HRP20130951T1 - Spojevi heksahidrooksazinopteridina za uporabu kao inhibitori mtor - Google Patents
Spojevi heksahidrooksazinopteridina za uporabu kao inhibitori mtor Download PDFInfo
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- HRP20130951T1 HRP20130951T1 HRP20130951AT HRP20130951T HRP20130951T1 HR P20130951 T1 HRP20130951 T1 HR P20130951T1 HR P20130951A T HRP20130951A T HR P20130951AT HR P20130951 T HRP20130951 T HR P20130951T HR P20130951 T1 HRP20130951 T1 HR P20130951T1
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- HR
- Croatia
- Prior art keywords
- methyl
- optionally substituted
- phenyl
- oxazino
- oxo
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims 18
- 229940124302 mTOR inhibitor Drugs 0.000 title 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 12
- 239000001257 hydrogen Substances 0.000 claims 12
- 125000003118 aryl group Chemical group 0.000 claims 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 8
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 125000000217 alkyl group Chemical group 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 6
- 125000001475 halogen functional group Chemical group 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000003282 alkyl amino group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 2
- AAKIKBVXVQWSEI-QHCPKHFHSA-N 1-[4-[(6as)-5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC=C(N(CC2CC2)C(=O)[C@@]2(C)N3CCOC2)C3=N1 AAKIKBVXVQWSEI-QHCPKHFHSA-N 0.000 claims 2
- YYVSGNQVBXYPOF-UHFFFAOYSA-N 1-[4-[5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC2CC2)C(=O)C2(C)N3CCOC2)C3=N1 YYVSGNQVBXYPOF-UHFFFAOYSA-N 0.000 claims 2
- 101100516572 Caenorhabditis elegans nhr-8 gene Proteins 0.000 claims 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000004104 aryloxy group Chemical group 0.000 claims 2
- 239000004202 carbamide Substances 0.000 claims 2
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- JHSSHWWGOJAIGL-UHFFFAOYSA-N 1-[4-(5,6a-dimethyl-4-morpholin-4-yl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(N(C)C(=O)C2(C)N3CCOC2)C3=N1 JHSSHWWGOJAIGL-UHFFFAOYSA-N 0.000 claims 1
- OWPVUCBHOPHEKZ-UHFFFAOYSA-N 1-[4-(5-cyclopropyl-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C2CC2)C(=O)C2(C)N3CCOC2)C3=N1 OWPVUCBHOPHEKZ-UHFFFAOYSA-N 0.000 claims 1
- RUNFCBGNWZNDOV-UHFFFAOYSA-N 1-[4-(6a-methyl-6-oxo-5-propan-2-yl-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl)phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C(C)C)C(=O)C2(C)N3CCOC2)C3=N1 RUNFCBGNWZNDOV-UHFFFAOYSA-N 0.000 claims 1
- TVISMJDQTRLBBY-JOCHJYFZSA-N 1-[4-[(6ar)-5-(2,2-difluoropropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@]1(C)C(=O)N(C2=CN=3)CC(F)(F)C)OCCN1C2=NC=3C(C=C1)=CC=C1NC(=O)NC1CC1 TVISMJDQTRLBBY-JOCHJYFZSA-N 0.000 claims 1
- LVTQZSLDDDGGBY-XMMPIXPASA-N 1-[4-[(6ar)-5-(3-methoxypropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@]1(C)C(=O)N(C2=CN=3)CCCOC)OCCN1C2=NC=3C(C=C1)=CC=C1NC(=O)NC1CC1 LVTQZSLDDDGGBY-XMMPIXPASA-N 0.000 claims 1
- LOTKWZIFCWBSHG-JOCHJYFZSA-N 1-[4-[(6ar)-5-(3-methoxypropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CCCOC)C(=O)[C@]2(C)N3CCOC2)C3=N1 LOTKWZIFCWBSHG-JOCHJYFZSA-N 0.000 claims 1
- QSUSKMROELIXNC-XMMPIXPASA-N 1-[4-[(6ar)-5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@@]1(C2=O)C)OCCN1C1=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C1N2CC1CC1 QSUSKMROELIXNC-XMMPIXPASA-N 0.000 claims 1
- AAKIKBVXVQWSEI-HSZRJFAPSA-N 1-[4-[(6ar)-5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC=C(N(CC2CC2)C(=O)[C@]2(C)N3CCOC2)C3=N1 AAKIKBVXVQWSEI-HSZRJFAPSA-N 0.000 claims 1
- YGGOLLYGDWXBBC-YCRPNKLZSA-N 1-[4-[(6ar)-5-[(2s)-2,3-dihydroxypropyl]-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C[C@H](O)CO)C(=O)[C@]2(C)N3CCOC2)C3=N1 YGGOLLYGDWXBBC-YCRPNKLZSA-N 0.000 claims 1
- IZCQVAPJLOTNAA-RUZDIDTESA-N 1-[4-[(6ar)-6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@@]1(C2=O)C)OCCN1C1=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C1N2C1CCOCC1 IZCQVAPJLOTNAA-RUZDIDTESA-N 0.000 claims 1
- NNIWQDRWZFLJHS-HSZRJFAPSA-N 1-[4-[(6ar)-6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C2CCOCC2)C(=O)[C@]2(C)N3CCOC2)C3=N1 NNIWQDRWZFLJHS-HSZRJFAPSA-N 0.000 claims 1
- OIWRCHCDWBRHIP-QKFKETGDSA-N 1-[4-[(6ar,9r)-5-(cyclopropylmethyl)-6a,9-dimethyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC2CC2)C(=O)[C@]2(C)N3C[C@@H](C)OC2)C3=N1 OIWRCHCDWBRHIP-QKFKETGDSA-N 0.000 claims 1
- TVISMJDQTRLBBY-QFIPXVFZSA-N 1-[4-[(6as)-5-(2,2-difluoropropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@@]1(C)C(=O)N(C2=CN=3)CC(F)(F)C)OCCN1C2=NC=3C(C=C1)=CC=C1NC(=O)NC1CC1 TVISMJDQTRLBBY-QFIPXVFZSA-N 0.000 claims 1
- LVTQZSLDDDGGBY-DEOSSOPVSA-N 1-[4-[(6as)-5-(3-methoxypropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@@]1(C)C(=O)N(C2=CN=3)CCCOC)OCCN1C2=NC=3C(C=C1)=CC=C1NC(=O)NC1CC1 LVTQZSLDDDGGBY-DEOSSOPVSA-N 0.000 claims 1
- LOTKWZIFCWBSHG-QFIPXVFZSA-N 1-[4-[(6as)-5-(3-methoxypropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CCCOC)C(=O)[C@@]2(C)N3CCOC2)C3=N1 LOTKWZIFCWBSHG-QFIPXVFZSA-N 0.000 claims 1
- QSUSKMROELIXNC-DEOSSOPVSA-N 1-[4-[(6as)-5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@]1(C2=O)C)OCCN1C1=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C1N2CC1CC1 QSUSKMROELIXNC-DEOSSOPVSA-N 0.000 claims 1
- YGGOLLYGDWXBBC-BTYIYWSLSA-N 1-[4-[(6as)-5-[(2s)-2,3-dihydroxypropyl]-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C[C@H](O)CO)C(=O)[C@@]2(C)N3CCOC2)C3=N1 YGGOLLYGDWXBBC-BTYIYWSLSA-N 0.000 claims 1
- IZCQVAPJLOTNAA-VWLOTQADSA-N 1-[4-[(6as)-6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@]1(C2=O)C)OCCN1C1=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C1N2C1CCOCC1 IZCQVAPJLOTNAA-VWLOTQADSA-N 0.000 claims 1
- NNIWQDRWZFLJHS-QHCPKHFHSA-N 1-[4-[(6as)-6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C2CCOCC2)C(=O)[C@@]2(C)N3CCOC2)C3=N1 NNIWQDRWZFLJHS-QHCPKHFHSA-N 0.000 claims 1
- RYYWQIJXZAXJSP-NRFANRHFSA-N 1-[4-[(6as)-6a-methyl-6-oxo-5-(2,2,2-trifluoroethyl)-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound C([C@]1(C(N(CC(F)(F)F)C2=CN=3)=O)C)OCCN1C2=NC=3C(C=C1)=CC=C1NC(=O)NC1CC1 RYYWQIJXZAXJSP-NRFANRHFSA-N 0.000 claims 1
- JPNLNDOCQLDJTD-PSLXWICFSA-N 1-[4-[(6as,7s)-5-(cyclopropylmethyl)-6a,7-dimethyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC2CC2)C(=O)[C@@]2(C)N3CCO[C@H]2C)C3=N1 JPNLNDOCQLDJTD-PSLXWICFSA-N 0.000 claims 1
- PUZOTKQOPASQPZ-UHFFFAOYSA-N 1-[4-[5-(2-hydroxy-2-methylpropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC(C)(C)O)C(=O)C2(C)N3CCOC2)C3=N1 PUZOTKQOPASQPZ-UHFFFAOYSA-N 0.000 claims 1
- QZVZXKDUOLRDKB-UHFFFAOYSA-N 1-[4-[5-(2-methoxyethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CCOC)C(=O)C2(C)N3CCOC2)C3=N1 QZVZXKDUOLRDKB-UHFFFAOYSA-N 0.000 claims 1
- LOTKWZIFCWBSHG-UHFFFAOYSA-N 1-[4-[5-(3-methoxypropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CCCOC)C(=O)C2(C)N3CCOC2)C3=N1 LOTKWZIFCWBSHG-UHFFFAOYSA-N 0.000 claims 1
- YQNDUXGTKLFCTQ-UHFFFAOYSA-N 1-[4-[5-(cyclobutylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC2CCC2)C(=O)C2(C)N3CCOC2)C3=N1 YQNDUXGTKLFCTQ-UHFFFAOYSA-N 0.000 claims 1
- AAKIKBVXVQWSEI-UHFFFAOYSA-N 1-[4-[5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC=C(N(CC2CC2)C(=O)C2(C)N3CCOC2)C3=N1 AAKIKBVXVQWSEI-UHFFFAOYSA-N 0.000 claims 1
- YGGOLLYGDWXBBC-ZDGMYTEDSA-N 1-[4-[5-[(2s)-2,3-dihydroxypropyl]-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C[C@H](O)CO)C(=O)C2(C)N3CCOC2)C3=N1 YGGOLLYGDWXBBC-ZDGMYTEDSA-N 0.000 claims 1
- HXWFXGTXNMXVTM-UHFFFAOYSA-N 1-[4-[5-[3-hydroxy-2-(hydroxymethyl)-2-methylpropyl]-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC(C)(CO)CO)C(=O)C2(C)N3CCOC2)C3=N1 HXWFXGTXNMXVTM-UHFFFAOYSA-N 0.000 claims 1
- GFBLZIWBIVLECA-KEJDIYNNSA-N 1-[4-[5-[[(4s)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl]-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C[C@@H]2OC(C)(C)OC2)C(=O)C2(C)N3CCOC2)C3=N1 GFBLZIWBIVLECA-KEJDIYNNSA-N 0.000 claims 1
- NHULRCMLFREZSI-UHFFFAOYSA-N 1-[4-[6a-methyl-5-(3-methylsulfonylpropyl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound N=1C=C2N(CCCS(C)(=O)=O)C(=O)C3(C)COCCN3C2=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 NHULRCMLFREZSI-UHFFFAOYSA-N 0.000 claims 1
- IZCQVAPJLOTNAA-UHFFFAOYSA-N 1-[4-[6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound O=C1C2(C)COCCN2C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C2N1C1CCOCC1 IZCQVAPJLOTNAA-UHFFFAOYSA-N 0.000 claims 1
- CILYOKRFAKTHSM-UHFFFAOYSA-N 1-[4-[6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC=C(N(C2CCOCC2)C(=O)C2(C)N3CCOC2)C3=N1 CILYOKRFAKTHSM-UHFFFAOYSA-N 0.000 claims 1
- NNIWQDRWZFLJHS-UHFFFAOYSA-N 1-[4-[6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C2CCOCC2)C(=O)C2(C)N3CCOC2)C3=N1 NNIWQDRWZFLJHS-UHFFFAOYSA-N 0.000 claims 1
- JCGKAJDXWPEOPB-UHFFFAOYSA-N 1-[4-[6a-methyl-5-[(1-methylpyrazol-3-yl)methyl]-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC2=NN(C)C=C2)C(=O)C2(C)N3CCOC2)C3=N1 JCGKAJDXWPEOPB-UHFFFAOYSA-N 0.000 claims 1
- RYYWQIJXZAXJSP-UHFFFAOYSA-N 1-[4-[6a-methyl-6-oxo-5-(2,2,2-trifluoroethyl)-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound N=1C=C2N(CC(F)(F)F)C(=O)C3(C)COCCN3C2=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 RYYWQIJXZAXJSP-UHFFFAOYSA-N 0.000 claims 1
- ZZRMDFGUCYWJPT-UHFFFAOYSA-N 1-[4-[6a-methyl-6-oxo-5-(oxolan-3-yl)-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound O=C1C2(C)COCCN2C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C2N1C1CCOC1 ZZRMDFGUCYWJPT-UHFFFAOYSA-N 0.000 claims 1
- UWUGKQBEAABTAQ-UHFFFAOYSA-N 1-[4-[6a-methyl-6-oxo-5-(oxolan-3-yl)-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C2COCC2)C(=O)C2(C)N3CCOC2)C3=N1 UWUGKQBEAABTAQ-UHFFFAOYSA-N 0.000 claims 1
- KYOHMTCOAOBBSY-UHFFFAOYSA-N 1-[4-[6a-methyl-6-oxo-5-(oxolan-3-ylmethyl)-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea Chemical compound O=C1C2(C)COCCN2C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C2N1CC1CCOC1 KYOHMTCOAOBBSY-UHFFFAOYSA-N 0.000 claims 1
- WSIYWSQOWQHEIF-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[5-(1,1-dioxothian-4-yl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]urea Chemical compound O=C1C2(C)COCCN2C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C2N1C1CCS(=O)(=O)CC1 WSIYWSQOWQHEIF-UHFFFAOYSA-N 0.000 claims 1
- TVISMJDQTRLBBY-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[5-(2,2-difluoropropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]urea Chemical compound N=1C=C2N(CC(F)(F)C)C(=O)C3(C)COCCN3C2=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 TVISMJDQTRLBBY-UHFFFAOYSA-N 0.000 claims 1
- LVTQZSLDDDGGBY-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[5-(3-methoxypropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]urea Chemical compound N=1C=C2N(CCCOC)C(=O)C3(C)COCCN3C2=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 LVTQZSLDDDGGBY-UHFFFAOYSA-N 0.000 claims 1
- QSUSKMROELIXNC-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]urea Chemical compound O=C1C2(C)COCCN2C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC=C2N1CC1CC1 QSUSKMROELIXNC-UHFFFAOYSA-N 0.000 claims 1
- DWTOLPUNYJBGHV-UHFFFAOYSA-N 1-ethyl-3-[4-[5-(3-methoxypropyl)-6a-methyl-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC=C(N(CCCOC)C(=O)C2(C)N3CCOC2)C3=N1 DWTOLPUNYJBGHV-UHFFFAOYSA-N 0.000 claims 1
- RPVQWTXQIUJOAZ-UHFFFAOYSA-N 1-methyl-3-[4-[5-(2-methylpropyl)-6-oxo-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(CC(C)C)C(=O)C2N3CCOC2)C3=N1 RPVQWTXQIUJOAZ-UHFFFAOYSA-N 0.000 claims 1
- ARTABERNTLYNPS-UHFFFAOYSA-N 2-[6a-methyl-2-[4-(methylcarbamoylamino)phenyl]-6-oxo-9,10-dihydro-7h-[1,4]oxazino[3,4-h]pteridin-5-yl]-2-methylpropanoic acid Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC=C(N(C(=O)C2(C)N3CCOC2)C(C)(C)C(O)=O)C3=N1 ARTABERNTLYNPS-UHFFFAOYSA-N 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
- 101100212791 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YBL068W-A gene Proteins 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000005553 heteroaryloxy group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000004257 pteridin-2-yl group Chemical group [H]C1=C([H])N=C2C([H])=NC(*)=NC2=N1 0.000 claims 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Claims (15)
1. Spoj sa formulom
[image]
naznačen time da
G1 je odabran iz skupine koja sadrži N i CR7;
G2 je odabran iz skupine koja sadrži C=O i CH2;
Ar je odabran iz skupine koja sadrži C4-14 aril i C1-10 heteroaril;
m je 0, 1, 2, 3, ili 4;
R1 je, svaki puta, neovisno odabran iz skupine koja sadrži halo, cijano, proizvoljno supstituirani C1-6 alkil, C1-8 sulfonil, proizvoljno supstituirani C2-4 alkenil, proizvoljno supstituirani C2-4alkinil, proizvoljno supstituirani C1-4 alkoksi, C0-8 alkilamino, proizvoljno supstituirani C4-14 aril, proizvoljno supstituirani C4-14 ariloksi, proizvoljno supstituirani C1-10 heteroariloksi, C1-5 oksikarbonil, C1-5 karboniloksi, proizvoljno supstituirani C3-8 cikloalkil, proizvoljno supstituirani C3-6 heterocikloalkil, proizvoljno supstituirani C1-10 heteroaril, hidroksi, nitro, -C(O)NR8R9, -NHC(O)NR8R9, -NHC(O)OR10, -NH(SO2)NHR8, -NHC(O)NHNR8R9, -NHC(S)NR8R9,
-NHC(=NR11)NR8R9, -NHC(SR12)NR8R9, i -NHC(=NR11)OR13;
R2 je odabran iz skupine koja sadrži vodik, halo, cijano, proizvoljno supstituirani C1-6 alkil, C1-8 sulfonil, proizvoljno supstituirani C2-4 alkenil, proizvoljno supstituirani C2-4alkinil, proizvoljno supstituirani C1-4alkoksi, C0-8alkilamino, proizvoljno supstituirani C4-14 aril, proizvoljno supstituirani C4-14 ariloksi, C1-5 oksikarbonil, C1-5 karboniloksi, proizvoljno supstituirani C3-6 heterocikloalkil, proizvoljno supstituirani C1-10 heteroaril, hidroksi, te nitro;
R3 je odabran iz skupine koja sadrži vodik, proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C3-8 cikloalkil, te proizvoljno supstituirani C3-6heterocikloalkil;
R4 je odabran iz skupine koja sadrži metil i trifluorometil;
R5 je odabran iz skupine koja sadrži vodik, halo, proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C2-4 alkenil, i proizvoljno supstituirani C3-8 cikloalkil;
R6 je odabran iz skupine koja sadrži vodik, halo, proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C2-4 alkenil, te proizvoljno supstituirani C3-8 cikloalkil; ili
R5 i R6 su uzeti zajedno da tvore proizvoljno supstituirani C1-C3alkilenil; ili
R4 i R5 su uzeti zajedno da tvore proizvoljno supstituirani C1-C3alkilenil; ili
R4 i R6 su uzeti zajedno da tvore proizvoljno supstituirani C1-C3alkilenil; i R7 je odabran iz skupine koja sadrži vodik, C0-8 alkilamino, C1-7 amido, C1-9 amid, C1-5 karbamoil, C1-6sulfonilamido, C0-6 sulfonilamino,C1-5 ureido, proizvoljno supstituirani C1-4 alkil, proizvoljno supstituirani C1-4 alkoksi, cijano, halo, hidroksil, nitro, C1-5 oksikarbonil, te C1-8 sulfonil;
R8 je, svaki puta, neovisno odabran iz skupine koja sadrži vodik, proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C3-8 cikloalkil, proizvoljno supstituirani C4-14 aril, proizvoljno supstituirani C3-6 heterocikloalkil, te proizvoljno supstituirani C1-10 heteroaril;
R9 je, svaki puta, neovisno odabran iz skupine koja sadrži vodik, proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C3-8 cikloalkil, proizvoljno supstituirani C4-14 aril, proizvoljno supstituirani C3-6 heterocikloalkil, te proizvoljno supstituirani C1-10 heteroaril;
R10 je, svaki puta, neovisno odabran iz skupine koja sadrži proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C3-8 cikloalkil, proizvoljno supstituirani C4-14 aril, te proizvoljno supstituirani C3-6 heterocikloalkil;
R11 je, svaki puta, neovisno odabran iz skupine koja sadrži vodik, proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C1-6 alkoksi, proizvoljno supstituirani C3-8 cikloalkil, proizvoljno supstituirani C4-14 aril, proizvoljno supstituirani C3-6 heterocikloalkil, proizvoljno supstituirani C1-10 heteroaril, cijano, i nitro;
R12 je, svaki puta, neovisno odabran iz skupine koja sadrži proizvoljno supstituirani C1-6 alkil i proizvoljno supstituirani fenil; i
R13 je, svaki puta, neovisno odabran iz skupine koja sadrži proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C3-8 cikloalkil, te proizvoljno supstituirani C4-14 aril;
ili farmaceutski prihvatljive soli gore navedenog.
2. Spoj prema zahtjevu 1 naznačen time da R4 je metil.
3. Spoj prema bilo kojem zahtjevu ili 2 naznačen time da Ar je C4-14 aril.
4. Spoj prema bilo kojem zahtjevu od 1 do 3 naznačen time da G1 je N.
5. Spoj prema bilo kojem zahtjevu od 1 do 4 naznačen time da G2 je C=O.
6. Spoj prema bilo kojem zahtjevu od 1 do 5 naznačen time da R3 je odabran iz skupine koja sadrži proizvoljno supstituirani C1-6 alkil, proizvoljno supstituirani C3-6 heterocikloalkil, te proizvoljno supstituirani C3-8 cikloalkil.
7. Spoj prema bilo kojem zahtjevu od 1 do 6 naznačen time da R3 je odabran iz skupine koja sadrži C1-4 alkil, C3-8 cikloalkilC1-4 alkil, te C3-8 cikloalkil.
8. Spoj prema bilo kojem zahtjevu od 1 do 7 naznačen time da R5 je vodik i R6 je vodik.
9. Spoj prema bilo kojem zahtjevu od 1 do 8 naznačen time da m je barem 1 i barem jedan R1 je odabran iz skupine koja sadrži -NHC(O)NR8R9, -NHC(O)OR10, i - NH(SO2)NHR8.
10. Spoj prema bilo kojem zahtjevu od 1 do 9 naznačen time da m je barem 1 i barem jedan R1 je odabran iz skupine koja sadrži -NHC(O)NR8R9 i R8 je vodik i R9 je odabran iz skupine koja sadrži C1-4 alkil, C3-8 cikloalkilC1-4 alkil, te C3-8 cikloalkil.
11. Spoj prema bilo kojem zahtjevu od 1 do 10 naznačen time da R2 je vodik.
12. Spoj prema zahtjevu 1 naznačen time da je odabran iz skupine koja sadrži:
1-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-etilurea;
1-ciklopropil-3-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(S)-1-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-etilurea;
(R)-1-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-etilurea;
(S)-1-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-etilurea;
(S)-1-ciklopropil-3-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(R)-1-ciklopropil-3-(4-(5-(ciklopropilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-(4-(5-isobutil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-metil-3-(4-(6a-metil-5-((1-metil-1H-pirazol-3-il)metil)-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-(4-(5-(3-hidroksi-2-(hidroksimetil)-2-metilpropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5,6a-dimetil-4-morfolino-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5-isopropil-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5-(ciklobutilmetil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5-ciklopropil-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-((6aS,7S)-5-(ciklopropilmetil)-6a,7-dimetil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-((6aR,9R)-5-(ciklopropilmetil)-6a,9-dimetil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
etil 2-metil-2-(6a-metil-2-(4-(3-metilureido)fenil)-6-okso-6a,7,9,10-tetrahidro-[1,4]oksazino[3,4-h]pteridin-5(6H)-il)propanoat;
2-metil-2-(6a-metil-2-(4-(3-metilureido)fenil)-6-okso-6a,7,9,10-tetrahidro-[1,4]oksazino[3,4-h]pteridin-5(6H)-il)propanska kiselina;
1-(4-(5-(((S)-2,2-dimetil-1,3-dioksolan-4-il)metil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5-((S)-2,3-dihidroksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-((S)-5-((S)-2,3-dihidroksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-((R)-5-((S)-2,3-dihidroksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-metil-3-(4-(6a-metil-6-okso-5-(tetrahidro-2H-piran-4-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(S)-1-metil-3-(4-(6a-metil-6-okso-5-(tetrahidro-2H-piran-4-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(R)-1-metil-3-(4-(6a-metil-6-okso-5-(tetrahidro-2H-piran-4-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-metil-3-(4-(6a-metil-5-neopentil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-metil-3-(4-(6a-metil-6-okso-5-(tetrahidrofuran-3-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-ciklopropil-3-(4-(6a-metil-6-okso-5-(tetrahidrofuran-3-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-etil-3-(4-(6a-metil-6-okso-5-(tetrahidro-2H-piran-4-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-ciklopropil-3-(4-(6a-metil-6-okso-5-(tetrahidro-2H-piran-4-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(S)-1-ciklopropil-3-(4-(6a-metil-6-okso-5-(tetrahidro-2H-piran-4-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(R)-1-ciklopropil-3-(4-(6a-metil-6-okso-5-(tetrahidro-2H-piran-4-il)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-(4-[5-(3-methoksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro[1,4]oksazino[3,4-h]pteridin-2-il]fenil)-3-metilurea;
(S)-1-(4-[5-(3-methoksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro[1,4]oksazino[3,4-h]pteridin-2-il]fenil)-3-metilurea;
(R)-1-(4-[5-(3-methoksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro[1,4]oksazino[3,4-h]pteridin-2-il]fenil)-3-metilurea;
1-(4-[5-(2-methoksietil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro[1,4]oksazino[3,4-h]pteridin-2-il]fenil)-3-metilurea;
1-etil-3-(4-(5-(3-methoksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-ciklopropil-3-(4-(5-(3-methoksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(S)-1-ciklopropil-3-(4-(5-(3-methoksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(R)-1-ciklopropil-3-(4-(5-(3-methoksipropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-(4-(5-(2-ethoksietil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-(4-(5-(2-hidroksi-2-metilpropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)-3-metilurea;
1-ciklopropil-3-(4-[5-(1,1-dioksidotetrahidro-2H-tiopiran-4-il)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro[1,4]oksazino[3,4-h]pteridin-2-il]fenil)urea;
1-ciklopropil-3-(4-(6a-metil-5-(3-(metilsulfonil)propil)-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-ciklopropil-3-(4-(5-(2,2-difluoropropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(S)-1-ciklopropil-3-(4-(5-(2,2-difluoropropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(R)-1-ciklopropil-3-(4-(5-(2,2-difluoropropil)-6a-metil-6-okso-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
1-ciklopropil-3-(4-(6a-metil-6-okso-5-(2,2,2-trifluoroetil)-5,6,6a,7,9,10-heksahidro[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(S)-1-ciklopropil-3-(4-(6a-metil-6-okso-5-(2,2,2-trifluoroetil)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea;
(R)-ciklopropil-3-(4-(6a-metil-6-okso-5-(2,2,2-trifluoroetil)-5,6,6a,7,9,10-heksahidro[1,4]oksazino[3,4-h]pteridin-2-il)fenil)urea; te
ciklopropil-3-(4-(6a-metil-6-okso-5-((tetrahidrofuran-3-il)metil)-5,6,6a,7,9,10-heksahidro-[1,4]oksazino[3,4-h]pteridinil)fenil)urea;
ili stereoizomer bilo kojeg od gore navedenih spojeva; ili
farmaceutski prihvatljiva sol bilo kojeg od gore navedenih spojeva.
13. Farmaceutski pripravak, naznačen time da sadrži spoj prema bilo kojem zahtjevu od 1 do 12 i farmaceutski prihvatljivu pomoćnu tvar.
14. Spoj prema bilo kojem zahtjevu od 1 do 12 naznačen time da je za uporabu kao lijek.
15. Kombinacija naznačena time da sadrži spoj prema bilo kojem zahtjevu od 1 do 12 i barem jedno dodatno farmakološki aktivno sredstvo.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US23806409P | 2009-08-28 | 2009-08-28 | |
| US31360810P | 2010-03-12 | 2010-03-12 | |
| PCT/US2010/046839 WO2011025889A1 (en) | 2009-08-28 | 2010-08-26 | HEXAHYDROOXAZINOPTERINE COMPOUNDS FOR USE AS mTOR INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20130951T1 true HRP20130951T1 (hr) | 2013-11-22 |
Family
ID=42768136
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20130951AT HRP20130951T1 (hr) | 2009-08-28 | 2013-10-09 | Spojevi heksahidrooksazinopteridina za uporabu kao inhibitori mtor |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US8163755B2 (hr) |
| EP (1) | EP2470546B1 (hr) |
| JP (1) | JP2013503183A (hr) |
| AR (1) | AR077974A1 (hr) |
| DK (1) | DK2470546T3 (hr) |
| ES (1) | ES2432315T3 (hr) |
| HR (1) | HRP20130951T1 (hr) |
| PL (1) | PL2470546T3 (hr) |
| PT (1) | PT2470546E (hr) |
| SI (1) | SI2470546T1 (hr) |
| TW (1) | TW201119656A (hr) |
| UY (1) | UY32863A (hr) |
| WO (1) | WO2011025889A1 (hr) |
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| JP2013515734A (ja) | 2009-12-23 | 2013-05-09 | エラン ファーマシューティカルズ，インコーポレイテッド | ポロ様キナーゼの阻害薬としてのプテリジノン |
| US9193721B2 (en) | 2010-04-14 | 2015-11-24 | Incyte Holdings Corporation | Fused derivatives as PI3Kδ inhibitors |
| WO2011163195A1 (en) | 2010-06-21 | 2011-12-29 | Incyte Corporation | Fused pyrrole derivatives as pi3k inhibitors |
| JP5961187B2 (ja) | 2010-12-20 | 2016-08-02 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｐｉ３ｋ阻害剤としてのｎ−（１−（置換フェニル）エチル）−９ｈ−プリン−６−アミン |
| AU2012213080B2 (en) | 2011-01-31 | 2014-03-27 | Novartis Ag | Novel heterocyclic derivatives |
| TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
| AR085406A1 (es) * | 2011-02-25 | 2013-09-25 | Takeda Pharmaceutical | Oxazinopteridinas y oxazinopteridinonas n-sustituidas |
| US9108984B2 (en) | 2011-03-14 | 2015-08-18 | Incyte Corporation | Substituted diamino-pyrimidine and diamino-pyridine derivatives as PI3K inhibitors |
| WO2012135009A1 (en) | 2011-03-25 | 2012-10-04 | Incyte Corporation | Pyrimidine-4,6-diamine derivatives as pi3k inhibitors |
| CA2846652C (en) | 2011-09-02 | 2019-11-05 | Incyte Corporation | Heterocyclylamines as pi3k inhibitors |
| WO2013061305A1 (en) | 2011-10-28 | 2013-05-02 | Novartis Ag | Novel purine derivatives and their use in the treatment of disease |
| AR090548A1 (es) | 2012-04-02 | 2014-11-19 | Incyte Corp | Azaheterociclobencilaminas biciclicas como inhibidores de pi3k |
| MX367055B (es) | 2012-06-26 | 2019-08-02 | Del Mar Pharmaceuticals | El uso de una composición que comprende dianhidrogalactitol, diacetildianhidrogalactitol, y dibromodulcitol, y análogos o derivados de cada uno para el tratamiento de malignidades resistentes a inhibidores de tirosina cinasa. |
| WO2014037480A1 (en) | 2012-09-10 | 2014-03-13 | F. Hoffmann-La Roche Ag | 6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
| TWI687220B (zh) | 2013-03-01 | 2020-03-11 | 美商英塞特控股公司 | 吡唑并嘧啶衍生物治療PI3Kδ相關病症之用途 |
| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| JP2016519684A (ja) | 2013-04-08 | 2016-07-07 | デニス エム ブラウン | 準最適に投与された薬物療法の有効性を改善するための及び／又は副作用を低減するための方法および組成物 |
| WO2015013579A1 (en) | 2013-07-26 | 2015-01-29 | Update Pharma Inc. | Compositions to improve the therapeutic benefit of bisantrene |
| JP6276852B2 (ja) * | 2013-10-15 | 2018-02-07 | ジン，ボハン | 新規化合物、使用およびそれらの調製のための方法 |
| DK3129021T3 (da) | 2014-04-08 | 2020-11-09 | Incyte Corp | Behandling af b-celle-maligniteter ved en kombination af jak- og pi3k-inhibitorer |
| WO2015191677A1 (en) | 2014-06-11 | 2015-12-17 | Incyte Corporation | Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors |
| ES2843522T3 (es) | 2015-02-27 | 2021-07-19 | Incyte Corp | Sales del inhibidor de PI3K y procesos para su preparación |
| WO2016183063A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Crystalline forms of a pi3k inhibitor |
| WO2016183060A1 (en) | 2015-05-11 | 2016-11-17 | Incyte Corporation | Process for the synthesis of a phosphoinositide 3-kinase inhibitor |
| US20160362424A1 (en) | 2015-05-11 | 2016-12-15 | Incyte Corporation | Salts of (s)-7-(1-(9h-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5h-thiazolo[3,2-a]pyrimidin-5-one |
| KR102017676B1 (ko) * | 2018-03-09 | 2019-09-03 | 연세대학교 원주산학협력단 | 익상편 예방 및 치료용 조성물 |
| WO2020076728A1 (en) | 2018-10-08 | 2020-04-16 | Takeda Pharmaceutical Company Limited | SUBSTITUTED OXAZINOPTERIDINONES AS INHIBITORS OF mTOR |
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| WO2003076440A1 (en) | 2002-03-06 | 2003-09-18 | Smithkline Beecham Corporation | Condensed heterocyclic compounds as calcitonin agonists |
| GB0415364D0 (en) | 2004-07-09 | 2004-08-11 | Astrazeneca Ab | Pyrimidine derivatives |
| EP1846410B1 (en) | 2005-02-10 | 2009-01-21 | Bristol-Myers Squibb Company | Dihydroquinazolinones as 5ht modulators |
| US8911498B2 (en) | 2005-02-10 | 2014-12-16 | DePuy Synthes Products, LLC | Intervertebral prosthetic disc |
| WO2008023180A1 (en) | 2006-08-24 | 2008-02-28 | Astrazeneca Ab | Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders |
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| US20090149458A1 (en) * | 2007-11-27 | 2009-06-11 | Wyeth | PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS |
| RU2014118677A (ru) * | 2010-10-08 | 2015-11-20 | Элан Фармасьютикалз, Инк. | Ингибиторы киназ типа polo |
-
2010
- 2010-08-26 WO PCT/US2010/046839 patent/WO2011025889A1/en active Application Filing
- 2010-08-26 PL PL10749736T patent/PL2470546T3/pl unknown
- 2010-08-26 EP EP10749736.4A patent/EP2470546B1/en not_active Not-in-force
- 2010-08-26 SI SI201030392T patent/SI2470546T1/sl unknown
- 2010-08-26 US US12/869,452 patent/US8163755B2/en active Active
- 2010-08-26 ES ES10749736T patent/ES2432315T3/es active Active
- 2010-08-26 AR ARP100103122A patent/AR077974A1/es unknown
- 2010-08-26 PT PT107497364T patent/PT2470546E/pt unknown
- 2010-08-26 JP JP2012526992A patent/JP2013503183A/ja not_active Ceased
- 2010-08-26 DK DK10749736.4T patent/DK2470546T3/da active
- 2010-08-27 TW TW099128976A patent/TW201119656A/zh unknown
- 2010-08-27 UY UY0001032863A patent/UY32863A/es not_active Application Discontinuation
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2012
- 2012-03-26 US US13/429,865 patent/US8268819B2/en active Active
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Also Published As
| Publication number | Publication date |
|---|---|
| AR077974A1 (es) | 2011-10-05 |
| SI2470546T1 (sl) | 2013-12-31 |
| DK2470546T3 (da) | 2013-10-14 |
| EP2470546A1 (en) | 2012-07-04 |
| TW201119656A (en) | 2011-06-16 |
| JP2013503183A (ja) | 2013-01-31 |
| PL2470546T3 (pl) | 2013-12-31 |
| UY32863A (es) | 2011-03-31 |
| US20110053921A1 (en) | 2011-03-03 |
| US8268819B2 (en) | 2012-09-18 |
| ES2432315T3 (es) | 2013-12-02 |
| WO2011025889A1 (en) | 2011-03-03 |
| US20120178924A1 (en) | 2012-07-12 |
| US8163755B2 (en) | 2012-04-24 |
| PT2470546E (pt) | 2013-10-14 |
| EP2470546B1 (en) | 2013-07-24 |
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