CZ395592A3 - 4-aryl-3-(heteroarylureido)quinoline derivatives, process of their preparation and use - Google Patents
4-aryl-3-(heteroarylureido)quinoline derivatives, process of their preparation and use Download PDFInfo
- Publication number
- CZ395592A3 CZ395592A3 CS923955A CS395592A CZ395592A3 CZ 395592 A3 CZ395592 A3 CZ 395592A3 CS 923955 A CS923955 A CS 923955A CS 395592 A CS395592 A CS 395592A CZ 395592 A3 CZ395592 A3 CZ 395592A3
- Authority
- CZ
- Czechia
- Prior art keywords
- group
- chlorophenyl
- ureido
- bis
- carbon atoms
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 53
- 238000000034 method Methods 0.000 title claims description 47
- 230000008569 process Effects 0.000 title claims description 19
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title claims description 4
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 102100030817 Liver carboxylesterase 1 Human genes 0.000 claims abstract description 7
- 101710181187 Liver carboxylesterase 1 Proteins 0.000 claims abstract description 7
- -1 nitro, carboxyl Chemical group 0.000 claims description 69
- 125000004432 carbon atom Chemical group C* 0.000 claims description 55
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 21
- 230000002401 inhibitory effect Effects 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 235000012000 cholesterol Nutrition 0.000 claims description 16
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 16
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 15
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 201000001320 Atherosclerosis Diseases 0.000 claims description 11
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 10
- 125000005843 halogen group Chemical group 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
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 8
- 230000031891 intestinal absorption Effects 0.000 claims description 7
- 125000003435 aroyl group Chemical group 0.000 claims description 6
- 238000011161 development Methods 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- CFJGASVGXKHFNU-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6,8-dimethylquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C(C)=CC(C)=C2)C2=C1C1=CC=CC=C1Cl CFJGASVGXKHFNU-UHFFFAOYSA-N 0.000 claims description 4
- WWQVNBJOLRCEGT-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-methylquinolin-3-yl]-3-(6-methoxyquinolin-5-yl)urea Chemical compound COC1=CC=C2N=CC=CC2=C1NC(=O)NC1=CN=C2C=CC(C)=CC2=C1C1=CC=CC=C1Cl WWQVNBJOLRCEGT-UHFFFAOYSA-N 0.000 claims description 4
- VDLRBVKSQXYLTL-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-propan-2-ylquinolin-3-yl]-3-(2,4,6-trimethylpyridin-3-yl)urea Chemical compound C=1C=CC=C(Cl)C=1C=1C2=CC(C(C)C)=CC=C2N=CC=1NC(=O)NC1=C(C)C=C(C)N=C1C VDLRBVKSQXYLTL-UHFFFAOYSA-N 0.000 claims description 4
- BLGFJUMDQXPRKF-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-propan-2-ylquinolin-3-yl]-3-(2,4-dimethoxy-6-methylpyridin-3-yl)urea Chemical compound COC1=CC(C)=NC(OC)=C1NC(=O)NC1=CN=C(C=CC(=C2)C(C)C)C2=C1C1=CC=CC=C1Cl BLGFJUMDQXPRKF-UHFFFAOYSA-N 0.000 claims description 4
- STVFOMFTEVLHRX-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)-2-methoxyquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound COC1=NC2=CC=C(Cl)C=C2C(C=2C(=CC=CC=2)Cl)=C1NC(=O)NC1=C(SC)C=C(C)N=C1SC STVFOMFTEVLHRX-UHFFFAOYSA-N 0.000 claims description 4
- MIYVCFGUUUOXDM-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-(6-methoxyquinolin-5-yl)urea Chemical compound COC1=CC=C2N=CC=CC2=C1NC(=O)NC1=CN=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1Cl MIYVCFGUUUOXDM-UHFFFAOYSA-N 0.000 claims description 4
- WKQRZWDHNZGYNK-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-(6-pentylsulfanylquinolin-5-yl)urea Chemical compound CCCCCSC1=CC=C2N=CC=CC2=C1NC(=O)NC1=CN=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1Cl WKQRZWDHNZGYNK-UHFFFAOYSA-N 0.000 claims description 4
- HFILHSXCOULMNF-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-[6-(4-methoxyphenyl)sulfanylquinolin-5-yl]urea Chemical compound C1=CC(OC)=CC=C1SC1=CC=C(N=CC=C2)C2=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1Cl HFILHSXCOULMNF-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229910052760 oxygen Chemical group 0.000 claims description 4
- 239000001301 oxygen Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 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 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 229910052722 tritium Inorganic materials 0.000 claims description 4
- UJHMZEFSYUKDFO-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-ethylquinolin-3-yl]-3-[2-methyl-4,6-bis(methylsulfanyl)pyrimidin-5-yl]urea Chemical compound C=1C=CC=C(Cl)C=1C=1C2=CC(CC)=CC=C2N=CC=1NC(=O)NC1=C(SC)N=C(C)N=C1SC UJHMZEFSYUKDFO-UHFFFAOYSA-N 0.000 claims description 3
- BBMDXKQMBSGXQK-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-methylquinolin-3-yl]-3-[2-methyl-4,6-bis(methylsulfanyl)pyrimidin-5-yl]urea Chemical compound CSC1=NC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(C)=C2)C2=C1C1=CC=CC=C1Cl BBMDXKQMBSGXQK-UHFFFAOYSA-N 0.000 claims description 3
- OVOORRBSCUQKOA-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-methylquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(C)=C2)C2=C1C1=CC=CC=C1Cl OVOORRBSCUQKOA-UHFFFAOYSA-N 0.000 claims description 3
- PQKKHZSZVUNNBM-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)-2-methoxyquinolin-3-yl]-3-(6-methylsulfanylquinolin-5-yl)urea Chemical compound CSC=1C=CC2=NC=CC=C2C=1NC(=O)NC=1C(OC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl PQKKHZSZVUNNBM-UHFFFAOYSA-N 0.000 claims description 3
- JFZZDTLNDQWGIG-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-(6-methylsulfanylquinolin-5-yl)urea Chemical compound CSC1=CC=C2N=CC=CC2=C1NC(=O)NC1=CN=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1Cl JFZZDTLNDQWGIG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- RAPMRHUHGAGZEN-UHFFFAOYSA-N 6-methylsulfanylquinoline Chemical compound N1=CC=CC2=CC(SC)=CC=C21 RAPMRHUHGAGZEN-UHFFFAOYSA-N 0.000 claims description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 150000003248 quinolines Chemical class 0.000 claims description 3
- BFCAHMANUCIKMY-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-ethylquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound C=1C=CC=C(Cl)C=1C=1C2=CC(CC)=CC=C2N=CC=1NC(=O)NC1=C(SC)C=C(C)N=C1SC BFCAHMANUCIKMY-UHFFFAOYSA-N 0.000 claims description 2
- LOSGGBZAEWLWDA-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-methylquinolin-3-yl]-3-(6-methylsulfanylquinolin-5-yl)urea Chemical compound CSC1=CC=C2N=CC=CC2=C1NC(=O)NC1=CN=C2C=CC(C)=CC2=C1C1=CC=CC=C1Cl LOSGGBZAEWLWDA-UHFFFAOYSA-N 0.000 claims description 2
- ALJNMAPKNAJYHK-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1Cl ALJNMAPKNAJYHK-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000005149 cycloalkylsulfinyl group Chemical group 0.000 claims description 2
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 2
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 2
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- PLKMLYJHIPTLFD-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-[2-methyl-4,6-bis(methylsulfanyl)pyrimidin-5-yl]urea Chemical compound CSC1=NC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1Cl PLKMLYJHIPTLFD-UHFFFAOYSA-N 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000005366 cycloalkylthio group Chemical group 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 14
- 239000003795 chemical substances by application Substances 0.000 abstract description 9
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000000879 anti-atherosclerotic effect Effects 0.000 abstract description 2
- 230000000055 hyoplipidemic effect Effects 0.000 abstract 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 230000037396 body weight Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 150000003230 pyrimidines Chemical class 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000007868 Raney catalyst Substances 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 241000282412 Homo Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000033227 intestinal cholesterol absorption Effects 0.000 description 4
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- HCTISZQLTGAYOX-UHFFFAOYSA-N 4,6-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=C(Cl)N=CN=C1Cl HCTISZQLTGAYOX-UHFFFAOYSA-N 0.000 description 3
- PHRKALCKJDMFMB-UHFFFAOYSA-N 6-chloro-4-(2-chlorophenyl)quinolin-3-amine Chemical compound NC1=CN=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1Cl PHRKALCKJDMFMB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 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 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 150000007514 bases Chemical class 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000000802 nitrating effect Effects 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 150000003222 pyridines Chemical class 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 235000011150 stannous chloride Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
- MZLFQBLHRDHRFT-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-ethylquinolin-3-yl]-3-(6-methylsulfanylquinolin-5-yl)urea Chemical compound C12=CC(CC)=CC=C2N=CC(NC(=O)NC=2C3=CC=CN=C3C=CC=2SC)=C1C1=CC=CC=C1Cl MZLFQBLHRDHRFT-UHFFFAOYSA-N 0.000 description 2
- IKUKWOSAKJWMIZ-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-propan-2-ylquinolin-3-yl]-3-(6-methylsulfanylquinolin-5-yl)urea Chemical compound CSC1=CC=C2N=CC=CC2=C1NC(=O)NC1=CN=C2C=CC(C(C)C)=CC2=C1C1=CC=CC=C1Cl IKUKWOSAKJWMIZ-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- LTDUAVSGOSFGMV-UHFFFAOYSA-N 6-methoxyquinolin-5-amine Chemical compound N1=CC=CC2=C(N)C(OC)=CC=C21 LTDUAVSGOSFGMV-UHFFFAOYSA-N 0.000 description 2
- VZIRTVZMIOEMFW-UHFFFAOYSA-N 6-methyl-2,4-bis(methylsulfanyl)-3-nitropyridine Chemical compound CSC1=CC(C)=NC(SC)=C1[N+]([O-])=O VZIRTVZMIOEMFW-UHFFFAOYSA-N 0.000 description 2
- FKOXWAMEBALEHI-UHFFFAOYSA-N 6-methylsulfanylquinolin-5-amine Chemical compound N1=CC=CC2=C(N)C(SC)=CC=C21 FKOXWAMEBALEHI-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 108010004103 Chylomicrons Proteins 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 238000006477 desulfuration reaction Methods 0.000 description 2
- 230000023556 desulfurization Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000001853 liver microsome Anatomy 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
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 239000012434 nucleophilic reagent Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000001119 stannous chloride Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 150000003585 thioureas Chemical class 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 150000003672 ureas Chemical class 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- WALZVVNZHRGZRS-UHFFFAOYSA-N (2-amino-5-chlorophenyl)-(2-chlorophenyl)methanone;hydrochloride Chemical compound Cl.NC1=CC=C(Cl)C=C1C(=O)C1=CC=CC=C1Cl WALZVVNZHRGZRS-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 1
- NXGHEDHQXXXTTP-UHFFFAOYSA-N 1,1-bis(methylsulfanyl)-2-nitroethene Chemical group CSC(SC)=C[N+]([O-])=O NXGHEDHQXXXTTP-UHFFFAOYSA-N 0.000 description 1
- GXMNIYMEMRNEMU-UHFFFAOYSA-N 1-[2,4-bis(ethylsulfanyl)pyridin-3-yl]-3-[6-chloro-4-(2-fluorophenyl)quinolin-3-yl]urea Chemical compound CCSC1=CC=NC(SCC)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1F GXMNIYMEMRNEMU-UHFFFAOYSA-N 0.000 description 1
- YGWRRBKEXZZFQR-UHFFFAOYSA-N 1-[2,4-bis(ethylsulfanyl)pyridin-3-yl]-3-[8-chloro-4-(2-chlorophenyl)-6-methylquinolin-3-yl]urea Chemical compound CCSC1=CC=NC(SCC)=C1NC(=O)NC1=CN=C(C(Cl)=CC(C)=C2)C2=C1C1=CC=CC=C1Cl YGWRRBKEXZZFQR-UHFFFAOYSA-N 0.000 description 1
- ZPJWMNBBSZDRSA-UHFFFAOYSA-N 1-[2,4-bis(methylsulfanyl)pyridin-3-yl]-3-[4-(2-chlorophenyl)-6-fluoroquinolin-3-yl]urea Chemical compound CSC1=CC=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(F)=C2)C2=C1C1=CC=CC=C1Cl ZPJWMNBBSZDRSA-UHFFFAOYSA-N 0.000 description 1
- YTCGLYVEACJHMT-UHFFFAOYSA-N 1-[2,4-bis(methylsulfanyl)pyridin-3-yl]-3-[6-chloro-4-(2,3,4-trimethoxyphenyl)quinolin-3-yl]urea Chemical compound COC1=C(OC)C(OC)=CC=C1C(C1=CC(Cl)=CC=C1N=C1)=C1NC(=O)NC1=C(SC)C=CN=C1SC YTCGLYVEACJHMT-UHFFFAOYSA-N 0.000 description 1
- JVSLUVWDCQYNRN-UHFFFAOYSA-N 1-[4,6-bis(ethylsulfanyl)-2-methylpyrimidin-5-yl]-3-[6-chloro-4-(2-methoxyphenyl)quinolin-3-yl]urea Chemical compound CCSC1=NC(C)=NC(SCC)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1OC JVSLUVWDCQYNRN-UHFFFAOYSA-N 0.000 description 1
- RJIXJFPQZGMSGE-UHFFFAOYSA-N 1-[4,6-bis(ethylsulfanyl)pyrimidin-5-yl]-3-[6-chloro-4-(2-methylphenyl)quinolin-3-yl]urea Chemical compound CCSC1=NC=NC(SCC)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1C RJIXJFPQZGMSGE-UHFFFAOYSA-N 0.000 description 1
- WTRVMDKVYWNFAF-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6,7-dimethylquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=C(C)C(C)=C2)C2=C1C1=CC=CC=C1Cl WTRVMDKVYWNFAF-UHFFFAOYSA-N 0.000 description 1
- NSORYEDAZLUQHZ-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-propan-2-ylquinolin-3-yl]-3-[2-methyl-4,6-bis(methylsulfanyl)pyrimidin-5-yl]urea Chemical compound CSC1=NC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(=C2)C(C)C)C2=C1C1=CC=CC=C1Cl NSORYEDAZLUQHZ-UHFFFAOYSA-N 0.000 description 1
- FHEYLYHJEAMTRR-UHFFFAOYSA-N 1-[4-(2-chlorophenyl)-6-propan-2-ylquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(=C2)C(C)C)C2=C1C1=CC=CC=C1Cl FHEYLYHJEAMTRR-UHFFFAOYSA-N 0.000 description 1
- HVBROZJUCLGBHD-UHFFFAOYSA-N 1-[6-(difluoromethoxy)-4-phenylquinolin-3-yl]-3-[2-methyl-4,6-bis(methylsulfanyl)pyrimidin-5-yl]urea Chemical compound CSC1=NC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(OC(F)F)=C2)C2=C1C1=CC=CC=C1 HVBROZJUCLGBHD-UHFFFAOYSA-N 0.000 description 1
- MSSRSQIUSLQOLT-UHFFFAOYSA-N 1-[6-(difluoromethylsulfanyl)-4-phenylquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(SC(F)F)=C2)C2=C1C1=CC=CC=C1 MSSRSQIUSLQOLT-UHFFFAOYSA-N 0.000 description 1
- AQRPBNGJYZYYON-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)-8-methylquinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C(C)=CC(Cl)=C2)C2=C1C1=CC=CC=C1Cl AQRPBNGJYZYYON-UHFFFAOYSA-N 0.000 description 1
- ZRYBPTZAJUMJBQ-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-(6-methylquinolin-5-yl)urea Chemical compound CC1=CC=C2N=CC=CC2=C1NC(=O)NC1=CN=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1Cl ZRYBPTZAJUMJBQ-UHFFFAOYSA-N 0.000 description 1
- CGOLIRYMVXYBJI-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-[2-(dimethylamino)-6-methyl-4-methylsulfanylpyridin-3-yl]urea Chemical compound CSC1=CC(C)=NC(N(C)C)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1Cl CGOLIRYMVXYBJI-UHFFFAOYSA-N 0.000 description 1
- ULSZNCHBQWXOHH-UHFFFAOYSA-N 1-[6-chloro-4-(2-chlorophenyl)quinolin-3-yl]-3-[6-methyl-2,4-bis(propan-2-ylsulfanyl)pyridin-3-yl]urea Chemical compound CC(C)SC1=CC(C)=NC(SC(C)C)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1Cl ULSZNCHBQWXOHH-UHFFFAOYSA-N 0.000 description 1
- XJBLYQJKHUJSFE-UHFFFAOYSA-N 1-[6-chloro-4-(2-methylphenyl)quinolin-3-yl]-3-[2-methyl-4,6-bis(methylsulfanyl)pyrimidin-5-yl]urea Chemical compound CSC1=NC(C)=NC(SC)=C1NC(=O)NC1=CN=C(C=CC(Cl)=C2)C2=C1C1=CC=CC=C1C XJBLYQJKHUJSFE-UHFFFAOYSA-N 0.000 description 1
- QSSJAQPITDPDRR-UHFFFAOYSA-N 1-[6-chloro-4-(3,4-dimethoxyphenyl)quinolin-3-yl]-3-[6-methyl-2,4-bis(methylsulfanyl)pyridin-3-yl]urea Chemical compound C1=C(OC)C(OC)=CC=C1C(C1=CC(Cl)=CC=C1N=C1)=C1NC(=O)NC1=C(SC)C=C(C)N=C1SC QSSJAQPITDPDRR-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 description 1
- MHUDSAALSISURX-UHFFFAOYSA-N 2,4,6-trimethylpyridin-3-amine Chemical compound CC1=CC(C)=C(N)C(C)=N1 MHUDSAALSISURX-UHFFFAOYSA-N 0.000 description 1
- AUDCNIVOQSQNFY-UHFFFAOYSA-N 2,4-bis(ethylsulfanyl)pyridin-3-amine Chemical compound CCSC1=CC=NC(SCC)=C1N AUDCNIVOQSQNFY-UHFFFAOYSA-N 0.000 description 1
- JHXPYRUSEULWFB-UHFFFAOYSA-N 2,4-bis(methylsulfanyl)pyridin-3-amine Chemical compound CSC1=CC=NC(SC)=C1N JHXPYRUSEULWFB-UHFFFAOYSA-N 0.000 description 1
- RTXYIHGMYDJHEU-UHFFFAOYSA-N 2,4-dichloro-3-nitropyridine Chemical class [O-][N+](=O)C1=C(Cl)C=CN=C1Cl RTXYIHGMYDJHEU-UHFFFAOYSA-N 0.000 description 1
- MTGIKTMXZFIZLS-UHFFFAOYSA-N 2,4-dichloro-6-methyl-3-nitropyridine Chemical compound CC1=CC(Cl)=C([N+]([O-])=O)C(Cl)=N1 MTGIKTMXZFIZLS-UHFFFAOYSA-N 0.000 description 1
- UAGKFAWCAWENHG-UHFFFAOYSA-N 3-isocyanato-6-methyl-2,4-bis(methylsulfanyl)pyridine Chemical compound CSC1=CC(C)=NC(SC)=C1N=C=O UAGKFAWCAWENHG-UHFFFAOYSA-N 0.000 description 1
- GVZVOMFUIQGLNA-UHFFFAOYSA-N 3-isocyanatoquinoline Chemical compound C1=CC=CC2=CC(N=C=O)=CN=C21 GVZVOMFUIQGLNA-UHFFFAOYSA-N 0.000 description 1
- ZXVRNZRQQRBDLX-UHFFFAOYSA-N 3-nitroquinoline Chemical compound C1=CC=CC2=CC([N+](=O)[O-])=CN=C21 ZXVRNZRQQRBDLX-UHFFFAOYSA-N 0.000 description 1
- MYNWUUDDOPUERP-UHFFFAOYSA-N 4-(2-chlorophenyl)-2-methylsulfanyl-3-nitro-6-propan-2-ylquinoline Chemical compound [O-][N+](=O)C=1C(SC)=NC2=CC=C(C(C)C)C=C2C=1C1=CC=CC=C1Cl MYNWUUDDOPUERP-UHFFFAOYSA-N 0.000 description 1
- YKLADUDJWOOFSX-UHFFFAOYSA-N 4-(2-chlorophenyl)-2-methylsulfanyl-3-nitroquinoline Chemical compound [O-][N+](=O)C=1C(SC)=NC2=CC=CC=C2C=1C1=CC=CC=C1Cl YKLADUDJWOOFSX-UHFFFAOYSA-N 0.000 description 1
- VTOUXLMONDHQQT-UHFFFAOYSA-N 4-(2-chlorophenyl)-6,8-dimethyl-2-methylsulfanyl-3-nitroquinoline Chemical compound [O-][N+](=O)C=1C(SC)=NC2=C(C)C=C(C)C=C2C=1C1=CC=CC=C1Cl VTOUXLMONDHQQT-UHFFFAOYSA-N 0.000 description 1
- BMAYAYYHUYGBNO-UHFFFAOYSA-N 4-(2-chlorophenyl)-6-ethyl-2-methylsulfanyl-3-nitroquinoline Chemical compound C12=CC(CC)=CC=C2N=C(SC)C([N+]([O-])=O)=C1C1=CC=CC=C1Cl BMAYAYYHUYGBNO-UHFFFAOYSA-N 0.000 description 1
- BQOONEKHBMPYON-UHFFFAOYSA-N 4-(2-chlorophenyl)-6-methyl-2-methylsulfanyl-3-nitroquinoline Chemical compound [O-][N+](=O)C=1C(SC)=NC2=CC=C(C)C=C2C=1C1=CC=CC=C1Cl BQOONEKHBMPYON-UHFFFAOYSA-N 0.000 description 1
- PQBQQBALCKZUHM-UHFFFAOYSA-N 4-(2-chlorophenyl)-6-methylquinolin-3-amine Chemical compound C12=CC(C)=CC=C2N=CC(N)=C1C1=CC=CC=C1Cl PQBQQBALCKZUHM-UHFFFAOYSA-N 0.000 description 1
- AUODFDJUGWITSR-UHFFFAOYSA-N 4-(2-chlorophenyl)-6-propan-2-ylquinolin-3-amine Chemical compound C12=CC(C(C)C)=CC=C2N=CC(N)=C1C1=CC=CC=C1Cl AUODFDJUGWITSR-UHFFFAOYSA-N 0.000 description 1
- BPSGVKFIQZZFNH-UHFFFAOYSA-N 4-hydroxy-2-methyl-1h-pyrimidin-6-one Chemical compound CC1=NC(O)=CC(=O)N1 BPSGVKFIQZZFNH-UHFFFAOYSA-N 0.000 description 1
- BKYGVGWYPFVKTK-UHFFFAOYSA-N 4-hydroxy-3-nitro-1h-pyridin-2-one Chemical class OC=1NC=CC(=O)C=1[N+]([O-])=O BKYGVGWYPFVKTK-UHFFFAOYSA-N 0.000 description 1
- QIKWTNPFTOEELW-UHFFFAOYSA-N 4-hydroxy-6-methyl-3-nitro-1h-pyridin-2-one Chemical compound CC1=CC(=O)C([N+]([O-])=O)=C(O)N1 QIKWTNPFTOEELW-UHFFFAOYSA-N 0.000 description 1
- HZCWTTHQRMHIIE-UHFFFAOYSA-N 4-methyl-3-nitro-1h-pyridin-2-one Chemical compound CC=1C=CNC(=O)C=1[N+]([O-])=O HZCWTTHQRMHIIE-UHFFFAOYSA-N 0.000 description 1
- DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical class N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 description 1
- 150000005008 5-aminopyrimidines Chemical class 0.000 description 1
- 150000005015 5-aminoquinolines Chemical class 0.000 description 1
- XIAWHVXDMIFNQR-UHFFFAOYSA-N 5-isocyanato-2-methyl-4,6-bis(methylsulfanyl)pyrimidine Chemical compound CSC1=NC(C)=NC(SC)=C1N=C=O XIAWHVXDMIFNQR-UHFFFAOYSA-N 0.000 description 1
- NOYDQGFVFOQSAJ-UHFFFAOYSA-N 5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=CN=C1 NOYDQGFVFOQSAJ-UHFFFAOYSA-N 0.000 description 1
- PTHNCDSHUBXVLW-UHFFFAOYSA-N 6-chloro-4-(2-chlorophenyl)-2-methylsulfanyl-3-nitroquinoline Chemical compound [O-][N+](=O)C=1C(SC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1Cl PTHNCDSHUBXVLW-UHFFFAOYSA-N 0.000 description 1
- GIMHFTJFCRTQRS-UHFFFAOYSA-N 6-chloro-5-nitroquinoline Chemical compound C1=CC=C2C([N+](=O)[O-])=C(Cl)C=CC2=N1 GIMHFTJFCRTQRS-UHFFFAOYSA-N 0.000 description 1
- GKJSZXGYFJBYRQ-UHFFFAOYSA-N 6-chloroquinoline Chemical compound N1=CC=CC2=CC(Cl)=CC=C21 GKJSZXGYFJBYRQ-UHFFFAOYSA-N 0.000 description 1
- RYJDGHWDTDEBGQ-UHFFFAOYSA-N 6-methoxy-5-nitroquinoline Chemical compound N1=CC=CC2=C([N+]([O-])=O)C(OC)=CC=C21 RYJDGHWDTDEBGQ-UHFFFAOYSA-N 0.000 description 1
- HFDLDPJYCIEXJP-UHFFFAOYSA-N 6-methoxyquinoline Chemical compound N1=CC=CC2=CC(OC)=CC=C21 HFDLDPJYCIEXJP-UHFFFAOYSA-N 0.000 description 1
- IQVWDAKMASGPBX-UHFFFAOYSA-N 6-methyl-2,4-bis(methylsulfanyl)pyridin-3-amine Chemical compound CSC1=CC(C)=NC(SC)=C1N IQVWDAKMASGPBX-UHFFFAOYSA-N 0.000 description 1
- URGZMAYEXNPXEH-UHFFFAOYSA-N 6-methylsulfanyl-5-nitroquinoline Chemical compound N1=CC=CC2=C([N+]([O-])=O)C(SC)=CC=C21 URGZMAYEXNPXEH-UHFFFAOYSA-N 0.000 description 1
- SHVCSCWHWMSGTE-UHFFFAOYSA-N 6-methyluracil Chemical compound CC1=CC(=O)NC(=O)N1 SHVCSCWHWMSGTE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910000838 Al alloy Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000238017 Astacoidea Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 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
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241001562081 Ikeda Species 0.000 description 1
- LCGISIDBXHGCDW-VKHMYHEASA-N L-glutamine amide Chemical compound NC(=O)[C@@H](N)CCC(N)=O LCGISIDBXHGCDW-VKHMYHEASA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 1
- 108010054082 Sterol O-acyltransferase Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- JRBRVDCKNXZZGH-UHFFFAOYSA-N alumane;copper Chemical compound [AlH3].[Cu] JRBRVDCKNXZZGH-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 150000005005 aminopyrimidines Chemical class 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- QDWJUBJKEHXSMT-UHFFFAOYSA-N boranylidynenickel Chemical compound [Ni]#B QDWJUBJKEHXSMT-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 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 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- RPMXALUWKZHYOV-UHFFFAOYSA-N nitroethene Chemical group [O-][N+](=O)C=C RPMXALUWKZHYOV-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- GGOZGYRTNQBSSA-UHFFFAOYSA-N pyridine-2,3-diol Chemical compound OC1=CC=CN=C1O GGOZGYRTNQBSSA-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- XMIAFAKRAAMSGX-UHFFFAOYSA-N quinolin-5-amine Chemical compound C1=CC=C2C(N)=CC=CC2=N1 XMIAFAKRAAMSGX-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000005978 reductive desulfurization reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical group [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69232391A | 1991-04-26 | 1991-04-26 | |
| PCT/US1992/001801 WO1992019614A1 (en) | 1991-04-26 | 1992-03-16 | 4-aryl-3-(heteroarylureido)quinoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ395592A3 true CZ395592A3 (en) | 1994-02-16 |
Family
ID=24780107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS923955A CZ395592A3 (en) | 1991-04-26 | 1992-03-16 | 4-aryl-3-(heteroarylureido)quinoline derivatives, process of their preparation and use |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0590094A1 (OSRAM) |
| JP (1) | JPH0776215B2 (OSRAM) |
| CN (1) | CN1066068A (OSRAM) |
| AU (1) | AU1879792A (OSRAM) |
| BR (1) | BR9205939A (OSRAM) |
| CA (1) | CA2108014A1 (OSRAM) |
| CZ (1) | CZ395592A3 (OSRAM) |
| DE (1) | DE9290049U1 (OSRAM) |
| FI (1) | FI934710A7 (OSRAM) |
| HU (1) | HUT65748A (OSRAM) |
| IE (1) | IE921330A1 (OSRAM) |
| IL (1) | IL101627A0 (OSRAM) |
| MX (1) | MX9201916A (OSRAM) |
| NO (1) | NO933837L (OSRAM) |
| NZ (1) | NZ242493A (OSRAM) |
| PT (1) | PT100426A (OSRAM) |
| TW (1) | TW197436B (OSRAM) |
| WO (1) | WO1992019614A1 (OSRAM) |
| YU (1) | YU44592A (OSRAM) |
| ZA (1) | ZA922976B (OSRAM) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2125325T3 (es) * | 1992-01-23 | 1999-03-01 | Pfizer | Derivados de 4-fenil-3-(heteroarilureido)-1,2-dihidro-2-oxoquinolina como agentes antihipercolesterolemicos y antiateroscleroticos. |
| US5565472A (en) * | 1992-12-21 | 1996-10-15 | Pfizer Inc. | 4-aryl-3-(heteroarylureido)-1,2-dihydro-2-oxo-quinoline derivatives as antihypercholesterolemic and antiatherosclerotic agents |
| NZ264063A (en) * | 1993-08-13 | 1995-11-27 | Nihon Nohyaku Co Ltd | N-(2-phenylpyrid-3-yl)- and n-(4-phenylpyrimidin-5-yl)-n'-phenylurea derivatives and pharmaceutical compositions |
| US5843957A (en) * | 1995-05-19 | 1998-12-01 | Sumitomo Pharmaceuticals Company, Ltd. | Naphthyridine derivatives |
| AU699091B2 (en) * | 1995-05-31 | 1998-11-19 | Dainippon Sumitomo Pharma Co., Ltd. | Novel naphthyridine derivatives |
| EP0947515A4 (en) * | 1996-11-26 | 2002-10-23 | Sumitomo Pharma | NEW NAPHTHYRIDINE DERIVATIVES |
| CA2321237A1 (en) | 1998-02-25 | 1999-09-02 | Masami Muraoka | Pyridone derivatives and process for producing the same |
| US6452008B2 (en) | 1998-02-25 | 2002-09-17 | Sumitomo Pharmaceuticals Company, Limited | Pyridone derivatives and process for preparing the same |
| SV2005001973A (es) | 2003-12-12 | 2005-11-04 | Wyeth Corp | Quinolinas utiles en el tratamiento de enfermedades cardiovasculares ref. wyth0090-504 (am101500) |
| CN103601677B (zh) * | 2013-11-19 | 2015-11-18 | 清华大学 | 制备2-烷硫基喹啉衍生物的方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE892088L (en) * | 1988-07-12 | 1990-01-12 | William Henry Deryk Morris | Quinoline derivatives, their production and use |
| WO1991004027A1 (en) * | 1989-09-15 | 1991-04-04 | Pfizer Inc. | New n-aryl and n-heteroarylamide and urea derivatives as inhibitors of acyl coenzyme a: cholesterol acyl transferase (acat) |
| TW205037B (OSRAM) * | 1989-10-06 | 1993-05-01 | Takeda Pharm Industry Co Ltd |
-
1992
- 1992-03-16 WO PCT/US1992/001801 patent/WO1992019614A1/en not_active Application Discontinuation
- 1992-03-16 EP EP92923349A patent/EP0590094A1/en not_active Withdrawn
- 1992-03-16 BR BR9205939A patent/BR9205939A/pt not_active Application Discontinuation
- 1992-03-16 JP JP4510186A patent/JPH0776215B2/ja not_active Expired - Lifetime
- 1992-03-16 AU AU18797/92A patent/AU1879792A/en not_active Abandoned
- 1992-03-16 FI FI934710A patent/FI934710A7/fi unknown
- 1992-03-16 HU HU9303025A patent/HUT65748A/hu active IP Right Revival
- 1992-03-16 CZ CS923955A patent/CZ395592A3/cs unknown
- 1992-03-16 CA CA002108014A patent/CA2108014A1/en not_active Abandoned
- 1992-03-16 DE DE9290049U patent/DE9290049U1/de not_active Expired - Lifetime
- 1992-03-17 TW TW081102005A patent/TW197436B/zh active
- 1992-03-24 ZA ZA922976A patent/ZA922976B/xx unknown
- 1992-04-16 IL IL101627A patent/IL101627A0/xx unknown
- 1992-04-24 MX MX9201916A patent/MX9201916A/es not_active IP Right Cessation
- 1992-04-24 IE IE133092A patent/IE921330A1/en not_active Application Discontinuation
- 1992-04-24 YU YU44592A patent/YU44592A/sh unknown
- 1992-04-24 PT PT100426A patent/PT100426A/pt not_active Application Discontinuation
- 1992-04-24 NZ NZ242493A patent/NZ242493A/en unknown
- 1992-04-25 CN CN92103010A patent/CN1066068A/zh active Pending
-
1993
- 1993-10-25 NO NO933837A patent/NO933837L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE9290049U1 (de) | 1994-01-05 |
| EP0590094A1 (en) | 1994-04-06 |
| TW197436B (OSRAM) | 1993-01-01 |
| NZ242493A (en) | 1994-08-26 |
| HUT65748A (en) | 1994-07-28 |
| MX9201916A (es) | 1992-11-01 |
| CA2108014A1 (en) | 1992-10-27 |
| NO933837L (no) | 1993-10-25 |
| JPH06501025A (ja) | 1994-01-27 |
| BR9205939A (pt) | 1994-09-27 |
| IL101627A0 (en) | 1992-12-30 |
| YU44592A (sh) | 1994-12-28 |
| FI934710L (fi) | 1993-10-25 |
| ZA922976B (en) | 1993-10-25 |
| AU1879792A (en) | 1992-12-21 |
| PT100426A (pt) | 1993-08-31 |
| FI934710A0 (fi) | 1993-10-25 |
| HU9303025D0 (en) | 1994-01-28 |
| WO1992019614A1 (en) | 1992-11-12 |
| JPH0776215B2 (ja) | 1995-08-16 |
| CN1066068A (zh) | 1992-11-11 |
| FI934710A7 (fi) | 1993-10-25 |
| IE921330A1 (en) | 1992-11-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5596001A (en) | 4-aryl-3-(heteroarylureido)quinoline derivatves | |
| EP1254138B1 (en) | Pyridine derivatives inhibiting angiogenesis and/or vegf receptor tyrosine kinase | |
| US5885996A (en) | Antiproliferative quinazolines | |
| AU740318B2 (en) | Dihydropyrimidines | |
| TWI411437B (zh) | ４－嘧啶磺醯胺衍生物 | |
| AU2010210178B2 (en) | Indole derivatives as anticancer agents | |
| JP4155827B2 (ja) | オキサゾロ−およびフロピリミジンならびに腫瘍に対する医薬としてのその使用 | |
| US4636506A (en) | 7-heterocyclic-1,4-dihydroquinolones | |
| US5565472A (en) | 4-aryl-3-(heteroarylureido)-1,2-dihydro-2-oxo-quinoline derivatives as antihypercholesterolemic and antiatherosclerotic agents | |
| KR20060124727A (ko) | 당뇨병의 치료에 유용한 헤테로아릴아미노피라졸 유도체 | |
| CZ395592A3 (en) | 4-aryl-3-(heteroarylureido)quinoline derivatives, process of their preparation and use | |
| CA2128093C (en) | 4-aryl-3-(heteroarylureido)-1,2-dihydro-2-oxoquinoline derivatives as antihypercholesterolemic and antiatherosclerotic agents | |
| CS241549B2 (en) | Method of 1,4-dihydropyridines production | |
| SK15082002A3 (sk) | Derivát pyridín-1-oxidu a spôsob jeho transformácie na farmaceuticky účinné zlúčeniny | |
| IE54496B1 (en) | 4-(1-oxido-pyridine)-1,4-dihydropyridine derivatives and pharmaceutical use thereof | |
| JPS6024794B2 (ja) | オキサジアゾロピリミジン誘導体 | |
| CA2260057A1 (en) | Novel compounds | |
| EP0218423B1 (en) | 9-(Substituted thio)-4H-pyrido[1,2-a]pyrimidin-4-one derivatives, their manufacture and use | |
| Tandel et al. | Design, synthesis and biological potential of some isoxazole and hydroxypyrimidine derivatives containing pyrido [2, 3-d] pyrimidine nucleus via chalcone series | |
| WO2002083650A1 (en) | Novel sulfonylamino-pyrimidines | |
| JPS61140568A (ja) | キナゾリン誘導体及びそれを有効成分とする血圧降下剤 | |
| Bertacche et al. | Synthesis of 4-dialkylaminopyridine derivatives through ring-rearrangement of 3-nitro-2H-pyran-2-one acetamidines | |
| Zimmer et al. | Synthesis of 8‐Substituted Xanthines and Their Oxidative Skeleton Rearrangement to 1‐Oxo‐2, 4, 7, 9‐tetraazaspiro [4, 5] dec‐2‐ene‐6, 8, 10‐triones | |
| WO1997000875A1 (en) | Benzimidazole derivatives containing fused pyridine | |
| KR100267595B1 (ko) | 신규한 이소퀴놀린계 항암 활성 화합물 |