CA2431100C - Dihydroindole and tetrahydroquinoline derivatives - Google Patents
Dihydroindole and tetrahydroquinoline derivatives Download PDFInfo
- Publication number
- CA2431100C CA2431100C CA002431100A CA2431100A CA2431100C CA 2431100 C CA2431100 C CA 2431100C CA 002431100 A CA002431100 A CA 002431100A CA 2431100 A CA2431100 A CA 2431100A CA 2431100 C CA2431100 C CA 2431100C
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- dihydro
- allyl
- amino
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 title description 3
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 138
- 238000011282 treatment Methods 0.000 claims abstract description 39
- 150000002148 esters Chemical class 0.000 claims abstract description 37
- 238000011321 prophylaxis Methods 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 15
- 201000005577 familial hyperlipidemia Diseases 0.000 claims abstract description 14
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 11
- 208000019553 vascular disease Diseases 0.000 claims abstract description 11
- 208000002705 Glucose Intolerance Diseases 0.000 claims abstract description 9
- 208000031888 Mycoses Diseases 0.000 claims abstract description 9
- 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 9
- 201000001883 cholelithiasis Diseases 0.000 claims abstract description 9
- 208000001130 gallstones Diseases 0.000 claims abstract description 9
- 201000009104 prediabetes syndrome Diseases 0.000 claims abstract description 9
- 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 8
- 229910052720 vanadium Inorganic materials 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 197
- -1 5-{5-[Ethyl-(2-hydroxy-ethyl)-amino]-pent-1-ynyl}-6-fluoro-2,3-dihydro-indole-carboxylic acid 4-chloro-phenyl ester Chemical compound 0.000 claims description 109
- 239000000203 mixture Substances 0.000 claims description 44
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 35
- 239000000460 chlorine Chemical group 0.000 claims description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 30
- 108010059597 Lanosterol synthase Proteins 0.000 claims description 25
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 229910052801 chlorine Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 230000003463 hyperproliferative effect Effects 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 11
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 10
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 9
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 claims description 8
- 208000030852 Parasitic disease Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 230000036281 parasite infection Effects 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
- 229910052770 Uranium Inorganic materials 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 229910052721 tungsten Inorganic materials 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- MSZJEPVVQWJCIF-UHFFFAOYSA-N butylazanide Chemical compound CCCC[NH-] MSZJEPVVQWJCIF-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- KEOLJAPWYNIYSB-UHFFFAOYSA-N phenyl 6-fluoro-5-[5-[methyl(propyl)amino]pentyl]-2,3-dihydroindole-1-carboxylate Chemical compound C1=2C=C(F)C(CCCCCN(C)CCC)=CC=2CCN1C(=O)OC1=CC=CC=C1 KEOLJAPWYNIYSB-UHFFFAOYSA-N 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- VJROPLWGFCORRM-UHFFFAOYSA-N 2-methylbutan-1-amine Chemical compound CCC(C)CN VJROPLWGFCORRM-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 claims description 2
- 108091006662 SLC9B1 Proteins 0.000 claims description 2
- 102100022894 Sodium/hydrogen exchanger 9B1 Human genes 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 108020001305 NR1 subfamily Proteins 0.000 claims 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 2
- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 claims 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- UOVHUKALBVIUIA-ONEGZZNKSA-N [4-(4-chlorophenyl)phenyl]-[5-[(e)-3-(dimethylamino)prop-1-enyl]-2,3-dihydroindol-1-yl]methanone Chemical compound C1CC2=CC(/C=C/CN(C)C)=CC=C2N1C(=O)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 UOVHUKALBVIUIA-ONEGZZNKSA-N 0.000 claims 1
- NHENIDFQHLFNCW-HWKANZROSA-N [4-(4-chlorophenyl)phenyl]-[6-[(e)-3-(dimethylamino)prop-1-enyl]-3,4-dihydro-2h-quinolin-1-yl]methanone Chemical compound C1CCC2=CC(/C=C/CN(C)C)=CC=C2N1C(=O)C(C=C1)=CC=C1C1=CC=C(Cl)C=C1 NHENIDFQHLFNCW-HWKANZROSA-N 0.000 claims 1
- MSMPLXRSOJIFRU-GQCTYLIASA-N [4-(4-chlorophenyl)phenyl]-[6-[(e)-3-piperidin-1-ylprop-1-enyl]-3,4-dihydro-2h-quinolin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C1=CC=C(C(=O)N2C3=CC=C(\C=C\CN4CCCCC4)C=C3CCC2)C=C1 MSMPLXRSOJIFRU-GQCTYLIASA-N 0.000 claims 1
- PYGUNRFYGSTNSM-VOTSOKGWSA-N [5-[(e)-3-(dimethylamino)prop-1-enyl]-2,3-dihydroindol-1-yl]-(4-phenylphenyl)methanone Chemical compound C1CC2=CC(/C=C/CN(C)C)=CC=C2N1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 PYGUNRFYGSTNSM-VOTSOKGWSA-N 0.000 claims 1
- GAZTZPKDWRNADT-GQCTYLIASA-N [6-[(e)-3-(dimethylamino)prop-1-enyl]-3,4-dihydro-2h-quinolin-1-yl]-[6-(4-methylphenyl)pyridin-3-yl]methanone Chemical compound C1CCC2=CC(/C=C/CN(C)C)=CC=C2N1C(=O)C(C=N1)=CC=C1C1=CC=C(C)C=C1 GAZTZPKDWRNADT-GQCTYLIASA-N 0.000 claims 1
- LEVKKZKUBVUNQB-UHFFFAOYSA-N [6-[3-(dimethylamino)propyl]-3,4-dihydro-2h-quinolin-1-yl]-(4-phenylphenyl)methanone Chemical compound C1CCC2=CC(CCCN(C)C)=CC=C2N1C(=O)C(C=C1)=CC=C1C1=CC=CC=C1 LEVKKZKUBVUNQB-UHFFFAOYSA-N 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- YJJAYCCFZFDAHI-UHFFFAOYSA-N ethyl 6-[3-(dimethylamino)propyl]-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound CN(C)CCCC1=CC=C2N(C(=O)OCC)CCCC2=C1 YJJAYCCFZFDAHI-UHFFFAOYSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 101150009274 nhr-1 gene Proteins 0.000 claims 1
- 229940058690 lanosterol Drugs 0.000 abstract description 8
- 101710095468 Cyclase Proteins 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 112
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 62
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 54
- 150000001412 amines Chemical class 0.000 description 39
- 239000012948 isocyanate Substances 0.000 description 38
- 239000003921 oil Substances 0.000 description 37
- 235000019198 oils Nutrition 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 239000000741 silica gel Substances 0.000 description 36
- 229910002027 silica gel Inorganic materials 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
- 238000004440 column chromatography Methods 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 30
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 27
- 239000012230 colorless oil Substances 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
- 125000004432 carbon atom Chemical group C* 0.000 description 24
- 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 description 24
- 238000001704 evaporation Methods 0.000 description 23
- 230000008020 evaporation Effects 0.000 description 23
- 235000019253 formic acid Nutrition 0.000 description 22
- 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 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- UHBGYFCCKRAEHA-UHFFFAOYSA-N P-toluamide Chemical compound CC1=CC=C(C(N)=O)C=C1 UHBGYFCCKRAEHA-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000012071 phase Substances 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
- 125000000217 alkyl group Chemical group 0.000 description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 15
- SHNMAZJVVFUXAQ-UHFFFAOYSA-N 2h-quinoline-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)CC=CC2=C1 SHNMAZJVVFUXAQ-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- IOXXVNYDGIXMIP-UHFFFAOYSA-N n-methylprop-2-en-1-amine Chemical compound CNCC=C IOXXVNYDGIXMIP-UHFFFAOYSA-N 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 108010028554 LDL Cholesterol Proteins 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 11
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 11
- 238000001035 drying Methods 0.000 description 11
- 238000005984 hydrogenation reaction Methods 0.000 description 11
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000012876 carrier material Substances 0.000 description 10
- 235000012000 cholesterol Nutrition 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 150000002430 hydrocarbons Chemical group 0.000 description 8
- UTWGRMYWDUMKNY-UHFFFAOYSA-N indole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)C=CC2=C1 UTWGRMYWDUMKNY-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical class NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 8
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 7
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 7
- 239000005711 Benzoic acid Substances 0.000 description 7
- 229960004365 benzoic acid Drugs 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 7
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 6
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 6
- RYWGPCLTVXMMHO-UHFFFAOYSA-N (4-chlorophenyl) carbonochloridate Chemical compound ClC(=O)OC1=CC=C(Cl)C=C1 RYWGPCLTVXMMHO-UHFFFAOYSA-N 0.000 description 6
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 6
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 6
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 6
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- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- BLXKHEUAKLQEMG-UHFFFAOYSA-N n-(2,4-difluorophenyl)sulfamoyl chloride Chemical compound FC1=CC=C(NS(Cl)(=O)=O)C(F)=C1 BLXKHEUAKLQEMG-UHFFFAOYSA-N 0.000 description 1
- GNQZBZVLWVTROL-UHFFFAOYSA-N n-(2,5-difluorophenyl)sulfamoyl chloride Chemical compound FC1=CC=C(F)C(NS(Cl)(=O)=O)=C1 GNQZBZVLWVTROL-UHFFFAOYSA-N 0.000 description 1
- GLLOHZQKWOMVPE-UHFFFAOYSA-N n-(3,4-difluorophenyl)sulfamoyl chloride Chemical compound FC1=CC=C(NS(Cl)(=O)=O)C=C1F GLLOHZQKWOMVPE-UHFFFAOYSA-N 0.000 description 1
- SOJHGFBIRSMXDU-UHFFFAOYSA-N n-(3-fluorophenyl)sulfamoyl chloride Chemical compound FC1=CC=CC(NS(Cl)(=O)=O)=C1 SOJHGFBIRSMXDU-UHFFFAOYSA-N 0.000 description 1
- MRJGQLHGBRMASH-UHFFFAOYSA-N n-(4-bromophenyl)-6-[4-(diethylamino)butoxy]-3,4-dihydro-2h-quinoline-1-carboxamide Chemical compound C1CCC2=CC(OCCCCN(CC)CC)=CC=C2N1C(=O)NC1=CC=C(Br)C=C1 MRJGQLHGBRMASH-UHFFFAOYSA-N 0.000 description 1
- BJXKXMSPQMNDCE-UHFFFAOYSA-N n-(4-bromophenyl)sulfamoyl chloride Chemical compound ClS(=O)(=O)NC1=CC=C(Br)C=C1 BJXKXMSPQMNDCE-UHFFFAOYSA-N 0.000 description 1
- BRILQXRAARKYQS-UHFFFAOYSA-N n-(4-chlorophenyl)sulfamoyl chloride Chemical compound ClC1=CC=C(NS(Cl)(=O)=O)C=C1 BRILQXRAARKYQS-UHFFFAOYSA-N 0.000 description 1
- YWPIMVUCLRVUIE-UHFFFAOYSA-N n-(4-cyanophenyl)sulfamoyl chloride Chemical compound ClS(=O)(=O)NC1=CC=C(C#N)C=C1 YWPIMVUCLRVUIE-UHFFFAOYSA-N 0.000 description 1
- XNKZWQJLJWLNGJ-UHFFFAOYSA-N n-(4-fluorophenyl)sulfamoyl chloride Chemical compound FC1=CC=C(NS(Cl)(=O)=O)C=C1 XNKZWQJLJWLNGJ-UHFFFAOYSA-N 0.000 description 1
- CTFBDJCYUWONRY-UHFFFAOYSA-N n-(4-methoxyphenyl)sulfamoyl chloride Chemical compound COC1=CC=C(NS(Cl)(=O)=O)C=C1 CTFBDJCYUWONRY-UHFFFAOYSA-N 0.000 description 1
- YBVNKMPQGIJNCH-UHFFFAOYSA-N n-(4-methylphenyl)sulfamoyl chloride Chemical compound CC1=CC=C(NS(Cl)(=O)=O)C=C1 YBVNKMPQGIJNCH-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CLYYLYYRTGRJTL-UHFFFAOYSA-N n-butylsulfamoyl chloride Chemical compound CCCCNS(Cl)(=O)=O CLYYLYYRTGRJTL-UHFFFAOYSA-N 0.000 description 1
- ANORDWOIBSUYBN-UHFFFAOYSA-N n-chloro-1-phenylmethanamine Chemical compound ClNCC1=CC=CC=C1 ANORDWOIBSUYBN-UHFFFAOYSA-N 0.000 description 1
- VGEMYWDUTPQWBN-UHFFFAOYSA-N n-ethyl-2-methoxyethanamine Chemical compound CCNCCOC VGEMYWDUTPQWBN-UHFFFAOYSA-N 0.000 description 1
- QECNBMJRDWINKS-UHFFFAOYSA-N n-fluoro-1-phenylmethanamine Chemical compound FNCC1=CC=CC=C1 QECNBMJRDWINKS-UHFFFAOYSA-N 0.000 description 1
- SGSHEKZPIDTZJQ-UHFFFAOYSA-N n-phenylsulfamoyl chloride Chemical compound ClS(=O)(=O)NC1=CC=CC=C1 SGSHEKZPIDTZJQ-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000013146 percutaneous coronary intervention Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000011324 primary prophylaxis Methods 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000018770 reduced food intake Nutrition 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004141 reverse cholesterol transport Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- OUXVVTOJLSUKRW-UHFFFAOYSA-N tert-butyl 5-(5-methylsulfonyloxypentyl)-2,3-dihydroindole-1-carboxylate Chemical compound CS(=O)(=O)OCCCCCC1=CC=C2N(C(=O)OC(C)(C)C)CCC2=C1 OUXVVTOJLSUKRW-UHFFFAOYSA-N 0.000 description 1
- PTYHAGBRBKLTDR-UHFFFAOYSA-N tert-butyl 6-(4-bromobut-2-enoxy)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound BrCC=CCOC1=CC=C2N(C(=O)OC(C)(C)C)CCCC2=C1 PTYHAGBRBKLTDR-UHFFFAOYSA-N 0.000 description 1
- LNXYBGFLJPKXEK-UHFFFAOYSA-N tert-butyl 6-(5-bromopentoxy)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound BrCCCCCOC1=CC=C2N(C(=O)OC(C)(C)C)CCCC2=C1 LNXYBGFLJPKXEK-UHFFFAOYSA-N 0.000 description 1
- GKZKGOWBYJQQJI-UHFFFAOYSA-N tert-butyl 6-(5-hydroxypent-1-ynyl)-3,4-dihydro-2h-quinoline-1-carboxylate Chemical compound OCCCC#CC1=CC=C2N(C(=O)OC(C)(C)C)CCCC2=C1 GKZKGOWBYJQQJI-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 1
- RSPCKAHMRANGJZ-UHFFFAOYSA-N thiohydroxylamine Chemical compound SN RSPCKAHMRANGJZ-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000005490 tosylate group Chemical group 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
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- JQZIKLPHXXBMCA-UHFFFAOYSA-N triphenylmethanethiol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(S)C1=CC=CC=C1 JQZIKLPHXXBMCA-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 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
- C07D215/20—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P31/10—Antimycotics
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00128063.5 | 2000-12-21 | ||
| EP00128063 | 2000-12-21 | ||
| PCT/EP2001/014620 WO2002050041A1 (en) | 2000-12-21 | 2001-12-12 | Dihydroindole and tetrahydroquinoline derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2431100A1 CA2431100A1 (en) | 2002-06-27 |
| CA2431100C true CA2431100C (en) | 2009-03-24 |
Family
ID=8170751
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002431100A Expired - Fee Related CA2431100C (en) | 2000-12-21 | 2001-12-12 | Dihydroindole and tetrahydroquinoline derivatives |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US6706751B2 (enExample) |
| EP (1) | EP1358162B1 (enExample) |
| JP (1) | JP4068459B2 (enExample) |
| KR (1) | KR100530408B1 (enExample) |
| CN (1) | CN1208322C (enExample) |
| AR (1) | AR035408A1 (enExample) |
| AT (1) | ATE317386T1 (enExample) |
| AU (2) | AU1917602A (enExample) |
| BR (1) | BR0116263A (enExample) |
| CA (1) | CA2431100C (enExample) |
| DE (1) | DE60117096T2 (enExample) |
| ES (1) | ES2257381T3 (enExample) |
| MX (1) | MXPA03005395A (enExample) |
| WO (1) | WO2002050041A1 (enExample) |
| ZA (1) | ZA200304646B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20040522A1 (es) | 2002-05-29 | 2004-09-28 | Novartis Ag | Derivados de diarilurea dependientes de la cinasa de proteina |
| HRP20050181A2 (en) * | 2002-08-29 | 2006-03-31 | Merck & Co. Inc. | Indoles having anti-diabetic activity |
| JP4479656B2 (ja) * | 2003-08-08 | 2010-06-09 | 宇部興産株式会社 | アルキニル基置換縮合ヘテロ環化合物及びその製法並びにそれを使用する有機エレクトロルミネッセンス素子 |
| TWI329102B (en) * | 2006-08-15 | 2010-08-21 | Nat Health Research Institutes | Thiourea compounds and method for inhibiting hepatitis c virus infection |
| WO2008124300A1 (en) * | 2007-04-10 | 2008-10-16 | National Health Research Institutes | Hepatitis c virus inhibitors |
| WO2008154091A1 (en) * | 2007-06-08 | 2008-12-18 | National Health Research Institutes | Thiourea derivatives |
| TWI361808B (en) * | 2008-01-08 | 2012-04-11 | Nat Health Research Institutes | Imidazolidinone and imidazolidinethione derivatives |
| US8198284B2 (en) * | 2008-04-30 | 2012-06-12 | National Health Research Institutes | Treatment of neurodegenerative disorders with thiourea compounds |
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|---|---|---|---|---|
| US3997542A (en) * | 1975-06-23 | 1976-12-14 | Sterling Drug Inc. | 1-(Halogenated-acetyl)-1,2,3,4-tetrahydro-6-quinolinols and esters thereof |
| NZ227042A (en) | 1987-11-27 | 1991-05-28 | Banyu Pharma Co Ltd | Substituted alkylamine derivatives and pharmaceutical compositions |
| US5288749A (en) | 1991-12-20 | 1994-02-22 | Abbott Laboratories | Tertiary and secondary amines as alpha-2 antagonists and serotonin uptake inhibitors |
| TW438774B (en) | 1993-07-14 | 2001-06-07 | Hoffmann La Roche | Pharmaceutical composition for lowering cholesterol containing phenalkylamines and certain novel phenalkylamines |
| AU1608397A (en) | 1996-02-02 | 1997-08-22 | Zeneca Limited | Heterocyclic compounds useful as pharmaceutical agents |
| DE19727117A1 (de) | 1997-06-26 | 1999-01-07 | Boehringer Ingelheim Pharma | Phenylalkylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US7229986B2 (en) | 2000-05-16 | 2007-06-12 | Takeda Pharmaceutical Company Ltd. | Melanin-concentrating hormone antagonist |
-
2001
- 2001-12-11 US US10/014,959 patent/US6706751B2/en not_active Expired - Fee Related
- 2001-12-12 AU AU1917602A patent/AU1917602A/xx active Pending
- 2001-12-12 DE DE60117096T patent/DE60117096T2/de not_active Expired - Lifetime
- 2001-12-12 MX MXPA03005395A patent/MXPA03005395A/es active IP Right Grant
- 2001-12-12 KR KR10-2003-7008393A patent/KR100530408B1/ko not_active Expired - Fee Related
- 2001-12-12 WO PCT/EP2001/014620 patent/WO2002050041A1/en not_active Ceased
- 2001-12-12 ES ES01271362T patent/ES2257381T3/es not_active Expired - Lifetime
- 2001-12-12 JP JP2002551538A patent/JP4068459B2/ja not_active Expired - Fee Related
- 2001-12-12 AT AT01271362T patent/ATE317386T1/de not_active IP Right Cessation
- 2001-12-12 AU AU2002219176A patent/AU2002219176B2/en not_active Ceased
- 2001-12-12 BR BR0116263-2A patent/BR0116263A/pt not_active IP Right Cessation
- 2001-12-12 CA CA002431100A patent/CA2431100C/en not_active Expired - Fee Related
- 2001-12-12 EP EP01271362A patent/EP1358162B1/en not_active Expired - Lifetime
- 2001-12-12 CN CNB018210120A patent/CN1208322C/zh not_active Expired - Fee Related
- 2001-12-20 AR ARP010105925A patent/AR035408A1/es unknown
-
2003
- 2003-06-13 ZA ZA200304646A patent/ZA200304646B/en unknown
- 2003-08-26 US US10/648,451 patent/US7102007B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004519441A (ja) | 2004-07-02 |
| US7102007B2 (en) | 2006-09-05 |
| AR035408A1 (es) | 2004-05-26 |
| CN1481366A (zh) | 2004-03-10 |
| ATE317386T1 (de) | 2006-02-15 |
| BR0116263A (pt) | 2003-12-30 |
| US20030004156A1 (en) | 2003-01-02 |
| DE60117096D1 (de) | 2006-04-20 |
| EP1358162A1 (en) | 2003-11-05 |
| KR100530408B1 (ko) | 2005-11-22 |
| WO2002050041A1 (en) | 2002-06-27 |
| AU2002219176B2 (en) | 2006-02-09 |
| JP4068459B2 (ja) | 2008-03-26 |
| US20050020624A1 (en) | 2005-01-27 |
| KR20030063453A (ko) | 2003-07-28 |
| ZA200304646B (en) | 2004-09-13 |
| EP1358162B1 (en) | 2006-02-08 |
| AU1917602A (en) | 2002-07-01 |
| MXPA03005395A (es) | 2003-09-25 |
| CN1208322C (zh) | 2005-06-29 |
| CA2431100A1 (en) | 2002-06-27 |
| US6706751B2 (en) | 2004-03-16 |
| DE60117096T2 (de) | 2006-11-23 |
| ES2257381T3 (es) | 2006-08-01 |
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| EEER | Examination request | ||
| MKLA | Lapsed |