JPWO2015046278A1 - 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 - Google Patents
新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 Download PDFInfo
- Publication number
- JPWO2015046278A1 JPWO2015046278A1 JP2015539283A JP2015539283A JPWO2015046278A1 JP WO2015046278 A1 JPWO2015046278 A1 JP WO2015046278A1 JP 2015539283 A JP2015539283 A JP 2015539283A JP 2015539283 A JP2015539283 A JP 2015539283A JP WO2015046278 A1 JPWO2015046278 A1 JP WO2015046278A1
- Authority
- JP
- Japan
- Prior art keywords
- group
- optionally substituted
- ethyl
- hydrogen atom
- amino
- 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
- 150000003839 salts Chemical class 0.000 title claims abstract description 76
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 70
- 239000002184 metal Substances 0.000 title claims abstract description 70
- 150000002739 metals Chemical class 0.000 title claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 129
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 126
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims abstract description 61
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 14
- 239000013522 chelant Substances 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 200
- -1 substituted Chemical class 0.000 claims description 189
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 84
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 claims description 71
- 102000006495 integrins Human genes 0.000 claims description 61
- 108010044426 integrins Proteins 0.000 claims description 61
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 48
- 125000006239 protecting group Chemical group 0.000 claims description 45
- 238000004519 manufacturing process Methods 0.000 claims description 43
- 238000011282 treatment Methods 0.000 claims description 41
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 27
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 229940124597 therapeutic agent Drugs 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 23
- 230000002285 radioactive effect Effects 0.000 claims description 23
- 238000003745 diagnosis Methods 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 19
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims description 16
- 238000002560 therapeutic procedure Methods 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 14
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004434 sulfur atom Chemical group 0.000 claims description 7
- 125000001821 azanediyl group Chemical group [H]N(*)* 0.000 claims description 6
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 6
- 231100000433 cytotoxic Toxicity 0.000 claims description 6
- 230000001472 cytotoxic effect Effects 0.000 claims description 6
- 231100000065 noncytotoxic Toxicity 0.000 claims description 6
- 230000002020 noncytotoxic effect Effects 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- 229910052782 aluminium Inorganic materials 0.000 claims description 5
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 5
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 3
- BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 claims description 3
- 239000007983 Tris buffer Substances 0.000 claims description 3
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims description 3
- LGGRGKCHOVCCND-UHFFFAOYSA-N 5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanamide Chemical compound C1CCNC2=NC(CCCCC(=O)N)=CC=C21 LGGRGKCHOVCCND-UHFFFAOYSA-N 0.000 claims description 2
- 125000005522 oxopentanoic acid group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- SDKPSXWGRWWLKR-UHFFFAOYSA-M sodium;9,10-dioxoanthracene-1-sulfonate Chemical compound [Na+].O=C1C2=CC=CC=C2C(=O)C2=C1C=CC=C2S(=O)(=O)[O-] SDKPSXWGRWWLKR-UHFFFAOYSA-M 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 429
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 350
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 294
- 239000000203 mixture Substances 0.000 description 243
- 239000000243 solution Substances 0.000 description 218
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 207
- 239000002904 solvent Substances 0.000 description 200
- 230000002829 reductive effect Effects 0.000 description 187
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 168
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 162
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 113
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 97
- 206010028980 Neoplasm Diseases 0.000 description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
- 238000002953 preparative HPLC Methods 0.000 description 86
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 78
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 78
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 66
- 125000001424 substituent group Chemical group 0.000 description 65
- 238000010898 silica gel chromatography Methods 0.000 description 64
- 238000004809 thin layer chromatography Methods 0.000 description 58
- 239000007864 aqueous solution Substances 0.000 description 57
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 56
- 239000012044 organic layer Substances 0.000 description 54
- 238000004128 high performance liquid chromatography Methods 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 47
- 229920006395 saturated elastomer Polymers 0.000 description 47
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 46
- 239000007788 liquid Substances 0.000 description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- 239000011780 sodium chloride Substances 0.000 description 39
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 38
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 36
- 238000003384 imaging method Methods 0.000 description 35
- 238000001914 filtration Methods 0.000 description 34
- 238000000746 purification Methods 0.000 description 34
- 239000010949 copper Substances 0.000 description 33
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 229910052739 hydrogen Inorganic materials 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 229910052763 palladium Inorganic materials 0.000 description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 26
- 239000012298 atmosphere Substances 0.000 description 26
- 239000001257 hydrogen Substances 0.000 description 26
- 239000002198 insoluble material Substances 0.000 description 26
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 235000011114 ammonium hydroxide Nutrition 0.000 description 22
- 210000004027 cell Anatomy 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 201000011510 cancer Diseases 0.000 description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
- 238000012360 testing method Methods 0.000 description 20
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 19
- 239000005695 Ammonium acetate Substances 0.000 description 19
- 229940043376 ammonium acetate Drugs 0.000 description 19
- 235000019257 ammonium acetate Nutrition 0.000 description 19
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 18
- 235000019253 formic acid Nutrition 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 17
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 16
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 description 16
- 235000011054 acetic acid Nutrition 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- 210000000692 cap cell Anatomy 0.000 description 14
- 239000002953 phosphate buffered saline Substances 0.000 description 14
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 230000035508 accumulation Effects 0.000 description 13
- 238000009825 accumulation Methods 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 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 12
- 239000002585 base Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 239000003643 water by type Substances 0.000 description 11
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 10
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 10
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 210000003462 vein Anatomy 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 229940098779 methanesulfonic acid Drugs 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000011593 sulfur Substances 0.000 description 8
- 206010002091 Anaesthesia Diseases 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 230000037005 anaesthesia Effects 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 208000005017 glioblastoma Diseases 0.000 description 7
- 201000001441 melanoma Diseases 0.000 description 7
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 description 6
- 229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 6
- 150000008282 halocarbons Chemical class 0.000 description 6
- 238000002372 labelling Methods 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- 102200082402 rs751610198 Human genes 0.000 description 6
- 239000007974 sodium acetate buffer Substances 0.000 description 6
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 5
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 5
- 241000282693 Cercopithecidae Species 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229960005219 gentisic acid Drugs 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 229960002725 isoflurane Drugs 0.000 description 5
- 229910021645 metal ion Inorganic materials 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 150000007530 organic bases Chemical class 0.000 description 5
- 230000002688 persistence Effects 0.000 description 5
- 235000017281 sodium acetate Nutrition 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 0 C*C(*)=*C[*@@](C)*=C(C)OCC*C(N(*)**N(*)**)=O Chemical compound C*C(*)=*C[*@@](C)*=C(C)OCC*C(N(*)**N(*)**)=O 0.000 description 4
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 description 4
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- 239000007821 HATU Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 108010031318 Vitronectin Proteins 0.000 description 4
- 102100035140 Vitronectin Human genes 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 4
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 4
- 229940039227 diagnostic agent Drugs 0.000 description 4
- 239000000032 diagnostic agent Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 235000004515 gallic acid Nutrition 0.000 description 4
- 229940074391 gallic acid Drugs 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000001632 sodium acetate Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 3
- MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical compound C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 description 3
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
- XQPYRJIMPDBGRW-UHFFFAOYSA-N 2-[2-[2-(9h-fluoren-9-ylmethoxycarbonylamino)ethoxy]ethoxy]acetic acid Chemical compound C1=CC=C2C(COC(=O)NCCOCCOCC(=O)O)C3=CC=CC=C3C2=C1 XQPYRJIMPDBGRW-UHFFFAOYSA-N 0.000 description 3
- NXMFJCRMSDRXLD-UHFFFAOYSA-N 2-aminopyridine-3-carbaldehyde Chemical compound NC1=NC=CC=C1C=O NXMFJCRMSDRXLD-UHFFFAOYSA-N 0.000 description 3
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010060862 Prostate cancer Diseases 0.000 description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
- 206010041067 Small cell lung cancer Diseases 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 125000003435 aroyl group Chemical group 0.000 description 3
- 238000000376 autoradiography Methods 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 3
- 238000002224 dissection Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000686 essence Substances 0.000 description 3
- XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000007917 intracranial administration Methods 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 3
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 125000002755 pyrazolinyl group Chemical group 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 230000036326 tumor accumulation Effects 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- QBPPRVHXOZRESW-UHFFFAOYSA-N 1,4,7,10-tetraazacyclododecane Chemical compound C1CNCCNCCNCCN1 QBPPRVHXOZRESW-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- UDOPJKHABYSVIX-UHFFFAOYSA-N 2-[4,7,10-tris(carboxymethyl)-6-[(4-isothiocyanatophenyl)methyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound C1N(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CCN(CC(O)=O)C1CC1=CC=C(N=C=S)C=C1 UDOPJKHABYSVIX-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VIINUIVVPDAAMU-UHFFFAOYSA-N 4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CCC1=CC=C(CCCN2)C2=N1 VIINUIVVPDAAMU-UHFFFAOYSA-N 0.000 description 2
- FNQOZVBPYZGHNO-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxybutan-2-one Chemical compound CC(=O)CCO[Si](C)(C)C(C)(C)C FNQOZVBPYZGHNO-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108090001008 Avidin Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 241000725101 Clea Species 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 229910052688 Gadolinium Inorganic materials 0.000 description 2
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 229910052765 Lutetium Inorganic materials 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 231100000987 absorbed dose Toxicity 0.000 description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 125000005263 alkylenediamine group Chemical group 0.000 description 2
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 239000002839 antibiotic anticancer agent Substances 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- QMMFTRJQCCVPCE-UHFFFAOYSA-N benzyl n-(2-aminoethyl)carbamate Chemical compound NCCNC(=O)OCC1=CC=CC=C1 QMMFTRJQCCVPCE-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 238000007413 biotinylation Methods 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 229950008138 carmellose Drugs 0.000 description 2
- 230000021164 cell adhesion Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 150000004696 coordination complex Chemical class 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical compound CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- CBOQJANXLMLOSS-UHFFFAOYSA-N ethyl vanillin Chemical compound CCOC1=CC(C=O)=CC=C1O CBOQJANXLMLOSS-UHFFFAOYSA-N 0.000 description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 229910052733 gallium Inorganic materials 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 229940125697 hormonal agent Drugs 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- UKCIUOYPDVLQFW-UHFFFAOYSA-K indium(3+);trichloride;tetrahydrate Chemical compound O.O.O.O.Cl[In](Cl)Cl UKCIUOYPDVLQFW-UHFFFAOYSA-K 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 2
- 208000023589 ischemic disease Diseases 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- OHSVLFRHMCKCQY-UHFFFAOYSA-N lutetium atom Chemical compound [Lu] OHSVLFRHMCKCQY-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 108010082117 matrigel Proteins 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 125000001800 methanetriyl group Chemical group C(*)(*)* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 231100000782 microtubule inhibitor Toxicity 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- PJUIMOJAAPLTRJ-UHFFFAOYSA-N monothioglycerol Chemical compound OCC(O)CS PJUIMOJAAPLTRJ-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229940127084 other anti-cancer agent Drugs 0.000 description 2
- 229960003330 pentetic acid Drugs 0.000 description 2
- 108040007629 peroxidase activity proteins Proteins 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 2
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 229910052716 thallium Inorganic materials 0.000 description 2
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000003325 tomography Methods 0.000 description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- ZYZHMSJNPCYUTB-CYBMUJFWSA-N (1r)-n-benzyl-1-phenylethanamine Chemical compound N([C@H](C)C=1C=CC=CC=1)CC1=CC=CC=C1 ZYZHMSJNPCYUTB-CYBMUJFWSA-N 0.000 description 1
- IFOJOAWVOCABAY-JEDNCBNOSA-N (2S)-2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid chloromethane Chemical compound CCl.CC(C)(C)OC(=O)NC[C@H](N)C(O)=O IFOJOAWVOCABAY-JEDNCBNOSA-N 0.000 description 1
- UMRUUWFGLGNQLI-QFIPXVFZSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UMRUUWFGLGNQLI-QFIPXVFZSA-N 0.000 description 1
- BGGHCRNCRWQABU-JTQLQIEISA-N (2s)-2-amino-5-oxo-5-phenylmethoxypentanoic acid Chemical compound OC(=O)[C@@H](N)CCC(=O)OCC1=CC=CC=C1 BGGHCRNCRWQABU-JTQLQIEISA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonic acid Chemical compound CC1=CC(C)=C(S(O)(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- GDUSYVYMSBNFTK-UHFFFAOYSA-N 2-[4,7,10-tris(2-oxo-2-phenylmethoxyethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound C1CN(CC(=O)OCC=2C=CC=CC=2)CCN(CC(=O)OCC=2C=CC=CC=2)CCN(CC(=O)O)CCN1CC(=O)OCC1=CC=CC=C1 GDUSYVYMSBNFTK-UHFFFAOYSA-N 0.000 description 1
- RVUXZXMKYMSWOM-UHFFFAOYSA-N 2-[4,7,10-tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound CC(C)(C)OC(=O)CN1CCN(CC(O)=O)CCN(CC(=O)OC(C)(C)C)CCN(CC(=O)OC(C)(C)C)CC1 RVUXZXMKYMSWOM-UHFFFAOYSA-N 0.000 description 1
- HHLZCENAOIROSL-UHFFFAOYSA-N 2-[4,7-bis(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound OC(=O)CN1CCNCCN(CC(O)=O)CCN(CC(O)=O)CC1 HHLZCENAOIROSL-UHFFFAOYSA-N 0.000 description 1
- SYFGLWDDLZQFNI-UHFFFAOYSA-N 2-[4-(carboxymethyl)-1,4,8,11-tetrazabicyclo[6.6.2]hexadecan-11-yl]acetic acid Chemical compound C1CN(CC(O)=O)CCCN2CCN(CC(=O)O)CCCN1CC2 SYFGLWDDLZQFNI-UHFFFAOYSA-N 0.000 description 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical group NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- MXIIFPFEQROLEO-UHFFFAOYSA-N 3,3,3-triethoxyprop-1-yne Chemical compound CCOC(OCC)(OCC)C#C MXIIFPFEQROLEO-UHFFFAOYSA-N 0.000 description 1
- CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 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
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- AVYQPULWSBXEOF-UHFFFAOYSA-N 4-(4-chlorosulfonyl-3,5-dimethylphenoxy)butanoic acid Chemical compound CC1=CC(OCCCC(O)=O)=CC(C)=C1S(Cl)(=O)=O AVYQPULWSBXEOF-UHFFFAOYSA-N 0.000 description 1
- GRJZJFUBQYULKL-UHFFFAOYSA-N 4-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1C=CN2 GRJZJFUBQYULKL-UHFFFAOYSA-N 0.000 description 1
- RYVOZMPTISNBDB-UHFFFAOYSA-N 4-bromo-2-fluorophenol Chemical compound OC1=CC=C(Br)C=C1F RYVOZMPTISNBDB-UHFFFAOYSA-N 0.000 description 1
- PIIZYNQECPTVEO-UHFFFAOYSA-N 4-nitro-m-cresol Chemical compound CC1=CC(O)=CC=C1[N+]([O-])=O PIIZYNQECPTVEO-UHFFFAOYSA-N 0.000 description 1
- GJAACFNQDNFJNX-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1,8-naphthyridine-2-carbaldehyde Chemical compound C1CCNC2=NC(C=O)=CC=C21 GJAACFNQDNFJNX-UHFFFAOYSA-N 0.000 description 1
- IZOQMUVIDMLRDC-UHFFFAOYSA-N 5-aceto valeric acid Chemical compound CC(=O)CCCCC(O)=O IZOQMUVIDMLRDC-UHFFFAOYSA-N 0.000 description 1
- VNYBIBSZZDAEOK-UHFFFAOYSA-N 5-bromopyridin-3-ol Chemical compound OC1=CN=CC(Br)=C1 VNYBIBSZZDAEOK-UHFFFAOYSA-N 0.000 description 1
- BKLJUYPLUWUEOQ-UHFFFAOYSA-N 6-bromopyridin-2-amine Chemical compound NC1=CC=CC(Br)=N1 BKLJUYPLUWUEOQ-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- OSAHCBHKCKPJGI-UHFFFAOYSA-N 7-keto-n-caprylic acid Chemical compound CC(=O)CCCCCC(O)=O OSAHCBHKCKPJGI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 description 1
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 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 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 208000005440 Basal Cell Neoplasms Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010061692 Benign muscle neoplasm Diseases 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- FZDFGHZZPBUTGP-UHFFFAOYSA-N CC(CN(CC(Cc(cc1)ccc1N=C=S)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O Chemical compound CC(CN(CC(Cc(cc1)ccc1N=C=S)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O FZDFGHZZPBUTGP-UHFFFAOYSA-N 0.000 description 1
- VEIVPVCEHYXING-UHFFFAOYSA-N CNC(CNC(CCCCc1nc(NCCC2)c2cc1)=O)C(O)=O Chemical compound CNC(CNC(CCCCc1nc(NCCC2)c2cc1)=O)C(O)=O VEIVPVCEHYXING-UHFFFAOYSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
- NPPUXPSUEYNEQO-UHFFFAOYSA-N Cc1cc(OCCCC(NCCNC(C(CS(O)(=O)=O)N)=O)=O)cc(C)c1C Chemical compound Cc1cc(OCCCC(NCCNC(C(CS(O)(=O)=O)N)=O)=O)cc(C)c1C NPPUXPSUEYNEQO-UHFFFAOYSA-N 0.000 description 1
- VHYQCFXZOLSIJJ-UHFFFAOYSA-N Cc1cc(OCCCC(NCCNC(C(CS(O)(=O)=O)N)=O)=O)cc(C)c1S(NC(CNC(c1ccc(CCc2nc(NCCC3)c3cc2)cc1)=O)C(O)=O)(=O)=O Chemical compound Cc1cc(OCCCC(NCCNC(C(CS(O)(=O)=O)N)=O)=O)cc(C)c1S(NC(CNC(c1ccc(CCc2nc(NCCC3)c3cc2)cc1)=O)C(O)=O)(=O)=O VHYQCFXZOLSIJJ-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 208000005243 Chondrosarcoma Diseases 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 229910052692 Dysprosium Inorganic materials 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 208000006168 Ewing Sarcoma Diseases 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 235000016623 Fragaria vesca Nutrition 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 1
- 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 206010018852 Haematoma Diseases 0.000 description 1
- 208000008051 Hereditary Nonpolyposis Colorectal Neoplasms Diseases 0.000 description 1
- 208000017095 Hereditary nonpolyposis colon cancer Diseases 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 229910052689 Holmium Inorganic materials 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010021042 Hypopharyngeal cancer Diseases 0.000 description 1
- 206010056305 Hypopharyngeal neoplasm Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000002146 L01XE16 - Crizotinib Substances 0.000 description 1
- 239000002138 L01XE21 - Regorafenib Substances 0.000 description 1
- 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 1
- 206010023825 Laryngeal cancer Diseases 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 206010062038 Lip neoplasm Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 201000005027 Lynch syndrome Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000009018 Medullary thyroid cancer Diseases 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229940122255 Microtubule inhibitor Drugs 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 240000008790 Musa x paradisiaca Species 0.000 description 1
- 235000018290 Musa x paradisiaca Nutrition 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 201000004458 Myoma Diseases 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-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
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 208000003076 Osteolysis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010033701 Papillary thyroid cancer Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 208000007452 Plasmacytoma Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000037276 Primitive Peripheral Neuroectodermal Tumors Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
- 206010061934 Salivary gland cancer Diseases 0.000 description 1
- 229910052772 Samarium Inorganic materials 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 206010043276 Teratoma Diseases 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- NSOXQYCFHDMMGV-UHFFFAOYSA-N Tetrakis(2-hydroxypropyl)ethylenediamine Chemical compound CC(O)CN(CC(C)O)CCN(CC(C)O)CC(C)O NSOXQYCFHDMMGV-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010062129 Tongue neoplasm Diseases 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 1
- 206010046392 Ureteric cancer Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 108010048673 Vitronectin Receptors Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical group C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- WXIONIWNXBAHRU-UHFFFAOYSA-N [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylidene]-dimethylazanium Chemical compound C1=CN=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 WXIONIWNXBAHRU-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 102000019997 adhesion receptor Human genes 0.000 description 1
- 108010013985 adhesion receptor Proteins 0.000 description 1
- 201000006966 adult T-cell leukemia Diseases 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical group 0.000 description 1
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000010108 arterial embolization Effects 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 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
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229910052797 bismuth Inorganic materials 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
- 230000000903 blocking effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229960003261 carmofur Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- OIQPTROHQCGFEF-UHFFFAOYSA-L chembl1371409 Chemical compound [Na+].[Na+].OC1=CC=C2C=C(S([O-])(=O)=O)C=CC2=C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 OIQPTROHQCGFEF-UHFFFAOYSA-L 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960005061 crizotinib Drugs 0.000 description 1
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 150000003983 crown ethers Chemical group 0.000 description 1
- 238000000315 cryotherapy Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000004976 cyclobutylene group Chemical group 0.000 description 1
- 125000004977 cycloheptylene group Chemical group 0.000 description 1
- UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 1
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000004978 cyclooctylene group Chemical group 0.000 description 1
- 125000004979 cyclopentylene group Chemical group 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 125000004980 cyclopropylene group Chemical group 0.000 description 1
- XVOYSCVBGLVSOL-UHFFFAOYSA-N cysteic acid Chemical compound OC(=O)C(N)CS(O)(=O)=O XVOYSCVBGLVSOL-UHFFFAOYSA-N 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- GRGJVECUQLAEDM-LMOVPXPDSA-N dibenzyl (2s)-2-aminopentanedioate;hydrochloride Chemical compound Cl.C([C@H](N)C(=O)OCC=1C=CC=CC=1)CC(=O)OCC1=CC=CC=C1 GRGJVECUQLAEDM-LMOVPXPDSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 1
- VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- BJAJDJDODCWPNS-UHFFFAOYSA-N dotp Chemical compound O=C1N2CCOC2=NC2=C1SC=C2 BJAJDJDODCWPNS-UHFFFAOYSA-N 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- LBKRGPWRBHUMBR-UHFFFAOYSA-N ethyl 4-(1,8-naphthyridin-2-yl)butanoate Chemical compound C1=CC=NC2=NC(CCCC(=O)OCC)=CC=C21 LBKRGPWRBHUMBR-UHFFFAOYSA-N 0.000 description 1
- HJOKHYAUMWNBJB-UHFFFAOYSA-N ethyl 4-(3-bromopropyl)benzoate Chemical compound CCOC(=O)C1=CC=C(CCCBr)C=C1 HJOKHYAUMWNBJB-UHFFFAOYSA-N 0.000 description 1
- CKAGLAFXBLZHAS-UHFFFAOYSA-N ethyl 4-ethynylbenzoate Chemical compound CCOC(=O)C1=CC=C(C#C)C=C1 CKAGLAFXBLZHAS-UHFFFAOYSA-N 0.000 description 1
- PZNHMXAOMDQLLE-UHFFFAOYSA-N ethyl 5-bromothiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(Br)S1 PZNHMXAOMDQLLE-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 229940073505 ethyl vanillin Drugs 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000008369 fruit flavor Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 201000010175 gallbladder cancer Diseases 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-L glutarate(2-) Chemical compound [O-]C(=O)CCCC([O-])=O JFCQEDHGNNZCLN-UHFFFAOYSA-L 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 201000006866 hypopharynx cancer Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000005835 indanylene group Chemical group 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical group NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052746 lanthanum Inorganic materials 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 206010023841 laryngeal neoplasm Diseases 0.000 description 1
- 229910052745 lead Inorganic materials 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 201000006721 lip cancer Diseases 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 125000003099 maleoyl group Chemical group C(\C=C/C(=O)*)(=O)* 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229910001512 metal fluoride Inorganic materials 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- GDJLJNFNXINTHS-FYZOBXCZSA-N methyl (2r)-2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](N)CNC(=O)OC(C)(C)C GDJLJNFNXINTHS-FYZOBXCZSA-N 0.000 description 1
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004957 naphthylene group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229950007221 nedaplatin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 125000005961 oxazepanyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 230000005408 paramagnetism Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 208000016802 peripheral primitive neuroectodermal tumor Diseases 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000010665 pine oil Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 208000015768 polyposis Diseases 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 150000004032 porphyrins Chemical group 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- MREOOEFUTWFQOC-UHFFFAOYSA-M potassium;5-chloro-4-hydroxy-1h-pyridin-2-one;4,6-dioxo-1h-1,3,5-triazine-2-carboxylate;5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione Chemical compound [K+].OC1=CC(=O)NC=C1Cl.[O-]C(=O)C1=NC(=O)NC(=O)N1.O=C1NC(=O)C(F)=CN1C1OCCC1 MREOOEFUTWFQOC-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229960002185 ranimustine Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 229960004836 regorafenib Drugs 0.000 description 1
- FNHKPVJBJVTLMP-UHFFFAOYSA-N regorafenib Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 FNHKPVJBJVTLMP-UHFFFAOYSA-N 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride 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
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 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
- 229960001674 tegafur Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- CQXDYHPBXDZWBA-UHFFFAOYSA-N tert-butyl 2,2,2-trichloroethanimidate Chemical compound CC(C)(C)OC(=N)C(Cl)(Cl)Cl CQXDYHPBXDZWBA-UHFFFAOYSA-N 0.000 description 1
- ORUGTGTZBRUQIT-UHFFFAOYSA-N tert-butyl n-pyridin-2-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC=N1 ORUGTGTZBRUQIT-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 201000006134 tongue cancer Diseases 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000002306 tributylsilyl group Chemical group C(CCC)[Si](CCCC)(CCCC)* 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- PCMOZDDGXKIOLL-SGNQUONSSA-K trichloroyttrium-90 Chemical compound [Cl-].[Cl-].[Cl-].[90Y+3] PCMOZDDGXKIOLL-SGNQUONSSA-K 0.000 description 1
- IINACGXCEZNYTF-UHFFFAOYSA-K trichloroyttrium;hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Cl-].[Y+3] IINACGXCEZNYTF-UHFFFAOYSA-K 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 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
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 239000008371 vanilla flavor Substances 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 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
- 239000000341 volatile oil Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0482—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group chelates from cyclic ligands, e.g. DOTA
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/0606—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Optics & Photonics (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
キレン基を示し;L4およびnは、前記と同様の意味を有する。)で表される基を示す。)である、〔1〕に記載の化合物もしくはその塩またはそれらと金属との錯体。〔3〕 R3cが、一般式(2b)
7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)チオウレイド)フェニル)プロピル)(カルボキシメチル)アミノ)プロパン−2−イル)アザンジイル)二酢酸、(S)−2,2’,2’’−(10−(2−((2−(4−(4−(N−(1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’,2’’’−(2−(4−(3−((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)チオウレイド)ベンジル)−1,4,7,10−テトラアザシクロドデカン−1,4,7,10−テトライル)四酢酸、2,2’−((1−(((S)−2−(ビス(カルボキシメチル)アミノ)−3−(4−(3−((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)チオウレイド)フェニル)プロピル)(カルボキシメチル)アミノ)プロパン−2−イル)アザンジイル)二酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(4−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ブタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(6−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ヘキサンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、
〔8〕 金属が、細胞傷害性放射性金属である、〔1〕〜〔7〕のいずれか一に記載の錯体。〔9〕 細胞傷害性放射性金属が、64Cu、67Cu、90Y、166Ho、153Sm、177Luおよび225Acからなる群から選択される金属である〔8〕に記載の錯体。〔10〕 〔8〕または〔9〕に記載の錯体を含有する医薬組成物。〔11〕 医薬組成物が、インテグリンが関与する疾患の治療の処置剤である〔10〕に記載の医薬組成物。〔12〕 金属が、細胞非傷害性放射性金属である〔1〕〜〔7〕のいずれか一に記載の錯体。〔13〕 細胞非傷害性放射性金属が、18Fアルミニウム錯体、111In、64Cu、67Ga、68Gaおよび89Zrからなる群から選択される金属である〔12〕に記載の錯体。〔14〕 〔12〕または〔13〕に記載の錯体を含有する医薬組成物。〔15〕 医薬組成物が、インテグリンが関与する疾患の診断の処置剤である〔14〕に記載の医薬組成物。〔16〕 〔1〕〜〔7〕のいずれかに記載の化合物またはその塩を含有し、金属を加えることにより診断または治療の処置剤を調製するキット。〔17〕 一般式(S1a)
カルボニル基を意味する。 アルC1−6アルコキシカルボニル基とは、ベンジルオキシカルボニルおよびフェネチルオキシカルボニル基などのC6−10アルC1−6アルキルオキシカルボニル基を意味する。
とは、ジエチルエーテル、ジイソプロピルエーテル、ジオキサン、テトラヒドロフラン、アニソール、エチレングリコールジメチルエーテル、ジエチレングリコールジメチルエーテルまたはジエチレングリコールジエチルエーテルを意味する。 アルコール類とは、メタノール、エタノール、プロパノール、2−プロパノール、ブタノールまたは2−メチル−2−プロパノールを意味する。 ケトン類とは、アセトン、2−ブタノン、4−メチル−2−ペンタノンまたはメチルイソブチルケトンを意味する。 エステル類とは、酢酸メチル、酢酸エチル、酢酸プロピルまたは酢酸ブチルを意味する。 アミド類とは、N,N−ジメチルホルムアミド、N,N−ジメチルアセトアミドまたはN−メチルピロリドンを意味する。 ニトリル類とは、アセトニトリルまたはプロピオニトリルを意味する。 スルホキシド類とは、ジメチルスルホキシドまたはスルホランを意味する。 芳香族炭化水素類とは、ベンゼン、トルエンまたはキシレンを意味する。
R1としては、水素原子または置換されてもよいC1−6アルキル基が好ましく、水素原子がより好ましい。
R1のC1−6アルキル基の置換基としては、置換基群αから選ばれる1つ以上の基が挙げられる。
基、置換されてもよいジ(C1−6アルキル)アミノ基、L5との結合手またはR8と一緒になって置換されてもよいC1−6アルキレン基である。 R9としては、水素原子またはR8と一緒になって置換されてもよいC1−6アルキレン基が好ましく、R8と一緒になって置換されてもよいC1−6アルキレン基がより好ましい。 R9のC1−6アルキル基の置換基としては、置換基群αから選ばれる1つ以上の基が挙げられる。 R8と一緒になって形成されるC1−6アルキレン基の置換基としては、置換基群βから選ばれる1つ以上の基が挙げられる。
R12のC1−6アルキル基、C1−6アルキルアミノ基およびジ(C1−6アルキル)アミノ基の置換基としては、置換基群αから選ばれる1つ以上の基が挙げられる。
イル)三酢酸(実施例1、化合物番号:A8) 2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例2、化合物番号:B2) 2,2’,2’’−(10−((4R,7R,10R)−19−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,11,16−ペンタオキソ−4,7,10−トリス(スルホメチル)−3,6,9,12,15−ペンタアザノナデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例3、化合物番号:C3) (S)−2,2’,2’’−(10−(19−(4−(N−(1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,11,16−トリオキソ−6,9−ジオキサ−3,12,15−トリアザノナデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例4、化合物番号:D3) 2,2’,2’’−(10−((S)−4−(4−アミノブチル)−22−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,14,19−テトラオキソ−9,12−ジオキサ−3,6,15,18−テトラアザドコシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例5、化合物番号:E3) (S)−2,2’,2’’−(10−(28−(4−(N−(1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,11,20,25−テトラオキソ−6,9,15,18−テトラオキサ−3,12,21,24−テトラアザオクタコシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例6、化合物番号:F3) 2,2’,2’’−(10−((R)−22−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,14,19−テトラオキソ−4−(スルホメチル)−9,12−ジオキサ−3,6,15,18−テトラアザドコシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例7、化合物番号:G3) 2,2’,2’’−(10−((9R)−18−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−4−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)カルバモイル)−2,7,10,15−テトラオキソ−9−(スルホメチル)−3,8,11,14−テトラアザオクタデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例8、化合物番号:H9)
’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(6−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ヘキサンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例23、化合物番号:W10) 2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(5−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)チオフェン−2−カルボキサミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例24、化合物番号:X9) 2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)フェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸六ナトリウム塩(実施例25、化合物番号:Y13) 2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(4−(3−(ピリジン−2−イルアミノ)プロピル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸(実施例26、化合物番号:Z8)
2,2’−(7−((R)−1−カルボキシ−4−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−4−オキソブチル)−1,4,7−トリアゾナン−1,4−ジイル)二酢酸(実施例27、化合物番号:Aa7)
5−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−(11−(カルボキシメチル)−1,4,8,11−テトラアザビシクロ[6.6.2]ヘキサデカン−4−イル)−5−オキソペンタン酸(実施例28、化合物番号:Ab9−aおよびAb9−b(Ab9−aおよびAb9−bは立体異性体である。))
Re、192Ir、197Hg、198Au、199Au、201Tl、203Hg、211At、212Bi、212Pb、213Bi、217Bi、223Ra、225Acおよび227Thなどからなる群より選ばれる放射性金属の金属イオン)を金属成分とする錯体が挙げられる。
体製剤、坐剤、点眼剤、点鼻剤、点耳剤、貼付剤、軟膏剤または注射剤などの形態で経口または非経口で投与することができる。また投与方法、投与量および投与回数は、患者の年齢、体重および症状に応じて適宜選択することができる。通常、成人に対しては、経口または非経口(たとえば、注射、点滴および直腸部位への投与など)投与することができる。
した。HBTU(10.0mg)を加え、1時間攪拌した後、水(300μL)を加えた。分取HPLCで精製し、(C2)(4.1mg)を得た。LC/MS(ACQUITY)rt(min):1.16MS(ESI,m/z):852.3[M+2H]2+,850.3[M-2H]2-
および3mol/L水酸化リチウム水溶液(35μL)の混合物を室温で90分間撹拌した。TFAを加え、溶媒を減圧下で留去した。得られた残渣にTFA/トリエチルシラン(95/5)(1mL)を加え、90分間撹拌した後、TFAを減圧下で留去した。得られた残渣に50%アセトニトリル水溶液(800μL)を加え、分取HPLCで精製し、(H9)(2.7mg)を得た。LC/MS(SunFire)rt(min):10.25MS(ESI,m/z):721.30[M+3H]3+,1078.80[M-2H]2-
れた残渣をシリカゲルカラムクロマトグラフィー(ヘキサン/酢酸エチル=4/1)で精製し、(J1)(1.13g)を得た。TLC Rf:0.19(ヘキサン/酢酸エチル=2/1)
2-((tert-ブトキシカルボニル)アミノ)ペンタンジオアート(12.5mg)の混合物に、DMF(0.4mL)およびDIEA(30μL)を加え、室温で24時間攪拌した。水(0.1mL)を加えた後、減圧下で溶媒を留去し、TFA/トリエチルシラン(95/5)(1mL)を加え、室温で1時間攪拌した。減圧下でTFAを留去し、50%アセトニトリル水溶液(1.5mL)を加え、分取HPLCで精製し、(L8)(24.8mg)を得た。LC/MS(SunFire)rt(min):7.86MS(ESI,m/z):862.05[M+2H]2+,859.95[M-2H]2-
2回洗浄し、飽和塩化ナトリウム水溶液(300mL)で洗浄し、無水硫酸ナトリウムで乾燥した。減圧下で溶媒を留去し、得られた残渣をシリカゲルカラムクロマトグラフィー(ヘキサン/酢酸エチル=9/1〜4/1)で精製し、(Q2)(5.38g)を得た。TLC Rf:0.40(ヘキサン/酢酸エチル=4/1)1H-NMR(300MHz,CDCl3)δ:7.48(1H,d,J=15.6Hz),7.17-7.26(2H,m),6.91(1H,t,J=5.1Hz),6.22(1H,d,J=15.6Hz),4.16(2H,q,J=7.2Hz),4.11(2H,t,J=6.0Hz),2.54(2H,t,J=7.2Hz),2.15(2H,tt,J=6.0,7.2Hz),1.55(9H,s),1.26(3H,t,J=7.2Hz)LC/MS(ACQUITY)rt(min):1.94MS(ESI,m/z):297.1[M-tBu]+
(ESI,m/z):321.3[M+H]+
、飽和塩化ナトリウム水溶液(30mL)で1回、順次洗浄し、無水硫酸ナトリウムで乾燥させた。減圧下で溶媒を留去し、得られた残渣をシリカゲルカラムクロマトグラフィー(ヘキサン/酢酸エチル=95/5〜60/40)で精製し、(Aa4)(1.04g)を得た。LC/MS(ACQUITY)rt(min):1.63MS(ESI,m/z):634.7[M+H]+
に[111In]塩化インジウム溶液(80MBq、100μL)を添加した。100℃で15分間加熱した後、室温で5分間放置し、[111In]-(P2)を得た。逆相TLC(Whatman、KC18F、展開溶媒:メタノール/0.5mol/L酢酸アンモニウム水溶液(50/50))で分析した結果、放射標識化合物のRf値は0.4であった。調製直後および室温24時間後の放射化学的純度は、いずれも95%以上であった。
Claims (26)
- 一般式(1)
但し、R8、R9、R10、R11およびR12のいずれか1つが、L5との結合手を示し、他の4つは、L5との結合手を示さず; L4は、 置換されてもよい2価の芳香族炭化水素基、 置換されてもよい2価の複素環式基または 結合手を示し;
L5は、 置換されてもよいC1−6アルキレン基、 置換されてもよい−O−C1−6アルキレン基(式中、左側の結合手が、L4に結合する。)または 置換されてもよい−NH−C1−6アルキレン基(式中、左側の結合手が、L4に結合する。)を示し; mは、 0または1を示し; nは、 1〜3の整数を示し; pは、 0または1を示し; 但し、R8が、L5との結合手である場合、L4は、置換されてもよい2価の芳香族炭化水素基を示す。)で表される基を示す。)を示し; 但し、Z1、Z2、Z3、Z4およびZ5のうちの少なくとも一つは、 CR3a(式中、R3aは、一般式(2)
- Z1、Z2、Z4およびZ5が、同一または異なって、CR3b(式中、 R3bは、 水素原子、 ハロゲン原子、 置換されてもよいC1−6アルキル基または 置換されてもよいC1−6アルコキシ基を示す。)であり; Z3が、 CR3c (式中、 R3cは、 一般式(2a)
- A1が、 ポリアザマクロサイクリック構造を有する基、 ポリアミノポリカルボン酸構造を有する基または ポリアミノポリホスホン酸構造を有する基である、請求項1〜3のいずれか一項に記載の化合物もしくはその塩またはそれらと金属との錯体。
- A1が、一般式(5)、(6)、(7)、(8)、(9)、(10)、(11)または(12)
- 一般式(1)で表される化合物またはその塩が、2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R,10R)−19−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,11,16−ペンタオキソ−4,7,10−トリス(スルホメチル)−3,6,9,12,15−ペンタアザノナデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、(S)−2,2’,
2’’−(10−(19−(4−(N−(1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,11,16−トリオキソ−6,9−ジオキサ−3,12,15−トリアザノナデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((S)−4−(4−アミノブチル)−22−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,14,19−テトラオキソ−9,12−ジオキサ−3,6,15,18−テトラアザドコシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、(S)−2,2’,2’’−(10−(28−(4−(N−(1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,11,20,25−テトラオキソ−6,9,15,18−テトラオキサ−3,12,21,24−テトラアザオクタコシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((R)−22−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,14,19−テトラオキソ−4−(スルホメチル)−9,12−ジオキサ−3,6,15,18−テトラアザドコシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((9R)−18−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−4−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)カルバモイル)−2,7,10,15−テトラオキソ−9−(スルホメチル)−3,8,11,14−テトラアザオクタデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R)−16−((5−(2−カルボキシ−1−(5−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エトキシ)−1H−インドール−1−イル)エチル)ピリジン−3−イル)オキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R)−16−((5−(2−カルボキシ−1−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)−1H−インドール−1−イル)エチル)ピリジン−3−イル)オキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((R)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4S,9R)−18(4−(N−((S)−2−(4−(2−(6−アミノピリジン−2−イル)エチル)ベンズアミド)−1−カルボキシエチル)スルファモイル)−3,5−ジメチルフェノキシ)−4−(((R)−1−((2−(4−(4−(N−((S)−2−(4−(2−(6−アミノピリジン−2−イル)エチル)ベンズアミド)−1−カルボキシエチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)カルバモイル)−2,7,10,15−テトラオキソ−9−(スルホメチル)−3,8,11,14−テトラアザオクタデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−2−(4−(2−(6−アミノピリジン−2−イル)エチル)ベンズアミド)−1−カルボキシエチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−2−(4−(2−(6−アミノピリジン−2−イル)エチル)ベンズアミド)−1−カルボキシエチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R)−16−(4−((S)−2−カルボキシ−1−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)−2−フルオロフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’−((1−(((S)−2−(ビス(カルボキシメチル)アミノ)−3−(4−(3−((R)−1−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)チオウレイド)フェニル)プロピル)(カルボキシメチル)アミノ)プロパン−2−イル)アザンジイル)二酢酸、(S)−2,2’,2’’−(10−(2−((2−(4−(4−(N−(1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’,2’’’−(2−(4−(3−((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)チオウレイド)ベンジル)−1,4,7,10−テトラアザシクロドデカン−1,4,7,10−テトライル)四酢酸、2,2’−((1−(((S)−2−(ビス(カルボキシメチル)アミノ)−3−(4−(3−((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)チオウレイド)フェニル)プロピル)(カルボキシメチル)アミノ)プロパン−2−イル)アザンジイル)二酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(4−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ブタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−(2−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(6−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ヘキサンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−オキソエチル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(5−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)チオフェン−2−カルボキサミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸、2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(4−(2−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)エチル)ベンズアミド)エチル)スルファモイル)フェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカン−1,4,7−トリイル)三酢酸六ナトリウム塩、2,2’,2’’−(10−((4R,7R)−16−(4−(N−((S)−1−カルボキシ−2−(4−(3−(ピリジン−2−イルアミノ)プロピル)ベンズアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)−2,5,8,13−テトラオキソ−4,7−ビス(スルホメチル)−3,6,9,12−テトラアザヘキサデシル)−1,4,7,10−テトラアザシクロドデカ
ン−1,4,7−トリイル)三酢酸、
2,2’−(7−((R)−1−カルボキシ−4−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−4−オキソブチル)−1,4,7−トリアゾナン−1,4−ジイル)二酢酸および
5−(((R)−1−((2−(4−(4−(N−((S)−1−カルボキシ−2−(5−(5,6,7,8−テトラヒドロ−1,8−ナフチリジン−2−イル)ペンタンアミド)エチル)スルファモイル)−3,5−ジメチルフェノキシ)ブタンアミド)エチル)アミノ)−1−オキソ−3−スルホプロパン−2−イル)アミノ)−2−(11−(カルボキシメチル)−1,4,8,11−テトラアザビシクロ[6.6.2]ヘキサデカン−4−イル)−5−オキソペンタン酸
からなる群から選択される化合物またはその塩である、請求項1に記載の化合物もしくはその塩またはそれらと金属との錯体。 - 金属が、細胞傷害性放射性金属である、請求項1〜7のいずれか一項に記載の錯体。
- 細胞傷害性放射性金属が、64Cu、67Cu、90Y、166Ho、153Sm、177Luおよび225Acからなる群から選択される金属である請求項8に記載の錯体。
- 請求項8または9に記載の錯体を含有する医薬組成物。
- 医薬組成物が、インテグリンが関与する疾患の治療の処置剤である請求項10に記載の医薬組成物。
- 金属が、細胞非傷害性放射性金属である請求項1〜7のいずれか一項に記載の錯体。
- 細胞非傷害性放射性金属が、18Fアルミニウム錯体、111In、64Cu、67Ga、68Gaおよび89Zrからなる群から選択される金属である請求項12に記載の錯体。
- 請求項12または13に記載の錯体を含有する医薬組成物。
- 医薬組成物が、インテグリンが関与する疾患の診断の処置剤である請求項14に記載の医薬組成物。
- 請求項1〜7のいずれかに記載の化合物またはその塩を含有し、金属を加えることにより診断または治療の処置剤を調製するキット。
- 一般式(S1a)
- 一般式(S1a)
- Z1、Z2、Z4およびZ5が、同一または異なって、CR3b(式中、 R3bは、 水素原子、 ハロゲン原子、 置換されてもよいC1−6アルキル基または 置換されてもよいC1−6アルコキシ基を示す。)であり; Z3が、 CR3c(式中、 R3cは、 一般式(2a)
- インテグリンが関与する疾患の治療の処置に使用するための、請求項8または9に記載の錯体。
- インテグリンが関与する疾患の診断の処置に使用するための、請求項12または13に記載の錯体。
- インテグリンが関与する疾患の治療の処置剤を製造するための、請求項8または9に記載の錯体の使用。
- インテグリンが関与する疾患の診断の処置剤を製造するための、請求項12または13に記載の錯体の使用。
- 請求項8または9に記載の錯体を投与することを特徴とする、インテグリンが関与する疾患の治療の処置方法。
- 請求項12または13に記載の錯体を投与することを特徴とする、インテグリンが関与する疾患の診断の処置方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2013196712 | 2013-09-24 | ||
JP2013196712 | 2013-09-24 | ||
PCT/JP2014/075332 WO2015046278A1 (ja) | 2013-09-24 | 2014-09-24 | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017179764A Division JP6532515B2 (ja) | 2013-09-24 | 2017-09-20 | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2015046278A1 true JPWO2015046278A1 (ja) | 2017-03-09 |
JP6215335B2 JP6215335B2 (ja) | 2017-10-18 |
Family
ID=52743412
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015539283A Active JP6215335B2 (ja) | 2013-09-24 | 2014-09-24 | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 |
JP2017179764A Active JP6532515B2 (ja) | 2013-09-24 | 2017-09-20 | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017179764A Active JP6532515B2 (ja) | 2013-09-24 | 2017-09-20 | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 |
Country Status (17)
Country | Link |
---|---|
US (2) | US11426473B2 (ja) |
EP (3) | EP3929196B1 (ja) |
JP (2) | JP6215335B2 (ja) |
CA (1) | CA2961935C (ja) |
CY (1) | CY1124794T1 (ja) |
DK (2) | DK3050878T3 (ja) |
ES (2) | ES2957460T3 (ja) |
FI (1) | FI3929196T3 (ja) |
HR (2) | HRP20231143T1 (ja) |
HU (2) | HUE063437T2 (ja) |
IL (1) | IL251500A (ja) |
LT (2) | LT3050878T (ja) |
PL (2) | PL3050878T3 (ja) |
PT (2) | PT3050878T (ja) |
RS (2) | RS62591B1 (ja) |
SI (2) | SI3929196T1 (ja) |
WO (1) | WO2015046278A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6215335B2 (ja) | 2013-09-24 | 2017-10-18 | 富士フイルム株式会社 | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 |
MX2017012184A (es) * | 2015-03-25 | 2018-01-09 | Fujifilm Corp | Metodo para manufacturar compuesto novedoso que contiene nitrogeno o sal del mismo e intermediario de manufacturacion del compuesto novedoso que contiene nitrogeno o sal del mismo. |
CN116390766A (zh) * | 2020-10-22 | 2023-07-04 | 日本医事物理股份有限公司 | 放射性锆络合物的制造方法 |
JPWO2022085571A1 (ja) * | 2020-10-22 | 2022-04-28 | ||
US20240050597A1 (en) | 2020-12-21 | 2024-02-15 | Advanced Accelerator Applications International Sa | Radiolabelled alpha-v beta-3 and/or alpha-v beta-5 integrins antagonist for use as theragnostic agent |
WO2022192503A1 (en) * | 2021-03-10 | 2022-09-15 | Da Zen Theranostics, Inc. | Heptamethine carbocyanine dye-cross-bridged tetraamine cyclam (ctc) chelator conjugates, their stable complexes with copper-64, and uses thereof |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000035488A2 (en) * | 1998-12-18 | 2000-06-22 | Du Pont Pharmaceuticals Company | Vitronectin receptor antagonist pharmaceuticals |
WO2001098294A2 (en) * | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals for use in combination therapy |
JP2002508355A (ja) * | 1997-12-17 | 2002-03-19 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
JP2003520271A (ja) * | 2000-01-24 | 2003-07-02 | メルク エンド カムパニー インコーポレーテッド | αvインテグリン受容体拮抗薬 |
US20050154185A1 (en) * | 1998-12-18 | 2005-07-14 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
WO2013045333A1 (fr) * | 2011-09-26 | 2013-04-04 | Guerbet | Nanoemulsions et leur utilisation comme agents de contraste |
Family Cites Families (136)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0416740A3 (en) | 1989-08-08 | 1991-08-28 | Beecham Group P.L.C. | Novel compounds with renin-inhibiting activity |
WO1996015110A1 (en) | 1994-11-15 | 1996-05-23 | Moreno Paolini | N-hydroxypiperidines as superoxide radicals scavengers |
DE19534177A1 (de) | 1995-09-15 | 1997-03-20 | Merck Patent Gmbh | Cyclische Adhäsionsinhibitoren |
US5952306A (en) | 1996-01-16 | 1999-09-14 | Merck & Co., Inc. | Integrin receptor antagonists |
WO1997026250A1 (en) | 1996-01-16 | 1997-07-24 | Merck & Co., Inc. | Integrin receptor antagonists |
US6211184B1 (en) | 1996-08-29 | 2001-04-03 | Merck & Co., Inc. | Integrin antagonists |
EP0934305A4 (en) | 1996-08-29 | 2001-04-11 | Merck & Co Inc | INTEGRINE ANTAGONISTS |
JP2001504456A (ja) | 1996-10-30 | 2001-04-03 | メルク エンド カンパニー インコーポレーテッド | インテグリン拮抗薬 |
US5919792A (en) | 1996-10-30 | 1999-07-06 | Merck & Co., Inc. | Integrin antagonists |
US5952341A (en) | 1996-10-30 | 1999-09-14 | Merck & Co., Inc. | Integrin antagonists |
DE69736812T2 (de) | 1996-11-27 | 2007-08-09 | Bristol-Myers Squibb Pharma Co. | Neue integrin rezeptor antagonisten |
EP1007026A4 (en) | 1997-01-17 | 2002-08-07 | Merck & Co Inc | INTEGRIN ANTAGONISTS |
US6017925A (en) | 1997-01-17 | 2000-01-25 | Merck & Co., Inc. | Integrin antagonists |
WO1998044797A1 (en) | 1997-04-07 | 1998-10-15 | Merck & Co., Inc. | A method of treating cancer |
AU7105498A (en) | 1997-04-14 | 1998-11-11 | Merck & Co., Inc. | Combination therapy for the prevention and treatment of osteoporosis |
US6294549B1 (en) | 1997-07-23 | 2001-09-25 | Merck & Co., Inc. | Method for eliciting an αvβ5 or dual αvβ3/αvβ5 antagonizing effect |
US6017926A (en) | 1997-12-17 | 2000-01-25 | Merck & Co., Inc. | Integrin receptor antagonists |
ES2243016T3 (es) | 1997-12-17 | 2005-11-16 | MERCK & CO., INC. | Antagonistas de receptores de integrinas. |
ES2243015T3 (es) | 1997-12-17 | 2005-11-16 | MERCK & CO., INC. | Antagonistas del receptor de integrina. |
US6048861A (en) | 1997-12-17 | 2000-04-11 | Merck & Co., Inc. | Integrin receptor antagonists |
US6211191B1 (en) | 1997-12-17 | 2001-04-03 | Merck & Co., Inc. | Integrin receptor antagonists |
WO1999030709A1 (en) | 1997-12-17 | 1999-06-24 | Merck & Co., Inc. | Integrin receptor antagonists |
US6066648A (en) | 1997-12-17 | 2000-05-23 | Merck & Co., Inc. | Integrin receptor antagonists |
CA2323208A1 (en) | 1998-03-10 | 1999-09-16 | James M. Samanen | Vitronectin receptor antagonists |
US20020147334A1 (en) | 1998-03-10 | 2002-10-10 | Smithkline Beecham Corporation | Vitronectin Receptor Antagonists |
US6524553B2 (en) | 1998-03-31 | 2003-02-25 | Bristol-Myers Squibb Pharma Company | Quinolone vitronectin receptor antagonist pharmaceuticals |
US6537520B1 (en) | 1998-03-31 | 2003-03-25 | Bristol-Myers Squibb Pharma Company | Pharmaceuticals for the imaging of angiogenic disorders |
WO2000006169A1 (en) | 1998-07-29 | 2000-02-10 | Merck & Co., Inc. | Integrin receptor antagonists |
AU748621B2 (en) | 1998-08-13 | 2002-06-06 | Merck & Co., Inc. | Integrin receptor antagonists |
UA71586C2 (en) | 1998-12-04 | 2004-12-15 | Smithkline Beecham Corp | A vitronectin receptor antagonist |
US6245294B1 (en) | 1998-12-17 | 2001-06-12 | The United States Of America As Represented By The Secretary Of Agriculture | Method and apparatus for surface treatment of materials |
AU766822B2 (en) | 1998-12-18 | 2003-10-23 | Du Pont Pharmaceuticals Company | Vitronectin receptor antagonist pharmaceuticals |
US6649645B1 (en) | 1998-12-23 | 2003-11-18 | Pharmacia Corporation | Combination therapy of radiation and a COX-2 inhibitor for treatment of neoplasia |
BR9916536A (pt) | 1998-12-23 | 2002-01-02 | Searle & Co | Método para o tratamento ou prevenção de um distúrbio de neoplasia em um mamìfero em necessidade deste tratamento ou prevenção, e, combinação |
US6833373B1 (en) | 1998-12-23 | 2004-12-21 | G.D. Searle & Co. | Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia |
WO2000046215A1 (en) | 1999-02-03 | 2000-08-10 | Merck & Co., Inc. | Benzazepine derivatives as alpha-v integrin receptor antagonists |
WO2000061545A1 (en) | 1999-04-14 | 2000-10-19 | American Home Products Corporation | Methods for solid phase combinatorial synthesis of integrin inhibitors |
SK17442001A3 (sk) | 1999-06-02 | 2002-03-05 | Merck & Co., Inc. | Deriváty kyseliny nonánovej, farmaceutický prostriedok s ich obsahom a ich použitie |
JP2003502373A (ja) | 1999-06-23 | 2003-01-21 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体アンタゴニスト |
EP1065207A1 (en) | 1999-07-02 | 2001-01-03 | Aventis Pharma Deutschland GmbH | Naphthyridine derivatives, processes for their preparation, their use, and pharmaceutical compositions comprising them |
US6514964B1 (en) | 1999-09-27 | 2003-02-04 | Amgen Inc. | Fused cycloheptane and fused azacycloheptane compounds and their methods of use |
JP2003510360A (ja) | 1999-10-04 | 2003-03-18 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
DE10027514A1 (de) | 2000-06-06 | 2002-01-03 | Basf Ag | Liganden von Integrinrezeptoren |
DE10039998A1 (de) | 2000-08-11 | 2002-02-21 | Basf Ag | Neue substituierte Diareno-azepin-Derivate als Integrin Liganden |
DE10028575A1 (de) | 2000-06-14 | 2002-03-14 | Basf Ag | Integrinliganden |
CZ20021508A3 (cs) | 1999-11-08 | 2002-10-16 | Merck & Co., Inc. | Způsob výroby imidazolidinonových derivátů |
US6407241B1 (en) | 1999-11-08 | 2002-06-18 | Merck & Co., Inc. | Process and intermediates for the preparation of imidazolidinone αv integrin antagonists |
AU768875B2 (en) | 1999-11-23 | 2004-01-08 | Merck Sharp & Dohme Corp. | Process and intermediates to a tetrahydro-(1,8)-naphthyridine |
US6849639B2 (en) | 1999-12-14 | 2005-02-01 | Amgen Inc. | Integrin inhibitors and their methods of use |
WO2001053297A1 (en) | 2000-01-20 | 2001-07-26 | Merck & Co., Inc. | Alpha v integrin receptor antagonists |
AU2001269821A1 (en) | 2000-06-15 | 2001-12-24 | Barbara Chen | Cycloalkyl alkanoic acids as integrin receptor antagonists |
US6921767B2 (en) | 2000-06-15 | 2005-07-26 | Pharmacia Corporation | Cycloalkyl alkanoic acids as integrin receptor antagonists derivatives |
ATE353219T1 (de) | 2000-07-26 | 2007-02-15 | Merck & Co Inc | Alpha v integrin-rezeptor-antagonisten |
AU2001288485A1 (en) | 2000-08-29 | 2002-03-13 | Balekudru Devadas | Compounds containing a bicyclic ring system useful as alpha v beta 3 antagonists |
US6531494B1 (en) | 2001-08-29 | 2003-03-11 | Pharmacia Corporation | Gem-substituted αvβ3 antagonists |
BR0113671A (pt) | 2000-08-30 | 2004-01-06 | Pharmacia Corp | Antagonistas de integrina alfa v beta 3 gem-substituìda |
DE10042655A1 (de) | 2000-08-31 | 2002-03-14 | Aventis Pharma Gmbh | Verfahren zur Herstellung von Inhibitoren der Zell-Adhäsion |
AU2001289865B2 (en) | 2000-09-08 | 2007-03-01 | Pharmacia Italia S.P.A. | Exemestane as chemopreventing agent |
EP1322310A4 (en) | 2000-09-13 | 2004-09-15 | Merck & Co Inc | ALPHA V INTEGRIN RECEPTOR ANTAGONISTS |
CA2421652A1 (en) | 2000-09-14 | 2002-03-21 | Merck And Co., Inc. | Alpha v integrin receptor antagonists |
WO2002022616A2 (en) | 2000-09-14 | 2002-03-21 | Merck & Co., Inc. | Alpha v integrin receptor antagonists |
EP1322311A1 (en) | 2000-09-18 | 2003-07-02 | Merck & Co., Inc. | Treatment of inflammation with a combination of a cyclooxygenase-2 inhibitor and an integrin alpha-v antagonist |
AU2001296950A1 (en) | 2000-10-05 | 2002-04-15 | Merck & Co., Inc. | Process for preparation of integrin receptor antagonist intermediates |
DE60118025T2 (de) | 2000-10-24 | 2006-11-23 | Merck & Co., Inc. | Dibenzoxazepin-alpha-v-integrin-rezeptorantagonist |
US6444680B1 (en) | 2000-11-30 | 2002-09-03 | Merck & Co., Inc. | Amine salts of an integrin receptor antagonist |
JP2004517853A (ja) | 2001-01-03 | 2004-06-17 | メルク エンド カムパニー インコーポレーテッド | 歯周病の治療方法及び治療用組成物 |
MXPA03006607A (es) | 2001-01-26 | 2003-09-22 | Upjohn Co | Metodo combinado para tratar trastornos dependientes de hormonas. |
US20040082557A1 (en) | 2001-01-26 | 2004-04-29 | Wajszczuk Charles Paul | Methods for treating estrogen-dependent disorders |
WO2002060438A1 (en) | 2001-01-29 | 2002-08-08 | 3-Dimensional Pharmaceuticals, Inc. | Substituted indoles and their use as integrin antagonists |
US6764842B2 (en) | 2001-03-28 | 2004-07-20 | Merck & Co., Inc. | Enantioselective bioreduction for the preparation of integrin receptor antagonist intermediates |
US6872730B2 (en) | 2001-04-27 | 2005-03-29 | 3-Dimensional Pharmaceuticals, Inc. | Substituted benzofurans and benzothiophenes, methods of making and methods of use as integrin antagonists |
EP1387688A2 (en) | 2001-05-03 | 2004-02-11 | Merck & Co., Inc. | Benzazepinone alpha v integrin receptor antagonists |
US6509347B2 (en) | 2001-06-11 | 2003-01-21 | Merck & Co., Inc. | Crystalline forms of an integrin receptor antagonist |
US20040043988A1 (en) | 2001-06-15 | 2004-03-04 | Khanna Ish Kurmar | Cycloalkyl alkanoic acids as intergrin receptor antagonists |
PE20030120A1 (es) | 2001-06-19 | 2003-02-12 | Merck & Co Inc | Sal amina de un antagonista de receptor de integrin |
US6838074B2 (en) | 2001-08-08 | 2005-01-04 | Bristol-Myers Squibb Company | Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent |
US20040030134A1 (en) | 2001-10-01 | 2004-02-12 | Mcwilliams James Christopher | Process for preparation of integrin receptor antagonist intermediates |
WO2003032961A2 (en) | 2001-10-10 | 2003-04-24 | Pharmacia Italia Spa | Methods for preventing and treating bone loss with steroid compounds |
EP1444231A4 (en) | 2001-11-06 | 2005-11-09 | Merck & Co Inc | AMINO SALTS OF AN INTEGRIN RECEPTOR ANTAGONIST |
JP2005511581A (ja) | 2001-11-07 | 2005-04-28 | メルク エンド カムパニー インコーポレーテッド | 有糸分裂キネシン阻害剤 |
US20040053968A1 (en) | 2001-12-28 | 2004-03-18 | Hartman George D. | Methods and compositions for treating peridontal disease |
US20030171368A1 (en) | 2002-02-06 | 2003-09-11 | Werner Seitz | Pyrimidinonesulfamoylureas` |
AU2003216374A1 (en) | 2002-02-27 | 2003-09-09 | Merck And Co., Inc. | Malonate-claisen rearrangement for preparation of integrin receptor antagonist intermediates |
WO2004013070A2 (en) | 2002-08-01 | 2004-02-12 | Nuevolution A/S | Multi-step synthesis of templated molecules |
US20040224986A1 (en) | 2002-08-16 | 2004-11-11 | Bart De Corte | Piperidinyl targeting compounds that selectively bind integrins |
RU2333210C2 (ru) | 2002-08-16 | 2008-09-10 | Янссен Фармацевтика Н.В. | Соединения пиперидинила, селективно связывающие интегрины |
CA2499149A1 (en) | 2002-09-20 | 2004-04-01 | Merck & Co., Inc. | Mannitol formulation for integrin receptor antagonist |
LT2348125T (lt) | 2002-10-30 | 2017-09-11 | Nuevolution A/S | Bifunkcinio komplekso sintezės būdas |
US6908921B2 (en) | 2002-12-13 | 2005-06-21 | Merck & Co., Inc. | Quinoxalinone derivatives as bradykinin B1 antagonists |
US20050020591A1 (en) | 2002-12-13 | 2005-01-27 | Dai-Shi Su | 2-Quinoxalinone derivatives as bradykinin antagonists and novel compounds |
US20050043344A1 (en) | 2002-12-20 | 2005-02-24 | Pharmacia Corporation | Heteroarylalkanoic acids as integrin receptor antagonists derivatives |
AU2003297408A1 (en) | 2002-12-20 | 2004-07-22 | Pharmacia Corporation | Thiazole compounds as integrin receptor antagonists derivatives |
EP1572691A1 (en) | 2002-12-20 | 2005-09-14 | Pharmacia Corporation | Pyrazole compounds as integrin receptor antagonists derivatives |
EP1603392A2 (en) | 2003-03-07 | 2005-12-14 | The University Of Toledo | Paclitaxel hybrid derivatives |
WO2004078109A2 (en) | 2003-03-07 | 2004-09-16 | Merck Sharp & Dohme Limited | PROCESS FOR SYNTHESISING USEFUL INTERMEDIATES FOR THE PREPARATION OF ανβ3 RECEPTOR ANTAGONISTS |
US7482357B2 (en) | 2003-06-30 | 2009-01-27 | Merck & Co., Inc. | 17-acetamido-4-azasteroid derivatives as androgen receptor modulators |
US7351711B2 (en) | 2003-07-31 | 2008-04-01 | Janssen Pharmaceutical, N.V. | Tricyclic indanyls as integrin inhibitors |
US9016221B2 (en) | 2004-02-17 | 2015-04-28 | University Of Florida Research Foundation, Inc. | Surface topographies for non-toxic bioadhesion control |
US7650848B2 (en) | 2004-02-17 | 2010-01-26 | University Of Florida Research Foundation, Inc. | Surface topographies for non-toxic bioadhesion control |
US7117807B2 (en) | 2004-02-17 | 2006-10-10 | University Of Florida Research Foundation, Inc. | Dynamically modifiable polymer coatings and devices |
FR2870541B1 (fr) | 2004-05-18 | 2006-07-14 | Proskelia Sas | Derives de pyrimidines antigonistes du recepteur de la vitronectine |
EP1781635B1 (en) | 2004-07-29 | 2012-06-13 | Merck Sharp & Dohme Corp. | Potassium channel inhibitors |
US20080064716A1 (en) | 2004-10-14 | 2008-03-13 | Pharmacia | Biphenyl Integrin Antagonists |
WO2006108040A1 (en) | 2005-04-05 | 2006-10-12 | Janssen Pharmaceutica, N.V. | Substituted indoles and their use as integrin antagonists |
JP2008542276A (ja) | 2005-05-23 | 2008-11-27 | メルク エンド カムパニー インコーポレーテッド | プロリンビスアミドオレキシン受容体アンタゴニスト |
AR059224A1 (es) | 2006-01-31 | 2008-03-19 | Jerini Ag | Compuestos para la inhibicion de integrinas y uso de estas |
JP2009539815A (ja) | 2006-06-09 | 2009-11-19 | アストラゼネカ アクチボラグ | 固形腫瘍の治療用のa5b1アンタゴニストとしてのN−(ベンゾイル)−O−[2−(ピリジン−2−イルアミノ)エチル]−L−チロシン誘導体と関連化合物 |
EP2117604B1 (en) | 2007-01-11 | 2017-07-26 | Immunomedics, Inc. | Methods and compositions for improved f-18 labeling of proteins, peptides and other molecules |
WO2008093064A1 (en) | 2007-01-29 | 2008-08-07 | Astrazeneca Ab | L-ALANINE DERIVATIVES AS α5 BETA 1 ANTAGONISTS |
WO2008093065A1 (en) | 2007-01-29 | 2008-08-07 | Astrazeneca Ab | L-ALANINE DERIVATIVES AS α5βL ANTAGONISTS |
WO2008125811A1 (en) | 2007-04-11 | 2008-10-23 | Astrazeneca Ab | N-[HETEROARYLCARBONYL]-S-THIENYL-L-ALANINE DERIVATIVES AS α5β1 ANTAGONISTS |
TWI465251B (zh) | 2008-01-08 | 2014-12-21 | Lantheus Medical Imaging Inc | 作為顯影劑的n-烷氧基醯胺共軛物 |
DE102009000854A1 (de) | 2009-02-13 | 2010-08-19 | Ernst-Moritz-Arndt-Universität Greifswald | Osteopontin-Rezeptor-Liganden zur Behandlung des chronischen Nierenversagens |
KR101106433B1 (ko) | 2009-04-03 | 2012-01-18 | 서울대학교산학협력단 | 암 조직의 타겟팅을 위한 마크로사이클릭 아미노산 계열의 유도체 및 그의 방사성 또는 비방사성 금속 표지화합물 |
US9556201B2 (en) | 2009-10-29 | 2017-01-31 | Glaxosmithkline Llc | Bicyclic pyridines and analogs as sirtuin modulators |
US8349830B2 (en) | 2009-10-30 | 2013-01-08 | Merck Sharp & Dohme | Aryl aminopyridine PDE10 inhibitors |
KR101383655B1 (ko) | 2010-05-24 | 2014-04-10 | 주식회사 바이오이미징코리아 | 트리카르보닐 테크네슘-99m 또는 레늄-188 표지 고리 알지디 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 신생혈관 관련 질환의 진단 또는 치료용 약학적 조성물 |
FR2968999B1 (fr) * | 2010-12-20 | 2013-01-04 | Guerbet Sa | Nanoemulsion de chelate pour irm |
US20120289481A1 (en) | 2011-05-13 | 2012-11-15 | O'neil Jennifer | Compositions and methods for treating cancer |
JP6205354B2 (ja) | 2011-07-06 | 2017-09-27 | ギリアード サイエンシーズ, インコーポレイテッド | Hivの処置のための化合物 |
WO2013048996A1 (en) | 2011-09-30 | 2013-04-04 | Ge Healthcare Limited | Method for the purification of a peptide-based imaging agent precursor |
EP2920178B1 (en) | 2012-11-16 | 2016-12-21 | Merck Patent GmbH | Novel heterocyclic derivatives as modulators of kinase activity (p70s6 and akt) |
FR3001154B1 (fr) * | 2013-01-23 | 2015-06-26 | Guerbet Sa | Magneto-emulsion vectorisee |
US8901144B2 (en) | 2013-02-07 | 2014-12-02 | Scifluor Life Sciences, Llc | Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives |
ES2763556T3 (es) | 2013-02-07 | 2020-05-29 | Scifluor Life Sciences Inc | Antagonistas fluorados de integrina |
GB201305668D0 (en) | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
JP6067181B2 (ja) | 2013-04-30 | 2017-01-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アルドステロンシンターゼ阻害薬 |
JP6215335B2 (ja) * | 2013-09-24 | 2017-10-18 | 富士フイルム株式会社 | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 |
WO2015073575A2 (en) | 2013-11-12 | 2015-05-21 | Centre For Probe Development And Commercialization | Residualizing linkers and uses thereof |
CA2974060C (en) | 2015-02-05 | 2022-08-30 | Piramal Enterprises Limited | Compounds containing carbon-carbon linker as gpr120 agonists |
JP6286467B2 (ja) | 2015-03-25 | 2018-02-28 | 富士フイルム株式会社 | インテグリンが関与する疾患の診断または治療の処置剤 |
MX2017012184A (es) | 2015-03-25 | 2018-01-09 | Fujifilm Corp | Metodo para manufacturar compuesto novedoso que contiene nitrogeno o sal del mismo e intermediario de manufacturacion del compuesto novedoso que contiene nitrogeno o sal del mismo. |
WO2017070793A1 (en) | 2015-10-30 | 2017-05-04 | Trillium Therapeutics Inc. | Novel fluorinated heterocycle derivatives and their uses as therapeutic agents |
ITUB20160191A1 (it) | 2016-01-21 | 2017-07-21 | Invectors S R L | Kit per la preparazione di doxorubicina liposomiale funzionalizzata con peptidi per il target selettivo di recettori sovra espressi da cellule tumorali |
KR102411532B1 (ko) | 2016-09-09 | 2022-06-22 | 노파르티스 아게 | 엔도솜 톨-유사 수용체의 억제제로서의 화합물 및 조성물 |
US20210276971A1 (en) | 2018-06-20 | 2021-09-09 | The Research Foundation For The State University Of New York | Triazamacrocycle-derived chelator compositions for coordination of imaging and therapy metal ions and methods of using same |
-
2014
- 2014-09-24 JP JP2015539283A patent/JP6215335B2/ja active Active
- 2014-09-24 PT PT148498983T patent/PT3050878T/pt unknown
- 2014-09-24 RS RS20211416A patent/RS62591B1/sr unknown
- 2014-09-24 PL PL14849898T patent/PL3050878T3/pl unknown
- 2014-09-24 DK DK14849898.3T patent/DK3050878T3/da active
- 2014-09-24 HR HRP20231143TT patent/HRP20231143T1/hr unknown
- 2014-09-24 LT LTEPPCT/JP2014/075332T patent/LT3050878T/lt unknown
- 2014-09-24 DK DK21187649.5T patent/DK3929196T3/da active
- 2014-09-24 RS RS20230762A patent/RS64535B1/sr unknown
- 2014-09-24 HU HUE21187649A patent/HUE063437T2/hu unknown
- 2014-09-24 HR HRP20211836TT patent/HRP20211836T1/hr unknown
- 2014-09-24 ES ES21187649T patent/ES2957460T3/es active Active
- 2014-09-24 EP EP21187649.5A patent/EP3929196B1/en active Active
- 2014-09-24 WO PCT/JP2014/075332 patent/WO2015046278A1/ja active Application Filing
- 2014-09-24 EP EP14849898.3A patent/EP3050878B1/en active Active
- 2014-09-24 CA CA2961935A patent/CA2961935C/en active Active
- 2014-09-24 FI FIEP21187649.5T patent/FI3929196T3/fi active
- 2014-09-24 PL PL21187649.5T patent/PL3929196T3/pl unknown
- 2014-09-24 SI SI201432043T patent/SI3929196T1/sl unknown
- 2014-09-24 ES ES14849898T patent/ES2899860T3/es active Active
- 2014-09-24 LT LTEP21187649.5T patent/LT3929196T/lt unknown
- 2014-09-24 EP EP23188351.3A patent/EP4249471A3/en active Pending
- 2014-09-24 PT PT211876495T patent/PT3929196T/pt unknown
- 2014-09-24 SI SI201431914T patent/SI3050878T1/sl unknown
- 2014-09-24 HU HUE14849898A patent/HUE057203T2/hu unknown
-
2016
- 2016-03-23 US US15/078,738 patent/US11426473B2/en active Active
-
2017
- 2017-04-02 IL IL251500A patent/IL251500A/en unknown
- 2017-09-20 JP JP2017179764A patent/JP6532515B2/ja active Active
-
2021
- 2021-12-02 CY CY20211101053T patent/CY1124794T1/el unknown
-
2022
- 2022-06-16 US US17/842,418 patent/US20230136073A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002508355A (ja) * | 1997-12-17 | 2002-03-19 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
WO2000035488A2 (en) * | 1998-12-18 | 2000-06-22 | Du Pont Pharmaceuticals Company | Vitronectin receptor antagonist pharmaceuticals |
US20050154185A1 (en) * | 1998-12-18 | 2005-07-14 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
JP2003520271A (ja) * | 2000-01-24 | 2003-07-02 | メルク エンド カムパニー インコーポレーテッド | αvインテグリン受容体拮抗薬 |
WO2001098294A2 (en) * | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals for use in combination therapy |
WO2013045333A1 (fr) * | 2011-09-26 | 2013-04-04 | Guerbet | Nanoemulsions et leur utilisation comme agents de contraste |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6532515B2 (ja) | 新規な含窒素化合物もしくはその塩またはそれらと金属との錯体 | |
CN109641910A (zh) | 吡咯并苯二氮*及其缀合物 | |
CN102317257B (zh) | 制备不对称双(缩氨基硫脲)的方法 | |
JP6411634B2 (ja) | 新規な含窒素化合物またはその塩の製造方法およびそれらの製造中間体 | |
CA2413957A1 (en) | Vitronectin receptor antagonist pharmaceuticals for use in combination therapy | |
TW201034691A (en) | Technetium-and rhenium-bis(heteroaryl) complexes and methods of use thereof | |
KR102658933B1 (ko) | 이중 표적화 화합물 및 이의 제조 방법과 응용 | |
EP1311292A2 (en) | Vitronectin receptor antagonist pharmaceuticals | |
CA2349333A1 (en) | Vitronectin receptor antagonist pharmaceuticals | |
JP2005538030A (ja) | 組み合わせ療法での使用のための血管新生障害の画像診断用医薬 | |
PT1140203E (pt) | Medicamentos antagonistas do receptor da vitronectina | |
JP6286467B2 (ja) | インテグリンが関与する疾患の診断または治療の処置剤 | |
AU2001272965B2 (en) | Vitronectin receptor antagonist pharmaceuticals | |
WO2001060820A2 (en) | Matrix metalloproteinase inhibitors and uses thereof | |
AU2001272965A1 (en) | Vitronectin receptor antagonist pharmaceuticals | |
TW202330539A (zh) | 用於治療、預防或管理過度增生性病症之化合物、醫藥組合物及方法 | |
KR20230141776A (ko) | 표적화 방사선요법에 사용하기 위한 다량체 킬레이트화제화합물 | |
JP2023554079A (ja) | リガンド及びそれらの使用 | |
MXPA01006151A (en) | Vitronectin receptor antagonist pharmaceuticals |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170425 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170623 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170705 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170809 |
|
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: 20170822 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170920 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6215335 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S533 | Written request for registration of change of name |
Free format text: JAPANESE INTERMEDIATE CODE: R313533 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313115 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |