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|Abstract:||Fluorenes bearing a 9-aminoalkyl substituent are useful antiarrhythmic agents. Pharmaceutical formulations containing such compounds are provided, as well as a method of treatment.|
|Inventor(s):||Lacefield; William B. (Indianapolis, IN), Simon; Richard L. (Greenwood, IN)|
|Assignee:||Eli Lilly and Company (Indianapolis, IN)|
1. A pharmaceutical formulation useful in the treatment of cardiac arrhythmias which comprises a carrier or diluent admixed with an antiarrhythmic amount of a 9-aminoalkylfluorene
antiarrhythmic agent of the formula ##STR12## wherein: R.sup.o is hydroxy, cyano, CONR.sup.4 R.sup.5 or COOR.sup.9 in which R.sup.4 and R.sup.5 independently are hydrogen or C.sub.1 -C.sub.6 alkyl and R.sup.9 is hydrogen or C.sub.1 -C.sub.4 alkyl;
R.sup.2 and R.sup.3 independently are hydrogen, C.sub.1 -C.sub.6 alkyl, CH.sub.2 C.sub.2 -C.sub.5 alkenyl, phenyl-C.sub.1 -C.sub.3 alkyl; or taken together with the nitrogen to which they are attached are a cyclic group of the formula ##STR13## in which R.sup.8 is hydrogen or C.sub.1 -C.sub.4 alkyl; A is CH.sub.2, O or NH; and y is zero or one; provided that R.sup.2 is hydrogen when R.sup.1 is hydroxy;
n is 3, 4 or 5;
R.sup.6 and R.sup.7 independently are hydrogen, C.sub.1 -C.sub.4 alkyl or halogen; and the pharmaceutically acceptable salts thereof.
2. The formulation of claim 1 wherein R.sup.o is hydroxy, cyano or CONR.sup.4 R.sup.5.
3. The formulation of claim 2 wherein n is 3.
4. The formulation of claim 3 wherein R.sup.2 is hydrogen.
5. The formulation of claim 4 wherein R.sup.3 is C.sub.1 -C.sub.6 alkyl.
6. The formulation of claim 5 wherein R.sup.6 and R.sup.7 both are hydrogen.
7. The formulation of claim 6 wherein R.sup.3 is C.sub.1 -C.sub.3 alkyl.
8. The formulation of claim 7 wherein R.sup.3 is isopropyl.
9. The formulation of claim 8 wherein the active ingredient is 9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene.
10. The formulation of claim 6 wherein the active ingredient is a pharmaceutically acceptable salt.
11. The formulation of claim 10 wherein the active ingredient is 9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene hydrochloride.
12. The formulation of claim 1 wherein R.sup.o is COOR.sup.9.
13. The formulation of claim 12 wherein R.sup.9 is C.sub.1 -C.sub.4 alkyl.
14. The formulation of claim 1 wherein n is 4.
15. The formulation of claim 1 wherein n is 5.
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