NO329224B1 - N-((3okso-2,3-dihydro-IH-isoindol-1-yl)acetyl)guanidinderivater, anvendelse derav, farmasoytisk sammensetning inneholdende en slik forbindelse samt fremgangsmater for fremstilling av forbindelsene - Google Patents

Info

Publication number

NO329224B1

NO329224B1 NO20045660A NO20045660A NO329224B1 NO 329224 B1 NO329224 B1 NO 329224B1 NO 20045660 A NO20045660 A NO 20045660A NO 20045660 A NO20045660 A NO 20045660A NO 329224 B1 NO329224 B1 NO 329224B1

Authority

NO

Norway

Prior art keywords

oxo

dihydro

isoindol

guanidine

acetyl

Prior art date

2002-06-03

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 116
• 238000000034 method Methods 0.000 title claims abstract description 28
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
• MGRUNSIBUNAFKA-UHFFFAOYSA-N n-(diaminomethylidene)-2-(3-oxo-1,2-dihydroisoindol-1-yl)acetamide Chemical class C1=CC=C2C(CC(=O)NC(=N)N)NC(=O)C2=C1 MGRUNSIBUNAFKA-UHFFFAOYSA-N 0.000 title claims description 4
• 238000011282 treatment Methods 0.000 claims abstract description 67
• 239000003814 drug Substances 0.000 claims abstract description 46
• 238000011321 prophylaxis Methods 0.000 claims abstract description 26
• 206010019280 Heart failures Diseases 0.000 claims abstract description 16
• 238000002360 preparation method Methods 0.000 claims abstract description 15
• 230000006378 damage Effects 0.000 claims abstract description 14
• 206010003119 arrhythmia Diseases 0.000 claims abstract description 6
• 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 5
• 230000002829 reductive effect Effects 0.000 claims description 166
• 239000000203 mixture Substances 0.000 claims description 162
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 117
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 84
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 84
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 68
• 150000003839 salts Chemical class 0.000 claims description 66
• 125000004432 carbon atom Chemical group C* 0.000 claims description 63
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 43
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 claims description 42
• -1 isobutyl-1-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl Chemical group 0.000 claims description 35
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 34
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 34
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• 125000000217 alkyl group Chemical group 0.000 claims description 24
• 239000001257 hydrogen Substances 0.000 claims description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 21
• 230000002265 prevention Effects 0.000 claims description 20
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 19
• 238000004519 manufacturing process Methods 0.000 claims description 18
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• 229910052801 chlorine Inorganic materials 0.000 claims description 9
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• 229910052731 fluorine Inorganic materials 0.000 claims description 9
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• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 6
• 230000008569 process Effects 0.000 claims description 6
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• NASPYBSHSKLICW-UHFFFAOYSA-N 2-[6-chloro-2-(2-methylpropyl)-3-oxo-1h-isoindol-1-yl]-n-(diaminomethylidene)acetamide Chemical compound ClC1=CC=C2C(=O)N(CC(C)C)C(CC(=O)NC(N)=N)C2=C1 NASPYBSHSKLICW-UHFFFAOYSA-N 0.000 claims description 5
• IXLFTXVHUXKCOF-UHFFFAOYSA-N 2-[6-tert-butyl-2-(2-methylpropyl)-3-oxo-1h-isoindol-1-yl]-n-(diaminomethylidene)acetamide Chemical compound CC(C)(C)C1=CC=C2C(=O)N(CC(C)C)C(CC(=O)NC(N)=N)C2=C1 IXLFTXVHUXKCOF-UHFFFAOYSA-N 0.000 claims description 5
• 208000007536 Thrombosis Diseases 0.000 claims description 5
• 150000001412 amines Chemical class 0.000 claims description 5
• 230000001451 cardiotoxic effect Effects 0.000 claims description 5
• VRJWRXOULMHABM-UHFFFAOYSA-N n-(diaminomethylidene)-2-(2-ethyl-3-oxo-1h-isoindol-1-yl)acetamide Chemical compound C1=CC=C2C(=O)N(CC)C(CC(=O)NC(N)=N)C2=C1 VRJWRXOULMHABM-UHFFFAOYSA-N 0.000 claims description 5
• TXIRKRZTAUCXFR-UHFFFAOYSA-N n-(diaminomethylidene)-2-(3-oxo-2-propyl-1h-isoindol-1-yl)acetamide Chemical compound C1=CC=C2C(=O)N(CCC)C(CC(=O)NC(N)=N)C2=C1 TXIRKRZTAUCXFR-UHFFFAOYSA-N 0.000 claims description 5
• MCPKTJONHSDICE-UHFFFAOYSA-N n-(diaminomethylidene)-2-[2-(2-methylpropyl)-3-oxo-1h-isoindol-1-yl]propanamide Chemical compound C1=CC=C2C(=O)N(CC(C)C)C(C(C)C(=O)NC(N)=N)C2=C1 MCPKTJONHSDICE-UHFFFAOYSA-N 0.000 claims description 5
• WAUWJQZUDXRPSW-UHFFFAOYSA-N n-(diaminomethylidene)-2-[2-(2-methylpropyl)-3-oxo-5-(trifluoromethyl)-1h-isoindol-1-yl]acetamide Chemical compound C1=C(C(F)(F)F)C=C2C(=O)N(CC(C)C)C(CC(=O)NC(N)=N)C2=C1 WAUWJQZUDXRPSW-UHFFFAOYSA-N 0.000 claims description 5
• OGUGQVIXYWOEAI-UHFFFAOYSA-N n-(diaminomethylidene)-2-[2-(2-methylpropyl)-3-oxo-5-propan-2-yloxy-1h-isoindol-1-yl]acetamide Chemical compound C1=C(OC(C)C)C=C2C(=O)N(CC(C)C)C(CC(=O)NC(N)=N)C2=C1 OGUGQVIXYWOEAI-UHFFFAOYSA-N 0.000 claims description 5
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• JVQNGJRCVOTKNF-UHFFFAOYSA-N n-(diaminomethylidene)-2-[4-methyl-2-(2-methylpropyl)-3-oxo-1h-isoindol-1-yl]acetamide Chemical compound C1=CC(C)=C2C(=O)N(CC(C)C)C(CC(=O)NC(N)=N)C2=C1 JVQNGJRCVOTKNF-UHFFFAOYSA-N 0.000 claims description 5
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• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• KWKPPZVLRABURT-UHFFFAOYSA-N 1-ethoxyethenoxy(trimethyl)silane Chemical group CCOC(=C)O[Si](C)(C)C KWKPPZVLRABURT-UHFFFAOYSA-N 0.000 claims description 4
• QRJBIYOIRJRIBT-UHFFFAOYSA-N 2-[2-(cyclopropylmethyl)-3-oxo-1h-isoindol-1-yl]-n-(diaminomethylidene)acetamide Chemical compound O=C1C2=CC=CC=C2C(CC(=O)NC(=N)N)N1CC1CC1 QRJBIYOIRJRIBT-UHFFFAOYSA-N 0.000 claims description 4
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