CA1164464A - Derives de l'indole ayant une activite sur le systeme cardiovasculaire - Google Patents

Derives de l'indole ayant une activite sur le systeme cardiovasculaire

Info

Publication number: CA1164464A
Authority: CA; Canada
Prior art keywords: group; products; formula; lower alkyl; atom
Prior art date: 1979-08-17
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.): Expired

Application number

CA000426344A

Other languages

English (en)

Inventor

Jean Wagnon

Henri Demarne

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.)

Sanofi SA

Original Assignee

Sanofi SA

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.)

1979-08-17

Filing date

1983-04-20

Publication date

1984-03-27

1979-08-17 Priority claimed from FR7920907A external-priority patent/FR2463765A1/fr

1983-04-20 Application filed by Sanofi SA filed Critical Sanofi SA

1983-04-20 Priority to CA000426344A priority Critical patent/CA1164464A/fr

1984-03-27 Application granted granted Critical

1984-03-27 Publication of CA1164464A publication Critical patent/CA1164464A/fr

Status Expired legal-status Critical Current

Links

210000000748 cardiovascular system Anatomy 0.000 title abstract description 3
150000002475 indoles Chemical class 0.000 title 1
125000000217 alkyl group Chemical group 0.000 claims abstract description 14
125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
229910052736 halogen Inorganic materials 0.000 claims abstract description 6
150000002367 halogens Chemical class 0.000 claims abstract description 6
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
239000001257 hydrogen Substances 0.000 claims abstract description 6
150000003839 salts Chemical class 0.000 claims abstract description 5
239000000126 substance Substances 0.000 claims abstract description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
125000002252 acyl group Chemical group 0.000 claims abstract description 3
125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract 5
238000004519 manufacturing process Methods 0.000 claims abstract 2
125000004429 atom Chemical group 0.000 claims description 8
238000000034 method Methods 0.000 claims description 6
230000008569 process Effects 0.000 claims description 5
239000003638 chemical reducing agent Substances 0.000 claims description 3
WAGPFYGOLZGETK-UHFFFAOYSA-N 1-(1h-indol-2-yl)propan-2-one Chemical compound C1=CC=C2NC(CC(=O)C)=CC2=C1 WAGPFYGOLZGETK-UHFFFAOYSA-N 0.000 claims description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
125000002619 bicyclic group Chemical group 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
150000002466 imines Chemical class 0.000 claims description 2
125000001041 indolyl group Chemical group 0.000 claims description 2
150000007522 mineralic acids Chemical class 0.000 claims description 2
150000007524 organic acids Chemical class 0.000 claims description 2
235000005985 organic acids Nutrition 0.000 claims description 2
239000012279 sodium borohydride Substances 0.000 claims description 2
229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
239000002904 solvent Substances 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 abstract description 2
239000003814 drug Substances 0.000 abstract description 2
229940079593 drug Drugs 0.000 abstract 1
125000000623 heterocyclic group Chemical group 0.000 abstract 1
150000002431 hydrogen Chemical class 0.000 abstract 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
239000000203 mixture Substances 0.000 description 9
102000005962 receptors Human genes 0.000 description 9
108020003175 receptors Proteins 0.000 description 9
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
150000001875 compounds Chemical class 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 4
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
241000282472 Canis lupus familiaris Species 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 4
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 4
229960001317 isoprenaline Drugs 0.000 description 4
239000012528 membrane Substances 0.000 description 4
229960002748 norepinephrine Drugs 0.000 description 4
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
230000009471 action Effects 0.000 description 3
230000008485 antagonism Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000006073 displacement reaction Methods 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
239000003446 ligand Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
108060003345 Adrenergic Receptor Proteins 0.000 description 2
102000017910 Adrenergic receptor Human genes 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
241000700159 Rattus Species 0.000 description 2
208000001871 Tachycardia Diseases 0.000 description 2
230000004872 arterial blood pressure Effects 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
229960002896 clonidine Drugs 0.000 description 2
JVHCMYZFGCOCTD-UHFFFAOYSA-N dihydroalprenolol Chemical compound CCCC1=CC=CC=C1OCC(O)CNC(C)C JVHCMYZFGCOCTD-UHFFFAOYSA-N 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
-1 hydroxy- Chemical class 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
230000007935 neutral effect Effects 0.000 description 2
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
230000004044 response Effects 0.000 description 2
239000000829 suppository Substances 0.000 description 2
230000006794 tachycardia Effects 0.000 description 2
UDQCRUSSQAXPJY-VIFPVBQESA-N (2s)-2-amino-3-(1h-indol-3-yl)propan-1-ol Chemical compound C1=CC=C2C(C[C@@H](CO)N)=CNC2=C1 UDQCRUSSQAXPJY-VIFPVBQESA-N 0.000 description 1
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
RAQPZQAQMHUKTB-TYYBGVCCSA-N (e)-but-2-enedioic acid;methanol Chemical compound OC.OC(=O)\C=C\C(O)=O RAQPZQAQMHUKTB-TYYBGVCCSA-N 0.000 description 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
206010015856 Extrasystoles Diseases 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
241000218737 Mycobacterium phage Power Species 0.000 description 1
208000012902 Nervous system disease Diseases 0.000 description 1
208000025966 Neurological disease Diseases 0.000 description 1
235000019482 Palm oil Nutrition 0.000 description 1
206010033557 Palpitations Diseases 0.000 description 1
208000000418 Premature Cardiac Complexes Diseases 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
241000011102 Thera Species 0.000 description 1
206010047281 Ventricular arrhythmia Diseases 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000001800 adrenalinergic effect Effects 0.000 description 1
230000002776 aggregation Effects 0.000 description 1
238000004220 aggregation Methods 0.000 description 1
230000002744 anti-aggregatory effect Effects 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940030611 beta-adrenergic blocking agent Drugs 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
208000006218 bradycardia Diseases 0.000 description 1
230000036471 bradycardia Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
150000003943 catecholamines Chemical class 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
238000002955 isolation Methods 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
239000007788 liquid Substances 0.000 description 1
230000004807 localization Effects 0.000 description 1
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000002540 palm oil Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
229960001412 pentobarbital Drugs 0.000 description 1
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
150000003138 primary alcohols Chemical group 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
210000003752 saphenous vein Anatomy 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000243 solution Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000002627 tracheal intubation Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Landscapes

Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000426344A 1979-08-17 1983-04-20 Derives de l'indole ayant une activite sur le systeme cardiovasculaire Expired CA1164464A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000426344A CA1164464A (fr)	1979-08-17	1983-04-20	Derives de l'indole ayant une activite sur le systeme cardiovasculaire

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
FR7920907		1979-08-17
FR7920907A FR2463765A1 (fr)	1979-08-17	1979-08-17	Nouveaux derives de l'indole actifs sur le systeme cardiovasculaire
CA000359075A CA1161849A (fr)	1979-08-17	1980-08-15	Derives de l'indole agissant sur le systeme cardio- vasculaire
CA000426344A CA1164464A (fr)	1979-08-17	1983-04-20	Derives de l'indole ayant une activite sur le systeme cardiovasculaire

Publications (1)

Publication Number	Publication Date
CA1164464A true CA1164464A (fr)	1984-03-27

Family

ID=27166796

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000426344A Expired CA1164464A (fr)	1979-08-17	1983-04-20	Derives de l'indole ayant une activite sur le systeme cardiovasculaire

Country Status (1)

Country	Link
CA (1)	CA1164464A (fr)

1983
- 1983-04-20 CA CA000426344A patent/CA1164464A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2001-03-27	MKEX	Expiry

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KR880001988B1 (ko)	1988-10-10	헤테로사이클릭 화합물의 제조방법
GB1569251A (en)	1980-06-11	Pyridobenzodiazepines
CA1164464A (fr)	1984-03-27	Derives de l'indole ayant une activite sur le systeme cardiovasculaire
US4285935A (en)	1981-08-25	Dehydropeptide compounds, their production and their medical use
JPS59144763A (ja)	1984-08-18	１−〔１−ベンズイミダゾリル〕−ｎ−〔２−（４−ヒドロキシ−３−メトキシフエニル）−２−ヒドロキシエチル〕−３−アミノブタン化合物、該化合物を含有する医薬、及び該化合物の製
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