Claims for Patent: 4,315,935

Summary for Patent: 4,315,935

Title:	N,N\'-Bis[substituted-1,2,3,4-tetrahydroisoquinolinolyl]disulfonylimides and antiallergic compositions and method of use
Abstract:	Imidodisulfamide derivatives useful in the treatment of allergic conditions are prepared by reaction of an appropriately substituted tetrahydroisoquinoline and bis(chlorosulfonyl)imide in the presence of a tertiary amine.
Inventor(s):	Ali; Fadia E. (Cherry Hill, NJ)
Assignee:	SmithKline Corporation (Philadelphia, PA)
Application Number:	06/159,340
Patent Claims:	1. A compound of the formula (I) ##STR14## in which X is hydrogen, methyl, bromo or chloro; and Y is a benzeneaminosulfonyl radical of the formula ##STR15## in which R is hydrogen or methyl; R.sub.1 is hydrogen, bromo, chloro, nitro, methyl, trifluoromethyl or methoxy; and R.sub.2 is hydrogen, chloro or methyl provided that when R.sub.2 is chloro, R.sub.1 is chloro, methyl or trifluoromethyl and when R.sub.2 is methyl, R.sub.1 is methyl; or an alkali metal salt of said compound. 2. A compound according to claim 1 of the formula (II) ##STR16## in which X.sub.1 is hydrogen, methyl, bromo or chloro; R is hydrogen or methyl; R.sub.1 is hydrogen, bromo, chloro, nitro, methyl, trifluoromethyl or methoxy; and R.sub.2 is hydrogen, chloro or methyl provided that when R.sub.2 is chloro, R.sub.1 is chloro, methyl or trifluoromethyl and when R.sub.2 is methyl, R.sub.1 is methyl; or an alkali metal salt of said compound. 3. A compound according to claim 2 in which X.sub.1 is hydrogen. 4. A compound according to claim 3, in which R and R.sub.2 are each hydrogen and R.sub.1 is hydrogen, 3- or 4-bromo, 2-, 3- or 4-chloro, 3-nitro, 3- or 4-trifluoromethyl or 4-methoxy. 5. A compound according to claim 3 in which R is hydrogen, R.sub.2 is 3-chloro and R.sub.1 is 4-chloro or 4-methyl. 6. A compound according to claim 3 which is N,N'-bis[7-(4-chloro-3-trifluoromethylbenzeneaminosulfonyl)-1,2,3,4-tetrah ydroisoquinolyl]disulfonylimide or an alkali metal salt thereof. 7. A compound according to claim 3 which is N,N'-bis[7-(3,4-dimethylbenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoquinoly l]disulfonylimide or an alkali metal salt thereof. 8. A compound according to claim 3 which is N,N'-bis[7-(3-chlorobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoquinolyl]di sulfonylimide or an alkali metal salt thereof. 9. A compound according to claim 3 which is N,N'-bis[7-(3-bromobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoquinolyl]dis ulfonylimide or an alkali metal salt thereof. 10. A compound according to claim 3 which is N,N'-bis[7-(N-methyl-4-chlorobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoqu inolyl]disulfonylimide or an alkali metal salt thereof. 11. A compound according to claim 3 which is N,N'-bis[7-(3-chloro-4-methylbenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoqu inolyl]disulfonylimide or an alkali metal salt thereof. 12. A compound according to claim 3 which is N,N'-bis[7-(3-trifluoromethylbenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoqu inolyl]disulfonylimide or an alkali metal salt thereof. 13. A compound according to claim 1 of the formula (III) ##STR17## in which X.sub.2 is methyl, bromo or chloro; R is hydrogen or methyl; R.sub.1 is hydrogen, bromo, chloro, nitro, methyl, trifluoromethyl or methoxy; and R.sub.2 is hydrogen, chloro or methyl provided that when R.sub.2 is chloro, R.sub.1 is chloro, methyl or trifluoromethyl and when R.sub.2 is methyl, R.sub.1 is methyl or an alkali metal salt thereof. 14. A compound according to claim 1 of the formula (IV) ##STR18## in which X.sub.3 is hydrogen, methyl, bromo or chloro; R is hydrogen or methyl; R.sub.1 is hydrogen, bromo, chloro, nitro, methyl, trifluoromethyl or methoxy; and R.sub.2 is hydrogen, chloro or methyl provided that when R.sub.2 is chloro, R.sub.1 is chloro, methyl or trifluoromethyl and when R.sub.2 is methyl, R.sub.1 is methyl or an alkali metal salt thereof. 15. A compound according to claim 14 which is N,N'-bis[7-chloro-8-(3-chlorobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoqu inolyl]disulfonylimide or an alkali metal salt thereof. 16. A compound according to claim 1 of the formula (V) ##STR19## in which X.sub.4 is methyl, bromo or chloro; R is hydrogen or methyl; R.sub.1 is hydrogen, bromo, chloro, nitro, methyl, trifluoromethyl or methoxy; and R.sub.2 is hydrogen, chloro or methyl provided that when R.sub.2 is chloro, R.sub.1 is chloro, methyl or trifluoromethyl and when R.sub.2 is methyl, R.sub.1 is methyl or an alkali metal salt thereof. 17. A compound according to claim 16 which is N,N'-bis[8-chloro-5-(3-chlorobenzeneaminosulfonyl)-1,2,3,4-tetrahydroisoqu inolyl]disulfonylimide or an alkali metal salt thereof. 18. A pharmaceutical composition for inhibiting the symptoms of asthma comprising a pharmaceutical carrier or diluent and an amount sufficient to produce said inhibition of a compound of claim 1. 19. A pharmaceutical composition according to claim 18 in a form suitable for administration by inhalation. 20. A pharmaceutical composition according to claim 18 comprising a solution or suspension of the active ingredient in sterile water. 21. A pharmaceutical composition according to claim 18 in the form of an aerosol formulation. 22. A pharmaceutical composition according to claim 18 in which the pharmaceutical carrier or diluent is a solid. 23. A method of inhibiting the symptoms of asthma which comprises administering to a subject in need of said inhibition a therapeutically effective amount for producing said inhibition of a compound of claim 1. 24. The method according to claim 23 in which the active ingredient is administered in a daily dosage regimen of from about 0.5 mg. to about 2000 mg. 25. A method of antagonizing the effects of SRS-A on bronchial smooth muscle which comprises administering to a subject in need of said antagonism an amount sufficient to produce said antagonism of a compound of claim 1.

Details for Patent 4,315,935

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2000-04-14