IL126840A - History of dystmycin, a process for their preparation and use in the production of anti-tumor and anti-viral substances - Google Patents

History of dystmycin, a process for their preparation and use in the production of anti-tumor and anti-viral substances

Info

Publication number: IL126840A
Authority: IL; Israel
Prior art keywords: methyl; carboxamido; pyrrole; chloroethyl; aminocinnamoylamido
Prior art date: 1996-05-14

Application number

IL12684097A

Other languages

English (en)

Hebrew (he)

Other versions

IL126840A0 (en

Original Assignee

Pharmacia & Upjohn Spa

Priority date (The priority date 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 date listed.)

1996-05-14

Filing date

1997-04-24

Publication date

2002-03-10

1997-04-24 Application filed by Pharmacia & Upjohn Spa filed Critical Pharmacia & Upjohn Spa

1999-09-22 Publication of IL126840A0 publication Critical patent/IL126840A0/xx

2002-03-10 Publication of IL126840A publication Critical patent/IL126840A/en

Links

UPBAOYRENQEPJO-UHFFFAOYSA-N n-[5-[[5-[(3-amino-3-iminopropyl)carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]-4-formamido-1-methylpyrrole-2-carboxamide Chemical class CN1C=C(NC=O)C=C1C(=O)NC1=CN(C)C(C(=O)NC2=CN(C)C(C(=O)NCCC(N)=N)=C2)=C1 UPBAOYRENQEPJO-UHFFFAOYSA-N 0.000 title claims description 15
239000002246 antineoplastic agent Substances 0.000 title claims description 12
238000004519 manufacturing process Methods 0.000 title claims description 11
239000003443 antiviral agent Substances 0.000 title claims description 6
230000000259 anti-tumor effect Effects 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 104
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
239000001257 hydrogen Substances 0.000 claims abstract description 26
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 10
125000005843 halogen group Chemical group 0.000 claims abstract description 9
125000001188 haloalkyl group Chemical group 0.000 claims abstract description 7
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 152
GNFWGDKKNWGGJY-UHFFFAOYSA-N propanimidamide Chemical compound CCC(N)=N GNFWGDKKNWGGJY-UHFFFAOYSA-N 0.000 claims description 31
238000000034 method Methods 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 27
KEWLVUBYGUZFKX-UHFFFAOYSA-N 2-ethylguanidine Chemical compound CCNC(N)=N KEWLVUBYGUZFKX-UHFFFAOYSA-N 0.000 claims description 20
-1 and C^C Chemical group 0.000 claims description 20
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
125000005999 2-bromoethyl group Chemical group 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 11
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
RLZPCFQNZGINRP-UHFFFAOYSA-N n'-hydroxypropanimidamide Chemical compound CCC(N)=NO RLZPCFQNZGINRP-UHFFFAOYSA-N 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 7
206010028980 Neoplasm Diseases 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 5
125000001246 bromo group Chemical group Br* 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 5
229940080818 propionamide Drugs 0.000 claims description 5
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 5
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
229940014800 succinic anhydride Drugs 0.000 claims description 4
208000036142 Viral infection Diseases 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
230000009385 viral infection Effects 0.000 claims description 3
201000011510 cancer Diseases 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 claims 2
229940034982 antineoplastic agent Drugs 0.000 claims 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 55
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
239000000243 solution Substances 0.000 description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
239000000543 intermediate Substances 0.000 description 24
239000000203 mixture Substances 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 17
DFWRZHZPJJAJMX-UHFFFAOYSA-N propanimidamide;hydrochloride Chemical compound Cl.CCC(N)=N DFWRZHZPJJAJMX-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 15
239000002904 solvent Substances 0.000 description 15
238000003818 flash chromatography Methods 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 13
GVSGVBVZXJOLDD-UHFFFAOYSA-N (n'-ethylcarbamimidoyl)azanium;chloride Chemical compound [Cl-].CCN=C(N)[NH3+] GVSGVBVZXJOLDD-UHFFFAOYSA-N 0.000 description 11
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
239000000047 product Substances 0.000 description 10
239000007858 starting material Substances 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
241000700605 Viruses Species 0.000 description 8
235000015497 potassium bicarbonate Nutrition 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
229910000028 potassium bicarbonate Inorganic materials 0.000 description 7
239000011736 potassium bicarbonate Substances 0.000 description 7
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 7
229940126062 Compound A Drugs 0.000 description 6
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
238000001914 filtration Methods 0.000 description 6
208000032839 leukemia Diseases 0.000 description 6
108010042747 stallimycin Proteins 0.000 description 6
229920002261 Corn starch Polymers 0.000 description 5
241001529936 Murinae Species 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
239000008120 corn starch Substances 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
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 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
239000008101 lactose Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
206010039491 Sarcoma Diseases 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
230000002152 alkylating effect Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
229950009902 stallimycin Drugs 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
230000004083 survival effect Effects 0.000 description 3
238000011282 treatment Methods 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
KYJBBNCBVZZHOA-UHFFFAOYSA-N 2-(2-aminoethyl)guanidine;dihydrochloride Chemical compound Cl.Cl.NCCN=C(N)N KYJBBNCBVZZHOA-UHFFFAOYSA-N 0.000 description 2
WJLVJDGAGUZERK-UHFFFAOYSA-N 2-amino-5-chloro-3-phenylpent-2-enoic acid Chemical compound OC(=O)C(N)=C(CCCl)C1=CC=CC=C1 WJLVJDGAGUZERK-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 2
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
235000010443 alginic acid Nutrition 0.000 description 2
229920000615 alginic acid Polymers 0.000 description 2
229940041181 antineoplastic drug Drugs 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
125000005518 carboxamido group Chemical group 0.000 description 2
238000004113 cell culture Methods 0.000 description 2
230000010261 cell growth Effects 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
231100000135 cytotoxicity Toxicity 0.000 description 2
230000003013 cytotoxicity Effects 0.000 description 2
229960001760 dimethyl sulfoxide Drugs 0.000 description 2
JNWPZWCAGJSQTK-UHFFFAOYSA-N ethyl 3-[4-(ethylamino)phenyl]prop-2-enoate Chemical compound CCNC1=CC=C(C=CC(=O)OCC)C=C1 JNWPZWCAGJSQTK-UHFFFAOYSA-N 0.000 description 2
239000008187 granular material Substances 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
229960000908 idarubicin Drugs 0.000 description 2
238000001802 infusion Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000002452 interceptive effect Effects 0.000 description 2
238000010255 intramuscular injection Methods 0.000 description 2
239000007927 intramuscular injection Substances 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
239000000843 powder Substances 0.000 description 2
229960004063 propylene glycol Drugs 0.000 description 2
235000013772 propylene glycol Nutrition 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000000376 reactant Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
239000008107 starch Substances 0.000 description 2
229940032147 starch Drugs 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
210000001519 tissue Anatomy 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
238000002054 transplantation Methods 0.000 description 2
210000004881 tumor cell Anatomy 0.000 description 2
230000004614 tumor growth Effects 0.000 description 2
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
FSUPKDUNLKQBCN-UHFFFAOYSA-N 1H-pyrrole-2-carboximidamide Chemical compound NC(=N)C1=CC=CN1 FSUPKDUNLKQBCN-UHFFFAOYSA-N 0.000 description 1
QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
HPOIUFVUSUIDOF-UHFFFAOYSA-N 2-ethylguanidine dihydrochloride Chemical compound Cl.Cl.CCNC(N)=N HPOIUFVUSUIDOF-UHFFFAOYSA-N 0.000 description 1
RRQIDLYKQXIIIK-UHFFFAOYSA-N 3-[3-[2-chloroethyl(ethyl)amino]phenyl]prop-2-enoic acid Chemical compound ClCCN(CC)C1=CC=CC(C=CC(O)=O)=C1 RRQIDLYKQXIIIK-UHFFFAOYSA-N 0.000 description 1
BZUXKVDJQBVGIC-UHFFFAOYSA-N 3-[4-[2-chloroethyl(ethyl)amino]-3,5-dimethylphenyl]prop-2-enoic acid Chemical compound ClCCN(CC)C1=C(C)C=C(C=CC(O)=O)C=C1C BZUXKVDJQBVGIC-UHFFFAOYSA-N 0.000 description 1
ABAIFLLZXZLKOZ-UHFFFAOYSA-N 3-[4-[2-chloroethyl(ethyl)amino]-3-methoxyphenyl]prop-2-enoic acid Chemical compound ClCCN(CC)C1=CC=C(C=CC(O)=O)C=C1OC ABAIFLLZXZLKOZ-UHFFFAOYSA-N 0.000 description 1
JWQNZFGLXCVKLV-UHFFFAOYSA-N 3-[4-[2-chloroethyl(ethyl)amino]-3-methylphenyl]prop-2-enoic acid Chemical compound ClCCN(CC)C1=CC=C(C=CC(O)=O)C=C1C JWQNZFGLXCVKLV-UHFFFAOYSA-N 0.000 description 1
KFVOPRFELMRLSU-UHFFFAOYSA-N 3-[4-[2-chloroethyl(ethyl)amino]phenyl]prop-2-enoic acid Chemical compound ClCCN(CC)C1=CC=C(C=CC(O)=O)C=C1 KFVOPRFELMRLSU-UHFFFAOYSA-N 0.000 description 1
ZNHONXNBTHOMCE-UHFFFAOYSA-N 3-[4-[2-chloroethyl(methyl)amino]-3,5-dimethylphenyl]prop-2-enoic acid Chemical compound ClCCN(C)C1=C(C)C=C(C=CC(O)=O)C=C1C ZNHONXNBTHOMCE-UHFFFAOYSA-N 0.000 description 1
BSQAQDMBWQCLGI-UHFFFAOYSA-N 3-[4-[2-chloroethyl(methyl)amino]-3-methoxyphenyl]prop-2-enoic acid Chemical compound COC1=CC(C=CC(O)=O)=CC=C1N(C)CCCl BSQAQDMBWQCLGI-UHFFFAOYSA-N 0.000 description 1
MWEJIRLBFZZXSD-UHFFFAOYSA-N 3-[4-[2-chloroethyl(methyl)amino]-3-methylphenyl]prop-2-enoic acid Chemical compound ClCCN(C)C1=CC=C(C=CC(O)=O)C=C1C MWEJIRLBFZZXSD-UHFFFAOYSA-N 0.000 description 1
XMUHKJQGMQTRMI-UHFFFAOYSA-N 3-[4-[2-chloroethyl(methyl)amino]phenyl]prop-2-enoic acid Chemical compound ClCCN(C)C1=CC=C(C=CC(O)=O)C=C1 XMUHKJQGMQTRMI-UHFFFAOYSA-N 0.000 description 1
VHAIHFVXQYTLHN-UHFFFAOYSA-N 3-[4-[2-chloroethyl(propyl)amino]-3,5-dimethylphenyl]prop-2-enoic acid Chemical compound CCCN(CCCl)C1=C(C)C=C(C=CC(O)=O)C=C1C VHAIHFVXQYTLHN-UHFFFAOYSA-N 0.000 description 1
PEEDXKZJZPTUQW-UHFFFAOYSA-N 3-[4-[2-chloroethyl(propyl)amino]-3-methoxyphenyl]prop-2-enoic acid Chemical compound CCCN(CCCl)C1=CC=C(C=CC(O)=O)C=C1OC PEEDXKZJZPTUQW-UHFFFAOYSA-N 0.000 description 1
CYMXDSOQCKXKQO-UHFFFAOYSA-N 3-[4-[2-chloroethyl(propyl)amino]-3-methylphenyl]prop-2-enoic acid Chemical compound CCCN(CCCl)C1=CC=C(C=CC(O)=O)C=C1C CYMXDSOQCKXKQO-UHFFFAOYSA-N 0.000 description 1
LBCQFKINCYOICE-UHFFFAOYSA-N 3-[4-[2-chloroethyl(propyl)amino]phenyl]prop-2-enoic acid Chemical compound CCCN(CCCl)C1=CC=C(C=CC(O)=O)C=C1 LBCQFKINCYOICE-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 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
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-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
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
206010005003 Bladder cancer Diseases 0.000 description 1
108010006654 Bleomycin Proteins 0.000 description 1
JZAHVNBKPCLLPS-UHFFFAOYSA-N Br.CCC(N)=N Chemical compound Br.CCC(N)=N JZAHVNBKPCLLPS-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
241000709687 Coxsackievirus Species 0.000 description 1
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000709661 Enterovirus Species 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
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 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
208000002250 Hematologic Neoplasms Diseases 0.000 description 1
208000009889 Herpes Simplex Diseases 0.000 description 1
208000007514 Herpes zoster Diseases 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
229930192392 Mitomycin Natural products 0.000 description 1
241000713862 Moloney murine sarcoma virus Species 0.000 description 1
241000714177 Murine leukemia virus Species 0.000 description 1
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 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 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
206010061535 Ovarian neoplasm Diseases 0.000 description 1
238000003482 Pinner synthesis reaction Methods 0.000 description 1
241000725643 Respiratory syncytial virus Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
229930006000 Sucrose Natural products 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
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
206010046865 Vaccinia virus infection Diseases 0.000 description 1
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000002723 alicyclic group Chemical group 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
150000001409 amidines Chemical class 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
238000011319 anticancer therapy Methods 0.000 description 1
125000003118 aryl group Chemical group 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
239000011230 binding agent Substances 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
201000001531 bladder carcinoma Diseases 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
230000037396 body weight Effects 0.000 description 1
206010006007 bone sarcoma Diseases 0.000 description 1
201000008275 breast carcinoma Diseases 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
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
230000000120 cytopathologic effect Effects 0.000 description 1
230000001085 cytostatic effect Effects 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
230000006198 deformylation Effects 0.000 description 1
238000006344 deformylation reaction Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
235000013681 dietary sucrose Nutrition 0.000 description 1
206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
PRAHCKGOTFKWKD-UHFFFAOYSA-N dimethyl(propyl)azanium;chloride Chemical compound Cl.CCCN(C)C PRAHCKGOTFKWKD-UHFFFAOYSA-N 0.000 description 1
FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
229960004679 doxorubicin Drugs 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000009510 drug design Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
208000023965 endometrium neoplasm Diseases 0.000 description 1
229960001904 epirubicin Drugs 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
NRPMBSHHBFFYBF-VMPITWQZSA-N ethyl (e)-3-(4-aminophenyl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CC=C(N)C=C1 NRPMBSHHBFFYBF-VMPITWQZSA-N 0.000 description 1
NKJZZGKORLMOJX-UHFFFAOYSA-N ethyl 3-[3-(ethylamino)phenyl]prop-2-enoate Chemical compound CCNC1=CC=CC(C=CC(=O)OCC)=C1 NKJZZGKORLMOJX-UHFFFAOYSA-N 0.000 description 1
AJJSDDXRPITUII-UHFFFAOYSA-N ethyl 3-[3-methoxy-4-(propylamino)phenyl]prop-2-enoate Chemical compound CCCNC1=CC=C(C=CC(=O)OCC)C=C1OC AJJSDDXRPITUII-UHFFFAOYSA-N 0.000 description 1
YARVMHCCBOBKPT-UHFFFAOYSA-N ethyl 3-[4-(ethylamino)-3,5-dimethylphenyl]prop-2-enoate Chemical compound CCNC1=C(C)C=C(C=CC(=O)OCC)C=C1C YARVMHCCBOBKPT-UHFFFAOYSA-N 0.000 description 1
CVUQDKFMNFNGOH-UHFFFAOYSA-N ethyl 3-[4-(methylamino)phenyl]prop-2-enoate Chemical compound CCOC(=O)C=CC1=CC=C(NC)C=C1 CVUQDKFMNFNGOH-UHFFFAOYSA-N 0.000 description 1
OZFOPBZCIXTUEU-UHFFFAOYSA-N ethyl 3-[4-(propylamino)phenyl]prop-2-enoate Chemical compound CCCNC1=CC=C(C=CC(=O)OCC)C=C1 OZFOPBZCIXTUEU-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
229960005420 etoposide Drugs 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
239000000284 extract Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
229960002949 fluorouracil Drugs 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
230000012010 growth Effects 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
LFXAECSQJSRSTP-UHFFFAOYSA-N hydron;methyl carbamimidothioate;iodide Chemical compound I.CSC(N)=N LFXAECSQJSRSTP-UHFFFAOYSA-N 0.000 description 1
150000002463 imidates Chemical class 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
230000005918 in vitro anti-tumor Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
229960004393 lidocaine hydrochloride Drugs 0.000 description 1
YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005296 lung carcinoma Diseases 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
229960001924 melphalan Drugs 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
229960004857 mitomycin Drugs 0.000 description 1
238000002156 mixing Methods 0.000 description 1
RXVOYBXRQYBBCE-UHFFFAOYSA-N n,n-dimethylpropan-1-amine;dihydrochloride Chemical compound Cl.Cl.CCCN(C)C RXVOYBXRQYBBCE-UHFFFAOYSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
230000009826 neoplastic cell growth Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
108020004707 nucleic acids Proteins 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
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
210000001672 ovary Anatomy 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
125000005010 perfluoroalkyl group Chemical group 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229940068965 polysorbates Drugs 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000010076 replication Effects 0.000 description 1
230000001850 reproductive effect Effects 0.000 description 1
201000006845 reticulosarcoma Diseases 0.000 description 1
208000029922 reticulum cell sarcoma Diseases 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000007789 sealing Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
238000005549 size reduction Methods 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
229920003109 sodium starch glycolate Polymers 0.000 description 1
229940079832 sodium starch glycolate Drugs 0.000 description 1
239000008109 sodium starch glycolate Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
210000004872 soft tissue Anatomy 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
DELUVOHSQVQCPQ-UHFFFAOYSA-N tert-butyl N-(2-aminoethyl)-N-carbamimidoylcarbamate hydroiodide Chemical compound I.C(=O)(OC(C)(C)C)N(C(=N)N)CCN DELUVOHSQVQCPQ-UHFFFAOYSA-N 0.000 description 1
AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
208000010570 urinary bladder carcinoma Diseases 0.000 description 1
208000007089 vaccinia Diseases 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Virology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Pyrrole Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

IL12684097A 1996-05-14 1997-04-24 History of dystmycin, a process for their preparation and use in the production of anti-tumor and anti-viral substances IL126840A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9610079.7A GB9610079D0 (en)	1996-05-14	1996-05-14	Distamycin deriratives process for preparing them and their use as antitumor and antiviral agents
PCT/EP1997/002158 WO1997043258A1 (en)	1996-05-14	1997-04-24	Distamycin derivatives, process for preparing them, and their use as antitumor and antiviral agents

Publications (2)

Publication Number	Publication Date
IL126840A0 IL126840A0 (en)	1999-09-22
IL126840A true IL126840A (en)	2002-03-10

Family

ID=10793694

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL12684097A IL126840A (en)	1996-05-14	1997-04-24	History of dystmycin, a process for their preparation and use in the production of anti-tumor and anti-viral substances

Country Status (26)

Country	Link
US (1)	US6177408B1 (de)
EP (1)	EP0912509B1 (de)
JP (1)	JP2000510129A (de)
CN (1)	CN1089755C (de)
AR (1)	AR007108A1 (de)
AT (1)	ATE203011T1 (de)
AU (1)	AU721140B2 (de)
BR (1)	BR9709451A (de)
CA (1)	CA2253652A1 (de)
DE (1)	DE69705622T2 (de)
DK (1)	DK0912509T3 (de)
EA (1)	EA002273B1 (de)
ES (1)	ES2160951T3 (de)
GB (1)	GB9610079D0 (de)
GR (1)	GR3036824T3 (de)
HU (1)	HUP9901387A3 (de)
IL (1)	IL126840A (de)
MY (1)	MY118004A (de)
NO (1)	NO311886B1 (de)
NZ (1)	NZ332923A (de)
PL (1)	PL329878A1 (de)
PT (1)	PT912509E (de)
TW (1)	TW498066B (de)
UA (1)	UA45457C2 (de)
WO (1)	WO1997043258A1 (de)
ZA (1)	ZA973883B (de)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9806689D0 (en) *	1998-03-27	1998-05-27	Pharmacia & Upjohn Spa	Acryloyl derivatives analogous to distamycin,process for preparing them,and their use as antitumour and antiviral agents
GB9806692D0 (en) *	1998-03-27	1998-05-27	Pharmacia & Upjohn Spa	Benzoheterocyclic distamycin derivatives, process for preparing them and their use as antitumour agents
GB9812211D0 (en)	1998-06-05	1998-08-05	Pharmacia & Upjohn Spa	Cinnamoyl distamycin analogous derivatives,process for their preparation,and their use as antitumor agents
GB9816653D0 (en) *	1998-07-30	1998-09-30	Pharmacia & Upjohn Spa	Oxidised sulfurated distamycin derivatives process for preparing them and their use as antitumor agents
GB9816652D0 (en) *	1998-07-30	1998-09-30	Pharmacia & Upjohn Spa	Sulfurated distamycin derivatives process for preparing them and their use as antitumor agents
GB9928703D0 (en) *	1999-12-03	2000-02-02	Pharmacia & Upjohn Spa	Acryloyl peptidic derivatives,process for their preparation and their use as antitumour agents
US6559125B1 (en)	2000-01-28	2003-05-06	California Institute Of Technology	Polyamide-alkylator conjugates and related products and method
GB0011059D0 (en)	2000-05-08	2000-06-28	Pharmacia & Upjohn Spa	Use of substituted acryloyl distamycin derivatives in the treatment of tumours associated with high levels of glutathione
GB0015446D0 (en)	2000-06-23	2000-08-16	Pharmacia & Upjohn Spa	Combined therapy against tumors comprising substituted acryloyl distamycin derivates,taxanes and/or antimetabolites
GB0015447D0 (en)	2000-06-23	2000-08-16	Pharmacia & Upjohn Spa	Combined therapy against tumors comprising substituted acryloyl derivates and alkylating agents
GB0016447D0 (en) *	2000-07-04	2000-08-23	Pharmacia & Upjohn Spa	Process for preparing distamycin derivatives
GB0017852D0 (en) *	2000-07-20	2000-09-06	Pharmacia & Upjohn Spa	Process for preparing distamycin derivatives
GB0029004D0 (en)	2000-11-28	2001-01-10	Pharmacia & Upjohn Spa	Process for preparing distamycin derivatives
JP2005505508A (ja) *	2001-06-13	2005-02-24	ジーンソフトファーマシューティカルズインコーポレイテッド	抗感染活性を有するベンゾチオフェン化合物
US20030236198A1 (en) *	2001-06-13	2003-12-25	Genesoft, Inc.	Antipathogenic benzamide compounds
US6969592B2 (en)	2001-09-26	2005-11-29	Pharmacia Italia S.P.A.	Method for predicting the sensitivity to chemotherapy
KR102573190B1 (ko)	2015-10-16	2023-09-01	삼성전자주식회사	전자장치 및 전자장치 제조방법

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8612218D0 (en) *	1986-05-20	1986-06-25	Erba Farmitalia	Site specific alkylating agents
GB9416005D0 (en) *	1994-08-08	1994-09-28	Erba Carlo Spa	Peptidic compounds analogous to distamycin a and process for their preparation

1996
- 1996-05-14 GB GBGB9610079.7A patent/GB9610079D0/en active Pending
1997
- 1997-04-24 UA UA98126575A patent/UA45457C2/uk unknown
- 1997-04-24 NZ NZ332923A patent/NZ332923A/xx unknown
- 1997-04-24 PL PL97329878A patent/PL329878A1/xx unknown
- 1997-04-24 DK DK97920753T patent/DK0912509T3/da active
- 1997-04-24 JP JP09540439A patent/JP2000510129A/ja not_active Withdrawn
- 1997-04-24 DE DE69705622T patent/DE69705622T2/de not_active Expired - Fee Related
- 1997-04-24 HU HU9901387A patent/HUP9901387A3/hu unknown
- 1997-04-24 ES ES97920753T patent/ES2160951T3/es not_active Expired - Lifetime
- 1997-04-24 CN CN97195530A patent/CN1089755C/zh not_active Expired - Fee Related
- 1997-04-24 US US09/147,264 patent/US6177408B1/en not_active Expired - Fee Related
- 1997-04-24 EP EP97920753A patent/EP0912509B1/de not_active Expired - Lifetime
- 1997-04-24 EA EA199801013A patent/EA002273B1/ru not_active IP Right Cessation
- 1997-04-24 BR BR9709451A patent/BR9709451A/pt not_active Application Discontinuation
- 1997-04-24 WO PCT/EP1997/002158 patent/WO1997043258A1/en not_active Ceased
- 1997-04-24 IL IL12684097A patent/IL126840A/en not_active IP Right Cessation
- 1997-04-24 AT AT97920753T patent/ATE203011T1/de not_active IP Right Cessation
- 1997-04-24 CA CA002253652A patent/CA2253652A1/en not_active Abandoned
- 1997-04-24 AU AU27016/97A patent/AU721140B2/en not_active Ceased
- 1997-04-24 PT PT97920753T patent/PT912509E/pt unknown
- 1997-05-05 TW TW086106038A patent/TW498066B/zh not_active IP Right Cessation
- 1997-05-06 ZA ZA9703883A patent/ZA973883B/xx unknown
- 1997-05-13 MY MYPI97002075A patent/MY118004A/en unknown
- 1997-05-13 AR ARP970101989A patent/AR007108A1/es unknown
1998
- 1998-11-13 NO NO19985307A patent/NO311886B1/no unknown
2001
- 2001-10-08 GR GR20010401685T patent/GR3036824T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
MY118004A (en)	2004-08-30
EA199801013A1 (ru)	1999-06-24
BR9709451A (pt)	1999-08-10
DE69705622T2 (de)	2002-05-08
NO985307D0 (no)	1998-11-13
AU721140B2 (en)	2000-06-22
DE69705622D1 (de)	2001-08-16
PL329878A1 (en)	1999-04-12
HK1020734A1 (en)	2000-05-19
UA45457C2 (uk)	2002-04-15
EA002273B1 (ru)	2002-02-28
AU2701697A (en)	1997-12-05
ATE203011T1 (de)	2001-07-15
JP2000510129A (ja)	2000-08-08
HUP9901387A3 (en)	2002-10-28
CA2253652A1 (en)	1997-11-20
PT912509E (pt)	2001-12-28
AR007108A1 (es)	1999-10-13
NO985307L (no)	1999-01-12
CN1089755C (zh)	2002-08-28
NO311886B1 (no)	2002-02-11
IL126840A0 (en)	1999-09-22
GB9610079D0 (en)	1996-07-17
CN1222144A (zh)	1999-07-07
TW498066B (en)	2002-08-11
HUP9901387A2 (hu)	2000-04-28
DK0912509T3 (da)	2001-10-22
EP0912509B1 (de)	2001-07-11
EP0912509A1 (de)	1999-05-06
WO1997043258A1 (en)	1997-11-20
ES2160951T3 (es)	2001-11-16
GR3036824T3 (en)	2002-01-31
ZA973883B (en)	1997-12-08
NZ332923A (en)	2000-03-27
US6177408B1 (en)	2001-01-23

Legal Events

Date	Code	Title
2002-08-14	FF	Patent granted
2002-08-14	KB	Patent renewed
2003-06-24	KB	Patent renewed
2008-01-06	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0937070B1 (de)	2003-12-03	Benzoheterocyclische distamycinderivate, verfahren zu ihrer herstellung und ihre verwendung als antitumor- und antivirale mittel
EP0912509B1 (de)	2001-07-11	Distamycin derivate, verfahren zu ihrer herstellung sowie ihre verwendung als antitumor und antiviral wirkstoffe
CA2244139C (en)	2005-06-07	Distamycin derivatives, process for preparing them, and their use as antitumor and antiviral agents
NZ220361A (en)	1990-04-26	Distamycin a analogs and pharmaceutical compositions
EP0915845B1 (de)	2001-09-12	Acryloyl-substituierte distamycin-derivate, verfahren zu ihrer herstellung und ihre verwendung als antitumor- und antivirale mittel
EP1064281B1 (de)	2005-05-25	Benzoheterocyclische distamycinderivate, verfahren zu ihrer herstellung und ihre verwendung als antitumormittel
MXPA97001949A (en)	1997-06-01	Derivatives of distamycine substituted with bis- (2-haloethyl) aminophenylene as anatomy agents yantivira
CA2199635A1 (en)	1997-02-06	Bis-(2-haloethyl)aminophenyl substituted distamycin derivatives as antitumor and antiviral agents
WO1999050265A1 (en)	1999-10-07	Acryloyl derivatives analogous to distamycin, process for preparing them, and their use as antitumor agents
EP1100777B1 (de)	2003-05-28	Thioethergruppen enthaltende distamycin-derivate, verfahren zu ihrer herstellung und ihre verwendung als antitumormittel
EP1084120B1 (de)	2004-03-10	Analoga von distamycin-zimtsäurederivaten, verfahren zu ihrer herstellung und ihre verwendung als antitumormittel
KR100469778B1 (ko)	2005-05-16	디스타마이신유도체,이의제조방법,및항종양성및항바이러스성제제로서의이들의용도
MXPA98009426A (en)	1999-10-14	Derivatives of distamycine, processes for the preparation of them and their use as antitumoral agents and antivira
MXPA99000875A (en)	1999-10-14	Acryloyl substituted distamycin derivatives, process for preparing them, and their use as antitumor and antiviral agents
HK1020948B (en)	2003-12-12	Acryloyl substituted distamycin derivatives, process for preparing them, and their use as antitumor and antiviral agents