BG65897B1 - Антитуморни аналози на ет - 743 - Google Patents

Info

Publication number

BG65897B1

BG65897B1 BG107302A BG10730202A BG65897B1 BG 65897 B1 BG65897 B1 BG 65897B1 BG 107302 A BG107302 A BG 107302A BG 10730202 A BG10730202 A BG 10730202A BG 65897 B1 BG65897 B1 BG 65897B1

Authority

BG

Bulgaria

Prior art keywords

compound

coch

formula

alkyl

group

Prior art date

2000-05-15

Links

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• 230000000259 anti-tumor effect Effects 0.000 title abstract description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 271
• -1 hydroxymethylene group Chemical group 0.000 claims abstract description 139
• 229910052739 hydrogen Inorganic materials 0.000 claims description 84
• 125000004432 carbon atom Chemical group C* 0.000 claims description 71
• 239000001257 hydrogen Substances 0.000 claims description 68
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 68
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 61
• 125000006239 protecting group Chemical group 0.000 claims description 49
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 45
• 235000001014 amino acid Nutrition 0.000 claims description 33
• 125000002252 acyl group Chemical group 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 30
• 238000002360 preparation method Methods 0.000 claims description 29
• 125000003342 alkenyl group Chemical group 0.000 claims description 20
• 150000001413 amino acids Chemical class 0.000 claims description 19
• 150000002431 hydrogen Chemical class 0.000 claims description 19
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 17
• 229910052799 carbon Inorganic materials 0.000 claims description 16
• 206010028980 Neoplasm Diseases 0.000 claims description 12
• 150000001944 cysteine derivatives Chemical class 0.000 claims description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 125000004442 acylamino group Chemical group 0.000 claims description 10
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
• 235000018417 cysteine Nutrition 0.000 claims description 9
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 9
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 150000003573 thiols Chemical class 0.000 claims description 7
• 239000004475 Arginine Substances 0.000 claims description 6
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 6
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 6
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 6
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 6
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
• 235000004279 alanine Nutrition 0.000 claims description 6
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 6
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• 239000004474 valine Substances 0.000 claims description 6
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 5
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 3
• 101150065749 Churc1 gene Proteins 0.000 claims description 3
• 102100038239 Protein Churchill Human genes 0.000 claims description 3
• 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 claims description 3
• 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• KTHDTJVBEPMMGL-VKHMYHEASA-N N-acetyl-L-alanine Chemical compound OC(=O)[C@H](C)NC(C)=O KTHDTJVBEPMMGL-VKHMYHEASA-N 0.000 claims description 2
• 230000001681 protective effect Effects 0.000 claims 2
• 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 150000003839 salts Chemical class 0.000 claims 1
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
• PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical group C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 abstract description 22
• 125000001424 substituent group Chemical group 0.000 abstract description 18
• 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 abstract description 8
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 901
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 708
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 469
• 239000000243 solution Substances 0.000 description 321
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 304
• 235000019439 ethyl acetate Nutrition 0.000 description 301
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 266
• 238000005481 NMR spectroscopy Methods 0.000 description 208
• 239000011541 reaction mixture Substances 0.000 description 179
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 175
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 146
• 239000007787 solid Substances 0.000 description 144
• 239000012044 organic layer Substances 0.000 description 134
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 129
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 125
• 229910052938 sodium sulfate Inorganic materials 0.000 description 125
• 235000011152 sodium sulphate Nutrition 0.000 description 125
• 238000003818 flash chromatography Methods 0.000 description 117
• 239000000377 silicon dioxide Substances 0.000 description 114
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 100
• 238000006243 chemical reaction Methods 0.000 description 96
• 239000002904 solvent Substances 0.000 description 95
• 239000000543 intermediate Substances 0.000 description 68
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 63
• 235000017557 sodium bicarbonate Nutrition 0.000 description 63
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 61
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 60
• 239000000203 mixture Substances 0.000 description 57
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical class CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 51
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 50
• 229920006395 saturated elastomer Polymers 0.000 description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
• 238000000034 method Methods 0.000 description 46
• 206010025323 Lymphomas Diseases 0.000 description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
• 229910001961 silver nitrate Inorganic materials 0.000 description 30
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 29
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• 125000004093 cyano group Chemical group *C#N 0.000 description 25
• 229930190585 Saframycin Natural products 0.000 description 24
• 125000003118 aryl group Chemical group 0.000 description 24
• 239000012267 brine Substances 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• 239000007858 starting material Substances 0.000 description 23
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
• 229940024606 amino acid Drugs 0.000 description 21
• 125000003277 amino group Chemical group 0.000 description 20
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 18
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 18
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
• 239000000460 chlorine Substances 0.000 description 18
• QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 18
• 238000000746 purification Methods 0.000 description 18
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 16
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
• GKUZBRIJGIGFKC-UHFFFAOYSA-N Safracin B Natural products OC1C(N2C)CC3=CC(C)=C(OC)C(O)=C3C2C(C2)N1C(CNC(=O)C(C)N)C1=C2C(=O)C(C)=C(OC)C1=O GKUZBRIJGIGFKC-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 15
• 239000012346 acetyl chloride Substances 0.000 description 15
• GKUZBRIJGIGFKC-XPXFATIHSA-N antibiotic em 5519 Chemical compound C([C@@H](N1C)[C@@H]2O)C3=CC(C)=C(OC)C(O)=C3[C@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O GKUZBRIJGIGFKC-XPXFATIHSA-N 0.000 description 14
• 125000004122 cyclic group Chemical group 0.000 description 13
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• 239000003814 drug Substances 0.000 description 12
• 125000004151 quinonyl group Chemical group 0.000 description 12
• BHINEHROXMLHMV-BVRLQDJESA-N C([C@H](N1C)[C@@H]2C#N)C3=CC(C)=C(OC)C(O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O Chemical compound C([C@H](N1C)[C@@H]2C#N)C3=CC(C)=C(OC)C(O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)[C@H](C)N)C2=C1C(=O)C(C)=C(OC)C2=O BHINEHROXMLHMV-BVRLQDJESA-N 0.000 description 11
• 229940079593 drug Drugs 0.000 description 11
• 238000010189 synthetic method Methods 0.000 description 11
• 229960000977 trabectedin Drugs 0.000 description 11
• 230000009466 transformation Effects 0.000 description 11
• SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 10
• XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 description 10
• 210000001744 T-lymphocyte Anatomy 0.000 description 10
• 150000001408 amides Chemical class 0.000 description 10
• 125000003710 aryl alkyl group Chemical group 0.000 description 10
• JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 description 10
• 230000015572 biosynthetic process Effects 0.000 description 9
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
• 229910000024 caesium carbonate Inorganic materials 0.000 description 9
• 208000032839 leukemia Diseases 0.000 description 9
• AZQWKYJCGOJGHM-UHFFFAOYSA-N para-benzoquinone Natural products O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
• 229940117953 phenylisothiocyanate Drugs 0.000 description 9
• 230000008569 process Effects 0.000 description 9
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
• 230000010933 acylation Effects 0.000 description 8
• 238000005917 acylation reaction Methods 0.000 description 8
• 125000003545 alkoxy group Chemical group 0.000 description 8
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 8
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 8
• 229910052760 oxygen Inorganic materials 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 229930188681 renieramycin Natural products 0.000 description 8
• JNEGMBHBUAJRSX-SHUHUVMISA-N saframycin a Chemical compound C([C@H](N1C)[C@@H]2C#N)C(C(C(C)=C(OC)C3=O)=O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O JNEGMBHBUAJRSX-SHUHUVMISA-N 0.000 description 8
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
• 229960002433 cysteine Drugs 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 239000012467 final product Substances 0.000 description 7
• 150000002367 halogens Chemical class 0.000 description 7
• 125000000623 heterocyclic group Chemical group 0.000 description 7
• 201000001441 melanoma Diseases 0.000 description 7
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• 208000005243 Chondrosarcoma Diseases 0.000 description 6
• 201000008808 Fibrosarcoma Diseases 0.000 description 6
• 102100021888 Helix-loop-helix protein 1 Human genes 0.000 description 6
• 101000897691 Homo sapiens Helix-loop-helix protein 1 Proteins 0.000 description 6
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
• 201000000582 Retinoblastoma Diseases 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
• 230000002378 acidificating effect Effects 0.000 description 6
• 230000001154 acute effect Effects 0.000 description 6
• UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
• 125000005110 aryl thio group Chemical group 0.000 description 6
• 210000000481 breast Anatomy 0.000 description 6
• DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 6
• 230000001684 chronic effect Effects 0.000 description 6
• 101150016491 chsA gene Proteins 0.000 description 6
• 210000001072 colon Anatomy 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 230000007062 hydrolysis Effects 0.000 description 6
• 238000006460 hydrolysis reaction Methods 0.000 description 6
• 125000000468 ketone group Chemical group 0.000 description 6
• 210000003734 kidney Anatomy 0.000 description 6
• 210000004185 liver Anatomy 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
• 229910052757 nitrogen Inorganic materials 0.000 description 6
• 210000001672 ovary Anatomy 0.000 description 6
• 210000000496 pancreas Anatomy 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• 239000011734 sodium Substances 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 210000002784 stomach Anatomy 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 5
• UFWYPWFCNWILJC-UHFFFAOYSA-N Saframycin Mx 2 Natural products COC1C2CN3C(CC4=C(C3CNC(=O)C(C)N)C(=O)C(=C(C)C4=O)OC)C(N2C)c5c(O)c(OC)c(C)c(O)c15 UFWYPWFCNWILJC-UHFFFAOYSA-N 0.000 description 5
• 229960003767 alanine Drugs 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 239000003242 anti bacterial agent Substances 0.000 description 5
• 229940088710 antibiotic agent Drugs 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 229960003121 arginine Drugs 0.000 description 5
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