JP2013512215A - 二環式ヘテロアリールのベンゼン縮合６員酸素含有ヘテロ環誘導体 - Google Patents

Info

Publication number

JP2013512215A

JP2013512215A JP2012540402A JP2012540402A JP2013512215A JP 2013512215 A JP2013512215 A JP 2013512215A JP 2012540402 A JP2012540402 A JP 2012540402A JP 2012540402 A JP2012540402 A JP 2012540402A JP 2013512215 A JP2013512215 A JP 2013512215A

Authority

JP

Japan

Prior art keywords

chroman

pyrrolo

pyrimidin

amino

cis

Prior art date

2009-11-25

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• Discuss

• 125000000623 heterocyclic group Chemical group 0.000 title claims description 53
• 229910052760 oxygen Inorganic materials 0.000 title claims description 15
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title description 7
• 239000001301 oxygen Substances 0.000 title description 6
• 125000001072 heteroaryl group Chemical group 0.000 title description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 title 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 362
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 53
• 201000010099 disease Diseases 0.000 claims abstract description 37
• 239000003814 drug Substances 0.000 claims abstract description 30
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 238000004519 manufacturing process Methods 0.000 claims abstract description 17
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 276
• 238000000034 method Methods 0.000 claims description 198
• -1 hydroxy, amino Chemical group 0.000 claims description 149
• 150000003839 salts Chemical class 0.000 claims description 68
• 125000000217 alkyl group Chemical group 0.000 claims description 57
• 125000001424 substituent group Chemical group 0.000 claims description 50
• 229920006395 saturated elastomer Polymers 0.000 claims description 39
• 206010028980 Neoplasm Diseases 0.000 claims description 37
• 230000000694 effects Effects 0.000 claims description 32
• 125000004429 atom Chemical group 0.000 claims description 24
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 125000003545 alkoxy group Chemical group 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 19
• 229910052739 hydrogen Inorganic materials 0.000 claims description 19
• 230000005764 inhibitory process Effects 0.000 claims description 19
• 229910052717 sulfur Inorganic materials 0.000 claims description 19
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
• 208000035475 disorder Diseases 0.000 claims description 16
• 239000001257 hydrogen Substances 0.000 claims description 16
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 15
• 230000001404 mediated effect Effects 0.000 claims description 15
• 229940079593 drug Drugs 0.000 claims description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• 125000004432 carbon atom Chemical group C* 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
• 125000006413 ring segment Chemical group 0.000 claims description 12
• 125000004414 alkyl thio group Chemical group 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 11
• 125000005843 halogen group Chemical group 0.000 claims description 11
• 230000001028 anti-proliverative effect Effects 0.000 claims description 10
• 125000004043 oxo group Chemical group O=* 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 8
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 8
• 208000020990 adrenal cortex carcinoma Diseases 0.000 claims description 8
• 208000007128 adrenocortical carcinoma Diseases 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 8
• 125000004434 sulfur atom Chemical group 0.000 claims description 8
• 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 7
• 239000003937 drug carrier Substances 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 125000003003 spiro group Chemical group 0.000 claims description 7
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 6
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
• 125000003282 alkyl amino group Chemical group 0.000 claims description 6
• 150000002367 halogens Chemical class 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 5
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 5
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 5
• 201000001441 melanoma Diseases 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 201000008968 osteosarcoma Diseases 0.000 claims description 5
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
• 206010006187 Breast cancer Diseases 0.000 claims description 4
• 208000026310 Breast neoplasm Diseases 0.000 claims description 4
• 208000002699 Digestive System Neoplasms Diseases 0.000 claims description 4
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
• 206010033128 Ovarian cancer Diseases 0.000 claims description 4
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
• 206010060862 Prostate cancer Diseases 0.000 claims description 4
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
• 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
• 125000004122 cyclic group Chemical group 0.000 claims description 4
• 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 claims description 4
• 201000005202 lung cancer Diseases 0.000 claims description 4
• 208000020816 lung neoplasm Diseases 0.000 claims description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
• 201000002528 pancreatic cancer Diseases 0.000 claims description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
• 201000002510 thyroid cancer Diseases 0.000 claims description 4
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
• 208000006168 Ewing Sarcoma Diseases 0.000 claims description 3
• 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
• 208000034578 Multiple myelomas Diseases 0.000 claims description 3
• 206010029260 Neuroblastoma Diseases 0.000 claims description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
• 206010038389 Renal cancer Diseases 0.000 claims description 3
• 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
• 206010069351 acute lung injury Diseases 0.000 claims description 3
• 125000004423 acyloxy group Chemical group 0.000 claims description 3
• 125000001589 carboacyl group Chemical group 0.000 claims description 3
• 201000010982 kidney cancer Diseases 0.000 claims description 3
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
• 238000007363 ring formation reaction Methods 0.000 claims description 3
• 206010046766 uterine cancer Diseases 0.000 claims description 3
• XRVHJTJZLIVDQA-UHFFFAOYSA-N 1-[[3-[4-amino-5-(2-phenyl-3,4-dihydro-2h-chromen-7-yl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]methyl]piperidin-4-ol Chemical compound C1=2C(N)=NC=NC=2N(C2CC(CN3CCC(O)CC3)C2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=C1 XRVHJTJZLIVDQA-UHFFFAOYSA-N 0.000 claims description 2
• IHXVQVHYGOMGDE-UHFFFAOYSA-N 4-[[3-[4-amino-5-(2-phenyl-3,4-dihydro-2h-chromen-7-yl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]methyl]-1-methylpiperazin-2-one Chemical compound C1C(=O)N(C)CCN1CC1CC(N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3C=CC=CC=3)=C2)C1 IHXVQVHYGOMGDE-UHFFFAOYSA-N 0.000 claims description 2
• PHVIIBUNLRRJSZ-BEDZIMQSSA-N C([C@H]1C[C@H](C1)N1C=C(C2=C(N)N=CN=C21)C1=CC=C2CCC(OC2=C1)COCC)N1CCS(=O)CC1 Chemical compound C([C@H]1C[C@H](C1)N1C=C(C2=C(N)N=CN=C21)C1=CC=C2CCC(OC2=C1)COCC)N1CCS(=O)CC1 PHVIIBUNLRRJSZ-BEDZIMQSSA-N 0.000 claims description 2
• BNNWRUYZDOLKJC-AQKFKSFVSA-N C1([C@@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CO)C2)=CC=CC=C1 Chemical compound C1([C@@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CO)C2)=CC=CC=C1 BNNWRUYZDOLKJC-AQKFKSFVSA-N 0.000 claims description 2
• RSBQTLSGSPBIIE-NNKBHPLTSA-N C1([C@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CN3[C@@H](CCC3)CO)C2)=CC=CC=C1 Chemical compound C1([C@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CN3[C@@H](CCC3)CO)C2)=CC=CC=C1 RSBQTLSGSPBIIE-NNKBHPLTSA-N 0.000 claims description 2
• BNNWRUYZDOLKJC-QGCDCVKKSA-N C1([C@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CO)C2)=CC=CC=C1 Chemical compound C1([C@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CO)C2)=CC=CC=C1 BNNWRUYZDOLKJC-QGCDCVKKSA-N 0.000 claims description 2
• 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 2
• QZSDGBOGOGOEHX-KQYMJHLBSA-N C12=C(N)N=CN=C2N([C@@H]2C[C@@H](C2)CN2C[C@@]3(C[C@]2(CS3(=O)=O)[H])[H])C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=N1 Chemical compound C12=C(N)N=CN=C2N([C@@H]2C[C@@H](C2)CN2C[C@@]3(C[C@]2(CS3(=O)=O)[H])[H])C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=N1 QZSDGBOGOGOEHX-KQYMJHLBSA-N 0.000 claims description 2
• WGBJMKBGDNBCMU-MAOIWGCQSA-N C1=2C(N)=NC=NC=2N([C@H]2CC[C@H](CC2)NC(=O)C2CC2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=C1 Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CC[C@H](CC2)NC(=O)C2CC2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=C1 WGBJMKBGDNBCMU-MAOIWGCQSA-N 0.000 claims description 2
• PXXZPGFGDTVGOE-RZJSWYKGSA-N C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CC=C2C1=CC=CC=C1 Chemical compound C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CC=C2C1=CC=CC=C1 PXXZPGFGDTVGOE-RZJSWYKGSA-N 0.000 claims description 2
• NSUWQVFRRVVGTH-UHGJSFDGSA-N C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CCC12CCCCC1 Chemical compound C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CCC12CCCCC1 NSUWQVFRRVVGTH-UHGJSFDGSA-N 0.000 claims description 2
• UKIFTTIWWVAGHO-NSWDLBSPSA-N C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=N1 Chemical compound C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=N1 UKIFTTIWWVAGHO-NSWDLBSPSA-N 0.000 claims description 2
• ZOPMETKNELTEBW-NSWDLBSPSA-N C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=N1 Chemical compound C1=2C(N)=NC=NC=2N([C@H]2C[C@@H](CN3CCS(=O)CC3)C2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=N1 ZOPMETKNELTEBW-NSWDLBSPSA-N 0.000 claims description 2
• WNKDWFNWCAHYJJ-NSWDLBSPSA-N C1C(=O)N(C)CCN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3N=CC=CC=3)=C2)C1 Chemical compound C1C(=O)N(C)CCN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3N=CC=CC=3)=C2)C1 WNKDWFNWCAHYJJ-NSWDLBSPSA-N 0.000 claims description 2
• UFCGRTAECNYGTK-YHQISMHQSA-N C1C(=O)N(C)CCN1[C@@H]1CC[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3C=CC=CC=3)=C2)CC1 Chemical compound C1C(=O)N(C)CCN1[C@@H]1CC[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3C=CC=CC=3)=C2)CC1 UFCGRTAECNYGTK-YHQISMHQSA-N 0.000 claims description 2
• LEPZORHVXIZEEV-MAOIWGCQSA-N C1C[C@@H](NC(=O)C(C)C)CC[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2C=CC=CC=2)=C1 Chemical compound C1C[C@@H](NC(=O)C(C)C)CC[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2C=CC=CC=2)=C1 LEPZORHVXIZEEV-MAOIWGCQSA-N 0.000 claims description 2
• ITBXFQFOWLZLON-HCGNOCCLSA-N C1C[C@@H](NC(=O)C)CC[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2C=CC=CC=2)=C1 Chemical compound C1C[C@@H](NC(=O)C)CC[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2C=CC=CC=2)=C1 ITBXFQFOWLZLON-HCGNOCCLSA-N 0.000 claims description 2
• UFHSIIUDAJRVOQ-JQUQNNEZSA-N C1[C@@H](CNC(=O)C)C[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2N=CC=CC=2)=C1 Chemical compound C1[C@@H](CNC(=O)C)C[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2N=CC=CC=2)=C1 UFHSIIUDAJRVOQ-JQUQNNEZSA-N 0.000 claims description 2
• NAFUXRLPEGOBPU-FGZXBEKLSA-N C=12C(N)=NC=CN2C([C@H]2C[C@@H](CN3C(=NC=C3)CO)C2)=NC=1C(C=C1O2)=CC=C1CCC2C1=CC=CC=C1 Chemical compound C=12C(N)=NC=CN2C([C@H]2C[C@@H](CN3C(=NC=C3)CO)C2)=NC=1C(C=C1O2)=CC=C1CCC2C1=CC=CC=C1 NAFUXRLPEGOBPU-FGZXBEKLSA-N 0.000 claims description 2
• DBZXVGWMVCAJQO-CTZQYXLCSA-N NC(=O)[C@@H]1CCCN1C[C@@H]1C[C@H](C=2N3C=CN=C(N)C3=C(C=3C=C4O[C@@H](CCC4=CC=3)C=3C=CC=CC=3)N=2)C1 Chemical compound NC(=O)[C@@H]1CCCN1C[C@@H]1C[C@H](C=2N3C=CN=C(N)C3=C(C=3C=C4O[C@@H](CCC4=CC=3)C=3C=CC=CC=3)N=2)C1 DBZXVGWMVCAJQO-CTZQYXLCSA-N 0.000 claims description 2
• DBZXVGWMVCAJQO-ZZQRAECTSA-N NC(=O)[C@@H]1CCCN1C[C@@H]1C[C@H](C=2N3C=CN=C(N)C3=C(C=3C=C4O[C@H](CCC4=CC=3)C=3C=CC=CC=3)N=2)C1 Chemical compound NC(=O)[C@@H]1CCCN1C[C@@H]1C[C@H](C=2N3C=CN=C(N)C3=C(C=3C=C4O[C@H](CCC4=CC=3)C=3C=CC=CC=3)N=2)C1 DBZXVGWMVCAJQO-ZZQRAECTSA-N 0.000 claims description 2
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
• 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims 1
• RHLVCLIPMVJYKS-UHFFFAOYSA-N 3-octanone Chemical compound CCCCCC(=O)CC RHLVCLIPMVJYKS-UHFFFAOYSA-N 0.000 claims 1
• YEVAYMGEDSOBMB-SDKMGWRVSA-N CC1=NN=NN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3C=CC=CC=3)=C2)C1 Chemical compound CC1=NN=NN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3C=CC=CC=3)=C2)C1 YEVAYMGEDSOBMB-SDKMGWRVSA-N 0.000 claims 1
• 208000015634 Rectal Neoplasms Diseases 0.000 claims 1
• 125000003277 amino group Chemical group 0.000 claims 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
• 210000001072 colon Anatomy 0.000 claims 1
• 206010038038 rectal cancer Diseases 0.000 claims 1
• 201000001275 rectum cancer Diseases 0.000 claims 1
• 230000002062 proliferating effect Effects 0.000 abstract description 8
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 266
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 178
• 239000000543 intermediate Substances 0.000 description 166
• 239000000203 mixture Substances 0.000 description 107
• 239000011541 reaction mixture Substances 0.000 description 95
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
• 238000004128 high performance liquid chromatography Methods 0.000 description 82
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
• 235000019439 ethyl acetate Nutrition 0.000 description 61
• 238000005481 NMR spectroscopy Methods 0.000 description 58
• 239000007787 solid Substances 0.000 description 58
• 238000006243 chemical reaction Methods 0.000 description 53
• 239000012267 brine Substances 0.000 description 52
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 52
• 108010031794 IGF Type 1 Receptor Proteins 0.000 description 51
• 239000012044 organic layer Substances 0.000 description 48
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 44
• 239000011734 sodium Substances 0.000 description 42
• 239000000243 solution Substances 0.000 description 41
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 38
• 210000004027 cell Anatomy 0.000 description 38
• 239000000741 silica gel Substances 0.000 description 36
• 229910002027 silica gel Inorganic materials 0.000 description 36
• 238000003756 stirring Methods 0.000 description 33
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
• 229910052938 sodium sulfate Inorganic materials 0.000 description 32
• 235000011152 sodium sulphate Nutrition 0.000 description 32
• 102000038455 IGF Type 1 Receptor Human genes 0.000 description 29
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 29
• 239000012071 phase Substances 0.000 description 29
• 239000002904 solvent Substances 0.000 description 28
• 238000004587 chromatography analysis Methods 0.000 description 27
• 238000003818 flash chromatography Methods 0.000 description 27
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 26
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
• 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 24
• 239000004480 active ingredient Substances 0.000 description 24
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 23
• 230000002829 reductive effect Effects 0.000 description 23
• 239000000047 product Substances 0.000 description 22
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
• 201000011510 cancer Diseases 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
• 239000000460 chlorine Substances 0.000 description 18
• 230000000875 corresponding effect Effects 0.000 description 17
• 229910052805 deuterium Inorganic materials 0.000 description 17
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• 239000007858 starting material Substances 0.000 description 16
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 16
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 241001465754 Metazoa Species 0.000 description 15
• 239000012300 argon atmosphere Substances 0.000 description 15
• 239000006260 foam Substances 0.000 description 15
• 238000003556 assay Methods 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 14
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
• 238000001704 evaporation Methods 0.000 description 13
• 239000003921 oil Substances 0.000 description 13
• 235000019198 oils Nutrition 0.000 description 13
• 229910000029 sodium carbonate Inorganic materials 0.000 description 13
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• 241000124008 Mammalia Species 0.000 description 12
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 229910052786 argon Inorganic materials 0.000 description 12
• 238000002953 preparative HPLC Methods 0.000 description 12
• 125000006239 protecting group Chemical group 0.000 description 12
• 230000001225 therapeutic effect Effects 0.000 description 12
• 238000005160 1H NMR spectroscopy Methods 0.000 description 11
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 11
• 238000004440 column chromatography Methods 0.000 description 11
• 239000003112 inhibitor Substances 0.000 description 11
• 230000026731 phosphorylation Effects 0.000 description 11
• 238000006366 phosphorylation reaction Methods 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
• 229910004298 SiO 2 Inorganic materials 0.000 description 10
• 239000003480 eluent Substances 0.000 description 10
• 230000008020 evaporation Effects 0.000 description 10
• 238000010348 incorporation Methods 0.000 description 10
• 239000012074 organic phase Substances 0.000 description 10
• 230000002441 reversible effect Effects 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• FLDSMVTWEZKONL-AWEZNQCLSA-N 5,5-dimethyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,4,7,8-tetrahydrooxepino[4,5-c]pyrazole-3-carboxamide Chemical compound CC1(CC2=C(NN=C2C(=O)N[C@@H]2C(N(C3=C(OC2)C=CC=C3)C)=O)CCO1)C FLDSMVTWEZKONL-AWEZNQCLSA-N 0.000 description 9
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
• 239000000654 additive Substances 0.000 description 9
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
• 235000011114 ammonium hydroxide Nutrition 0.000 description 9
• 102000005962 receptors Human genes 0.000 description 9
• 108020003175 receptors Proteins 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 8
• 230000001419 dependent effect Effects 0.000 description 8
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 230000003287 optical effect Effects 0.000 description 8
• 229910000160 potassium phosphate Inorganic materials 0.000 description 8
• 235000011009 potassium phosphates Nutrition 0.000 description 8
• 230000008569 process Effects 0.000 description 8
• 229910052708 sodium Inorganic materials 0.000 description 8
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
• 102000001253 Protein Kinase Human genes 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 7
• 230000004663 cell proliferation Effects 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 239000013058 crude material Substances 0.000 description 7
• 125000000753 cycloalkyl group Chemical group 0.000 description 7
• 238000001514 detection method Methods 0.000 description 7
• 108060006633 protein kinase Proteins 0.000 description 7
• 230000009467 reduction Effects 0.000 description 7
• 238000006722 reduction reaction Methods 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 238000004809 thin layer chromatography Methods 0.000 description 7
• 239000003643 water by type Substances 0.000 description 7
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 6
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
• 239000003085 diluting agent Substances 0.000 description 6
• 239000008103 glucose Substances 0.000 description 6
• 238000011534 incubation Methods 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 125000003367 polycyclic group Chemical group 0.000 description 6
• 235000011056 potassium acetate Nutrition 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 238000010626 work up procedure Methods 0.000 description 6
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
• 102100037852 Insulin-like growth factor I Human genes 0.000 description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
• 229920002472 Starch Polymers 0.000 description 5
• XXWVPUXHMGODLR-UHFFFAOYSA-N [3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)cyclobutyl]methanol Chemical compound C1=C(I)C=2C(N)=NC=NC=2N1C1CC(CO)C1 XXWVPUXHMGODLR-UHFFFAOYSA-N 0.000 description 5
• 235000019270 ammonium chloride Nutrition 0.000 description 5
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 125000001188 haloalkyl group Chemical group 0.000 description 5
• 150000002431 hydrogen Chemical class 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 230000001613 neoplastic effect Effects 0.000 description 5
• 150000007524 organic acids Chemical class 0.000 description 5
• 229940002612 prodrug Drugs 0.000 description 5
• 239000000651 prodrug Substances 0.000 description 5
• 230000000069 prophylactic effect Effects 0.000 description 5
• 235000018102 proteins Nutrition 0.000 description 5
• 102000004169 proteins and genes Human genes 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 125000000547 substituted alkyl group Chemical group 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• 238000002965 ELISA Methods 0.000 description 4
• 108010069236 Goserelin Proteins 0.000 description 4
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 4
• 102000004877 Insulin Human genes 0.000 description 4
• 108090001061 Insulin Proteins 0.000 description 4
• 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• 102000029749 Microtubule Human genes 0.000 description 4
• 108091022875 Microtubule Proteins 0.000 description 4
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
• 241000283973 Oryctolagus cuniculus Species 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 108060006706 SRC Proteins 0.000 description 4
• 102000001332 SRC Human genes 0.000 description 4
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 230000001772 anti-angiogenic effect Effects 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 238000003821 enantio-separation Methods 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 238000004108 freeze drying Methods 0.000 description 4
• 229940093915 gynecological organic acid Drugs 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 229940125396 insulin Drugs 0.000 description 4
• 210000004688 microtubule Anatomy 0.000 description 4
• 150000007522 mineralic acids Chemical class 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 235000005985 organic acids Nutrition 0.000 description 4
• 102000004196 processed proteins & peptides Human genes 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 150000004944 pyrrolopyrimidines Chemical class 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 229940100445 wheat starch Drugs 0.000 description 4
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• VQAJLVYCXAMTKA-UHFFFAOYSA-N 2-(oxolan-2-yl)-3,4-dihydro-2h-chromene Chemical group C1CCOC1C1OC2=CC=CC=C2CC1 VQAJLVYCXAMTKA-UHFFFAOYSA-N 0.000 description 3
• ORVCATCRRUXRCE-UHFFFAOYSA-N 2-iodooxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1OI ORVCATCRRUXRCE-UHFFFAOYSA-N 0.000 description 3
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 3
• BFMWYHSUNFBBEX-GOSISDBHSA-N 4,4,5,5-tetramethyl-2-[(2r)-2-phenyl-3,4-dihydro-2h-chromen-7-yl]-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(CC[C@@H](O2)C=3C=CC=CC=3)C2=C1 BFMWYHSUNFBBEX-GOSISDBHSA-N 0.000 description 3
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
• KFUMHIDDQQILEL-UHFFFAOYSA-N 7-Hydroxyflavan Natural products O1C2=CC(O)=CC=C2CCC1C1=CC=CC=C1 KFUMHIDDQQILEL-UHFFFAOYSA-N 0.000 description 3
• OAVGCTZDWADVIB-UHFFFAOYSA-N 7-bromo-2-phenylchromen-4-one Chemical compound C=1C(Br)=CC=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 OAVGCTZDWADVIB-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 3
• 229940122815 Aromatase inhibitor Drugs 0.000 description 3
• 239000005711 Benzoic acid Substances 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• 102000001301 EGF receptor Human genes 0.000 description 3
• 108060006698 EGF receptor Proteins 0.000 description 3
• DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 3
• 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 3
• 101150026109 INSR gene Proteins 0.000 description 3
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 3
• 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 description 3
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 3
• 150000001204 N-oxides Chemical class 0.000 description 3
• 108091000080 Phosphotransferase Proteins 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 229960003437 aminoglutethimide Drugs 0.000 description 3
• ROBVIMPUHSLWNV-UHFFFAOYSA-N aminoglutethimide Chemical compound C=1C=C(N)C=CC=1C1(CC)CCC(=O)NC1=O ROBVIMPUHSLWNV-UHFFFAOYSA-N 0.000 description 3
• YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 230000000259 anti-tumor effect Effects 0.000 description 3
• 239000003886 aromatase inhibitor Substances 0.000 description 3
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 3
• 235000010233 benzoic acid Nutrition 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000011575 calcium Substances 0.000 description 3
• 229910052791 calcium Inorganic materials 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 229910002091 carbon monoxide Inorganic materials 0.000 description 3
• 229960004562 carboplatin Drugs 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 239000008004 cell lysis buffer Substances 0.000 description 3
• 238000004296 chiral HPLC Methods 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 239000002027 dichloromethane extract Substances 0.000 description 3
• 231100000673 dose–response relationship Toxicity 0.000 description 3
• 238000010828 elution Methods 0.000 description 3
• 238000001952 enzyme assay Methods 0.000 description 3
• 229960005420 etoposide Drugs 0.000 description 3
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 3
• 239000012467 final product Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 239000001530 fumaric acid Substances 0.000 description 3
• 235000011087 fumaric acid Nutrition 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 235000003642 hunger Nutrition 0.000 description 3
• 229960000908 idarubicin Drugs 0.000 description 3
• 229960001101 ifosfamide Drugs 0.000 description 3
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 3
• 239000003446 ligand Substances 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 239000002207 metabolite Substances 0.000 description 3
• 238000002156 mixing Methods 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 229910052759 nickel Inorganic materials 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
• 102000020233 phosphotransferase Human genes 0.000 description 3
• 125000006684 polyhaloalkyl group Polymers 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 238000011533 pre-incubation Methods 0.000 description 3
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 3
• 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 3
• 239000000376 reactant Substances 0.000 description 3
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 238000013207 serial dilution Methods 0.000 description 3
• 229960003787 sorafenib Drugs 0.000 description 3
• 230000037351 starvation Effects 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 150000003462 sulfoxides Chemical class 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 239000000454 talc Substances 0.000 description 3
• 229910052623 talc Inorganic materials 0.000 description 3
• 235000012222 talc Nutrition 0.000 description 3
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 3
• 229960001278 teniposide Drugs 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 229960000575 trastuzumab Drugs 0.000 description 3
• VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 3
• 229910052720 vanadium Inorganic materials 0.000 description 3
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
• IYEZFWFKNLUIKG-AWEZNQCLSA-N (2s)-7-bromo-2-phenyl-3,4-dihydro-2h-chromene Chemical compound C1([C@@H]2CCC3=CC=C(C=C3O2)Br)=CC=CC=C1 IYEZFWFKNLUIKG-AWEZNQCLSA-N 0.000 description 2
• 0 **(C1)CC1*(*C(C12)c3ccc(C=CC(*)O4)c4c3)*1*=CN=C2N Chemical compound **(C1)CC1*(*C(C12)c3ccc(C=CC(*)O4)c4c3)*1*=CN=C2N 0.000 description 2
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 2
• KYPVDKAIGIDYLB-UHFFFAOYSA-N 2-phenyl-3,4-dihydro-2h-chromene-4,7-diol Chemical compound O1C2=CC(O)=CC=C2C(O)CC1C1=CC=CC=C1 KYPVDKAIGIDYLB-UHFFFAOYSA-N 0.000 description 2
• UKFXXJWJPKHOGD-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-(2-phenyl-4h-chromen-7-yl)-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(CC=C(O2)C=3C=CC=CC=3)C2=C1 UKFXXJWJPKHOGD-UHFFFAOYSA-N 0.000 description 2
• TYKRRHOXCWJNOI-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-[2-(oxolan-2-yl)-3,4-dihydro-2h-chromen-7-yl]-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(CCC(O2)C3OCCC3)C2=C1 TYKRRHOXCWJNOI-UHFFFAOYSA-N 0.000 description 2
• CLPFFLWZZBQMAO-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 CLPFFLWZZBQMAO-UHFFFAOYSA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• HENMNOOOBNVJGT-UHFFFAOYSA-N 5-bromo-7-[3-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]cyclobutyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=C(Br)C=2C(N)=NC=NC=2N1C(C1)CC1CN1CCS(=O)(=O)CC1 HENMNOOOBNVJGT-UHFFFAOYSA-N 0.000 description 2
• OGWKCGZFUXNPDA-CFWMRBGOSA-N 5j49q6b70f Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 OGWKCGZFUXNPDA-CFWMRBGOSA-N 0.000 description 2
• SWAJPHCXKPCPQZ-UHFFFAOYSA-N 7-hydroxyflavanone Chemical compound O1C2=CC(O)=CC=C2C(=O)CC1C1=CC=CC=C1 SWAJPHCXKPCPQZ-UHFFFAOYSA-N 0.000 description 2
• MQGPSCMMNJKMHQ-UHFFFAOYSA-N 7-hydroxyflavone Chemical compound C=1C(O)=CC=C(C(C=2)=O)C=1OC=2C1=CC=CC=C1 MQGPSCMMNJKMHQ-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 206010004146 Basal cell carcinoma Diseases 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• 229940122361 Bisphosphonate Drugs 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• VJMYPQSBJYOAGH-TYABSZSSSA-N C1C[C@@H](N)CC[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2C=CC=CC=2)=C1 Chemical compound C1C[C@@H](N)CC[C@H]1N1C2=NC=NC(N)=C2C(C=2C=C3OC(CCC3=CC=2)C=2C=CC=CC=2)=C1 VJMYPQSBJYOAGH-TYABSZSSSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 2
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 2
• 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 102400001368 Epidermal growth factor Human genes 0.000 description 2
• 101800003838 Epidermal growth factor Proteins 0.000 description 2
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 2
• 229940124226 Farnesyltransferase inhibitor Drugs 0.000 description 2
• VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 102400000932 Gonadoliberin-1 Human genes 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• 101500026183 Homo sapiens Gonadoliberin-1 Proteins 0.000 description 2
• 101000852815 Homo sapiens Insulin receptor Proteins 0.000 description 2
• 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 2
• MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 2
• 102100036721 Insulin receptor Human genes 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 2
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
• 239000002147 L01XE04 - Sunitinib Substances 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• 229940124761 MMP inhibitor Drugs 0.000 description 2
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 2
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 2
• 206010027476 Metastases Diseases 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 229920002556 Polyethylene Glycol 300 Polymers 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• 239000004793 Polystyrene Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 102000013275 Somatomedins Human genes 0.000 description 2
• 108010090804 Streptavidin Proteins 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
• IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 2
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 2
• 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• 102000004243 Tubulin Human genes 0.000 description 2
• 108090000704 Tubulin Proteins 0.000 description 2
• 108091008605 VEGF receptors Proteins 0.000 description 2
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
• AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 2
• 229960002184 abarelix Drugs 0.000 description 2
• 108010023617 abarelix Proteins 0.000 description 2
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 230000000996 additive effect Effects 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 239000000556 agonist Substances 0.000 description 2
• 229960004343 alendronic acid Drugs 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 229960002932 anastrozole Drugs 0.000 description 2
• 230000002280 anti-androgenic effect Effects 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 239000000051 antiandrogen Substances 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• 150000001540 azides Chemical class 0.000 description 2
• 229930195545 bengamide Natural products 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 150000004663 bisphosphonates Chemical class 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 229940047495 celebrex Drugs 0.000 description 2
• 229960000590 celecoxib Drugs 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 230000006037 cell lysis Effects 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 239000013522 chelant Substances 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 229960002286 clodronic acid Drugs 0.000 description 2
• 229940111134 coxibs Drugs 0.000 description 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• JCWIWBWXCVGEAN-UHFFFAOYSA-L cyclopentyl(diphenyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 JCWIWBWXCVGEAN-UHFFFAOYSA-L 0.000 description 2
• 229960004397 cyclophosphamide Drugs 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 239000000824 cytostatic agent Substances 0.000 description 2
• 230000001085 cytostatic effect Effects 0.000 description 2
• 231100000433 cytotoxic Toxicity 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 150000001975 deuterium Chemical group 0.000 description 2
• CVKBMWWNKUWISK-UHFFFAOYSA-L dichloromethane;dichloropalladium Chemical compound ClCCl.Cl[Pd]Cl CVKBMWWNKUWISK-UHFFFAOYSA-L 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 229960003668 docetaxel Drugs 0.000 description 2
• 229960004679 doxorubicin Drugs 0.000 description 2
• 229940116977 epidermal growth factor Drugs 0.000 description 2
• 229960001904 epirubicin Drugs 0.000 description 2
• 229930013356 epothilone Natural products 0.000 description 2
• HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 2
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 229940011871 estrogen Drugs 0.000 description 2
• 239000000262 estrogen Substances 0.000 description 2
• 239000000328 estrogen antagonist Substances 0.000 description 2
• 229960004585 etidronic acid Drugs 0.000 description 2
• 238000000105 evaporative light scattering detection Methods 0.000 description 2
• 229960000255 exemestane Drugs 0.000 description 2
• 229950011548 fadrozole Drugs 0.000 description 2
• 229960004421 formestane Drugs 0.000 description 2
• OSVMTWJCGUFAOD-KZQROQTASA-N formestane Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1O OSVMTWJCGUFAOD-KZQROQTASA-N 0.000 description 2
• 238000001640 fractional crystallisation Methods 0.000 description 2
• 229960002258 fulvestrant Drugs 0.000 description 2
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 2
• 229960001442 gonadorelin Drugs 0.000 description 2
• 229960002913 goserelin Drugs 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
• 229940022353 herceptin Drugs 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 229940121372 histone deacetylase inhibitor Drugs 0.000 description 2
• 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 229960005236 ibandronic acid Drugs 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 125000002346 iodo group Chemical group I* 0.000 description 2
• 229960004768 irinotecan Drugs 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
• 230000000155 isotopic effect Effects 0.000 description 2
• 150000002576 ketones Chemical group 0.000 description 2
• 229940043355 kinase inhibitor Drugs 0.000 description 2
• 229960003881 letrozole Drugs 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 239000012280 lithium aluminium hydride Substances 0.000 description 2
• 239000006166 lysate Substances 0.000 description 2
• 229960003646 lysine Drugs 0.000 description 2
• 239000012139 lysis buffer Substances 0.000 description 2
• 229940124302 mTOR inhibitor Drugs 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 2
• 229960002510 mandelic acid Drugs 0.000 description 2
• 230000010534 mechanism of action Effects 0.000 description 2
• 239000012528 membrane Substances 0.000 description 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
• 229910052751 metal Chemical class 0.000 description 2
• 239000002184 metal Chemical class 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 2
• 229960001156 mitoxantrone Drugs 0.000 description 2
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
• 125000006682 monohaloalkyl group Chemical group 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 229960001756 oxaliplatin Drugs 0.000 description 2
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 229960003978 pamidronic acid Drugs 0.000 description 2
• WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• 125000005936 piperidyl group Chemical group 0.000 description 2
• 239000004033 plastic Substances 0.000 description 2
• 229920003023 plastic Polymers 0.000 description 2
• 150000003058 platinum compounds Chemical class 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 229920001155 polypropylene Polymers 0.000 description 2
• 229920002223 polystyrene Polymers 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 238000004237 preparative chromatography Methods 0.000 description 2
• 238000012746 preparative thin layer chromatography Methods 0.000 description 2
• 150000003141 primary amines Chemical class 0.000 description 2
• 238000000159 protein binding assay Methods 0.000 description 2
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 2
• BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical compound [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 2
• 229960002119 raloxifene hydrochloride Drugs 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 229960000759 risedronic acid Drugs 0.000 description 2
• 229960004641 rituximab Drugs 0.000 description 2
• CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 description 2
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
• 235000012239 silicon dioxide Nutrition 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• 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 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• 125000003107 substituted aryl group Chemical group 0.000 description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 206010042863 synovial sarcoma Diseases 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 229960001603 tamoxifen Drugs 0.000 description 2
• 239000011975 tartaric acid Substances 0.000 description 2
• 235000002906 tartaric acid Nutrition 0.000 description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
• 229960005324 tiludronic acid Drugs 0.000 description 2
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 2
• 229960000303 topotecan Drugs 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
• 229960003048 vinblastine Drugs 0.000 description 2
• KDQAABAKXDWYSZ-PNYVAJAMSA-N vinblastine sulfate Chemical compound OS(O)(=O)=O.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 KDQAABAKXDWYSZ-PNYVAJAMSA-N 0.000 description 2
• 229960004982 vinblastine sulfate Drugs 0.000 description 2
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
• AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 description 2
• 229960002110 vincristine sulfate Drugs 0.000 description 2
• XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 2
• 229960004276 zoledronic acid Drugs 0.000 description 2
• AADVCYNFEREWOS-UHFFFAOYSA-N (+)-DDM Natural products C=CC=CC(C)C(OC(N)=O)C(C)C(O)C(C)CC(C)=CC(C)C(O)C(C)C=CC(O)CC1OC(=O)C(C)C(O)C1C AADVCYNFEREWOS-UHFFFAOYSA-N 0.000 description 1
• DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
• SJONZERYRAVRSB-FHAQVOQBSA-N (1s,4s)-2-thia-5-azabicyclo[2.2.1]heptane;hydrochloride Chemical compound Cl.C1S[C@@H]2CN[C@H]1C2 SJONZERYRAVRSB-FHAQVOQBSA-N 0.000 description 1
• BSUMQUSUEWBSKU-UHFFFAOYSA-N (2-phenyl-3,4-dihydro-2h-chromen-7-yl) trifluoromethanesulfonate Chemical compound O1C2=CC(OS(=O)(=O)C(F)(F)F)=CC=C2CCC1C1=CC=CC=C1 BSUMQUSUEWBSKU-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• IYEZFWFKNLUIKG-CQSZACIVSA-N (2r)-7-bromo-2-phenyl-3,4-dihydro-2h-chromene Chemical compound C1([C@H]2CCC3=CC=C(C=C3O2)Br)=CC=CC=C1 IYEZFWFKNLUIKG-CQSZACIVSA-N 0.000 description 1
• DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
• DFFCWOHBSZTMHR-LBPRGKRZSA-N (2s)-2-(furan-2-yl)-3,4-dihydro-2h-chromen-7-ol Chemical compound C1([C@@H]2CCC3=CC=C(C=C3O2)O)=CC=CO1 DFFCWOHBSZTMHR-LBPRGKRZSA-N 0.000 description 1
• FXURNNUJVHBUTP-RYUDHWBXSA-N (2s)-2-[(2s)-oxolan-2-yl]-3,4-dihydro-2h-chromen-7-ol Chemical compound C([C@H]1[C@@H]2CCC3=CC=C(C=C3O2)O)CCO1 FXURNNUJVHBUTP-RYUDHWBXSA-N 0.000 description 1
• RGDMVPSSBUZUQA-UHFFFAOYSA-N (3-aminocyclobutyl)methyl benzoate Chemical compound C1C(N)CC1COC(=O)C1=CC=CC=C1 RGDMVPSSBUZUQA-UHFFFAOYSA-N 0.000 description 1
• SQWZFLMPDUSYGV-POHAHGRESA-N (5Z)-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)\C1=C\C1=CC=C(N=CC=N2)C2=C1 SQWZFLMPDUSYGV-POHAHGRESA-N 0.000 description 1
• SRLVNYDXMUGOFI-YWEYNIOJSA-N (5e)-5-[(2,2-difluoro-1,3-benzodioxol-5-yl)methylene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2OC(F)(F)OC2=CC=C1\C=C1/SC(=O)NC1=O SRLVNYDXMUGOFI-YWEYNIOJSA-N 0.000 description 1
• SDGWAUUPHUBJNQ-WTKPLQERSA-N (5z)-5-(1,3-benzodioxol-5-ylmethylidene)-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)\C1=C\C1=CC=C(OCO2)C2=C1 SDGWAUUPHUBJNQ-WTKPLQERSA-N 0.000 description 1
• OYYVWNDMOQPMGE-SDQBBNPISA-N (5z)-5-[[5-(4-fluoro-2-hydroxyphenyl)furan-2-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound OC1=CC(F)=CC=C1C(O1)=CC=C1\C=C/1C(=O)NC(=O)S\1 OYYVWNDMOQPMGE-SDQBBNPISA-N 0.000 description 1
• LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• HEUBAVZAMIRYAO-FNORWQNLSA-N (e)-1-(4-bromo-2-hydroxyphenyl)-3-pyridin-2-ylprop-2-en-1-one Chemical compound OC1=CC(Br)=CC=C1C(=O)\C=C\C1=CC=CC=N1 HEUBAVZAMIRYAO-FNORWQNLSA-N 0.000 description 1
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
• DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
• XGRPNDOJYZDAPH-UHFFFAOYSA-N 1,2-dicyclohexyl-3-(2,6-dimethoxyphenyl)benzene Chemical group COC1=CC=CC(OC)=C1C1=CC=CC(C2CCCCC2)=C1C1CCCCC1 XGRPNDOJYZDAPH-UHFFFAOYSA-N 0.000 description 1
• YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
• CNAHTBMMJSMMEC-UHFFFAOYSA-N 1,4-thiazinane 1-oxide;hydrochloride Chemical compound Cl.O=S1CCNCC1 CNAHTBMMJSMMEC-UHFFFAOYSA-N 0.000 description 1
• LQCMMXGKEGWUIM-UHFFFAOYSA-N 1-(4-bromo-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC=C(Br)C=C1O LQCMMXGKEGWUIM-UHFFFAOYSA-N 0.000 description 1
• KTVGYAJQQQUOQX-UHFFFAOYSA-N 1-(hydroxymethyl)cyclobutan-1-ol Chemical compound OCC1(O)CCC1 KTVGYAJQQQUOQX-UHFFFAOYSA-N 0.000 description 1
• 102000001556 1-Phosphatidylinositol 4-Kinase Human genes 0.000 description 1
• 108010029190 1-Phosphatidylinositol 4-Kinase Proteins 0.000 description 1
• XXBHYBVDFNEYRQ-UHFFFAOYSA-N 1-[4-[3-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)cyclobutyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C1CC(N2C3=NC=NC(Cl)=C3C=C2)C1 XXBHYBVDFNEYRQ-UHFFFAOYSA-N 0.000 description 1
• YABJJWZLRMPFSI-UHFFFAOYSA-N 1-methyl-5-[[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]-4-pyridinyl]oxy]-N-[4-(trifluoromethyl)phenyl]-2-benzimidazolamine Chemical compound N=1C2=CC(OC=3C=C(N=CC=3)C=3NC(=CN=3)C(F)(F)F)=CC=C2N(C)C=1NC1=CC=C(C(F)(F)F)C=C1 YABJJWZLRMPFSI-UHFFFAOYSA-N 0.000 description 1
• KJCIMSSFGUGTGA-UHFFFAOYSA-N 1-methylpiperazin-2-one Chemical compound CN1CCNCC1=O KJCIMSSFGUGTGA-UHFFFAOYSA-N 0.000 description 1
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
• VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
• IWWLVWWEZSOTJH-UHFFFAOYSA-N 2,3-dihydroxy-4-(4-methylbenzoyl)oxy-4-oxobutanoic acid Chemical compound CC1=CC=C(C(=O)OC(=O)C(O)C(O)C(O)=O)C=C1 IWWLVWWEZSOTJH-UHFFFAOYSA-N 0.000 description 1
• QEBITPOSBYZLCY-UHFFFAOYSA-N 2-(4,6-dichloropyrimidin-5-yl)acetaldehyde Chemical compound ClC1=NC=NC(Cl)=C1CC=O QEBITPOSBYZLCY-UHFFFAOYSA-N 0.000 description 1
• ZIVVMVYVPFOWOB-UHFFFAOYSA-N 2-(7-bromo-3,4-dihydro-2h-chromen-2-yl)pyridine Chemical compound O1C2=CC(Br)=CC=C2CCC1C1=CC=CC=N1 ZIVVMVYVPFOWOB-UHFFFAOYSA-N 0.000 description 1
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
• DDCCYDLROVRJDO-UHFFFAOYSA-N 2-(furan-2-yl)-3,4-dihydro-2h-chromene-4,7-diol Chemical compound O1C2=CC(O)=CC=C2C(O)CC1C1=CC=CO1 DDCCYDLROVRJDO-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
• OYWXJLMHLLRBGY-UHFFFAOYSA-N 2-[2-(ethoxymethyl)-3,4-dihydro-2h-chromen-7-yl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound C1=C2OC(COCC)CCC2=CC=C1B1OC(C)(C)C(C)(C)O1 OYWXJLMHLLRBGY-UHFFFAOYSA-N 0.000 description 1
• WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
• PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
• ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical compound OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• LTQBUWVDIKUNHJ-UHFFFAOYSA-N 2-thia-5-azabicyclo[2.2.1]heptane Chemical compound C1SC2CNC1C2 LTQBUWVDIKUNHJ-UHFFFAOYSA-N 0.000 description 1
• HSUKCUAUTQWJEO-UHFFFAOYSA-N 3-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)cyclobutane-1-carbaldehyde Chemical compound C1=C(I)C=2C(Cl)=NC=NC=2N1C1CC(C=O)C1 HSUKCUAUTQWJEO-UHFFFAOYSA-N 0.000 description 1
• FPKSUOLZSZJTKP-UHFFFAOYSA-N 3-(8-amino-1-iodoimidazo[1,5-a]pyrazin-3-yl)-1-methylcyclobutan-1-ol Chemical compound C1C(C)(O)CC1C1=NC(I)=C2N1C=CN=C2N FPKSUOLZSZJTKP-UHFFFAOYSA-N 0.000 description 1
• KKXBOEQHFRBSDD-UHFFFAOYSA-N 3-[4-amino-5-[3-(7-oxabicyclo[2.2.1]heptan-4-ylmethoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutan-1-ol Chemical compound C1=C(C=2C=C(OCC34CCC(CC3)O4)C=CC=2)C=2C(N)=NC=NC=2N1C1CC(O)C1 KKXBOEQHFRBSDD-UHFFFAOYSA-N 0.000 description 1
• VIPCYZVURGQBRM-UHFFFAOYSA-N 3-amino-1-(hydroxymethyl)cyclobutan-1-ol Chemical compound NC1CC(O)(CO)C1 VIPCYZVURGQBRM-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• BFMWYHSUNFBBEX-SFHVURJKSA-N 4,4,5,5-tetramethyl-2-[(2s)-2-phenyl-3,4-dihydro-2h-chromen-7-yl]-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(CC[C@H](O2)C=3C=CC=CC=3)C2=C1 BFMWYHSUNFBBEX-SFHVURJKSA-N 0.000 description 1
• BMBNOZMBQFSRJB-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-spiro[3,4-dihydrochromene-2,1'-cyclohexane]-7-yl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(CCC2(CCCCC2)O2)C2=C1 BMBNOZMBQFSRJB-UHFFFAOYSA-N 0.000 description 1
• HXTWKHXDFATMSP-UHFFFAOYSA-N 4-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC(Br)=CC=C1C=O HXTWKHXDFATMSP-UHFFFAOYSA-N 0.000 description 1
• GVSNQMFKEPBIOY-UHFFFAOYSA-N 4-methyl-2h-triazole Chemical compound CC=1C=NNN=1 GVSNQMFKEPBIOY-UHFFFAOYSA-N 0.000 description 1
• JCIDEANDDNSHQC-UHFFFAOYSA-N 4H-chromene Chemical compound C1=CC=C2CC=COC2=C1 JCIDEANDDNSHQC-UHFFFAOYSA-N 0.000 description 1
• FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• YBPIBGNBHHGLEB-UHFFFAOYSA-N 6-amino-N-[3-[4-(4-morpholinyl)-2-pyrido[2,3]furo[2,4-b]pyrimidinyl]phenyl]-3-pyridinecarboxamide Chemical compound C1=NC(N)=CC=C1C(=O)NC1=CC=CC(C=2N=C3C4=CC=CN=C4OC3=C(N3CCOCC3)N=2)=C1 YBPIBGNBHHGLEB-UHFFFAOYSA-N 0.000 description 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
• SWAJPHCXKPCPQZ-AWEZNQCLSA-N 7-Hydroxyflavanone Natural products C1([C@@H]2CC(=O)C3=CC=C(C=C3O2)O)=CC=CC=C1 SWAJPHCXKPCPQZ-AWEZNQCLSA-N 0.000 description 1
• IYEZFWFKNLUIKG-UHFFFAOYSA-N 7-bromo-2-phenyl-3,4-dihydro-2h-chromene Chemical compound O1C2=CC(Br)=CC=C2CCC1C1=CC=CC=C1 IYEZFWFKNLUIKG-UHFFFAOYSA-N 0.000 description 1
• PEHVGBZKEYRQSX-UHFFFAOYSA-N 7-deaza-adenine Chemical class NC1=NC=NC2=C1C=CN2 PEHVGBZKEYRQSX-UHFFFAOYSA-N 0.000 description 1
• CPRAGQJXBLMUEL-UHFFFAOYSA-N 9-(1-anilinoethyl)-7-methyl-2-(4-morpholinyl)-4-pyrido[1,2-a]pyrimidinone Chemical compound C=1C(C)=CN(C(C=C(N=2)N3CCOCC3)=O)C=2C=1C(C)NC1=CC=CC=C1 CPRAGQJXBLMUEL-UHFFFAOYSA-N 0.000 description 1
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 1
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
• 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
• 208000005748 Aggressive Fibromatosis Diseases 0.000 description 1
• 239000012116 Alexa Fluor 680 Substances 0.000 description 1
• 102400000068 Angiostatin Human genes 0.000 description 1
• 108010079709 Angiostatins Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• YUXMAKUNSXIEKN-BTJKTKAUSA-N BGT226 Chemical compound OC(=O)\C=C/C(O)=O.C1=NC(OC)=CC=C1C1=CC=C(N=CC2=C3N(C=4C=C(C(N5CCNCC5)=CC=4)C(F)(F)F)C(=O)N2C)C3=C1 YUXMAKUNSXIEKN-BTJKTKAUSA-N 0.000 description 1
• CWHUFRVAEUJCEF-UHFFFAOYSA-N BKM120 Chemical compound C1=NC(N)=CC(C(F)(F)F)=C1C1=CC(N2CCOCC2)=NC(N2CCOCC2)=N1 CWHUFRVAEUJCEF-UHFFFAOYSA-N 0.000 description 1
• KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• BKCCHCLAFBYAFZ-UHFFFAOYSA-N C(C1=CC=CC=C1)OC(NC1CC(C1)(CO)O)=O.NC1CC(C1)(O)CO Chemical compound C(C1=CC=CC=C1)OC(NC1CC(C1)(CO)O)=O.NC1CC(C1)(O)CO BKCCHCLAFBYAFZ-UHFFFAOYSA-N 0.000 description 1
• LKAFAZPZBINVMF-PHIMTYICSA-N C([C@H]1C[C@H](C1)N1C=2N=CN=C(C=2C(Br)=C1)Cl)N1CCS(=O)(=O)CC1 Chemical compound C([C@H]1C[C@H](C1)N1C=2N=CN=C(C=2C(Br)=C1)Cl)N1CCS(=O)(=O)CC1 LKAFAZPZBINVMF-PHIMTYICSA-N 0.000 description 1
• GVFKXIRQDKOQSC-PHIMTYICSA-N C([C@H]1C[C@H](C1)N1C=2N=CN=C(C=2C(I)=C1)N)N1CCS(=O)CC1 Chemical compound C([C@H]1C[C@H](C1)N1C=2N=CN=C(C=2C(I)=C1)N)N1CCS(=O)CC1 GVFKXIRQDKOQSC-PHIMTYICSA-N 0.000 description 1
• HGDLVBXRKPOVHH-KHMOSXFSSA-N C1([C@@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)=CC=CC=C1 Chemical compound C1([C@@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)=CC=CC=C1 HGDLVBXRKPOVHH-KHMOSXFSSA-N 0.000 description 1
• HGDLVBXRKPOVHH-UGIARPQZSA-N C1([C@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)=CC=CC=C1 Chemical compound C1([C@H]2CCC3=CC=C(C=C3O2)C2=CN(C=3N=CN=C(C2=3)N)[C@H]2C[C@@H](CN3CCS(=O)(=O)CC3)C2)=CC=CC=C1 HGDLVBXRKPOVHH-UGIARPQZSA-N 0.000 description 1
• QDSQGOQSFFUWCB-PTEGZUARSA-N C1=2C(N)=NC=NC=2N([C@@H]2C[C@@H](O)C2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=C1 Chemical compound C1=2C(N)=NC=NC=2N([C@@H]2C[C@@H](O)C2)C=C1C(C=C1O2)=CC=C1CCC2C1=CC=CC=C1 QDSQGOQSFFUWCB-PTEGZUARSA-N 0.000 description 1
• URPMHZGVDUDPCW-USZNOCQGSA-N C1=C(I)C2=C(N)N=CN=C2N1[C@@H](C1)C[C@@H]1CN1C[C@]2([H])C[C@@]1([H])CS2(=O)=O Chemical compound C1=C(I)C2=C(N)N=CN=C2N1[C@@H](C1)C[C@@H]1CN1C[C@]2([H])C[C@@]1([H])CS2(=O)=O URPMHZGVDUDPCW-USZNOCQGSA-N 0.000 description 1
• BAZLVVDXPIMQCF-PHIMTYICSA-N C1C(=O)N(C)CCN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(I)=C2)C1 Chemical compound C1C(=O)N(C)CCN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(I)=C2)C1 BAZLVVDXPIMQCF-PHIMTYICSA-N 0.000 description 1
• OVRHWRSDYXEDFC-TXEJJXNPSA-N C1CN(C(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(Br)=C2)C1 Chemical compound C1CN(C(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(Br)=C2)C1 OVRHWRSDYXEDFC-TXEJJXNPSA-N 0.000 description 1
• RVOCNWZSWZKQPG-YHQISMHQSA-N C1CN(C(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3C=CC=CC=3)=C2)C1 Chemical compound C1CN(C(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C4OC(CCC4=CC=3)C=3C=CC=CC=3)=C2)C1 RVOCNWZSWZKQPG-YHQISMHQSA-N 0.000 description 1
• KEXXPPTWAWAWRS-DTORHVGOSA-N C1[C@@H](CNC(=O)C)C[C@H]1N1C2=NC=NC(N)=C2C(I)=C1 Chemical compound C1[C@@H](CNC(=O)C)C[C@H]1N1C2=NC=NC(N)=C2C(I)=C1 KEXXPPTWAWAWRS-DTORHVGOSA-N 0.000 description 1
• RQWBKKRISWZEQS-TXEJJXNPSA-N C1[C@H](C=O)C[C@@H]1NC(=O)OCC1=CC=CC=C1 Chemical compound C1[C@H](C=O)C[C@@H]1NC(=O)OCC1=CC=CC=C1 RQWBKKRISWZEQS-TXEJJXNPSA-N 0.000 description 1
• BAOZTHAMMVVXCM-UHFFFAOYSA-N CCCC[SiH3].Brc1ccc2CCC(Oc2c1)c1ccccc1 Chemical compound CCCC[SiH3].Brc1ccc2CCC(Oc2c1)c1ccccc1 BAOZTHAMMVVXCM-UHFFFAOYSA-N 0.000 description 1
• AMDDSQIJYFQDDW-KBTIHESUSA-N C[C@H](C1)C[C@]1(CN1)OC1=O Chemical compound C[C@H](C1)C[C@]1(CN1)OC1=O AMDDSQIJYFQDDW-KBTIHESUSA-N 0.000 description 1
• FYUZZLBBCICMQL-GRQBKTHUSA-N C[C@H](CCC1O2)CC1OC2=O Chemical compound C[C@H](CCC1O2)CC1OC2=O FYUZZLBBCICMQL-GRQBKTHUSA-N 0.000 description 1
• KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 101150065749 Churc1 gene Proteins 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• JIOWEIWPALPKSD-UHFFFAOYSA-N ClC1=NC=C(CC=O)C(Cl)=N1.C1C(CO)(O)CC1N1C2=NC=NC(Cl)=C2C=C1 Chemical compound ClC1=NC=C(CC=O)C(Cl)=N1.C1C(CO)(O)CC1N1C2=NC=NC(Cl)=C2C=C1 JIOWEIWPALPKSD-UHFFFAOYSA-N 0.000 description 1
• PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 240000008067 Cucumis sativus Species 0.000 description 1
• 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
• 206010059352 Desmoid tumour Diseases 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
• AADVCYNFEREWOS-OBRABYBLSA-N Discodermolide Chemical compound C=C\C=C/[C@H](C)[C@H](OC(N)=O)[C@@H](C)[C@H](O)[C@@H](C)C\C(C)=C/[C@H](C)[C@@H](O)[C@@H](C)\C=C/[C@@H](O)C[C@@H]1OC(=O)[C@H](C)[C@@H](O)[C@H]1C AADVCYNFEREWOS-OBRABYBLSA-N 0.000 description 1
• MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
• 101001053785 Drosophila melanogaster Dual specificity mitogen-activated protein kinase kinase dSOR1 Proteins 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 102400001047 Endostatin Human genes 0.000 description 1
• 108010079505 Endostatins Proteins 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[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 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
• 102000007317 Farnesyltranstransferase Human genes 0.000 description 1
• 108010007508 Farnesyltranstransferase Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 239000012981 Hank's balanced salt solution Substances 0.000 description 1
• 102000003964 Histone deacetylase Human genes 0.000 description 1
• 108090000353 Histone deacetylase Proteins 0.000 description 1
• 101000605630 Homo sapiens Phosphatidylinositol 3-kinase catalytic subunit type 3 Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 108060003951 Immunoglobulin Proteins 0.000 description 1
• 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
• 229910010082 LiAlH Inorganic materials 0.000 description 1
• 229940123917 Lipid kinase inhibitor Drugs 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• GPVKLYONJSSZFL-UHFFFAOYSA-N NSC 750259 Natural products CCC(C)C=CC(O)C(O)C(O)C(OC)C(=O)NC1CCCCNC1=O GPVKLYONJSSZFL-UHFFFAOYSA-N 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• PEJKZDJNLZYWHV-KQYMJHLBSA-N O=[SH2]1[C@@H]2CN([C@H](C1)C2)C[C@H]1C[C@H](C1)N1C=C(C2=C1N=CN=C2N)C1=CC=C2CCC(OC2=C1)C1=NC=CC=C1 Chemical compound O=[SH2]1[C@@H]2CN([C@H](C1)C2)C[C@H]1C[C@H](C1)N1C=C(C2=C1N=CN=C2N)C1=CC=C2CCC(OC2=C1)C1=NC=CC=C1 PEJKZDJNLZYWHV-KQYMJHLBSA-N 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• SUDAHWBOROXANE-VIFPVBQESA-N PD 0325901-Cl Chemical compound OC[C@H](O)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F SUDAHWBOROXANE-VIFPVBQESA-N 0.000 description 1
• TUVCWJQQGGETHL-UHFFFAOYSA-N PI-103 Chemical compound OC1=CC=CC(C=2N=C3C4=CC=CN=C4OC3=C(N3CCOCC3)N=2)=C1 TUVCWJQQGGETHL-UHFFFAOYSA-N 0.000 description 1
• 229940116355 PI3 kinase inhibitor Drugs 0.000 description 1
• 239000002033 PVDF binder Substances 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 102100038329 Phosphatidylinositol 3-kinase catalytic subunit type 3 Human genes 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
• 102100038239 Protein Churchill Human genes 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 1
• 238000003428 Staudinger Azide reduction reaction Methods 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[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 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 0.000 description 1
• HGVNLRPZOWWDKD-UHFFFAOYSA-N ZSTK-474 Chemical compound FC(F)C1=NC2=CC=CC=C2N1C(N=1)=NC(N2CCOCC2)=NC=1N1CCOCC1 HGVNLRPZOWWDKD-UHFFFAOYSA-N 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• BSUMQUSUEWBSKU-CQSZACIVSA-N [(2r)-2-phenyl-3,4-dihydro-2h-chromen-7-yl] trifluoromethanesulfonate Chemical compound C1([C@H]2CCC3=CC=C(C=C3O2)OS(=O)(=O)C(F)(F)F)=CC=CC=C1 BSUMQUSUEWBSKU-CQSZACIVSA-N 0.000 description 1
• HVVNJUAVDAZWCB-YFKPBYRVSA-N [(2s)-pyrrolidin-2-yl]methanol Chemical compound OC[C@@H]1CCCN1 HVVNJUAVDAZWCB-YFKPBYRVSA-N 0.000 description 1
• VKIJXFIYBAYHOE-VOTSOKGWSA-N [(e)-2-phenylethenyl]boronic acid Chemical compound OB(O)\C=C\C1=CC=CC=C1 VKIJXFIYBAYHOE-VOTSOKGWSA-N 0.000 description 1
• UHRLTPSBJYDWKU-UHFFFAOYSA-N [3-(4-chloro-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)cyclobutyl]methanol Chemical compound C1C(CO)CC1N1C2=NC=NC(Cl)=C2C(I)=C1 UHRLTPSBJYDWKU-UHFFFAOYSA-N 0.000 description 1
• ZBNWLRGIOOFBJO-UHFFFAOYSA-N [3-(4-chloropyrrolo[2,3-d]pyrimidin-7-yl)cyclobutyl]methyl benzoate Chemical compound C1=CC=2C(Cl)=NC=NC=2N1C(C1)CC1COC(=O)C1=CC=CC=C1 ZBNWLRGIOOFBJO-UHFFFAOYSA-N 0.000 description 1
• NJVHJTQSGGRHGP-UHFFFAOYSA-K [Li].[Al+3].[Cl-].[Cl-].[Cl-] Chemical compound [Li].[Al+3].[Cl-].[Cl-].[Cl-] NJVHJTQSGGRHGP-UHFFFAOYSA-K 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 229940037127 actonel Drugs 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
• 229940009456 adriamycin Drugs 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 229940110282 alimta Drugs 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 150000001414 amino alcohols Chemical group 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 1
• 229960005471 androstenedione Drugs 0.000 description 1
• AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 150000004056 anthraquinones Chemical class 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 229940045985 antineoplastic platinum compound Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 229940078010 arimidex Drugs 0.000 description 1
• 229940087620 aromasin Drugs 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 229940120638 avastin Drugs 0.000 description 1
• 125000003725 azepanyl group Chemical group 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• ZUDYPQRUOYEARG-UHFFFAOYSA-L barium(2+);dihydroxide;octahydrate Chemical compound O.O.O.O.O.O.O.O.[OH-].[OH-].[Ba+2] ZUDYPQRUOYEARG-UHFFFAOYSA-L 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• FBFHMVNWSYOAKD-UHFFFAOYSA-N benzyl n-[3-hydroxy-3-(hydroxymethyl)cyclobutyl]carbamate Chemical compound C1C(CO)(O)CC1NC(=O)OCC1=CC=CC=C1 FBFHMVNWSYOAKD-UHFFFAOYSA-N 0.000 description 1
• 229960000397 bevacizumab Drugs 0.000 description 1
• 229960000997 bicalutamide Drugs 0.000 description 1
• 201000000053 blastoma Diseases 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 239000008366 buffered solution Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 229940088954 camptosar Drugs 0.000 description 1
• 229940127093 camptothecin Drugs 0.000 description 1
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
• 230000005907 cancer growth Effects 0.000 description 1
• 229960004117 capecitabine Drugs 0.000 description 1
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 229940097647 casodex Drugs 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000004709 cell invasion Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 229960005395 cetuximab Drugs 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 239000012069 chiral reagent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 229960002436 cladribine Drugs 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 230000002079 cooperative effect Effects 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 150000005676 cyclic carbonates Chemical class 0.000 description 1
• KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
• ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 description 1
• 229950006418 dactolisib Drugs 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 150000002009 diols Chemical group 0.000 description 1
• 150000002016 disaccharides Chemical class 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
• VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
• LLRANSBEYQZKFY-UHFFFAOYSA-N dodecanoic acid;propane-1,2-diol Chemical compound CC(O)CO.CCCCCCCCCCCC(O)=O LLRANSBEYQZKFY-UHFFFAOYSA-N 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• FSIRXIHZBIXHKT-MHTVFEQDSA-N edatrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CC(CC)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FSIRXIHZBIXHKT-MHTVFEQDSA-N 0.000 description 1
• 229950006700 edatrexate Drugs 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 238000001962 electrophoresis Methods 0.000 description 1
• 229940120655 eloxatin Drugs 0.000 description 1
• 201000008184 embryoma Diseases 0.000 description 1
• 229940082789 erbitux Drugs 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• 229960005309 estradiol Drugs 0.000 description 1
• 229930182833 estradiol Natural products 0.000 description 1
• 102000015694 estrogen receptors Human genes 0.000 description 1
• 108010038795 estrogen receptors Proteins 0.000 description 1
• 229960003399 estrone Drugs 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• UHYNYIGCGVDBTC-UHFFFAOYSA-N ethyl 1h-imidazole-2-carboxylate Chemical compound CCOC(=O)C1=NC=CN1 UHYNYIGCGVDBTC-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
• 229960000752 etoposide phosphate Drugs 0.000 description 1
• 229960005167 everolimus Drugs 0.000 description 1
• 229940085363 evista Drugs 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 229940087476 femara Drugs 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 235000013312 flour Nutrition 0.000 description 1
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
• 229960005304 fludarabine phosphate Drugs 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 229960002949 fluorouracil Drugs 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 229940001490 fosamax Drugs 0.000 description 1
• HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 238000003304 gavage Methods 0.000 description 1
• 229960002584 gefitinib Drugs 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 230000008570 general process Effects 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229960002743 glutamine Drugs 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 229960003690 goserelin acetate Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 150000008282 halocarbons Chemical class 0.000 description 1
• 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000006359 hepatoblastoma Diseases 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
• 229940125697 hormonal agent Drugs 0.000 description 1
• 208000027706 hormone receptor-positive breast cancer Diseases 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 229920001477 hydrophilic polymer Polymers 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• SMKLPBPDGBAFRQ-UHFFFAOYSA-N imidazo[1,5-a]pyrazin-8-amine Chemical class NC1=NC=CN2C=NC=C12 SMKLPBPDGBAFRQ-UHFFFAOYSA-N 0.000 description 1
• 102000018358 immunoglobulin Human genes 0.000 description 1
• 229940072221 immunoglobulins Drugs 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
• 201000002313 intestinal cancer Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229940084651 iressa Drugs 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 238000000021 kinase assay Methods 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 229960004891 lapatinib Drugs 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 201000005249 lung adenocarcinoma Diseases 0.000 description 1
• 208000037841 lung tumor Diseases 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• AYTAYKXVFZPRAF-KQQUZDAGSA-N n'-[(e)-dimethylaminomethylideneamino]-n,n-dimethylmethanimidamide Chemical compound CN(C)\C=N\N=C\N(C)C AYTAYKXVFZPRAF-KQQUZDAGSA-N 0.000 description 1
• BLCLNMBMMGCOAS-UHFFFAOYSA-N n-[1-[[1-[[1-[[1-[[1-[[1-[[1-[2-[(carbamoylamino)carbamoyl]pyrrolidin-1-yl]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amin Chemical compound C1CCC(C(=O)NNC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)C(COC(C)(C)C)NC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 BLCLNMBMMGCOAS-UHFFFAOYSA-N 0.000 description 1
• LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• CTMCWCONSULRHO-UHQPFXKFSA-N nemorubicin Chemical compound C1CO[C@H](OC)CN1[C@@H]1[C@H](O)[C@H](C)O[C@@H](O[C@@H]2C3=C(O)C=4C(=O)C5=C(OC)C=CC=C5C(=O)C=4C(O)=C3C[C@](O)(C2)C(=O)CO)C1 CTMCWCONSULRHO-UHQPFXKFSA-N 0.000 description 1
• 229950010159 nemorubicin Drugs 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000003472 neutralizing effect Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012454 non-polar solvent Substances 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 239000002736 nonionic surfactant Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 230000009701 normal cell proliferation Effects 0.000 description 1
• 238000010606 normalization Methods 0.000 description 1
• 238000011580 nude mouse model Methods 0.000 description 1
• 238000013392 nude mouse xenograft model Methods 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 229960001972 panitumumab Drugs 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
• 238000006303 photolysis reaction Methods 0.000 description 1
• 230000015843 photosynthesis, light reaction Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
• LHNIIDJUOCFXAP-UHFFFAOYSA-N pictrelisib Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 LHNIIDJUOCFXAP-UHFFFAOYSA-N 0.000 description 1
• 229960005141 piperazine Drugs 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 235000008476 powdered milk Nutrition 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 150000003138 primary alcohols Chemical class 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 description 1
• BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 102000009929 raf Kinases Human genes 0.000 description 1
• 108010077182 raf Kinases Proteins 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• 229960004432 raltitrexed Drugs 0.000 description 1
• 229940099538 rapamune Drugs 0.000 description 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 235000009566 rice Nutrition 0.000 description 1
• 229960000371 rofecoxib Drugs 0.000 description 1
• RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
• 238000001896 rotating frame Overhauser effect spectroscopy Methods 0.000 description 1
• VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
• 229950009213 rubitecan Drugs 0.000 description 1
• 229950003647 semaxanib Drugs 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 208000015891 sexual disease Diseases 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 229960002930 sirolimus Drugs 0.000 description 1
• 229940112726 skelid Drugs 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 238000003797 solvolysis reaction Methods 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 238000012916 structural analysis Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000005846 sugar alcohols Chemical class 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
• 238000005694 sulfonylation reaction Methods 0.000 description 1
• WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
• 229960001796 sunitinib Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 229940034785 sutent Drugs 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 229940120982 tarceva Drugs 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 229940063683 taxotere Drugs 0.000 description 1
• 229960001674 tegafur Drugs 0.000 description 1
• WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
• 229960000235 temsirolimus Drugs 0.000 description 1
• 229960003604 testosterone Drugs 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 229960003433 thalidomide Drugs 0.000 description 1
• 229940034915 thalomid Drugs 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
• ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• OBAJXDYVZBHCGT-UHFFFAOYSA-N tris(pentafluorophenyl)borane Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1B(C=1C(=C(F)C(F)=C(F)C=1F)F)C1=C(F)C(F)=C(F)C(F)=C1F OBAJXDYVZBHCGT-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 208000025421 tumor of uterus Diseases 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229940033942 zoladex Drugs 0.000 description 1
• CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/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)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
• 229950009819 zotarolimus Drugs 0.000 description 1