NZ529256A - 4-amino-5-phenyl-7-cyclobutyl-pyrrolo (2,3-d) pyrimidine derivatives - Google Patents

Info

Publication number

NZ529256A

NZ529256A NZ529256A NZ52925602A NZ529256A NZ 529256 A NZ529256 A NZ 529256A NZ 529256 A NZ529256 A NZ 529256A NZ 52925602 A NZ52925602 A NZ 52925602A NZ 529256 A NZ529256 A NZ 529256A

Authority

NZ

New Zealand

Prior art keywords

lower alkyl

amino

phenyl

pyrrolo

pyrimidin

Prior art date

2001-05-14

Links

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• Global Dossier
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• OVPLBDSXFCRGJY-UHFFFAOYSA-N 7-cyclobutyl-5-phenylpyrrolo[2,3-d]pyrimidin-4-amine Chemical class C1=2C(N)=NC=NC=2N(C2CCC2)C=C1C1=CC=CC=C1 OVPLBDSXFCRGJY-UHFFFAOYSA-N 0.000 title abstract 2
• 238000000034 method Methods 0.000 claims abstract description 64
• 230000008569 process Effects 0.000 claims abstract description 46
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 42
• 201000010099 disease Diseases 0.000 claims abstract description 37
• 238000011282 treatment Methods 0.000 claims abstract description 31
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
• 230000005764 inhibitory process Effects 0.000 claims abstract description 16
• 238000002360 preparation method Methods 0.000 claims abstract description 15
• 241001465754 Metazoa Species 0.000 claims abstract description 12
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 10
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 498
• 150000001875 compounds Chemical class 0.000 claims description 329
• -1 heterocyclic radical Chemical class 0.000 claims description 140
• 150000003254 radicals Chemical class 0.000 claims description 84
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 82
• 150000003839 salts Chemical class 0.000 claims description 69
• 229910052740 iodine Inorganic materials 0.000 claims description 55
• 229910052736 halogen Inorganic materials 0.000 claims description 50
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 49
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 48
• 229910052760 oxygen Inorganic materials 0.000 claims description 48
• 239000001301 oxygen Substances 0.000 claims description 48
• 125000003545 alkoxy group Chemical group 0.000 claims description 47
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 46
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 45
• 150000002367 halogens Chemical class 0.000 claims description 43
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 238000006243 chemical reaction Methods 0.000 claims description 38
• 125000003282 alkyl amino group Chemical group 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 35
• 239000000203 mixture Substances 0.000 claims description 27
• 150000002431 hydrogen Chemical class 0.000 claims description 26
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 22
• 239000004202 carbamide Substances 0.000 claims description 22
• 239000007858 starting material Substances 0.000 claims description 22
• 229910052717 sulfur Inorganic materials 0.000 claims description 22
• 239000011593 sulfur Chemical group 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• MINLECAKOASWQA-UHFFFAOYSA-N 7-[3-(aminomethyl)cyclobutyl]-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1C(CN)CC1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 MINLECAKOASWQA-UHFFFAOYSA-N 0.000 claims description 20
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
• 239000004480 active ingredient Substances 0.000 claims description 14
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 14
• 239000002253 acid Substances 0.000 claims description 13
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 13
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
• 125000006239 protecting group Chemical group 0.000 claims description 11
• 230000004663 cell proliferation Effects 0.000 claims description 10
• 230000001419 dependent effect Effects 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 239000012280 lithium aluminium hydride Substances 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 8
• 125000001589 carboacyl group Chemical group 0.000 claims description 8
• 125000004432 carbon atom Chemical group C* 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000002757 morpholinyl group Chemical group 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 125000004423 acyloxy group Chemical group 0.000 claims description 7
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 150000004702 methyl esters Chemical class 0.000 claims description 6
• 125000005936 piperidyl group Chemical group 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 5
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
• 241000080590 Niso Species 0.000 claims description 4
• 229920002472 Starch Polymers 0.000 claims description 4
• 125000002947 alkylene group Chemical group 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000000524 functional group Chemical group 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• 229940100445 wheat starch Drugs 0.000 claims description 4
• NTMLQBGOQOGFFT-IYARVYRRSA-N C1[C@@H](C(=O)OC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1Br Chemical compound C1[C@@H](C(=O)OC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1Br NTMLQBGOQOGFFT-IYARVYRRSA-N 0.000 claims description 3
• MGADSANUGJPJTF-MXVIHJGJSA-N C1[C@@H](C(=O)OC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1C Chemical compound C1[C@@H](C(=O)OC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1C MGADSANUGJPJTF-MXVIHJGJSA-N 0.000 claims description 3
• 239000007818 Grignard reagent Substances 0.000 claims description 3
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 3
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 3
• 125000005037 alkyl phenyl group Chemical group 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
• 150000004795 grignard reagents Chemical class 0.000 claims description 3
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
• 229940047889 isobutyramide Drugs 0.000 claims description 3
• GQGMUKOYILWOIQ-UHFFFAOYSA-N 6-methyl-5-(3-phenylmethoxyphenyl)-7-[3-(pyrrolidin-1-ylmethyl)cyclobutyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C12=C(N)N=CN=C2N(C2CC(CN3CCCC3)C2)C(C)=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 GQGMUKOYILWOIQ-UHFFFAOYSA-N 0.000 claims description 2
• PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 claims description 2
• NBXXTMKKVACZJZ-HCGLCNNCSA-N C1=2C(N)=NC=NC=2N([C@@H]2C[C@@H](CNC(=O)CN3CCOCC3)C2)C=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2C[C@@H](CNC(=O)CN3CCOCC3)C2)C=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 NBXXTMKKVACZJZ-HCGLCNNCSA-N 0.000 claims description 2
• LDRXGQRNDOVOLA-MXVIHJGJSA-N C1[C@@H](C(=O)N(C)C)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 Chemical compound C1[C@@H](C(=O)N(C)C)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 LDRXGQRNDOVOLA-MXVIHJGJSA-N 0.000 claims description 2
• IHDHVOBYVYYNDS-XUTJKUGGSA-N CCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 IHDHVOBYVYYNDS-XUTJKUGGSA-N 0.000 claims description 2
• VFKIZJLNGDYBKT-AQYVVDRMSA-N CCOCC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CCOCC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 VFKIZJLNGDYBKT-AQYVVDRMSA-N 0.000 claims description 2
• WNITTZHCPWNCNO-HCGLCNNCSA-N Cc1c(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc2n1[C@H]1C[C@H](CN2CCC(O)CC2)C1 Chemical compound Cc1c(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc2n1[C@H]1C[C@H](CN2CCC(O)CC2)C1 WNITTZHCPWNCNO-HCGLCNNCSA-N 0.000 claims description 2
• OBOLLMDLQKRYKB-DUYHBEBVSA-N Cc1cccc(CNC(=O)NC[C@H]2C[C@@H](C2)n2cc(-c3cccc(OCc4ccccc4)c3)c3c(N)ncnc23)c1 Chemical compound Cc1cccc(CNC(=O)NC[C@H]2C[C@@H](C2)n2cc(-c3cccc(OCc4ccccc4)c3)c3c(N)ncnc23)c1 OBOLLMDLQKRYKB-DUYHBEBVSA-N 0.000 claims description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 2
• UZEIODJMSHKOGA-NDZWVUITSA-N Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC23CC4CC(CC(C4)C2)C3)C1 Chemical compound Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC23CC4CC(CC(C4)C2)C3)C1 UZEIODJMSHKOGA-NDZWVUITSA-N 0.000 claims description 2
• 150000001412 amines Chemical class 0.000 claims description 2
• 150000004820 halides Chemical class 0.000 claims description 2
• 239000008101 lactose Substances 0.000 claims description 2
• 125000006501 nitrophenyl group Chemical group 0.000 claims description 2
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 2
• 235000012239 silicon dioxide Nutrition 0.000 claims description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 4
• 239000007903 gelatin capsule Substances 0.000 claims 2
• 235000019359 magnesium stearate Nutrition 0.000 claims 2
• 239000000454 talc Substances 0.000 claims 2
• 229910052623 talc Inorganic materials 0.000 claims 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
• IONLBUKCCPUJIH-HCGLCNNCSA-N C1=2C(N)=NC=NC=2N([C@@H]2C[C@@H](CN3CCCCC3)C2)C=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2C[C@@H](CN3CCCCC3)C2)C=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 IONLBUKCCPUJIH-HCGLCNNCSA-N 0.000 claims 1
• FITJQXRHQKAHRQ-WGSAOQKQSA-N C1[C@@H](C(=O)NC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 Chemical compound C1[C@@H](C(=O)NC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 FITJQXRHQKAHRQ-WGSAOQKQSA-N 0.000 claims 1
• MINLECAKOASWQA-UAPYVXQJSA-N C1[C@@H](CN)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 Chemical compound C1[C@@H](CN)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 MINLECAKOASWQA-UAPYVXQJSA-N 0.000 claims 1
• WBYYXJHMBIEJCC-AFARHQOCSA-N C1[C@@H](CNC(=O)N(CC)CC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 Chemical compound C1[C@@H](CNC(=O)N(CC)CC)C[C@@H]1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 WBYYXJHMBIEJCC-AFARHQOCSA-N 0.000 claims 1
• YXDCWJMOUVTHNI-AQYVVDRMSA-N CC(C)(C)C(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CC(C)(C)C(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 YXDCWJMOUVTHNI-AQYVVDRMSA-N 0.000 claims 1
• VCEIHCLYWKZRCQ-AFARHQOCSA-N CCCCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CCCCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 VCEIHCLYWKZRCQ-AFARHQOCSA-N 0.000 claims 1
• PYYNBGZIQCNCCI-XUTJKUGGSA-N CCOC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CCOC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 PYYNBGZIQCNCCI-XUTJKUGGSA-N 0.000 claims 1
• WNLYZRUMUOYMRP-KESTWPANSA-N CCc1c(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc2n1[C@H]1C[C@H](CO)C1 Chemical compound CCc1c(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc2n1[C@H]1C[C@H](CO)C1 WNLYZRUMUOYMRP-KESTWPANSA-N 0.000 claims 1
• HODGCSQBGRCWLO-HCGLCNNCSA-N CN(C)CCCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CN(C)CCCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 HODGCSQBGRCWLO-HCGLCNNCSA-N 0.000 claims 1
• MEDPKRVFVDCJBF-YOCNBXQISA-N CN1CCN(CCOC(=O)NC[C@H]2C[C@@H](C2)n2cc(-c3cccc(OCc4ccccc4)c3)c3c(N)ncnc23)CC1 Chemical compound CN1CCN(CCOC(=O)NC[C@H]2C[C@@H](C2)n2cc(-c3cccc(OCc4ccccc4)c3)c3c(N)ncnc23)CC1 MEDPKRVFVDCJBF-YOCNBXQISA-N 0.000 claims 1
• OOFFWNVNYZXYNM-ALOJWSFFSA-N CN1CCN(C[C@H]2C[C@@H](C2)n2c(C)c(-c3cccc(OCc4ccccc4)c3)c3c(N)ncnc23)CC1 Chemical compound CN1CCN(C[C@H]2C[C@@H](C2)n2c(C)c(-c3cccc(OCc4ccccc4)c3)c3c(N)ncnc23)CC1 OOFFWNVNYZXYNM-ALOJWSFFSA-N 0.000 claims 1
• UNFLVZMMYVSVKS-HCGLCNNCSA-N COc1ccc(cc1)S(=O)(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound COc1ccc(cc1)S(=O)(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 UNFLVZMMYVSVKS-HCGLCNNCSA-N 0.000 claims 1
• ZYTNWUOCGAJUTN-WGSAOQKQSA-N NC=1C2=C(N=CN=1)N(C(=C2C1=CC(=CC=C1)OCC1=CC=CC=C1)CC)[C@@H]1C[C@H](C1)C(=O)O Chemical compound NC=1C2=C(N=CN=1)N(C(=C2C1=CC(=CC=C1)OCC1=CC=CC=C1)CC)[C@@H]1C[C@H](C1)C(=O)O ZYTNWUOCGAJUTN-WGSAOQKQSA-N 0.000 claims 1
• RLCZUYQBURMNDZ-AFARHQOCSA-N Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)N2CCOCC2)C1 Chemical compound Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)N2CCOCC2)C1 RLCZUYQBURMNDZ-AFARHQOCSA-N 0.000 claims 1
• LPQONMCVBNYRRX-YOCNBXQISA-N Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)NCCCN2CCOCC2)C1 Chemical compound Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)NCCCN2CCOCC2)C1 LPQONMCVBNYRRX-YOCNBXQISA-N 0.000 claims 1
• HTRBGRLCGGGPPN-YOCNBXQISA-N Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)NCc2ccccc2)C1 Chemical compound Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)NCc2ccccc2)C1 HTRBGRLCGGGPPN-YOCNBXQISA-N 0.000 claims 1
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 1
• LLRANSBEYQZKFY-UHFFFAOYSA-N dodecanoic acid;propane-1,2-diol Chemical compound CC(O)CO.CCCCCCCCCCCC(O)=O LLRANSBEYQZKFY-UHFFFAOYSA-N 0.000 claims 1
• 239000008187 granular material Substances 0.000 claims 1
• 239000002245 particle Substances 0.000 claims 1
• 239000000843 powder Substances 0.000 claims 1
• 229940080818 propionamide Drugs 0.000 claims 1
• 125000006413 ring segment Chemical group 0.000 claims 1
• 239000007901 soft capsule Substances 0.000 claims 1
• 238000005303 weighing Methods 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 abstract description 24
• 230000002062 proliferating effect Effects 0.000 abstract description 7
• 241000282412 Homo Species 0.000 abstract description 4
• 241000124008 Mammalia Species 0.000 abstract description 4
• 239000003814 drug Substances 0.000 abstract description 4
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 140
• 238000004128 high performance liquid chromatography Methods 0.000 description 138
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