Antiarrhythmic agents

Novel 1-aryl-1-benzocycloalkyl-4-aminobutanes and 1-aryl-1-benzocycloalkyl-4-amino-1-butenes are useful as antiarrhythmic agents.

BACKGROUND OF THE INVENTION 
This invention relates to certain butylamines and butenylamines. In 
particular, this invention relates to certain butyl and butenylamines 
having aryl and benzocycloalkyl disubstitution in the 4-position. The 
novel compounds provided herein are valuable pharmacological agents, 
especially useful in the treatment of cardiac arrhythmias in humans. 
There are several types of arrhythmias which afflict mankind, and each type 
may have a different underlying condition as its cause. The more serious 
conditions causing arrhythmias are generally myocardial infarction and 
digitalis toxicity. When treating arrhythmias, it is important to 
understand the pharmacologic action of the drug being used, and it is 
important to remember that the pharmacologic action of the drug selected 
may vary, depending on the state of the myocardium. Several drugs are 
available for treating cardiac arrhythmias. Quinidine is a drug that 
depresses myocardial contractility and decreases the rate of conduction in 
the myocardium. It is used mainly to prevent tachyarrhythmias; however, 
several undesirable side effects normally accompany its use. Procainamide 
has practically the same pharmacological actions as quinidine, with about 
the same effect on arrhythmias; however procainamide is safer than 
quinidine for intravenous use. Lidocaine is considered one of the most 
effective antiarrhythmic agents and is used primarily to combat 
ventricular tachyarrhythmias. It is especially useful in patients with 
recent myocardial infarction. Lidocaine doesn't cause a drop in blood 
pressure as does quinidine and procainamide; however, lidocaine does 
display toxic effects on the central nervous system, evidenced by symptoms 
such as drowsiness, twitchings and convulsions. 
Research scientists are constantly looking for new antiarrhythmic agents 
because of the severity of these diseases of the heart, and because of the 
serious side effects commonly encountered with the use of currently 
available drugs. Several indanyl derivatives have recently been prepared 
which have displayed varying degrees of antiarrhythmic activity. For 
example, very potent antiarrhythmic agents, which are 
N,N-dialkyl-N'-(2-indanyl)-N'-phenyl alkylene diamines, are described in 
Canadian Pat. No. 910907. 
The compounds of this invention are butylamine and butenylamine derivatives 
which display antiarrhythmic activity. It is an object of this invention 
to provide novel compounds which are useful in treating cardiac 
arrhythmias. 
SUMMARY OF THE INVENTION 
The compounds of this invention have the formula 
##STR1## 
in which m is 0, 1, or 2; n is 0, 1, or 2, m + n is 2 or 3; R.sub.1 and 
R.sub.2 independently are hydrogen, C.sub.1 -C.sub.4 alkyl, or a lower 
alkenyl group having the formula CH.sub.2 R.sub.4, in which R.sub.4 is 
C.sub.2 -C.sub.5 alkenyl, or R.sub.1 and R.sub.2 together with the 
adjacent nitrogen atom form a heterocyclic ring system; R.sub.3 is 
hydrogen, methyl, methoxy, trifluoromethyl, or halogen. X and Y are both 
hydrogen, or taken together X and Y form a double bond. The 
pharmaceutically acceptable acid addition salts are included within the 
scope of the invention. Also included herein are the pharmaceutically 
acceptable quaternary ammonium salts of the tertiary amines of this 
invention. 
The novel compounds provided by the present invention are prepared by 
treating a readily available 1-aryl-1-benzocycloalkyl-1-butene, which 
butene bears in the 4-position a displaceable group such as a chlorine or 
bromine atom for instance, with an amine to provide the desired 
1-aryl-1-benzocycloalkyl-4-amino-1-butenes of the invention. Reduction of 
the butenes thus formed leads to the corresponding aminobutanes of the 
invention. 
The compounds of this invention are useful in converting heart arrhythmias 
to a normal rhythm. 
DETAILED DESCRIPTION OF THE INVENTION 
As hereinbefore indicated, the compounds of this invention have the formula 
##STR2## 
R.sub.1 and R.sub.2 in the above formula are the same or are different and 
are selected from among hydrogen, C.sub.1 -C.sub.4 alkyl, or CH.sub.2 
R.sub.4, wherein R.sub.4 is C.sub.2 -C.sub.5 alkenyl, or R.sub.1 and 
R.sub.2 together with the adjacent nitrogen atom form a ring system 
selected from among pyrrolidino, piperidone, or morpholino. 
Examples of C.sub.1 -C.sub.4 alkyl groups include both straight and 
branched chain lower alkyl groups such as methyl, ethyl, n-propyl, 
isopropyl, n-butyl, isobutyl, and like groups. 
R.sub.1 and R.sub.2 also can be alkenyl groups of the formula CH.sub.2 
R.sub.4, examples of which include 2-propenyl, 2-butenyl, 3-butenyl, 
3-methyl-2-butenyl, 3-methyl-3-pentenyl, 4-hexenyl, 5-hexenyl, and the 
like. R.sub.3 in the above formula is a phenyl substituent selected from 
among hydrogen, methyl, methoxy, trifluoromethyl and halogen. The term 
"halogen" as used herein refers to fluorine, chlorine, bromine, and 
iodine. The preferred compounds of the invention are those wherein R.sub.3 
is hydrogen. 
X and Y are both hydrogen, or taken together, X and Y form a double bond. 
The aminobutenes and the aminobutanes of this invention are disubstituted 
in the 4-position with a phenyl group and with a benzocycloalkyl group. As 
indicated in the above formula, the benzocycloalkyl group can be an 
indanyl group or a tetrahydronaphthyl group. For example, when m is 0 and 
n is 2, the substituent is a 1-indanyl group, and when m is 1 and n is 1, 
the substituent is a 2-indanyl group. Similarly, when m is 0 and n is 3, 
the substituent is a 1-(1,2,3,4-tetrahydronaphthyl) group, and when m is 1 
and n is 2, the substituent is a 2-(1,2,3,4-tetrahydronaphthyl group. 
The pharmaceutically acceptable acid addition salts of the amines are 
included within the scope of this invention. Pharmaceutically acceptable 
salts of amines are well known to those in the art, and it is generally 
recognized that the particular salt formed is not critical. The salt 
formed, however, must be pharmaceutically acceptable and substantially 
non-toxic to animal organisms. Typical acid addition salts are those 
prepared with the mineral acids, especially those prepared with acids such 
as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, and like 
acids. Organic acids such as formic, acetic, butyric, citric, maleic, 
succinic, oxalic, benozic, methanesulfonic, p-toluenesulfonic, and the 
like, can also be used to form acceptable salts. 
Pharmaceutically acceptable quaternary ammonium salts are also included 
herein and are important pharmacological agents. The particular salt 
formed is not critical, but the salt must be substantially non-toxic to 
animal organisms. Any of a number of anions can be associated with 
quaternary salts, and these are well known to chemists and biologists. 
Preferred quaternary ammonium salts are those prepared with C.sub.1 
-C.sub.4 lower alkyl alkylating agents. Generally, these salts are 
prepared by treating the amine with alkylating agents such as alkyl 
halides, alkylsulfates, arylsulfonates, and the like. Typical alkylating 
agents include methyl iodide, ethyl bromide, n-propyl chloride, dimethyl 
sulfate, isopropyl bromide, isobutyl iodide, and the like. Other 
acceptable salts are prepared with CH.sub.2 R.sub.4 alkylating agents, 
wherein R.sub.4 is as defined hereinabove. Examples of these alkylating 
agents include allyl bromide, 3-butenyl iodide, 3-pentenyl chloride, 
4-pentenyl chloride, 5-hexenyl iodide, and the like. When the anion of a 
quaternary ammonium salt is a halide ion, these anions can be replaced by 
other anions if desired, for example by metathesis. An anion such as 
sulfate, sulfonate, nitrate, hydroxide, perchlorate, tetrafluoroborate, 
acetate, butyrate, and the like, can be incorporated into the ammonium 
salt if desired. 
Illustrative examples of compounds provided by the present invention are as 
follows: 
1-Phenyl-1-(2-indanyl)-4-aminobutane; 
1-Phenyl-1-(2-indanyl)-4-methylamino-1-butene; 
1 -Phenyl-1-(2-indanyl)-4-isobutylaminobutane; 
1-(4-Trifluoromethylphenyl)-1-(2-indany;l)-4-allylamino-1-butene; 
1-(3-Chlorophenyl)-1-(2-indanyl)-4-amino-1-butene; 
1-(2-Methylphenyl)-1-(2-indanyl)-4-methylaminobutane; 
1-Phenyl-1-(2-indanyl)-4-amino-1-butene hydrobromide; 
1-Phenyl-1-(2-indanyl)-4-aminobutane hydroacetate; 
1-Phenyl-1-(1-indanyl)-4-n-propylaminobutane hydroiodide; 
1-Phenyl-1-(2-indanyl)-4-n-butylamino-1-butene hydrogen nitrate; 
1-Phenyl-1-(2-indanyl)-4-(5-hexenylamino)butane hydrogen maleate; 
1-Phenyl-1-(2-indanyl)-4-diethylaminobutane; 
1-Phenyl-1-(2-indanyl)-4-diisopropylaminobutane; 
1-(3-chlorophenyl)-1-(1-indanyl)-4-dimethylamino-butane; 
1-(4-methylphenyl)-1-(2-indanyl)-4di-n-propyl-l-butene; 
1-Phenyl-1-(2-indanyl)-4-diethylamino-1-butene; 
1-(3-methoxyphenyl)-1-(2-indanyl)-4-n-butylmethyl-amino-1-butene; 
1-Phenyl-1-(2-indanyl)-4-piperidinobutane; 
1-Phenyl-1-(2-indanyl)-4-morpholinobutane; 
1-Phenyl-1-(2-indanyl)-4-pyrrolidinobutane; 
1-(4-Trifluoromethylphenyl)-1-(2-indanyl)-4-diethylaminobutane 
hydrochloride; 
[4-Phenyl-4-(2-indanyl)butyl]triethylammonium iodide; 
[4-Phenyl-4-(2-indanyl)butyl]diethylmethylammonium methanesulfate; 
[4-Phenyl-4-(1-indanyl)-3-butenyl]allyldiethylammonium bromide; 
[4-Phenyl-4-(2-indanyl)-3-butenyl]trimethylammonium hydroxide. 
1-Phenyl-1-[1-(1,2,3,4-tetrahydronaphthyl)]-4-di-isopropylaminobutane; 
1-Phenyl-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-isopropylmethylaminobutane; 
1-(2-Bromophenyl)-1-[-(1,2,3,4-tetrahydronaphthyl)]-4-diethylaminobutane 
hydroacetate; 
1-(3-Iodophenyl)-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-aminobutane 
hydrobromide; 
1-(3-Methylphenyl)-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-piperadinobutane 
methiodide; 
1-(4-Trifluoromethylphenyl)-1-[1-(1,2,3,4-tetrahydronaphthyl)]-4-allylmethy 
lamino-1-butene; 
1-Phenyl-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-di-isopropylaminobutane 
hydroiodide; 
1-(4-Iodophenyl)-1-[1-(1,2,3,4-tetrahydronaphthyl)]-4-di-n-butylamino-1-but 
ene; 
1-(2-Methylphenyl)-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-di-allylamino-1-but 
ene hydrochloride; 
1-(4-Methoxyphenyl)-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-ethylaminobutane; 
1-(3-Methoxyphenyl)-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-diethylaminobutane 
hydrochloride; 
1-(2-Methoxyphenyl)-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-morpholinobutane; 
[4-Phenyl-4-[2-(1,2,3,4-tetrahydronaphthyl)]butyl]-trimethylammonium 
methanesulfate 
In accordance with the invention, the butenyl compounds are prepared by 
reacting an amine with a suitably substituted butene bearing a readily 
displaceable group. More specifically, a 
1-aryl-1-benzocycloalkyl-1-butene, with a displaceable group in the 
4-position, is treated with an amine, thereby providing the aminobutenes 
of this invention. Some examples of amines useful in preparing compounds 
disclosed herein include ammonia, methylamine, ethylamine, isopropylamine, 
n-butylamine, allylamine, 4-hexenylamine, dimethylamine, diethylamine, 
diisopropylamine, diallylamine, methylethylamine, methylallylamine, 
ethyl(2-methyl-3-butenyl)amine, trimethylamine, triethylamine, 
tri-n-propylamine, triallylamine, tri-3-hexenylamine, piperadine, 
pyrrolidine, morpholine, and the like. Preferred butene starting materials 
are those wherein the displaceable group is a halogen atom, especially 
chlorine, bromine, or iodide. Typical butenes useful in preparing the 
compounds of the invention include 
1-phenyl-1-(2-indanyl)-4-chloro-1-butene, 
1-(3-methoxyphenyl)-1-(1-indanyl)-4-bromo-1-butene, 
1-(4-chlorophenyl)-1-[1-(1,2,3,4-tetrahydronaphthyl)]-4-iodo-1-butene, 
1-phenyl-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-chloro-1-butene, and the 
like. The amine and the suitably substituted butene are normally 
commingled in approximately equimolar quantities, although an excess of 
either reactant can be employed if desired. The reaction is best carried 
out in an unreactive organic solvent. A suitably solvent can be selected 
from among any of a number of unreactive organic solvents, including 
alcohols such as methanol, ethanol, isopropanol; chlorinated hydrocarbons 
such as chloroform or dichloromethane; aromatic solvents such as benzene, 
toluene, or xylene; ethers such as diethyl ether, 1,2-dimethoxyethane or 
dioxane, and the like. Mixtures of solvents can be used if desired, for 
example a mixture of ethanol and benzene or ethanol and water. A preferred 
reaction solvent is ethyl alcohol, or alternatively a mixture of ethyl 
alcohol and benzene. The reaction is substantially complete after about 10 
to 20 hours when carried out at a temperature below about 150.degree. C. 
Generally, the temperature is maintained in the range of about 50.degree. 
to 100.degree. C. The product is a primary, secondary, or tertiary amine, 
or a quaternary ammonium salt, depending upon the particular aminating 
agent used in the reaction. When the aminating agent is a tertiary amine 
for example, the product is the corresponding quaternary ammonium salt. 
Generally, the quaternary ammonium salts are highly crystalline solids and 
can be filtered from the reaction mixture and further purified if desired, 
for example by recrystallization. When the product is a primary, secondary 
or tertiary amine, such product can be isolated either as the free amine 
or as an acid addition salt by suitable adjustment of the pH. For example, 
the reaction mixture can be evaporated to dryness and the residue 
redissolved in water. The pH of the aqueous solution can be adjusted to 
about 8 to 10 by the addition of a suitable base, such as aqueous sodium 
hydroxide for example. The basic solution is then extracted with a 
suitable water immiscible organic solvent, such as ethyl acetate or 
diethyl ether for instance, and the organic solution can then be 
evaporated to give the product in the form of the free amine. The free 
amine can be further purified if desired by standard methods such as 
distillation, chromatography, crystallization, or the like. Alternatively, 
the free amine can be isolated as an acid addition salt by treating the 
amine with a suitable acid, especially a mineral acid such as hydrochloric 
or hydrobromic acid for example, in a mutual solvent such as ethyl acetate 
or diethyl ether, thereby precipitating the corresponding acid addition 
salt. Generally, the amine acid addition salts are highly crystalline 
solids and can be filtered and further purified if desired by 
recrystallization from solvents such as ethanol, ethyl acetate, water, or 
the like. When desired, the acid addition salts can be converted back to 
the free amine by basification, for example by the addition of an 
appropriate base such as sodium hydroxide or sodium bicarbonate. 
The preferred aminobutenes of the invention are those wherein the amine is 
a tertiary amine, such as a dialkylaminobutene for instance. These 
tertiary amines can be converted to quaternary ammonium salts by normal 
procedures that are discussed in detail hereinbelow. Additionally, the 
primary and secondary aminobutenes can be converted to secondary, tertiary 
and quaternary compounds by general alkylation procedures that are 
discussed hereinbelow. The aminobutenes of this invention exist as cis and 
trans isomers, as well as mixtures thereof. It will be understood that the 
separated isomers, as well as the mixtures of geometrical isomers, are 
included within the scope of this invention. 
In a further embodiment of the invention, the aminobutenes prepared as 
described hereinabove are reduced to provide the aminobutanes of the 
invention. More specifically, the aminobutenes can be reduced by 
hydrogenation wherein the aminobutene is dissolved in an inert solvent and 
hydrogenated with hydrogen in the presence of a suitable hydrogenation 
catalyst. Suitable inert solvents include alcohols such as methanol or 
ethanol; esters such as methyl acetate or ethyl acetate; or ethers such as 
diethyl ether or tetrahydrofuran. The particular solvent selected for the 
reaction is not critical, but preferably the solvent used is one in which 
the aminobutene is at least partially soluble. Suitable hydrogenation 
catalysts include certain noble metals such as platinum, palladium, or 
rhodium, as well as active grades of Raney nickel. The noble metal 
catalysts may be employed as finely divided metals, such as that obtained 
by the hydrogenation of platinum oxide in the hydrogenation apparatus for 
example. Alternatively, the metal catalysts can be employed as deposited 
on the surface of an inert support such as carbon, alumina, barium 
sulfate, calcium carbonate, or the like. A preferred hydrogenation 
catalyst, for example, is palladium on carbon. The reduction reaction is 
generally carried out at a temperature below about 100.degree. C., 
preferably at a temperature in the range of about 0.degree. to 50.degree. 
C. The hydrogen gas pressure is normally maintained in the range of about 
30 to 2000 p.s.i., preferably at about 50 to 100 p.s.i., and the reaction 
is substantially complete after about 2 to 20 hours. The aminobutanes thus 
prepared can be recovered by removal of the hydrogenation catalyst, for 
example by filtration, and evaporation of the solvent to provide the free 
amine. Further purification can be accomplished, if desired, by normal 
procedures such as distillation or chromatography. The acid addition salts 
are readily obtained by reaction of the aminobutane with the appropriate 
acid, as described hereinabove for the aminobutenes. 
An alternative method of preparation of the aminobutanes of the invention 
comprises catalytic reduction of 1-aryl-1-benzocycloalkyl-4-halo-1-butenes 
to provide the corresponding halobutanes, which can then be aminated with 
an appropriate amine to provide the desired 
1-aryl-1-benzocycloalkyl-4-aminobutanes. 
It is to be understood that reduction of a butene provides a butane which 
possess an asymmetric center and thus exists as d and l stereoisomers. 
Both the d and the l isomer, as well as the dl mixture, are included 
within the scope of the present invention. 
As hereinbefore indicated, the aminobutenes and aminobutanes, wherein the 
amino group is primary, secondary, or tertiary, can be converted to 
pharmaceutically acceptable acid addition salts by the reaction of the 
appropriate acid with the free amine in a mutual solvent. Similarly, these 
aminobutenes and aminobutanes can be converted to quaternary ammonium 
salts which are valuable pharmacological agents. Generally, a tertiary 
amine, for example a 1-aryl-1-benzocycloalkyl-4-dialkylaminobutane, is 
treated with an alkylating agent in an unreactive solvent to provide the 
corresponding quaternary ammonium salt. Typical unreactive solvents 
include acetone, benzene, diethyl ether, methanol, tetrahydrofuran, or the 
like. Typical alkylating agents used to quaternize the amine are lower 
alkyl halides such as methyl chloride, ethyl iodide, allyl bromide, as 
well as alkyl sulfates such as methyl sulfate or ethyl sulfate. The 
reactants are normally employed in approximately equimolar amounts; 
however, an excess of either can be used if desired. The product 
quaternary salts are typically crystalline solids and are generally 
recovered by filtration. When the quaternary salt has a halogen anion, 
such as chloride or iodide for example, these anions can be converted to 
other anions when desired, as indicated hereinabove. More specifically, a 
quaternary ammonium halide can be reacted with aqueous silver oxide to 
afford silver halide and the corresponding quaternary ammonium hydroxide. 
The quaternary ammonium hydroxide can then be neutralized with an 
appropriate acid, such as methanesulfonic acid, acetic acid, butyric acid, 
nitric acid, p-toluene-sulfonic acid, or the like, thereby providing the 
corresponding pharmaceutically acceptable quaternary ammonium salt. 
Alkylation of aminobutenes and aminobutanes, wherein the amino group is 
primary or secondary, can be carried out when desired. For example, a 
primary aminobutane can be further alkylated with an appropriate 
alkylating agent to provide the corresponding secondary aminobutane, which 
can be alkylated still further to provide the corresponding tertiary 
amine. The alkylation reactions are general and are well known to those in 
the art. 
As hereinbefore indicated, the preferred starting materials for the 
compounds of this invention are 1-aryl-1-benzocycloalkyl-4-halobutenes. 
These compounds are readily available from known starting materials. More 
specifically, the disubstituted halobutenes are generally prepared from 
benzocycloalkyl aryl ketones, which compounds are well known. In 
particular, a benzocycloalkyl aryl ketone, such as 2-indanyl phenyl ketone 
for example, is treated with a cyclopropyl Grignard reagent to provide a 
benzocycloalkyl aryl cyclopropyl carbinol. The cyclopropyl carbinol is 
treated with an acid, especially a mineral acid such as hydrochloric or 
hydroiodic acid for example, thereby opening the cyclopropyl ring and 
dehydrating the alcohol to afford the corresponding disubstituted butenyl 
halide. 
The reaction of a benzocycloalkyl aryl ketone with a cyclopropyl Grignard 
reagent is preferably carried out in an unreactive organic solvent. 
Solvents generally used for Grignard reactions are well known to those in 
the art and include solvents such as diethyl ether, diglyme, 
1,2-dimethoxyethane, dioxane, furan, tetrahydrofuran, and the like. The 
particular solvent selected is not of a critical nature. The Grignard 
reagent is prepared by established procedures which comprise reacting 
magnesium metal with the appropriate alkyl halide, in particular a 
cyclopropyl halide such as cyclopropyl bromide for example. The 
cyclopropyl magnesium halide is then reacted with the benzocycloalkyl aryl 
ketone, normally in an equimolar amount; however, either can be used in 
excess of the other if desired. Preferably, the Grignard reagent is 
employed in slight excess of the ketone in order to ensure more complete 
reaction. The reaction is generally carried out at a temperature below 
about 150.degree., the most convenient temperature being the reflux 
temperature of the particular solvent being used. The reaction is 
substantially complete within about 2 to 12 hours, although longer 
reaction times are generally not detrimental to the production of the 
product. The product, a cyclopropyl benzocycloalkyl aryl carbinol, is 
recovered by hydrolyzing the reaction mixture with a proton source, such 
as water for example, and extraction of the product into a suitable 
solvent, such as diethyl ether or ethyl acetate. Evaporation of the 
solvent affords the desired carbinol which can be used directly, or if 
desired, the carbinol can be further purified by standard procedures, such 
as distillation or chromatography for example. 
The cyclopropyl benzocycloalkyl aryl carbinol is treated with a suitable 
acid to effect ring opening of the cyclopropyl ring system and concomitant 
dehydration. Preferred acids for the reaction include the mineral acids 
such as hydrochloric, hydrobromic, or hydroiodic acid. Acids such as 
methanesulfonic or p-toluenesulfonic acid can be used if desired. The 
reaction is generally carried out in an essentially anhydrous organic 
solvent; however, the particular solvent is not critical. Typical solvents 
generally employed include lower alkanoic acids such as formic acid, 
acetic acid or propionic acid; ethers such as dioxane; or amides such as 
N,N-dimethylformamide can also be used. The reaction is carried out at a 
temperature below about 70.degree. C, preferably at a temperature in the 
range of about 0.degree. to 30.degree. C. The reaction is normally 
complete within about 1 hour to about 8 hours. The product, a 
benzocycloalkyl aryl butene, can be recovered by diluting the reaction 
mixture with a suitable solvent, preferably water, and extracting the 
butene into a water immiscible solvent such as diethyl ether or ethyl 
acetate. If desired, the butene can be further purified by normal 
procedures such as distillation, crystallization or chromatography. 
The compounds of this invention are useful pharmacological agents, 
especially in the treatment of cardiac arrhythmias in humans. The 
compounds can be administered by the oral route or by the parenteral 
route, and in cases of severe arrhythmias, it may be desirable to 
administer the compounds intraveneously. Generally, a compound of this 
invention can be employed in combination with one or more pharmaceutically 
acceptable diluents or carriers. For oral administration, for example, the 
compound of this invention can be mixed with carriers such as starch 
powder, sucrose, cellulose, magnesium stearate, and the like. The dose can 
be formulated as a tablet or as a capsule. The normal adult oral dose will 
contain from about 0.005 to about 2.0 g. of active ingredient, and will be 
administered to a patient suffering from an arrhythmia at intervals of 
about 4 to 10 hours until a tolerance level has been reached, or until a 
conversion to a normal rhythm is maintained. The pharmaceutical 
preparations may contain, in addition to the active component of the 
present invention, one or more other pharmacologically active substances, 
especially other antiarrhythmic agents such as lidocaine for example. 
In the case of parenteral administration, the intravenous route is 
preferred. A suitable pharmaceutical preparation for intravenous 
administration will include a compound of this invention in the amount of 
from about 0.1 to about 1.0 g. admixed with a suitable carrier such as 5 
percent aqueous glucose or 0.9 percent saline solution for example, 
generally in the amount of about 50 to 100 cc. of solution. Such a 
solution can be administered dropwise to a patient suffering from an 
arrhythmia over a period of from 5 to about 60 minutes. The compounds of 
this invention are especially useful in patients refractory to other 
antiarrhythmic agents such as procainamide or quinidine for example. 
The following detailed examples are added to more fully illustrate, but not 
to limit, the scope of the invention.

EXAMPLE 1 
1-Phenyl-1-(2-indanyl)-4-diethylamino-1-butene 
To a solution of 29.5 g. of 1-phenyl-1-(2-indanyl)-4-chloro-1-butene in 125 
cc. of 95 percent (v/v) ethanolbenzene (commercial 2B ethanol) was added 
100 cc. of diethylamine in one portion. The reaction mixture was shaken 
and heated in a sealed bomb to about 100.degree. C for 16 hours. The 
reaction mixture was cooled to about 25.degree. C. and the solvent was 
removed under reduced pressure to afford the product as an oily residue. 
The oil was dissolved in 400 cc. of diethyl ether and shaken with 5N 
sodium hydroxide and washed with water. The ethereal solution was dried 
and the solvent was removed under reduced pressure, affording 
1-phenyl-1-(2-indanyl)-4-diethylamino-1-butene. 
EXAMPLES 2-5 
The following aminobutenes are prepared by the procedure of example 1, from 
the corresponding halobutene and amine. 
1-Phenyl-1-(1-indanyl)-4-methylamino-1-butene; 
1-(4-Chlorophenyl)-1-(2-indanyl)-4-amino-1-butene; 
1-(4-Methylphenyl)-1-(2-indanyl)-4-allylmethalamino-1-butene; 
1-Phenyl-1-[2-(1,2,3,4-tetrahydronaphthyl)]-4-ethylisopropylamino-1-butene. 
EXAMPLE 6 
1-Phenyl-1-(2-indanyl)-4-diethylamino-1-butene hydrogen oxalate 
A solution of 693 mg. of oxalic acid in 20 cc. of ethyl acetate was added 
to a solution of 1-phenyl-1-(2-indanyl)-4-diethyl aminobutene in 30 cc. of 
ethyl acetate. The reaction mixture was allowed to stand at room 
temperature for 2 hours, at which time the crystalline product was 
filtered to provide the oxalate salt of 
1-phenyl-1-(2-indanyl)-4-diethylamino-1-butene. M.P. 
98.degree.-101.degree. C. 
EXAMPLE 7 
1-Phenyl-1-(2-indanyl)-4-diethylamino-1-butene hydrochloride 
Dry hydrogen chloride gas was bubbled into a solution of 
1-phenyl-1-(2-indanyl)-4-diethylamino-1-butene in diethyl ether. The 
ethereal solution was concentrated under reduced pressure to provide the 
product as a white solid residue which was purified by recrystallization 
from an ethyl acetateligroin solvent mixture. Crystalline 
1-phenyl-1-(2-indanyl)-4-diethylamino-1-butene hydrochloride was recovered 
by filtration. M.P. 110.degree.-112.degree. C. 
Analysis, Calc. for C.sub.23 H.sub.30 NCl (percent): C, 77.61; H, 8.50; N, 
3.99; Cl, 9.96. 
Found (percent): C, 77.41; H, 8.61; N, 3.76; Cl, 10.17. 
EXAMPLE 8 
1-Phenyl-1-(2-indanyl)-4-diethylaminobutane 
A solution of 23.5 g. of 1-phenyl-1-(2-indanyl)-4-diethylamino-1-butene in 
375 cc. of 95 percent (v/v) ethanolbenzene was stirred while 1.5 g. of 5 
percent palladium on carbon was added in one portion. The reaction mixture 
was stirred for 6 hours at 24.degree. C. under a hydrogen gas atmosphere 
at 60 p.s.i. After filtering off the hydrogenation catalyst, the filtrate 
was concentrated to dryness under reduced pressure to provide 
1-phenyl-1-(2-indanyl)-4-diethylaminobutane. 
EXAMPLES 9-11 
The following aminobutanes are prepared by the method of Example 8 from the 
corresponding aminobutenes: 
1-Phenyl-1-(2-indanyl)-4-aminobutane; 
1-Phenyl-1-(2-indanyl)-4-ethylaminobutane; 
1-(4-Chlorophenyl)-1-[1-(1,2,3,4-tetrahydronaphthyl)]-4-diethylaminobutane. 
EXAMPLE 12 
1-Phenyl-1-(2-indanyl)-4-diethylaminobutane hydrochloride 
To a solution of 1-phenyl-1-(2-indanyl)-4-diethylaminobutane in diethyl 
ether was added anhydrous hydrogen chloride gas. The reaction mixture 
stood at room temperature for 20 minutes, and the solvent was then removed 
under reduced pressure, leaving the product as a solid residue. The 
product was recrystallized from ethyl acetate, affording 
1-phenyl-1-(2-indanyl)-4-diethylaminobutane hydrochloride. M.P. 
132.degree.-34.degree. C. 
Analysis, Calc. for C.sub.23 H.sub.32 NCl (percent): C, 77.17; H, 9.01; N, 
3.91; Cl, 9.90. 
Found (percent): C, 77.09; H, 8.98; N, 3.81; Cl, 9.99. 
EXAMPLE 13 
4-Phenyl-4-(2-indanyl)-butyldiethylmethylammonium methanesulfate 
To a stirred solution of 3.14 g. of 
1-phenyl-1-(2-indanyl)-4-diethylaminobutane in 50 cc. of benzene was added 
1.26 g. of dimethyl sulfate. The reaction mixture was stirred at room 
temperature for 12 hours. The crystalline product was filtered off and 
recrystallized from ethyl acetate and methanol, providing 3.85 g. of 
4-phenyl-4-(2-indanyl)-butyldiethylmethylammonium methanesulfate. M.P. 
118.degree.-121.degree. C. 
Analysis, Calc. for C.sub.25 H.sub.37 NO.sub.4 S (percent): C, 67.08; H, 
8.33; N, 3.13; S, 7.16. 
Found (percent): C, 67.37; H, 8.11; N, 3.17; S, 7.01. 
EXAMPLE 14 
1-Phenyl-1-(2-indanyl)-4-methyl-n-propylaminobutane 
A solution of 1-phenyl-1-(2-indanyl)-4-bromobutane in ethanol was stirred 
at room temperature while methylpropylamine was added. The reaction 
mixture was stirred several hours at about 100.degree. C. After cooling 
the reaction mixture to room temperature, the solvent was removed under 
reduced pressure, affording 
1-phenyl-1-(2-indanyl)-4-methyl-n-propyl-aminobutane.