SK14022003A3 - 4-Amino-5-fenyl-7-cyklobutylpyrolo[2,3-d]pyrimidínové deriváty, spôsob ich prípravy a ich použitie - Google Patents

Info

Publication number

SK14022003A3

SK14022003A3 SK1402-2003A SK14022003A SK14022003A3 SK 14022003 A3 SK14022003 A3 SK 14022003A3 SK 14022003 A SK14022003 A SK 14022003A SK 14022003 A3 SK14022003 A3 SK 14022003A3

Authority

SK

Slovakia

Prior art keywords

lower alkyl

amino

pyrimidin

benzyloxyphenyl

pyrrolo

Prior art date

2001-05-14

Links

• Espacenet
• 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 claims abstract description 5
• 238000000034 method Methods 0.000 claims abstract description 135
• 238000002360 preparation method Methods 0.000 claims abstract description 48
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 37
• 201000010099 disease Diseases 0.000 claims abstract description 36
• 238000011282 treatment Methods 0.000 claims abstract description 27
• 230000008569 process Effects 0.000 claims abstract description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 241001465754 Metazoa Species 0.000 claims abstract description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 567
• 150000001875 compounds Chemical class 0.000 claims description 333
• -1 heterocyclic radical Chemical class 0.000 claims description 300
• 229910052757 nitrogen Inorganic materials 0.000 claims description 101
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 80
• 150000003839 salts Chemical group 0.000 claims description 72
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 71
• 150000003254 radicals Chemical class 0.000 claims description 69
• 125000003545 alkoxy group Chemical group 0.000 claims description 61
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 61
• 125000003277 amino group Chemical group 0.000 claims description 46
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 40
• 238000006243 chemical reaction Methods 0.000 claims description 39
• 125000005843 halogen group Chemical group 0.000 claims description 35
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 35
• 229910052717 sulfur Inorganic materials 0.000 claims description 33
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 31
• 229910052760 oxygen Inorganic materials 0.000 claims description 30
• 239000007858 starting material Substances 0.000 claims description 28
• 239000001301 oxygen Substances 0.000 claims description 27
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• 239000000203 mixture Substances 0.000 claims description 24
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 21
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 21
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 21
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
• 239000011593 sulfur Chemical group 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
• 229910052736 halogen Chemical group 0.000 claims description 19
• 125000003282 alkyl amino group Chemical group 0.000 claims description 18
• 125000000623 heterocyclic group Chemical group 0.000 claims description 16
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
• 125000001589 carboacyl group Chemical group 0.000 claims description 14
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 12
• 150000002367 halogens Chemical class 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
• 125000006239 protecting group Chemical group 0.000 claims description 11
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 10
• 230000001419 dependent effect Effects 0.000 claims description 10
• 230000005764 inhibitory process Effects 0.000 claims description 10
• 125000002757 morpholinyl group Chemical group 0.000 claims description 10
• 125000004434 sulfur atom Chemical group 0.000 claims description 10
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
• 230000004663 cell proliferation Effects 0.000 claims description 9
• TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 239000012280 lithium aluminium hydride Substances 0.000 claims description 9
• 125000005936 piperidyl group Chemical group 0.000 claims description 9
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 9
• 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 8
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 8
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 8
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 8
• 239000002253 acid Substances 0.000 claims description 8
• 239000004202 carbamide Substances 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 125000004423 acyloxy group Chemical group 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 229910052739 hydrogen Inorganic materials 0.000 claims description 5
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
• 125000005037 alkyl phenyl group Chemical group 0.000 claims description 4
• 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 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
• 125000000524 functional group Chemical group 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• 239000001257 hydrogen Substances 0.000 claims description 4
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 4
• 150000004702 methyl esters Chemical class 0.000 claims description 4
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 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
• 239000007818 Grignard reagent Substances 0.000 claims description 3
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 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
• ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 3
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 150000004795 grignard reagents Chemical class 0.000 claims description 3
• CBTGNLZUIZHUHY-UHFFFAOYSA-N methyl cyclobutanecarboxylate Chemical compound COC(=O)C1CCC1 CBTGNLZUIZHUHY-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical compound NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 claims description 2
• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims description 2
• ICHGNLVHYDFSAR-RZFKFIIISA-N C12=C(N)N=CN=C2N([C@@H]2C[C@@H](CNC3CCOCC3)C2)C(C)=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 Chemical compound C12=C(N)N=CN=C2N([C@@H]2C[C@@H](CNC3CCOCC3)C2)C(C)=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 ICHGNLVHYDFSAR-RZFKFIIISA-N 0.000 claims description 2
• ZXYAKTRUTLRFEX-YFJLJUBXSA-N C1C(C)OC(C)CN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)=C2)C1 Chemical compound C1C(C)OC(C)CN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)=C2)C1 ZXYAKTRUTLRFEX-YFJLJUBXSA-N 0.000 claims description 2
• CZOJVEPPEOWDQJ-YFJLJUBXSA-N CC1CCC(C)N1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)=C2)C1 Chemical compound CC1CCC(C)N1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)=C2)C1 CZOJVEPPEOWDQJ-YFJLJUBXSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• 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 description 2
• OQIGTHHTVJUMHD-KESTWPANSA-N CNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 OQIGTHHTVJUMHD-KESTWPANSA-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
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
• AMEJSINMHMEDLL-AFARHQOCSA-N Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CN2CCC(O)CC2)C1 Chemical compound Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CN2CCC(O)CC2)C1 AMEJSINMHMEDLL-AFARHQOCSA-N 0.000 claims description 2
• 125000002947 alkylene group Chemical group 0.000 claims description 2
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
• BUCAFRXFNHCHRU-UHFFFAOYSA-N n-[[3-[4-amino-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]methyl]acetamide Chemical compound C1C(CNC(=O)C)CC1N1C2=NC=NC(N)=C2C(C=2C=C(OCC=3C=CC=CC=3)C=CC=2)=C1 BUCAFRXFNHCHRU-UHFFFAOYSA-N 0.000 claims description 2
• 125000006501 nitrophenyl group Chemical group 0.000 claims description 2
• RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 claims description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 5
• WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 claims 2
• 125000004494 ethyl ester group Chemical group 0.000 claims 2
• 229940047889 isobutyramide Drugs 0.000 claims 2
• 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims 1
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
• KUUHULDUODEQHB-AFARHQOCSA-N C1=2C(N)=NC=NC=2N([C@@H]2C[C@@H](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](CN3CCOCC3)C2)C=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 KUUHULDUODEQHB-AFARHQOCSA-N 0.000 claims 1
• REXRZICSDNALRF-HCGLCNNCSA-N C1CN(C)CCN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)=C2)C1 Chemical compound C1CN(C)CCN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)=C2)C1 REXRZICSDNALRF-HCGLCNNCSA-N 0.000 claims 1
• XRMMWXGVGDPTGL-AQYVVDRMSA-N CC(C)(C)NC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CC(C)(C)NC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 XRMMWXGVGDPTGL-AQYVVDRMSA-N 0.000 claims 1
• JTAVVFISQTXCHE-AFARHQOCSA-N CN(C)CCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound CN(C)CCNC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 JTAVVFISQTXCHE-AFARHQOCSA-N 0.000 claims 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
• PNEPNZDINPZUFR-UAPYVXQJSA-N NC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 Chemical compound NC(=O)NC[C@H]1C[C@@H](C1)n1cc(-c2cccc(OCc3ccccc3)c2)c2c(N)ncnc12 PNEPNZDINPZUFR-UAPYVXQJSA-N 0.000 claims 1
• FVDWCEYQBCTACG-AFARHQOCSA-N Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CN2CCSCC2)C1 Chemical compound Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CN2CCSCC2)C1 FVDWCEYQBCTACG-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
• KDJUOUXKVYJHEQ-ALOJWSFFSA-N Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)NCCN2CCOCC2)C1 Chemical compound Nc1ncnc2n(cc(-c3cccc(OCc4ccccc4)c3)c12)[C@H]1C[C@H](CNC(=O)NCCN2CCOCC2)C1 KDJUOUXKVYJHEQ-ALOJWSFFSA-N 0.000 claims 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 1
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims 1
• 125000004404 heteroalkyl group Chemical group 0.000 claims 1
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
• HWIGZMADSFQMOI-UHFFFAOYSA-N methyl 2-(2,4-dichlorophenoxy)acetate Chemical compound COC(=O)COC1=CC=C(Cl)C=C1Cl HWIGZMADSFQMOI-UHFFFAOYSA-N 0.000 claims 1
• JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical class NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 claims 1
• HNDXKIMMSFCCFW-UHFFFAOYSA-M propane-2-sulfonate Chemical compound CC(C)S([O-])(=O)=O HNDXKIMMSFCCFW-UHFFFAOYSA-M 0.000 claims 1
• 125000006413 ring segment Chemical group 0.000 claims 1
• 206010028980 Neoplasm Diseases 0.000 abstract description 24
• 230000002062 proliferating effect Effects 0.000 abstract description 8
• 241000282412 Homo Species 0.000 abstract description 6
• 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
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
• 241000208199 Buxus sempervirens Species 0.000 description 76
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
• 210000004027 cell Anatomy 0.000 description 33
• 239000000243 solution Substances 0.000 description 33
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 108010031794 IGF Type 1 Receptor Proteins 0.000 description 29
• 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 29
• 238000005160 1H NMR spectroscopy Methods 0.000 description 27
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 239000011541 reaction mixture Substances 0.000 description 26
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
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