CA2244860A1 - Derives d'acides carboxyliques a effet inhibant l'agregation - Google Patents
Derives d'acides carboxyliques a effet inhibant l'agregation Download PDFInfo
- Publication number
- CA2244860A1 CA2244860A1 CA 2244860 CA2244860A CA2244860A1 CA 2244860 A1 CA2244860 A1 CA 2244860A1 CA 2244860 CA2244860 CA 2244860 CA 2244860 A CA2244860 A CA 2244860A CA 2244860 A1 CA2244860 A1 CA 2244860A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- alkyl
- phenyl
- ethyl
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title claims abstract description 14
- 230000002776 aggregation Effects 0.000 title abstract description 8
- 238000004220 aggregation Methods 0.000 title abstract description 8
- 230000002401 inhibitory effect Effects 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 111
- 239000000203 mixture Substances 0.000 claims abstract description 78
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 6
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 4
- 150000007524 organic acids Chemical class 0.000 claims abstract description 4
- 235000005985 organic acids Nutrition 0.000 claims abstract description 4
- -1 C1-3-alkoxycarbonyl Chemical group 0.000 claims description 127
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 84
- 125000004432 carbon atom Chemical group C* 0.000 claims description 68
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 46
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 44
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 239000002253 acid Substances 0.000 claims description 29
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 22
- 230000001681 protective effect Effects 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 20
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 150000002170 ethers Chemical class 0.000 claims description 16
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 238000001727 in vivo Methods 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 8
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 6
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 6
- 238000001149 thermolysis Methods 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- ZVILACSSLWPPDC-QAQDUYKDSA-N C1C[C@@H](OCC(=O)O)CC[C@@H]1N1C(=O)CN(CCC2CCNCC2)CC1 Chemical compound C1C[C@@H](OCC(=O)O)CC[C@@H]1N1C(=O)CN(CCC2CCNCC2)CC1 ZVILACSSLWPPDC-QAQDUYKDSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000006556 (C1-C5) alkylsulphonyl group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 4
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 4
- NKBPUPBXXRTPSR-UHFFFAOYSA-N 2-[2-(carboxymethoxy)-4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(OCC(=O)O)=CC=C1N1CCN(CCC2CCNCC2)CC1 NKBPUPBXXRTPSR-UHFFFAOYSA-N 0.000 claims description 4
- DKSXCLLWYVAJBE-UHFFFAOYSA-N 2-[4-[2-oxo-4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1N1C(=O)CN(CCC2CCNCC2)CC1 DKSXCLLWYVAJBE-UHFFFAOYSA-N 0.000 claims description 4
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004803 chlorobenzyl group Chemical group 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 claims description 4
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 230000002829 reductive effect Effects 0.000 claims description 4
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- MPQBEASWRLTJQJ-UHFFFAOYSA-N 2-[4-[2-methyl-4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetic acid Chemical compound C1CN(C=2C=CC(OCC(O)=O)=CC=2)C(C)CN1CCC1CCNCC1 MPQBEASWRLTJQJ-UHFFFAOYSA-N 0.000 claims description 3
- CUICRKRIEAAIAM-UAPYVXQJSA-N CN([C@@H]1CC[C@H](CC1)C=1C=CC(OCC(O)=O)=CC=1)CC1CCNCC1 Chemical compound CN([C@@H]1CC[C@H](CC1)C=1C=CC(OCC(O)=O)=CC=1)CC1CCNCC1 CUICRKRIEAAIAM-UAPYVXQJSA-N 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 230000008619 cell matrix interaction Effects 0.000 claims description 3
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- ZFEVAJVJDTWRKC-UHFFFAOYSA-N 1-[[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]methyl]cyclohexa-2,4-diene-1-carboxylic acid Chemical compound C=1C=C(N2CCN(CCC3CCNCC3)CC2)C=CC=1OCC1(C(=O)O)CC=CC=C1 ZFEVAJVJDTWRKC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 claims description 2
- 150000008575 L-amino acids Chemical class 0.000 claims description 2
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 2
- 125000005293 bicycloalkoxy group Chemical group 0.000 claims description 2
- 125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 2
- 125000002243 cyclohexanonyl group Chemical group *C1(*)C(=O)C(*)(*)C(*)(*)C(*)(*)C1(*)* 0.000 claims description 2
- SEYRUDDLXGCOBV-UHFFFAOYSA-N cyclohexyl 2-[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetate Chemical compound C1CCCCC1OC(=O)COC(C=C1)=CC=C1N(CC1)CCN1CCC1CCNCC1 SEYRUDDLXGCOBV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- ZEBUTPHKOYBNKD-UHFFFAOYSA-N cyclopentyl 2-[2-(2-cyclopentyloxy-2-oxoethoxy)-4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetate Chemical compound C1CCCC1OC(=O)COC1=CC=C(N2CCN(CCC3CCNCC3)CC2)C=C1OCC(=O)OC1CCCC1 ZEBUTPHKOYBNKD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
- 125000005550 pyrazinylene group Chemical group 0.000 claims description 2
- 125000005551 pyridylene group Chemical group 0.000 claims description 2
- 125000005576 pyrimidinylene group Chemical group 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 44
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 8
- 241000555028 Sternidius alpha Species 0.000 claims 8
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- LVQTUWHFAAXGDB-UHFFFAOYSA-N 2-[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1N1CCN(CCC2CCNCC2)CC1 LVQTUWHFAAXGDB-UHFFFAOYSA-N 0.000 claims 1
- 125000006357 methylene carbonyl group Chemical group [H]C([H])([*:1])C([*:2])=O 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 615
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 555
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 207
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 190
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 182
- 239000000741 silica gel Substances 0.000 description 168
- 229910002027 silica gel Inorganic materials 0.000 description 168
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 117
- 238000001819 mass spectrum Methods 0.000 description 95
- 238000002844 melting Methods 0.000 description 95
- 230000008018 melting Effects 0.000 description 95
- 239000000243 solution Substances 0.000 description 93
- 229910021529 ammonia Inorganic materials 0.000 description 91
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 235000011167 hydrochloric acid Nutrition 0.000 description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 53
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 50
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 35
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- 239000003921 oil Substances 0.000 description 33
- 235000019198 oils Nutrition 0.000 description 33
- 239000002904 solvent Substances 0.000 description 33
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 30
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 238000004587 chromatography analysis Methods 0.000 description 27
- 239000003480 eluent Substances 0.000 description 26
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 150000003254 radicals Chemical group 0.000 description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 23
- 229910052739 hydrogen Inorganic materials 0.000 description 23
- 239000001257 hydrogen Substances 0.000 description 23
- 239000003054 catalyst Substances 0.000 description 22
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- 229960000583 acetic acid Drugs 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
- 238000005984 hydrogenation reaction Methods 0.000 description 14
- 235000011054 acetic acid Nutrition 0.000 description 13
- 229940024606 amino acid Drugs 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000001117 sulphuric acid Substances 0.000 description 10
- 235000011149 sulphuric acid Nutrition 0.000 description 10
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
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- 230000003480 fibrinolytic effect Effects 0.000 description 2
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- 239000012442 inert solvent Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- WRZBLDDHUMBLKP-UHFFFAOYSA-N methyl 2-(4-aminophenyl)acetate;hydrochloride Chemical compound Cl.COC(=O)CC1=CC=C(N)C=C1 WRZBLDDHUMBLKP-UHFFFAOYSA-N 0.000 description 2
- SKWUAKYCSMHOAD-UHFFFAOYSA-N methyl 2-(n-acetyl-4-piperazin-1-ylanilino)acetate;hydrochloride Chemical compound Cl.C1=CC(N(C(C)=O)CC(=O)OC)=CC=C1N1CCNCC1 SKWUAKYCSMHOAD-UHFFFAOYSA-N 0.000 description 2
- RPTMYYHFVQUXJG-UHFFFAOYSA-N methyl 2-(n-butylsulfonyl-4-piperazin-1-ylanilino)acetate;hydrochloride Chemical compound Cl.C1=CC(N(CC(=O)OC)S(=O)(=O)CCCC)=CC=C1N1CCNCC1 RPTMYYHFVQUXJG-UHFFFAOYSA-N 0.000 description 2
- CMZPKTDCECCYKP-UHFFFAOYSA-N methyl 2-[2-(2-methoxy-2-oxoethoxy)-4-nitrophenoxy]acetate Chemical compound COC(=O)COC1=CC=C([N+]([O-])=O)C=C1OCC(=O)OC CMZPKTDCECCYKP-UHFFFAOYSA-N 0.000 description 2
- NLGQOJRMRFVMFF-UHFFFAOYSA-N methyl 2-[3-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.COC(=O)COC1=CC=CC(N2CCN(CCC3CCNCC3)CC2)=C1 NLGQOJRMRFVMFF-UHFFFAOYSA-N 0.000 description 2
- CFQQPHIRMLEWDE-UHFFFAOYSA-N methyl 2-[4-[4-(2-piperazin-1-ylethyl)piperazin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCN(CCN2CCNCC2)CC1 CFQQPHIRMLEWDE-UHFFFAOYSA-N 0.000 description 2
- XMLIVAVTKFDMQX-UHFFFAOYSA-N methyl 2-[4-[4-(2-piperazin-1-ylethyl)piperazin-1-yl]phenyl]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(CC(=O)OC)=CC=C1N1CCN(CCN2CCNCC2)CC1 XMLIVAVTKFDMQX-UHFFFAOYSA-N 0.000 description 2
- ADCWYEBEARSKAR-UHFFFAOYSA-N methyl 2-[4-[4-(2-piperidin-4-ylacetyl)piperazin-1-yl]phenoxy]acetate;hydrochloride Chemical compound Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCN(C(=O)CC2CCNCC2)CC1 ADCWYEBEARSKAR-UHFFFAOYSA-N 0.000 description 2
- DQOFMOMCMWYJNI-UHFFFAOYSA-N methyl 2-[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]propanoate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OC(C)C(=O)OC)=CC=C1N1CCN(CCC2CCNCC2)CC1 DQOFMOMCMWYJNI-UHFFFAOYSA-N 0.000 description 2
- PWVBFZHGZMXUMI-UHFFFAOYSA-N methyl 2-[4-[4-(piperidin-4-ylcarbamoyl)piperazin-1-yl]phenoxy]acetate;hydrochloride Chemical compound Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCN(C(=O)NC2CCNCC2)CC1 PWVBFZHGZMXUMI-UHFFFAOYSA-N 0.000 description 2
- BSJWANUVOYLSFQ-UHFFFAOYSA-N methyl 2-[4-[4-(piperidin-4-ylmethoxy)piperidin-1-yl]phenoxy]acetate;hydrochloride Chemical compound Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCC(OCC2CCNCC2)CC1 BSJWANUVOYLSFQ-UHFFFAOYSA-N 0.000 description 2
- XSVJFIFZEBHBKY-UHFFFAOYSA-N methyl 2-[4-[4-[(1-benzylpiperidin-4-yl)carbamoyl]piperazin-1-yl]phenoxy]acetate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1CCN(C(=O)NC2CCN(CC=3C=CC=CC=3)CC2)CC1 XSVJFIFZEBHBKY-UHFFFAOYSA-N 0.000 description 2
- WGXDSDAXDUKWHR-UHFFFAOYSA-N methyl 2-[4-[4-[(benzylamino)-piperidin-4-ylmethyl]piperidin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCC(C(NCC=2C=CC=CC=2)C2CCNCC2)CC1 WGXDSDAXDUKWHR-UHFFFAOYSA-N 0.000 description 2
- KKXRUCSZPCFZGK-UHFFFAOYSA-N methyl 2-[4-[4-[2-phenylethyl(piperidin-4-yl)amino]piperidin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCC(N(CCC=2C=CC=CC=2)C2CCNCC2)CC1 KKXRUCSZPCFZGK-UHFFFAOYSA-N 0.000 description 2
- OMLUDQTUEMXICH-UHFFFAOYSA-N methyl 2-[4-[4-[methyl(piperidin-4-ylmethyl)amino]piperidin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCC(N(C)CC2CCNCC2)CC1 OMLUDQTUEMXICH-UHFFFAOYSA-N 0.000 description 2
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- OMAMYYNVHINXGD-UHFFFAOYSA-N methyl 3-(4-chlorophenyl)-2-[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]propanoate;dihydrochloride Chemical compound Cl.Cl.C=1C=C(N2CCN(CCC3CCNCC3)CC2)C=CC=1OC(C(=O)OC)CC1=CC=C(Cl)C=C1 OMAMYYNVHINXGD-UHFFFAOYSA-N 0.000 description 2
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- WAJQRSJLOAFJMA-UHFFFAOYSA-N methyl 1-[[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]methyl]cyclohexa-2,4-diene-1-carboxylate;dihydrochloride Chemical compound Cl.Cl.C=1C=C(N2CCN(CCC3CCNCC3)CC2)C=CC=1OCC1(C(=O)OC)CC=CC=C1 WAJQRSJLOAFJMA-UHFFFAOYSA-N 0.000 description 1
- PZUTXFJKMUIAKA-UHFFFAOYSA-N methyl 2-(4-benzylpiperazin-1-yl)acetate Chemical compound C1CN(CC(=O)OC)CCN1CC1=CC=CC=C1 PZUTXFJKMUIAKA-UHFFFAOYSA-N 0.000 description 1
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- WTZCKBGEPPMCCS-UHFFFAOYSA-N methyl 2-[4-(4-benzylpiperazin-1-yl)-2-(2-methoxy-2-oxoethoxy)phenoxy]acetate Chemical compound C1=C(OCC(=O)OC)C(OCC(=O)OC)=CC=C1N1CCN(CC=2C=CC=CC=2)CC1 WTZCKBGEPPMCCS-UHFFFAOYSA-N 0.000 description 1
- IUWDZUAKIYRBGG-UHFFFAOYSA-N methyl 2-[4-(4-benzylpiperazin-1-yl)phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1N1CCN(CC=2C=CC=CC=2)CC1 IUWDZUAKIYRBGG-UHFFFAOYSA-N 0.000 description 1
- BWIFMURGDJPGNY-UHFFFAOYSA-N methyl 2-[4-[1-(2-piperidin-4-ylethyl)piperidin-4-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1C1CCN(CCC2CCNCC2)CC1 BWIFMURGDJPGNY-UHFFFAOYSA-N 0.000 description 1
- KAPBROQYMJQFQX-UHFFFAOYSA-N methyl 2-[4-[2-methyl-4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1C(C)CN(CCC2CCNCC2)CC1 KAPBROQYMJQFQX-UHFFFAOYSA-N 0.000 description 1
- QPAPAEJVVTYBLE-UHFFFAOYSA-N methyl 2-[4-[4-(2-oxo-2-piperazin-1-ylethyl)piperazin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCN(CC(=O)N2CCNCC2)CC1 QPAPAEJVVTYBLE-UHFFFAOYSA-N 0.000 description 1
- LFCDYELREYYQGH-UHFFFAOYSA-N methyl 2-[4-[4-(2-piperazin-1-ylacetyl)piperazin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCN(C(=O)CN2CCNCC2)CC1 LFCDYELREYYQGH-UHFFFAOYSA-N 0.000 description 1
- GMWDNUKNTCFELB-UHFFFAOYSA-N methyl 2-[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCN(CCC2CCNCC2)CC1 GMWDNUKNTCFELB-UHFFFAOYSA-N 0.000 description 1
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- PYRHXZUKJRPQLL-UHFFFAOYSA-N methyl 2-[4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]piperidin-1-yl]acetate;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CC(=O)OC)CCC1N1CCN(CCC2CCNCC2)CC1 PYRHXZUKJRPQLL-UHFFFAOYSA-N 0.000 description 1
- MABAFTKETKLYKK-UHFFFAOYSA-N methyl 2-[4-[4-(piperidin-4-ylmethylamino)piperidin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCC(NCC2CCNCC2)CC1 MABAFTKETKLYKK-UHFFFAOYSA-N 0.000 description 1
- VGPFRPHAJBHGAM-UHFFFAOYSA-N methyl 2-[4-[4-[(piperidin-4-ylamino)methyl]piperidin-1-yl]phenoxy]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(OCC(=O)OC)=CC=C1N1CCC(CNC2CCNCC2)CC1 VGPFRPHAJBHGAM-UHFFFAOYSA-N 0.000 description 1
- DOVAXCATWCGLKB-UHFFFAOYSA-N methyl 2-[4-amino-2-(2-methoxy-2-oxoethoxy)phenoxy]acetate;hydrochloride Chemical compound Cl.COC(=O)COC1=CC=C(N)C=C1OCC(=O)OC DOVAXCATWCGLKB-UHFFFAOYSA-N 0.000 description 1
- OSRVKJMDMFMRKZ-UHFFFAOYSA-N methyl 2-[n-acetyl-4-[4-(2-piperidin-4-ylethyl)piperazin-1-yl]anilino]acetate;dihydrochloride Chemical compound Cl.Cl.C1=CC(N(C(C)=O)CC(=O)OC)=CC=C1N1CCN(CCC2CCNCC2)CC1 OSRVKJMDMFMRKZ-UHFFFAOYSA-N 0.000 description 1
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- AYGALXIVUZOHJO-UHFFFAOYSA-N tert-butyl 4-[2-[1-[4-(2-ethoxy-2-oxoethoxy)phenyl]piperidin-4-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1N1CCC(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 AYGALXIVUZOHJO-UHFFFAOYSA-N 0.000 description 1
- ZQDNDFJEGIJSDL-UHFFFAOYSA-N tert-butyl 4-[2-[4-[2,4-bis(2-ethoxy-2-oxoethoxy)phenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound CCOC(=O)COC1=CC(OCC(=O)OCC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 ZQDNDFJEGIJSDL-UHFFFAOYSA-N 0.000 description 1
- RWOMJFYZBKQATF-UHFFFAOYSA-N tert-butyl 4-[2-[4-[3,4-bis(2-methoxy-2-oxoethoxy)phenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=C(OCC(=O)OC)C(OCC(=O)OC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 RWOMJFYZBKQATF-UHFFFAOYSA-N 0.000 description 1
- CKFODIRFKJCIHW-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(1-ethoxy-2-methyl-1-oxopropan-2-yl)oxyphenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OC(C)(C)C(=O)OCC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 CKFODIRFKJCIHW-UHFFFAOYSA-N 0.000 description 1
- ITFSPYXGIMHDQT-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(1-methoxy-1-oxopropan-2-yl)oxyphenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OC(C)C(=O)OC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 ITFSPYXGIMHDQT-UHFFFAOYSA-N 0.000 description 1
- ULYICLLIGGDXHL-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(2-ethoxy-2-oxoethoxy)phenyl]-2,5-dioxopiperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1N1C(=O)CN(CCC2CCN(CC2)C(=O)OC(C)(C)C)C(=O)C1 ULYICLLIGGDXHL-UHFFFAOYSA-N 0.000 description 1
- RPSRWLBDGUNKIF-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(2-ethoxy-2-oxoethoxy)phenyl]-2-oxopiperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1N1CC(=O)N(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 RPSRWLBDGUNKIF-UHFFFAOYSA-N 0.000 description 1
- MNMGGIPMIDJQDP-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(2-ethoxy-2-oxoethoxy)phenyl]-3-[(4-methoxyphenyl)methyl]-2-oxopiperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1N1C(CC=2C=CC(OC)=CC=2)C(=O)N(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 MNMGGIPMIDJQDP-UHFFFAOYSA-N 0.000 description 1
- JSSNGHQRDZQOCU-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(2-ethoxy-2-oxoethoxy)phenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OCC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 JSSNGHQRDZQOCU-UHFFFAOYSA-N 0.000 description 1
- XRRNDYIJEDDQLT-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(2-methoxy-2-oxoethoxy)phenyl]-3-methylpiperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1C(C)CN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 XRRNDYIJEDDQLT-UHFFFAOYSA-N 0.000 description 1
- KCBPEIQHBYNRJY-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(2-methoxy-2-oxoethoxy)phenyl]piperidin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC)=CC=C1C1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 KCBPEIQHBYNRJY-UHFFFAOYSA-N 0.000 description 1
- QFWNOXMQAXMUEY-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(2-oxooxolan-3-yl)oxyphenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CCN1CCN(C=2C=CC(OC3C(OCC3)=O)=CC=2)CC1 QFWNOXMQAXMUEY-UHFFFAOYSA-N 0.000 description 1
- POMNAOHCCDOIAF-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(3-ethoxy-2-methyl-3-oxopropoxy)phenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(C)C(=O)OCC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 POMNAOHCCDOIAF-UHFFFAOYSA-N 0.000 description 1
- LHYQHBJGUHFSBQ-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-(3-methoxy-3-oxopropyl)phenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(CCC(=O)OC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 LHYQHBJGUHFSBQ-UHFFFAOYSA-N 0.000 description 1
- OGPXFVSBVSQKLV-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-[(1-methoxycarbonylcyclohexa-2,4-dien-1-yl)methyl]phenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C=1C=C(N2CCN(CCC3CCN(CC3)C(=O)OC(C)(C)C)CC2)C=CC=1CC1(C(=O)OC)CC=CC=C1 OGPXFVSBVSQKLV-UHFFFAOYSA-N 0.000 description 1
- YVBDCOSUQHNQQP-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-[(2-ethoxy-2-oxoethyl)amino]phenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C1=CC(NCC(=O)OCC)=CC=C1N1CCN(CCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 YVBDCOSUQHNQQP-UHFFFAOYSA-N 0.000 description 1
- BELRTOLWAAHCJR-UHFFFAOYSA-N tert-butyl 4-[2-[4-[4-[3-(4-chlorophenyl)-1-methoxy-1-oxopropan-2-yl]oxyphenyl]piperazin-1-yl]ethyl]piperidine-1-carboxylate Chemical compound C=1C=C(N2CCN(CCC3CCN(CC3)C(=O)OC(C)(C)C)CC2)C=CC=1OC(C(=O)OC)CC1=CC=C(Cl)C=C1 BELRTOLWAAHCJR-UHFFFAOYSA-N 0.000 description 1
- QMASALVNJUYOKI-UHFFFAOYSA-N tert-butyl 4-[3-(2-ethoxy-2-oxoethoxy)phenyl]piperazine-1-carboxylate Chemical compound CCOC(=O)COC1=CC=CC(N2CCN(CC2)C(=O)OC(C)(C)C)=C1 QMASALVNJUYOKI-UHFFFAOYSA-N 0.000 description 1
- WPHQWCMXHOEPTJ-UHFFFAOYSA-N tert-butyl 4-[4-(2-methoxy-2-oxoethoxy)phenyl]piperazine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 WPHQWCMXHOEPTJ-UHFFFAOYSA-N 0.000 description 1
- RMSGQTUOCGJVRY-UHFFFAOYSA-N tert-butyl 4-[4-[acetyl-(2-methoxy-2-oxoethyl)amino]phenyl]piperazine-1-carboxylate Chemical compound C1=CC(N(C(C)=O)CC(=O)OC)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 RMSGQTUOCGJVRY-UHFFFAOYSA-N 0.000 description 1
- KZPGZIRQNHLDPQ-UHFFFAOYSA-N tert-butyl 4-[[1-[4-(2-methoxy-2-oxoethoxy)phenyl]piperidin-4-yl]-(2-phenylethyl)amino]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1CCC(N(CCC=2C=CC=CC=2)C2CCN(CC2)C(=O)OC(C)(C)C)CC1 KZPGZIRQNHLDPQ-UHFFFAOYSA-N 0.000 description 1
- STIKMCWJSHSSIK-UHFFFAOYSA-N tert-butyl 4-[[1-[4-(2-methoxy-2-oxoethoxy)phenyl]piperidin-4-yl]oxymethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1CCC(OCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 STIKMCWJSHSSIK-UHFFFAOYSA-N 0.000 description 1
- DNQBMADVGFHBCL-UHFFFAOYSA-N tert-butyl 4-[[4-[4-(2-methoxy-2-oxoethoxy)phenyl]piperazin-1-yl]oxymethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1CCN(OCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 DNQBMADVGFHBCL-UHFFFAOYSA-N 0.000 description 1
- CQOUQKYBKGBTTB-UHFFFAOYSA-N tert-butyl 4-[[4-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]cyclohexyl]iminomethyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC(C)(C)C)=CC=C1C1CCC(N=CC2CCN(CC2)C(=O)OC(C)(C)C)CC1 CQOUQKYBKGBTTB-UHFFFAOYSA-N 0.000 description 1
- QTTHBYZSJOPRTQ-UHFFFAOYSA-N tert-butyl 4-[[[1-[4-(2-methoxy-2-oxoethoxy)phenyl]piperidin-4-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1=CC(OCC(=O)OC)=CC=C1N1CCC(NCC2CCN(CC2)C(=O)OC(C)(C)C)CC1 QTTHBYZSJOPRTQ-UHFFFAOYSA-N 0.000 description 1
- UCEQGHSEFNDTHD-UHFFFAOYSA-N tert-butyl 4-[amino-[1-[4-(2-methoxy-2-oxoethoxy)phenyl]piperidin-4-yl]methyl]piperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)C(C1CCN(CC1)C1=CC=C(C=C1)OCC(=O)OC)N UCEQGHSEFNDTHD-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- CWLNAJYDRSIKJS-UHFFFAOYSA-N triethoxymethoxyethane Chemical compound CCOC(OCC)(OCC)OCC CWLNAJYDRSIKJS-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 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
- 229960004418 trolamine Drugs 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229940019333 vitamin k antagonists Drugs 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention a pour objet des dérivés d'acides carboxyliques de formule générale (I), dans laquelle R¿a? à R¿c?, A, B, D, E et X¿1? à X¿3? sont tels que définis dans la revendication 1, leurs tautomères, leur stéréoisomères, y compris leurs mélanges et leurs sels, en particulier leurs sels physiologiquement tolérés avec des acides organiques ou des bases, lesquels présentent des propriétés pharmacologiques remarquables, avantageusement des effets inhibant l'agrégation. L'invention a également pour objet des médicaments renfermant ces composés, leur utilisation et leurs procédés de fabrication.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19614204A DE19614204A1 (de) | 1996-04-10 | 1996-04-10 | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19614204.0 | 1996-04-10 | ||
| PCT/EP1997/001698 WO1997037975A1 (fr) | 1996-04-10 | 1997-04-04 | Derives d'acides carboxyliques a effet inhibant l'agregation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2244860A1 true CA2244860A1 (fr) | 1997-10-16 |
Family
ID=29421560
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2244860 Abandoned CA2244860A1 (fr) | 1996-04-10 | 1997-04-04 | Derives d'acides carboxyliques a effet inhibant l'agregation |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2244860A1 (fr) |
-
1997
- 1997-04-04 CA CA 2244860 patent/CA2244860A1/fr not_active Abandoned
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |