JP2016510723A - 転移抑制活性を有するリン含有糖アナログ複素環 - Google Patents
転移抑制活性を有するリン含有糖アナログ複素環 Download PDFInfo
- Publication number
- JP2016510723A JP2016510723A JP2015558539A JP2015558539A JP2016510723A JP 2016510723 A JP2016510723 A JP 2016510723A JP 2015558539 A JP2015558539 A JP 2015558539A JP 2015558539 A JP2015558539 A JP 2015558539A JP 2016510723 A JP2016510723 A JP 2016510723A
- Authority
- JP
- Japan
- Prior art keywords
- group
- cancer
- formula
- optionally substituted
- compound
- Prior art date
- 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.)
- Granted
Links
- 206010027476 Metastases Diseases 0.000 title claims abstract description 65
- 230000009401 metastasis Effects 0.000 title claims abstract description 30
- 235000000346 sugar Nutrition 0.000 title description 19
- 230000002401 inhibitory effect Effects 0.000 title description 10
- 229910052698 phosphorus Inorganic materials 0.000 title description 7
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title description 3
- 239000011574 phosphorus Substances 0.000 title description 3
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 142
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 99
- 201000011510 cancer Diseases 0.000 claims abstract description 76
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 32
- -1 1H- [1,2,3] triazolyl group Chemical group 0.000 claims description 50
- 238000011282 treatment Methods 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 125000003107 substituted aryl group Chemical group 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 22
- 208000005017 glioblastoma Diseases 0.000 claims description 21
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 125000002252 acyl group Chemical group 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 10
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
- UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical group OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 claims description 9
- 125000003368 amide group Chemical group 0.000 claims description 9
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 125000004185 ester group Chemical group 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 6
- 125000001391 thioamide group Chemical group 0.000 claims description 6
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
- 229910052757 nitrogen Chemical group 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- BGPJLYIFDLICMR-UHFFFAOYSA-N 1,4,2,3-dioxadithiolan-5-one Chemical group O=C1OSSO1 BGPJLYIFDLICMR-UHFFFAOYSA-N 0.000 claims description 4
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 150000002430 hydrocarbons Chemical class 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 claims description 4
- 229910052711 selenium Inorganic materials 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000005587 carbonate group Chemical group 0.000 claims description 3
- 231100000433 cytotoxic Toxicity 0.000 claims description 3
- 230000001472 cytotoxic effect Effects 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 125000000565 sulfonamide group Chemical group 0.000 claims description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 13
- 210000004027 cell Anatomy 0.000 description 86
- 241000699670 Mus sp. Species 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 23
- 238000002347 injection Methods 0.000 description 19
- 239000007924 injection Substances 0.000 description 19
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- 238000013508 migration Methods 0.000 description 15
- 230000005012 migration Effects 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 13
- 230000001093 anti-cancer Effects 0.000 description 13
- 239000003981 vehicle Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 230000001028 anti-proliverative effect Effects 0.000 description 10
- 230000037396 body weight Effects 0.000 description 10
- 210000004185 liver Anatomy 0.000 description 10
- 239000002609 medium Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 210000000056 organ Anatomy 0.000 description 10
- 235000002639 sodium chloride Nutrition 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 206010061289 metastatic neoplasm Diseases 0.000 description 9
- 238000007920 subcutaneous administration Methods 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000001394 metastastic effect Effects 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- JKTYGPATCNUWKN-UHFFFAOYSA-N 4-nitrobenzyl alcohol Chemical compound OCC1=CC=C([N+]([O-])=O)C=C1 JKTYGPATCNUWKN-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 7
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical group CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 7
- 230000034994 death Effects 0.000 description 7
- 201000001441 melanoma Diseases 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical group FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 108010067306 Fibronectins Proteins 0.000 description 6
- 102000016359 Fibronectins Human genes 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 108010031318 Vitronectin Proteins 0.000 description 6
- 102100035140 Vitronectin Human genes 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 239000007788 liquid Substances 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
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 201000002313 intestinal cancer Diseases 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- IRTWXRWGKPXWAV-UHFFFAOYSA-N oxaphosphinane Chemical compound C1CCPOC1 IRTWXRWGKPXWAV-UHFFFAOYSA-N 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 229960004964 temozolomide Drugs 0.000 description 5
- 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 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 101000656751 Haloarcula marismortui (strain ATCC 43049 / DSM 3752 / JCM 8966 / VKM B-1809) 30S ribosomal protein S24e Proteins 0.000 description 4
- 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 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 150000002772 monosaccharides Chemical group 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 125000004437 phosphorous atom Chemical group 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000008247 solid mixture Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 210000000130 stem cell Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000033115 angiogenesis Effects 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 108010057670 laminin 1 Proteins 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 208000020816 lung neoplasm Diseases 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 208000037819 metastatic cancer Diseases 0.000 description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 3
- 238000011580 nude mouse model Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 208000011581 secondary neoplasm Diseases 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 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 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000004471 Glycine Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- VVUHUDLLBPXWMP-UHFFFAOYSA-N O=P1CCCCO1 Chemical class O=P1CCCCO1 VVUHUDLLBPXWMP-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 235000005811 Viola adunca Nutrition 0.000 description 2
- 240000009038 Viola odorata Species 0.000 description 2
- 235000013487 Viola odorata Nutrition 0.000 description 2
- 235000002254 Viola papilionacea Nutrition 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000003698 anagen phase Effects 0.000 description 2
- 238000011394 anticancer treatment Methods 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 2
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 230000005907 cancer growth Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000011247 coating layer Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000005075 mammary gland Anatomy 0.000 description 2
- 125000000311 mannosyl group Chemical group C1([C@@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000013152 negative regulation of cell migration Effects 0.000 description 2
- 150000002482 oligosaccharides Polymers 0.000 description 2
- 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 2
- 239000008188 pellet Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229960004063 propylene glycol Drugs 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 210000004885 white matter Anatomy 0.000 description 2
- 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
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 102100035248 Alpha-(1,3)-fucosyltransferase 4 Human genes 0.000 description 1
- 238000006677 Appel reaction Methods 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-WHZQZERISA-N D-aldose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-WHZQZERISA-N 0.000 description 1
- WQZGKKKJIJFFOK-IVMDWMLBSA-N D-allopyranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-IVMDWMLBSA-N 0.000 description 1
- YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010056474 Erythrosis Diseases 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108700023372 Glycosyltransferases Proteins 0.000 description 1
- 102000051366 Glycosyltransferases Human genes 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 101001022185 Homo sapiens Alpha-(1,3)-fucosyltransferase 4 Proteins 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VSOAQEOCSA-N L-altropyranose Chemical compound OC[C@@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-VSOAQEOCSA-N 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 206010027462 Metastases to ovary Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- MNLRQHMNZILYPY-MDMHTWEWSA-N N-acetyl-alpha-D-muramic acid Chemical compound OC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)O[C@H](O)[C@@H]1NC(C)=O MNLRQHMNZILYPY-MDMHTWEWSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 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 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 231100000229 OECD 452 Chronic Toxicity Study Toxicity 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 229930182475 S-glycoside Natural products 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 102000019259 Succinate Dehydrogenase Human genes 0.000 description 1
- 108010012901 Succinate Dehydrogenase Proteins 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 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 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 230000008649 adaptation response Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005138 alkoxysulfonyl group Chemical group 0.000 description 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- SRBFZHDQGSBBOR-STGXQOJASA-N alpha-D-lyxopyranose Chemical compound O[C@@H]1CO[C@H](O)[C@@H](O)[C@H]1O SRBFZHDQGSBBOR-STGXQOJASA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 125000005142 aryl oxy sulfonyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000010461 azide-alkyne cycloaddition reaction Methods 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 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 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- JJWKPURADFRFRB-UHFFFAOYSA-N carbonyl sulfide Chemical compound O=C=S JJWKPURADFRFRB-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 208000030499 combat disease Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical group C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 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
- 239000006071 cream Substances 0.000 description 1
- 238000000315 cryotherapy Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004981 cycloalkylmethyl group Chemical group 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 125000000600 disaccharide group Chemical group 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002303 glucose derivatives Chemical class 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 230000036252 glycation Effects 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 231100000226 haematotoxicity Toxicity 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 229940072106 hydroxystearate Drugs 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 150000002453 idose derivatives Chemical class 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 201000010893 malignant breast melanoma Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 150000002703 mannose derivatives Chemical class 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- ZUYQAYFMISSPTF-UHFFFAOYSA-N methoxy-oxo-phenylphosphanium Chemical compound CO[P+](=O)C1=CC=CC=C1 ZUYQAYFMISSPTF-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100001221 nontumorigenic Toxicity 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- DINDDLKALYXESU-UHFFFAOYSA-N oxaphosphinan-3-ol Chemical compound OC1CCCOP1 DINDDLKALYXESU-UHFFFAOYSA-N 0.000 description 1
- RGFHLQGHCYAKTD-UHFFFAOYSA-N oxazaphosphinane Chemical compound C1CONPC1 RGFHLQGHCYAKTD-UHFFFAOYSA-N 0.000 description 1
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical group [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- GCSHUYKULREZSJ-UHFFFAOYSA-N phenyl(pyridin-2-yl)methanone Chemical group C=1C=CC=NC=1C(=O)C1=CC=CC=C1 GCSHUYKULREZSJ-UHFFFAOYSA-N 0.000 description 1
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 208000011571 secondary malignant neoplasm Diseases 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000011521 systemic chemotherapy Methods 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 230000008685 targeting Effects 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003569 thioglycosides Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea group Chemical group NC(=S)N UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 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
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- 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 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 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
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000003021 water soluble solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
- C07F9/657163—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom
- C07F9/657172—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and one oxygen atom being part of a (thio)phosphinic acid ester: (X = O, S)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/665—Phosphorus compounds having oxygen as a ring hetero atom, e.g. fosfomycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/67—Phosphorus compounds having sulfur as a ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
- C07F9/65522—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Zは、O、S、Se、NH基もしくはNR6基(式中、R6は、任意選択的に置換されたアリール基もしくはアルキル基、好ましくは酸素原子である)を表す、
R1は、水素原子、任意選択的に置換されたアルキル基もしくはアリール基を表す、
R2aは、水素もしくはハロゲン原子、特にフッ素原子、アジド基(N3)、カーボネート基もしくはジチオカーボネート基、1H−[1,2,3]トリアゾリル基または−X−R2基(式中、Xは、酸素、硫黄もしくはセレン原子を表す)、NHもしくはNR7基(式中、R7は、任意選択的に置換されたアリール基もしくはアルキル基である)を表す、Xは、好ましくはOもしくはNHを表す、およびR2は、任意選択的に置換されたアリール基もしくはアルキル基、水素原子、トリクロロアセトイミデート基(−C(=NH)CCl3)、アシル基、ホルミル基、スルホニル基、スルフィニル基、tert−ブチルジフェニルシリル基、アリル基、サッカリル基、エステル基、アミド基、チオアミド基もしくはスルホンアミド基を表す、またはX−R2は、P(O)R2’R6’基(式中、R2’およびR6’は、相互から独立して、任意選択的に置換されたアリール基もしくはアルキル基、OH基、アルコキシ基もしくはアリールオキシを表す)を表す、
R3およびR4は、相互から独立して、任意選択的に置換されたアリール基もしくはアルキル基、水素原子、トリクロロアセトイミデート基、アシル基、ホルミル基、スルホニル基、スルフィニル基、tert−ブチルジフェニルシリル基、アリル基、エステル基、アミド基、チオアミド基、スルホンアミド基もしくはサッカリル基を表す、またはR3およびR4は、一緒にまとめて、式−R3−R4−(式中、−R3−R4−は、好ましくはイソプロピリデン基、ベンジリデン基、ジフェニルメチリデン基、シクロヘキシルメチリデン基およびそれらの置換アナログ、例えば、4−メトキシベンジリデン基もしくは直鎖状アルキレン基、例えばエチレン基(プロパン−1,2−ジオール基を形成できるように)の二価ラジカルを表す、
R5は、水素原子または好ましくは酸素、硫黄および窒素から選択される1個以上のヘテロ原子、より好ましくは酸素を含む炭化水素系基を表す。
本明細書において既に上記で述べたように、式(1)の化合物は、抗増殖性抗癌活性の他に、それらが癌細胞の遊走を阻害もしくは低減させるという意味での転移抑制活性を有するので、そこで任意のタイプの抗癌組成物中に使用できる有効成分を構成する。
他に特に指示しない限り、NMRスペクトルは、CDCl3中で400.13MHz(1H)で作動するBrueker Avance 400分光計上で記録した。化学シフトは、1Hおよび13Cについてppm/TMSで表示した;結合定数nJはHzで表示した。スペクトルが一次である場合、または一次であると見なせる場合、信号は文字s(一重項)、d(二重項)、t(三重項)、q(四重項)、m(多重項)およびこれらの文字の組み合わせによって表示した。広帯域信号は、文字bが先行するこれらの文字の1つで表示した。
− SNB75は、一次培養由来の、つまり原発性悪性癌腫瘍由来のヒト膠芽腫細胞系である。この細胞系は、NCIに寄託された一群の59種の癌細胞系の一部を形成する。Welcome Trust Sanger研究所によって発行されたCosmic寄託番号は905982である。この細胞系は、Mr.Souhgheng Ning(スタンフォード大学医療センター放射線腫瘍学科のM.D.Ph.D)から供給された。この細胞系は、10%ウシ胎児血清を補給したHam’s F−12およびDMEM(1/1)中で培養した。実験は、指数増殖期にある細胞を用いて実施した。
− Gli4(またはGli4F11)およびGli7は、ヒト膠芽腫由来の癌系統細胞の培養(一次培養)である。これらの細胞系は、動物において多能性および腫瘍原性であるCD133+、CD15+である。これらの細胞系はJ.P.Hugnotによって樹立され(INM INSERM U−1051 Eq.4)、Guichet,P.O.et al,Glia 2013,61(2),225−239に記載されている。
− C6は、ラット膠芽腫細胞系である。この細胞系は、寄託番号CCL−107を付してATCCに寄託されている。
− MDAMB−435は、乳房黒色腫由来の黒色腫細胞系である。この細胞系は、NCIに寄託された一群の59種の癌細胞系の一部を形成する。この細胞系は、寄託番号HTB−129を付してATCCに寄託されている。この細胞系は、10%ウシ胎児血清を補給したHam’s F−12およびDMEM(1/1)中で培養した。実験は指数増殖期にある細胞を用いて実施した。
b.1)化合物3.48a(4,5−ビス−ベンジルオキシ−6−ベンジルオキシメチル−2−フェニル−2−オキソ−2λ5−[1,2]オキサホスフィナン−3−オール)
500mg(0.9mmol)の特許出願の国際公開第2009/004096号パンフレットに記載されたP−H結合を含む式3.47のジアステレオマーの混合物、125mgのテトラキス(トリフェニルホスフィン)パラジウム(0.09mmol、0.1当量)、5mlの無水トルエン、ヨードベンゼンもしくはブロモベンゼン(0.9mmol、1当量)および365μlのトリエチルアミン(2.7mmol、3当量)は、凝縮器を装備した窒素雰囲気下の三つ口フラスコ内へ連続的に導入した。反応媒質は、磁気攪拌装置を用いて4時間にわたり70℃で維持した。反応媒質をセライトに通してろ過し、そこで得られたろ液を減圧下で蒸発させた。油性残留物はその後、81/19のモル比で得られた2つのジアステレオマー3.48aおよび3.48bの分離を可能にするために、シリカゲルクロマトグラフィ(100/0〜50/50のCH2Cl2/EtOAc勾配)によって精製した。ジアステレオ異性体3.48aは、総収率60%で、無色固体の形態で得られた(C32H33O6P、M=544.59g/mol)。この化合物を調製するためにより効率的な方法は、刊行物J.Med.Chem.2012,55,2196−2211に記載されている。
HRMS+(NBA):理論質量545.2093;試験質量545.2104.
安息香酸無水物(132mg、0.58mmol)、ピリジン(25μL、0.39mmol)およびDMAP(4.8mg、0.039mmol)を窒素雰囲気下で、無水CH2Cl2(3ml)中の特許出願の国際公開第2009/004096号パンフレットに記載された化合物3.3aの溶液(150mg、0.39mmol)に加えた。反応混合液を室温で一晩攪拌した。有機溶液を水および飽和塩化ナトリウム水溶液で洗浄した。結合有機相を硫酸ナトリウムの上方に通して乾燥させ、ろ過し、真空下で濃縮した。残留物を最小必要量のCH2Cl2中に溶解させ、ヘキサンから再沈降させた。化合物4.2aは、無色固体の形態で、総収率78%(149mg)で得られた。
1H NMR(400.13MHz,CDCl3):δ1.19(s,3H,CH3),1.24(s,3H,CH3),1.30(s,3H,CH3),1.38(s,3H,CH3),3.30(dd,1H,3JH−H=3.3Hz,3JH−H=7.6Hz,4CH),3.67(dd,1H,3JH−H=5.9Hz,3JH−H=7.2Hz,5CH),3.81(dd,1H,2JH−H=3.8Hz,3JH−H=2.0Hz,2CH),3.97(m,2H,6CH2),4.29(td,1H,3JH−H=3.3Hz,3CH),4.48(ddd,2H,2JH−H=41.8Hz,3JH−H=6.3Hz,2JH−H=3.5Hz,7CH2),4.66(dd,1H,3JH−H=5.1Hz,3JH−H=3.6Hz,1CH),4.81(s,1H,NH),7.22−7.47(m,5H,CHAr).
31P NMR(161.97MHz,CDCl3):δ38.31.1HNMR(400.13MHz,CDCl3):δ1.35(s,3H,CH3),1.37(s,3H,CH3),1.40(s,3H,CH3),1.45(s,3H,CH3),3.35(dd,1H,3JH−H=4.3Hz,2JP−H=7.6Hz,1CH),3.94(bs,2H,7CH2),4.14(m,2H,6CH2),4.43(m,1H,3CH),4.49(qd,1H,3JH−H=1.8Hz,3JH−H=7.6Hz,4CH),4.58(m,1H,5CH),4.69(ddd,1H,3JP−H=21.2Hz,3JH−H=4.3Hz,3JH−H=6.6Hz,2CH),7.23−7.97(m,5H,CHAr).13CNMR(100.61MHz,CDCl3):δ24.66(1s,1C,CH3),25.26(1s,1C,CH3),26.31(1s,1C,CH3),27.01(1s,1C,CH3),52.97(d,1C,1JP−C=87.3Hz,1CH),53.05(s,1C,7CH2),66.81(s,1C,6CH2),72.56(d,1C,2JP−C=3.6Hz,2CH),73.70(d,1C,3JP−C=5.1Hz,5CH),73.81(d,1C,3JP−C=8.7Hz,3CH),75.47(d,1C,2JP−C=1.5Hz,4CH),109.10(s,1C,Cq),110.01(s,1C,Cq),127.27(s,2C,CHANIm),128.14(s,2C,CHANIo),128.79(s,1C,CHArm),128.30(s,1C,CHArm),129.57(d,1C,JP−C=138.9Hz,CqAr),129.60(s,1C,CHANIp),131.82(s,1C,CHAro),131.97(s,1C,CHAro),132.87(s,1C,CHArp),138.94(d,1C,3JP−C=17.4Hz,CqAr).IR(KBrペレット):3351ff(νNH),2980ff,2894ff(νCHAlk),1491ff,1439ff,1370f,1265f,1205FF,1167f,1128m(νC−O−C),1059f(νP=O),962m(νP−O−C),925m(δCHAr),891m,817f,733F,713f,693F.MSFAB+(NBA):m/z(%)475[MH+H+](90%);474[M+H+](50%).HRMS+(NBA):理論質量474.2046;試験質量474.2058.
31P NMR(161.97MHz,CDCl3):δ37.46.1HNMR(400.13MHz,CDCl3):δ1.38(s,3H,CH3),1.41(s,3H,CH3),1.44(s,3H,CH3),1.50(s,3H,CH3),1.86(bs,2H,NH2),3.49(dd,1H,2JP−H=5.2Hz,3JH−H=6.4Hz,1CH),4.11(m,2H,6CH2),4.39−4.58(m,4H,3CH+5CH+2CH+4CH),7.39−7.87(m,5H,CHAr).13CNMR(100.61MHz,CDCl3):δ25.04(s,1C,CH3),25.27(s,1C,CH3),26.93(s,1C,CH3),26.95(s,1C,CH3),48.78(d,1C,1JP−C=91.6Hz,1CH),66.78(s,1C,6CH2),72.85(d,1C,2JP−C=3Hz,2CH),73.27(d,1C,2JP−C=5.1Hz,4CH),73.97(d,1C,3JP−C=9.5Hz,3CH),78.33(s,1C,5CH),109.23(d,1C,Cq),109.96(d,1C,Cq),128.71(d,1C,2JP−C=138Hz,CqAr),128.41(s,1C,CHAr),128.52(s,1C,CHAr),131.92(s,1C,CHAr),132.02(s,1C,CHAr),133.02(s,1C,CHArp).IR(KBrペレット):3287f(νOH),2987ff,2937ff(νCHAlk),1593ff(νNH),1439ff,1372f,1207FF(νP=O),1159m(νC−O−C),1124F(νC−O),1060FF,958F(νP−O−C),920f,890m,836m,798f,727F,694F.MSFAB+(NBA):m/z(%)767[2M+H+](10%),384[M+H+](90%).HRMS+(NBA):理論質量384.1576;試験質量384.1567.
酢酸無水物(72μL、0.76mmol)およびトリエチルアミン(60μL、0.42mmol)を無水CH2Cl2(5mL)中の以前に得られた化合物5.5dの溶液(145mg、0.38mmol)に窒素雰囲気下で加えた。反応混合液を室温で2時間攪拌した。有機溶液を飽和炭酸水素ナトリウム水溶液で洗浄した。結合有機相を硫酸ナトリウムの上方に通して乾燥させ、ろ過し、真空下で濃縮した。次に残留物をシリカゲルクロマトグラフィ(50/50/0〜0/95/5のヘプタン/EtOAc/EtOH勾配)上で精製した。得られた無色固体を最小必要量のジエチルエーテル中に溶解させ、ヘキサンから再沈降させた。化合物5.6dは、12%の総収率で得られた(20mg)。
式3.48aおよび4.2aの化合物は水中、数多くの水溶性溶媒中で不溶性であり、シクロデキストリン中では錯体形成不能である。下記の2種の調製物は、化合物3.48aおよび4.2aに特に適合するので、約20〜100mg/kgの濃度で静脈内投与によるin vivo投与を可能にする。
化合物3.48aおよび4.2aの急性毒性試験は、50、25、10、5および1mg/kgの濃度範囲について健常マウスを対象に実施した。50mg/kgの最高用量についてさえ、死亡は観察されなかった。
SNB75皮下モデル(図1)
100μLの無菌PBS(リン酸緩衝食塩液、Fisher製)中の5×106個のSNB75細胞の懸濁液を各マウスに注射した(麻酔を伴わない皮下投与)。マウスが0.13〜0.033mm3の容積の腫瘍を提示し時点に、各群が同等数の大、中および小腫瘍を含有するように群を形成した。各群マウス7匹を含む5群を用いて試験手順を実施した。以下に記載する5種の調製物中1種を用いて5群のマウスを処置した:
A群:100μLのNaClの注射による処置(コントロール、No.1)。
B群:100〜150μLの量の調製物2を用いて、マウスの体重にしたがって10mg/kgの割合で化合物3.48aを用いた処置。
C群:100〜150μLの量の調製物2を用いて、マウスの体重にしたがって5mg/kgの割合で化合物3.48aを用いた処置。
D群:100〜150μLの量を用いて、マウスの体重にしたがって20mg/kgの割合でテモゾロミドを用いた処置。テモゾロミドは、Schering Plough研究所によってTemodalの名称で販売されている比較抗癌有効成分である。テモゾロミドは、多形性膠芽腫を治療するために適応である。40mg/kgの用量は実験期間の終了前にマウス死亡を生じさせるので、用量を20mg/kgに限定した。
E群:化合物3.48aを含有していない調製物2の、マウスの体重にしたがって100〜150μLの注射による処置(コントロール、No.2)。
2×105個のGli4細胞を1群のマウスに注射した(右側線条体注射、注射座標:プレグマ 0 L−L:L:−1.5mm P:−3.5〜2.5)。マウスは、直ちに週3回、化合物3.48aを10mg/kgで用いて(調製物1、B群)または同一処置手順にしたがって100μLのNaClを使用して(A群)4週間にわたり処置し、10週間後に犠死させた。
100μLの無菌PBS(リン酸緩衝食塩液、Fisher製)中の1×106個のMDAMB−435細胞の懸濁液を各マウスに注射した(左後四半身の乳腺中に麻酔を伴わない皮下投与)。マウス3匹の予備コントロール群が最初の転移(肝臓、腸、卵巣)を提示した時点に、マウス8匹の4群を用いて試験手順を実施した。以下に記載する5種の調製物中1種を用いて5群のマウスを処置した:
A群:100μLのNaClの注射による処置(コントロール、No.1)。
B群:化合物4.2aを含有していない100〜150μLの調製物2を用いて、マウスの体重にしたがった注射による処置(コントロール、No.2)。
C群:100〜150μLの量の調製物2を用いて、マウスの体重にしたがって、10mg/kgの割合で化合物4.2aを用いた処置。
D群:100〜150μLの量の調製物2を用いて、マウスの体重にしたがって、5mg/kgの割合で化合物4.2aを用いた処置。
細胞系MDAMB−435およびA431は、96ウエルプレート内に1ウエル当たり細胞3,000個の密度で播種した。24時間後、100% DMSO中に再懸濁させた化合物4.2aおよび5.6dは、0.3%の最終一定量のDMSOに対して0〜0.001〜0.010〜0.1〜1〜10〜50μMの濃度で加えた。培養をさらに72時間保持し、次にMTT比色試験を実施した。PBS中で5mg/mLのMTTの100μL溶液を培養媒質に加え、これを3時間にわたり培養させた。培養媒質を取り除き、細胞は、イソプロパノール中の100μLの4mM HCl溶媒、0.1% Nondet P−40(NP40)を加えることによって溶解させた。黄色テトラゾリウムMTT塩(3−(4,5−ジメチルチアゾール−2−イル)−2,5−ジフェニルテトラゾリウムブロミド)は、活性生細胞のミトコンドリアコハク酸デヒドロゲナーゼによって還元させられると、青紫色のホルマザン生成物を形成する。この媒質はその後、黄色から青紫色に変化する。590nmでのこの着色強度は試験中に存在する生細胞数に比例し、これらの細胞の代謝活性の指標を生じる。
化合物3.48a、4.2aおよび5.6dが癌細胞(一方ではヒト膠芽腫系SNB75またはヒト膠芽腫Gli4F1の一次培養ならびに他方ではMDAMB 435およびA431)の遊走に及ぼす作用は、ボイデンチャンバ内での標準遊走試験(24時間にわたる細胞の処置)を実施することによって決定した。
Claims (13)
- 癌に罹患した患者における転移の発生を低減もしくは予防する目的で使用するための化合物であって、以下の一般式:
Yは、酸素、硫黄もしくはセレン原子、好ましくは酸素原子を表す、
Zは、O、S、Se、NHもしくはNR6基(式中、R6は、任意選択的に置換されたアリール基もしくはアルキル基である)、好ましくは酸素原子を表す、
R1は、水素原子、任意選択的に置換されたアルキル基もしくはシクロアルキル基、またはアリール基もしくはヘテロアリール基を表す、
R2aは、水素もしくはハロゲン原子、アジド基(N3)、カーボネート基もしくはジチオカーボネート基、1H−[1,2,3]トリアゾリル基または−X−R2基(式中、Xは、酸素、硫黄もしくはセレン原子、NH基もしくはNR7基(式中、R7は、任意選択的に置換されたアリール基、ヘテロアリール基、アルキル基もしくはシクロアルキル基を表す)を表す、Xは、好ましくはOもしくはNHを表す、およびR2は、任意選択的に置換されたアリール基、ヘテロアリール基、アルキル基もしくはシクロアルキル基、水素原子、トリクロロアセトイミデート基(−C(=NH)CCl3)、アシル基、ホルミル基、スルホニル基、スルフィニル基、tert−ブチルジフェニルシリル基、アリル基、サッカリル基、エステル基、アミド基、チオアミド基もしくはスルホンアミド基を表す、またはX−R2は、P(O)R2’R6’基(式中、R2およびR6’は、相互から独立して、任意選択的に置換されたアリール基、ヘテロアリール基、アルキル基もしくはシクロアルキル基、OH基、アルコキシ基もしくはアリールオキシ基を表す)を表す、
R3およびR4は、相互から独立して、任意選択的に置換されたアリール基、ヘテロアリール基、アルキル基もしくはシクロアルキル基、水素原子、トリクロロアセトイミデート基、アシル基、ホルミル基、スルホニル基、スルフィニル基、tert−ブチルジフェニルシリル基、アリル基、エステル基、アミド基、チオアミド基、スルホンアミド基もしくはサッカリル基を表す、またはR3およびR4は、一緒にまとめて、式−R3−R4−(式中、−R3−R4−は、好ましくは任意選択的に置換されたイソプロピリデン基、ベンジリデン基、ジフェニルメチリデン基、シクロヘキシルメチリデン基、好ましくは4−メトキシベンジリデン基もしくは直鎖状アルキレン基、好ましくはエチレン基を表す)の二価ラジカルを表す、
R5は、水素原子または好ましくは酸素、硫黄および窒素から選択される1個以上のヘテロ原子、より好ましくは酸素を含む炭化水素系基を表す)に対応する化合物。 - Y=Z=Oを特徴とする、請求項1に記載の化合物。
- R5基は、下記の基:
- 式(2)または(3):
- 式:
- 式:
- R2aは、-X−R2基(式中、X=NHである)を表すことを特徴とする、請求項1〜5のいずれか一項に記載の化合物。
- X−R2は、NHC(O)R12基(式中、R12は、アリール基もしくはヘテロアリール基、任意選択的に置換されたアルキル基もしくはシクロアルキル基を表す)であることを特徴とする、請求項7に記載の化合物。
- R2aは、-X−R2基(式中、R2は、アリール基もしくはヘテロアリール基、好ましくはヘテロアリール基を表す)を表すことを特徴とする、請求項1〜5のいずれか一項に記載の化合物。
- 癌に罹患した患者における転移の発生を低減もしくは予防する目的で使用するための医薬組成物であって、前記医薬組成物は、請求項1〜9のいずれか一項に規定した式(1)の少なくとも1つの化合物を1種以上の医薬上許容される賦形剤および/またはビヒクルと組み合わせて含むことを特徴とする医薬組成物。
- 前記患者は、多形性膠芽腫、乳癌および非小細胞肺癌から選択される癌、好ましくは多形性膠芽腫に罹患していることを特徴とする、請求項10に記載の医薬組成物。
- 少なくとも1種の有機溶媒および少なくとも1種の界面活性剤を含むことを特徴とする、請求項10または11に記載の医薬組成物。
- 癌の治療に使用するための併用製剤であって、前記併用製剤が、
i)少なくとも1種の細胞毒性化合物、および
ii)転移の発生を低減もしくは予防する目的で使用するための、請求項1〜9のいずれか一項に記載の式(1)の少なくとも1種の化合物を含むことを特徴とする併用製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1351654 | 2013-02-25 | ||
FR1351654A FR3002451B1 (fr) | 2013-02-25 | 2013-02-25 | Heterocycles phosphores analogues de sucres a activite antimetastatique |
PCT/FR2014/050409 WO2014128429A1 (fr) | 2013-02-25 | 2014-02-25 | Hétérocycles phosphorés analogues de sucres à activité antimétastatique |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016510723A true JP2016510723A (ja) | 2016-04-11 |
JP6588341B2 JP6588341B2 (ja) | 2019-10-09 |
Family
ID=48795645
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015558539A Active JP6588341B2 (ja) | 2013-02-25 | 2014-02-25 | 転移抑制活性を有するリン含有糖アナログ複素環 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20150376216A1 (ja) |
EP (1) | EP2958569B1 (ja) |
JP (1) | JP6588341B2 (ja) |
CN (1) | CN105263501A (ja) |
AU (1) | AU2014220455B2 (ja) |
CA (1) | CA2902276C (ja) |
FR (1) | FR3002451B1 (ja) |
WO (1) | WO2014128429A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019529552A (ja) * | 2016-09-20 | 2019-10-17 | フォスティン | 3−ヒドロキシ−4,5−ビス−ベンジルオキシ−6−ベンジルオキシメチル−2−フェニル−2−オキソ−2λ5−[1,2]オキサホスフィナンの結晶多形体 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017173360A2 (en) * | 2016-03-31 | 2017-10-05 | Stcube, Inc. | Combination treatments directed toward programmed death ligand-1 (pd-l1) positive cancers |
AU2022209089A1 (en) | 2021-01-13 | 2023-07-06 | Phost'in Therapeutics | Cyclic oxaphosphinane compounds and analogues thereof for treating fibrotic diseases |
WO2023222866A1 (en) | 2022-05-20 | 2023-11-23 | Phost'in Therapeutics | Dose and regimen for a heterocyclic phosphinic compound |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009004096A1 (en) * | 2007-07-05 | 2009-01-08 | Centre National De La Recherche Scientifique | New phosphorus containing heterocyclic compounds, sugar analogues, and compositions having anti-cancer activity containing the same |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2744483B1 (en) * | 2011-08-15 | 2020-04-29 | Jyant Technologies | Delivery system for specifically targeting cancer cells and method of use thereof |
-
2013
- 2013-02-25 FR FR1351654A patent/FR3002451B1/fr active Active
-
2014
- 2014-02-25 CN CN201480010238.0A patent/CN105263501A/zh active Pending
- 2014-02-25 CA CA2902276A patent/CA2902276C/fr active Active
- 2014-02-25 WO PCT/FR2014/050409 patent/WO2014128429A1/fr active Application Filing
- 2014-02-25 US US14/769,928 patent/US20150376216A1/en not_active Abandoned
- 2014-02-25 AU AU2014220455A patent/AU2014220455B2/en active Active
- 2014-02-25 EP EP14711831.9A patent/EP2958569B1/fr active Active
- 2014-02-25 JP JP2015558539A patent/JP6588341B2/ja active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009004096A1 (en) * | 2007-07-05 | 2009-01-08 | Centre National De La Recherche Scientifique | New phosphorus containing heterocyclic compounds, sugar analogues, and compositions having anti-cancer activity containing the same |
Non-Patent Citations (2)
Title |
---|
CRISTAU, HENRI-JEAN ET AL.,: "First synthesis of P-aryl-phosphinosugars, organophosphorus analogues of C-arylglycosides", TETRAHEDRON LETTERS, vol. (2005), 46(21), 3741-3744, JPN6017050858, 2005, ISSN: 0004019407 * |
LUDOVIC CLARION ET AL.,: "Oxaphosphinanes: new therapeutic perspectives for glioblastoma", JOURNAL OF MEDICINAL CHEMISTRY, vol. (2012), 55(5), 2196-2211, JPN6017050857, 2012, ISSN: 0004019406 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019529552A (ja) * | 2016-09-20 | 2019-10-17 | フォスティン | 3−ヒドロキシ−4,5−ビス−ベンジルオキシ−6−ベンジルオキシメチル−2−フェニル−2−オキソ−2λ5−[1,2]オキサホスフィナンの結晶多形体 |
JP7235661B2 (ja) | 2016-09-20 | 2023-03-08 | フォスティン | 3-ヒドロキシ-4,5-ビス-ベンジルオキシ-6-ベンジルオキシメチル-2-フェニル-2-オキソ-2λ5-[1,2]オキサホスフィナンの結晶多形体 |
Also Published As
Publication number | Publication date |
---|---|
FR3002451B1 (fr) | 2015-06-26 |
CA2902276A1 (fr) | 2014-08-28 |
JP6588341B2 (ja) | 2019-10-09 |
US20150376216A1 (en) | 2015-12-31 |
EP2958569B1 (fr) | 2021-01-13 |
AU2014220455B2 (en) | 2018-07-19 |
WO2014128429A1 (fr) | 2014-08-28 |
AU2014220455A1 (en) | 2015-09-17 |
EP2958569A1 (fr) | 2015-12-30 |
CN105263501A (zh) | 2016-01-20 |
FR3002451A1 (fr) | 2014-08-29 |
CA2902276C (fr) | 2022-05-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2017293781B2 (en) | Compounds, compositions, and methods for the treatment of disease | |
BR112019023733A2 (pt) | Compostos para o tratamento de distúrbios de resistência à insulina sistêmica e o uso dos mesmos | |
US9351988B2 (en) | Macrocyclic lactones and use thereof | |
JP6588341B2 (ja) | 転移抑制活性を有するリン含有糖アナログ複素環 | |
JP2009538317A (ja) | 癌治療のための置換ジアリールウレアを用いた薬物の組み合わせ | |
AU2014324634A1 (en) | Methods and compositions for treating and/or preventing mucositis | |
CN101787064B (zh) | 阿糖胞苷衍生物及其在抗癌抗肿瘤中的用途 | |
CN110382490A (zh) | 喹唑啉类化合物及其制备方法、用途和药物组合物 | |
CN104138369B (zh) | 抗癌药物 | |
CN105377848A (zh) | 取代的三唑并吡啶的前体药物衍生物 | |
TW201733596A (zh) | 尿苷類磷醯胺前藥、其製備方法及其藥物組合物 | |
JP7101279B2 (ja) | 新規なベンゾイミダゾール誘導体、この製造方法及び、これの抗がん剤の用途 | |
CN105960399B (zh) | 酶抑制剂环氧酮化合物 | |
JP2003520819A (ja) | 新規な化合物 | |
JP2669762B2 (ja) | 2―(1―ヒドロキシエチル)―5―ヒドロキシナフト〔2,3―b〕フラン―4,9―ジオンを含有する発癌プロモーション阻害剤 | |
KR102205795B1 (ko) | 백금 항암제인 카보플라틴을 폴리숙신이미드에 결합시킨 개량 항암제 | |
TW202135792A (zh) | 治療癌症之方法 | |
CN101787065B (zh) | 阿糖胞苷前药衍生物及其在抗癌抗肿瘤中的用途 | |
RU2801306C2 (ru) | Новое фосфатэфирное соединение, имеющее пирролопиримидиновый скелет, или его фармацевтически приемлемая соль | |
KR20050038632A (ko) | 양성 및 악성 종양 질환의 치료를 위한 디스오라졸 및 이의유도체를 함유하는 의약 | |
BR112019016089A2 (pt) | composições e métodos para modulação de ppp2r1a | |
CN106995368B (zh) | 一种非atp竞争性fgfr1抑制剂及其应用 | |
KR101323698B1 (ko) | Azt의 변형된 5'-포스포네이트 - 잠재적 항바이러스제 | |
EP3777852A1 (en) | Pharmaceutical composition including 1,2-naphthoquinone derivative compound for prevention or treatment of solid cancers or blood cancers | |
TW202404609A (zh) | 雜環次膦酸化合物之劑量及投藥方案 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151224 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A712 Effective date: 20151224 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20151224 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160202 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170117 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20171225 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180116 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180416 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180607 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180607 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20180724 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181120 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20190226 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190423 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190717 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190719 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190820 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190912 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6588341 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |