KR20100014974A - 아미드 화합물 및 이의 항종양제로서의 용도 - Google Patents
아미드 화합물 및 이의 항종양제로서의 용도 Download PDFInfo
- Publication number
- KR20100014974A KR20100014974A KR1020097018936A KR20097018936A KR20100014974A KR 20100014974 A KR20100014974 A KR 20100014974A KR 1020097018936 A KR1020097018936 A KR 1020097018936A KR 20097018936 A KR20097018936 A KR 20097018936A KR 20100014974 A KR20100014974 A KR 20100014974A
- Authority
- KR
- South Korea
- Prior art keywords
- nmr
- mhz
- mmol
- cdcl
- alkyl
- 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.)
- Withdrawn
Links
- -1 Amide compounds Chemical class 0.000 title description 26
- 239000002246 antineoplastic agent Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- 210000004027 cell Anatomy 0.000 claims abstract description 20
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 12
- 230000004069 differentiation Effects 0.000 claims abstract description 11
- 102000003964 Histone deacetylase Human genes 0.000 claims abstract description 10
- 108090000353 Histone deacetylase Proteins 0.000 claims abstract description 10
- 229940079593 drug Drugs 0.000 claims abstract description 10
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 230000001939 inductive effect Effects 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 230000011712 cell development Effects 0.000 claims abstract description 6
- 230000035755 proliferation Effects 0.000 claims abstract description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000000694 effects Effects 0.000 claims abstract description 5
- 210000005170 neoplastic cell Anatomy 0.000 claims abstract description 5
- 208000011571 secondary malignant neoplasm Diseases 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 202
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 125000002947 alkylene group Chemical group 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004450 alkenylene group Chemical group 0.000 claims description 2
- 125000000732 arylene group Chemical group 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 210
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 192
- 238000005160 1H NMR spectroscopy Methods 0.000 description 137
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 132
- 235000019439 ethyl acetate Nutrition 0.000 description 105
- 238000003818 flash chromatography Methods 0.000 description 94
- 239000002253 acid Substances 0.000 description 79
- 239000000543 intermediate Substances 0.000 description 76
- 239000000203 mixture Substances 0.000 description 70
- 239000000243 solution Substances 0.000 description 63
- 239000003921 oil Substances 0.000 description 57
- 235000019198 oils Nutrition 0.000 description 57
- 239000012230 colorless oil Substances 0.000 description 55
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 150000004702 methyl esters Chemical class 0.000 description 45
- 238000004128 high performance liquid chromatography Methods 0.000 description 41
- 238000000746 purification Methods 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 150000001336 alkenes Chemical group 0.000 description 29
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 25
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
- 238000003756 stirring Methods 0.000 description 23
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 239000003054 catalyst Substances 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 20
- 150000002678 macrocyclic compounds Chemical class 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- 150000003931 anilides Chemical class 0.000 description 18
- 239000012300 argon atmosphere Substances 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 15
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 15
- 0 *c1ccc2[n]ccc2c1 Chemical compound *c1ccc2[n]ccc2c1 0.000 description 14
- 229910052786 argon Inorganic materials 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000000284 extract Substances 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 150000001299 aldehydes Chemical class 0.000 description 9
- 150000001540 azides Chemical class 0.000 description 9
- 150000001993 dienes Chemical group 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000003541 multi-stage reaction Methods 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 238000007039 two-step reaction Methods 0.000 description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 8
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- FWPKDESKJMMUSR-UHFFFAOYSA-N n-hydroxyhexanamide Chemical compound CCCCCC(=O)NO FWPKDESKJMMUSR-UHFFFAOYSA-N 0.000 description 7
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- JUQLUIFNNFIIKC-UHFFFAOYSA-N 2-aminopimelic acid Chemical compound OC(=O)C(N)CCCCC(O)=O JUQLUIFNNFIIKC-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 6
- 238000005937 allylation reaction Methods 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000010626 work up procedure Methods 0.000 description 6
- SDTORDSXCYSNTD-UHFFFAOYSA-N 1-methoxy-4-[(4-methoxyphenyl)methoxymethyl]benzene Chemical compound C1=CC(OC)=CC=C1COCC1=CC=C(OC)C=C1 SDTORDSXCYSNTD-UHFFFAOYSA-N 0.000 description 5
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- IQUPABOKLQSFBK-UHFFFAOYSA-N 2-nitrophenol Chemical class OC1=CC=CC=C1[N+]([O-])=O IQUPABOKLQSFBK-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- 235000019502 Orange oil Nutrition 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000008241 heterogeneous mixture Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- VVDIWAYJRNKZLB-UHFFFAOYSA-N methyl 8-anilino-7-[(3-methoxyphenyl)methoxy]-8-oxooctanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC=CC(OC)=C1 VVDIWAYJRNKZLB-UHFFFAOYSA-N 0.000 description 5
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 5
- 239000010502 orange oil Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 5
- FIOJWGRGPONADF-UHFFFAOYSA-N (sulfinylamino)benzene Chemical class O=S=NC1=CC=CC=C1 FIOJWGRGPONADF-UHFFFAOYSA-N 0.000 description 4
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 4
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 4
- 150000001448 anilines Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- KUVIRDUPAGKTER-UHFFFAOYSA-N n-phenylmethoxyaniline Chemical compound C=1C=CC=CC=1CONC1=CC=CC=C1 KUVIRDUPAGKTER-UHFFFAOYSA-N 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 150000003138 primary alcohols Chemical class 0.000 description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 238000010792 warming Methods 0.000 description 4
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound 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 IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 3
- WJXSWCUQABXPFS-UHFFFAOYSA-N 3-hydroxyanthranilic acid Chemical compound NC1=C(O)C=CC=C1C(O)=O WJXSWCUQABXPFS-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- FSNCEEGOMTYXKY-JTQLQIEISA-N Lycoperodine 1 Natural products N1C2=CC=CC=C2C2=C1CN[C@H](C(=O)O)C2 FSNCEEGOMTYXKY-JTQLQIEISA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000000411 inducer Substances 0.000 description 3
- AFFLGGQVNFXPEV-UHFFFAOYSA-N n-decene Natural products CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 3
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 2
- JRKLDYQREJAUNQ-UHFFFAOYSA-N 1-(4-methoxyphenyl)but-3-en-1-ol Chemical compound COC1=CC=C(C(O)CC=C)C=C1 JRKLDYQREJAUNQ-UHFFFAOYSA-N 0.000 description 2
- UJUNUASMYSTBSK-UHFFFAOYSA-N 1-(bromomethyl)-3-phenoxybenzene Chemical compound BrCC1=CC=CC(OC=2C=CC=CC=2)=C1 UJUNUASMYSTBSK-UHFFFAOYSA-N 0.000 description 2
- GIGRWGTZFONRKA-UHFFFAOYSA-N 1-(bromomethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CBr)C=C1 GIGRWGTZFONRKA-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
- GUJOESXAMZYYCF-UHFFFAOYSA-N 2-[(3-methoxyphenyl)methoxy]octanedioic acid Chemical compound COC1=CC=CC(COC(CCCCCC(O)=O)C(O)=O)=C1 GUJOESXAMZYYCF-UHFFFAOYSA-N 0.000 description 2
- FXDSFJYWNYIQGW-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methoxy]octanedioic acid Chemical compound COC1=CC=C(COC(CCCCCC(O)=O)C(O)=O)C=C1 FXDSFJYWNYIQGW-UHFFFAOYSA-N 0.000 description 2
- LYFNCKPMTCSLBV-UHFFFAOYSA-N 2-hydroxyheptanedioic acid Chemical compound OC(=O)C(O)CCCCC(O)=O LYFNCKPMTCSLBV-UHFFFAOYSA-N 0.000 description 2
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BWKDAAFSXYPQOS-UHFFFAOYSA-N Benzaldehyde glyceryl acetal Chemical compound O1CC(O)COC1C1=CC=CC=C1 BWKDAAFSXYPQOS-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- UBJVUCKUDDKUJF-UHFFFAOYSA-N Diallyl sulfide Chemical compound C=CCSCC=C UBJVUCKUDDKUJF-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 238000006809 Jones oxidation reaction Methods 0.000 description 2
- 239000003810 Jones reagent Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- XNCNNDVCAUWAIT-UHFFFAOYSA-N Methyl heptanoate Chemical compound CCCCCCC(=O)OC XNCNNDVCAUWAIT-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- IOTNGHGVXXMLBK-UHFFFAOYSA-N [3-methoxy-5-[(2-nitrophenoxy)methyl]phenyl]methanol Chemical compound COC1=CC(CO)=CC(COC=2C(=CC=CC=2)[N+]([O-])=O)=C1 IOTNGHGVXXMLBK-UHFFFAOYSA-N 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000012888 bovine serum Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical compound [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 description 2
- 229940125810 compound 20 Drugs 0.000 description 2
- ZKXWKVVCCTZOLD-FDGPNNRMSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical compound [Cu].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O ZKXWKVVCCTZOLD-FDGPNNRMSA-N 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000005828 desilylation reaction Methods 0.000 description 2
- XXTZHYXQVWRADW-UHFFFAOYSA-N diazomethanone Chemical compound [N]N=C=O XXTZHYXQVWRADW-UHFFFAOYSA-N 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- XMJFRJQQPLMBOA-UHFFFAOYSA-N methyl 7-anilino-7-oxo-6-phenylmethoxyheptanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCC(=O)OC)OCC1=CC=CC=C1 XMJFRJQQPLMBOA-UHFFFAOYSA-N 0.000 description 2
- IGGJCZWCOLENGD-UHFFFAOYSA-N methyl 8-anilino-7-[(3,5-dimethoxyphenyl)methoxy]-8-oxooctanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC(OC)=CC(OC)=C1 IGGJCZWCOLENGD-UHFFFAOYSA-N 0.000 description 2
- SONJSYVLGLPOAA-UHFFFAOYSA-N methyl 8-anilino-7-hydroxy-8-oxooctanoate Chemical compound COC(=O)CCCCCC(O)C(=O)NC1=CC=CC=C1 SONJSYVLGLPOAA-UHFFFAOYSA-N 0.000 description 2
- ZXXAKEVFKHLQGX-UHFFFAOYSA-N methyl 8-anilino-8-oxo-7-[[4-(trifluoromethyl)phenyl]methoxy]octanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC=C(C(F)(F)F)C=C1 ZXXAKEVFKHLQGX-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 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 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000003865 nucleic acid synthesis inhibitor Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229950009215 phenylbutanoic acid Drugs 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000000861 pro-apoptotic effect Effects 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 230000001012 protector Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 150000003333 secondary alcohols Chemical class 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 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 2
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 2
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LEYPWUWYYCKVRK-ZCFIWIBFSA-N (2R)-2-methoxyheptanedioic acid Chemical compound CO[C@@H](C(O)=O)CCCCC(O)=O LEYPWUWYYCKVRK-ZCFIWIBFSA-N 0.000 description 1
- FXDSFJYWNYIQGW-AWEZNQCLSA-N (2S)-2-[(4-methoxyphenyl)methoxy]octanedioic acid Chemical compound COC1=CC=C(CO[C@@H](CCCCCC(O)=O)C(O)=O)C=C1 FXDSFJYWNYIQGW-AWEZNQCLSA-N 0.000 description 1
- LEYPWUWYYCKVRK-LURJTMIESA-N (2S)-2-methoxyheptanedioic acid Chemical compound CO[C@H](C(O)=O)CCCCC(O)=O LEYPWUWYYCKVRK-LURJTMIESA-N 0.000 description 1
- WMWCYDKMYWDWEE-ZETCQYMHSA-N (2s)-2,7-dimethoxy-7-oxoheptanoic acid Chemical compound CO[C@H](C(O)=O)CCCCC(=O)OC WMWCYDKMYWDWEE-ZETCQYMHSA-N 0.000 description 1
- XJROLFSMUBKARW-VIFPVBQESA-N (2s)-2-acetyloxy-8-methoxy-8-oxooctanoic acid Chemical compound COC(=O)CCCCC[C@@H](C(O)=O)OC(C)=O XJROLFSMUBKARW-VIFPVBQESA-N 0.000 description 1
- KGANAERDZBAECK-UHFFFAOYSA-N (3-phenoxyphenyl)methanol Chemical compound OCC1=CC=CC(OC=2C=CC=CC=2)=C1 KGANAERDZBAECK-UHFFFAOYSA-N 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-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
- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
- ZKSOJQDNSNJIQW-UHFFFAOYSA-N 1-(bromomethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CBr)=C1 ZKSOJQDNSNJIQW-UHFFFAOYSA-N 0.000 description 1
- IKSNDOVDVVPSMA-UHFFFAOYSA-N 1-(bromomethyl)-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(CBr)C=C1 IKSNDOVDVVPSMA-UHFFFAOYSA-N 0.000 description 1
- WZRKSPFYXUXINF-UHFFFAOYSA-N 1-(bromomethyl)-4-methylbenzene Chemical compound CC1=CC=C(CBr)C=C1 WZRKSPFYXUXINF-UHFFFAOYSA-N 0.000 description 1
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 1
- GKAPRCQFPCUDSU-UHFFFAOYSA-N 1-hex-5-enoxy-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1OCCCCC=C GKAPRCQFPCUDSU-UHFFFAOYSA-N 0.000 description 1
- HFPOUXUCWPUERC-UHFFFAOYSA-N 1-methoxy-4-(sulfinylamino)benzene Chemical compound COC1=CC=C(N=S=O)C=C1 HFPOUXUCWPUERC-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- IQTAGROHONJFNV-UHFFFAOYSA-N 2-[(3,5-dimethoxyphenyl)methoxy]octanedioic acid Chemical compound COC1=CC(COC(CCCCCC(O)=O)C(O)=O)=CC(OC)=C1 IQTAGROHONJFNV-UHFFFAOYSA-N 0.000 description 1
- PBENMWCGPADIIA-UHFFFAOYSA-N 2-[(3-ethenyl-5-methoxyphenyl)methoxy]aniline Chemical compound C=CC1=CC(OC)=CC(COC=2C(=CC=CC=2)N)=C1 PBENMWCGPADIIA-UHFFFAOYSA-N 0.000 description 1
- OYZWOGVQRIAXMH-UHFFFAOYSA-N 2-[(4-bromophenyl)methoxy]octanedioic acid Chemical compound OC(=O)CCCCCC(C(O)=O)OCC1=CC=C(Br)C=C1 OYZWOGVQRIAXMH-UHFFFAOYSA-N 0.000 description 1
- IARKSLINHVMGBR-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methoxy]heptanedioic acid Chemical compound COC1=CC=C(COC(CCCCC(O)=O)C(O)=O)C=C1 IARKSLINHVMGBR-UHFFFAOYSA-N 0.000 description 1
- YMSWQOCKPJYZQW-UHFFFAOYSA-N 2-[(4-methylphenyl)methoxy]octanedioic acid Chemical compound CC1=CC=C(COC(CCCCCC(O)=O)C(O)=O)C=C1 YMSWQOCKPJYZQW-UHFFFAOYSA-N 0.000 description 1
- PYBTYHCPXKYMIU-UHFFFAOYSA-N 2-[[4-(trifluoromethyl)phenyl]methoxy]octanedioic acid Chemical compound OC(=O)CCCCCC(C(O)=O)OCC1=CC=C(C(F)(F)F)C=C1 PYBTYHCPXKYMIU-UHFFFAOYSA-N 0.000 description 1
- BMTSZVZQNMNPCT-UHFFFAOYSA-N 2-aminopyridin-3-ol Chemical compound NC1=NC=CC=C1O BMTSZVZQNMNPCT-UHFFFAOYSA-N 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- XDUYCQGUCYFKAL-UHFFFAOYSA-N 2-hex-5-enoxyaniline Chemical compound NC1=CC=CC=C1OCCCCC=C XDUYCQGUCYFKAL-UHFFFAOYSA-N 0.000 description 1
- QGSGJCNWXMPJBD-UHFFFAOYSA-N 2-hydroxy-7-methoxy-7-oxoheptanoic acid Chemical compound COC(=O)CCCCC(O)C(O)=O QGSGJCNWXMPJBD-UHFFFAOYSA-N 0.000 description 1
- PLOLVIIKIIYJDS-UHFFFAOYSA-N 2-hydroxy-8-methoxy-8-oxooctanoic acid Chemical compound COC(=O)CCCCCC(O)C(O)=O PLOLVIIKIIYJDS-UHFFFAOYSA-N 0.000 description 1
- DHNJFWLYLQPITF-UHFFFAOYSA-N 2-hydroxyoctanedioic acid Chemical compound OC(=O)C(O)CCCCCC(O)=O DHNJFWLYLQPITF-UHFFFAOYSA-N 0.000 description 1
- LEYPWUWYYCKVRK-UHFFFAOYSA-N 2-methoxyheptanedioic acid Chemical compound COC(C(O)=O)CCCCC(O)=O LEYPWUWYYCKVRK-UHFFFAOYSA-N 0.000 description 1
- DGODVNLBEDIZHQ-UHFFFAOYSA-N 2-methoxyoctanedioic acid Chemical compound COC(C(O)=O)CCCCCC(O)=O DGODVNLBEDIZHQ-UHFFFAOYSA-N 0.000 description 1
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical class [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
- OMZYZJGCDKWDBN-UHFFFAOYSA-N 2-phenylmethoxyheptanedioic acid Chemical compound OC(=O)CCCCC(C(O)=O)OCC1=CC=CC=C1 OMZYZJGCDKWDBN-UHFFFAOYSA-N 0.000 description 1
- AVSICCJQRKSYHP-UHFFFAOYSA-N 2-phenylmethoxyoctanedioic acid Chemical compound OC(=O)CCCCCC(C(O)=O)OCC1=CC=CC=C1 AVSICCJQRKSYHP-UHFFFAOYSA-N 0.000 description 1
- ANLKJTVUTKDNOV-UHFFFAOYSA-N 2-prop-2-enyl-1h-indole Chemical class C1=CC=C2NC(CC=C)=CC2=C1 ANLKJTVUTKDNOV-UHFFFAOYSA-N 0.000 description 1
- QGDKNOIUJDZPFX-UHFFFAOYSA-N 2-propoxyheptanedioic acid Chemical compound CCCOC(C(O)=O)CCCCC(O)=O QGDKNOIUJDZPFX-UHFFFAOYSA-N 0.000 description 1
- OIIBRAGQGFLUFI-UHFFFAOYSA-N 3-amino-1h-pyridin-4-one Chemical compound NC1=CNC=CC1=O OIIBRAGQGFLUFI-UHFFFAOYSA-N 0.000 description 1
- USEGQJLHQSTGHW-UHFFFAOYSA-N 3-bromo-2-methylprop-1-ene Chemical compound CC(=C)CBr USEGQJLHQSTGHW-UHFFFAOYSA-N 0.000 description 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- JCSHMIONODUEGB-UHFFFAOYSA-N 3-nitro-4-pent-4-enoxypyridine Chemical compound [O-][N+](=O)C1=CN=CC=C1OCCCC=C JCSHMIONODUEGB-UHFFFAOYSA-N 0.000 description 1
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical class C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-M 4-nitrobenzoate Chemical compound [O-]C(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-M 0.000 description 1
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 description 1
- IDZRMPHYXNSSOB-UHFFFAOYSA-N 4-pent-4-enoxypyridin-3-amine Chemical compound NC1=CN=CC=C1OCCCC=C IDZRMPHYXNSSOB-UHFFFAOYSA-N 0.000 description 1
- RIMXEJYJXDBLIE-UHFFFAOYSA-N 6-bromohex-1-ene Chemical compound BrCCCCC=C RIMXEJYJXDBLIE-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- DFQZIOAEKMMJRC-UHFFFAOYSA-N CC(C)(OC1CCC(OC)=O)OC1=O Chemical compound CC(C)(OC1CCC(OC)=O)OC1=O DFQZIOAEKMMJRC-UHFFFAOYSA-N 0.000 description 1
- BWJFUEKXSSYBAO-UHFFFAOYSA-N CC(C)(OC1CCCCC(O)=O)OC1=O Chemical compound CC(C)(OC1CCCCC(O)=O)OC1=O BWJFUEKXSSYBAO-UHFFFAOYSA-N 0.000 description 1
- PGWYMFVFGMXKNQ-UHFFFAOYSA-N CC1C(NC(C(CCCCCC(NO)=O)OCc2cc(OC)cc(OC)c2)=O)=CC=CC1 Chemical compound CC1C(NC(C(CCCCCC(NO)=O)OCc2cc(OC)cc(OC)c2)=O)=CC=CC1 PGWYMFVFGMXKNQ-UHFFFAOYSA-N 0.000 description 1
- QFWVNEBRTUUHIE-UHFFFAOYSA-N COc1cc(CO)cc(CO)c1 Chemical compound COc1cc(CO)cc(CO)c1 QFWVNEBRTUUHIE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- IIWBTJMYBKIWNY-UHFFFAOYSA-N Cl.CCCCCC(=O)NO Chemical compound Cl.CCCCCC(=O)NO IIWBTJMYBKIWNY-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- 241000124008 Mammalia Species 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000872931 Myoporum sandwicense Species 0.000 description 1
- BNQSTAOJRULKNX-UHFFFAOYSA-N N-(6-acetamidohexyl)acetamide Chemical compound CC(=O)NCCCCCCNC(C)=O BNQSTAOJRULKNX-UHFFFAOYSA-N 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- DGQYQVJKMZAQBV-UHFFFAOYSA-N ONC(CCCCC(C(Nc1ccccc1)=O)OCc1ccccc1)=O Chemical compound ONC(CCCCC(C(Nc1ccccc1)=O)OCc1ccccc1)=O DGQYQVJKMZAQBV-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 229940123752 RNA synthesis inhibitor Drugs 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229930189037 Trapoxin Natural products 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- FYGNJYLXDRROPN-UHFFFAOYSA-N [2-(4-phenylmethoxyphenyl)-1,3-thiazol-4-yl]methanamine Chemical compound NCC1=CSC(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=N1 FYGNJYLXDRROPN-UHFFFAOYSA-N 0.000 description 1
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 1
- 229960004176 aclarubicin Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- QQQCWVDPMPFUGF-ZDUSSCGKSA-N alpinetin Chemical compound C1([C@H]2OC=3C=C(O)C=C(C=3C(=O)C2)OC)=CC=CC=C1 QQQCWVDPMPFUGF-ZDUSSCGKSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 239000011609 ammonium molybdate Substances 0.000 description 1
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
- 235000018660 ammonium molybdate Nutrition 0.000 description 1
- 229940010552 ammonium molybdate Drugs 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940090047 auto-injector Drugs 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- OZECDDHOAMNMQI-UHFFFAOYSA-H cerium(3+);trisulfate Chemical compound [Ce+3].[Ce+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O OZECDDHOAMNMQI-UHFFFAOYSA-H 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzylether Substances C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940069096 dodecene Drugs 0.000 description 1
- 238000011918 double bond oxidative cleavage Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- ADTIBIOIERBRIB-UHFFFAOYSA-N eta-Oxy-caprylsaeure-methylester Natural products COC(=O)CCCCCCCO ADTIBIOIERBRIB-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 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
- 238000007429 general method Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
- 238000011905 homologation Methods 0.000 description 1
- 238000007163 homologation reaction Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 102000054896 human PML Human genes 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- KNONKIHTJXXNFJ-NRFANRHFSA-N methyl (6s)-7-[tert-butyl(diphenyl)silyl]oxy-6-methoxyheptanoate Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(OC[C@H](CCCCC(=O)OC)OC)C1=CC=CC=C1 KNONKIHTJXXNFJ-NRFANRHFSA-N 0.000 description 1
- BZRBQTSDUWHKRH-ZDUSSCGKSA-N methyl (6s)-7-anilino-6-methoxy-7-oxoheptanoate Chemical compound COC(=O)CCCC[C@H](OC)C(=O)NC1=CC=CC=C1 BZRBQTSDUWHKRH-ZDUSSCGKSA-N 0.000 description 1
- GBFYGZNWRPUWJL-OAQYLSRUSA-N methyl (7r)-8-[tert-butyl(diphenyl)silyl]oxy-7-hydroxyoctanoate Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(OC[C@H](O)CCCCCC(=O)OC)C1=CC=CC=C1 GBFYGZNWRPUWJL-OAQYLSRUSA-N 0.000 description 1
- RNFUZEBPZQPFHS-OAQYLSRUSA-N methyl (7r)-8-anilino-7-[(4-methoxyphenyl)methoxy]-8-oxooctanoate Chemical compound O([C@H](CCCCCC(=O)OC)C(=O)NC=1C=CC=CC=1)CC1=CC=C(OC)C=C1 RNFUZEBPZQPFHS-OAQYLSRUSA-N 0.000 description 1
- SONJSYVLGLPOAA-CYBMUJFWSA-N methyl (7r)-8-anilino-7-hydroxy-8-oxooctanoate Chemical compound COC(=O)CCCCC[C@@H](O)C(=O)NC1=CC=CC=C1 SONJSYVLGLPOAA-CYBMUJFWSA-N 0.000 description 1
- KKNRJMMREMVRJK-DEOSSOPVSA-N methyl (7s)-8-[tert-butyl(diphenyl)silyl]oxy-7-[(2-methylpropan-2-yl)oxycarbonylamino]octanoate Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(OC[C@H](CCCCCC(=O)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 KKNRJMMREMVRJK-DEOSSOPVSA-N 0.000 description 1
- GBFYGZNWRPUWJL-NRFANRHFSA-N methyl (7s)-8-[tert-butyl(diphenyl)silyl]oxy-7-hydroxyoctanoate Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)(OC[C@@H](O)CCCCCC(=O)OC)C1=CC=CC=C1 GBFYGZNWRPUWJL-NRFANRHFSA-N 0.000 description 1
- RNFUZEBPZQPFHS-NRFANRHFSA-N methyl (7s)-8-anilino-7-[(4-methoxyphenyl)methoxy]-8-oxooctanoate Chemical compound O([C@@H](CCCCCC(=O)OC)C(=O)NC=1C=CC=CC=1)CC1=CC=C(OC)C=C1 RNFUZEBPZQPFHS-NRFANRHFSA-N 0.000 description 1
- SONJSYVLGLPOAA-ZDUSSCGKSA-N methyl (7s)-8-anilino-7-hydroxy-8-oxooctanoate Chemical compound COC(=O)CCCCC[C@H](O)C(=O)NC1=CC=CC=C1 SONJSYVLGLPOAA-ZDUSSCGKSA-N 0.000 description 1
- GGSUOVYLKCOAIQ-UHFFFAOYSA-N methyl 6-[10-(4-methoxyphenyl)-3-oxo-5,11-dioxa-2-azabicyclo[10.4.0]hexadeca-1(16),12,14-trien-4-yl]hexanoate Chemical compound O1C2=CC=CC=C2NC(=O)C(CCCCCC(=O)OC)OCCCCC1C1=CC=C(OC)C=C1 GGSUOVYLKCOAIQ-UHFFFAOYSA-N 0.000 description 1
- OBPHODDDZTUOMY-UHFFFAOYSA-N methyl 7-(2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl)hept-2-enoate Chemical compound COC(=O)C=CCCCCC1OC(C)(C)OC1=O OBPHODDDZTUOMY-UHFFFAOYSA-N 0.000 description 1
- KXHYWVQDVCJJJZ-UHFFFAOYSA-N methyl 7-anilino-6-[(4-methoxyphenyl)methoxy]-7-oxoheptanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCC(=O)OC)OCC1=CC=C(OC)C=C1 KXHYWVQDVCJJJZ-UHFFFAOYSA-N 0.000 description 1
- NMAXFHMZUMCBBK-UHFFFAOYSA-N methyl 7-anilino-6-hydroxy-7-oxoheptanoate Chemical compound COC(=O)CCCCC(O)C(=O)NC1=CC=CC=C1 NMAXFHMZUMCBBK-UHFFFAOYSA-N 0.000 description 1
- BZRBQTSDUWHKRH-UHFFFAOYSA-N methyl 7-anilino-6-methoxy-7-oxoheptanoate Chemical compound COC(=O)CCCCC(OC)C(=O)NC1=CC=CC=C1 BZRBQTSDUWHKRH-UHFFFAOYSA-N 0.000 description 1
- FEUMTTDUYSKWED-UHFFFAOYSA-N methyl 7-anilino-7-oxo-6-propoxyheptanoate Chemical compound COC(=O)CCCCC(OCCC)C(=O)NC1=CC=CC=C1 FEUMTTDUYSKWED-UHFFFAOYSA-N 0.000 description 1
- XKDCMMMIFVPWKI-UHFFFAOYSA-N methyl 7-hydroxy-8-(4-methoxyanilino)-8-oxooctanoate Chemical compound COC(=O)CCCCCC(O)C(=O)NC1=CC=C(OC)C=C1 XKDCMMMIFVPWKI-UHFFFAOYSA-N 0.000 description 1
- BBUPVWSIFYJSMX-UHFFFAOYSA-N methyl 8-(4-methoxyanilino)-7-[(4-methoxyphenyl)methoxy]-8-oxooctanoate Chemical compound C=1C=C(OC)C=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC=C(OC)C=C1 BBUPVWSIFYJSMX-UHFFFAOYSA-N 0.000 description 1
- PPZBUJURNSUKGW-UHFFFAOYSA-N methyl 8-(4-methoxyanilino)-8-oxo-7-phenylmethoxyoctanoate Chemical compound C=1C=C(OC)C=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC=CC=C1 PPZBUJURNSUKGW-UHFFFAOYSA-N 0.000 description 1
- QXMVBURPOIZXPZ-UHFFFAOYSA-N methyl 8-anilino-7-[(4-bromophenyl)methoxy]-8-oxooctanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC=C(Br)C=C1 QXMVBURPOIZXPZ-UHFFFAOYSA-N 0.000 description 1
- RNFUZEBPZQPFHS-UHFFFAOYSA-N methyl 8-anilino-7-[(4-methoxyphenyl)methoxy]-8-oxooctanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC=C(OC)C=C1 RNFUZEBPZQPFHS-UHFFFAOYSA-N 0.000 description 1
- XODNCVDPRFJDLW-UHFFFAOYSA-N methyl 8-anilino-7-[(4-methylphenyl)methoxy]-8-oxooctanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCC(=O)OC)OCC1=CC=C(C)C=C1 XODNCVDPRFJDLW-UHFFFAOYSA-N 0.000 description 1
- LQWSTMAAIQMLGH-UHFFFAOYSA-N methyl 8-anilino-7-methoxy-8-oxooctanoate Chemical compound COC(=O)CCCCCC(OC)C(=O)NC1=CC=CC=C1 LQWSTMAAIQMLGH-UHFFFAOYSA-N 0.000 description 1
- YWHCKJVIMMXZAJ-UHFFFAOYSA-N methyl 8-anilino-8-oxo-7-[(3-phenoxyphenyl)methoxy]octanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCC(=O)OC)OCC(C=1)=CC=CC=1OC1=CC=CC=C1 YWHCKJVIMMXZAJ-UHFFFAOYSA-N 0.000 description 1
- LVKZFFZWSSWNMK-UHFFFAOYSA-N methyl 9-anilino-8-[(4-methoxyphenyl)methoxy]-9-oxononanoate Chemical compound C=1C=CC=CC=1NC(=O)C(CCCCCCC(=O)OC)OCC1=CC=C(OC)C=C1 LVKZFFZWSSWNMK-UHFFFAOYSA-N 0.000 description 1
- AQPZNQPTSMSNOL-UHFFFAOYSA-N methyl 9-anilino-8-hydroxy-9-oxononanoate Chemical compound COC(=O)CCCCCCC(O)C(=O)NC1=CC=CC=C1 AQPZNQPTSMSNOL-UHFFFAOYSA-N 0.000 description 1
- CPDQGHVRVJFVQA-UHFFFAOYSA-N methyl 9-anilino-8-methoxy-9-oxononanoate Chemical compound COC(=O)CCCCCCC(OC)C(=O)NC1=CC=CC=C1 CPDQGHVRVJFVQA-UHFFFAOYSA-N 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- ARHBOFOEZHVZGQ-UHFFFAOYSA-N n-(1h-indol-3-ylmethoxy)aniline Chemical compound C=1NC2=CC=CC=C2C=1CONC1=CC=CC=C1 ARHBOFOEZHVZGQ-UHFFFAOYSA-N 0.000 description 1
- BYDKWDBDTCCLPK-UHFFFAOYSA-N n-hydroxy-6-[10-(4-methoxyphenyl)-3-oxo-5,11-dioxa-2-azabicyclo[10.4.0]hexadeca-1(16),12,14-trien-4-yl]hexanamide Chemical compound C1=CC(OC)=CC=C1C1OC2=CC=CC=C2NC(=O)C(CCCCCC(=O)NO)OCCCC1 BYDKWDBDTCCLPK-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000004999 nitroaryl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- JGHZJRVDZXSNKQ-UHFFFAOYSA-N octanoic acid methyl ester Natural products CCCCCCCC(=O)OC JGHZJRVDZXSNKQ-UHFFFAOYSA-N 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- CLDWGXZGFUNWKB-UHFFFAOYSA-M silver;benzoate Chemical compound [Ag+].[O-]C(=O)C1=CC=CC=C1 CLDWGXZGFUNWKB-UHFFFAOYSA-M 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 208000000649 small cell carcinoma Diseases 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229950009390 symclosene Drugs 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- AWARHXCROCWEAK-UHFFFAOYSA-N tert-butyl n-prop-2-enylcarbamate Chemical compound CC(C)(C)OC(=O)NCC=C AWARHXCROCWEAK-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 108010060597 trapoxin A Proteins 0.000 description 1
- 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 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000000717 tumor promoter Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
- C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
- C07D273/01—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having one nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07104071 | 2007-03-13 | ||
| EP07104071.1 | 2007-03-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20100014974A true KR20100014974A (ko) | 2010-02-11 |
Family
ID=39535770
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020097018936A Withdrawn KR20100014974A (ko) | 2007-03-13 | 2008-03-12 | 아미드 화합물 및 이의 항종양제로서의 용도 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20100113504A1 (enExample) |
| EP (1) | EP2137169A1 (enExample) |
| JP (1) | JP2010520915A (enExample) |
| KR (1) | KR20100014974A (enExample) |
| CN (1) | CN101641341A (enExample) |
| AU (1) | AU2008225833A1 (enExample) |
| BR (1) | BRPI0809000A2 (enExample) |
| CA (1) | CA2677874A1 (enExample) |
| EA (1) | EA200970848A1 (enExample) |
| IL (1) | IL200188A0 (enExample) |
| MX (1) | MX2009009374A (enExample) |
| WO (1) | WO2008110583A1 (enExample) |
| ZA (1) | ZA200907077B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2230227A1 (en) * | 2009-03-20 | 2010-09-22 | Bracco Imaging S.p.A | Process for the preparation of triiodinated carboxylic aromatic derivatives |
| JP2013508323A (ja) * | 2009-10-21 | 2013-03-07 | シグマ−タウ・インドゥストリエ・ファルマチェウチケ・リウニテ・ソシエタ・ペル・アチオニ | 合成大環状アミドｈｄａｃ６阻害剤化合物およびそれらの治療剤としての用途 |
| CN109516926B (zh) * | 2018-07-27 | 2021-09-17 | 四川大学 | 一种荜茇明碱衍生物制备及用途 |
| EP3941457A4 (en) * | 2019-03-21 | 2023-04-26 | Merck Sharp & Dohme LLC | HISTONE-DEACETYLASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF HIV INFECTION |
| CN120924186B (zh) * | 2025-10-14 | 2025-12-23 | 长沙市芯星新能源科技有限公司 | 负极粘结剂、锂离子电池负极及其制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0014254A (pt) * | 1999-09-08 | 2002-08-27 | Sloan Kettering Inst Cancer | Nova classe de agentes de citodiferenciação e inibidores de desacetilase de histona, e métodos de uso dos mesmos |
| US20060264415A1 (en) * | 2005-04-01 | 2006-11-23 | Methylgene Inc. | Inhibitors of histone deacetylase |
-
2008
- 2008-03-12 JP JP2009553140A patent/JP2010520915A/ja not_active Withdrawn
- 2008-03-12 AU AU2008225833A patent/AU2008225833A1/en not_active Abandoned
- 2008-03-12 CA CA002677874A patent/CA2677874A1/en not_active Abandoned
- 2008-03-12 US US12/528,912 patent/US20100113504A1/en not_active Abandoned
- 2008-03-12 BR BRPI0809000-9A2A patent/BRPI0809000A2/pt not_active IP Right Cessation
- 2008-03-12 WO PCT/EP2008/052965 patent/WO2008110583A1/en not_active Ceased
- 2008-03-12 CN CN200880008093A patent/CN101641341A/zh active Pending
- 2008-03-12 KR KR1020097018936A patent/KR20100014974A/ko not_active Withdrawn
- 2008-03-12 MX MX2009009374A patent/MX2009009374A/es not_active Application Discontinuation
- 2008-03-12 EA EA200970848A patent/EA200970848A1/ru unknown
- 2008-03-12 EP EP08717710A patent/EP2137169A1/en not_active Withdrawn
-
2009
- 2009-07-30 IL IL200188A patent/IL200188A0/en unknown
- 2009-10-12 ZA ZA200907077A patent/ZA200907077B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200907077B (en) | 2010-07-28 |
| EA200970848A1 (ru) | 2010-02-26 |
| US20100113504A1 (en) | 2010-05-06 |
| EP2137169A1 (en) | 2009-12-30 |
| WO2008110583A1 (en) | 2008-09-18 |
| IL200188A0 (en) | 2010-04-15 |
| BRPI0809000A2 (pt) | 2014-11-11 |
| CA2677874A1 (en) | 2008-09-18 |
| MX2009009374A (es) | 2009-09-21 |
| AU2008225833A1 (en) | 2008-09-18 |
| JP2010520915A (ja) | 2010-06-17 |
| CN101641341A (zh) | 2010-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2638923C2 (ru) | Синтез карбамоилпиридоновых ингибиторов интегразы ВИЧ и промежуточных соединений | |
| CA2802216C (en) | Tetrahydrocarboline derivative and its use as an enpp2 inhibitor | |
| US8816122B2 (en) | Prostratin analogs, bryostatin analogs, prodrugs, synthetic methods, and methods of use | |
| WO2014150677A1 (en) | Inhibitors of indoleamine 2,3-dioxygenase (ido) | |
| KR20050087865A (ko) | ＨＩＶ 인테그라제 억제제로서 유용한테트라하이드로-4Ｈ-피리도[1,2-ａ]피리미딘 및 관련화합물 | |
| EA024681B1 (ru) | Имидазопиридины в качестве противовирусных средств против респираторно-синцитиального вируса | |
| EA020885B1 (ru) | Ингибиторы протеинкиназы и их применение | |
| KR20140059164A (ko) | 트라이사이클릭 자이라제 억제제 | |
| KR20100014974A (ko) | 아미드 화합물 및 이의 항종양제로서의 용도 | |
| DE69533043T2 (de) | Acrylamid-derivate und verfahren zu deren herstellung | |
| SK17022001A3 (sk) | Deriváty a analógy galantamínu | |
| ES2587952T3 (es) | Compuestos químicos | |
| CN109422737B (zh) | 咪唑酮类雄激素受体拮抗剂、其制备方法和用途 | |
| JP2025156455A (ja) | チアゾロ［５，４－ｂ］ピリジンＭＡＬＴ－１阻害剤 | |
| KR20020032618A (ko) | 히드록삼산 유도체 화합물, 그 제조 방법 및 그 화합물을유효 성분으로 하는 의약 | |
| KR20180073517A (ko) | 트리프톨리드의 c14-히드록실 에스테르화 아미노산 유도체, 및 그의 제조 방법 및 용도 | |
| JP4779058B2 (ja) | α−アミノ基−Ｎ−置換アミド化合物、該化合物を含む薬剤組成物及びその用途 | |
| TWI659022B (zh) | 作為d-胺基酸氧化酶(daao)抑制劑之新穎經取代苯并咪唑衍生物 | |
| US12377070B2 (en) | Substituted sulfoximine derivatives | |
| KR102717168B1 (ko) | 표적 단백질의 분해를 유도하기 위한 데그라듀서, 이의 제조방법 및 이를 유효성분으로 함유하는 표적 단백질 관련 질환의 예방 또는 치료용 약학적 조성물 | |
| HUP0400620A2 (hu) | Ingerlő aminosavak prekurzorok és ezeket tartalmazó gyógyászati készítmények, valamint eljárás a vegyületek előállítására | |
| EA026676B1 (ru) | Спироциклические циклопропановые аминокислоты и лекарственные средства на их основе | |
| CN114524821B (zh) | 螺旋吡咯烷衍生的抗病毒药物 | |
| JP2025528916A (ja) | Ｊａｋキナーゼ阻害剤のプロドラッグ | |
| HK1140477A (en) | Amide compounds and their use as antitumor agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20090910 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |