SK284434B6 - Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze - Google Patents
Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze Download PDFInfo
- Publication number
- SK284434B6 SK284434B6 SK662-98A SK66298A SK284434B6 SK 284434 B6 SK284434 B6 SK 284434B6 SK 66298 A SK66298 A SK 66298A SK 284434 B6 SK284434 B6 SK 284434B6
- Authority
- SK
- Slovakia
- Prior art keywords
- alkyl
- formula
- substituted
- halogen
- alkoxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000008569 process Effects 0.000 title claims abstract description 5
- 238000002360 preparation method Methods 0.000 title claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
- 150000002460 imidazoles Chemical class 0.000 title claims description 11
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title claims description 9
- 239000013067 intermediate product Substances 0.000 title 1
- 239000000825 pharmaceutical preparation Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 156
- 239000000203 mixture Substances 0.000 claims abstract description 91
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 109
- 239000000543 intermediate Substances 0.000 claims description 65
- -1 2-quinolylmethoxy Chemical group 0.000 claims description 63
- 229910052739 hydrogen Inorganic materials 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 63
- 229910052736 halogen Inorganic materials 0.000 claims description 50
- 150000002367 halogens Chemical class 0.000 claims description 50
- 125000003545 alkoxy group Chemical group 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- 150000002431 hydrogen Chemical class 0.000 claims description 43
- 239000002904 solvent Substances 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 27
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- BKYBFFVPONLJLQ-UHFFFAOYSA-N 3-benzazepine-3-carboxylic acid Chemical compound C1=CN(C(=O)O)C=CC2=CC=CC=C21 BKYBFFVPONLJLQ-UHFFFAOYSA-N 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000005493 quinolyl group Chemical group 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 239000012442 inert solvent Substances 0.000 claims description 10
- 125000002971 oxazolyl group Chemical group 0.000 claims description 9
- 244000052769 pathogen Species 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000008177 pharmaceutical agent Substances 0.000 claims description 7
- 150000001204 N-oxides Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 230000032050 esterification Effects 0.000 claims description 2
- 238000005886 esterification reaction Methods 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 230000000118 anti-neoplastic effect Effects 0.000 claims 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- RTKPBQOFWIQRSO-UHFFFAOYSA-N ethyl 11-[1-[2-[4-(quinolin-2-ylmethoxy)phenyl]ethyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OCC)=CN=C2C1=C1CCN(CCC=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)CC1 RTKPBQOFWIQRSO-UHFFFAOYSA-N 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- YGGCJLOLGMGBQM-UHFFFAOYSA-N methyl 11-[1-[[3,5-dimethoxy-4-(quinolin-2-ylmethoxy)phenyl]methyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CC=2C=C(OC)C(OCC=3N=C4C=CC=CC4=CC=3)=C(OC)C=2)CC1 YGGCJLOLGMGBQM-UHFFFAOYSA-N 0.000 claims 1
- 239000007800 oxidant agent Substances 0.000 claims 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
- 150000003053 piperidines Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 8
- 238000009472 formulation Methods 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 238000002651 drug therapy Methods 0.000 abstract description 2
- 125000000815 N-oxide group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 29
- 239000000460 chlorine Substances 0.000 description 27
- 150000003254 radicals Chemical class 0.000 description 24
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002244 precipitate Substances 0.000 description 18
- 239000003480 eluent Substances 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 206010028980 Neoplasm Diseases 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- 206010059866 Drug resistance Diseases 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000002246 antineoplastic agent Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 229940009456 adriamycin Drugs 0.000 description 10
- 229940127089 cytotoxic agent Drugs 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000011521 glass Substances 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000824 cytostatic agent Substances 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 238000010934 O-alkylation reaction Methods 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 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 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 230000002140 halogenating effect Effects 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- OTKFCIVOVKCFHR-UHFFFAOYSA-N (Methylsulfinyl)(methylthio)methane Chemical compound CSCS(C)=O OTKFCIVOVKCFHR-UHFFFAOYSA-N 0.000 description 3
- DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 description 3
- YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical compound C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 238000007126 N-alkylation reaction Methods 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000003266 anti-allergic effect Effects 0.000 description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 230000000973 chemotherapeutic effect Effects 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000001085 cytostatic effect Effects 0.000 description 3
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 3
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 229930192474 thiophene Natural products 0.000 description 3
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 description 2
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- LLKFNPUXQZHIAE-UHFFFAOYSA-N 5-(3-aminopropyl)-8-bromo-3-methyl-2h-pyrazolo[4,3-c]quinolin-4-one Chemical compound O=C1N(CCCN)C2=CC=C(Br)C=C2C2=C1C(C)=NN2 LLKFNPUXQZHIAE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010001986 Amoebic dysentery Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- HVODDRKCLFQWKT-UHFFFAOYSA-N C1=CN(C=CC2=C1C=CC=C2)CO Chemical compound C1=CN(C=CC2=C1C=CC=C2)CO HVODDRKCLFQWKT-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-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
- 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 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- 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 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 2
- 229960000723 ampicillin Drugs 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 230000037396 body weight Effects 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229960003350 isoniazid Drugs 0.000 description 2
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 229960001962 mefloquine Drugs 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229940126701 oral medication Drugs 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 1
- OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
- NNQBAGFIYBBAFL-UHFFFAOYSA-N 1-(diethoxymethyl)imidazole Chemical compound CCOC(OCC)N1C=CN=C1 NNQBAGFIYBBAFL-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- VTBVELSLEWQFDL-UHFFFAOYSA-N 10-piperidin-4-yl-5,10-dihydroimidazo[1,2-b]isoquinoline Chemical compound C1CNCCC1C1C2=CC=CC=C2CN2C=CN=C21 VTBVELSLEWQFDL-UHFFFAOYSA-N 0.000 description 1
- GKTUOCXSVQTQJF-UHFFFAOYSA-N 11-(1-methylpiperidin-4-ylidene)-5,6-dihydroimidazo[2,1-b][3]benzazepine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CCN2C=CN=C21 GKTUOCXSVQTQJF-UHFFFAOYSA-N 0.000 description 1
- NWMRTUTXGPXHGP-UHFFFAOYSA-N 11-piperidin-4-ylidene-5,6-dihydroimidazo[2,1-b][3]benzazepine Chemical compound C1CNCCC1=C1C2=CC=CC=C2CCN2C=CN=C21 NWMRTUTXGPXHGP-UHFFFAOYSA-N 0.000 description 1
- NQZLDYNWFMODIM-UHFFFAOYSA-N 1h-azepin-3-ol Chemical compound OC1=CNC=CC=C1 NQZLDYNWFMODIM-UHFFFAOYSA-N 0.000 description 1
- YCCILVSKPBXVIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)ethanol Chemical compound OCCC1=CC=C(O)C=C1 YCCILVSKPBXVIP-UHFFFAOYSA-N 0.000 description 1
- WDETYCRYUBGKCE-UHFFFAOYSA-N 2-(chloromethyl)quinolin-1-ium;chloride Chemical compound Cl.C1=CC=CC2=NC(CCl)=CC=C21 WDETYCRYUBGKCE-UHFFFAOYSA-N 0.000 description 1
- MGDNFZAPRFRURE-UHFFFAOYSA-N 2-[3-(quinolin-2-ylmethoxy)phenoxy]ethanol Chemical compound OCCOC1=CC=CC(OCC=2N=C3C=CC=CC3=CC=2)=C1 MGDNFZAPRFRURE-UHFFFAOYSA-N 0.000 description 1
- YREPFXKCJCGZGE-UHFFFAOYSA-N 2-[3-(quinolin-2-ylmethoxy)phenoxy]ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCOC1=CC=CC(OCC=2N=C3C=CC=CC3=CC=2)=C1 YREPFXKCJCGZGE-UHFFFAOYSA-N 0.000 description 1
- ALWMUKPTEITREM-UHFFFAOYSA-N 2-[4-(quinolin-2-ylmethoxy)phenoxy]ethyl methanesulfonate Chemical compound C1=CC(OCCOS(=O)(=O)C)=CC=C1OCC1=CC=C(C=CC=C2)C2=N1 ALWMUKPTEITREM-UHFFFAOYSA-N 0.000 description 1
- HQVRLBYYRRAXFL-UHFFFAOYSA-N 2-[4-(quinolin-2-ylmethoxy)phenyl]ethanol Chemical compound C1=CC(CCO)=CC=C1OCC1=CC=C(C=CC=C2)C2=N1 HQVRLBYYRRAXFL-UHFFFAOYSA-N 0.000 description 1
- YAWWQIFONIPBKT-HXUWFJFHSA-N 2-[[(2r)-2-butyl-6,7-dichloro-2-cyclopentyl-1-oxo-3h-inden-5-yl]oxy]acetic acid Chemical compound C1([C@@]2(C(C3=C(Cl)C(Cl)=C(OCC(O)=O)C=C3C2)=O)CCCC)CCCC1 YAWWQIFONIPBKT-HXUWFJFHSA-N 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 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
- UFINMQZIYXBSNL-UHFFFAOYSA-N 3-(quinolin-2-ylmethoxy)phenol Chemical compound OC1=CC=CC(OCC=2N=C3C=CC=CC3=CC=2)=C1 UFINMQZIYXBSNL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- LWRSXRUZFMJORB-UHFFFAOYSA-N 3-benzazepine-3-carbaldehyde Chemical compound C1=CN(C=O)C=CC2=CC=CC=C21 LWRSXRUZFMJORB-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- WQNRSTKWEWMTKF-UHFFFAOYSA-N 3-chloro-11-piperidin-4-ylidene-5,6-dihydroimidazo[2,1-b][3]benzazepine Chemical compound C12=CC=CC=C2CCN2C(Cl)=CN=C2C1=C1CCNCC1 WQNRSTKWEWMTKF-UHFFFAOYSA-N 0.000 description 1
- NNJZADJXPQFKOE-UHFFFAOYSA-N 4-(quinolin-2-ylmethoxy)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCC1=CC=C(C=CC=C2)C2=N1 NNJZADJXPQFKOE-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- QWLHJVDRPZNVBS-UHFFFAOYSA-N 4-phenoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OC1=CC=CC=C1 QWLHJVDRPZNVBS-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- ZTKRFVPOAIBCSQ-UHFFFAOYSA-N CS(=O)(=O)OCC1=CC=C(C=C1)OCC2=NC3=CC=CC=C3C=C2 Chemical compound CS(=O)(=O)OCC1=CC=C(C=C1)OCC2=NC3=CC=CC=C3C=C2 ZTKRFVPOAIBCSQ-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- FOHHNHSLJDZUGQ-VWLOTQADSA-N Halofantrine Chemical compound FC(F)(F)C1=CC=C2C([C@@H](O)CCN(CCCC)CCCC)=CC3=C(Cl)C=C(Cl)C=C3C2=C1 FOHHNHSLJDZUGQ-VWLOTQADSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 240000005265 Lupinus mutabilis Species 0.000 description 1
- 235000008755 Lupinus mutabilis Nutrition 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- WQKZOPJGWITKEC-UHFFFAOYSA-N N1C(CCCC1)=C1N=C2C(=CC=CC=N2)N1 Chemical class N1C(CCCC1)=C1N=C2C(=CC=CC=N2)N1 WQKZOPJGWITKEC-UHFFFAOYSA-N 0.000 description 1
- RSQWIJXAEXUNEH-UHFFFAOYSA-N OC(CN1C=CC(C=CC=C2)=C2C=C1)=O Chemical compound OC(CN1C=CC(C=CC=C2)=C2C=C1)=O RSQWIJXAEXUNEH-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 235000002357 Ribes grossularia Nutrition 0.000 description 1
- 244000171263 Ribes grossularia Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000007651 Rubus glaucus Species 0.000 description 1
- 235000011034 Rubus glaucus Nutrition 0.000 description 1
- 235000009122 Rubus idaeus Nutrition 0.000 description 1
- 235000019095 Sechium edule Nutrition 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- GFRGAAWGWBUSEB-UHFFFAOYSA-N [3-(quinolin-2-ylmethoxy)phenyl]methyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CC=CC(OCC=2N=C3C=CC=CC3=CC=2)=C1 GFRGAAWGWBUSEB-UHFFFAOYSA-N 0.000 description 1
- GELXFVQAWNTGPQ-UHFFFAOYSA-N [N].C1=CNC=N1 Chemical compound [N].C1=CNC=N1 GELXFVQAWNTGPQ-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
- 150000001538 azepines Chemical class 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- ZDKRMIJRCHPKLW-UHFFFAOYSA-N benzyl methanesulfonate Chemical compound CS(=O)(=O)OCC1=CC=CC=C1 ZDKRMIJRCHPKLW-UHFFFAOYSA-N 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- JQXXHWHPUNPDRT-YOPQJBRCSA-N chembl1332716 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CCN(C)CC1 JQXXHWHPUNPDRT-YOPQJBRCSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 229940075894 denatured ethanol Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 1
- 229940043276 diisopropanolamine Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- UEDZHBJQHGVXQY-UHFFFAOYSA-N ethyl 4-(3-chloro-5,6-dihydroimidazo[2,1-b][3]benzazepin-11-ylidene)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=CC=CC=C2CCN2C(Cl)=CN=C21 UEDZHBJQHGVXQY-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229960003242 halofantrine Drugs 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- DEGGRNHUDQHJOQ-UHFFFAOYSA-N methyl 11-[1-[2-[4-(naphthalen-1-ylmethoxy)phenyl]ethyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CCC=2C=CC(OCC=3C4=CC=CC=C4C=CC=3)=CC=2)CC1 DEGGRNHUDQHJOQ-UHFFFAOYSA-N 0.000 description 1
- BYDXDJKUMAQVNF-UHFFFAOYSA-N methyl 11-[1-[2-[4-(naphthalen-2-ylmethoxy)phenyl]ethyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CCC=2C=CC(OCC=3C=C4C=CC=CC4=CC=3)=CC=2)CC1 BYDXDJKUMAQVNF-UHFFFAOYSA-N 0.000 description 1
- UHTKAUBOWHDYSP-UHFFFAOYSA-N methyl 11-[1-[3-[4-(quinolin-2-ylmethoxy)phenyl]propyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CCCC=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)CC1 UHTKAUBOWHDYSP-UHFFFAOYSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-BKFZFHPZSA-N potassium-44 Chemical compound [44K] ZLMJMSJWJFRBEC-BKFZFHPZSA-N 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 229960005206 pyrazinamide Drugs 0.000 description 1
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 1
- 229960000611 pyrimethamine Drugs 0.000 description 1
- JADFCQKRKICRKI-UHFFFAOYSA-N quinoline;sulfane Chemical compound S.N1=CC=CC2=CC=CC=C21 JADFCQKRKICRKI-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 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
- 230000007017 scission Effects 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- KCDXJAYRVLXPFO-UHFFFAOYSA-N syringaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1O KCDXJAYRVLXPFO-UHFFFAOYSA-N 0.000 description 1
- COBXDAOIDYGHGK-UHFFFAOYSA-N syringaldehyde Natural products COC1=CC=C(C=O)C(OC)=C1O COBXDAOIDYGHGK-UHFFFAOYSA-N 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- MDDPTCUZZASZIQ-UHFFFAOYSA-N tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] MDDPTCUZZASZIQ-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/04—Amoebicides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96200755 | 1996-03-19 | ||
| PCT/EP1997/001264 WO1997034897A1 (en) | 1996-03-19 | 1997-03-11 | Fused imidazole derivatives as multidrug resistance modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK66298A3 SK66298A3 (en) | 1999-06-11 |
| SK284434B6 true SK284434B6 (sk) | 2005-04-01 |
Family
ID=8223797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK662-98A SK284434B6 (sk) | 1996-03-19 | 1997-03-11 | Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze |
Country Status (30)
| Country | Link |
|---|---|
| US (3) | US6218381B1 (es) |
| EP (1) | EP0888352B1 (es) |
| JP (3) | JP3630434B2 (es) |
| KR (2) | KR100349500B1 (es) |
| CN (1) | CN1083453C (es) |
| AR (1) | AR006271A1 (es) |
| AT (1) | ATE241626T1 (es) |
| BG (1) | BG62734B1 (es) |
| BR (1) | BR9708140A (es) |
| CA (1) | CA2237594C (es) |
| CZ (1) | CZ294060B6 (es) |
| DE (1) | DE69722389T2 (es) |
| EA (1) | EA001004B1 (es) |
| EE (1) | EE03773B1 (es) |
| ES (1) | ES2200159T3 (es) |
| HK (1) | HK1015769A1 (es) |
| HR (1) | HRP970161B1 (es) |
| HU (1) | HU224528B1 (es) |
| ID (1) | ID16375A (es) |
| IL (1) | IL124572A (es) |
| MX (1) | MX9804426A (es) |
| MY (1) | MY118282A (es) |
| NO (1) | NO310659B1 (es) |
| NZ (1) | NZ330466A (es) |
| PL (1) | PL193444B1 (es) |
| SK (1) | SK284434B6 (es) |
| TR (1) | TR199801191T2 (es) |
| TW (1) | TW527186B (es) |
| WO (1) | WO1997034897A1 (es) |
| ZA (1) | ZA972351B (es) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69811689T2 (de) * | 1997-09-18 | 2003-12-18 | Janssen Pharmaceutica N.V., Beerse | Kondensierte imidazolderivate zur erhöhung der oralen bioverfügbarkeit von pharmazeutika |
| IL138767A0 (en) * | 1998-04-01 | 2001-10-31 | Rtp Pharma Inc | Anticancer compositions |
| US6743794B2 (en) | 1999-12-22 | 2004-06-01 | Eli Lilly And Company | Methods and compounds for inhibiting MRP1 |
| US6693099B2 (en) | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
| CA2448735C (en) | 2001-06-12 | 2008-10-28 | Janssen Pharmaceutica N.V. | Novel substituted tetracyclic imidazole derivatives, processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine |
| MXPA04004867A (es) * | 2001-11-23 | 2004-07-30 | Janssen Pharmaceutica Nv | El uso de antihistaminicos para la reduccion aguda de presion intracraneal elevada. |
| GB0301736D0 (en) * | 2003-01-24 | 2003-02-26 | Xenova Ltd | Pharmaceutical compounds |
| EP2978765B1 (en) * | 2013-03-25 | 2018-05-02 | Crystal Pharma S.A.U | Methods for the preparation of alcaftadine |
| CN103408549B (zh) * | 2013-06-14 | 2016-01-20 | 苏州汇和药业有限公司 | 一种阿卡他定中间体的制备方法 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2418502C3 (de) * | 1974-04-11 | 1980-04-24 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Dichlorbenzyl- [2-( a -imidazolylbutyl)-phenyl] -äther und -thioäther, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel |
| US4153719A (en) * | 1977-09-06 | 1979-05-08 | Sterling Drug Inc. | Aromatic diketones |
| JPS56125326A (en) * | 1980-03-07 | 1981-10-01 | Asahi Kagaku Kogyo Kk | Preparation of chlorinated phenoxytoluenes in high selectivity |
| US4778931A (en) | 1982-12-01 | 1988-10-18 | Usv Pharmaceutical Corporation | Certain [3-(1-hydroxy hexyl-tetrahydro)naphthalenes], the corresponding naphthalenes having anti-inflammatory and anti-allergic activity |
| US4794188A (en) | 1982-12-01 | 1988-12-27 | Usv Pharmaceutical Corporation | Certain unsymmetrical quinolinyl ethers having anti-inflammatory and anti-allergic activity |
| US4567184A (en) | 1982-12-01 | 1986-01-28 | Usv Pharmaceutical Corporation | Certain aryl or hetero-aryl derivatives of 1-hydroxy-pentane or 1-hydroxy-hexane which are useful for treating inflammation and allergies |
| US4588722A (en) | 1984-01-09 | 1986-05-13 | Janssen Pharmaceutica N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives |
| JPS61151176A (ja) * | 1984-12-24 | 1986-07-09 | Sumitomo Chem Co Ltd | ベンズイミダゾール誘導体およびそれを有効成分とする殺虫、殺ダニ剤 |
| US4631287A (en) * | 1985-04-16 | 1986-12-23 | Usv Pharmaceutical Corp. | Aryl and heteroaryl ethers as agents for the treatment of hypersensitive ailments |
| US4840971A (en) * | 1986-04-07 | 1989-06-20 | Sumitomo Chemical Company, Limited | Novel ether compound, a process for manufacturing the same, a composition containing the same and a use thereof |
| JPS6475441A (en) * | 1987-09-16 | 1989-03-22 | Sumitomo Chemical Co | Production of optically active ether compound |
| JPH01254680A (ja) * | 1988-04-01 | 1989-10-11 | Sumitomo Chem Co Ltd | 複素環化合物、その製造法およびそれを有効成分とする殺菌剤 |
| AU8902591A (en) * | 1990-10-10 | 1992-05-20 | Schering Corporation | Substituted imidazobenzazepines and imidazopyridoazepines |
| IL101850A (en) | 1991-06-13 | 1996-01-31 | Janssen Pharmaceutica Nv | History 11-) 4-Pipridinyl (-Imidazo] B-1, 2 [] 3 [Benzazepine, their preparation and pharmaceutical preparations containing them |
| IL101851A (en) | 1991-06-13 | 1996-05-14 | Janssen Pharmaceutica Nv | History 01 -) 4 - Pipridinyl - and Pipridinylidene (- Imidazo] A-1,2 [Pirolo, Thiano or Purano (] 3,2 [Azpin, their preparation and pharmaceutical preparations containing them and composition |
| GB9122590D0 (en) * | 1991-10-24 | 1991-12-04 | Lilly Industries Ltd | Pharmaceutical compounds |
| ES2135463T3 (es) * | 1992-02-06 | 1999-11-01 | Merrell Pharma Inc | Inversion de la resistencia multi-medicamento por medio de derivados de trifenil-piperidina. |
| RU2134269C1 (ru) | 1992-12-04 | 1999-08-10 | Жансен Фармасетика Н.В. | Производные имидазо/1,2а/тиено/2,3-d/азепинов, способ их получения, промежуточные для их получения, фармацевтическая композиция и способ их получения |
| WO1994022842A1 (en) | 1993-03-29 | 1994-10-13 | Basf Aktiengesellschaft | 1-amino-3-phenoxy propane derivatives as modulators of multi-drug resistance |
| US5674866A (en) | 1993-07-13 | 1997-10-07 | Janssen Pharmaceutica N.V. | Antiallergic imidazoazepines |
| US5486612A (en) * | 1993-12-14 | 1996-01-23 | Eli Lilly And Company | N-benzyl dihydroindole LTD4 antagonists |
| US5596008A (en) * | 1995-02-10 | 1997-01-21 | G. D. Searle & Co. | 3,4-Diaryl substituted pyridines for the treatment of inflammation |
| FR2731708B1 (fr) | 1995-03-13 | 1997-04-30 | Synthelabo | Derives de piperidine, leur procede de preparation et leur application en therapeutique |
| TW382017B (en) | 1995-12-27 | 2000-02-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-(fused imidazole)-piperidine derivatives |
-
1997
- 1997-03-05 TW TW086102623A patent/TW527186B/zh not_active IP Right Cessation
- 1997-03-11 ES ES97908226T patent/ES2200159T3/es not_active Expired - Lifetime
- 1997-03-11 DE DE69722389T patent/DE69722389T2/de not_active Expired - Fee Related
- 1997-03-11 EA EA199800586A patent/EA001004B1/ru unknown
- 1997-03-11 CA CA002237594A patent/CA2237594C/en not_active Expired - Fee Related
- 1997-03-11 KR KR1020017008287A patent/KR100349500B1/ko not_active IP Right Cessation
- 1997-03-11 NZ NZ330466A patent/NZ330466A/xx unknown
- 1997-03-11 SK SK662-98A patent/SK284434B6/sk not_active IP Right Cessation
- 1997-03-11 US US09/142,932 patent/US6218381B1/en not_active Expired - Fee Related
- 1997-03-11 PL PL97327985A patent/PL193444B1/pl not_active IP Right Cessation
- 1997-03-11 AT AT97908226T patent/ATE241626T1/de not_active IP Right Cessation
- 1997-03-11 JP JP53312197A patent/JP3630434B2/ja not_active Expired - Fee Related
- 1997-03-11 TR TR1998/01191T patent/TR199801191T2/xx unknown
- 1997-03-11 IL IL12457297A patent/IL124572A/en not_active IP Right Cessation
- 1997-03-11 CZ CZ19981529A patent/CZ294060B6/cs not_active IP Right Cessation
- 1997-03-11 CN CN97192399A patent/CN1083453C/zh not_active Expired - Fee Related
- 1997-03-11 EP EP97908226A patent/EP0888352B1/en not_active Expired - Lifetime
- 1997-03-11 HU HU9900415A patent/HU224528B1/hu not_active IP Right Cessation
- 1997-03-11 EE EE9800281A patent/EE03773B1/xx not_active IP Right Cessation
- 1997-03-11 WO PCT/EP1997/001264 patent/WO1997034897A1/en active IP Right Grant
- 1997-03-11 KR KR1019980703754A patent/KR100330698B1/ko not_active IP Right Cessation
- 1997-03-11 BR BR9708140A patent/BR9708140A/pt not_active IP Right Cessation
- 1997-03-17 MY MYPI97001123A patent/MY118282A/en unknown
- 1997-03-18 ZA ZA972351A patent/ZA972351B/xx unknown
- 1997-03-18 AR ARP970101072A patent/AR006271A1/es unknown
- 1997-03-19 HR HR970161A patent/HRP970161B1/xx not_active IP Right Cessation
- 1997-03-19 ID IDP970888A patent/ID16375A/id unknown
-
1998
- 1998-05-11 NO NO19982124A patent/NO310659B1/no not_active IP Right Cessation
- 1998-05-18 BG BG102459A patent/BG62734B1/bg active Active
- 1998-06-03 MX MX9804426A patent/MX9804426A/es not_active IP Right Cessation
-
1999
- 1999-02-20 HK HK99100695A patent/HK1015769A1/xx not_active IP Right Cessation
-
2001
- 2001-02-02 US US09/775,524 patent/US6476018B1/en not_active Expired - Fee Related
- 2001-06-01 JP JP2001167003A patent/JP4205319B2/ja not_active Expired - Fee Related
-
2002
- 2002-07-02 US US10/187,665 patent/US20030087895A1/en not_active Abandoned
-
2003
- 2003-10-08 JP JP2003349802A patent/JP4251447B2/ja not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP4310091A1 (en) | Pyrimidine-fused cyclic compound, preparation method therefor and use thereof | |
| KR0184017B1 (ko) | 이미다조[2,1-b][3]벤즈아제핀 유도체,조성물 및 사용방법 | |
| CZ20011082A3 (cs) | Tetrahydropyridoethery | |
| KR102455518B1 (ko) | ＲＯＳ1 저해제로서 치환된 4,5,6,7-테트라히드로피라졸로[1,5-ａ]피리미딘 유도체 및 2,3-디히드로-1Ｈ-이미다조[1,2-ｂ]피라졸 유도체 | |
| JP2023524821A (ja) | Ｅｎｐｐ１のイミノスルファノン阻害剤 | |
| JP2017508777A5 (es) | ||
| SK284434B6 (sk) | Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze | |
| US6544979B1 (en) | Fused imidazole derivatives for improving oral bioavailability of pharmaceutical agents | |
| EP0672047B1 (en) | ANTIALLERGIC IMIDAZO[1,2-a]THIENO[ 2,3-d]AZEPINE DERIVATIVES | |
| EP4223753A1 (en) | Aroyl substituted tricyclic compound, preparation method therefor and use thereof | |
| EP0675889B1 (en) | Antiallergic triazolo(pyrrolo, thieno or furano)azepine derivatives | |
| AU709683C (en) | Fused imidazole derivatives as multidrug resistance modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20100311 |