Claims for Patent: 5,223,510

Summary for Patent: 5,223,510

Title:	Alkylaminoalkyl derivatives of benzofuran, benzothiophene, indole and indolizine, process for their preparation and compositions containing them
Abstract:	The subject of the invention is benzofuran, benzothiophene, indole or indolizine compounds of general formula: I in which: Het represents one of the groups: in which T,T' and T''represent particularly a group: R and Ra, identical or different, represent X represent -O- or -S- Y represents a radical These compounds are useful as medecines particularly for the treatment of pathological syndroms of the cardio-vascular system.
Inventor(s):	Jean Gubin, Pierre Chatelain, Jean Lucchetti, Gilbert Rosseels, Henri Inion
Assignee:	SABIFU , Sanofi SA
Application Number:	US07/736,580
Patent Claims:	1. A benzofuran, benzothiophene, indole or indolizine compound of formula: ##STR118## in which: Het represents one of: ##STR119## in which: T represents: ##STR120## in which: R and Ra, identical or different, represent:hydrogen, C1 -C4 alkyl SO2 R' in which R' represents a linear or branched C1 -C6 alkyl, trifluoromethyl, phenyl, phenyl substituted by a C1 -C4 alkyl, benzyl, benzyl substituted by C1 -C4 alkyl, benzoyl or benzoyl substituted by C1 -C4 alkyl, and Ra and R' forming with the nitrogen atom to which they are attached a ring bearing from 3 to 6 carbon atoms, T' represents:hydrogen nitro ##STR121## as previously defined, T" represents: benzyloxycarbonylamino ##STR122## in which T"1 represents hydrogen or C1 -C4 alkyl ##STR123## in which T"2 and T"3, identical or different, represent hydrogen or C1 -C4 alkyl or T"2 and T"3 form with the nitrogen atom to which they are attached a ring having from 4 to 6 carbon atoms ##STR124## as defined previously X represents --O-- or --S-- Y represents ##STR125## in which R5 represents hydrogen, C1 -C4 alkyl or an acyl of formula ##STR126## in which R'4 represents C1 -C4 alkyl R1 represents C1 -C6 alkyl, phenyl, phenyl substituted by C1 -C4 alkyl or halogenophenyl R2 represents:hydrogen a linear or branched C1 -C6 alkyl R3 represents:a linear or branched C1 -C6 alkyl Alk--R6 in which Alk represents a simple bond or a linear or branched C1 -C5 alkylene and R6 represents pyridyl, phenyl, phenoxy, 3,4-methylenedioxy phenyl or phenyl or phenoxy substituted by one or more substituents, identical or different, selected from halogen, C1 -C4 alkyl or C1 -C4 alkoxy, R2 and R3, when they are taken together, represent C3 -C6 alkylene or alkenylene or C3 -C6 alkylene or alkenylene substituted by phenyl, 3-oxo-1,5-pentamethylene, 3-aza 1,5-pentamethylene, 3-methylaza 1,5-pentamethylene, 3-phenylaza 1,5-pentamethylene or --CH--CH--N═CH--, R4 represents:hydrogen C1 -C4 alkyl --SO2 R'1 in which R'1 represents C1 -C4 alkyl, phenyl, phenyl substituted by C1 -C4 alkyl, benzyl, or benzyl substituted by C1 -C4 alkyl ##STR127## in which R'4 and R"4, identical or different, represent C1 -C4 alkyl and m represents an integer from 1 to 3 A represents --O--, --S-- or ##STR128## W, W' and Z are such that: when identical, W and W' represent ##STR129## or N, Z represents --O-- or --S-- when W represents ##STR130## and W' represents ##STR131## Z represents --CH═C'--R'8 R8 and R'8 being identical or different and representing hydrogen, a halogen atom, C1 -C4 alkyl or C1 -C4 alkoxy, n represents an integer from 1 to 5 provided that when R4 represents --SO2 R'1, T' represents hydrogen, nitro or cyclised ##STR132## or a pharmaceutically acceptable salt thereof. 2. A compound according to claim 1 in which R represents --SO2 R' and Ra represents hydrogen. 3. A compound according to claim 1 in which Y represents ##STR133## 4. A compound according to claim 1 in which the moiety ##STR134## represents benzoyl. 5. A compound according to claim 1 in which the moiety ##STR135## represents 4-benzoyl oxy. 6. A compound according to claim 1 in which R1, R2 and R3 represent n-butyl and n represents 3. 7. A compound according to claim 1 in which X represents --O--. 8. A compound according to claim 1 in which the chain ##STR136## is at position 4. 9. A compound according to claim 1 in which the pharmaceutically acceptable salt is the oxalate, fumarate, hydrochloride or p-toluenesulfonate. 10. A compound according to claim 1 selected from:2-n-butyl 3-[4-(3-di-n-butylamino-propoxy)benzoyl]5-methylsulfonamido benzofuran, 2-n-butyl 3-{4-[3-(N-methyl N-3,4-dimethoxy-β-phenethyl)aminopropoxy]benzoyl} 5-methylsulfonamido benzofuran, 2-isopropyl 3-[4-(3-di-n-butylamino-propoxy)benzoyl]5-methylsulfonamido benzofuran, 5-amino 3-[4-(3-di-n-butylamino-propoxy)benzoyl]2-n-butyl 1-methyl indole,or pharmaceutically acceptable salts thereof. 11. A pharmaceutical composition containing as active ingredient at least one derivative of benzofuran, benzothiophene, indole or indolizine according to claim 1, in combination with a pharmaceutical vehicle or excipient. 12. A pharmaceutical composition containing as active ingredient at least one derivative according to claim 10, in combination with a pharmaceutical vehicle or excipient. 13. A method for the treatment of angina pectoris comprising administering to an animal in need thereof a pharmaceutical composition according to claim 11 containing from 50 to 500 mg of active ingredient. 14. A method of using at least one derivative of benzofuran, benzothiophene, indole or indolizine according to claim 1 comprising combining the derivative with a pharmaceutical vehicle or a suitable excipient for the production of a medicine designed for the treatment of angina pectoris. 15. A method for the treatment of hypertension comprising administering to an animal in need thereof a pharmaceutical composition according to claim 11 containing from 50 to 500 mg of active ingredient. 16. A method for the treatment of arrhythmias comprising administering to an animal in need thereof a pharmaceutical composition according to claim 11 containing from 50 to 500 mg of active ingredient. 17. A method for the treatment of cerebral circulatory insufficiency comprising administering to an animal in need thereof a pharmaceutical composition according to claim 11 containing from 50 to 500 mg of active ingredient. 18. A method of using at least one derivative of benzofuran, benzothiophene, indole or indolizine according to claim 1 comprising combining the derivative with a pharmaceutical vehicle or a suitable excipient for the production of a medicine designed for the treatment of hypertension. 19. A method of using at least one derivative of benzofuran, benzothiophene, indole or indolizine according to claim 1 comprising combining the derivative with a pharmaceutical vehicle or a suitable excipient for the production of a medicine designed for the treatment of arrhythmias. 20. A method of using at least one derivative of benzofuran, benzothiophene, indole or indolizine according to claim 1 comprising combining the derivative with a pharmaceutical vehicle or a suitable excipient for the production of a medicine designed for the treatment of cerebral circulatory insufficiency. 21. A veterinary composition containing as active ingredient at least one derivative of benzofuran, benzothiophene, indole or indolizine according to claim 1, in combination with a pharmaceutical vehicle or excipient. 22. A method for the treatment of angina pectoris comprising administering to an animal in need thereof a veterinary composition according to claim 11 containing from 50 to 500 mg of active ingredient. 23. A method for the treatment of hypertension comprising administering to an animal in need thereof a veterinary composition according to claim 11 containing from 50 to 500 mg of active ingredient. 24. A method for the treatment of arrhythmias comprising administering to an animal in need thereof a veterinary composition according to claim 11 containing from 50 to 500 mg of active ingredient. 25. A method for the treatment of cerebral circulatory insufficiency comprising administering to an animal in need thereof a veterinary composition according to claim 11 containing from 50 to 500 mg of active ingredient. 26. A veterinary composition containing as active ingredient at least one derivative according to claim 10, in combination with a pharmaceutical vehicle or excipient.