JP2002543163A5 - - Google Patents

Info

Publication number

JP2002543163A5

JP2002543163A5 JP2000615058A JP2000615058A JP2002543163A5 JP 2002543163 A5 JP2002543163 A5 JP 2002543163A5 JP 2000615058 A JP2000615058 A JP 2000615058A JP 2000615058 A JP2000615058 A JP 2000615058A JP 2002543163 A5 JP2002543163 A5 JP 2002543163A5

Authority

JP

Japan

Prior art keywords

mmol

nmr

cdcl

added

polyamine

Prior art date

2000-04-27

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

Pending

Links

• Espacenet
• Global Dossier
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• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 212
• 229920000768 polyamine Polymers 0.000 description 188
• 150000001875 compounds Chemical class 0.000 description 141
• 210000004027 cells Anatomy 0.000 description 140
• 239000000203 mixture Substances 0.000 description 125
• XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
• 239000000243 solution Substances 0.000 description 90
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 88
• 239000011541 reaction mixture Substances 0.000 description 85
• 229920001184 polypeptide Polymers 0.000 description 84
• 239000000562 conjugate Substances 0.000 description 72
• 206010060862 Prostate cancer Diseases 0.000 description 71
• 239000007787 solid Substances 0.000 description 71
• 102100011339 KLK3 Human genes 0.000 description 70
• 108010072866 Prostate-Specific Antigen Proteins 0.000 description 70
• 238000005160 1H NMR spectroscopy Methods 0.000 description 67
• LKYXEULZVGJVTG-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH] LKYXEULZVGJVTG-UHFFFAOYSA-N 0.000 description 62
• 230000000694 effects Effects 0.000 description 60
• 238000000338 in vitro Methods 0.000 description 59
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 58
• AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-Benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 54
• 239000002904 solvent Substances 0.000 description 54
• HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 51
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
• 230000004083 survival Effects 0.000 description 50
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
• 230000001965 increased Effects 0.000 description 48
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
• 238000003786 synthesis reaction Methods 0.000 description 47
• 238000004440 column chromatography Methods 0.000 description 46
• 230000002829 reduced Effects 0.000 description 45
• 210000002307 Prostate Anatomy 0.000 description 44
• 230000015572 biosynthetic process Effects 0.000 description 44
• 238000000034 method Methods 0.000 description 44
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 43
• 230000002194 synthesizing Effects 0.000 description 42
• VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
• 235000019439 ethyl acetate Nutrition 0.000 description 38
• 239000000741 silica gel Substances 0.000 description 38
• 229910002027 silica gel Inorganic materials 0.000 description 38
• 229960001866 silicon dioxide Drugs 0.000 description 38
• 150000001413 amino acids Chemical class 0.000 description 35
• 125000003342 alkenyl group Chemical group 0.000 description 33
• -1 aminopropyl group Chemical group 0.000 description 33
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 201000011510 cancer Diseases 0.000 description 32
• UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
• 235000001014 amino acid Nutrition 0.000 description 31
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 30
• 125000000217 alkyl group Chemical group 0.000 description 29
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
• 238000006243 chemical reaction Methods 0.000 description 28
• 239000000047 product Substances 0.000 description 28
• 238000000746 purification Methods 0.000 description 27
• 201000010099 disease Diseases 0.000 description 26
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
• 125000003277 amino group Chemical group 0.000 description 25
• 239000008079 hexane Substances 0.000 description 25
• 150000004053 quinones Chemical class 0.000 description 25
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
• PFNFFQXMRSDOHW-UHFFFAOYSA-N Spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 23
• 239000010432 diamond Substances 0.000 description 23
• 239000011734 sodium Substances 0.000 description 23
• KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 239000003814 drug Substances 0.000 description 21
• 238000002360 preparation method Methods 0.000 description 21
• 125000000304 alkynyl group Chemical group 0.000 description 20
• 125000003118 aryl group Chemical group 0.000 description 20
• 125000000753 cycloalkyl group Chemical group 0.000 description 20
• 229910052739 hydrogen Inorganic materials 0.000 description 20
• 125000006239 protecting group Chemical group 0.000 description 20
• 239000000758 substrate Substances 0.000 description 20
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Carbodicyclohexylimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 19
• 102000004190 Enzymes Human genes 0.000 description 19
• 108090000790 Enzymes Proteins 0.000 description 19
• 125000000392 cycloalkenyl group Chemical group 0.000 description 19
• 229940079593 drugs Drugs 0.000 description 19
• 238000003756 stirring Methods 0.000 description 19
• 229940019746 Antifibrinolytic amino acids Drugs 0.000 description 18
• 229940021015 I.V. solution additive Amino Acids Drugs 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 238000005804 alkylation reaction Methods 0.000 description 17
• 150000001408 amides Chemical class 0.000 description 17
• 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 17
• 229910052757 nitrogen Inorganic materials 0.000 description 17
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
• 206010028980 Neoplasm Diseases 0.000 description 16
• 238000003776 cleavage reaction Methods 0.000 description 16
• 239000000284 extract Substances 0.000 description 16
• SJRJJKPEHAURKC-UHFFFAOYSA-N n-methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 16
• 239000011780 sodium chloride Substances 0.000 description 16
• BZKBCQXYZZXSCO-UHFFFAOYSA-N sodium hydride Inorganic materials [H-].[Na+] BZKBCQXYZZXSCO-UHFFFAOYSA-N 0.000 description 16
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 15
• 102000004225 Cathepsin B Human genes 0.000 description 15
• 108090000712 Cathepsin B Proteins 0.000 description 15
• 229940088598 Enzyme Drugs 0.000 description 15
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 15
• 230000002401 inhibitory effect Effects 0.000 description 15
• CSCPPACGZOOCGX-WFGJKAKNSA-N Deuterated acetone Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 14
• RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
• 239000003480 eluent Substances 0.000 description 14
• 238000001704 evaporation Methods 0.000 description 14
• 238000001914 filtration Methods 0.000 description 14
• 230000012010 growth Effects 0.000 description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
• 239000002244 precipitate Substances 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• 150000003839 salts Chemical class 0.000 description 14
• 239000012047 saturated solution Substances 0.000 description 14
• 210000004881 tumor cells Anatomy 0.000 description 14
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 13
• 229920003013 deoxyribonucleic acid Polymers 0.000 description 13
• 238000003818 flash chromatography Methods 0.000 description 13
• 239000002609 media Substances 0.000 description 13
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 12
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
• GGCZERPQGJTIQP-UHFFFAOYSA-M Sodium 2-anthraquinonesulfonate Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)[O-])=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-M 0.000 description 12
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M Sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
• ATHGHQPFGPMSJY-UHFFFAOYSA-N Spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 12
• 235000019270 ammonium chloride Nutrition 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• QDHHCQZDFGDHMP-UHFFFAOYSA-N monochloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• 210000002966 Serum Anatomy 0.000 description 11
• 229910052799 carbon Inorganic materials 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 239000001257 hydrogen Substances 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 229940063675 spermine Drugs 0.000 description 11
• ILAHWRKJUDSMFH-UHFFFAOYSA-N Boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
• 240000001178 Ficus deltoidea Species 0.000 description 10
• JYOAXOMPIXKMKK-UHFFFAOYSA-N Leucyl-Glutamine Chemical compound CC(C)CC(N)C(=O)NC(C(O)=O)CCC(N)=O JYOAXOMPIXKMKK-UHFFFAOYSA-N 0.000 description 10
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N Triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
• 230000004663 cell proliferation Effects 0.000 description 10
• 239000000463 material Substances 0.000 description 10
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 238000006722 reduction reaction Methods 0.000 description 10
• 210000001519 tissues Anatomy 0.000 description 10
• PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 9
• 206010006187 Breast cancer Diseases 0.000 description 9
• CSFWPUWCSPOLJW-UHFFFAOYSA-N Lawsone Chemical compound C1=CC=C2C(=O)C(O)=CC(=O)C2=C1 CSFWPUWCSPOLJW-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 238000007792 addition Methods 0.000 description 9
• 230000001028 anti-proliferant Effects 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 239000007864 aqueous solution Substances 0.000 description 9
• 230000021615 conjugation Effects 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
• 206010009944 Colon cancer Diseases 0.000 description 8
• 230000035492 administration Effects 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• 239000000969 carrier Substances 0.000 description 8
• 230000000445 cytocidal Effects 0.000 description 8
• 231100000409 cytocidal Toxicity 0.000 description 8
• 230000001085 cytostatic Effects 0.000 description 8
• 239000000824 cytostatic agent Substances 0.000 description 8
• 238000010511 deprotection reaction Methods 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
• YNPFMWCWRVTGKJ-UHFFFAOYSA-N mianserin hydrochloride Chemical compound [H+].[Cl-].C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 YNPFMWCWRVTGKJ-UHFFFAOYSA-N 0.000 description 8
• 150000002825 nitriles Chemical class 0.000 description 8
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
• 235000021317 phosphate Nutrition 0.000 description 8
• 239000000651 prodrug Substances 0.000 description 8
• 229940002612 prodrugs Drugs 0.000 description 8
• 201000002028 prostate disease Diseases 0.000 description 8
• 231100000486 side effect Toxicity 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 230000001225 therapeutic Effects 0.000 description 8
• 230000001988 toxicity Effects 0.000 description 8
• 231100000419 toxicity Toxicity 0.000 description 8
• ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
• KETQAJRQOHHATG-UHFFFAOYSA-N 1,2-Naphthoquinone Chemical compound C1=CC=C2C(=O)C(=O)C=CC2=C1 KETQAJRQOHHATG-UHFFFAOYSA-N 0.000 description 7
• RHHDMTSHWRREPK-UHFFFAOYSA-N 1,2-dimethoxynaphthalene Chemical compound C1=CC=CC2=C(OC)C(OC)=CC=C21 RHHDMTSHWRREPK-UHFFFAOYSA-N 0.000 description 7
• 229940105324 1,2-naphthoquinone Drugs 0.000 description 7
• SESFRYSPDFLNCH-UHFFFAOYSA-N Benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 7
• 208000003174 Brain Neoplasms Diseases 0.000 description 7
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 7
• XDRYMKDFEDOLFX-UHFFFAOYSA-N Pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 7
• 239000003098 androgen Substances 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 230000010261 cell growth Effects 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 238000009833 condensation Methods 0.000 description 7
• 230000005494 condensation Effects 0.000 description 7
• 238000001816 cooling Methods 0.000 description 7
• 239000012091 fetal bovine serum Substances 0.000 description 7
• OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
• 239000005457 ice water Substances 0.000 description 7
• XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 7
• 201000005202 lung cancer Diseases 0.000 description 7
• UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 7
• 239000010452 phosphate Substances 0.000 description 7
• 201000007094 prostatitis Diseases 0.000 description 7
• FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-Naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 6
• WLLMLMUVKXSBFF-UHFFFAOYSA-N 4-(6-iodohexoxy)naphthalene-1,2-dione Chemical compound C1=CC=C2C(OCCCCCCI)=CC(=O)C(=O)C2=C1 WLLMLMUVKXSBFF-UHFFFAOYSA-N 0.000 description 6
• CQPGDDAKTTWVDD-UHFFFAOYSA-N 4-bromobutanenitrile Chemical compound BrCCCC#N CQPGDDAKTTWVDD-UHFFFAOYSA-N 0.000 description 6
• 229960000583 Acetic Acid Drugs 0.000 description 6
• VOXJFDDEZQQRTR-UHFFFAOYSA-N N-[(3,4-dimethoxynaphthalen-1-yl)methyl]butan-1-amine Chemical compound C1=CC=C2C(CNCCCC)=CC(OC)=C(OC)C2=C1 VOXJFDDEZQQRTR-UHFFFAOYSA-N 0.000 description 6
• 241001274216 Naso Species 0.000 description 6
• 238000002835 absorbance Methods 0.000 description 6
• 230000000259 anti-tumor Effects 0.000 description 6
• 230000002354 daily Effects 0.000 description 6
• UPCIBFUJJLCOQG-UHFFFAOYSA-L ethyl-[2-[2-[ethyl(dimethyl)azaniumyl]ethyl-methylamino]ethyl]-dimethylazanium;dibromide Chemical compound [Br-].[Br-].CC[N+](C)(C)CCN(C)CC[N+](C)(C)CC UPCIBFUJJLCOQG-UHFFFAOYSA-L 0.000 description 6
• 230000001605 fetal Effects 0.000 description 6
• CPELXLSAUQHCOX-UHFFFAOYSA-N hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 235000018102 proteins Nutrition 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 229940063673 spermidine Drugs 0.000 description 6
• UCMIRNVEIXFBKS-UHFFFAOYSA-N β-Alanine Chemical group NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
• 125000000614 1,2-naphthoquinonyl group Chemical group C1(C(C(=CC2=CC=CC=C12)*)=O)=O 0.000 description 5
• SSAGXZBZROBVPE-UHFFFAOYSA-N 3,4-dimethoxynaphthalene-1-carbaldehyde Chemical compound C1=CC=CC2=C(OC)C(OC)=CC(C=O)=C21 SSAGXZBZROBVPE-UHFFFAOYSA-N 0.000 description 5
• XHCKCHBRVJUMFY-UHFFFAOYSA-N 7-(4-aminophenyl)heptan-1-ol Chemical compound NC1=CC=C(CCCCCCCO)C=C1 XHCKCHBRVJUMFY-UHFFFAOYSA-N 0.000 description 5
• AVWFDKUDGAMKOL-UHFFFAOYSA-N 7-[4-(acridin-9-ylamino)phenyl]heptan-1-ol Chemical compound C1=CC(CCCCCCCO)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 AVWFDKUDGAMKOL-UHFFFAOYSA-N 0.000 description 5
• 108010016626 Dipeptides Proteins 0.000 description 5
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• 241001465754 Metazoa Species 0.000 description 5
• IBQOKTSSFKTYFB-UHFFFAOYSA-N N-[4-(7-iodoheptyl)phenyl]acridin-9-amine Chemical compound C1=CC(CCCCCCCI)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 IBQOKTSSFKTYFB-UHFFFAOYSA-N 0.000 description 5
• BHSGVHDCJOSQRP-UHFFFAOYSA-N N-[4-[8-(3,4-dimethoxynaphthalen-1-yl)octa-1,7-dienyl]phenyl]acetamide Chemical compound C=12C=CC=CC2=C(OC)C(OC)=CC=1C=CCCCCC=CC1=CC=C(NC(C)=O)C=C1 BHSGVHDCJOSQRP-UHFFFAOYSA-N 0.000 description 5
• 229910019023 PtO Inorganic materials 0.000 description 5
• KIDHWZJUCRJVML-UHFFFAOYSA-N Putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 5
• NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
• QIGBRXMKCJKVMJ-UHFFFAOYSA-N benzohydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 5
• 238000004113 cell culture Methods 0.000 description 5
• 239000012230 colorless oil Substances 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 5
• 239000005556 hormone Substances 0.000 description 5
• UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 108090000765 processed proteins & peptides Proteins 0.000 description 5
• 102000004196 processed proteins & peptides Human genes 0.000 description 5
• 125000004151 quinonyl group Chemical group 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 235000009518 sodium iodide Nutrition 0.000 description 5
• 238000001665 trituration Methods 0.000 description 5
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