AMINOBENZOIC ACID DERIVATIVES, THEIR PREPARATION AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS OR AS INTERMEDIATES

OBTENTION ET EMPLOI DE DERIVES D'ACIDE AMINOBENZOIQUE COMME PRODUITS PHARMACEUTIQUES OU INTERMEDIAIRES DE CES DERNIERS

English Abstract

Abstract
Aminobenzoic acid derivatives are disclosed of the general formual:
<IMG> (I)
whreein
R1 represents a hydrogen or halogen atom,
R2 and R3 each represents alkyl, cycloalkyl, phenylalkyl or pyridyl, or
together represent a cyclic imino group or one of the radicals R2 and R3
represents a hydrogen atom,
A represnets a cycloalkylene group or an optionally substituted or interrupted
alkylene group,
X represents an oxygen atom or an imino group and
Y represents a hydroxy or amino group, a halogen atom, an aminobenzoyloxy or
aminobenzoic acid amido group or with the .alpha.- and .beta.-carbon atoms of the
radical A represents an oxiranyl or1,3-dioxolanyl group, as well as their
acid addition salts. These compounds exhibit valuable pharmacological
properties. Besides a secretolytic and/or antitussive activity, they
especially show an antiulcus activity. Moreover, they represent intermediates
for thepreparation of compounds with an antiphlogistic activity.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the preparation of a novel aminobenzoic acid deri-
vative of the general formula:
<IMG> (I)
wherein
R1 represents a hydrogen, fluorine, chlorine or bromine atom, R2 and R3, which
may be the same or different, each represents a straight-chain or branched
alkyl group with 1 to 6 carbon atoms, which may be substituted by a phenyl
group or a dialkylamino group with 1 to 3 carbon atoms in each alkyl part,
pyridyl or cycloalkyl group with 5 to 7 carbon atoms or
R2 and R3 together with the nitrogen atom to which they are attached, repre-
sent a pyrrolidino, piperidino, hexamethylenimino, morpholino, N-arylpiperazino
or N-alkylpiperazino group, wherein the alkyl group may contain 1 to 3 carbon
atoms, or
one of the radicals R2 and R3 represents a hydrogen atom,
A represents a cycloalkylene group with 5 to 7 carbon atoms, a straight-chain
alkylene group with 2 to 10 carbon atoms, which may be substituted by 1 or 2
alkyl groups with 1 to 3 carbon atoms each, by 1 or 2 carbalkoxy groups with
altogether 2 to 4 carbon atoms each, by 1 or 2 phenyl groups, by 1 to 4
hydroxy groups and/or by a group of the formula:
<IMG> ,

wherein R1, R2, and R3 are as defined above, or may be interrupted by an
oxygen or sulfur atom, by a sulfoxide, sulfonyl, benzene, cyclohexane,
pyridine, piperazino or imino group, which imino group may be substituted by
an alkyl group with 1 to 6 carbon atoms, phenyl or phenylalkyl group with 1
to 3 carbon atoms in the alkyl part,
X represents an oxygen atom or an imino group and
Y represents a hydroxy or amino group, a chlorine, bromine or iodine atom,
a radical of the formula:
<IMG> ,
wherein R1, R2 and R3 are as defined above and Z represents an oxygen atom
or an imino group, or together with the .alpha.- and .beta.-carbon atoms of the radical
A, if it contains at least 3 carbon atoms, represents an oxiranyl group or
a 1,3-dioxolanyl group of the formula:
<IMG>
wherein
R4 and R5, which may be the same or different, each represents a hydrogen
atom, an alkyl group with 1 to 3 carbon atoms or a phenyl group, or its
physiologically compatible acid addition salt with an inorganic or organic
acid, which process comprises
reacting a carboxylic acid of the general formula:
56

<IMG> (II)
wherein
R1, R2 and R3 are as defined above, or a salt or a reactive derivative thereof
with a compound of the general formula:
H - X - A - Y (III)
wherein
A, X and Y are as defined above before or the group HX together with the .alpha.-
and .beta.-carbon atoms of the radical A represents an oxiranyl group, or a
reactive derivative thereof,
and, if desired, subsequently converting an obtained compound of general
formula I, wherein Y together with the .alpha.- and .beta.-carbon atoms of the radical
A, if it contains at least 3 carbon atoms, represents an oxiranyl group or
a 1, 3-dioxolanyl group of the formula:
<IMG>
wherein R4 and R5 are as defined above, into a corresponding dihydroxy compound
by means of hydrolysis, or
converting an obtained compound of general formula I, wherein Y represents a
hydroxyl group into a corresponding halogen compound by means of halogenation,
and/or converting an obtained compound of general formula I into a physiolog-
ically compatible acid addition salt with 1 to 3 equivalents of the corres-
ponding inorganic or organic acid.
57

2. A process as claimed in claim 1, wherein the reaction of the com-
pound of general formula III is carried out with a carboxylic acid of general
formula II or a functional derivative thereof, optionally in the presence of
an acid activating and/or dehydrating agent and at a temperature between -25
and 250°C.
3. A process as claimed in claim 1, wherein the reaction of the
carboxylic acid of general formula II or its salt with a reactive derivative
of a compound of general formula III is carried out at a temperature between
-20 and 250°C.
4. A process as claimed in claim 2, wherein as functional derivative
of the carboxylic acid of general formula II, an ester, imidazolide, acid
halogenide, anhydride, mixed anhydride, acyloxytriphenyl phosphonium salt,
N-acyloxyimide or isatoic acid anhydride (if the amino group is present in
2-position) is used.
5. A process as claimed in claim 3, wherein as reactive derivative of
the compound of general formula III, a phosphazo derivative (if HX represents
an amino group), an epoxide (if HX represents a hydroxy group), a halogenide
or an ester with a sulfonic or carboxylic acid is used.
6. A process as claimed in claim 3, wherein as salt of the carboxylic
acid of general formula II, the alkali, alkaline earth or silver salt is used.
7. A process as claimed in claims 1, 4 or 5, wherein the reaction is
carried out in a solvent and at a temperature between -10°C and the boiling
temperature of the solvent.
8. A process as claimed in claim 1, 4 or 5, wherein the reaction is
carried out in the presence of an inorganic or tertiary organic base.
58

9. A process as claimed in claim 1, 4 or 5, wherein the reaction
is carried out in the presence of a reaction accelerator selected from
sodium hydride, 4-dimethylamino pyridine, sodium iodide and potassium
iodide or in the presence of a crown ether as phase transfer catalyst.
10. A process as claimed in claim 1, wherein starting materials are
chosen in which R1 represents a chlorine or bromine atom, R2 and R3, which
may be the same or different, each represents an alkyl group with 1 to 4 car-
bon atoms, a cycloalkyl group with 5 to 7 carbon atoms, benzyl, 2-diethyl-
aminoethyl or pyridyl group or R2 and R3 together with the nitrogen atom to
which they are attached, represent the pyrrolidino, piperidino, hexamethyl-
enimino, morpholino or N-methylpiperazino group, or one of the radicals R2
and R3 represents a hydrogen atom,
A represents a straight-chain or branched alkylene group with 2 to 10 carbon
atoms, which may be substituted by 1 to 4 hydroxy groups and/or by 1 or 2
alkoxycarbonyl groups with altogether 2 or 3 carbon atoms each, an ethylene
group substituted by 1 or 2 phenyl groups, a cyclohexylene, pryidine-2,6-bis-
methylene, cyclohexane-1,4-bis-methylene, or p-xylylene group or a straight-
chain alkylene group with 4 to 6 carbon atoms, which is interrupted between
the carbon atoms 2 and 3 or between the carbon atoms 3 and 4 by an oxygen
or sulfur atom, by a sulfoxide, sulfonyl, amino, phenylamino, benzylamino,
piperazino or an alkylamino group with l to 4 carbon atoms,
X represents an oxygen atom or an imino group and
Y represents a hydroxy or amino group, a chlorine or bromine atom, a radical
of the formula:
<IMG> ,
59

wherein R1, R2 and R3 are as defined in claim 1 and Z represents an oxygen
atom or an imino group, or together with the .alpha.- and .beta.-carbon atoms of the
radical A, if it contains at least 3 carbon atoms, represent an oxiranyl
group or a 1,4-dioxolanyl group of formula
<IMG>
11. A process as claimed in claim 10, wherein starting materials
are chosen in which
R1, R2, R3, A and X are as defined in claim 10 and Y represents a hydroxy or
amino group or a radical of formula
<IMG> ,
wherein
R1, R2 and R3 are as defined in claim 10.
12. A process as claimed in claim 10, wherein starting materials are
chosen in which R1 represents a bromine atom,
R2 represents an alkyl group with 1 to 4 carbon atoms,
R3 represents a hydrogen atom, an alkyl group with 1 to 3 carbon atoms or a
cycloalkyl group with 5 to 7 carbon atoms or
R2 and R3 together with the nitrogen atom to which they are attached, repre-
sent a pyrrolidino or hexamethylenimino group,
A represents a straight-chain or branched alkylene group with 2 to 9 carbon

atoms, which may be substituted by 1 to 4 hydroxy groups and/or by 1 or 2
alkoxycarbonyl groups with altogether 2 or 3 carbon atoms each, a cyclohexyl-
ene group or a straight-chain alkylene group with 4 carbon atoms, which is
interrupted between the carbon atoms 2 and 3 by an oxygen atom, an amino or
methylamino group,
X represents an oxygen atom or an imino group and
Y represents a hydroxy group or a radical of formula
<IMG> ,
wherein R1, R2 and R3 have the meanings defined in claim 10.
13. A process as claimed in claim 10, wherein starting materials are
chosen in which
R1 represents a bromine atom,
R2 represents an alkyl group with 1 to 4 carbon atoms,
R3 represents an ethyl group or a cycloalkyl group with 5 to 7 carbon atoms or
R2 and R3 together with the nitrogen atom to which they are attached represent
a hexamethylenimino group,
A represents an ethylene group, which may be substituted by 1 or 2 alkoxy-
carbonyl groups with altogether 2 or 3 carbon atoms each, a 2-hydroxy-n-
propylene group, a straight-chained alkylene group with 3 to 5 carbon atoms,
n-hexylene group substituted by 4 hydroxy groups, a n-butyl group, which is
interrupted between the carbon atoms 2 and 3 by an oxygen atom or a methyl-
amino group,
X represents an oxygen atom or an imino group and
Y represents a hydroxy group or a radical of formula
61

<IMG> ,
wherein
R1, R2 and R3 are as defined in claim 10.
14. A process for preparing 1-[4-amino-3-bromo-5-(N-ethyl-cyclohexyl-
aminomethyl)-benzoyloxy]-2,3-dihydroxy-n-propane and the hydrochloride
thereof, which comprises reacting 4-amino-3-bromo-5-(N-ethyl-cyclohexyl-
aminomethyl)-benzoic acid sodium salt with 1-chloro-2,3-dihydroxy-n-propane
and, if desired, converting the product to the hydrochloride by means of
etheric hydrochloric acid.
15. A process for preparing 1-[4-amino-3-bromo-5-(N-cyclohexyl-n-
propylaminomethyl)-benzoyloxy]-2-hydroxy-ethane and the hydrochloride thereof,
which comprises reacting 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride-hydrochloride with ethylene glycol and, if desired, convert-
ing the hydrochloride to the free base by treatment with sodium hydroxide.
16. An aminobenzoic acid derivative of the general formula:
<IMG> (I)
wherein
R1 represents a hydrogen, fluorine, chlorine or bromine atom,
R2 and R3, which may be the same or different, each represents a straight-
chain or branched alkyl group with 1 to 6 carbon atoms, which may be sub-
stituted by a phenyl group or a dialkylamino group with 1 to 3 carbon atoms
in each alkyl part, pyridyl or cycloalkyl group with 5 to 7 carbon atoms, or
62

R2 and R3 together with the nitrogen atom to which they are attached, repre-
sent a pyrrolidino, piperidino, hexamethylenimino, morpholino, N-arylpiperazino,
or N-alkylpiperazino group, wherein the alkyl group may contain 1 to 3 carbon
atoms, or
one of the radicals R2 and R3 represents a hydrogen atom,
A represents a cycloalkylene group with 5 to 7 carbon atoms, a straight-chain
alkylene group with 2 to 10 carbon atoms, which may be substituted by 1 or
2 alkyl groups with 1 to 3 carbon atoms each, by 1 or 2 carbalkoxy groups
with altogether 2 to 4 carbon atoms each, by 1 or 2 phenyl groups, by 1 to 4
hydroxy groups and/or by a group of the formula
<IMG> ,
wherein R1, R2 and R3 are as defined above, or may be interrupted by an oxygen
or sulfur atom, by a sulfoxide, sulfonyl, benzene, cyclohexane, pyridine,
piperazino or imino group, which imino group may be substituted by an alkyl
group with 1 to 6 carbon atoms, by a phenyl or phenylalkyl group with 1 to 3
carbon atoms in the alkyl part,
X represents an oxygen atom or an imino group and
Y represents a hydroxy or amino group, a chlorine, bromine or iodine atom,
a radical of the formula
<IMG> ,
wherein R1, R2 and R3 are as defined as above and Z represents an oxygen atom
63

or an imino group or together with the .alpha.- and .beta.-carbon atoms of the radical
A, if it contains at least 3 carbon atoms, represents an oxiranyl group or
a 1,3-dioxolanyl group of the formula:
<IMG>
wherein R4 and R5, which may be the same or different, each represents a
hydrogen atom, an alkyl group with 1 to 3 carbon atoms or a phenyl group, or
a physiologically compatible acid addition salt thereof with an inorganic or
organic acid, whenever prepared by the process claimed in claim 1, or by an
obvious chemical equivalent thereof.
17. An aminobenzoic acid derivative of formula I or a physiologically
compatible acid addition salt thereof, wherein R1, R2, R3, A, X, Y and Z are
as defined in claim 10, whenever prepared by the process claimed in claim 10,
or by an obvious chemical equivalent thereof.
18. An aminobenzoic acid derivative of formula I or a physiologically
compatible acid addition salt thereof, wherein R1, R2, R3, A, X, Y and Z
are as defined in claim 11, whenever prepared by the process claimed in claim
11, or by an obvious chemical equivalent thereof.
19. An aminobenzoic acid derivative of formula I or a physiologically
compatible acid addition salt thereof, wherein R1, R2, R3, A, X, Y and Z
areas defined in claim 12, whenever prepared by the process claimed in claim
12, or by an obvious chemical equivalent thereof.
64

20. An aminobenzoic acid derivative of formula I or a physiologically
compatible acid addition salt thereof, wherein R1, R2, R3, A, X, Y and Z
are as defined in claim 13, whenever prepared by the process claimed in
claim 13, or by an obvious chemical equivalent thereof.
21. 1-[4-Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-oxy]-
2,3-dihydroxy-n-propane and the hydrochloride thereof, whenever prepared by
the process claimed in claim 14, or by an obvious chemical equivalent thereof.
22. 1-[4-Amino-3-bromo-5-(N-cyclohexyl-n-propylaminomethyl)-benzoyloxy]-
2-hydroxy-ethane and the hydrochloride thereof, whenever prepared by the
process claimed in claim 15, or by an obvious chemical equivalent thereof.

Description

1~4~93~
Dr. Karl Thomae GmbH
Case 5/759
Dr.Fl/ra
New Aminobenzoic Acid Derlvatives, their Preparation
and their Use a~ Pharmaceutical Compositions or as
Intermediates
The Present invention relate~ to new aminobenzoic acid deri-
vativee of general ~ormula
., ..................... I
R1
R2 ~ ~ C - X - A - Y
N - CH2 ~ ,(~)
3 NH2
to their physiologically compatible acid addition salt~ with
lnorganic or organic acids and to processes ior their prepa-
ration as well as to the use of the new aminobenzoic acid
derlvatlves as pharmaceutlcal composltions and as intermedi-
ate~ ~or the preparation o~ new antiphlogi~tic com-
pounds.
The new aminobenæoic acid derivatives and their physiologi-
cally compatible acid addition salts ~how valuable pharmacolo-
gical properties. Beside~ a secretolytic and/or antitussive acti-
vity they especially show an antiulcus activity and an inhibi-
ting activity on the gastric fluid secretion. Moreover, they
., , , ~

- ` 114~)934
represent valuable intermediate~ for the preparatlon
of compounds with an antiphlogistic activity. These compound~
can be obtained by reaction of an antiphlogistic containing
a carboxyl group with a compound of the above general formula I.
In the above general formula I
R1 represents a hydrogen, fluorine, chlorine or bromine atom,
R2 and R3, which may be the same or different, represent
straight-chained or branched alkyl group~ with 1 to 6 car-
bon atoms, which may be sub~tituted by a phenyl group or a
dialkylamlno gr~up with 1 to 3 carbon atoms in each
alkyl part, pyridyl or cycloalkyl groups with 5 to 7
carbon atom~, or
R2 and R3 together with the nitrogen atom to which they are
attached represent a pyrrolidinoj piperidino, hexamethylene-
lmino, morpholinoj N-arylpiperazinoj or N-Alkylpiperazino
group, whereby the alkyl group may contain 1 to 3 carbon
atoms; or
one of the radicals R2 or R3 represent also a hydrogen atom,
A repre~ents a cycloalkylene group with 5 to 7 carbon atoms,
a straight-chalned a~kylene group with 2 to 10 carbon atom~,
which may be ~ubstituted by 1 or 2 alkyl groups with 1 to
3 carbon atoms each, by 1 or 2 carbalkoxy groups with al-
together 2 to 4 carbon atoms each, by 1 or 2 phenyl groups,
by 1 to 4 hydroxy groups and/or by a group of formula
~ C~2 ~ 0 - C ~ ~ ~2
CH2 - N
R1 R3

114V934
whereby R1, R2 and R3 are defined as mentioned before,
or may be interrupted by an oxygen or sulfur atom, by
a sulfoxide, sulfonyl, benzene, cyclohexane, pyridine,
piperazino or imino group, whereby the imino group may
be substituted by an alkyl group with 1 to 6 carbon
atoms, by a phenyl or phenylalkyl group with 1 to 3
carbon atoms in the alkyl part,
X represents an oxygen or an imino group and
Y represents a hydroxy or amino group, a chlorine, bromine
or iodine atom, a radical of formula
_ Z - C ~ CH - N
R1 - R3
whereby R1, R2 and R3 are defined as mentioned before and
Z represents an oxygen atom or an imino group, or together
with the ~C- and B-carbon atoms Or the radical A, lr lt
contaln~ at least ~ carbon atoms, represents an oxlranyl
group, or a 1,3-dloxolanyl group Or formula
~.
- CH ~ CH2
~C~
R ~ ~ R
4 5
wherein
R4 and R5, which may be the same or different, represent
hydrogen atoms, alkyl groups with 1 to 3 carbon atoms or
phenyl groups.

1140934
The meanings mentioned before in the de~inition of the ra-
dicals R2 to R5, A and X may include for example for the
R2~
~ N - group the meaning of the methylamino, ethylamino,
n-propylamino, isopropylamino, n-butylamino, tert.butylamino,
n-pentylamino, n-hexylamino, dimethylamino, diethylamino,
di-n-propylamino, diisopropyla~ino, di-n-butylamino, di-n-
pentylamino, di-n-hexylamino, ethylmethylamino, ethyl-propyl-
amino, ethyl-butylamino, propyl-isopropylamino, propyl-butyl-
amino, methyl-cyclopentylamino, methyl-cyclohexylamino, methyl-
cycloheptylamino, ethyl-cyclopentylamino, ethyl-cyclohexylamino,
ethyl-cycloheptylamino, propyl-cyclopentylamino, propyl-cyclo-
hexylamino, propyl-cycloheptylamino, cyclopentylamino, cyclo-
hexylamino, cycloheptylamino, dicyclohexylamino, benzylamino,
methyl-benzylamino, ethyl-benzylamino, cyclohexyl-benzylamino,
.dibenzylamino, phenylethylamino, methyl-phenylethylamino,
ethyl-phenylethylamino, propyl-phenylethylamino, phenyl-propyl-
amino, phenylamino, methyl-phenylamlno, ethyl-phenylamino,
2-(dimothylamino)-ethylamlno, 2-(diethylamino)-ethylamino,
2-(dipropylamino)-ethylamino, 3-(dimethylamino)-propylamino,
3-(dipropylamino)-propylamino, N-methyl-2-(dimethylamino)-
othylamlno, N-ethyl-2-(diethylamino)-ethylamino, pyridylamino,
pyrrolidino, piperidino, hexamethylenimino, morpholino,
N-methyl-piperazino, N-ethyl-pipérazino, N-propyl-piperazino,
N-i~opropyl-piperazino, or N-phenyl-p1perazlno group,
~or A the meaning of the 1,2-cyclopentylene, 1,3-cyclopentylene,
1,2-cyclohexylene, 1,3-cyclohexylene, 1,4-cyclohexylene, 1,2-
cycloheptylene, 1,3-cycloheptylene, 1,4-cycloheptylene,
ethylene, n-propylene, n-butylene, n-pentylene, n-hexylene,
n-heptylene, n-octylene, n-nonylene, n-decylene, 1-methyl-
ethylene, 2-methyl-ethylene, 1,2-dimethyl-ethylene, 1-methyl-
propylene, 2-methyl-propylene, 3-methyl-propylene, 1,2-di-
methyl-propylene, 1,3-dimethyl-propylene, 2-methyl-2-propyl-
propylene, 1-methyl-butylene, 1-methyl-pentylene, 1-methoxy-

1 ~ 4fJ9 3 4
carbonyl-ethylene, 2-methoxy-carbonyl-ethylene, 1-ethoxy-
carbonyl-ethylene, 2-ethoxycarbonyl-ethylene,.1,2-diethoxy-
carbonyl-ethylene, 1-ethoxycarbonyl-propylene, 2-ethoxycar-
bonyl-propylene, 3-ethoxycarbonyl-propylene, 1-propoxycar-
bonyl-ethylene, 2-propoxycarbonyl-ethylene, 2-hydroxy-pro-
pylene, 2-hydroxy-butylene, 3-hydroxy-butylene, 2,3-dihydroxy-
butylene, 2-hydroxy-pentylene, 2,3,4-trihydroxy-pentylene,
2,3,4,5-tetrahydroxy-n-hexylene, 1-hydroxymethyl-ethylene,
2-hydroxymethyl-ethylene, 2-~-amino-3-bromo-5-diethylamino-
methyl-benzoyloxymethyl7ethylene, 2- ~ -amino-3-bromo-5-
(N-cyclohexyl-ethylaminomethyl)-benzoyloxymethyl7ethylene,
diethylene oxide, diethylene sulfide, diethylene sulfoxide,
diethylene sulfonyl, N,N-diethylene-amino, N,N-diethylene-
methylamino, N,N-diethylene-ethylamino, N,N-diethylene-propyl-
amino, N,N-diethylene-i~opropylamino, N,N-diethylene-butylamino,
N,N-diethylene-tert.butylamino, N,N-diethylene-hexylamino,
N,N-diethylene-phenylamino, N,N-diethylene-benzylamino, N,N-di-
ethylene-phenylpropylamino, ethylene-propylene oxide, N-ethy-
lene-N-propylene-methylamino, N-ethylene-N-butylene-ethylamino,
pyridine-bis-methylene, cyclohexane-bis-methylene, xylylene,
N,N'-dlethylene-piperazino, or N-ethylene-N'-propylene-piper-
azino group,
for R4 and R5 the meaning of the hydrogen atom, the methyl,
ethyl, propyl, i~opropyl or phenyl group and
for X the meaning of the oxygen atom or the imino group.
Preferrod compounds of general formula I are those, wherein
R1 repre~ents a chlorine or bromine atom,
R2 and R3, which may be the same or different, repre~ent
alkyl groups with 1 to 4 carbon atoms, cycloalkyl groups
with 5 to 7 carbon atoms, benzyl, 2-diethylaminoethyl or
pyridyl groups or R2 and R3 together with the nitrogen atom

114~?34
to whi~ch they are attached, represent the pyrrol~dino,
piperidino, hexamethylenimino, morpholino or N-methyl-
piperazino group or one of the radicals R2 or R3 repre-
sents also a hydrogen atom,
A represents a straight-chained or branched alkylene group
with 2 to 10 carbon atoms, which may be substituted by
1 to 4 hydroxy groups and/or by 1 or 2 alkoxycarbonyl
groups with altogether 2 or 3 carbon atoms each, an
ethylene group substituted by 1 or 2 phenyl groups,
a cyclohexylene, pyridine-2,6-bis-methylene, cyclohexane-
1,4-bis-methylene, or p-xylylene group,
or a straight-chained alkylene group with 4 to 6 carbon
atoms, which may be interrupted between the carbon atoms
2 and 3 or between the carbon atoms 3 and 4 by an oxygen
or suliur atom, by a sulioxide, sulfonyl, amino, phenyl-
amino, benzylamino, piperazino or an alkylamino group
with 1 to 4 carbon atoms,
X represent~ an oxygen atom or an imino group and
Y repre~ents a hydroxy or amino group, a chlorine or bromine
atom, a radlcal of formula
O _~ NN2
whereby R1, R2 and R3 have the meanings mentioned before and
Z represents an oxygen atom or an imino group, or together with
the ~ - and B-carbon atoms or the radical A, i~ it contains
at least 3 carbon atoms, represents an oxiranyl group, or
a 1,3-dioxolanyl group of ~ormula
_ CH ~ CH2
0 ,~ 0
CH3 - C`~ CH3

1~4~934
and their physiologically compatible acid addition salts.
Hereby, especially those compounds of general formula I
show valuable pharmacological properties, wherein Y
represents a hydroxy or amino group or a radical of
formula
~ ~ 2
CH - N ,
R1 2 - R3
Aminobenzoic acid derivatives o~ general formula I with
particularly valuable pharmacological properties are those,
wherein
R1 represents a bromine atom,
R2 repre~ents an al~yl group with 1 to 4 carbon atoms,
R3 repre~ent~ a hydrogen atom, an alkyl group with 1 to 3
carbon atoms or a cycloalkyl group wlth 5 to 7 carbon
atom~ or
R2 and R3 together with the nitrogen atom to which they
are attached, represent a pyrrolidino or hexamethylene
lmino group,
A represents a ~traight-chalned or branched alkylene group
with 2 to 9 carbon atoms, which may be substituted by 1 .
to 4 hydroxyl groups and/or by 1 or 2 alkoxycarbonyl groups
with altogether 2 or 3 carbon atoms each, a cyclohexylene
group or a straight-chained alkylene group wlth 4 carbon
atoms, which may be interrupted between the carbon atoms
2 and 3 by an oxygen atom, an amino or methylamino group,

- 8 -
1~4~)934
X represents an oxygen atom or an imino group and
Y represents a hydroxy group or a radical of formula
CH2 - N
1 3
whereby R1, R2 and R3 have the meanings mentioned
before, and their physiologically compatible acid
addition salts.
According to the invention the new compounds of general
formula I can be obtained according to the following process:
Reaction of a carboxylic acid of general formula
R1
R~ ~ ~ ,~II)
NH2
wherein
R1, R2 and R~ are defined as mentioned before, their salts
or reactive derivatives with a compound of general formula
H - X - A - Y ,(III)
wherein
A, X and Y are defined as mentioned before or the group HX
togethor with the ~ - and B-carbon atom~ of the radlcal A,
represents an ox~ranyl group, or their reactive derivatives.

1~4~934
Thus, the reaction concerns the acylation of a compound of
general formula III with a carboxylic acid of general for-
mula II or with their functional derivatives, optionally
in the presence of an acid activating and/or dehydrating
agent, the reaction of a carboxylic acid of general for-
mula II with a reactive derivative of a compound of general
formula III or the alkylation Or a salt of a carboxylic acid
of general formula II with a corresponding functional deri-
vative of a compound of general formula III.
Functional derivatives of a carboxylic acid of general for-
mula II may include for example their alkyl, aryl or aralkyl
esters such as the methyl, ethyl, phenyl or benzyl ester,
their imidazolides, their acid halogenides such as the acid
chloride or acid bromide, their anhydrides, their mixed an-
hydrides with aliphatic or aromatic carboxylic acids or car-
bonic esters, e.g. the acetic acid, propionic acid or the
ethyl carbonate, their acyloxy-triphenylphosphonium salts,
their N-acyloxyimides or, if the amino group is present in
2-position, also their isatol¢ aeld anhydrides, as-reactive
deriratlves of a compound of general formula III their
phosphazo derivatives, if HX represents an amino group, and,
lf HX represents a hydroxy group, their epoxides, halogenides
such as the chloride, bromide or iodide, their sulfonic acid
esters such as those of the methane sulfonic acid or p-tolu-
ene sulfonic acid or their esters with aliphatic or aromatic
carboxylic acids such as those of the acetic acid, propionic
acid or benzoic acid and as salts of a carboxylic acid of
general formula II their alkali and alkaline earth salts
such as the sodium, potassium or calcium salt or their silver
salt.
Dehydrating and/or acid activating agents may include for
example an ester of chloroformic acid such as the ethyl
chloroformate, thionyl chloride, phosphorus trichloride,
phosphorus pentoxide, N,N'-dicyclohexyl carbodilmide,
N,N'-carbonyl diimidazole, N,N'-thionyl-diimidazole or
boron trifluoride etherate.

- 10 -
114~934
The reaction is conveniently carried out in a so1vent such
as dichloro methane, chloroform, carbon tetrachloride, ether,
dioxane, tetrahydrofurane, benzene, toluene, dimethyl iorm-
amide or methanol optionally in the presence of an inorganic
base such as sodium carbonate or a tertiary organic base
such as triethylamine or pyridine, which simultaneously may
serve also as solvents, optionally in the pr~sence of an
acid activating agent at temperatures between -25 and 250C,
preferably, however, at temperatures between -10C and the
bolling temperature of the used solvent. Hereby, a functio-
nal derivative of a compound oi~ general formulae II and III
optionally formed in situ, needs not to be isolated, moreover,
the reaction can also be carried out without a solvent and/or
in the presence of a reaction accelerator such as sodium
hydride or 4-d~methylaminopyridine. Furthermore, the water
iormed during the reaction can be removed by azeotropic
distillation, e.g. by heating with toluene in a water sepa-
rator funnel, optionally in the presence of a drying agent
~uch as magnesium sulfate or a molecular sieve,
E~pecially advantageously, the reaction of an alkall aalt of
a carboxylic acid of general formula II can be carried out
with a compound of general formula III, wherein HX represents
a halogen atom such as the chlorine or bromine atom, in the
presence of a reaction accelerator such as an alkali iodide,
o.g sodlum or potassium iodide, or in the presence of a
phase transfer cata}yst such as a so-called crown ether,
e.g. 15-cro~n-5.
If a compound of general formula I i~ obtained according to
the inventlon, wherein Y together with the ~ - and B-carbon
atoms oi the radical A, if A at lea~t contains 3 carbon atoms,
ropre~ent~ an oxiranyl group or a 1,3-dioxolanyl group of
formula

114~34
- CH - CH2
~ C ~
R4 R5
this compound can be converted to a corresponding dihydroxy
compound by means of hydrolysis, or
a compound of general formula I, wherein Y repre~ents a
radical of formula
_ 0 - C ~ CN - N
R1 - R3
can be converted to a corresponding hydroxy compound by
means of partial hydrolysis, or
a compound oi general formula I, wherein Y represents the
hydroxy group, can be converted to the corresponding halogen
compound by means of a halogenation agent such as a phospho-
rou~ halogenide or thionyl halogenide.
The ~ub~equent hydrolysis is carried out in the presence of
an acid ~uch as acetic acid, hydrochloric acid or sulfuric
acid optlonally in a solvent such as water/isopropanol,
water/dioxane, water/tetrahydrofurane or water/dimethyl
formamide at temperatures between 0 and 100C, preferably
however, at temperature~ between 20 and 50C.
The subsequent partial hydrolysis is conveniently carried
out in a solvent such a~ isopropanol, tetrahydrofurane, dio-
xane or dimethyl formamide, preferably in the presence of
an equivalent of base, e.g. an aqueous solution of sodium
hydroxide, pota~ium hydroxide or pota~sium carbonate,

- 12 -
1140934
at temperatures between 20 and 150C, preferably, however,
between 25 and 75C.
The subsequent conversion of a hydroxy compound into the
corresponding halogen compound is conveniently carried
out with thionyl chloride, thionyl bromide, phosphorus
trichloride or phosphorus pentachloride optionally in
a solvent such as methylene chloride, chloroform or dime-
thyl formamide at temperatures up to the boiling temperature
of the reaction mixture.
Furthermore, the new compounds of general formula I can be
converted with inorganic or organic acids into their phy-
siologically compatible acid addition salts with 1 to 3 equi-
valents of the corresponding acid. Suitable acids may include
for example hydrochloric acid, hydrobromic acid, sulfuric
acid, phosphoric acid, lactic acid, citric acid, tartaric
acid, maleic acid or fumaric acid.
The compounds of general formulae II and III used as star-
tin8 materials are known from the literature respectively
they can be prepared according to known processes. Thus,
for example the benzoic acids of general formula II are
descrlbed ln the British patent 1,469,187 resp. they can
be prepared according to the processes described therein.
As already mentioned before, the new aminobenzoic acid deri-
vatives of general formula I and their salts represent valu-
able intermediates for the preparation of-new com-
pounds with an antiphlogistic activity (see German Offen-
legungsschrift 2,926,472, filed on June 30, 1979). These
compounds are obtained by reaction of an antiphlogistic
containlng a carboxyl group, with a compound of general
formula I prepared according to the invention, e~pecially by
linkage of the carboxyl group with the group Y of a com-
pound of general formula I.
As suitable antiphlogistics may for example the following
be considered:

934
1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid,
(~)-6-Methoxy- ~-methyl-2-naphthalene acetic acid,
2- ~ 2,6-Dichlorophenyl)-amino7phenylacetic acid,
3-Benzoyl-o~-methyl-phenylacetic acid,
~ -Methyl-4-(2-methylpropyl)-phenylacetic acid,
2-Fluoro- ~-methyl- ~ ,1'-biphenyl7-4-acetic acid,
4-(1,3-Dihydro-1-oxo-2H-isoindole-2-yl)- ~-methyl-phenyl-
acet$c acid,
Acetylsalicylic acid,
2- ~ 2,6-Dichloro-3-methylphenyl)-amino7benzoic acid,
2- ~ 3-Chloro-2-methylphenyl)-amino7benzoic acid,
5-Benzoyl-~ -methyl-2-thiophene acetic acid,
1-Methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-acetic acid,
5-Fluoro-2-methyl-1- ~ -(methylsulfinyl)-pheny17methylene7-
1H-indene-3-acetic acid,
6,11-Dihydro-11-oxo-dibenz ~ ,e70xepin-3-acetic acid,
6,11-Dihydro-11-oxo-dibenz ~ ,e70xepin-2-acetic acid,
oC-Methyl-5-oxo-5H-dibenzo ~ ,d7cycloheptene-2-acetic acid,
2-(4-Chlorophenyl)-~ -methyl-5-benzoxazole acetic acid,
6-Chloro- ~ -methyl-9H-carbazole-2-acetic acid,
-Ethyl-4-(2-methylpropyl)-phenylacetic acid,
~C-Methyl-3-phenoxy-phenylacetic acid,
2-(2,4-Dlchlorophenoxy)-phenylacetic acid,
-Oxo- ~ ,1'-blphenyl7-4-butanic acid,
2',4'-Di~luoro-4-hydroxy- ~ ,1'-biphenyl7-3-carboxylic acid,
1,3,4,9-Tetrahydro-1-propyl-pyrano ~ ,4-b7indole-1-acetic acid,
1,8-Dlethyl-1,3,4,9-tetrahydro-pyrano ~ ,4-b7indole-1-acetic acid,
2- ~ ,5-bis-(4-Chlorophenyl)-2-oxazolyl7thio7propanoic acid,
2- ~ -(Trifluoromethyl)-pheny_7amino7benzoic acid,
1-(4-Chlorophenyl)-2,5-dimethyl-1H-pyrrol-3-acetic acid,
3-Chloro-~ -methyl-4-(2-thienylcarbonyl)-phenylacetic acid,
2- ~ 3-Chloro-2-methylphenyl)-amino7-~-pyridine carboxylic acid,
2- ~ -Methyl-3-(trifluoromethyl)-phenyl7amino7-3-pyridine
carboxylic acid,
4-(4-Chlorophenyl)-2-phenyl-5-thiazoleacetic acid,
3-Chloro-4-(2,5-dihydro-1H-pyrrol-1-yl)-ac-methyl-phenyl-
acetic acid,
10-Methyl-10H-phenothiazine-2-acetic acid,

14 -
114~934
7-Methoxy- ~,10-dimethyl-1OH-phenothiazine-2-acetic acid,
5-Chloro-3-methyl-benzo ~ thiophene-2-acetic acid,
oC-Methyl-4-(2-thienylcarbonyl)-phenylacetic acid,
3-Chloro-4-cyclohexyl- r-oxo-phenylbutanoic acid,
2- ~ 2,3-Dimethylphenyl)-amino7benzoic acid and
2- ~ -(Trifluoromethyl)-phenyl7amino7-3-pyridine carboxylic
acid.
Moreover, the aminobenzoic acid derivatives of general
formula I prepared according to the invention and their
physiologically compatible acid addition salts show valuab-
le pharmacological properties. Besides a secretolytic andlor
an~ltusslve activity they especially show an antiulcus
activity and an inhibiting activity on the gastric ~luid
secretlon.
For example the following compounds were tested on their
biological activity:
A ~ 1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyloxy7-2,3-dihydroxy-n-propane-hydrochloride,
B ~ O,N-~is- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyl7-L-serine-methyl ester,
C ~ 1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyloxy7-2-hydroxy-ethane-hydrochloride,
D . 1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyloxy7-4-hydroxy-n-butane-hydrochloride,
E - 1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyloxv7-2- ~ -amino-~-bromo-5-(N-ethyl-cyclohexyl-
aminomethyl)-benzamido7ethane-dihydrochloride,
F . 1-(4-Amino-3-bromo-5-hexamethyleni~ino-benzoyloxy)-
5-hydroxy-n-pentane-dihydrochloride,
G 5 1- ~ -Amino-3-bromo-5-(N-ethyl-cyclopentylaminomethyl)-
b_nzoyloxv7-2-hydroxy-ethane-hydrochloride,

- - 15 -
1~4~)934
H = 1- ~ -Amino-3-bromo-5-(N-cyclohexyl-n-propylaminomethyl)-
benzoyloxv7-2-hydroxy-ethane-hydrochloride,
I = 1- ~ -Amino-~-bromo-5-(N-ethyl-cycloheptylaminomethyl)-
benzoyloxy7-2-hydroxy-ethane-hydrochloride,
K = 1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl7-D-mannitol-hydrochloride,
L ~ 2- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl7-(l)-tartaric-acid-diethyl-ester-hydrochloride,
M = N~ Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylox~7ethyl7-N-(2-hydroxyethyl)-methylamine
and
N ~ 2- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylo ~ -2'-hydroxy-diethyloxide.
1. Ulcus lnhibitin~ activitY:
The ulcu~ inhibiting activity was determined in rats
a~ a gastritis inhibiting activity (GOLDENBERG at al.,
Gastroenterology 69, 636 (1975)). 100 mg/kg of-the te~t
compound were ad~lni~tered-to ~tarved femal~ rat~ of a body
weight between 200 to 230 g by use of an oesophageal tube.
In an analogous manner a 1 % solution of tylose was admi-
ni~tered to a control group.
After 1 hour 3 ml of a 50 % ethanol solution were admini-
stered orally to all animals. After further 4 hours the
rats were kllled and the alteration of the mucosa of the
~tomach was measured visually by means of a scale from
O to 5.
O = no alterations
5 = numerous striped hemorrhagenic erosions.
The decrease of the hemorrhagenic erosions in the animals
with the test compound compared with the control animals
was measured in per cent.

- - 16
ll~V934
2. Acute toxicitY-
The acute toxicity of the test compounds (each 1000 mg/kg)
was determined in 3 male and 3 femal mice with a body
weight between 20 to 26 g after oral administration of
a æingle dose (observation time: 14 days).
The following table ~hows the results obtained:
re~t compound Decrease of the Number of animals
erosions which dled
. _
A - 89 % 0/6
B - 87 % 1/6
C - 84 X 0/6
D - 84 % 0/6
E - 88 % 0/6
F - 76 % 0/6
G - 64 % 0/6
H - 87 % 0/6
I - 77 % 0/6
K - 92 % 0/6
L - 77 % 0/6
M - 58 % 0/6
N - 65 % 0/6
Based on their biological propertie3 the compounds of
general ~ormula I and their physiologically compatible
acid addltion ~alts are therefore suitable in the treat-
ment oi the in~lamed mucosa. For pharmaceutical admini-
stration the compound~ of general formula I and their
physiologically compatible acid addition salts may be
incorporated into the con~entional preparations, optio-
nally in combination with other active ingredients.
Pre~erred rorms may include for example tablets, coated
tablets, capsules, powders, suppositories, drops or sus-
pensions. The single dose for adults contains from 25 to
250 mg, preferably however 50 to 150 mg of active ingredient,
2 to 4 times daily.

~14V934
- 17 -
Example 1
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-2,3-dihydroxv-n-pro~ane
70 g (0.185 mole) of 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoic acid sodium salt were suspended in 250 ml of
1-chloro-2,3-dihydroxy-n-propane and the suspension was heated
to 110 - 120C for 3 hours whilst stirring. Subsequently the
main amount o~ the excess 1-chloro-2,3-dihydroxy-n-propane was
distilled off at a pressure of 0.02 mm Hg. m e residue was
dissolved in a mixture of methylene chloride:methanol:conc. ammo-
nia (90:10:1) and chromatographed over silicagel. The obtained
viscous oil was dissolved in 130 ml of isopropanol and after
dilution with 200 ml of ethyl acetate it was converted to the
hydrochloride by means of etheric hydrochloric acid. After stan-
ding for 24 hours at 0 - 5C, the obtained crystals were suction
filtered, washed with little ether and dried.
M.p. of the hydrochloride: 167 - 173C.
Exam~le 2
1- ~ -Amlno-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoylox~7-
2-hYdroxv-ethane
41 g (0.1 mole) of 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzo~ chloride-hydrochloride were dissolved in 250 ml
of ethylene glycol and after addition of 17 g (0.22 mole) of py-
ridine the solution was heated to 105C for one hour. After coo-
ling to room temperature the mixture was diluted with 1 1 of
water. After addition of sodium hydroxide solution the mixture
was extracted with ether, the ether solution was dried over
sodium sulfate and evaporated to dryness. The residue was
chromatographed over silicagel (ethyl acetate). After evapo-
ration of the eluate a resin was obtained, which was converted
in crystals by trituration with petroleum ether. The crystals
obtained were recrystallized from ethanol.
M.p.: 72 - 75C.
";

`` 1145~34
- 18 -
Example 3
~ Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benz-
- amido7-3-hvdroxv-n-propane
30 g (0.073 mole) of 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyl chloride hydrochloride were dissolved in 400 ml
of tetrahydrofurane and slowly dropped to a solution of 15 g
(0.2 mole) of 3-amino-n-propanol in 300 ml of tetrahydrofurane.
The mixture was stirred for 30 minutes at 50C and then evapora-
ted in vacuo. The residue was partitioned between water and chlo-
roiorm. The chloroform phase was separated, dried and evaporated.
The residue was dissolved in isopropanol, acidified with ethano-
lic hydrochloric acid and diluted with ether. m e hydrochloride
was suction iiltered and dried.
M.p. of the hydrochloride: 110 - 11~C.
Exam~le 4
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzamido7-
4-hLdrox~-n-butane
27.5 g (0.067 mole) Or 4-amino-~-bromo-5-(N-ethyl-cyclohexyl-
aminomethyl)-benzoyl chloride hydrochloride were dissolved in
400 ml oi tetrahydroiurane and ~lowly dropped to a solution
oi 12 g ~0.1~5 mole) oi 4-amino-butanol . The mixture wa~
stirred ior 30 minutes at 50~ and evaporated in vacuo. The
residue was partitioned between water and chloroform. The chloro-
iorm phase was separated, dried and evaporated. The residue was
puriiied by chromatography on silicagel (chloroform:methanol
(9:1)). When evaporating the eluate an oil was obtained.
IR ~pqctrum (methylene chloride): amide-C0 1650 cm~
W spectrum (ethanol): 2 max 285 nm

114~34
- 19 -
Exam~le 5
~ Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-2.3-dihvdroxY-n-Pro~ane ,,
2.1 g (0.05 mole) of 1- ~ -amino-3-bromo-5-(N-ethyl-cyclohexyl-
aminomethyl)-benzoyloxy7-2,3-epoxy-n-propane were dissolved in
100 ml of water and 100 ml of methanol . The obtained solution
was adJusted to pH 2 - 3 by means of sulphuric acid and after
addition of approx. 20 mg of iron(III)-chloride refluxed for
2 hours. After cooling the mixture was neutralized, evaporated
to dryness in vacuo and the residue was purified by chromato-
graphy on silicagel (methylene chloride:methanol:conc. ammonia
(90:10:1)). The obtained oil was dissolved in isopropanol~. The
hydrochloride was brought to crystallization after addition oi
etheric hydrochloric acid and ethyl acetate.
M.p. of the hydrochloride: 167 - 173C.
am~le 6
1-(4-Amino-3-bromo-5-diethyla~inomethyl-benzoyloxy)-6-chloro-
n-hexane
5.2 g tO.013 mole) Or 1-(4-amino-3-bromo-5-diethylaminomethyl-
benzoyloxy)-6-hydroxy-n-hexane were dissolved in 15 ml oi chloro-
form and the mixture was stirred with 15 ml oi thionyl chloride
ior ~ hours at 60C. The reaction mixture was evaporated and
the re~idue was taken up in chloroiorm. The organic phase was
washed with sodium bicarbonate solution, dried and evaporated.
The residue obtained was dissolved in isopropanol and the hy-
drochloride was precipitated with etheric hydrochloric acid.
M. p. of the hydrochloride: 121 - 122C.

114~934
-- 20 --
Exam~le 7
N- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl7-
L-serine-methYlester
A solution of 27.4 g (0.07 mole) of 4-amino-3-bromo-5-(N-ethyl-
cyclohexylaminomethyl)-benzoic acid hydrochloride in 250 ml
- of dimethylformamide was mixed by small amounts with 13 g
(0.01 mole) of N,N'-carbonyl diimidazole whilst stirring
at room temperature. After the addition was finished the
mixture wa~ heated to 50C and kept at this temperature for
1 hour. After cooling to room temperature a solution
of 12.5 g (o.o8 mole) of L-serine methylester hydrochloride
and 8.1 g (0.08 mole) of triethylamine in 100 ml
o~ dimethylformamide was added whilst stirring and the mixture
~I was stirred for further i6 hours. Subsequently the solvent was
removed in vacuo and the residue was partitioned between water and
chloroform. The chloroform phase was washed with water,~
drled over sodium sulfate and evapora*ed in vacuo. A light
yellow oil was obtained, which was chromatographed over ~ilica-
i gel (500 g o~ silicagel, chloroform:ethyl acetate = 3:1).
A colorless ~oam was obtalned.
IR ~pectrum (methylene chloride): OH 3600 cm 1
NH2 344 cm 1
Ester CO 1745 cm 1
Amid-CO 1675 cm 1
W spectrum (ethanol): ~ max 230 nm (shoulder), 290 nm.
Exam~le 8
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl7-
mannltol
8.25 g (8.9 ~ mole) of 1,6-Bis- ~ -amino-~-bromo-5-(N-ethyl-
cyclohexylaminomethyl)-benzoy ~ -D-mannitol dihydrochloride
were dissolved in 250 ml of tetrahydrofurane and 100 ml of
water. A solution of 13.5 ml of 2N-sodium hydroxide
in 100 ml of tetrahydrofurane was added dropwisely whilst
. ~
.,,

934
- 21 -
stirring at room temperature. The reaction solution was
stirred for 2.5 hours at room temperature. After thin-layer
chromatographical evaluation the solution was mixed with
300 ml of ether and after short shaking the nascent phases
were separated. Subsequently the organic phase was extracted
with 2N-hydrochloric acid, the aqueous hydrochloric extracts
were made alkaline with conc. ammonia and extracted with
ether. The ether extracts were washed with water, dried
over magnesium sulfate and evaporated in vacuo. A~ter
subsequent chromatography of the evaporation residue over
silicagel (chloroform:methanol:conc. ammonia = 9:1:0.1),
the obtained fractio~ were evaporated in vacuo to dryness.
The evaporation residue was dissolved in 150 ml of ethyl ace-
tate and the calculated part of an etheric hydrochloric acid
was added to the solution. The obtained hydrochloride was
recrystallized from methanol/ethyl acetate after suction fil-
tration.
M.p. of the hydrochloride: 153 - 160C (decomp.).
ExamPle 9
Amino-3-bromo-5-(N-ethyl-cyclohexylaminomebhyl)-benzoyl-
oxY7-2,3-dihYdro-n-~ropane
9.8 g (0.025 mole) of 4-amino-3-bromo-5-(N-ethyl-cyclohexyl-
aminomethyl)-benzolc acid hydrochloride were suspended in
10 g (0.135 mole) of 2,3-epoxy-n-propanol and the suspen-
sion was heated for 3 hours to 60C after additian of 250 mg
of iron(III)-chloride. The reaction mixture was partitioned
between water and chloroform, the chloform phase was separated,
dried and evaporated to dryness. The residue was purified by
chromatography on silicagel (methylene chloride:methanol:conc.
ammonia = 90:10:1). m e eluate was evaporated, the residue
was dissolved in isopropanol and the hydrochloride was crystalli-
zed by addition of ethanolic hydrochloric ac~d/ethyl acetate.
M.p. of the hydrochloride: 167 - 173C.

11~0934
- 22 -
Exam~le 10
~ Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
ox~7-2-chloro-ethane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and 2-chloro-ethanol analogously
to Example 2.
M.p. Or the hydrochloride: 162 - 164C.
Example 11
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy7-
2-chloro-ethane
Prepared from 1- ~ -amino-3-bromo-5-~N-ethyl-cyclohexylamino-
methyl)-benzoylox~7-2-hydroxy-ethane and thionyl chloride
analogously to Example 6.
M.p. Or the hydrochloride: 162 - 164C.
Exam~le 12
1- ~ -Amlno-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxY7-
~-chloro-n-~ro~ane
Prepared rrom 1- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoylox~7-3-hydroxy-n-propane and thionyl chloride
analogously to Example 6.
M.p. Or the hydrochloride: 185 - 187C.

: 114~934
- 23 -
Exam~le 13
Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-4-chloro-n-butane
Prepared from 1- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyloxy7-4-hydroxy-n-butane and thionyl chloride
analogously to Example 6.
M.p. of the hydrochloride: 158 - 160C.
Exam~le 14
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxv7-5-chloro-n-~entane
Prepared from 1- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyloxy7-5-hydroxy-n-pentane and thionyl chloride
analogously to Example 6.
M.p. of the hydrochloride: 141 - 142.5C.
Exam~le 15
1- ~ -Amlno-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oro-n-he~tane
Prepared from 1- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyloxy7-7-hydroxy-n-heptane and thionyl chloride
analogously to Example 6.
M.p. o~ the hydrochloride: 129 - 1~1C.

34
24 --
Example 16
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-8-chloro-n-octane
Prepared from 1- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyloxY7-8-hydroxy-n-octane and thionyl chloride
analogcusly to Example 6.
M.p. of the hydrochloride: 114 - 117C.
Example 17
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-3-hydroxY-n-ProPane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyldhloride hydrochloride and 1,3-propandiol in the pre-
3ence of pyridine and triethylamine analogously to Example 2.
M.p. of the hydrochloride: 184 - 185C.
Example 18
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxv7-4,hydroxy-n-butane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and 1,4-butandiol in the pre-
~ence o~ pyridine and triethylamine analogoualy to Example 2.
M.p. of the hydrochloride: 148 - 150C.

114~934
- 25 --
Exam~le 19
1- ~-Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
ox~7-5-hvdrox~-n-~entane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and 1,5-pentanediol in the pre-
sence o~ pyridine and triethylamine analogously to Example 2.
M.p. of the hydrochloride: 158 - 160C.
Exam~le 20
1- ~ -Amino-~-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxv7-6-hydroxv-n-hexane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyldhloride hydrochloride and 1,6-hexanediol in the pre-
sence of pyridine and triethylamine analogously to Example 2.
M.p. of the hydrochloride: 98 - 101C.
Exam~le 21
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-7-hYdroxY-n-he~tane
Prepared irom 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchlorlde hydrochloride and 1,7-heptanediol in the pre-
sence of triethylamine and 4-dimethylamino-pyridine analogous-
ly to Example 2.
M.p. of the hydrochloride: 102 - 104C (decomp.).

114~)~34
- 26 -
Exam~le 22
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy7-
~3-hydroxY-n-octane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and 1,8-octanediol in the pre-
sence of triethylamine and 4-dimethylamino-pyridine analogous-
ly to Example 2.
M.p. o~ the hydrochloride: 99 - 103C.
Example 23
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxy7-
4-hYdroxY-cvclohexane
Prepared irom 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and 1,4-cyclohexanediol in the
presence of pyridine and triethylamine analogously to Example 2.
IR spectrum (methylene chloride): ester-CO 1700 cm 1
W spectrum (ethanol): ~ max 230 nm, 298 - 300 nm.
~'~
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxy7-2-hydroxY-n-~ro~ane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride-hydrochloride and 1,2-propanediol in the pre-
sence of pyridine analogously to Example 2. Oil.
IR spectrum (methylene chloride): Ester-CO 1710 cm 1
W spectrum (ethanol): ~ max 2~0 nm (shoulder), 297 nm.

1~ 4~934
- 27 -
Example 25
2- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxv7-3-h~roxv-n-butane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and 2,3-butanediol in the pre-
sence of pyridine analogously to Example 2. Oil.
IR spectrum (methylene chloride): Ester-CO 1705 cm 1
W spectrum (ethanol): ~ max 230 nm (shoulder), 299 nm.
Exam~le 26
N,O-Bis- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylamino)-benzoyl7-
L-serine-methvlester
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoic acid imidazolide and L-serine methylester analogously
to Example 7.
Foam.
IR spectrum (~ethylene chloride): Amide-CO 1660 cm 1
Ester-CO 1710 and 1730 cm 1
W spectrum (ethanol): ~ max 230 nm (shoulder), Z95 nm.
Example 27
2- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl7-
(+)-tartaric acid dieth~lester
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and (+)-tartaric acid diethylester
analogously to Example 2. Oil.
C24H~5BrN27 (543 5)
Calc.: C 53.04 H 6.49 Br 14.70 N 5.15
Found: 53.30 6.59 14.55 5.12

V934
-- 28 --
Example 28
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
ox~7-2,3-epoxy-n-proPane _ _
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoic acid sodium salt and 2,3-epoxy-propylchloride analogous-
ly to Example 1. (The product was puri~ied by chromatography on
silicagel ). Oil.
IR spectrum (methylene chloride): Ester-CO 1705 cm 1
W spectrum (ethanol): ~ max 300 nm.
Exam~le 29
2- ~-Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-2'-hvdroxy-diethYloxide
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and 2,2'-dihydroxy-diethyloxide
analogously to Example 2. Oil.
C20H31BrN24 (443 4)
Calc.: C 54.18 H 7.05 ~r 18.02 N 6.32
Found: 53.90 7.19 18.25 6.26
~ le 30
N- r- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
ox~7-ethYl7-N-(2-hvdroxvethYl)-methvlamine
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and N-methyl-diethanolamine ana-
logously to Example 2. Oil.
21 34 3 3 (45 4)
Calc.: C 55.26 H 7.51 Br 17.51 N 9.21
Found: 55.30 7.62 17.75 9.06

- 29 -
Example 31
1-/2- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoYloxY7-ethyl7-4-(2-hYdroxvethvl)-piPerazine
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-.
methyl)-benzoylchloride hydrochloride and 1,4-bis-(2-hydroxy-
ethyl)-piperazine analogously to Example 2. Oil.
IR spectrum (methylene chloride): Ester-CO 1710 cm
N-alkyl 2830 cm 1
W spectrum (ethanol): 2 max 300 nm.
Exam~le 32
1- ~ - ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoYloxY7-proPYl7-4-(2-hydroxvethvl)-piperazine
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoic acid sodium salt and 1-(3-chloropropyl)-
4-(2-hydroxyethyl)-piperazine analogously to Exampl~ 1.
M.p. of the trihydrogene maleinate: 144 - 146C (decomp.).
Exam~le 33
1,6-Bis- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
_nz ~ -D-mannitol-dihydrochloride
Prepared from 2-mole of 4-amino-3-bromo-5-(N-ethyl-cyclohexyl-
aminomethyl)-benzoylchloride hydrochloride and 1 mole of
D-mannitol analogously to Example 2. The dihydrochloride sin-
tered from 130C and was decomposed at 220C.
IR spectrum (KBr): Ester-CO 1710 cm 1
N-alkyl 2840 cm 1
UV spectrum (ethanol): 2 max 230 nm, 295 nm.

1~4~)934
- 30 -
Example 34
1-/~-Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzovloxY7-2-hYdroxy-3-chloro-n-propane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoic acid hydrochloride and epichlorohydrin
analogously to Example 9. Oil.
IR spectrum (methylene chloride): Ester-CO 1710 cm 1
W spectrum (ethanol): 1 max 300 nm.
Exam~le 35
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benz-
amido7-2-hYdroxy-ethane
Prepared ~rom 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyl chloride hydrochloride and ethanolamine
analogously to Example 4.
M.p. of the hydro¢hloride: from 65C (decomp.).
Exam~le 36
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benz-
amido7-5-hydroxY-n-~entane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and 5-amino-pentanol -1 analo-
gously to Example 4. Oil.
IR spectrum (methylene chloride): Amide-CO 1650 cm 1
UV spectrum (ethanol): ~ max 285 nm.

- 1140934
- 31 -
Exam~le 37
1-~;-Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benz-
amido7-6-h~drox~r-n-hexane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoylchloride hydrochloride and 6-amino-hexanol-1
analogously to Example 4. Oil.
IR spectrum (methylene chloride): Amide-CO 1650 cm
W spectrum (ethynol): ;~ max 285 nm.
Exam~le 38
trans-1-~;-Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzamido7-4-hydrox~-c~clohexane
Prepared ~rom 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoylchloride hydrochloride and 4-trans-hydroxy-
cyclohexylamine in the presence of pyridine and triethyl-
amine analogously to Example 4.
M.p. of the dihydrochloride: 176C (decomp.).
ExamPle 39
N-~-Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl7-
D-~luco~amine
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and D-glucosamine analogously to
Example 3.
M.p.: 100 - 190C tslow decomposition whilst foaming).
C22H24BrN306 (516-5)
Calc.: C 51.16 H 6.64 Br 15.47 N 8.14
Found: 51.00 6.87 15.30 8.00

4~i~
- 32 -
Exam~le 40
~ Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benz-
amid_7-2-/~-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoYloxY7-ethane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and ethanolamine in the presence
of triethylamine analogously to Example 2.
M.p. of the dihydrochloride: from 170C (decomp.).
Exam~le 41
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzamido7-
2-amino-ethane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and ethylene diamine analogously
to Example 4.
M.p.: ~rom 85C (decomp.).
Exam~le 42
1,2-Bis- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzamido7-ethane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoylchloride hydrochloride and ethylene diamine analogo~sly
to Example 4.
M.p.: 218 - 219C
,
ExamPle 43
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-2-chloro-
ethane
, Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyl-

1~4V934
`` - 33 -
oxy)-2-hydroxy-ethane and thionylchloride analogously to
Example 6.
M. p . of the hydrochloride: 142 - 145C.
Example 44
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-3-chloro-
n-~ropane
Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyl-
oxy)-3-hydroxy-n-propane and thionylchloride analogously to
Example 6.
M.p. of the hydrochloride: 167 - 168C.
ExamPle 45
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-4-chloro-
n-butane
Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyl-
oxy)-4-hydroxy-n-butane and thionylchloride analogously to
Example 6.
M,p. of the hydrochloride: 159 - 162C.
Example 46
1-(4-Amino-3-bromo-5-dlethylaminomethyl-benzoyloxy)-5-chloro-
n-Pentane
Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyl-
oxy)-5-hydroxy-n-pentane and thionylchloride analogously to
Example 6.
M.p. of the hydrochloride: 117 - 119C.

114~934
- 34 -
Exam~le 47
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-6-chloro-
n-hexane
Prepared from 1-(4-amino-3-bromo-5-diethylaminomethyl-benzoyl-
oxy)-6-hydroxy-n-hexane and thionylchloride analogously to
Example 6.
M.p. oi~ the hydrochloride: 121 - 122C.
Example 48
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-2-hydroxy-
ethane
Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl-
chloride-hydrochloride and ethylene glycol in the presence of
pyridine analogously to Example 2.
M.p. of the hydrochloride: 151 - 152C.
Exam~le 49
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-3-hydroxy-
n-propane
Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl
chloride hydrochloride and 1,3-propanediol in the presence
o~ pyridine and triethylamine analogously to Example 2.
M.p. of the hydrochloride: 139 - 141C.

113450~34
Example 50
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-4-hydroxy-
n-butane
. _
Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl
chloride hydrochloride and 1,4-butanediol in the presence
of pyridine and triethylamine analogously to Example 2.
M.p. of the hydrochloride: 163 - 165C.
Exam~le 51
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-5-hydroxy-
n-Pentane
Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoyl
chloride hydrochloride and 1,5-pentanediol in the presence
of pyridine and triethylamine analogously to Example 2.
M.p. of the hydrochloride: 137.5 - 138.5C.
ExamPle 52
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-2,3-dihy-
droxy-n-propane
Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoic
acid sodium salt and 3-chloro-1,2-propanediol analogously
to Example 1.
Mass spectrum: M+ 374/6 m/e (monobromine)
Calc.: C15H2~BrN24 (374/6)

1~4~934
,
- 36 -
ExamPle 5~
1-(4-Amino-3-bromo-5-diethylaminomethyl-benzoyloxy)-2-hydroxy-
~chloro-n-~ro~ane
Prepared from 4-amino-3-bromo-5-diethylaminomethyl-benzoic
acid and epichlorohydrin analogously to Example 9.
IR spectrum (methylene chloride): Ester-C0 1715 cm 1
W spectrum (ethanol): R max 230 nm, 298 - 300 nm.
Example 54
1-(4-Amino-3-bromo-5-hexamethyleneiminomethyl-benzoyloxy)-
~-chloro-n-~entane
. _
Prepared from 1-(4-amino-3-bromo-5-hexamethyleneiminomethyl-
benzoyloxy)-5-hydroxy-n-pentane and thionylchloride analogous-
ly to Example 6.
M.p, of the hydrochloride: 160 - 162C.
Exam~le 55
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclopentylaminomethyl)-benzoyl-
oxv7-5-chloro-n-~entane
Prepared from 1- ~ -amino-3-bromo-5-(N-ethyl-cyclopentylamino-
methyl)-benzoyloxY7-5-hydroxy-n-pentane and thionylchloride
analogously to Example 6.
M.p. of the hydrochloride: 131 - 133C.

934
- 37 -
Example 56
1- ~ -Amino-3-bromo-5-(N-ethyl-cycloheptylaminomethyl)-benzoyl-
7-5-chloro-n-Pentane
Prepared from 1- ~-amino-3-bromo-5-(N-ethyl-cycloheptylamino-
methyl)-benzoyloxy7-5-hydroxy-n-pentane and thionyl chloride
analogously to Example 6.
M.p. of the hydrochloride: 156 - 158C.
Example 57
1-/~-Amino-3-bromo-5-(N-cyclohexyl-n-propylaminomethyl)-benzoyl-
oxY7-5-chloro-n-Dentane
Prepared from 1- ~-amino-3-bromo-5-(N-cyclohexyl-n-propylamino-
methyl)-benzoyloxy7-5-hydroxy-n-pentane and thionyl chloride
analogously to Example 6.
M,p. of the hydrochloride: 145 - 147C.
ExamDle ~
1-(4-Amino-3-bromo-5-dimethylaminomethyl-benzoyloxy)-2-hydroxy-
ethane
Prepared from 4-amino-3-bromo-5-dimethylaminomethyl-benzoyl
~hloride-hydrochloride and ethylene glycol in the presence
of pyridine analogously to Example 2.
M.p. of the hydrochloride: 80 - 81C.

--` 114~)934
- 38 -
Example 59
1-(4-Amino-3-bromo-5-isopropylaminomethyl-benzoyloxy)-
2-hYdroxv-ethane
.
Prepared from 4-amino-3-bromo-5-isopropylaminomethyl-benzoyl
chloride hydrochloride and ethylene glycol in the presence
of pyridine analogously to Example 2.
M.p. of the hydrochloride: 90 - 93C.
Examle 60
1- ~-Amino-3-bromo-5-(N-methyl-n-propylaminomethyl)-benzoyl-
oxv7- 2-hvdroxv-ethane
Prepared from 4-amino-3-bromo-5-(N-methyl-n-propylaminomethyl)-
benzoylchloride hydrochloride and ethylene glycol in the pre-
sence of pyridine analogously to Example 2.
M.p. of the hydrochloride: 124 - 128C.
Exam~le 61
1-(4-Amino-3-bromo-5-tert.butylaminomethyl-benzoyloxy)-2-hy-
droxv-ethane
. _ .
Prepared ~rom 4-amino-3-bromo-5-tert.butylaminomethyl-benzoyl
chloride hydrochloride and ethylene glycol in the presence of
pyridine analogously to Example 2.
M.p. of the hydrochloride: 192 - 194C~

- 1~40934
- 39 -
Exam~le 62
1-(4-Amino-3-bromo-5-cyclohexylaminomethyl-benzoyloxy)-2-hy-
droxY-ethane
Prepared from 4-amino-3-bromo-5-cyclohexylaminomethyl-benzoyl
chloride hydrochloride and ethylene glycol in the presence o~
pyridine analogously to Example 2.
M.p. of the dihydrochloride: 149C (decomp.).
Example 63
1- ~ -Amino-3-bromo-5-(N-cyclohexyl-methylaminomethyl)-benzoyl-
oxY7-2-h~droxr-ethane
Prepared from 4-amino-3-bromo-5-(N-cyclohexyl-methylamino-
methyl)-benzoylchloride hydrochloride and ethylene glycol in
the presence of pyridine analogously to Example 2.
M.p, of the hydrochloride: 169 - 171C.
Examsle 64
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclopentylaminomethyl)-benzoyl-
ox~7-2-hydrox.y-ethane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclopentylamino-
methyl)-benzoylchloride hydrochloride and ethylene glycol in
the presence of pyridine analogously to Example 2.
M.p. of the hydrochloride: 186 - 187C.

114Q934
~ 40 ~
Exam~le 65
1- ~ -Amino-3-bromo-5-(N-ethyl-cycloheptylaminomethyl)-benzoyl-
oxv7-2-hydroxY-ethane
_ _ _ _
Prepared from 4-amino-3-bromo-5-(N-ethyl-cycloheptylamino-
methyl)-benzoylchloride hydrochloride and ethylene glycol
in the presence of pyridine analogously to Example 2.
N.p. o~ the hydrochloride: 166 - 168C.
Example 66
1- ~ -Amino-3-bromo-5-(N-cyclohexyl-n-propylaminomethyl)-benzoyl-
oxv7-2-hydroxv-ethane
Prepared from 4-amino-3-bromo-5-(N-cyclohexyl-n-propylamino-
methyl)-benzoylchloride hydrochloride and ethylene glycol in
the presence of pyridine analogously to Example 2.
M.p. of the hydrochloride: 194 - 196C.
Example 67
1- ~ -Amino-3-bromo-5-(4-pyridylaminomethyl)-benzoylox~7-2-hy-
droxv-ethane
Prepared from 4-amino-3-bromo-5-(4-pyridylaminomethyl)-benzoyl
chloride hydrochloride and ethylene glycol in the presence of
pyridine analogou31y to Example 2.
M.p. o~ the hydrochloride: 2~7 - 218C.

934
- 41 -
Exam~le 68
1-(4-Amino-3-bromo-5-pyrrolidinomethyl-benzoyloxy)-2-hydroxy-
ethane
Prepared from 4-amino-3-bromo-5-pyrrolidinomethyl-benzoyl
chloride hydrochloride and ethylene glycol in the presence
of pyridine analogously to Example 2.
M.p. of the hydrochloride: 213 - 214C.
Examle 69
1-(4-Amino-3-bromo-5-piperidinomethyl-benzoyloxy)-2-hydroxy-
ethane
_ _ . . ... _
Prepared from 4-amino-3-bromo-5-piperidinomethyl-benzoyl
chloride hydrochloride and ethylene gIycol in the presence -
of pyrldlne analogously to Example 2.
M.p. of the hydrochloride: 214 - 216C.
Exam~le 70
1-(4-Amino-3-bromo-5-morpholinomethyl-benzoyloxy)-2-hydroxy-
ethane
Prepared from 4-amino-3-bromo-5-morpholinomethyl-benzoyl
chloride hydrochloride and ethylene glycol in the presence of
pyridine analogously to Example 2.
M.p of the hydrochloride: 179 - 181C.

114C~934
- 42
Example 71
1- ~ -Amino-3-bromo-5-(4-methyl-piperazinomethyl)-benzoyloxy~-
2-hvdroxY-ethane
Prepared from 4-amino-3-bromo-5-(4-methyl-piperazinomethyl)-
benzoylchloride dihydrochloride and ethylene glycol in the
presence of pyridine analogously to Example 2.
M.p. o~ the dihydrochloride:-163 - 165C.
Exam~le 72
1-(4-Amino-3-bromo-5-hexamethyleneiminomethyl-benzoyloxy)-
2-hydrox~-ethane
Prepared from 4-amino-~-bromo-5-hexamethyleneiminomethyl)-benzoyl
chloride dihydrochloride and ethylene glycol in the presence of
pyridine analogously to Example 2.
M.p. of the hydrochloride; 209C (decomp.).
ExamPle 73
~ Amino-3-bromo-5-(2-diethylaminoethylaminomethyl)-benzoyl-
oxY7-2-hvdroxY-ethane
_
Prepared from 4-amino-3-bromo-5-(2-diethylaminoethylamino-
methyl)-benzoylchloride dihydrochloride and ethylene glycol
in the presence of pyridine analogously to Example 2.
M.p o~ the dihydrochloride: 87 - 90C (decomp.).

114~)934
- 43 -
Example ?4
1- ~ -Amino-3-bromo-5-(N-ethyl-cycloheptylaminomethyl)-benzoyl-
oxy7- 5-h~droxY-n-Pentane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cycloheptylamino-
methyl)-benzoylchloride-hydrochloride and 1,5-pentanediol
in the presence of pyridine analogously to Example 2.
M.p. of the hydrochloride: 162 - 163C.
Example 75
1- ~ -Amino-3-bromo-5-(N-cyclohexyl-n-propylaminomethyl)-
benzoyloxY7-~-hydroxv-n-Pentane
Prepared from 4-amino-3-bromo-5-(N-cyclohexyl-n-propylamino-
methyl)-benzoylchloride hydrochloride and 1,5-pentanediol
in the presence Or trlethylamine and 4-dimethylaminopyridine
analogously to Example 2.
M.p. of the hydrochlorlde: 140 - 142C.
Exam~le 76
4- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxy-methY17-2,2-dimeth~1-1.3-dioxolane
5 g (0.013 mole) of 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyloxy-ethane were heated for 3 hours to 100C in
20 g of 2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane together with
0.1 g of sodium hydride. The ethanol , which was formed du-
ring the reaction was distilled off. After cooling the reaction
mixture was partitioned between water and methylene chloride. The
organic phase was separated , dried over sodium sulfate and
evaporated. The remaining residue was dissolved in warm iso-

---"; 1140934
-- 44 -
propanol and after longer standlng in the cold~ crystals
were obtained, which were suction filtered, washed with litt-
le isopropanol and dried.
M.p.: 78 - 83C.
Example 77
1- ~ -Amino_3-bromo-5-(N-ethyl-cyclohexylaminomethyl-benzoyl-
oxY7-2.3-dihvdroxY-n-p_o~ane
4.7 g (0.1 mole) of 4- ~ -amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl-benzoyloxymethyl7-2,2-dimethyl-1,3-dioxolane were dissolved
in 30 ml of dioxane. To this solution 2N hydrochloric acid was
added until pH 0.6 was reached and the mixture was kept standing
for 48 hours at room temperature. The solution was made weakly
alkaline with 2N ammonia and extracted thrice with
methylene chloride. The organic phase was dried over sodium
sulfate and evaporated. The residue was dissolved in lsopropanol
and convertod to the hydrochloride by means o~ etheric hydro-
chlorid acid. After longer standing in the cold, crystals were
obtained, which were suction filtered and dried.
M.p.: 167 - 173C.
Ex8m~1e 78
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyloxY7-
2.3-dihYdroxY-n-~roPane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyloxy-ethane and glycerine analogously to Example 76. The
reaction can be carried out without a solvent or in a solvent
such as ethylene glycol diethylether.
M.p. o~ the hydrochloride: 167 - 173C.

V934
-- 45 --
Exam~le 79
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-1-Phen~1-2-hvdroxv-ethane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoic acid sodium salt and 1-phenyl-2-hydroxy-
ethyl chloride analogously to Example 1. Oil.
IR spectrum (methylene chloride): OH 3600 cm 1
NH2 3440 cm 1
N-alkyl 2930 cm 1
Ester-CO 1710 cm 1
W spectrum (~thanol): ~ max 230 nm, 297 nm.
Example 80
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxr7-2-~henYl-2-hvdroxv-ethane
Prepared ~rom 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and phenyl ethyleneglycol ana-
logously to Example 2. Oil.
IR ~pectrum (methylene chloride): OH 3600 cm~1
NH2 3450 cm 1
N-alkyl : 2950 cm 1
Ester-CO 1710 cm 1
W spectrum (ethanol): ~ max 293 nm.
Exam~le 81
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxv7-1~2-di~henvl-2-hYdroxv-ethane ,_
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylamino-
methyl)-benzoyl chloride hydrochloride and 1,2-diphenyl-
ethylene glycol analogously to Example 2. Oil.
`"'

34
- 46 -
IR spectrum (methylene chloride): OH 3600 cm 1
NH2 3450 cm 1
N-alkyl 2940 cm 1
Ester-CO 1725 cm 1
W spectrum (ethanol): ~ max 295 nm.
Exam~le 82
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxv7-2-hvdroxYmethyl-2-methYl-n-~entane
Prepared from 4-amino-3-bromo-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and 2,2-bis-hydroxymethyl -
n-pentane analogously to Example 2. Oil.
IR spectrum (methylene chloride): OH 3620 cm 1
NH2 3460 cm 1
N-alkyl 2960 cm 1
Ester-CO 1705 cm 1
W spectrum (ethanol): ~ max 288 nm.
Example 83~
2- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxy-methYl7-6-hYdroxYmethyl-pyridine
Prepared ~rom 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and 2,6-bis-hydroxymethyl-pyri-
dine analogously to Example 2. Oil.
IR spectrum ~methylene chloride): OH 3610 cm 1
NH2 3440 cm 1
N-alkyl 2920 cm 1
Ester-CO 1710 cm~
W spectrum ~ethanol): ~ max 230 nm, 298 nm.

--: 1140934
- 47 -
Exam~le 84
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
ox~rmethY17-4-hYdrox~,rmethvl-benzene
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and 1,4-bi~-hydroxymethyl-benze-
ne analogously to Example 2. Oil.
IR spectrum (methylene chloride): OH 3600 cm 1
NH2 3450 cm 1
N-alkyl 2940 cm 1
Ester-CO 1705 cm 1
W spectrum (ethanol): ~ max 295 nm.
Exam~le 85
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
ox~,rmethvl7-4-hYdrox~methyl-cYclohexane
Prepared ~rom 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride-hydrochloride and 1,4-bis-hydroxymethyl-cyc-
lohexane analogously to Example 2. Oll.
IR spectrum (methylene chloride): OH 3600 cm 1
NH2 3440 cm 1
N-alkyl 2910 cm 1
Ester-CO 1695 cm 1
W spectrum (ethanol): ~ max 294 nm.
Exam~le 86
1-(4-Amlno-3-bromo-5-dlmethylaminomethyl-benzoyloxy)-
~-hvdroxv-n-pentane
Prepared from 4-amino-3-bromo-5-dimethylaminomethyl-benzoyl
chloride hydrochloride and 1,5-dihydroxy-n-pentane analagous-
ly to Example 2, however, in the presence of trlethylamine and
4-dimethylamino pyridine instead of pyridine.
M.p. of the hydrochloride: 155 - 157C.
,. ..

934
- 48
Example 87
1-(4-Amino-3-bromo-5-morpholinomethyl-benzoyloxy)-5-hydroxy-
n-pentane
Prepared from 4-amino-3-bromo-5-morpholinomethyl-benzoyl
chloride hydrochloride and 1,5-dihydroxy-n-pentane analo-
gously to Example 86.
M.p. of the hydrochloride: 205 - 207C.
Exam~le 88
1-(4-Amino-3-bromo-5-piperidinomethyl-benzoyloxy)-5-hydroxy-
n-~entane
Prepared irom 4-amino-3-bromo-5-piperidinomethyl-benzoyl
chloride hydrochloride and 1,5-dihydroxy-n-pentane analogous-
ly to Example 86.
M.p. of the hydrochloride: 186 - 188C.
Exam~le 89
1- ~ -Amlno-3-bromo-5-(4-methyl-piperazinomethyl~-benzoylox~7-
5-h~droxY-n-~entane
Prepared from 4-amino-3-bromo-5-(4-methyl-piperazinomethyl)-
benzoyl chloride hydrochloride and 1,5-dihydroxy-n-pentane
analogously to Example 86.
M.p. of the dihydrochloride: 182 - 185C.
Exam~le 90
1- ~ -Amino-3-bromo-5-(N-cyclohexyl-methylaminomethyl)-benzoyl-
gxY7-5-hvdroxY-n-~entane
Prepared rrom 4-amino-3-bromo-5-(N-cyclohexyl-methylamino-
methyl)-benzoyl chloride hydrochloride and 1,5-dihydroxy-
n-pentane analogously to Example 86.
M.p. of the dihydrochloride: 123 - 126C.

1140934
- 49 -
Example 91
1- ~ -Amino-3-bromo-5-(4-methylpiperazinomethyl)-benzoyloxy7-
4-h~droxY-n-butane
Prepared from 4-amino-3-bromo-5-(4-methylpiperazinomethyl)-
benzoyl chloride hydrochloride and 1,4-dihydroxy-n-butane
analogously to Example 86.
M.p. of the dihydrochloride: 200 - 202C.
Exam~le 92
1-(4-Amino-3-bromo-5-hexamethylen~mlnomethyl-benzoyloxy)-
4-hYdroxy-n-butane
Prepared from 4-amino-3-bromo-5-hexamethyleniminomethyl-
benzoyl chloride hydrochloride and 1,4-dihydroxy-n-butane
analogously to Example 86.
M.p. of the hydrochloride: 159 - 161C.
Exam~le 93
1- ~ -Amino-3-bromo-5-(N-cyclohexyl-methylaminomethyl)-benzoyl-
oxY7-4-hydroxy-n-butane
Prepared from 4-amino-3-bromo-5-(N-cyclohexyl-methylamlno-
methyl)-benzoyl chloride hydrochloride and 1,4-dihydroxy-
n-butane analogou~ly to Example 86.
M.p. of the hydrochloride: 163 - 165C.
Exam~le 94
1-(4-Amino-3-bromo-5-pyrrolidinomethyl-benzoyloxy)-4-hydroxy-
n-butane
Prepared from 4-amino-3-bromo-5-pyrrolidinomethyl-benzoyl
chloride hydrochloride and 1,4-dihydroxy-n-butane analogous-
ly to Example 86.
M.p. of the hydrochloride: 140 - 144C.
,,

11~0934
- 50 -
Example 95
1-(4-Amino-3-bromo-5-morpholinomethyl-benzoyloxy)-4-hydroxy-
n-butane
Prepared from 4-amino-3-bromo-5-morpholinomethyl-benzoyl
chloride and 1,4-dihydroxy-n-butane analogously to Example 86.
M.p. of the hydrochloride: 182 - 184C.
Example 96
1-(4-Amino-3-bromo-5-piperidinomethyl-benzoyloxy)-4-hydroxy-
n-butane
Prepared fro~ 4-amino-3-bromo-5-piperidinomethyl-benzoyl
chloride hydrochloride and 1,4-dihydroxy-n-butane analogous-
ly to Example 86.
M.p. of the hydrochloride: 170 - 172C.
Exam~le 97
1- ~ -Amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-benzoyl-
oxY7-9 -hvdroxv-n-nonane
Prepared from 4-amino-3-bromo-5-(N-ethyl-cyclohexylaminomethyl)-
benzoyl chloride hydrochloride and 1,9-dihydroxy-n-nonane ana-
logously to Example 86.
M.p. of the hydrochloride: 73 - 76C.

ll~V934
- 51 -
Exam~le I
Coated tablets containing 50 mg o~ -amino-3-bromo-5-(N-ethyl-
cyclohexylaminomethyl)-benzoyloxv7-2,3-dihydroxy-n-propane-
hvdrochloride
Composition:
1 coated tablet core contains:
Active ingredient 50.0 mg
CaHP04 50.0 mg
Corn starch 2C.0 mg
Soluble starch 4.0 mg
Magnesium stearate 1.O mg
125.0 mg
Method of preParation:
The active ingredient was mixed with CaHP04 and corn starch,
granulated (1.5 mm mesh size) with an aqueous solution of the
soluble starch, and after drying at 50C in an air circulating
drier passed through a screen of 1.0 mm mesh size. After addi-
tion of the lubricant the mixture was pressed into coated tab-
let cores.
Coatin~:
Coating was performed in a coating vessel according to a con-
ventional method of sugar-coating.
Description: Coated tablet core: Coated tablet:
~eight: 125 mg 165 mg
Diameter: 7 mm, biconvex
Exam~le II
Tablets containing 100 mg of 1- ~ -amino-3-bromo-5-(N-ethyl-cyclohexYl-
aminomethvl)-benzoyloxy7-2,3-dihydroxy-n-propane-hvdrochloride
1 tablet contains:
.,

114~)934
52 --
Active ingredient 100.0 mg
Corn starch 30.0 mg
Lactose 42.0 mg
Polyvinyl pyrrolidone 7.0 mg
Magnesium stearate 1.0 mg
180.0 mg
Method of Pre~aration:
The active ingredient was mixed with the starch and lactose
and the mixture was homogeneously moistened with an aqueous
solution of the polyvinyl pyrrolidone. The moist mass was
stroken through a screen, dried at 50C in an air circulating
drier and after again screening (1.5 mm mesh size) mixed with
the lubricant. The prepared mixture was pressed into tablets.
Weight: 180 mg
Diameter: 8 mm, biplanar, bilateral facet and unilateral
notch.
Exam~le III
Ampoules containing 75 mg of 1~ amino-3-bromo-5-(N-ethyl-
cyclohexylaminomethyl)-benzoyloxv7-2,3-dihydroxy-n-propane-
~,rochloride
1 ampoule contains:
Active ingredient 75.0 mg
Sorbite 150,0 mg
Water ~or injection purposes ad5.0 ml
Method of preparation:
The active ingredient and isotonanes were dissolved in water
for injection purposes, sterile filtered and filled up into
5-ml ampoules.

114~)934
-- 53 --
Example IV
Juice containing 100 mg of 1- ~ -amino-3-bromo-5-(N-ethyl-
cyclohexylaminomethyl)-benzoyloxy7-2,3-dihydroxy-n-propane-
hYdrochloride Per 5 ml
100 ml of ~uice contain:
Active ingredient 2.0 g
Hydroxyethyl cellulose 0.15 g
Tartaric acid 0.1 g
Sorbite solution 70 % 30.0 g
Glycerine 10.0 g
Benzoic acid 0.15 g
Aroma 0.2 g
Dist. water ad 100.0 ml
Method of ~re~aration:
Distilled water was heated to 70C. Herein the hydroxyethyl
cellulose, benzoic acid and tartaric acid were dissolved whilst
8tirring. The solution was cooled to room temperature and here-
by the glycerine and the sorbite solution were added whilst
stlrrlng. The active ingredient was added at room temperature
and stirred up to its complete solutlon. Subsequently the
aroma was added and air was evacuated with stirring.
Exam~le V
Suppositories containing 150 mg of 1- ~ -amino-3-bromo-5-
(N-ethyl-cyclohexylaminomethyl)-benzoyloxy7-2,3-dihydroxy-n-
ro~ane hYdrochloride
1 suppository contains:
Active ingredient ~ 0.15 g
Hard ~at (e.g. Witepsol H 19 and W 45) 1.55 g
1.70 g
~r~ a~k

1140934
- 54 -
Method of ~reparation:
The hard fat was molten. The active ingredient was homogene-
ously dispersed in the melt at 38C. The melt was cooled to
35C and poured ~nto weakly pre-cooled suppository forms.
Weight of suppository: 1.7 g
Exam~le VI
Hard gelatine capsules containing 100 mg of 1- ~ -amino-3-bromo-
5-(N-ethyl cyclohexylaminomethyl)-benzoYloxY7-2,3-dihydroxy-n-pro-
E~ne hydrochloride
1 capsule contains:
Active ingredient 100.0 mg
Corn starch 90.0 mg
Lactose, pulv. 58.0 mg
Magnesium stearate 2.0 mg
250.0 mg
Method of ~reParation:
The acti~e ingredient, the corn starch and the lactose as well
as the previously screened magnesium stearate were roughly mixed.
Thls mixture was passed through a screen and subsequently homo-
geneously mixed in a powder mixer.
The mixture was filled into capsules of size 1.
5lt