CA2566543A1 - Derives du benzoylbenzofurane pour le traitement de l'arythmie cardiaque - Google Patents

Derives du benzoylbenzofurane pour le traitement de l'arythmie cardiaque Download PDF

Info

Publication number: CA2566543A1
Authority: CA; Canada
Prior art keywords: compound; alkyl; substituted; aryl; salt
Prior art date: 1993-06-16
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

Application number

CA002566543A

Other languages

English (en)

Inventor

Pascal Druzgala

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

ARYx Therapeutics Inc

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1993-06-16

Filing date

1994-06-16

Publication date

1994-12-22

1993-06-16 Priority claimed from US08/078,371 external-priority patent/US5364880A/en

1994-06-16 Application filed by Individual filed Critical Individual

1994-12-22 Publication of CA2566543A1 publication Critical patent/CA2566543A1/fr

Status Abandoned legal-status Critical Current

Links

206010003119 arrhythmia Diseases 0.000 title claims abstract description 15
DZRJNLPOTUVETG-UHFFFAOYSA-N 1-benzofuran-2-yl(phenyl)methanone Chemical class C=1C2=CC=CC=C2OC=1C(=O)C1=CC=CC=C1 DZRJNLPOTUVETG-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 96
206010019280 Heart failures Diseases 0.000 claims abstract description 19
206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 18
125000000217 alkyl group Chemical group 0.000 claims abstract description 16
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 15
125000003118 aryl group Chemical group 0.000 claims abstract description 12
150000003839 salts Chemical class 0.000 claims abstract description 12
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 10
-1 O-acyl Chemical group 0.000 claims abstract description 10
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 10
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 10
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims abstract description 10
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 9
150000004820 halides Chemical class 0.000 claims abstract description 7
150000001412 amines Chemical class 0.000 claims abstract description 6
150000003573 thiols Chemical class 0.000 claims abstract description 6
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims abstract description 5
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims abstract description 5
WEDKTMOIKOKBSH-UHFFFAOYSA-N 4,5-dihydrothiadiazole Chemical compound C1CN=NS1 WEDKTMOIKOKBSH-UHFFFAOYSA-N 0.000 claims abstract description 5
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims abstract description 5
125000002252 acyl group Chemical group 0.000 claims abstract description 5
125000004122 cyclic group Chemical group 0.000 claims abstract description 5
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 5
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
RLTPJVKHGBFGQA-UHFFFAOYSA-N thiadiazolidine Chemical compound C1CSNN1 RLTPJVKHGBFGQA-UHFFFAOYSA-N 0.000 claims abstract description 5
CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims abstract description 5
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206010047281 Ventricular arrhythmia Diseases 0.000 claims description 6
208000001871 Tachycardia Diseases 0.000 claims description 5
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 3
150000002688 maleic acid derivatives Chemical class 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
206010065341 Ventricular tachyarrhythmia Diseases 0.000 claims 2
206010049447 Tachyarrhythmia Diseases 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
238000000034 method Methods 0.000 abstract description 20
230000002194 synthesizing effect Effects 0.000 abstract description 3
ITPDYQOUSLNIHG-UHFFFAOYSA-N Amiodarone hydrochloride Chemical compound [Cl-].CCCCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(I)=C(OCC[NH+](CC)CC)C(I)=C1 ITPDYQOUSLNIHG-UHFFFAOYSA-N 0.000 description 60
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229940126062 Compound A Drugs 0.000 description 48
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 48
230000000694 effects Effects 0.000 description 38
239000000203 mixture Substances 0.000 description 31
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YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 14
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 10
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
230000003288 anthiarrhythmic effect Effects 0.000 description 9
238000003786 synthesis reaction Methods 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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238000002360 preparation method Methods 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
230000006793 arrhythmia Effects 0.000 description 6
230000037024 effective refractory period Effects 0.000 description 6
238000007914 intraventricular administration Methods 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
238000012360 testing method Methods 0.000 description 6
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YUTFQTAITWWGFH-UHFFFAOYSA-N 1-(1-benzofuran-2-yl)ethanone Chemical compound C1=CC=C2OC(C(=O)C)=CC2=C1 YUTFQTAITWWGFH-UHFFFAOYSA-N 0.000 description 5
XTVSVNDNDFORGK-UHFFFAOYSA-N 2-(2-benzofuran-1-yl)acetic acid Chemical compound C1=CC=CC2=C(CC(=O)O)OC=C21 XTVSVNDNDFORGK-UHFFFAOYSA-N 0.000 description 5
238000010009 beating Methods 0.000 description 5
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230000013577 regulation of ventricular cardiomyocyte membrane repolarization Effects 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
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LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 4
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SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 4
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AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
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229960002769 zofenopril Drugs 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002566543A 1993-06-16 1994-06-16 Derives du benzoylbenzofurane pour le traitement de l'arythmie cardiaque Abandoned CA2566543A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US08/078,371 US5364880A (en)	1993-06-16	1993-06-16	Compound for treatment of cardiac arrhythmia, synthesis, and methods of use
US078,371		1993-06-16
CA002164633A CA2164633C (fr)	1993-06-16	1994-06-16	Derives du benzoylbenzofurane pour le traitement de l'arythmie cardiaque

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002164633A Division CA2164633C (fr)	1993-06-16	1994-06-16	Derives du benzoylbenzofurane pour le traitement de l'arythmie cardiaque

Publications (1)

Publication Number	Publication Date
CA2566543A1 true CA2566543A1 (fr)	1994-12-22

Family

ID=37682476

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002566543A Abandoned CA2566543A1 (fr)	1993-06-16	1994-06-16	Derives du benzoylbenzofurane pour le traitement de l'arythmie cardiaque

Country Status (1)

Country	Link
CA (1)	CA2566543A1 (fr)

1994
- 1994-06-16 CA CA002566543A patent/CA2566543A1/fr not_active Abandoned

Publication	Publication Date	Title
US5849788A (en)	1998-12-15	Compound for treatment of cardiac arphythmia, synthesis, and methods of use
US4929636A (en)	1990-05-29	Positive inotrophic benzothiazole and benzothiophene compositions and method of use therefor
US4103012A (en)	1978-07-25	Indolizine derivatives, pharmaceutical compositions and methods containing same
US6316487B1 (en)	2001-11-13	Compounds for treatment of cardiac arrhythmia synthesis, and methods of use
IE841881L (en)	1985-01-22	Benzothiazepinones
AU2002360582B2 (en)	2009-06-11	Novel compounds for the treatment of cardiac arrhythmia, synthesis, and methods of use
US6362223B1 (en)	2002-03-26	Enantiomeric compounds for treatment of cardiac arrhythmias and methods of use
US7037933B2 (en)	2006-05-02	Compounds for treatment of cardiac arrhythmia, synthesis, and methods of use
US6818782B2 (en)	2004-11-16	Enantiomeric compounds for treatment of cardiac arrhythmias and methods of use
CA2566543A1 (fr)	1994-12-22	Derives du benzoylbenzofurane pour le traitement de l'arythmie cardiaque
US5070094A (en)	1991-12-03	N-benzyltropaneamides
AU2002211479B2 (en)	2007-08-30	Benzoylbenzofurane derivatives for treatment of cardiac arrhythmia
CA2392016C (fr)	2010-04-13	Composes enantiomeres pour le traitement des arythmies cardiaques et procedes d'utilisation
WO2002038557A9 (fr)	2003-09-18	Nouveaux composes destines au traitement d'arythmie cardiaque, synthese et procedes d'utilisation
US20080114059A1 (en)	2008-05-15	Novel Compounds For Treatment of Cardiac Arrhythmia and Methods of Use
AU2002211479A1 (en)	2002-07-25	Benzoylbenzofurane derivatives for treatment of cardiac arrhythmia

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2007-05-04	EEER	Examination request
2009-01-13	FZDE	Dead