啉化合物 |
| US12503471B2 (en) | 2019-11-19 | 2025-12-23 | Hoffmann-La Roche Inc. | Triazatricycle compounds for the treatment of autoimmune disease |
| CN114728976B (zh) * | 2019-11-19 | 2024-08-16 | 豪夫迈·罗氏有限公司 | 用于治疗自身免疫性疾病的氢-1H-吡咯并[1,2-a]吡嗪化合物 |
| WO2021110614A1 (en) | 2019-12-03 | 2021-06-10 | F. Hoffmann-La Roche Ag | HYDROPYRIDO[1,2-α]PYRAZINE COMPOUNDS FOR THE TREATMENT OF AUTOIMMUNE DISEASE |
| US20240317735A1 (en) | 2020-07-14 | 2024-09-26 | Hoffmann-La Roche Inc. | Hydroisoquinoline or hydronaphthyridine compounds for the treatment of autoimmune disease |
| WO2022022489A1 (zh) * | 2020-07-27 | 2022-02-03 | 江苏恒瑞医药股份有限公司 | 吲哚稠环类衍生物、其制备方法及其在医药上的应用 |
| CN114057759B (zh) * | 2020-08-07 | 2023-05-16 | 江苏恒瑞医药股份有限公司 | 稠合四环类衍生物、其制备方法及其在医药上的应用 |
| AU2021385752A1 (en) * | 2020-11-26 | 2023-06-29 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Fused tricyclic compound, preparation method therefor and application thereof in medicine |
| WO2023025109A1 (zh) * | 2021-08-23 | 2023-03-02 | 上海维申医药有限公司 | 一类Toll样受体抑制剂及其制备和应用 |
| CN114656363A (zh) * | 2022-03-28 | 2022-06-24 | 南京林业大学 | 一种钯催化芳香酯类化合物的合成方法 |
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| US4273773A (en) | 1979-09-24 | 1981-06-16 | American Home Products Corporation | Antihypertensive tricyclic isoindole derivatives |
| BRPI0418127A (pt) | 2003-12-24 | 2007-04-27 | Biota Scient Management | uso de um composto, seus sais, e derivados farmaceuticamente aceitáveis dos mesmos, método para o tratamento de infecções envolvendo vìrus da sub-famìlia pneumovirinae, formulação farmacêutica, métodos para tratar mamìferos infectados e para prevenir a infecção de mamìferos com vìrus da sub-famìlia pneumovirinae, composto, seus sais, e derivados farmaceuticamente aceitáveis dos mesmos, composto e a forma n-óxido e sal piridìnio do mesmo, e, método de separação de enantiÈmeros de um composto |
| WO2011106276A1 (en) * | 2010-02-25 | 2011-09-01 | Merck Sharp & Dohme Corp. | Task channel antagonists |
| SG11201509520QA (en) | 2013-05-24 | 2015-12-30 | Janssen Sciences Ireland Uc | Pyridone derivatives for the treatment of viral infections and further diseases |
| JP6223563B2 (ja) | 2013-10-14 | 2017-11-01 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 選択的に置換されたキノリン化合物 |
| CN105636945B (zh) | 2013-10-14 | 2017-11-17 | 卫材R&D管理有限公司 | 选择性取代的喹啉化合物 |
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| SI3692040T1 (sl) | 2017-10-05 | 2023-05-31 | Glaxosmithkline Intellectual Property Development Limited | Kemijske spojine |
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-
2019
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- 2019-06-03 MX MX2020012827A patent/MX2020012827A/es unknown
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- 2019-06-03 SG SG11202011137SA patent/SG11202011137SA/en unknown
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- 2019-06-03 CA CA3098291A patent/CA3098291A1/en active Pending
- 2019-06-03 MA MA052747A patent/MA52747A/fr unknown
- 2019-06-03 PE PE2020001875A patent/PE20210131A1/es unknown
- 2019-06-03 CR CR20200584A patent/CR20200584A/es unknown
- 2019-06-03 WO PCT/EP2019/064323 patent/WO2019233941A1/en not_active Ceased
- 2019-06-03 KR KR1020207034855A patent/KR20210018818A/ko not_active Ceased
- 2019-06-03 CN CN201980035182.7A patent/CN112204028B/zh active Active
- 2019-06-03 AU AU2019280728A patent/AU2019280728A1/en not_active Abandoned
- 2019-06-04 TW TW108119369A patent/TW202016111A/zh unknown
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2020
- 2020-11-25 CL CL2020003065A patent/CL2020003065A1/es unknown
- 2020-11-26 CO CONC2020/0014677A patent/CO2020014677A2/es unknown
- 2020-12-01 IL IL279144A patent/IL279144A/en unknown
- 2020-12-04 PH PH12020552092A patent/PH12020552092A1/en unknown
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