RU2616619C2 - Морфолино-замещенные производные мочевины или карбамата в качестве ингибиторов mtor - Google Patents

Info

Publication number

RU2616619C2

RU2616619C2 RU2014109747A RU2014109747A RU2616619C2 RU 2616619 C2 RU2616619 C2 RU 2616619C2 RU 2014109747 A RU2014109747 A RU 2014109747A RU 2014109747 A RU2014109747 A RU 2014109747A RU 2616619 C2 RU2616619 C2 RU 2616619C2

Authority

RU

Russia

Prior art keywords

phenyl

triazin

methylsulfonyl

urea

methylmorpholino

Prior art date

2011-09-21

Links

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• Global Dossier
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• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title description 24
• 229940124302 mTOR inhibitor Drugs 0.000 title description 21
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical class NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 title 1
• 150000003672 ureas Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 126
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims abstract description 80
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims abstract description 80
• 238000000034 method Methods 0.000 claims abstract description 41
• 239000003814 drug Substances 0.000 claims abstract description 30
• 238000011282 treatment Methods 0.000 claims abstract description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 14
• 238000004519 manufacturing process Methods 0.000 claims abstract description 13
• 230000002265 prevention Effects 0.000 claims abstract description 10
• 208000037765 diseases and disorders Diseases 0.000 claims abstract description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 5
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 69
• 150000003839 salts Chemical class 0.000 claims description 60
• 125000000217 alkyl group Chemical group 0.000 claims description 49
• 201000010099 disease Diseases 0.000 claims description 49
• -1 8-oxa-3-azabicyclo [3.2.1] octan-3-yl Chemical group 0.000 claims description 47
• 208000035475 disorder Diseases 0.000 claims description 20
• 206010028980 Neoplasm Diseases 0.000 claims description 19
• 230000004900 autophagic degradation Effects 0.000 claims description 19
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 18
• 201000011510 cancer Diseases 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 13
• 239000004202 carbamide Substances 0.000 claims description 11
• 230000004770 neurodegeneration Effects 0.000 claims description 11
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 11
• 230000002062 proliferating effect Effects 0.000 claims description 10
• 125000006413 ring segment Chemical group 0.000 claims description 10
• 206010052779 Transplant rejections Diseases 0.000 claims description 9
• 230000002757 inflammatory effect Effects 0.000 claims description 9
• 241000124008 Mammalia Species 0.000 claims description 8
• 230000001363 autoimmune Effects 0.000 claims description 8
• 208000030159 metabolic disease Diseases 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
• 230000000172 allergic effect Effects 0.000 claims description 7
• 208000010668 atopic eczema Diseases 0.000 claims description 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 230000001900 immune effect Effects 0.000 claims description 7
• 208000036142 Viral infection Diseases 0.000 claims description 6
• 230000015572 biosynthetic process Effects 0.000 claims description 6
• 239000010802 sludge Substances 0.000 claims description 6
• 230000009385 viral infection Effects 0.000 claims description 6
• ZVVZLBPJNXSTDA-UHFFFAOYSA-N [4-[4-(3-methylmorpholin-4-yl)-6-(2-methylsulfonylpyridin-3-yl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CC1COCCN1C1=NC(=NC(=N1)C=1C(=NC=CC=1)S(=O)(=O)C)C1=CC=C(C=C1)NC(N)=O ZVVZLBPJNXSTDA-UHFFFAOYSA-N 0.000 claims description 5
• 208000016097 disease of metabolism Diseases 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• JTWIUWYFTTUDAS-INIZCTEOSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 JTWIUWYFTTUDAS-INIZCTEOSA-N 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• GHPKGLRLNYQRBA-SFHVURJKSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC=3C=NC=CC=3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 GHPKGLRLNYQRBA-SFHVURJKSA-N 0.000 claims description 3
• 150000001721 carbon Chemical group 0.000 claims description 3
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 230000006806 disease prevention Effects 0.000 claims description 3
• 229910052731 fluorine Inorganic materials 0.000 claims description 3
• SQWAKKGIJSCBDW-OOJLDXBWSA-N 1-(2,2-difluorocyclopropyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3C(C3)(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 SQWAKKGIJSCBDW-OOJLDXBWSA-N 0.000 claims description 2
• WYVZYLFSFLZJLE-AWEZNQCLSA-N 1-(2,2-difluoroethyl)-3-[4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-[(3s)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(F)F)=CC=2)=NC(C=2C(=CC=C(F)C=2)S(C)(=O)=O)=N1 WYVZYLFSFLZJLE-AWEZNQCLSA-N 0.000 claims description 2
• VGGRTBRWWUFDQE-HNNXBMFYSA-N 1-(2,2-difluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 VGGRTBRWWUFDQE-HNNXBMFYSA-N 0.000 claims description 2
• BTUQEGIDVUWXLY-SFHVURJKSA-N 1-(2,2-dimethylpropyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(C)(C)C)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 BTUQEGIDVUWXLY-SFHVURJKSA-N 0.000 claims description 2
• WQSLRAHWQAGEEV-HNNXBMFYSA-N 1-(2-fluoroethyl)-3-[4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-[(3s)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=NC(C=2C(=CC=C(F)C=2)S(C)(=O)=O)=N1 WQSLRAHWQAGEEV-HNNXBMFYSA-N 0.000 claims description 2
• DWHLEZSBYLJWAP-INIZCTEOSA-N 1-(2-fluoroethyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCF)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 DWHLEZSBYLJWAP-INIZCTEOSA-N 0.000 claims description 2
• MZIHKPPULSTVPI-BJQOMGFOSA-N 1-(3-amino-4,4,4-trifluorobutyl)-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCC(N)C(F)(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 MZIHKPPULSTVPI-BJQOMGFOSA-N 0.000 claims description 2
• CBTGCCPITWABCX-HNNXBMFYSA-N 1-[4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-[(3s)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCCO)=CC=2)=NC(C=2C(=CC=C(F)C=2)S(C)(=O)=O)=N1 CBTGCCPITWABCX-HNNXBMFYSA-N 0.000 claims description 2
• NQDNTFVBTMDPOY-AWEZNQCLSA-N 1-[4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-[(3s)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=C(F)C=2)S(C)(=O)=O)=N1 NQDNTFVBTMDPOY-AWEZNQCLSA-N 0.000 claims description 2
• SVVLFAXKYZRIEU-HNNXBMFYSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(2,2,2-trifluoroethyl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(F)(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 SVVLFAXKYZRIEU-HNNXBMFYSA-N 0.000 claims description 2
• IQZVHHCWLJKABG-SFHVURJKSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(2-methylpropyl)urea Chemical compound C1=CC(NC(=O)NCC(C)C)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 IQZVHHCWLJKABG-SFHVURJKSA-N 0.000 claims description 2
• OBNUCJQVVUPBMF-OOJLDXBWSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(3,3,3-trifluoro-2-hydroxypropyl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NCC(O)C(F)(F)F)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 OBNUCJQVVUPBMF-OOJLDXBWSA-N 0.000 claims description 2
• QUUFTKOHCWDTPU-INIZCTEOSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(oxetan-3-yl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3COC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 QUUFTKOHCWDTPU-INIZCTEOSA-N 0.000 claims description 2
• DTJJNINJMPHAGI-DIMJTDRSSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-(oxolan-3-yl)urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3COCC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 DTJJNINJMPHAGI-DIMJTDRSSA-N 0.000 claims description 2
• WTVPWCNBRLNHIC-KRWDZBQOSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-propan-2-ylurea Chemical compound C1=CC(NC(=O)NC(C)C)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 WTVPWCNBRLNHIC-KRWDZBQOSA-N 0.000 claims description 2
• NBMCWYMOBZCRCH-KRWDZBQOSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-propylurea Chemical compound C1=CC(NC(=O)NCCC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 NBMCWYMOBZCRCH-KRWDZBQOSA-N 0.000 claims description 2
• OBQBFVXXGFPXMM-SFHVURJKSA-N 1-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC=3C=CN=CC=3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 OBQBFVXXGFPXMM-SFHVURJKSA-N 0.000 claims description 2
• SNXHGDLEEWPMMH-KRWDZBQOSA-N 1-cyclobutyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CCC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 SNXHGDLEEWPMMH-KRWDZBQOSA-N 0.000 claims description 2
• HGOXTLYZGOXGIM-IBGZPJMESA-N 1-cyclohexyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CCCCC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 HGOXTLYZGOXGIM-IBGZPJMESA-N 0.000 claims description 2
• FZJLSYYBXRUXGH-SFHVURJKSA-N 1-cyclopentyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CCCC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 FZJLSYYBXRUXGH-SFHVURJKSA-N 0.000 claims description 2
• LLYIELJURDPGCH-KRWDZBQOSA-N 1-cyclopropyl-3-[4-[4-(2-ethylsulfonylphenyl)-6-[(3s)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CCS(=O)(=O)C1=CC=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 LLYIELJURDPGCH-KRWDZBQOSA-N 0.000 claims description 2
• KZICCAFBGTVPIO-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(2-methylsulfonylphenyl)-6-(1,4-oxazepan-4-yl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=NC(N2CCOCCC2)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 KZICCAFBGTVPIO-UHFFFAOYSA-N 0.000 claims description 2
• KYANJFCYCNOTEN-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(2-methylsulfonylphenyl)-6-morpholin-4-yl-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=NC(N2CCOCC2)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 KYANJFCYCNOTEN-UHFFFAOYSA-N 0.000 claims description 2
• WLORGJWWSIEHGH-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(3,3-dimethylmorpholin-4-yl)-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CC1(C)COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 WLORGJWWSIEHGH-UHFFFAOYSA-N 0.000 claims description 2
• RRBDAWQZDGPPKD-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(3-ethylmorpholin-4-yl)-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CCC1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 RRBDAWQZDGPPKD-UHFFFAOYSA-N 0.000 claims description 2
• PJLYVQWIEXBFKX-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CS(=O)(=O)C1=CC=C(F)C=C1C1=NC(N2CC3CCC(O3)C2)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 PJLYVQWIEXBFKX-UHFFFAOYSA-N 0.000 claims description 2
• JTWIUWYFTTUDAS-MRXNPFEDSA-N 1-cyclopropyl-3-[4-[4-[(3r)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C[C@@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 JTWIUWYFTTUDAS-MRXNPFEDSA-N 0.000 claims description 2
• STZUVZVOVGSFFP-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-[3-(hydroxymethyl)morpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=NC(N2C(COCC2)CO)=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=N1 STZUVZVOVGSFFP-UHFFFAOYSA-N 0.000 claims description 2
• OWHWSFSRAOFWHP-HNNXBMFYSA-N 1-ethyl-3-[4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-[(3s)-3-methylmorpholin-4-yl]-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=C(F)C=2)S(C)(=O)=O)=N1 OWHWSFSRAOFWHP-HNNXBMFYSA-N 0.000 claims description 2
• SHEFEJGEGWCOJZ-INIZCTEOSA-N 1-ethyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 SHEFEJGEGWCOJZ-INIZCTEOSA-N 0.000 claims description 2
• YKIWVDVZGHLPNJ-HNNXBMFYSA-N 1-methyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-6-(2-methylsulfonylphenyl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2[C@H](COCC2)C)=NC(C=2C(=CC=CC=2)S(C)(=O)=O)=N1 YKIWVDVZGHLPNJ-HNNXBMFYSA-N 0.000 claims description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• XAVFYPNLILFEIF-UHFFFAOYSA-N CC1COCCN1C2=NC(=NC(=N2)C3=CC=CC=C3S(=O)(=O)N4CCCC4)C5=CC=C(C=C5)NC(=O)N Chemical compound CC1COCCN1C2=NC(=NC(=N2)C3=CC=CC=C3S(=O)(=O)N4CCCC4)C5=CC=C(C=C5)NC(=O)N XAVFYPNLILFEIF-UHFFFAOYSA-N 0.000 claims description 2
• ZHIBRAINUDOTCB-UHFFFAOYSA-N [4-[4-(5-fluoro-2-methylsulfonylphenyl)-6-(3-methylmorpholin-4-yl)-1,3,5-triazin-2-yl]phenyl]urea Chemical compound FC=1C=CC(=C(C=1)C1=NC(=NC(=N1)N1C(COCC1)C)C1=CC=C(C=C1)NC(=O)N)S(=O)(=O)C ZHIBRAINUDOTCB-UHFFFAOYSA-N 0.000 claims description 2
• 125000003566 oxetanyl group Chemical group 0.000 claims description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
• 230000000694 effects Effects 0.000 abstract description 21
• 229940079593 drug Drugs 0.000 abstract description 16
• 125000005843 halogen group Chemical group 0.000 abstract description 13
• 125000004432 carbon atom Chemical group C* 0.000 abstract description 4
• 239000000126 substance Substances 0.000 abstract description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 7
• 125000004429 atom Chemical group 0.000 abstract 3
• 239000000203 mixture Substances 0.000 description 39
• 210000004027 cell Anatomy 0.000 description 31
• 108090000623 proteins and genes Proteins 0.000 description 31
• 102000004169 proteins and genes Human genes 0.000 description 27
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 27
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