NO321576B1 - Nye morfolinderivater, fremgangsmater for fremstilling derav, anvendelser derav, og farmasoytiske preparater og medikamenter inneholdende de nevnte derivater. - Google Patents

Info

Publication number

NO321576B1

NO321576B1 NO20014632A NO20014632A NO321576B1 NO 321576 B1 NO321576 B1 NO 321576B1 NO 20014632 A NO20014632 A NO 20014632A NO 20014632 A NO20014632 A NO 20014632A NO 321576 B1 NO321576 B1 NO 321576B1

Authority

NO

Norway

Prior art keywords

compound

formula

mixture

methyl

salts

Prior art date

1999-03-25

Links

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• 238000000034 method Methods 0.000 title claims description 73
• 238000002360 preparation method Methods 0.000 title claims description 45
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• 230000008569 process Effects 0.000 title claims description 6
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• 239000008194 pharmaceutical composition Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 311
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
• 150000003839 salts Chemical class 0.000 claims description 44
• 238000011282 treatment Methods 0.000 claims description 36
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 239000002253 acid Substances 0.000 claims description 27
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims description 25
• 150000004677 hydrates Chemical class 0.000 claims description 23
• 239000012453 solvate Substances 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 22
• 208000002193 Pain Diseases 0.000 claims description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 16
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 150000007522 mineralic acids Chemical class 0.000 claims description 15
• 150000007524 organic acids Chemical class 0.000 claims description 15
• 238000004519 manufacturing process Methods 0.000 claims description 14
• 229910052801 chlorine Inorganic materials 0.000 claims description 13
• 125000006239 protecting group Chemical group 0.000 claims description 13
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 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 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
• QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims description 10
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
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• 125000003944 tolyl group Chemical group 0.000 claims description 3
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
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• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
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• 125000001424 substituent group Chemical group 0.000 claims description 2
• DXRQVHJALPBGNR-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-1-[2-[2-(4-cyclohexylpiperazin-1-yl)ethyl]-2-(3,4-dichlorophenyl)morpholin-4-yl]ethanone Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CC(=O)N2CC(CCN3CCN(CC3)C3CCCCC3)(OCC2)C=2C=C(Cl)C(Cl)=CC=2)=C1 DXRQVHJALPBGNR-UHFFFAOYSA-N 0.000 claims 1
• MRJMYJVXYFRICE-UHFFFAOYSA-N 2-[4-[2-[4-[2-[3,5-bis(trifluoromethyl)phenyl]acetyl]-2-(3,4-dichlorophenyl)morpholin-2-yl]ethyl]piperazin-1-yl]-2-methylpropanamide Chemical compound C1CN(C(C)(C)C(N)=O)CCN1CCC1(C=2C=C(Cl)C(Cl)=CC=2)OCCN(C(=O)CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C1 MRJMYJVXYFRICE-UHFFFAOYSA-N 0.000 claims 1
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• 239000002552 dosage form Substances 0.000 claims 1
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• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• 230000008673 vomiting Effects 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 185
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• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
• 239000000047 product Substances 0.000 description 96
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 95
• ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 73
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• 239000000706 filtrate Substances 0.000 description 13
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