NZ560828A - Quinolinone compounds as 5-HT4 receptor agonists - Google Patents

Info

Publication number

NZ560828A

NZ560828A NZ560828A NZ56082806A NZ560828A NZ 560828 A NZ560828 A NZ 560828A NZ 560828 A NZ560828 A NZ 560828A NZ 56082806 A NZ56082806 A NZ 56082806A NZ 560828 A NZ560828 A NZ 560828A

Authority

NZ

New Zealand

Prior art keywords

oct

compound

oxo

formula

isopropyl

Prior art date

2005-03-02

Links

• Espacenet
• Global Dossier
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• 108091005482 5-HT4 receptors Proteins 0.000 title claims abstract description 46
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 title abstract description 3
• 239000000018 receptor agonist Substances 0.000 title description 16
• 229940044601 receptor agonist Drugs 0.000 title description 16
• 150000001875 compounds Chemical class 0.000 claims abstract description 276
• 238000000034 method Methods 0.000 claims abstract description 94
• 150000003839 salts Chemical class 0.000 claims abstract description 52
• 239000012453 solvate Substances 0.000 claims abstract description 38
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 33
• 230000000694 effects Effects 0.000 claims abstract description 24
• 230000008569 process Effects 0.000 claims abstract description 19
• 230000004899 motility Effects 0.000 claims abstract description 14
• 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 182
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 87
• -1 C 1.3alkoxy Chemical group 0.000 claims description 73
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 63
• 239000001257 hydrogen Substances 0.000 claims description 59
• 229910052739 hydrogen Inorganic materials 0.000 claims description 59
• 229910052799 carbon Inorganic materials 0.000 claims description 46
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 44
• 150000001408 amides Chemical class 0.000 claims description 38
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 35
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 28
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 150000002431 hydrogen Chemical class 0.000 claims description 22
• 239000002253 acid Substances 0.000 claims description 20
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
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• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 11
• 229910052721 tungsten Inorganic materials 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 10
• 208000002551 irritable bowel syndrome Diseases 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 8
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 238000000338 in vitro Methods 0.000 claims description 5
• UUCJNYSXZJNSLE-UHFFFAOYSA-N 2-oxo-1-propan-2-ylquinoline-3-carboxylic acid Chemical compound C1=CC=C2C=C(C(O)=O)C(=O)N(C(C)C)C2=C1 UUCJNYSXZJNSLE-UHFFFAOYSA-N 0.000 claims description 4
• DDOWCQQXWQWZQD-UHFFFAOYSA-N 4-acetylpiperazine-1-carboxylic acid Chemical compound CC(=O)N1CCN(C(O)=O)CC1 DDOWCQQXWQWZQD-UHFFFAOYSA-N 0.000 claims description 4
• OHZUEFKOZYWUFF-UHFFFAOYSA-N 4-hydroxypiperidine-1-carboxylic acid Chemical compound OC1CCN(C(O)=O)CC1 OHZUEFKOZYWUFF-UHFFFAOYSA-N 0.000 claims description 3
• VETXQJLDLLEFBI-UHFFFAOYSA-N 4-methylsulfonylpiperazine-1-carboxylic acid Chemical compound CS(=O)(=O)N1CCN(C(O)=O)CC1 VETXQJLDLLEFBI-UHFFFAOYSA-N 0.000 claims description 3
• 150000001721 carbon Chemical group 0.000 claims description 3
• 150000004702 methyl esters Chemical class 0.000 claims description 3
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 claims description 2
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
• 125000001475 halogen functional group Chemical group 0.000 claims 4
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
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• 239000000543 intermediate Substances 0.000 abstract description 68
• 230000001404 mediated effect Effects 0.000 abstract description 9
• ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical class C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 abstract 1
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• 238000006243 chemical reaction Methods 0.000 description 49
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• 238000003786 synthesis reaction Methods 0.000 description 39
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• 238000004128 high performance liquid chromatography Methods 0.000 description 35
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
• 238000003556 assay Methods 0.000 description 33
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• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 30
• 238000002360 preparation method Methods 0.000 description 30
• 230000014759 maintenance of location Effects 0.000 description 29
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• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
• 239000007787 solid Substances 0.000 description 17
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
• 238000009472 formulation Methods 0.000 description 16
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
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• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 14
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• 238000002953 preparative HPLC Methods 0.000 description 9
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