CA2628040A1 - Alkylcarbamoyl naphthalenyloxy- octenoylhydroxyamide derivatives having inhibitory activity against histone deacetylase and preparation thereof - Google Patents
Alkylcarbamoyl naphthalenyloxy- octenoylhydroxyamide derivatives having inhibitory activity against histone deacetylase and preparation thereof Download PDFInfo
- Publication number
- CA2628040A1 CA2628040A1 CA002628040A CA2628040A CA2628040A1 CA 2628040 A1 CA2628040 A1 CA 2628040A1 CA 002628040 A CA002628040 A CA 002628040A CA 2628040 A CA2628040 A CA 2628040A CA 2628040 A1 CA2628040 A1 CA 2628040A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- yloxy
- naphthalen
- hydroxy
- octenediamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- -1 Alkylcarbamoyl naphthalenyloxy- octenoylhydroxyamide derivatives Chemical class 0.000 title claims abstract description 83
- 102000003964 Histone deacetylase Human genes 0.000 title claims abstract description 26
- 108090000353 Histone deacetylase Proteins 0.000 title claims abstract description 26
- 230000002401 inhibitory effect Effects 0.000 title abstract description 11
- 238000002360 preparation method Methods 0.000 title description 49
- 238000000034 method Methods 0.000 claims abstract description 223
- 150000001875 compounds Chemical class 0.000 claims description 423
- 150000001412 amines Chemical class 0.000 claims description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 32
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 13
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 claims description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical group [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 230000010933 acylation Effects 0.000 claims description 7
- 238000005917 acylation reaction Methods 0.000 claims description 7
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 claims description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 7
- HDUMAEHTJLXNPY-DJKKODMXSA-N (e)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)-n-(thiophen-2-ylmethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NCC1=CC=CS1 HDUMAEHTJLXNPY-DJKKODMXSA-N 0.000 claims description 6
- XMFQQXGTUUFSCH-DHRITJCHSA-N (e)-n-(1-benzylpyrrolidin-3-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC(C1)CCN1CC1=CC=CC=C1 XMFQQXGTUUFSCH-DHRITJCHSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 150000007522 mineralic acids Chemical class 0.000 claims description 6
- 150000007524 organic acids Chemical class 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 5
- LERXQMLCFARRIC-UFFVCSGVSA-N (e)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)-n-(1-propan-2-ylpyrrolidin-3-yl)oct-2-enediamide Chemical compound C1N(C(C)C)CCC1NC(=O)C(=C\CCCCC(=O)NO)\COC1=CC=CC2=CC=CC=C12 LERXQMLCFARRIC-UFFVCSGVSA-N 0.000 claims description 5
- QYDMVJAUGRVBAV-SSDVNMTOSA-N (e)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)-n-(2-piperidin-1-ylethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NCCN1CCCCC1 QYDMVJAUGRVBAV-SSDVNMTOSA-N 0.000 claims description 5
- JFVDRPFRDGMNPX-UFFVCSGVSA-N (e)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)-n-[3-(2-oxopyrrolidin-1-yl)propyl]oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NCCCN1CCCC1=O JFVDRPFRDGMNPX-UFFVCSGVSA-N 0.000 claims description 5
- KYNZFXFAZXHSCE-VXLYETTFSA-N (e)-n'-hydroxy-n-(1-methoxypropan-2-yl)-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC=C2C(OC/C(C(=O)NC(C)COC)=C\CCCCC(=O)NO)=CC=CC2=C1 KYNZFXFAZXHSCE-VXLYETTFSA-N 0.000 claims description 5
- MJKWUXCIQUYXRT-GIJQJNRQSA-N (e)-n'-hydroxy-n-(2-methoxyethyl)-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC=C2C(OC/C(C(=O)NCCOC)=C\CCCCC(=O)NO)=CC=CC2=C1 MJKWUXCIQUYXRT-GIJQJNRQSA-N 0.000 claims description 5
- HOXGFNNYDIAJHI-ODCIPOBUSA-N (e)-n'-hydroxy-n-(2-morpholin-4-ylethyl)-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NCCN1CCOCC1 HOXGFNNYDIAJHI-ODCIPOBUSA-N 0.000 claims description 5
- OMGXVMLJZNVWEK-DJKKODMXSA-N (e)-n'-hydroxy-n-(6-methoxypyridin-3-yl)-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=NC(OC)=CC=C1NC(=O)C(=C\CCCCC(=O)NO)\COC1=CC=CC2=CC=CC=C12 OMGXVMLJZNVWEK-DJKKODMXSA-N 0.000 claims description 5
- AHJMBYSCBHQGEN-LSFURLLWSA-N (e)-n'-hydroxy-n-[(4-methoxyphenyl)methyl]-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC(OC)=CC=C1CNC(=O)C(=C\CCCCC(=O)NO)\COC1=CC=CC2=CC=CC=C12 AHJMBYSCBHQGEN-LSFURLLWSA-N 0.000 claims description 5
- QCQOWAULLDMUBM-BHGWPJFGSA-N (e)-n-(1-cyclohexylpyrrolidin-3-yl)-n'-hydroxy-2-(naphthalen-2-yloxymethyl)oct-2-enediamide Chemical compound C=1C=C2C=CC=CC2=CC=1OC\C(=C/CCCCC(=O)NO)C(=O)NC(C1)CCN1C1CCCCC1 QCQOWAULLDMUBM-BHGWPJFGSA-N 0.000 claims description 5
- DWUWNRYOCMZDCK-AUEPDCJTSA-N (e)-n-(1-cyclopentylpiperidin-4-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC(CC1)CCN1C1CCCC1 DWUWNRYOCMZDCK-AUEPDCJTSA-N 0.000 claims description 5
- ZRMXVNQHSVWJKB-ODCIPOBUSA-N (e)-n-(1-cyclopropylpiperidin-4-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC(CC1)CCN1C1CC1 ZRMXVNQHSVWJKB-ODCIPOBUSA-N 0.000 claims description 5
- PLCUEFKAXZAWRU-DNTJNYDQSA-N (e)-n-(1-cyclopropylpyrrolidin-3-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC(C1)CCN1C1CC1 PLCUEFKAXZAWRU-DNTJNYDQSA-N 0.000 claims description 5
- FBMBRHBJRRMJMS-UFFVCSGVSA-N (e)-n-(1-ethylpiperidin-4-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1CN(CC)CCC1NC(=O)C(=C\CCCCC(=O)NO)\COC1=CC=CC2=CC=CC=C12 FBMBRHBJRRMJMS-UFFVCSGVSA-N 0.000 claims description 5
- JKQFTMSGBHBHQZ-UFFVCSGVSA-N (e)-n-(4-ethoxy-4-hydroxycyclohexa-1,5-dien-1-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC(OCC)(O)CC=C1NC(=O)C(=C\CCCCC(=O)NO)\COC1=CC=CC2=CC=CC=C12 JKQFTMSGBHBHQZ-UFFVCSGVSA-N 0.000 claims description 5
- DHFWZXUVQJZAMP-GIJQJNRQSA-N (e)-n-(furan-2-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC1=CC=CO1 DHFWZXUVQJZAMP-GIJQJNRQSA-N 0.000 claims description 5
- BXHBVPAEUJQWTL-DHRITJCHSA-N (e)-n-[1-(cyclohexylmethyl)pyrrolidin-3-yl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC(C1)CCN1CC1CCCCC1 BXHBVPAEUJQWTL-DHRITJCHSA-N 0.000 claims description 5
- WYGLRWIQXUIFSA-YDZHTSKRSA-N (e)-n-[2-(cyclohexen-1-yl)ethyl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NCCC1=CCCCC1 WYGLRWIQXUIFSA-YDZHTSKRSA-N 0.000 claims description 5
- SKPWWXCTAJXHBE-CIAFOILYSA-N (e)-n-[3-(dimethylamino)-2,2-dimethylpropyl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC=C2C(OC/C(C(=O)NCC(C)(C)CN(C)C)=C\CCCCC(=O)NO)=CC=CC2=C1 SKPWWXCTAJXHBE-CIAFOILYSA-N 0.000 claims description 5
- AUGCSOFQTDKPSO-RGVLZGJSSA-N (e)-n-[3-(dimethylamino)propyl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC=C2C(OC/C(C(=O)NCCCN(C)C)=C\CCCCC(=O)NO)=CC=CC2=C1 AUGCSOFQTDKPSO-RGVLZGJSSA-N 0.000 claims description 5
- NIFZMNPKVPWAMX-AUEPDCJTSA-N (e)-n-[[4-(dimethylamino)phenyl]methyl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC(N(C)C)=CC=C1CNC(=O)C(=C\CCCCC(=O)NO)\COC1=CC=CC2=CC=CC=C12 NIFZMNPKVPWAMX-AUEPDCJTSA-N 0.000 claims description 5
- PUBJTMOEOWHHLN-RGVLZGJSSA-N (e)-n-cyclohexyl-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC1CCCCC1 PUBJTMOEOWHHLN-RGVLZGJSSA-N 0.000 claims description 5
- GIWTZPKFKWISHH-YIXHJXPBSA-N (e)-n-hydroxy-8-(4-methylpiperazin-1-yl)-7-(naphthalen-1-yloxymethyl)-8-oxooct-2-enamide Chemical compound C1CN(C)CCN1C(=O)C(CCC\C=C\C(=O)NO)COC1=CC=CC2=CC=CC=C12 GIWTZPKFKWISHH-YIXHJXPBSA-N 0.000 claims description 5
- IIFGBVMCTLXABQ-KGVSQERTSA-N (e)-n-hydroxy-8-morpholin-4-yl-7-(naphthalen-1-yloxymethyl)-8-oxooct-2-enamide Chemical compound C=1C=CC2=CC=CC=C2C=1OCC(CCC/C=C/C(=O)NO)C(=O)N1CCOCC1 IIFGBVMCTLXABQ-KGVSQERTSA-N 0.000 claims description 5
- LDJNXXPHZUQXET-UHFFFAOYSA-N FC1(CC=C(C=C1)NC(C(=CCCCCC(=O)NO)COC1=CC=CC2=CC=CC=C12)=O)OCC Chemical compound FC1(CC=C(C=C1)NC(C(=CCCCCC(=O)NO)COC1=CC=CC2=CC=CC=C12)=O)OCC LDJNXXPHZUQXET-UHFFFAOYSA-N 0.000 claims description 5
- 229910020667 PBr3 Inorganic materials 0.000 claims description 5
- 125000005250 alkyl acrylate group Chemical group 0.000 claims description 5
- 230000001093 anti-cancer Effects 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 5
- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 claims description 5
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 4
- VLERWGIRJCSZBV-ODCIPOBUSA-N (e)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)-n-[[4-(trifluoromethoxy)phenyl]methyl]oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NCC1=CC=C(OC(F)(F)F)C=C1 VLERWGIRJCSZBV-ODCIPOBUSA-N 0.000 claims description 4
- BTXIRHGRWJVJEZ-ZMOGYAJESA-N (e)-n-[1-(cyclohexanecarbonyl)pyrrolidin-3-yl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC(C1)CCN1C(=O)C1CCCCC1 BTXIRHGRWJVJEZ-ZMOGYAJESA-N 0.000 claims description 4
- BSCYXQIPEYZODK-UHFFFAOYSA-N 3-(diethylamino)propyl-(ethyliminomethylidene)azanium;chloride Chemical compound Cl.CCN=C=NCCCN(CC)CC BSCYXQIPEYZODK-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 150000007529 inorganic bases Chemical class 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 4
- SPFCWPYSSCVUAF-ZVBGSRNCSA-N (e)-n'-hydroxy-n-(3-imidazol-1-ylpropyl)-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NCCCN1C=CN=C1 SPFCWPYSSCVUAF-ZVBGSRNCSA-N 0.000 claims description 3
- WJJUFDWLJQELQD-QGMBQPNBSA-N 3-[[(e)-8-(hydroxyamino)-2-(naphthalen-1-yloxymethyl)-8-oxooct-2-enoyl]amino]pyrrolidine-1-carboxylic acid Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC1CCN(C(O)=O)C1 WJJUFDWLJQELQD-QGMBQPNBSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 150000003235 pyrrolidines Chemical group 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000006636 (C3-C8) cycloalkylcarbonyl group Chemical group 0.000 claims description 2
- OXXIMKIBPBGDBZ-QGMBQPNBSA-N (e)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)-n-pyrrolidin-3-yloct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC\C(=C/CCCCC(=O)NO)C(=O)NC1CCNC1 OXXIMKIBPBGDBZ-QGMBQPNBSA-N 0.000 claims description 2
- QKBPIIMDVOBGJW-KEBDBYFISA-N (e)-n'-hydroxy-n-methyl-n-(1-methylpyrrolidin-3-yl)-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C=1C=CC2=CC=CC=C2C=1OC/C(=C\CCCCC(=O)NO)C(=O)N(C)C1CCN(C)C1 QKBPIIMDVOBGJW-KEBDBYFISA-N 0.000 claims description 2
- CKTLNGMIRRQTRD-KEBDBYFISA-N (e)-n-(1-ethylpyrrolidin-3-yl)-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1N(CC)CCC1NC(=O)C(=C\CCCCC(=O)NO)\COC1=CC=CC2=CC=CC=C12 CKTLNGMIRRQTRD-KEBDBYFISA-N 0.000 claims description 2
- VEMWMZCBSGFTJY-VXLYETTFSA-N (e)-n-[2-(dimethylamino)ethyl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC=C2C(OC/C(C(=O)NCCN(C)C)=C\CCCCC(=O)NO)=CC=CC2=C1 VEMWMZCBSGFTJY-VXLYETTFSA-N 0.000 claims description 2
- OGKNLQBPNNUKFC-RGVLZGJSSA-N (e)-n-[2-(dimethylamino)ethyl]-n'-hydroxy-n-methyl-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC=C2C(OC/C(C(=O)N(C)CCN(C)C)=C\CCCCC(=O)NO)=CC=CC2=C1 OGKNLQBPNNUKFC-RGVLZGJSSA-N 0.000 claims description 2
- OSHBDRAUCLJVJY-FSJBWODESA-N (e)-n-[2-[di(propan-2-yl)amino]ethyl]-n'-hydroxy-2-(naphthalen-1-yloxymethyl)oct-2-enediamide Chemical compound C1=CC=C2C(OC/C(C(=O)NCCN(C(C)C)C(C)C)=C\CCCCC(=O)NO)=CC=CC2=C1 OSHBDRAUCLJVJY-FSJBWODESA-N 0.000 claims description 2
- OKAMTPRCXVGTND-UHFFFAOYSA-N 2-methoxyoxolane Chemical compound COC1CCCO1 OKAMTPRCXVGTND-UHFFFAOYSA-N 0.000 claims description 2
- CFVWNXQPGQOHRJ-UHFFFAOYSA-N 2-methylpropyl prop-2-enoate Chemical compound CC(C)COC(=O)C=C CFVWNXQPGQOHRJ-UHFFFAOYSA-N 0.000 claims description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 2
- FKMUKFBHNSAVFW-UHFFFAOYSA-N [6-(trifluoromethyl)benzotriazol-1-yl] methanesulfonate Chemical compound C1=C(C(F)(F)F)C=C2N(OS(=O)(=O)C)N=NC2=C1 FKMUKFBHNSAVFW-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
- XNZFUKOVJVOLPE-UHFFFAOYSA-N furan;pyridine Chemical group C=1C=COC=1.C1=CC=NC=C1 XNZFUKOVJVOLPE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 150000003053 piperidines Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 claims description 2
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 230000007062 hydrolysis Effects 0.000 claims 2
- 238000006460 hydrolysis reaction Methods 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims 1
- 239000012964 benzotriazole Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 5
- 102000004190 Enzymes Human genes 0.000 abstract description 4
- 108090000790 Enzymes Proteins 0.000 abstract description 4
- 230000001629 suppression Effects 0.000 abstract description 4
- 230000009702 cancer cell proliferation Effects 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 151
- 239000007858 starting material Substances 0.000 description 147
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 111
- 239000002253 acid Substances 0.000 description 107
- 101150041968 CDC13 gene Proteins 0.000 description 105
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 105
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 81
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 69
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 48
- 150000004702 methyl esters Chemical class 0.000 description 48
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 47
- 238000005160 1H NMR spectroscopy Methods 0.000 description 35
- 238000000746 purification Methods 0.000 description 30
- 238000004128 high performance liquid chromatography Methods 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 26
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 20
- 150000003839 salts Chemical class 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 238000010898 silica gel chromatography Methods 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 15
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 11
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 11
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 11
- 229960000237 vorinostat Drugs 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 229940035423 ethyl ether Drugs 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- SXQCTESRRZBPHJ-UHFFFAOYSA-M lissamine rhodamine Chemical compound [Na+].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S([O-])(=O)=O)C=C1S([O-])(=O)=O SXQCTESRRZBPHJ-UHFFFAOYSA-M 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108010033040 Histones Proteins 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- SYBUMHRMIXCULT-UHFFFAOYSA-N tert-butyl n-(1-cyclopropylpyrrolidin-3-yl)carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C1CC1 SYBUMHRMIXCULT-UHFFFAOYSA-N 0.000 description 4
- SYXBLASQKPONBN-UHFFFAOYSA-N tert-butyl n-(1-propan-2-ylpiperidin-4-yl)carbamate Chemical compound CC(C)N1CCC(NC(=O)OC(C)(C)C)CC1 SYXBLASQKPONBN-UHFFFAOYSA-N 0.000 description 4
- 229940086542 triethylamine Drugs 0.000 description 4
- FOMMHHOTNLKIKT-UHFFFAOYSA-N (3-aminopyrrolidin-1-yl)-cyclohexylmethanone Chemical compound C1C(N)CCN1C(=O)C1CCCCC1 FOMMHHOTNLKIKT-UHFFFAOYSA-N 0.000 description 3
- DPEPZAJVZHRORQ-UHFFFAOYSA-N 1-cyclohexylpyrrolidin-3-amine Chemical compound C1C(N)CCN1C1CCCCC1 DPEPZAJVZHRORQ-UHFFFAOYSA-N 0.000 description 3
- HJJXAKRPWXVQGP-UHFFFAOYSA-N 1-cyclopentylpiperidin-4-amine Chemical compound C1CC(N)CCN1C1CCCC1 HJJXAKRPWXVQGP-UHFFFAOYSA-N 0.000 description 3
- XQRNOQYMHPJDCY-UHFFFAOYSA-N 1-cyclopropylpiperidin-4-amine Chemical compound C1CC(N)CCN1C1CC1 XQRNOQYMHPJDCY-UHFFFAOYSA-N 0.000 description 3
- PISMTKYGUDKXTE-UHFFFAOYSA-N 1-cyclopropylpyrrolidin-3-amine Chemical compound C1C(N)CCN1C1CC1 PISMTKYGUDKXTE-UHFFFAOYSA-N 0.000 description 3
- UFETTXCVHFVMPU-UHFFFAOYSA-N 1-ethylpiperidin-4-amine Chemical compound CCN1CCC(N)CC1 UFETTXCVHFVMPU-UHFFFAOYSA-N 0.000 description 3
- GOLVGZOPWLLUSF-UHFFFAOYSA-N 1-ethylpyrrolidin-3-amine Chemical compound CCN1CCC(N)C1 GOLVGZOPWLLUSF-UHFFFAOYSA-N 0.000 description 3
- SYMMPPWYYXRLJX-UHFFFAOYSA-N 1-propan-2-ylpyrrolidin-3-amine Chemical compound CC(C)N1CCC(N)C1 SYMMPPWYYXRLJX-UHFFFAOYSA-N 0.000 description 3
- OQBSJVBSUDKKCY-UHFFFAOYSA-N 2-pyrrolidin-3-yloct-2-enediamide Chemical compound NC(=O)CCCCC=C(C(N)=O)C1CCNC1 OQBSJVBSUDKKCY-UHFFFAOYSA-N 0.000 description 3
- 108010077544 Chromatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000006947 Histones Human genes 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 210000003483 chromatin Anatomy 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000006197 histone deacetylation Effects 0.000 description 3
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 3
- FXNPTFPQWVTMTN-SRZZPIQSSA-N (E)-1-(4-methylpiperazin-1-yl)-2-(naphthalen-1-yloxymethyl)oct-2-en-1-one Chemical compound CN1CCN(CC1)C(/C(=C/CCCCC)/COC1=CC=CC2=CC=CC=C12)=O FXNPTFPQWVTMTN-SRZZPIQSSA-N 0.000 description 2
- LIJLLDUDSVHFMZ-LDADJPATSA-N (E)-N,N-dimethyl-2-(naphthalen-1-yloxymethyl)oct-2-enamide Chemical compound CN(C(/C(=C/CCCCC)/COC1=CC=CC2=CC=CC=C12)=O)C LIJLLDUDSVHFMZ-LDADJPATSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ALOCUZOKRULSAA-UHFFFAOYSA-N 1-methylpiperidin-4-amine Chemical compound CN1CCC(N)CC1 ALOCUZOKRULSAA-UHFFFAOYSA-N 0.000 description 2
- ZRQQXFMGYSOKDF-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-amine Chemical compound CC(C)N1CCC(N)CC1 ZRQQXFMGYSOKDF-UHFFFAOYSA-N 0.000 description 2
- YSMWBHMJDOYACP-UHFFFAOYSA-N 2-(oxan-2-yloxy)oct-2-enediamide Chemical compound O1C(CCCC1)OC(C(=O)N)=CCCCCC(=O)N YSMWBHMJDOYACP-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- MKSTXMDSWOHKOR-UHFFFAOYSA-N 3-aminopyrrolidine-1-carboxylic acid Chemical compound NC1CCN(C(O)=O)C1 MKSTXMDSWOHKOR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000003893 Histone acetyltransferases Human genes 0.000 description 2
- 108090000246 Histone acetyltransferases Proteins 0.000 description 2
- 101000687448 Homo sapiens REST corepressor 1 Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 102100024864 REST corepressor 1 Human genes 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- LKXYJYDRLBPHRS-UHFFFAOYSA-N bromocyclopropane Chemical compound BrC1CC1 LKXYJYDRLBPHRS-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000006911 enzymatic reaction Methods 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- ATLBQTPBCVSZGU-UHFFFAOYSA-N methyl 6-hydroxyhex-2-enoate Chemical compound COC(=O)C=CCCCO ATLBQTPBCVSZGU-UHFFFAOYSA-N 0.000 description 2
- FDNFXHCDOASWAY-UHFFFAOYSA-N methyl 6-oxohexanoate Chemical compound COC(=O)CCCCC=O FDNFXHCDOASWAY-UHFFFAOYSA-N 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- WFKLUNLIZMWKNF-UHFFFAOYSA-N tert-butyl n-(1-benzylpiperidin-4-yl)carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1CC1=CC=CC=C1 WFKLUNLIZMWKNF-UHFFFAOYSA-N 0.000 description 2
- OWXMMRQDSKAHST-UHFFFAOYSA-N tert-butyl n-(1-cyclohexylpyrrolidin-3-yl)carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C1CCCCC1 OWXMMRQDSKAHST-UHFFFAOYSA-N 0.000 description 2
- XNNYFIMWBZGFIW-UHFFFAOYSA-N tert-butyl n-(1-cyclopentylpiperidin-4-yl)carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C1CCCC1 XNNYFIMWBZGFIW-UHFFFAOYSA-N 0.000 description 2
- QHPWESLNMUXZMX-UHFFFAOYSA-N tert-butyl n-(1-cyclopropylpiperidin-4-yl)carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)CCN1C1CC1 QHPWESLNMUXZMX-UHFFFAOYSA-N 0.000 description 2
- JUOXFFYHDMNFHE-UHFFFAOYSA-N tert-butyl n-(1-ethylpiperidin-4-yl)carbamate Chemical compound CCN1CCC(NC(=O)OC(C)(C)C)CC1 JUOXFFYHDMNFHE-UHFFFAOYSA-N 0.000 description 2
- WYPHJLKRZSTDMH-UHFFFAOYSA-N tert-butyl n-(1-ethylpyrrolidin-3-yl)carbamate Chemical compound CCN1CCC(NC(=O)OC(C)(C)C)C1 WYPHJLKRZSTDMH-UHFFFAOYSA-N 0.000 description 2
- IFWALANQXAWVQS-UHFFFAOYSA-N tert-butyl n-(1-methylpiperidin-4-yl)carbamate Chemical compound CN1CCC(NC(=O)OC(C)(C)C)CC1 IFWALANQXAWVQS-UHFFFAOYSA-N 0.000 description 2
- MMINECTYWKHJNS-UHFFFAOYSA-N tert-butyl n-[1-(cyclohexanecarbonyl)pyrrolidin-3-yl]carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1C(=O)C1CCCCC1 MMINECTYWKHJNS-UHFFFAOYSA-N 0.000 description 2
- DQQJBEAXSOOCPG-UHFFFAOYSA-N tert-butyl n-pyrrolidin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNC1 DQQJBEAXSOOCPG-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- RTKIYFITIVXBLE-QEQCGCAPSA-N trichostatin A Chemical compound ONC(=O)/C=C/C(/C)=C/[C@@H](C)C(=O)C1=CC=C(N(C)C)C=C1 RTKIYFITIVXBLE-QEQCGCAPSA-N 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
- JWOGUUIOCYMBPV-GMFLJSBRSA-N (3S,6S,9S,12R)-3-[(2S)-Butan-2-yl]-6-[(1-methoxyindol-3-yl)methyl]-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone Chemical compound N1C(=O)[C@H](CCCCCC(=O)CC)NC(=O)[C@H]2CCCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]1CC1=CN(OC)C2=CC=CC=C12 JWOGUUIOCYMBPV-GMFLJSBRSA-N 0.000 description 1
- PGLBECGNJJOIMN-YBFXNURJSA-N (E)-N-(2-hydroxyethyl)-N-methyl-2-(naphthalen-1-yloxymethyl)oct-2-enamide Chemical compound OCCN(C(/C(=C/CCCCC)/COC1=CC=CC2=CC=CC=C12)=O)C PGLBECGNJJOIMN-YBFXNURJSA-N 0.000 description 1
- SGCDUQZMWQBVFU-LSHDLFTRSA-N (E)-N-(2-morpholin-4-ylethyl)-2-(naphthalen-1-yloxymethyl)oct-2-enamide Chemical compound O1CCN(CC1)CCNC(/C(=C/CCCCC)/COC1=CC=CC2=CC=CC=C12)=O SGCDUQZMWQBVFU-LSHDLFTRSA-N 0.000 description 1
- WXMIBRJGLKWZQH-HZHRSRAPSA-N (E)-N-[2-(diethylamino)ethyl]-N-methyl-2-(naphthalen-1-yloxymethyl)oct-2-enamide Chemical compound C(C)N(CCN(C(/C(=C/CCCCC)/COC1=CC=CC2=CC=CC=C12)=O)C)CC WXMIBRJGLKWZQH-HZHRSRAPSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- PVJMGFMLSTXKKY-WKULSOCRSA-N (e)-n-(1-benzylpyrrolidin-3-yl)-2-(naphthalen-1-yloxymethyl)-n'-(oxan-2-yloxy)oct-2-enediamide Chemical compound C1CCCOC1ONC(=O)CCCC\C=C(/COC=1C2=CC=CC=C2C=CC=1)C(=O)NC(C1)CCN1CC1=CC=CC=C1 PVJMGFMLSTXKKY-WKULSOCRSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- HJORCZCMNWLHMB-UHFFFAOYSA-N 1-(3-aminopropyl)pyrrolidin-2-one Chemical compound NCCCN1CCCC1=O HJORCZCMNWLHMB-UHFFFAOYSA-N 0.000 description 1
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
- SBSSXCKDVHHANA-UHFFFAOYSA-N 1-(cyclohexylmethyl)pyrrolidin-3-amine Chemical compound C1C(N)CCN1CC1CCCCC1 SBSSXCKDVHHANA-UHFFFAOYSA-N 0.000 description 1
- YUBDLZGUSSWQSS-UHFFFAOYSA-N 1-benzylpiperidin-4-amine Chemical compound C1CC(N)CCN1CC1=CC=CC=C1 YUBDLZGUSSWQSS-UHFFFAOYSA-N 0.000 description 1
- QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 0.000 description 1
- NXMXETCTWNXSFG-UHFFFAOYSA-N 1-methoxypropan-2-amine Chemical compound COCC(C)N NXMXETCTWNXSFG-UHFFFAOYSA-N 0.000 description 1
- UNHOPMIDKWXFMF-UHFFFAOYSA-N 1-methylpyrrolidin-3-amine Chemical compound CN1CCC(N)C1 UNHOPMIDKWXFMF-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- OKIDBHHMCXAYLN-UHFFFAOYSA-N 1-phenyl-n-(trifluoromethoxy)methanamine Chemical compound FC(F)(F)ONCC1=CC=CC=C1 OKIDBHHMCXAYLN-UHFFFAOYSA-N 0.000 description 1
- OFZVOZGWCBEPBB-UHFFFAOYSA-N 2,3,4,5-tetrabutylfuran Chemical compound CCCCC=1OC(CCCC)=C(CCCC)C=1CCCC OFZVOZGWCBEPBB-UHFFFAOYSA-N 0.000 description 1
- GOWUDHPKGOIDIX-UHFFFAOYSA-N 2-(4-methyl-1-piperazinyl)ethanamine Chemical compound CN1CCN(CCN)CC1 GOWUDHPKGOIDIX-UHFFFAOYSA-N 0.000 description 1
- IUDMXOOVKMKODN-UHFFFAOYSA-N 2-(cyclohexen-1-yl)ethanamine Chemical compound NCCC1=CCCCC1 IUDMXOOVKMKODN-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- OBOSXEWFRARQPU-UHFFFAOYSA-N 2-n,2-n-dimethylpyridine-2,5-diamine Chemical compound CN(C)C1=CC=C(N)C=N1 OBOSXEWFRARQPU-UHFFFAOYSA-N 0.000 description 1
- AASLFZACKQKOAQ-UHFFFAOYSA-N 2-n-[2-(dimethylamino)ethyl]pyridine-2,5-diamine Chemical compound CN(C)CCNC1=CC=C(N)C=N1 AASLFZACKQKOAQ-UHFFFAOYSA-N 0.000 description 1
- CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 1
- PDJZOFLRRJQYBF-UHFFFAOYSA-N 4-(aminomethyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(CN)C=C1 PDJZOFLRRJQYBF-UHFFFAOYSA-N 0.000 description 1
- NKTAQFHZUKHHPT-UHFFFAOYSA-N 4-amino-1-ethoxycyclohexa-2,4-dien-1-ol Chemical compound CCOC1(O)CC=C(N)C=C1 NKTAQFHZUKHHPT-UHFFFAOYSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- DPOILWCKMSWUOX-UHFFFAOYSA-N 4-ethoxy-4-fluorocyclohexa-1,5-dien-1-amine Chemical compound CCOC1(F)CC=C(N)C=C1 DPOILWCKMSWUOX-UHFFFAOYSA-N 0.000 description 1
- VUVSPPNEKMQHAB-UHFFFAOYSA-N 4-ethoxy-4-methoxycyclohexa-1,5-dien-1-amine Chemical compound CCOC1(OC)CC=C(N)C=C1 VUVSPPNEKMQHAB-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- RJWLLQWLBMJCFD-UHFFFAOYSA-N 4-methylpiperazin-1-amine Chemical compound CN1CCN(N)CC1 RJWLLQWLBMJCFD-UHFFFAOYSA-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
- NZTCEWZBMOTKCJ-UHFFFAOYSA-N 6-(4-methylpiperazin-1-yl)pyridin-3-amine Chemical compound C1CN(C)CCN1C1=CC=C(N)C=N1 NZTCEWZBMOTKCJ-UHFFFAOYSA-N 0.000 description 1
- UUVDJIWRSIJEBS-UHFFFAOYSA-N 6-methoxypyridin-3-amine Chemical compound COC1=CC=C(N)C=N1 UUVDJIWRSIJEBS-UHFFFAOYSA-N 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101100459319 Arabidopsis thaliana VIII-2 gene Proteins 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 238000005712 Baylis-Hillman reaction Methods 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- BPUQSVHKVSDVSQ-BHGWPJFGSA-N CN1CCN(CC1)C(/C(=C/CCCCC(=O)NOC1OCCCC1)/COC1=CC=CC2=CC=CC=C12)=O Chemical compound CN1CCN(CC1)C(/C(=C/CCCCC(=O)NOC1OCCCC1)/COC1=CC=CC2=CC=CC=C12)=O BPUQSVHKVSDVSQ-BHGWPJFGSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 description 1
- 208000036566 Erythroleukaemia Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229940122498 Gene expression inhibitor Drugs 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 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 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 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
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- KKKCRSKYYRFFLL-UHFFFAOYSA-N N-naphthalen-1-ylperoxyoct-2-enamide Chemical class CCCCCC=CC(=O)NOOC1=CC=CC2=CC=CC=C21 KKKCRSKYYRFFLL-UHFFFAOYSA-N 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- JWOGUUIOCYMBPV-UHFFFAOYSA-N OT-Key 11219 Natural products N1C(=O)C(CCCCCC(=O)CC)NC(=O)C2CCCCN2C(=O)C(C(C)CC)NC(=O)C1CC1=CN(OC)C2=CC=CC=C12 JWOGUUIOCYMBPV-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 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
- 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
- 229920001615 Tragacanth Polymers 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000021841 acute erythroid leukemia Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229930186608 apicidin Natural products 0.000 description 1
- 108010082820 apicidin Proteins 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 201000006662 cervical adenocarcinoma Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 238000003381 deacetylation reaction Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- UTVVREMVDJTZAC-UHFFFAOYSA-N furan-2-amine Chemical compound NC1=CC=CO1 UTVVREMVDJTZAC-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 239000000815 hypotonic solution Substances 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000011061 large intestine cancer Diseases 0.000 description 1
- VVNXEADCOVSAER-UHFFFAOYSA-N lithium sodium Chemical compound [Li].[Na] VVNXEADCOVSAER-UHFFFAOYSA-N 0.000 description 1
- WAZWGFFJLSIDMX-UHFFFAOYSA-M lithium;iodide;hydrate Chemical compound [Li+].O.[I-] WAZWGFFJLSIDMX-UHFFFAOYSA-M 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- VIPCJSCBXJTMQM-UHFFFAOYSA-N methyl 6-oxohex-2-enoate Chemical compound COC(=O)C=CCCC=O VIPCJSCBXJTMQM-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
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- MKQLBNJQQZRQJU-UHFFFAOYSA-N morpholin-4-amine Chemical compound NN1CCOCC1 MKQLBNJQQZRQJU-UHFFFAOYSA-N 0.000 description 1
- ULDIVZQLPBUHAG-UHFFFAOYSA-N n',n',2,2-tetramethylpropane-1,3-diamine Chemical compound CN(C)CC(C)(C)CN ULDIVZQLPBUHAG-UHFFFAOYSA-N 0.000 description 1
- CURJNMSGPBXOGK-UHFFFAOYSA-N n',n'-di(propan-2-yl)ethane-1,2-diamine Chemical compound CC(C)N(C(C)C)CCN CURJNMSGPBXOGK-UHFFFAOYSA-N 0.000 description 1
- MKDYQLJYEBWUIG-UHFFFAOYSA-N n',n'-diethyl-n-methylethane-1,2-diamine Chemical compound CCN(CC)CCNC MKDYQLJYEBWUIG-UHFFFAOYSA-N 0.000 description 1
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- NFLXIAUKMQBTMN-UHFFFAOYSA-N n-benzylpyrrolidin-3-amine Chemical compound C=1C=CC=CC=1CNC1CCNC1 NFLXIAUKMQBTMN-UHFFFAOYSA-N 0.000 description 1
- 230000019569 negative regulation of cell differentiation Effects 0.000 description 1
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- SSUCKKNRCOFUPT-UHFFFAOYSA-N o-[tert-butyl(dimethyl)silyl]hydroxylamine Chemical compound CC(C)(C)[Si](C)(C)ON SSUCKKNRCOFUPT-UHFFFAOYSA-N 0.000 description 1
- LVBXEMGDVWVTGY-UHFFFAOYSA-N oct-2-enal Chemical compound CCCCCC=CC=O LVBXEMGDVWVTGY-UHFFFAOYSA-N 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
- 102000027450 oncoproteins Human genes 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 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
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- PHOIDJGLYWEUEK-UHFFFAOYSA-N tert-butyl n-(1-benzylpyrrolidin-3-yl)carbamate Chemical compound C1C(NC(=O)OC(C)(C)C)CCN1CC1=CC=CC=C1 PHOIDJGLYWEUEK-UHFFFAOYSA-N 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
-
- 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/10—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 no 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
- C07D207/12—Oxygen or sulfur atoms
-
- 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/10—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 no 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
- C07D307/66—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Hydrogenated Pyridines (AREA)
- Furan Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2005-0103693 | 2005-11-01 | ||
KR1020050103693A KR100696139B1 (ko) | 2005-11-01 | 2005-11-01 | 히스톤 디아세틸라제 저해활성을 갖는 알킬카바모일나프탈렌일옥시 옥테노일 하이드록시아마이드 유도체 및그의 제조방법 |
PCT/KR2006/004482 WO2007052938A1 (en) | 2005-11-01 | 2006-10-31 | Alkylcarbamoyl naphthalenyloxy- octenoylhydroxyamide derivatives having inhibitory activity against histone deacetylase and preparation thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2628040A1 true CA2628040A1 (en) | 2007-05-10 |
Family
ID=38006052
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002628040A Abandoned CA2628040A1 (en) | 2005-11-01 | 2006-10-31 | Alkylcarbamoyl naphthalenyloxy- octenoylhydroxyamide derivatives having inhibitory activity against histone deacetylase and preparation thereof |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1945606A4 (pt) |
JP (1) | JP2009513697A (pt) |
KR (1) | KR100696139B1 (pt) |
CN (1) | CN101300226B (pt) |
BR (1) | BRPI0618131A2 (pt) |
CA (1) | CA2628040A1 (pt) |
WO (1) | WO2007052938A1 (pt) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11655207B2 (en) | 2017-06-15 | 2023-05-23 | Crystalgenomics, Inc. | Pharmaceutically acceptable salt of alkylcarbamoyl naphthalenyloxy octenoylhydroxy amide or of derivative thereof and method for preparing same |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100814092B1 (ko) | 2006-11-03 | 2008-03-14 | 한국화학연구원 | 히스톤 디아세틸라제 저해활성을 갖는 알킬카바모일나프탈렌일옥시 옥테노일 하이드록시아마이드 유도체, 이의제조방법 및 이를 유효성분으로 하는 항암제용 약학조성물 |
WO2008054154A1 (en) * | 2006-11-03 | 2008-05-08 | Korea Research Institute Of Chemical Technology | Naphthalenyloxypropenyl derivatives having inhibitory activity against histone deacetylase and pharmaceutical composition comprising the same |
RU2453536C2 (ru) * | 2007-10-22 | 2012-06-20 | Оркид Рисерч Лабораториз Лимитед | Ингибиторы гистондезацетилазы |
EP2112152A1 (en) | 2008-04-22 | 2009-10-28 | GPC Biotech AG | Dihydropteridinones as Plk Inhibitors |
WO2010067980A2 (ko) * | 2008-12-11 | 2010-06-17 | 대한민국(관리부서 질병관리본부장) | 잠복성 hiv 감염 세포에서 hiv-1 프로바이러스를 재활성화시키는 히스톤 디아세틸라제 억제제 |
KR20190113639A (ko) * | 2018-03-28 | 2019-10-08 | 크리스탈지노믹스(주) | 섬유화증 예방 또는 치료용 약학 조성물 |
JP2022504055A (ja) * | 2018-10-29 | 2022-01-13 | クリスタルジェノミクス・インコーポレイテッド | アルキルカルバモイルナフタレンイルオキシオクテノイルヒドロキシアミドリン酸塩、酒石酸塩またはこれらの組み合わせを含む薬剤学的組成物及びその製造方法 |
CN110105213B (zh) * | 2019-06-06 | 2022-03-25 | 唐山师范学院 | 一种(e)-2-(萘基-1-氧甲基)-2-二辛烯酸-8-酯的合成方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2383999A1 (en) * | 1999-09-08 | 2001-03-15 | Sloan-Kettering Institute For Cancer Research | Novel class of cytodifferentiating agents and histone deacetylase inhibitors, and methods of use thereof |
CA2404002A1 (en) * | 2000-03-24 | 2001-09-27 | Methylgene, Inc. | Inhibitors of histone deacetylase |
KR20040090979A (ko) * | 2002-03-13 | 2004-10-27 | 얀센 파마슈티카 엔.브이. | 히스톤 데아세틸레이즈의 신규한 억제제 |
CA2476067C (en) * | 2002-03-13 | 2011-09-20 | Janssen Pharmaceutica N.V. | Carbonylamino-derivatives as novel inhibitors of histone deacetylase |
WO2003087066A1 (en) * | 2002-04-11 | 2003-10-23 | Sk Chemicals, Co., Ltd. | α,β-UNSATURATED HYDROXAMIC ACID DERIVATIVES AND THEIR USE AS HISTONE DEACETYLASE INHIBITORS |
ITMI20030025A1 (it) * | 2003-01-10 | 2004-07-11 | Italfarmaco Spa | Derivati dell'acido idrossammico ad attivita' antinfiammatoria. |
JP4612621B2 (ja) * | 2003-01-17 | 2011-01-12 | トポターゲット ユーケー リミテッド | Hdac阻害剤としてのエステル又はケトン結合を含むカルバミン酸化合物 |
US7652036B2 (en) * | 2003-02-25 | 2010-01-26 | Topotarget Uk Limited | Carbamic acid compounds comprising a bicyclic heteroaryl group as HDAC inhibitors |
-
2005
- 2005-11-01 KR KR1020050103693A patent/KR100696139B1/ko not_active IP Right Cessation
-
2006
- 2006-10-31 WO PCT/KR2006/004482 patent/WO2007052938A1/en active Application Filing
- 2006-10-31 BR BRPI0618131-7A patent/BRPI0618131A2/pt not_active IP Right Cessation
- 2006-10-31 JP JP2008538811A patent/JP2009513697A/ja not_active Withdrawn
- 2006-10-31 CN CN2006800407666A patent/CN101300226B/zh active Active
- 2006-10-31 CA CA002628040A patent/CA2628040A1/en not_active Abandoned
- 2006-10-31 EP EP06812321A patent/EP1945606A4/en not_active Withdrawn
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11655207B2 (en) | 2017-06-15 | 2023-05-23 | Crystalgenomics, Inc. | Pharmaceutically acceptable salt of alkylcarbamoyl naphthalenyloxy octenoylhydroxy amide or of derivative thereof and method for preparing same |
Also Published As
Publication number | Publication date |
---|---|
CN101300226A (zh) | 2008-11-05 |
KR100696139B1 (ko) | 2007-03-20 |
EP1945606A4 (en) | 2010-05-05 |
CN101300226B (zh) | 2012-05-30 |
WO2007052938A1 (en) | 2007-05-10 |
BRPI0618131A2 (pt) | 2011-08-16 |
JP2009513697A (ja) | 2009-04-02 |
EP1945606A1 (en) | 2008-07-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2628040A1 (en) | Alkylcarbamoyl naphthalenyloxy- octenoylhydroxyamide derivatives having inhibitory activity against histone deacetylase and preparation thereof | |
US5391577A (en) | N-phenylalkyl substituted α-amino carboxamide derivatives and process for their preparation | |
US5756817A (en) | O-carbamoyl-phenylalaninol compounds, their pharmaceutically useful salts and process for preparing the same | |
US20020045749A1 (en) | Antibacterial agents | |
KR20030059084A (ko) | 카르복사미드 화합물 및 이것의 사람 11cby 수용체의길항제로서의 용도 | |
NZ548530A (en) | Aryloxyalkylcarbamate-type derivatives, preparation method thereof and use of same in therapeutics | |
CA2596613A1 (fr) | Derives de n-[(4, 5-diphenyl-3 -alkyl-2-thienyl) methyl] amine (amide , thiouree et uree) comme antagonistes des recepteurs cb1 des cannabinoides | |
DE60306934T2 (de) | Verwendung von Nitrilenverbindungen als Arzneimittel | |
US7019003B2 (en) | Peptide deformylase inhibitors | |
US8853281B2 (en) | Cysteine protease inhibitors | |
EP0326106B1 (en) | Alkylene diamines | |
SI9620039A (sl) | Spojine pirolidinil hidroksamske kisline in postopek pridobivanja | |
KR100814092B1 (ko) | 히스톤 디아세틸라제 저해활성을 갖는 알킬카바모일나프탈렌일옥시 옥테노일 하이드록시아마이드 유도체, 이의제조방법 및 이를 유효성분으로 하는 항암제용 약학조성물 | |
US7375120B2 (en) | Peptide deformylase inhibitors | |
ES2346964T3 (es) | Derivados del acido hidroxamico. | |
WO2004052919A2 (en) | Peptide deformylase inhibitors | |
FR2911136A1 (fr) | Derives de n-(4-cyano-1h-pyrazol-3-yl)methylamine substitues leur preparation et leur application en therapeutique. | |
CN113121417A (zh) | 一种新型哌啶衍生物及其药物用途 | |
EP2582660B1 (en) | New cathepsin s protease inhibitors, useful in the treatment of e.g. autoimmune disorders, allergy and chronic pain conditions | |
US6797730B2 (en) | Peptide deformylase inhibitors | |
US20040097732A1 (en) | Peptide deformylase inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
FZDE | Discontinued |