HRP20201175T1 - Derivati 5-[2-(piridin-2-ilamino)-1,3-tiazol-5-il]-2,3-dihidro-1h-izoindol-1-ona i njihova upotreba kao dvostrukih inhibitora fosfatidilinozitola 3-kinaze delta i gama - Google Patents
Derivati 5-[2-(piridin-2-ilamino)-1,3-tiazol-5-il]-2,3-dihidro-1h-izoindol-1-ona i njihova upotreba kao dvostrukih inhibitora fosfatidilinozitola 3-kinaze delta i gama Download PDFInfo
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- HRP20201175T1 HRP20201175T1 HRP20201175TT HRP20201175T HRP20201175T1 HR P20201175 T1 HRP20201175 T1 HR P20201175T1 HR P20201175T T HRP20201175T T HR P20201175TT HR P20201175 T HRP20201175 T HR P20201175T HR P20201175 T1 HRP20201175 T1 HR P20201175T1
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- methyl
- pyridin
- dihydro
- thiazol
- amino
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- JTEFIQCSVCKGDP-UHFFFAOYSA-N 5-[2-(pyridin-2-ylamino)-1,3-thiazol-5-yl]-2,3-dihydroisoindol-1-one Chemical class N1=C(C=CC=C1)NC=1SC(=CN=1)C=1C=C2CNC(C2=CC=1)=O JTEFIQCSVCKGDP-UHFFFAOYSA-N 0.000 title 1
- 108091007960 PI3Ks Proteins 0.000 title 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 title 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 title 1
- 230000009977 dual effect Effects 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 13
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 150000003839 salts Chemical class 0.000 claims 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 5
- 125000005842 heteroatom Chemical group 0.000 claims 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 2
- BNXOEOMQSLPCKM-KRWDZBQOSA-N C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=CC=CC(=C2)N2CCCC2=O)S1 Chemical compound C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=CC=CC(=C2)N2CCCC2=O)S1 BNXOEOMQSLPCKM-KRWDZBQOSA-N 0.000 claims 2
- 239000005557 antagonist Substances 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 2
- 230000003637 steroidlike Effects 0.000 claims 2
- DHEKPZQWFVQYSO-DLBZAZTESA-N (2R)-N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-(methylsulfamoyl)-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-2-methoxy-N-methylpropanamide Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=CC=CC(=N1)N(C([C@@H](C)OC)=O)C)C)S(NC)(=O)=O)=O DHEKPZQWFVQYSO-DLBZAZTESA-N 0.000 claims 1
- DHEKPZQWFVQYSO-IRXDYDNUSA-N (2S)-N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-(methylsulfamoyl)-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-2-methoxy-N-methylpropanamide Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=CC=CC(=N1)N(C([C@H](C)OC)=O)C)C)S(NC)(=O)=O)=O DHEKPZQWFVQYSO-IRXDYDNUSA-N 0.000 claims 1
- DMIIPYYADLDKAX-HNNXBMFYSA-N 2-[(1S)-1-cyclopropylethyl]-5-[4-methyl-2-[[6-(2-oxoimidazolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-3H-isoindol-1-one Chemical compound C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=NC(=CC=C2)N2CCNC2=O)S1 DMIIPYYADLDKAX-HNNXBMFYSA-N 0.000 claims 1
- ZSEKNBCKQHQTBI-INIZCTEOSA-N 2-[(1S)-1-cyclopropylethyl]-5-[4-methyl-2-[[6-(2-oxopiperazin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-3H-isoindol-1-one Chemical compound C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=NC(=CC=C2)N2CCNCC2=O)S1 ZSEKNBCKQHQTBI-INIZCTEOSA-N 0.000 claims 1
- SFTPPASPRIXXIN-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-5-[4-methyl-2-[[6-(2-oxopiperidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-3H-isoindol-1-one Chemical compound C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=NC(=CC=C2)N2CCCCC2=O)S1 SFTPPASPRIXXIN-KRWDZBQOSA-N 0.000 claims 1
- KVKANZTYGYFKQY-INIZCTEOSA-N 2-[(1S)-1-cyclopropylethyl]-5-[4-methyl-2-[[6-(3-methyl-2-oxoimidazolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-3H-isoindol-1-one Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(N(CC1)C)=O)C)S(=O)(=O)C)=O KVKANZTYGYFKQY-INIZCTEOSA-N 0.000 claims 1
- RQZYVAOSDVOURA-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-(3,3-dimethyl-2-oxopiperazin-1-yl)pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(C(NCC1)(C)C)=O)C RQZYVAOSDVOURA-KRWDZBQOSA-N 0.000 claims 1
- RQLVMAYHFPSXMR-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-(5,5-dimethyl-2-oxopiperazin-1-yl)pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CNC(C1)(C)C)=O)C RQLVMAYHFPSXMR-KRWDZBQOSA-N 0.000 claims 1
- IKNJUYUINPOVDE-OXJNMPFZSA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-[(2R)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1[C@H](CCC1=O)CO)C IKNJUYUINPOVDE-OXJNMPFZSA-N 0.000 claims 1
- IKNJUYUINPOVDE-JXFKEZNVSA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-[(2S)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1[C@@H](CCC1=O)CO)C IKNJUYUINPOVDE-JXFKEZNVSA-N 0.000 claims 1
- UCWFGTHMIDAVDE-HNAYVOBHSA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-[(3R)-3-hydroxy-2-oxopyrrolidin-1-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C([C@@H](CC1)O)=O)C UCWFGTHMIDAVDE-HNAYVOBHSA-N 0.000 claims 1
- UCWFGTHMIDAVDE-KXBFYZLASA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C([C@H](CC1)O)=O)C UCWFGTHMIDAVDE-KXBFYZLASA-N 0.000 claims 1
- IUKKLFSDRNELCN-HNAYVOBHSA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-[(4R)-4-hydroxy-2-oxopyrrolidin-1-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(C[C@H](C1)O)=O)C IUKKLFSDRNELCN-HNAYVOBHSA-N 0.000 claims 1
- RNKHOYDAZIEJFF-SFHVURJKSA-N 2-[(1S)-1-cyclopropylethyl]-6-[2-[[6-[4-(2-hydroxyethyl)-2-oxopiperazin-1-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CN(CC1)CCO)=O)C RNKHOYDAZIEJFF-SFHVURJKSA-N 0.000 claims 1
- JCXVWMWEFKRQCE-INIZCTEOSA-N 2-[(1S)-1-cyclopropylethyl]-6-[4-methyl-2-[[6-(2-oxo-1,3-oxazolidin-3-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-N-(oxetan-3-yl)-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC1COC1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(OCC1)=O)C JCXVWMWEFKRQCE-INIZCTEOSA-N 0.000 claims 1
- VFBCXKOMIUXVNH-INIZCTEOSA-N 2-[(1S)-1-cyclopropylethyl]-6-[4-methyl-2-[[6-(2-oxoimidazolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-N-(oxetan-3-yl)-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC1COC1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(NCC1)=O)C VFBCXKOMIUXVNH-INIZCTEOSA-N 0.000 claims 1
- XLRIOJGDWOEVMT-SFHVURJKSA-N 2-[(1S)-1-cyclopropylethyl]-6-[4-methyl-2-[[6-(2-oxopiperazin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-N-propan-2-yl-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC(C)C)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CNCC1)=O)C XLRIOJGDWOEVMT-SFHVURJKSA-N 0.000 claims 1
- BHFJVMZATJXYCO-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-6-[4-methyl-2-[[6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-N-(oxetan-3-yl)-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC1COC1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CCC1)=O)C BHFJVMZATJXYCO-KRWDZBQOSA-N 0.000 claims 1
- ZGQXHYGEONUMTE-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-N-(oxetan-3-yl)-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC1COC1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(COCC1)=O)C ZGQXHYGEONUMTE-KRWDZBQOSA-N 0.000 claims 1
- PZHYYDQKVVSTEG-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-N-ethyl-6-[4-methyl-2-[[6-(2-oxopiperazin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NCC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CNCC1)=O)C PZHYYDQKVVSTEG-KRWDZBQOSA-N 0.000 claims 1
- ZYJKXKZHIIVJEB-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-(2-oxo-1,4-diazepan-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CNCCC1)=O)C ZYJKXKZHIIVJEB-KRWDZBQOSA-N 0.000 claims 1
- ZWZBXYCUIUOCOO-INIZCTEOSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-(2-oxopiperazin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CNCC1)=O)C ZWZBXYCUIUOCOO-INIZCTEOSA-N 0.000 claims 1
- SMSOEZUYBOCTCT-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-(2-oxopiperidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CCCC1)=O)C SMSOEZUYBOCTCT-KRWDZBQOSA-N 0.000 claims 1
- FZLQVDKBOUEZHS-INIZCTEOSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(COCC1)=O)C FZLQVDKBOUEZHS-INIZCTEOSA-N 0.000 claims 1
- MFYQUMRHYXKIOO-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-(4-methyl-2-oxopiperazin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CN(CC1)C)=O)C MFYQUMRHYXKIOO-KRWDZBQOSA-N 0.000 claims 1
- QWPSEEVUQYTULG-KRWDZBQOSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-(7-oxo-1,4-diazepan-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1CCNCCC1=O)C QWPSEEVUQYTULG-KRWDZBQOSA-N 0.000 claims 1
- TYTHLOGWHWLWET-WBVHZDCISA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-[(2R)-2-methyl-6-oxopiperazin-1-yl]pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1[C@@H](CNCC1=O)C)C TYTHLOGWHWLWET-WBVHZDCISA-N 0.000 claims 1
- TYTHLOGWHWLWET-RDJZCZTQSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-[(2S)-2-methyl-6-oxopiperazin-1-yl]pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1[C@H](CNCC1=O)C)C TYTHLOGWHWLWET-RDJZCZTQSA-N 0.000 claims 1
- KRJCGMRLWBVONG-SJORKVTESA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-[(3R)-3-methyl-2-oxopiperazin-1-yl]pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C([C@H](NCC1)C)=O)C KRJCGMRLWBVONG-SJORKVTESA-N 0.000 claims 1
- KRJCGMRLWBVONG-IRXDYDNUSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-[(3S)-3-methyl-2-oxopiperazin-1-yl]pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C([C@@H](NCC1)C)=O)C KRJCGMRLWBVONG-IRXDYDNUSA-N 0.000 claims 1
- YXGZTQDPLYDOCC-WBVHZDCISA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-[(5R)-5-methyl-2-oxopiperazin-1-yl]pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CN[C@@H](C1)C)=O)C YXGZTQDPLYDOCC-WBVHZDCISA-N 0.000 claims 1
- YXGZTQDPLYDOCC-RDJZCZTQSA-N 2-[(1S)-1-cyclopropylethyl]-N-methyl-6-[4-methyl-2-[[6-[(5S)-5-methyl-2-oxopiperazin-1-yl]pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(CN[C@H](C1)C)=O)C YXGZTQDPLYDOCC-RDJZCZTQSA-N 0.000 claims 1
- AICUMEFERAKQDF-KRWDZBQOSA-N 2-[(2S)-3,3-dimethylbutan-2-yl]-N-methyl-6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound CC([C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(COCC1)=O)C)(C)C AICUMEFERAKQDF-KRWDZBQOSA-N 0.000 claims 1
- NDSSKUUMDINTDG-HNNXBMFYSA-N 2-[(2S)-butan-2-yl]-N-methyl-6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C[C@@H](CC)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(COCC1)=O)C NDSSKUUMDINTDG-HNNXBMFYSA-N 0.000 claims 1
- -1 2-oxopyrrolidin-1-yl Chemical group 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- LOYIOALZAFIRRM-UHFFFAOYSA-N 2-tert-butyl-N-methyl-6-[4-methyl-2-[[6-(2-oxo-1,3-oxazinan-3-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C(C)(C)(C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(OCCC1)=O)C LOYIOALZAFIRRM-UHFFFAOYSA-N 0.000 claims 1
- TWLBPEXRIJIDLQ-ZDUSSCGKSA-N 3-[6-[[4-methyl-5-[7-methylsulfonyl-1-oxo-2-[(2S)-1,1,1-trifluoropropan-2-yl]-3H-isoindol-5-yl]-1,3-thiazol-2-yl]amino]pyridin-2-yl]-1,3-oxazolidin-2-one Chemical compound C[C@H](N1Cc2cc(cc(c2C1=O)S(C)(=O)=O)-c1sc(Nc2cccc(n2)N2CCOC2=O)nc1C)C(F)(F)F TWLBPEXRIJIDLQ-ZDUSSCGKSA-N 0.000 claims 1
- VLRSVMBPXWKSNE-INIZCTEOSA-N 4-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-methylsulfonyl-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]morpholin-3-one Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(COCC1)=O)C)S(=O)(=O)C)=O VLRSVMBPXWKSNE-INIZCTEOSA-N 0.000 claims 1
- BMEVMMHSZQHXGB-ZDUSSCGKSA-N 5-[4-methyl-2-[[6-(2-oxoimidazolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-2-[(2S)-1,1,1-trifluoropropan-2-yl]-3H-isoindol-1-one Chemical compound CC=1N=C(SC=1C=1C=C2CN(C(C2=C(C=1)S(=O)(=O)C)=O)[C@H](C(F)(F)F)C)NC1=NC(=CC=C1)N1C(NCC1)=O BMEVMMHSZQHXGB-ZDUSSCGKSA-N 0.000 claims 1
- LLUGOCWVLNJQNI-AWEZNQCLSA-N 5-[4-methyl-2-[[6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-2-[(2S)-1,1,1-trifluoropropan-2-yl]-3H-isoindol-1-one Chemical compound CC=1N=C(SC=1C=1C=C2CN(C(C2=C(C=1)S(=O)(=O)C)=O)[C@H](C(F)(F)F)C)NC1=NC(=CC=C1)N1C(CCC1)=O LLUGOCWVLNJQNI-AWEZNQCLSA-N 0.000 claims 1
- ZAWKCTQNKKDNMQ-YJBOKZPZSA-N 6-[2-[[6-[(3S)-3-hydroxy-2-oxopyrrolidin-1-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-3-oxo-N-propan-2-yl-2-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-isoindole-4-sulfonamide Chemical compound O[C@@H]1C(N(CC1)C1=CC=CC(=N1)NC=1SC(=C(N=1)C)C=1C=C(C=2C(N(CC=2C=1)[C@H](C(F)(F)F)C)=O)S(=O)(=O)NC(C)C)=O ZAWKCTQNKKDNMQ-YJBOKZPZSA-N 0.000 claims 1
- KDYQDNYXUAAXIW-UWJYYQICSA-N 6-[2-[[6-[(8aS)-1,4-dioxo-6,7,8,8a-tetrahydro-3H-pyrrolo[1,2-a]pyrazin-2-yl]pyridin-2-yl]amino]-4-methyl-1,3-thiazol-5-yl]-2-[(1S)-1-cyclopropylethyl]-N-methyl-3-oxo-1H-isoindole-4-sulfonamide Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C([C@H]2N(C(C1)=O)CCC2)=O)C KDYQDNYXUAAXIW-UWJYYQICSA-N 0.000 claims 1
- TWMIPMSAUTYVGK-HNNXBMFYSA-N 6-[4-methyl-2-[[6-(2-oxoimidazolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-N-propan-2-yl-2-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-isoindole-4-sulfonamide Chemical compound CC=1N=C(SC=1C=1C=C(C=2C(N(CC=2C=1)[C@H](C(F)(F)F)C)=O)S(=O)(=O)NC(C)C)NC1=NC(=CC=C1)N1C(NCC1)=O TWMIPMSAUTYVGK-HNNXBMFYSA-N 0.000 claims 1
- VFRMCSHREULMEB-INIZCTEOSA-N 6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-N-propan-2-yl-2-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-isoindole-4-sulfonamide Chemical compound CC=1N=C(SC=1C=1C=C(C=2C(N(CC=2C=1)[C@H](C(F)(F)F)C)=O)S(=O)(=O)NC(C)C)NC1=NC(=CC=C1)N1C(COCC1)=O VFRMCSHREULMEB-INIZCTEOSA-N 0.000 claims 1
- HXALBTBBYYKFPZ-KRWDZBQOSA-N 6-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-methylsulfonyl-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-7H-pyrrolo[3,4-b]pyridin-5-one Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=CC=CC(=N1)N1CC2=NC=CC=C2C1=O)C)S(=O)(=O)C)=O HXALBTBBYYKFPZ-KRWDZBQOSA-N 0.000 claims 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims 1
- UUXKXNLWIZYSGT-KRWDZBQOSA-N C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC1COC1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(OCCC1)=O)C Chemical compound C1(CC1)[C@H](C)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC1COC1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(OCCC1)=O)C UUXKXNLWIZYSGT-KRWDZBQOSA-N 0.000 claims 1
- KFNBJCXUFADQNW-INIZCTEOSA-N CC=1N=C(SC=1C=1C=C(C=2C(N(CC=2C=1)[C@H](C(F)(F)F)C)=O)S(=O)(=O)NC(C)C)NC1=NC(=CC=C1)N1C(OCCC1)=O Chemical compound CC=1N=C(SC=1C=1C=C(C=2C(N(CC=2C=1)[C@H](C(F)(F)F)C)=O)S(=O)(=O)NC(C)C)NC1=NC(=CC=C1)N1C(OCCC1)=O KFNBJCXUFADQNW-INIZCTEOSA-N 0.000 claims 1
- PDUCWDNFFQBFEQ-INIZCTEOSA-N CNS(=O)(=O)C1=C2C(CN([C@@H](C)C3CC3)C2=O)=CC(=C1)C1=C(C)N=C(NC2=NC(=CC=C2)N2CCCS2(=O)=O)S1 Chemical compound CNS(=O)(=O)C1=C2C(CN([C@@H](C)C3CC3)C2=O)=CC(=C1)C1=C(C)N=C(NC2=NC(=CC=C2)N2CCCS2(=O)=O)S1 PDUCWDNFFQBFEQ-INIZCTEOSA-N 0.000 claims 1
- XCOQTFFMFTWVMC-INIZCTEOSA-N C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=NC(=CC=C2)N2CCCOC2=O)S1 Chemical compound C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=NC(=CC=C2)N2CCCOC2=O)S1 XCOQTFFMFTWVMC-INIZCTEOSA-N 0.000 claims 1
- NTZMWNKORQPPBL-HNNXBMFYSA-N C[C@@H](CC)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(OCCC1)=O)C Chemical compound C[C@@H](CC)N1CC=2C=C(C=C(C=2C1=O)S(=O)(=O)NC)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(OCCC1)=O)C NTZMWNKORQPPBL-HNNXBMFYSA-N 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims 1
- 102000003676 Glucocorticoid Receptors Human genes 0.000 claims 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 claims 1
- TZUURZCAUFJVTJ-KRWDZBQOSA-N N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-(ethylsulfamoyl)-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-2-methoxy-N-methylacetamide Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=CC=CC(=N1)N(C(COC)=O)C)C)S(NCC)(=O)=O)=O TZUURZCAUFJVTJ-KRWDZBQOSA-N 0.000 claims 1
- FLUPYHUXCIWKAE-KRWDZBQOSA-N N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-(methylsulfamoyl)-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-2-ethoxy-N-methylacetamide Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=CC=CC(=N1)N(C(COCC)=O)C)C)S(NC)(=O)=O)=O FLUPYHUXCIWKAE-KRWDZBQOSA-N 0.000 claims 1
- YAOHUGMVFAJBNE-INIZCTEOSA-N N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-(methylsulfamoyl)-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-2-methoxy-N-methylacetamide Chemical compound C1(CC1)[C@H](C)N1C(C2=C(C=C(C=C2C1)C1=C(N=C(S1)NC1=CC=CC(=N1)N(C(COC)=O)C)C)S(NC)(=O)=O)=O YAOHUGMVFAJBNE-INIZCTEOSA-N 0.000 claims 1
- WEMBXYLJGBGCSQ-HNNXBMFYSA-N N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-(methylsulfamoyl)-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-N-methylacetamide Chemical compound CNS(=O)(=O)C1=C2C(CN([C@@H](C)C3CC3)C2=O)=CC(=C1)C1=C(C)N=C(NC2=CC=CC(=N2)N(C)C(C)=O)S1 WEMBXYLJGBGCSQ-HNNXBMFYSA-N 0.000 claims 1
- KWHLMLQDUKNHBO-HNNXBMFYSA-N N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-methylsulfonyl-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]-N-methylacetamide Chemical compound C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=CC=CC(=N2)N(C)C(C)=O)S1 KWHLMLQDUKNHBO-HNNXBMFYSA-N 0.000 claims 1
- VGBZVXNIRCSRBK-AWEZNQCLSA-N N-[6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-methylsulfonyl-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]pyridin-2-yl]acetamide Chemical compound C[C@@H](C1CC1)N1CC2=CC(=CC(=C2C1=O)S(C)(=O)=O)C1=C(C)N=C(NC2=CC=CC(NC(C)=O)=N2)S1 VGBZVXNIRCSRBK-AWEZNQCLSA-N 0.000 claims 1
- XDWSNPNGAFALHJ-HNNXBMFYSA-N N-ethyl-6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-2-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-isoindole-4-sulfonamide Chemical compound C(C)NS(=O)(=O)C=1C=2C(N(CC=2C=C(C=1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(COCC1)=O)C)[C@H](C(F)(F)F)C)=O XDWSNPNGAFALHJ-HNNXBMFYSA-N 0.000 claims 1
- YXDZBGGLBWHPEB-ZDUSSCGKSA-N N-methyl-6-[4-methyl-2-[[6-(2-oxoimidazolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-2-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-isoindole-4-sulfonamide Chemical compound CNS(=O)(=O)C=1C=2C(N(CC=2C=C(C=1)C1=C(N=C(S1)NC1=NC(=CC=C1)N1C(NCC1)=O)C)[C@H](C(F)(F)F)C)=O YXDZBGGLBWHPEB-ZDUSSCGKSA-N 0.000 claims 1
- GFTIJVHUHAMPLS-AWEZNQCLSA-N N-methyl-6-[4-methyl-2-[[6-(2-oxopyrrolidin-1-yl)pyridin-2-yl]amino]-1,3-thiazol-5-yl]-3-oxo-2-[(2S)-1,1,1-trifluoropropan-2-yl]-1H-isoindole-4-sulfonamide Chemical compound CNS(=O)(=O)c1cc(cc2CN([C@@H](C)C(F)(F)F)C(=O)c12)-c1sc(Nc2cccc(n2)N2CCCC2=O)nc1C GFTIJVHUHAMPLS-AWEZNQCLSA-N 0.000 claims 1
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000000048 adrenergic agonist Substances 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 102000014974 beta2-adrenergic receptor activity proteins Human genes 0.000 claims 1
- 108040006828 beta2-adrenergic receptor activity proteins Proteins 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 claims 1
- 239000003149 muscarinic antagonist Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (13)
1. Spoj s formulom (I)
[image]
naznačen time što
X je C(O) ili SO2;
Y je SO2NHR5 ili SO2R6;
R1 je odabran od C1-4alkila, pri čemu je navedeni C1-4alkil po izboru supstituiran s ciklopropilom, 0, 1 ili 2 CH3 i 0, 1, 2 ili 3 F;
R2 je odabran od H ili CH3;
R3 je odabran od H ili C1-3alkila;
R4 je odabran od C1-3alkila, pri čemu je navedeni C1-3alkil po izboru supstituiran s OC1-3alkilom; ili
R3 i R4 uzeti zajedno s N atomom i X tvore 5, 6 ili 7-člani cikloheteroalkilni prsten koji sadrži 0 ili 1 daljnjih heteroatoma koji se biraju od N ili O, pri čemu je navedeni cikloheteroalkilni prsten supstituiran s 0, 1 ili 2 supstituenata koji su neovisno odabrani od CH3, OH, CH2OH ili CH2CH2OH; ili
R3 i R4 uzeti zajedno s N atomom i X su odabrani od
[image]
R5 je odabran od C1-3alkila ili (oksetan-3-il);
R6 je odabran od C1-3alkila;
ili njegova farmaceutski prihvatljiva sol.
2. Spoj prema patentnom zahtjevu 1 naznačen time što
X je C(O);
Y je SO2NHR5 ili SO2R6;
R1 je odabran od C1-4alkila, pri čemu je navedeni C1-4alkil po izboru supstituiran s ciklopropilom, 0, 1 ili 2 CH3 i 0, 1, 2 ili 3 F;
R2 je CH3;
R3 i R4 uzeti zajedno s N atomom i X tvore 5, 6 ili 7-člani cikloheteroalkilni prsten koji sadrži 0 ili 1 daljnjih heteroatoma koji se biraju od N ili O, pri čemu je navedeni cikloheteroalkilni prsten supstituiran s 0, 1 ili 2 supstituenata koji su neovisno odabrani od CH3, OH, CH2OH ili CH2CH2OH;
R5 je odabran od C1-3alkila ili (oksetan-3-il);
R6 je odabran od C1-3alkila;
ili njegova farmaceutski prihvatljiva sol.
3. Spoj prema bilo kojem patentnom zahtjevu 1 ili patentnom zahtjevu 2 naznačen time što
Y je SO2R6;
R3 i R4 uzeti zajedno s N atomom i X tvore 5-člani cikloheteroalkilni prsten koji sadrži 0 ili 1 daljnjih heteroatoma koji se biraju od N ili O, pri čemu je navedeni cikloheteroalkilni prsten supstituiran s 0 ili 1 supstituenata koji su neovisno odabrani od CH3, OH, ili CH2OH;
R6 je CH3;
ili njegova farmaceutski prihvatljiva sol.
4. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3 naznačen time što
R1 je (1S)-1-ciklopropiletil;
ili njegova farmaceutski prihvatljiva sol.
5. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3 naznačen time što
R1 je (2S)-1,1,1-trifluoropropan-2-il;
ili njegova farmaceutski prihvatljiva sol.
6. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5 naznačen time što
R3 i R4 uzeti zajedno s N atomom i X tvore 2-oksopirolidin-1-il;
ili njegova farmaceutski prihvatljiva sol.
7. Spoj s formulom (I) prema patentnom zahtjevu 1 naznačen time što je odabran iz niza koji čine:
N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfonil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}acetamid,
N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfonil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-N-metilacetamid,
2-[(1S)-1-Ciklopropiletil]-5-(4-metil-2-{[6-(2-oksopiperidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2,3-dihidro-1H-izoindol-1-on,
2-[(1S)-1-Ciklopropiletil]-5-(4-metil-2-{[6-(3-metil-2-oksoimidazolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2,3-dihidro-1H-izoindol-1-on,
2-[(1S)-1-Ciklopropiletil]-5-(4-metil-2-{[6-(2-oksoimidazolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2,3-dihidro-1H-izoindol-1-on,
2-[(1S)-1-Ciklopropiletil]-5-(4-metil-2-{[6-(3-oksomorfolin-4-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)- 2,3-dihidro-1H-izoindol-1-on,
2-[(1S)-1-Ciklopropiletil]-5-(4-metil-2-{[6-(2-okso-1,3-oksazinan-3-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2,3-dihidro-1H-izoindol-1-on,
6-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfonil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-6,7-dihidro-5H-pirolo[3,4-b]piridin-5-on,
5-(4-Metil-2-{[6-(2-oksopirolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-1 -on,
5-(4-Metil-2-{[6-(2-oksoimidazolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-1 -on,
5-(4-Metil-2-{[6-(2-okso-1,3-oksazolidin-3-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-1-on,
N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfamoil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-N-metilacetamid,
N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfamoil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-2-metoksi-N-metilacetamid,
(2R)-N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfamoil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-2-metoksi-N-metilpropanamid,
(2S)-N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfamoil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-2-metoksi-N-metilpropanamid,
N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(metilsulfamoil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-2-etoksi-N-metilacetamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-(4-metil-2-{[6-(2-oksopiperidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-(4-metil-2-{[6-(3-oksomorfolin-4-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-(4-metil-2-{[6-(2-okso-1,3-oksazinan-3-il)piridin-2-il]amino[-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-(4-metil-2-{[6-(4-metil-2-oksopiperazin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-[2-({6-[(8aS)-1,4-dioksoheksahidropirolo[1,2-a]pirazin-2(1H)-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(2-{[6-(1,1-dioksido-1,2-tiazolidin-2-il)piridin-2-il]amino}-4-metil-1,3-tiazol-5-il)-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
N-Metil-6-(4-metil-2-{[6-(2-oksopirolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
N-{6-[(5-{2-[(1S)-1-Ciklopropiletil]-7-(etilsulfamoil)-1-okso-2,3-dihidro-1H-izoindol-5-il}-4-metil-1,3-tiazol-2-il)amino]piridin-2-il}-2-metoksi-N-metilacetamid,
N-Etil-6-(4-metil-2-{[6-(3-oksomorfolin-4-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
6-(4-Metil-2-{[6-(3-oksomorfolin-4-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-N-(propan-2-il)-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
6-(4-Metil-2-{[6-(2-okso-1,3-oksazinan-3-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-N-(propan-2-il)-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
6-(4-Metil-2-{[6-(2-oksoimidazolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-N-(propan-2-il)-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(4-metil-2-{[6-(3-oksomorfolin-4-il)piridin-2-il]amino}-1,3-tiazol-5-il)-N-(oksetan-3-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(4-metil-2-{[6-(2-oksopirolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-N-(oksetan-3-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(4-metil-2-{[6-(2-okso-1,3-oksazolidin-3-il)piridin-2-il]amino}-1,3-tiazol-5-il)-N-(oksetan-3-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(4-metil-2-{[6-(2-oksoimidazolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-N-(oksetan-3-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(4-metil-2-{[6-(2-okso-1,3-oksazinan-3-il)piridin-2-il]amino}-1,3-tiazol-5-il)-N-(oksetan-3-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
6-(4-Metil-2-{[6-(2-oksopiperidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-N-(oksetan-3-il)-3-okso-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
6-(4-Metil-2-{[6-(2-oksopirolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-N-(oksetan-3-il)-3-okso-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-tert-Butil-N-metil-6-(4-metil-2-{[6-(2-okso-1,3-oksazinan-3-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3 -dihidro-1H-izoindol-4-sulfonamid,
2-[(2S)-3,3-Dimetilbutan-2-il]-N-metil-6-(4-metil-2-{[6-(3-oksomorfolin-4-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-5-(4-metil-2-{[6-(2-oksopiperazin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2,3-dihidro-1H-izoindol-1-on,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-(4-metil-2-{[6-(2-oksopiperazin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-[4-metil-2-({6-[(5S)-5-metil-2-oksopiperazin-1-il]piridin-2-il}amino)-1,3-tiazol-5-il]-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-[4-metil-2-({6-[(3R)-3-metil-2-oksopiperazin-1-il]piridin-2-il}amino)-1,3-tiazol-5-il]-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-[4-metil-2-({6-[(3S)-3-metil-2-oksopiperazin-1-il]piridin-2-il}amino)-1,3-tiazol-5-il]-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-[4-metil-2-({6-[(5R)-5-metil-2-oksopiperazin-1-il]piridin-2-il}amino)-1,3-tiazol-5-il]-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-[4-metil-2-({6-[(2R)-2-metil-6-oksopiperazin-1-il]piridin-2-il}amino)-1,3-tiazol-5-il]-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(2-{[6-(3,3-dimetil-2-oksopiperazin-1-il)piridin-2-il]amino}-4-metil-1,3-tiazol-5-il)-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(2-{[6-(5,5-dimetil-2-oksopiperazin-1-il)piridin-2-il]amino}-4-metil-1,3-tiazol-5-il)-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-[4-metil-2-({6-[(2S)-2-metil-6-oksopiperazin-1-il]piridin-2-il}amino)-1,3-tiazol-5-il]-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-etil-6-(4-metil-2-{[6-(2-oksopiperazin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-(4-metil-2-{[6-(2-oksopiperazin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-N-(propan-2-il)-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-(4-metil-2-{[6-(2-okso-1,4-diazepan-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-N-metil-6-(4-metil-2-{[6-(7-okso-1,4-diazepan-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-[2-({6-[(3R)-3-hidroksi-2-oksopirolidin-1-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-[2-({6-[(4R)-4-hidroksi-2-oksopirolidin-1-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-[2-({6-[(3S)-3-hidroksi-2-oksopirolidin-1-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-[2-({6-[(2S)-2-(hidroksimetil)-5-oksopirolidin-1-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-[2-({6-[(2R)-2-(hidroksimetil)-5-oksopirolidin-1-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(1S)-1-Ciklopropiletil]-6-[2-({6-[4-(2-hidroksietil)-2-oksopiperazin-1-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-N-metil-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
6-[2-({6-[(3S)-3-Hidroksi-2-oksopirolidin-1-il]piridin-2-il}amino)-4-metil-1,3-tiazol-5-il]-3-okso-N-(propan-2-il)-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(2S)-Butan-2-il]-N-metil-6-(4-metil-2-{[6-(2-okso-1,3-oksazinan-3-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
2-[(2S)-Butan-2-il]-N-metil-6-(4-metil-2-{[6-(3-oksomorfolin-4-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2,3-dihidro-1H-izoindol-4-sulfonamid,
N-Metil-6-(4-metil-2-{[6-(2-oksoimidazolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-3-okso-2-[(2S)-1,1,1-trifluoropropan-2-il]-2,3-dihidro-1H-izoindol-4-sulfonamid,
i njihove farmaceutski prihvatljive soli.
8. Spoj prema patentnom zahtjevu 1 naznačen time što je 2-[(1S)-1-ciklopropiletil]-5-(4-metil-2-{[6-(2-oksopirolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2,3-dihidro-1H-izoindol-1-on,
[image]
ili njegova farmaceutski prihvatljiva sol.
9. Spoj prema patentnom zahtjevu 1 naznačen time što je 2-[(1S)-1-ciklopropiletil]-5-(4-metil-2-{[6-(2-oksopirolidin-1-il)piridin-2-il]amino}-1,3-tiazol-5-il)-7-(metilsulfonil)-2,3-dihidro-1H-izoindol-1-on,
[image]
10. Farmaceutski pripravak naznačen time što sadrži spoj formule (I) prema bilo kojem od patentnih zahtjeva 1 do 9 i farmaceutski prihvatljiv adjuvans, razrjeđivač ili nosač.
11. Spoj s formulom (I) prema bilo kojem od patentnih zahtjeva 1 do 9 naznačen time što je za upotrebu u terapiji.
12. Spoj s formulom (I) prema bilo kojem od patentnih zahtjeva 1 do 9 naznačen time što je za upotrebu u liječenju astme ili kronične opstruktivne plućne bolesti.
13. Kombinacija spoja s formulom (I) prema bilo kojem od patentnih zahtjeva 1 do 9 i jednog ili više sredstava neovisno odabranih od:
• agonista glukokortikoidnih receptora (steroidni ili ne steroidni);
• selektivnog agonista β2 adrenoceptora;
• antimuskarinskog sredstva;
• p38 antagonista;
• derivata ksantina; ili
• antagonista PDE4.
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| PCT/EP2017/073916 WO2018055040A1 (en) | 2016-09-22 | 2017-09-21 | 5-[2-(pyridin-2-ylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1 h-isoindol-1 -one derivatives and their use as dual inhibitors of phosphatidylinositol 3-kinase delta & gamma |
| EP17772381.4A EP3515910B1 (en) | 2016-09-22 | 2017-09-21 | 5-[2-(pyridin-2-ylamino)-1,3-thiazol-5-yl]-2,3-dihydro-1h-isoindol-1-one derivatives and their use as dual inhibitors of phosphatidylinositol 3-kinase delta & gamma |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11161838B2 (en) | 2018-11-13 | 2021-11-02 | Incyte Corporation | Heterocyclic derivatives as PI3K inhibitors |
| US11078204B2 (en) | 2018-11-13 | 2021-08-03 | Incyte Corporation | Heterocyclic derivatives as PI3K inhibitors |
| WO2020102216A1 (en) | 2018-11-13 | 2020-05-22 | Incyte Corporation | Substituted heterocyclic derivatives as pi3k inhibitors |
| WO2022017371A1 (zh) * | 2020-07-21 | 2022-01-27 | 中国医药研究开发中心有限公司 | 具有磷脂酰肌醇3-激酶δ和γ的双重抑制剂活性的杂环化合物及其医药用途 |
| WO2022023456A1 (en) | 2020-07-29 | 2022-02-03 | Astrazeneca Ab | Pharmaceutical compositions comprising nano embedded microparticles and methods of use |
| CN116813608B (zh) * | 2023-06-08 | 2024-03-22 | 英矽智能科技(上海)有限公司 | 噻唑类化合物及其应用 |
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|---|---|---|---|---|
| ATE318812T1 (de) * | 2000-12-21 | 2006-03-15 | Bristol Myers Squibb Co | Thiazolyl-inhibitoren von tyrosinkinasen der tec- familie |
| GB0305152D0 (en) * | 2003-03-06 | 2003-04-09 | Novartis Ag | Organic compounds |
| GB0320197D0 (en) * | 2003-08-28 | 2003-10-01 | Novartis Ag | Organic compounds |
| US20090233896A1 (en) * | 2005-06-09 | 2009-09-17 | Arrington Kenneth L | Inhibitors of checkpoint kinases |
| TW200911798A (en) * | 2007-08-02 | 2009-03-16 | Amgen Inc | PI3 kinase modulators and methods of use |
| UY33337A (es) | 2010-10-18 | 2011-10-31 | Respivert Ltd | DERIVADOS SUSTITUIDOS DE 1H-PIRAZOL[ 3,4-d]PIRIMIDINA COMO INHIBIDORES DE LAS FOSFOINOSITIDA 3-QUINASAS |
| US9056877B2 (en) | 2011-07-19 | 2015-06-16 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US8969363B2 (en) | 2011-07-19 | 2015-03-03 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| PE20141371A1 (es) | 2011-08-29 | 2014-10-13 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos |
| WO2013052699A2 (en) | 2011-10-04 | 2013-04-11 | Gilead Calistoga Llc | Novel quinoxaline inhibitors of pi3k |
| UA119315C2 (uk) | 2012-07-03 | 2019-06-10 | Гіліад Фармассет Елелсі | Інгібітори вірусу гепатиту с |
| TW201446767A (zh) | 2013-02-15 | 2014-12-16 | Almirall Sa | 作為磷脂肌醇3-激酶抑製劑之吡咯並三嗪衍生物 |
| CN111153905A (zh) | 2013-07-02 | 2020-05-15 | 理森制药股份公司 | PI3K蛋白激酶抑制剂，特别是δ抑制剂和/或γ抑制剂 |
| UY35675A (es) | 2013-07-24 | 2015-02-27 | Novartis Ag | Derivados sustituidos de quinazolin-4-ona |
| SG11201610745XA (en) | 2014-06-27 | 2017-01-27 | Rhizen Pharmaceuticals Sa | Substituted chromene derivatives as selective dual inhibitors of pi3 delta and gamma protein kinases |
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