Imidazopyridine compounds and processes for preparation thereof

The invention relates to an imidazopyridine compound of the formula: ##STR1## wherein R.sup.1 is lower alkynyl, lower alkynyloxy(lower)alkyl or N,N-di(lower)alkylamino(lower)alkynyl, PA0 R.sup.2 is lower alkyl, PA0 R.sup.3 is mono (or di or tri)-phenyl(lower)alkyl substituted by one or more substituent(s) selected from cyano, carbamoyl, mono (or di or tri(phenyl(lower)alkylamino, acylamino, carboxy, esterified carboxy, hydroxy, hydroxy(lower)alkyl, acyloxy(lower)alkyl, acyloxy, mono (or di or tri)phenyl(lower)alkoxy, lower alkoxy(lower)alkoxy, tetrahydropyranyloxy, and acylamino(lower)alkyl or mono (or di or tri) phenyl(lower)alkyl substituted by lower alkyl and one additional substituent selected from hydroxy(lower)alkyl, amino, N-lower alkyl-N-acylamino, mono (or di or tri)phenyl(lower)alkylamino, acylamino and lower alkylamino, and PA0 R.sup.4 is hydrogen or lower alkyl, and a pharmaceutically acceptable salt thereof, useful in the treatment of ulcers.

The present invention relates to novel imidazopyridine compounds and 
pharmaceutically acceptable salt threof. More particularly, it relates to 
novel imidazopyridine compounds and pharmaceutically acceptable salts 
thereof which have antiulcerative activity, to processes for preparation 
thereof, to pharmaceutical composition comprising the same, and to method 
of using the same therapeutically in the treatment of ulcer in human being 
or animals. 
Accordingly, one object of the present invention is to provide novel 
imidazopyridine compounds and pharmaceutically acceptable salt thereof, 
which are useful as a medicine for ulcer. 
Another object of the present invention is to provide processes for 
preparation of said imidazopyridine compounds and pharmaceutically 
acceptable salts thereof. 
A further object of the present invention is to provide pharmaceutical 
composition comprising, as an active ingredient, said imidazopyridine 
compounds or its pharmaceutically acceptable salt. 
Still further object of the present invention is to provide method of using 
said imidazopyridine compounds or its pharmaceutically acceptable salt in 
the treatment of ulcer in human being or animal. 
The imidazopyridine compounds of the present invention are novel and can be 
represented by the formula (I) : 
##STR2## 
wherein R.sup.1 is lower alkynyl, lower alkynyloxy(lower)alkyl or 
N,N-di(lower)alkylamino(lower)alkynyl, 
R.sup.2 is lower alkyl, 
R.sup.3 is ar(lower)alkyl substituted by one or more substituent(s) 
selected from cyano, trihalo(lower)alkyl, carbamoyl, protected amino, 
carboxy, protected carboxy, hydroxy, hydroxy(lower)alkyl, protected 
hydroxy(lower)alkyl, protected hydroxy and protected amino(lower)alkyl, or 
ar(lower)alkyl substituted by lower alkyl and one additional substituent 
selected from hydroxy(lower)alkyl, amino, N-lower alkyl-N-protected amino, 
protected amino and lower alkylamino, and 
R.sup.4 is hydrogen or lower alkyl. 
According to the present invention, the object compounds (I) can be 
prepared by the following processes. 
##STR3## 
wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each R.sub.a.sup.1 is 
lower alkynyl, 
R.sub.b.sup.1 is N,N-di(lower)alkylamino(lower)alkynyl, 
R.sub.a.sup.3 is ar(lower)alkyl substituted by protected 
hydroxy(lower)alkyl, 
R.sub.b.sup.3 is ar(lower)alkyl substituted by hydroxy-(lower)alkyl, 
R.sub.c.sup.3 is ar(lower)alkyl substituted by protected carboxy, 
R.sub.d.sup.3 is ar(lower)alkyl substituted by carboxy, 
R.sub.e.sup.3 is ar(lower)alkyl substituted by lower alkyl and one 
additional substituent selected from protected amino and N-lower 
alkyl-N-protected amino, 
R.sub.f.sup.3 is ar(lower)alkyl substituted by lower alkyl and one 
additional substituent selected from amino and lower alkylamino, 
R.sub.g.sup.3 is ar(lower)alkyl substituted by lower alkyl and lower 
alkanoylcarbonylamino, 
R.sub.h.sup.3 is ar(lower)alkyl substituted by lower alkyl and 
.alpha.-hydroxy(lower)alkanoylamino, 
R.sub.i.sup.3 is ar(lower)alkyl substituted by lower alkyl and one 
additional substituent selected from protected amino(lower)alkanoylamino 
and protected thioureido, 
R.sub.j.sup.3 is ar(lower)alkyl substituted by lower alkyl and one 
additional substituent selected from amino(lower)alkanoylamino and 
thioureido, 
R.sub.6.sup.5 is lower alkylene, 
R.sup.6 is lower alkynyl, 
R.sup.7 is lower alkyl, and 
Y is a leaving group. 
As to the starting compounds (II), (III), (IV), (VI) and (VII), some of 
them are novel and can be prepared by the procedures disclosed in the 
following Preparations 1 to 41. 
Suitable salts of the object compounds (I) are conventional non-toxic, 
pharmaceutically acceptable salts and may include a salt with a base or an 
acid addition salt such as a salt with an inorganic base, for example, an 
alkali metal salt (e.g. sodium salt, potassium salt, cesium salt, etc.), 
an alkaline earth metal salt (e.g. calcium salt, megnesium salt, etc.), an 
ammonium salt; a salt with an organic base, for example, an organic amine 
salt (e.g. triethylamine salt, pyridine salt, picoline salt, ethanolamine 
salt, triethanolamine salt, dicyclohexylamine salt, 
N,N'-dibenzylethylenediamine salt, etc.), etc.: an inorganic acid addition 
salt (e.g. hydrochloride, hydrobromide, sulfate, phosphate, etc.); an 
organic carboxylic or sulfonic acid addition salt (e.g. formate, acetate, 
trifluoroacetate, maleate, tartrate, methanesulfonate, benzenesulfonate, 
p-toluenesulfonate, etc.); a salt with a basic or acidic amino acid (e.g. 
arginine, aspartic acid, glutamic acid, etc.); and the like. 
In the above and subsequent descriptions of the present specification, 
suitable examples and illustrations of the various definitions which the 
present invention include within the scope thereof are explained in detail 
as follows. 
The term "lower" is intended to mean 1 to 6, preferably 1 to 4 carbon 
atom(s), unless otherwise indicated. 
Suitable "lower alkynyl" group and "lower alkynyl" moieties may be the ones 
having 2 to 6 carbon atoms and may include ethynyl, 1(or 2)-propynyl, 1(or 
2 or 3)-butynyl, 1(or 2 or 3 or 4)-pentynyl, 1(or 2 or 3 or 4 or 
5)-hexynyl, and the like. 
Suitable "lower alkyl" group and "lower alkyl" moieties may be the ones 
having 1 to 6 carbon atom(s) and may include methyl, ethyl, propyl, 
isopropyl, n-butyl, t-butyl, pentyl, hexyl and the like. 
Suitable "ar(lower)alkyl" may include mono(or di or tri)-phenyl(lower)alkyl 
such as benzyl, benzhydryl, trityl, phenethyl or the like. 
Suitable "protected amino" group and "protected amino" moieties may include 
an amino group substituted by a conventional amino-protective group which 
is used in peptide chemistry, for example, ar(lower)alkyl as mentioned 
above and acyl as mentioned below. 
Suitable "acyl" may include carbamoyl, thiocarbamoyl, sulfamoyl, an 
aliphatic acyl, an aromatic acyl, a heterocyclic acyl and an aliphatic 
acyl substituted with aromatic or heterocyclic group(s) derived from 
carbamic, sulfonic, carboxylic or carbonic acids and their thio acids. 
The aliphatic acyl may include saturated or unsaturated, acyclic or cyclic 
ones, such as lower alkanoyl (e.g. formyl, acetyl, propionyl, butyryl, 
isobutyryl, valeryl, isovaleryl, pivaloyl, hexanoyl, etc.,), lower 
alkanesulfonyl (e.g. mesyl, ethanesulfonyl, propanesulfonyl, etc.), lower 
alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, 
isopropoxycarbonyl, butoxycrbonyl, tert-butoxycarbonyl, etc.), lower 
alkenoyl (e.g. acryloyl, methacryloyl, crotonoyl, etc.), (C.sub.3 
-C.sub.7)-cycloalkanecarbonyl (e.g. cyclohexanecarbonyl, etc.), lower 
alkoxalyl (e.g. methoxalyl, ethoxalyl, etc.), lower alkanoylcarbonyl (e.g. 
pyruvoyl, etc.), and the like. 
The aromatic acyl may include aroyl (e.g. benzoyl, toluoyl, xyloyl, etc.), 
arenesulfonyl (e.g. benzenesulfonyl, tosyl, etc.), and the like. 
The heterocyclic acyl may include heterocyclic carbonyl (e.g. furoyl, 
thenoyl, nicotinoyl, isonicotinoyl, thiazolylcarbonyl, 
thiadiazolylcarbonyl, tetrazolylcarbonyl, etc.), and the like. 
The aliphatic acyl substituted with aromatic group(s) may include 
phenyl(lower)alkanoyl (e.g. phenylacetyl, phenylpropionyl, phenylhexanoyl, 
etc.), phenyl(lower)alkoxycarbonyl (e.g. benzyloxycarbonyl, 
phenethyloxycarbonyl, etc.), phenoxy(lower)alkanoyl (e.g. phenoxyacetyl, 
phenoxypropionyl, etc.), and the like. 
The aliphatic acyl substituted with heterocyclic group(s) may include 
thienylacetyl, imidazolylacetyl, furylacetyl, tetrazolylacetyl, 
thiazolylacetyl, thiadiazolylacetyl, thienylpropionyl, 
thiadiazolylpropionyl, and the like. 
These acyl groups may be further substituted with suitable substituent(s) 
such as hydroxy, amino, carboxy, lower alkyl (e.g. methyl, ethyl, propyl, 
isopropyl, butyl, pentyl, hexyl, etc.), halogen (e.g. chloride, bromine, 
iodine, fluorine), lower alkoxy (e.g. methoxy, ethoxy, propoxy, 
isopropoxy, butoxy, pentyloxy, hexyloxy, etc.), lower alkylthio (e.g. 
methylthio, ethylthio, propylthio, isopropylthio, butylthio, pentylthio, 
hexylthio, etc.), nitro, protected amino in which the amino protective 
moiety may be the same as those herein, aryl (e.g. phenyl, etc.), 
aroyl(e.g. benzoyl, etc.), aryloxy (e.g., benzyloxy, tolyloxy, etc.), 
protected hydroxy such as acyloxy, for example, lower alkanoyloxy (e.g. 
formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, 
isovaleryloxy, pivaloyloxy, hexanoyloxy, etc.), lower alkylamino (e.g. 
methylamino, ethylamino, etc.), and the like, and the preferable acyl 
having such substituent(s) may be mono (or di or tri) halo(lower)alkanoyl 
(e.g.,chloroacetyl, bromoacetyl, dichloroacetyl, trifluoroacetyl, etc.), 
amino(lower)alkanoyl (e.g., glycyl, aminopropionyl, diaminobutyryl, etc.), 
phenyl(lower)alkoxycarbonylamino(lower)alkanoyl (e.g., 
benzyloxycarbonylglycyl, etc.), lower alkanoyloxy(lower)alkanoyl (e.g., 
acetoxyacetyl, etc.), lower alkylcarbamoyl (e.g. methylcarbamoyl, 
ethylcarbamoyl, etc.), lower alkoxycarbonylamino(lower)alkanoyl (e.g. 
t-butoxycarbonylaminoacetyl, etc.), phenyl(lower)alkoxycarbonylcarbamoyl 
(e.g., benzyloxycarbonylcarbamoyl) phenyl(lower)alkoxy(lower)alkanoyl 
(e.g. benzyloxyacetyl, benzyloxypropionyl, etc.), carboxy(lower)alkanoyl 
(e.g., carboxyacetyl, carboxypropionyl, etc.), hydroxy(lower)alkanoyl 
(e.g. glycoloyl, hydroxypropionyl, hydroxybutyryl etc.), 
aroylthiocarbamoyl (e.g., benzoylthiocarbamoyl, etc.), etc. 
Suitable "protected carboxy" may include an esterified carboxy group. 
Suitable examples of the ester moiety of an "esterified carboxy" may be the 
ones such as lower alkyl ester (e.g. methyl ester, ethyl ester, propyl 
ester, isopropyl ester, butyl ester, isobutyl ester, tert-butyl ester, 
pentyl ester, hexyl ester, 1-cyclopropylethyl ester, etc.) which may have 
at least one suitable substituent(s), for example, lower 
alkanoyloxy(lower)alkyl ester (e.g. acetoxymethyl ester, 
propionyloxymethyl ester, butyryloxymethyl ester, valeryloxymethyl ester, 
pivaloyloxymethyl ester, hexanoyloxymethyl ester, 1(or 2)-acetoxyethyl 
ester, 1(or 2 or 3)-acetoxypropyl ester, 1(or 2 or 3 or 4)-acetoxybutyl 
ester, 1(or 2)-propionyloxyethyl ester, 1(or 2 or 3)-propionyloxypropyl 
ester, 1(or 2)-butyryloxyethyl ester, 1(ior 2)-isobutyryloxyethyl ester, 
1(or 2)-pivaloyloxyethyl ester, 1(or 2)-hexanoyloxyethyl ester, 
isobutyryloxymethyl ester, 2-ethylbutyryloxymethyl ester, 
3,3-dimethylbutyryloxymethyl ester, 1(or 2)-pentanoyloxyethyl ester, etc.) 
lower alkanesulfonyl(lower)alkyl ester (e.g. 2-mesylethyl ester, etc.), 
mono(or di or tri)-halo(lower)alkyl ester (e.g. 2-iodoethyl ester, 
2,2,2-trichloroethyl ester, etc.), lower alkoxycarbonyloxy(lower)alkyl 
ester (e.g. methoxycarbonyloxymethyl ester, ethoxycarbonyloxymethyl ester, 
2-methoxycarbonyloxyethyl ester, 1-ethoxycarbonyloxyethyl ester, 
1-isopropoxycarbonyloxyethyl ester, etc.), phtahlidylidene(lower)alkyl 
ester, or (5-lower alkyl-2-oxo-1,3-dioxol-4-yl)(lower)alkyl ester (e.g. 
(5-methyl-2-oxo-1,3-dioxol-4-yl) methyl ester, 
(5-ethyl-2-oxo-1,3-dioxol-4-yl)methyl ester, (5-propyl-2-oxo-1,3 
-dioxol-4-yl)ethyl ester, etc.; lower alkenyl ester (e.g. vinyl ester, 
allyl ester, etc.); lower alkynyl ester (e.g. ethynyl ester, propynyl 
ester, etc.); ar(lower)alkyl ester which may have at least one suitable 
substituent(s) (e.g. benzyl ester, 4-methoxybenzyl ester, 4-nitrobenzyl 
ester, phenethyl ester, trityl ester, benzhydryl ester, 
bis(methoxyphenyl)methyl ester, 3,4-dimethoxybenzyl ester, 
4-hydroxy-3,5-di-tert-butylbenzyl ester, etc.); aryl ester which may have 
at least one suitable substituent(s) (e.g. phenyl ester, 4-chlorophenyl 
ester, tolyl ester, tert-butylphenyl ester, xylyl ester, mesityl ester, 
cumenyl ester, etc.); phthalidyl ester; and the like. 
Preferable examples of the esterified carboxy as mentioned above may 
include lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, 
propoxycarbonyl, isopropoxycarbonyl butoxycarbonyl, isobutoxycarbonyl, 
tert-butoxycarbonyl, pentyloxycarbonyl, tert-pentyloxycarbonyl, 
hexyloxycarbonyl, 1-cyclopropylethoxycarbonyl, etc.). 
Suitable "hydroxy-protective group" in the term "protected hydroxy" may 
include aforesaid acyl, ar(lower)alkyl (e.g. benzyl, trityl, etc.), lower 
alkoxy(lower)alkyl (e.g. methoxymethyl, 1-methyl-1-methoxyethyl, 
methoxypropyl, etc.), tetrahydropyranyl, and the like. 
Suitable "N-lower alkyl-N-protected amino" may include N-lower 
alkyl-N-acylamino, in which the acyl moiety may be the same as the above, 
such as N-lower alkyl-N-lower alkoxycarbonylamino (e.g. 
N-methyl-N-methoxyarbonylamino, N-methyl-N-tert-butoxycarbonylamino, 
etc.), N-lower alkyl-N-lower alkanesulfonylamino (e.g. 
N-methyl-N-mesylamino, etc.), N-lower alkyl-N-carbamoylamino (e.g. 
N-methyl-N-carbamoylamino, etc.), N-lower alkyl-N-carbamoylamino 
substituted by lower alkyl (e.g. 1,3-dimethylureido, etc.), N-lower 
alkyl-N-lower alkanoylamino (e.g. N-methyl-N-acetylamino, etc.) and the 
like. 
Suitable "lower alkynyloxy(lower)alkyl" may be 2-propynyloxymethyl, and the 
like. 
Suitable "N,N-di(lower)alkylamino(lower)alkynyl" may be 
4-N,N-dimethylamino-2-butynyl and the like. 
Suitable "trihalo(lower)alkyl" may include trifluoro(lower)alkyl (e.g. 
trifluoromethyl, trifluoroethyl, etc.), and the like. 
Suitable "hydroxy(lower)alkyl" may include hydroxymethyl, hydroxyethyl, 
hydroxypropyl and the like. 
Suitable "protected hydroxy(lower)alkyl" may include acyloxy(lower)alkyl, 
in which the acyl moiety may be the same as the above, such as lower 
alkanoyloxy(lower)alkyl (e.g. formyloxymethyl, acetyloxymethyl, 
propionyloxymethyl, butyryloxymethyl, valeryloxymethyl, etc.), and the 
like. 
Suitable "protected amino(lower)alkyl" may include acylamino(lower)alkyl, 
in which the acyl moiety may be the same as the above, such as lower 
alkoxycarbonylamino(lower)alkyl (e.g. methoxycarbonylaminomethyl, 
ethoxycarbonylaminomethyl, etc.), and the like. 
Suitable "lower alkylamino" may include methylamino, ethylamino, 
propylamino, isopropylamino, butylamino, and the like. 
Suitable "ar(lower)alkyl substituted by protected hydroxy(lower)alkyl" may 
include ar(lower)alkyl substituted by acyloxy(lower)alkyl such as lower 
alkanoyloxy(lower) alkylbenzyl (e.g. formyloxymethylbenzyl, 
acetyloxymethylbenzyl, propionyloxymethylbenzyl, butyryloxymethylbenzyl, 
valeryloxymethylbenzyl, etc.), and the like. 
Suitable "ar(lower)alkyl substituted by hydroxy(lower)alkyl" may include 
hydroxy(lower)alkylbenzyl (e.g. hydroxymethylbenzyl, hydroxyethylbenzyl, 
hydroxypropylbenzyl, etc.), and the like. 
Suitable "ar(lower)alkyl substituted by protected carboxy" may include 
ar(lower)alkyl substituted by esterified carboxy, in which the esterified 
carboxy may be the same as the above, such as lower alkoxycarbonylbenzyl 
(e.g. methoxycarbonylbenzyl, ethoxycarbonylbenzyl, etc.), and the like. 
Suitable "ar(lower)alkyl substituted by carboxy" may include 
carboxybenzyl, and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and protected amino" 
may include ar(lower)alkyl substituted by lower alkyl and acylamino, in 
which the acyl moiety may be the same as the above, such as benzyl 
substituted by methyl and ureido (e.g. 2-methyl-6-ureidobenzyl, etc.), 
benzyl substituted by methyl and thioureido (e.g. b 
2-methyl-6-thioureidobenzyl, etc.), benzyl substituted by methyl and lower 
alkanoylamino (e.g. 6-formamido-2-methylbenzyl, 
3-acetamido-2-methylbenzyl, 5-acetamido-2-methylbenzyl, 
2-acetamido-6-methylbenzyl, 2-methyl-6propionamidobenzyl, 
2-acetamido-4-methylbenzyl, 2-butyramido-6-methylbenzyl, etc.), benzyl 
substituted by methyl and lower alkanesulfonylamino (e.g. 
2-methanesulfonylamino-6-methylbenzyl, etc.), benzyl substituted by methyl 
and lower alkoxycarbonylamino (e.g. 2-methoxycarbonylamino-6-methylbenzyl, 
2-ethoxycarbonylamino-6-methylbenzyl, 
2-methyl-6-i-propoxycarbonylaminobenzyl, 
2-t-butoxycarbonylamino-6-methylbenzyl, etc.), benzyl substituted by 
methyl and heterocyclic carbonylamino (e.g. 
2-isonicotinamido-6methylbenzyl, etc.), benzyl substituted by methyl and 
acylamino substituted with suitable substituent (e.g. 
6-methyl-2-(3-methylureido)benzyl, 2-(3-benzoylthioureido)-6-methylbenzyl, 
2-t-butoxycarbonyl-aminoacetamido-6-methylbenzyl, 
2-benzyloxycarbonylamino-6-methylbenzyl, 
2-(N-methoxycarbonyl-N-methylamino-6 -methylbenzyl, 
2-hydroxyacetamido-6-methylbenzyl, 2-acetoxyacetamido-6-methylbenzyl, 
2-methyl-6-pyruvamidobenzyl, 2-methoxalylamino-6-methylbenzyl, 
2-methyl-6-sulfamidobenzyl, 2-lactamido-6-methylbenzyl, 
2-aminoacetamido-6-methylbenzyl, etc.), and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and amino" may include 
benzyl substituted by methyl and amino (e.g. 2-amino-6-methylbenzyl, etc.) 
and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and lower 
alkanoylcarbonylamino" may include benzyl substituted by methyl and lower 
alkanoylcarbonylamino (e.g. 2-methyl-6-pyruvamidobenzyl, etc.), and the 
like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and 
.alpha.-hydroxy(lower)alkanoylamino" may include benzyl substituted by 
methyl and .alpha.-hydroxy(lower)alkanoylamino (e.g. 
2-lactamido-6-methylbenzyl, etc.), and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and protected 
amino(lower)alkanoylamino" may include ar(lower)alkyl substituted by lower 
alkyl and acylamino(lower)alkanoylamino, in which the acyl moiety may be 
the same as the above, such as benzyl substituted by methyl and 
acylamino(lower)alkanoylamino (e.g. 
2-t-butoxycarbonylaminoacetamido-6-methylbenzyl, etc.), and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and 
amino(lower)alkanoylamino" may include benzyl substituted by methyl and 
amino(lower)alkanoylamino (e.g. 2-aminoacetamido-6-methylbenzyl, etc.), 
and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and protected 
thioureido" may include ar(lower)alkyl substituted by lower alkyl and 
acylthioureido, in which the acyl moiety may be the same as those given 
above, such as benzyl substituted by methyl and 3-aroylthioureido (e.g. 
2-(3-benzoylthioureido)-6methylbenzyl, etc.), and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and thioureido" may 
include benzyl substituted by methyl and thioureido (e.g. 
2-methyl-6-thioureidobenzyl, etc.) and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and N-lower 
alkyl-N-protected amino" may include ar(lower)alkyl substituted by lower 
alkyl and N-lower alkyl-N-acylamino, in which the acyl moiety may be the 
same as the above, such as benzyl substituted by methyl and 
N-methyl-N-lower alkoxycarbonylamino (e.g. 
2-methyl-6-N-methyl-N-methoxycarbonylamino)benzyl, 
2-methyl-6-N-methyl-N-tert-butoxycarbonylamino)benzyl, etc.), benzyl 
substituted by methyl and N-methyl-N-lower alkaneamino (e.g. 
2-methyl-6-(N-methyl-N-mesylamino)benzyl, etc.), benzyl substituted by 
methyl and N-methyl-N-carbamoylamino (e.g. 
2-methyl-6-(N-methyl-N-carbamoylamino)benzyl, etc.), benzyl substituted by 
methyl and 1,3-di(lower)alkylureido (e.g. 
2-methyl-6-(1,3-dimethylureido)benzyl, etc.), benzyl substituted by methyl 
and N-methyl-N-lower alkanoylamino (e.g. 
2-methyl-6-(N-methyl-N-acetylamino)benzyl, etc.) and the like. 
Suitable "ar(lower)alkyl substituted by lower alkyl and lower alkylamino" 
may include benzyl substituted by methyl and lower alkylamino (e.g. 
2-methyl-6-methylaminobenzyl, etc.) and the like. 
Suitable "lower alkylene" may include methylene, ethylene, trimethylene, 
tetramethylene, pentamethylene, hexamethylene and the like. 
Suitable "protective" moiety in the term "protected thioureido" may include 
acyl such as carbamoyl, sulfamoyl, an aliphatic acyl, an aromatic acyl, a 
heterocyclic acyl and an aliphatic acyl substituted with aromatic or 
heterocyclic group(s) as mentioned above. 
Suitable "a leaving group" may include an acid residue such as halogen 
(e.g. fluorine, chlorine, bromine, iodine), acyloxy (e.g. acetoxy, 
tosyloxy, mesyloxy, etc.), and the like, a group of the formula: 
##STR4## 
wherein R.sup.8, R.sup.9 and are each lower alkyl as mentioned above, and 
Z is an acid residue as mentioned above, and the like. 
Preferred embodiments of the object compounds (I) are as follows. 
Preferred embodiment of R.sup.1 is lower alkynyl, lower 
alkynyloxy(lower)alkyl or N,N-di(lower)alkylamino-(lower)alkynyl. 
Preferred embodiment of R.sup.2 is lower alkyl. 
Preferred embodiment of R.sup.3 is benzyl substituted with cyano, 
trihalo(lower)alkyl, carbamoyl, lower alkanoylamino, ureido, lower 
alkoxycarbonylamino, carboxy, lower alkoxycarbonyl, hydroxy, 
hydroxy(lower)alkyl, lower alkanoyloxy(lower)alkyl, or lower 
alkoxy(lower)alkoxy, or lower alkoxycarbonylamino(lower)alkyl; or 
benzyl substituted with lower alkyl and one additional substituent selected 
from hydroxy, amino, lower alkanoylamino, lower alkanesulfonylamino, lower 
alkoxycarbonylamino, heterocyclic carbonylamino, ureido, ureido having 
lower alkyl, lower alkoxycarbonylamino(lower)alkanoylamino, 
phenyl(lower)alkoxycarbonylamino N-lower alkoxycarbonyl-N-lower 
alkylamino, hydroxy(lower)alkanoylamino, lower 
alkanoyloxy(lower)alkanoylamino, lower alkanoylcarbonylamino, lower 
alkoxycarbonylcarbonylamino, sulfamido, lower alkanoylamino having 
hydroxy, amino(lower)alkanoylamino, N-lower alkanoyl-N-lower alkylamino, 
N-carbamoyl-N-lower alkylamino, N-lower alkylaminocarbonyl-N-lower 
alkylamino, N-lower alkylsulfonyl-N-lower alkylamino, thioureido, 
protected thioureido, lower alkylamino. 
Preferred embodiment of R.sup.4 is hydrogen or lower alkyl. 
The processes for preparing the object compounds of the present invention 
are explained in detail in the following. 
PROCESS 1 
The object compound (I) or a salt thereof can be prepared by reacting the 
compound (II) or a salt thereof with the compound (III) or its reactive 
derivative at the hydroxy group. 
Suitable salts of the compound (II) can be referred to the acid addition 
salt as exemplified for the compound (I), and suitable reactive derivative 
of the compound (III) may be one, in which the hydroxy group is replaced 
by an acid residue such as halogen (e.g. halogen (e.g. fluorine, chlorine, 
bromine, iodine), acyloxy (e.g. acetoxy, tosyloxy, mesyloxy, etc.), and 
the like. 
This reaction is usually carried out in a solvent such as alcohol [e.g. 
methanol, ethanol, etc.], benzene, N,N-dimethylformamide, tetrahydrofuran, 
diethyl ethyl or any other solvent which does not adversely affect the 
reaction. 
The reaction may be carried out in the presence of an inorganic or an 
organic base such as an alkali metal hydroxide [e.g. sodium hydroxide, 
potassium hydroxide, etc.], an alkali metal carbonate [e.g. sodium 
carbonate, potassium carbonate, etc.], an alkali metal bicarbonate [e.g. 
sodium bicarbonate, potassium bicarbonate, etc.], tri(lower)alkylamine 
[e.g. trimethylamine, triethylamine, etc.], pyridine or its derivative 
[e.g. picoline, lutidine, 4-dimethylaminopyridine, etc.], or the like. In 
case that the base to be used is liquid, it can also be used as a solvent. 
In case that the compound (III) is used in a form of free hydroxy, the 
reaction can be carried out in the presence of a condensing agent such as 
N,N-dicyclohexylcarbodiimide; N-cyclohexyl-N'morpholinoethylcarbodiimide; 
N-cyclohexyl-N'-(4-diethylaminocyclohexyl)carbodiimide; 
N,N'-diethylcarbodiimide, N,N'-diisopropylcarbodiimide; 
N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide; 
N,N-carbonylbis-(2-methylimidazole); 
pentamethyleneketene-N-cyclohexylimine; diphenylketene-N-cyclohexylimine; 
ethoxyacetylene; 1-alkoxy-1-chloroethylene; 
1,1'-(carbonyldioxy)dibenzotriazole, 1, 1'-dibenzotriazolyloxallate 
trialkyl phosphite; ethyl polyphosphate; isopropyl polyphosphate; 
phosphorus oxychloride (phosphoryl chloride); phosphorus trichloride; 
thionyl chloride; oxalyl chloride; triphenylphosphine; 
2-ethyl-7-hydroxybenzisoxazolium salt; 
2-ethyl-5-(m-sulfophenyl)isoxazolium hydroxide intramolecular salt; 
1-(p-chlorobenzenesulfonyloxy)-6-chloro-1H-benzotriazole; so-called 
Vilsmeier reagent prepared by the reaction of dimethylformamide with 
thionyl chloride, phosgene, phosphorus oxychloride, etc.; or the like. 
The reaction temperature is not critical, and the reaction can be carried 
out under cooling, at ambient temperature or under warming or heating. 
PROCESS 2 
The object compound (Ia) or a salt thereof can be prepared by reacting the 
compound (IV) or a salt thereof with the compound (V) or a salt thereof. 
Suitable salts of the compounds (IV) and (Ia) can be referred to the ones 
as exemplified for the object compound (I). 
Suitable salts of the compound (V) are salts with a base such as an alkali 
metal salt (e.g. sodium salt, potassium salt, lithium salt, etc.), or the 
like. 
This reaction is usually carried out in the presence of a base such as 
alkali metal hydride (e.g. sodium hydride, potassium hydride, lithium 
hydride, etc.), alkali metal alkoxide (e.g. potassium t-butoxide, etc.), 
an alkali metal (e.g. sodium, potassium, lithium, etc.) or the like. 
This reaction is usually carried out in a solvent such as alcohol [e.g. 
methanol, ethanol, etc.], dimethyl sulfoxide, benzene, 
N,N-dimethylformamide, tetrahydrofuran, diethyl ether or any other solvent 
which does not adversely affect the reaction. 
In case that the compound (V) or a salt thereof to be used is liquid, it 
can also be used as a solvent. 
The reaction temperature is not critical, and the reaction can be carried 
out under cooling, at ambient temperature or under warming or heating. 
PROCESS 3 
The object compound (I) or a salt thereof can be prepared by reacting the 
compound (VI) or a salt thereof with the compound (VII) or its reactive 
derivative at the hydroxy group. 
Suitable salts of the compound (VI) can be referred to the salt as 
exemplified for the compound (I) and suitable reactive derivative of the 
compound (VII) may be the same as those given for the compound (III) in 
Process 1. 
This reaction is usually carried out in a solvent such as alcohol [e.g. 
methanol, ethanol, etc.], benzene, N,N-dimethylformamide, tetrahydrofuran, 
diethyl ether or any other solvent which does not adversely affect the 
reaction. 
The reaction may be carried out in the presence of an inorganic or an 
organic base such as an alkali metal hydroxide [e.g. sodium hydroxide, 
potassium hydroxide, etc.], a- alkali metal carbonate [e.g. sodium 
carbonate, potassium carbonate, etc.], an alkali metal bicarbonate [e.g. 
sodium bicarbonate, potassium bicarbonate, etc.], tri(lower)alkylamine 
[e.g. trimethylamine, triethylamine, etc.], pyridine or its derivative 
[e.g. picoline, lutidine, 4-dimethylaminopyridine, etc.], or the like. In 
case that the base to be used is liquid, it can also be used as a solvent. 
The reaction temperature is not critical, and the reaction can be carried 
out under cooling, at ambient temperature or under warming or heating. 
PROCESS 4 
The object compound (Ic) or a salt thereof can be prepared by subjecting 
the compound (Ib) or a salt thereof to elimination reaction of the hydroxy 
protective group in R.sub.a.sup.3. 
Suitable salts of the compounds (Ib) and (Ic) can be referred to the salt 
as exemplified for the compound (I). 
Suitable method for this elimination reaction may include conventional one 
such as hydrolysis, reduction, or the like. The hydrolysis is preferably 
carried out in the presence of a base or an acid. 
Suitable base may include, for example, an inorganic base such as alkali 
metal hydroxide (e.g. sodium hydroxide, potassium hydroxide, etc.), 
alkaline earth metal hydroxide (e.g. magnesium hydroxide, calcium 
hydroxide, etc.), alkali metal carbonate (e.g. sodium carbonate, potassium 
carbonate, etc.), alkaline earth metal carbonate (e.g. magnesium 
carbonate, calcium carbonate, etc.), alkali metal bicarbonate (e.g. sodium 
bicarbonate, potassium bicarbonate, etc.), alkali metal acetate (e.g. 
sodium acetate, potassium acetate, etc.), alkaline earth metal phosphate 
(e.g. magnesium phosphate, calcium phosphate, etc.), alkali metal hydrogen 
phosphate (e.g. disodium hydrogen phosphate, dipotassium hydrogen 
phosphate, etc.), or the like, and an organic base such as trialkylamine 
(e.g. trimethylamine, triethylamine, etc.), picoline, N-methylpyrrolidine, 
N-methylmorpholine, 1,5-diazabicyclo[4,3,0]non-5-one, 
1,4-diazabicyclo[2,2,2]octane, 1,5-diazabicyclo[5,4,0]undecene-5 or the 
like. The hydrolysis using a base is often carried out in water or a 
hydrophilic o-ganic solvent or a mixed solvent thereof. 
Suitable acid may include an organic acid (e.g. formic acid, acetic acid, 
propionic acid, etc.) and an inorganic acid (e.g. hydrochloric acid, 
hydrobromic acid, sulfuric acid, etc.). 
The present hydrolysis is usually carried out in an organic solvent, water 
or a mixed solvent thereof. 
The reaction temperature is not critical, and it may suitably be selected 
in accordance with the kind of the hydroxy protective group and the 
elimination method. 
PROCESS 5 
The object compound (Ie) or a salt thereof can be prepared by subjecting 
the compound (Id) or a salt thereof to elimination reaction of the carboxy 
protective group in R.sub.c.sup.3. 
Suitable salts of the compounds (Id) and (Ie) can be referred to the salts 
as exemplified for the compound (I). 
The present reaction can be carried out in a similar manner to that of 
Process 4 as mentioned above, and therefore the reaction mode and reaction 
conditions can be referred to those of Process 4. 
PROCESS 6 
The object compound (Ig) or a salt thereof can be prepared by subjecting 
the compound (If) or a salt thereof to elimination reaction of the amino 
protective group in R.sub.e.sup.3. 
Suitable salts of the compounds (If) and (Ig) can be referred to the salts 
as exemplified for the compound (I). 
The present reaction can be carried out in a similar manner to that of 
Process 4 as mentioned above, and therefore the reaction mode and reaction 
conditions can be referred to those of Process 4. 
PROCESS 7 
The object compound (If) or a salt thereof can be prepared by subjecting 
the compound (Ig) or its reactive derivative at the amino group or a salt 
thereof to introduction reaction of the amino protective group. 
Suitable reactive derivative at the amino group of the compound (Ig) may 
include Schiff's base type imino or its tautomeric enamine type isomer 
formed by the reaction of the compound (Ig) with a carbonyl compound such 
as aldehyde, ketone or the like; a silyl derivative formed by the reaction 
of the compound (Ig) with a silyl compound such as 
bis(trimethylsilyl)acetamide, mono(trimethylsilyl)acetamide or the like; a 
derivative formed by reaction of the compound (Ig) with phosphorus 
trichloride or phosgene, and the like. 
Suitable introducing agent to be used in the present reaction may include 
conventional one and can be shown by the formula: 
EQU R.sup.11 --OH (IX) 
(wherein R.sup.11 is acyl as exemplified above) or its reactive derivative 
or a salt thereof. 
Suitable salt of the compound (Ig) and (IX) may include an acid addition 
salt such as an organic acid salt (e.g. acetate, maleate, tartrate, 
methanesulfonate, benzenesulfonate, toluenesulfonate, etc.) or an 
inorganic acid salt (e.g. hydrochloride, hydrobromide, sulfate, phosphate, 
etc.); a metal salt (e.g. sodium salt, potassium salt, calcium salt, 
magnesium salt, etc.); ammonium salt; an organic amine salt (e.g. 
triethylamine salt, dicyclohexylamine salt, etc.), and the like. 
Suitable reactive derivative of the compound (IX) may include an acid 
halide, an acid anhydride, an activated amide, an activated ester, and the 
like. The suitable example may be an acid chloride, an acid azide; a mixed 
acid anhydride with an acid such as substituted phosphoric acid (e.g. 
dialkylphosphoric acid, phenylphosphoric acid, diphenylphosphoric acid, 
dibenzylphosphoric acid, halogenated phosphoric acid, etc.), 
dialkylphosphorous acid, sulforous acid, thiosulfuric acid, sulfuric acid, 
alkylcarbonic acid, aliphatic carboxylic acid (e.g. pivalic acid, 
pentanoic acid, isopentanoic acid, 2-ethylbutyric acid or trichloroacetic 
acid, etc.) or aromatic carboxylic acid (e.g. benzoic acid, etc.); a 
symmetrical acid anhydride; an activated amide with imidazole, 
4-substituted imidazole, dimethylpyrazole, triazole or tetrazole; or an 
activated ester (e.g. cyanomethyl ester, methoxymethyl ester, 
dimethyliminomethyl [(CH.sub.3).sub.2 N.sup.+=CH--]ester, vinyl ester, 
propargyl ester, p-nitrophenyl ester, 2,4-dinitrophenyl ester, 
trichlorophenyl ester, pentachlorophenyl ester, mesylphenyl ester, 
phenylazophenyl ester, phenyl thioester, p-nitrophenyl thioester, p-cresyl 
thioester, carboxymethyl thioester, pyranyl ester, pyridyl ester, 
piperidyl ester, 8-quinolyl thioester, etc.), or an ester with a N-hydroxy 
compound (e.g. N,N-dimethylhydroxylamine, 1-hydroxy-2-(1H)-pyridone, 
N-hydroxysuccinimide, N-hydroxyphthalimide, 
1-hydroxy-6-chloro-1H-benzotriazole, etc.), and the like. These reactive 
derivatives can optionally be selected from them according to the kind of 
the compound (IX) to be used. 
The reaction is usually carried out in a conventional solvent such as 
water, acetone, dioxane, acetonitrile, chloroform, methylene chloride, 
ethylene chloride, tetrahydrofuran, ethyl acetate, N,N-dimethylformamide, 
pyridine or any other organic solvent which does not adversely influence 
the reaction. These conventional solvent may also be used in a mixture 
with water. 
When the compound (IX) is used in free acid form or its salt form in the 
reaction, the reaction is preferably carried out in the presence of a 
conventional condensing agent such as N,N'-dicyclohexylcarbodiimide; 
N-cyclohexyl-N'-morpholinoethylcarbodiimide; 
N-cyclohexyl-N'-(4-diethylaminocyclohexyl)carbodiimide; 
N,N'-diethylcarbodiimide, N,N'-diisopropylcarbodiimide; 
N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide; 
N,N-carbonylbis-(2-methylimidazole); 
pentamethyleneketene-N-cyclohexylimine, diphenylketene-N-cyclohexylimine; 
ethoxyacetylene; 1-alkoxy-1-chloroethylene; trialkyl phosphite; ethyl 
polyphosphate; isopropyl polyphosphate phosphorus oxychloride (phosphoryl 
chloride); phosphorus trichloride; thionyl chloride; oxalyl chloride; 
triphenylphosphine; 2-ethyl-7-hydroxybenzisoxazolium salt; 
2-ethyl-5-(m-sulfophenyl)isoxazolium hydroxide intra-molecular salt; 
1-(p-chlorobenzenesulfonyloxy)-6-chloro-1H-benzotriazole; so-called 
Vilsmeier reagent prepared by the reaction of dimethylformamide with 
thionyl, chloride, phosgene, phosphorus oxychloride, etc.; or the like. 
The reaction may also be carried out in the presence of an inorganic or 
organic base such as an alkali metal bicarbonate, tri(lower)alkylamine, 
pyridine, N-(lower)alkylmorphorine, N,N-di(lower)alkylbenzylamine, or the 
like. The reaction temperature is not critical, and the reaction is 
usually carried out under cooling or at ambient temperature. 
PROCESS 8 
The object compound (Ii) or a salt thereof can be prepared by reducing a 
compound (Ih) or a salt thereof. 
The reduction can be carried out in a conventional manner, namely, chemical 
reduction or catalytic reduction. 
Suitable reducing agents to be used in chemical reduction are a metal 
hydride compound such as aluminum hydride compound [e.g. lithium aluminum 
hydride, sodium aluminum hydride, aluminum hydride, lithium 
trimethoxyaluminum hydride, lithium tri-t-butoxyaluminum hydride, etc.], 
borohydride compound [e.g. sodium borohydride, lithium borohydride, sodium 
cyanoborohydride, tetramethylammonium borohydride, etc.], borane, 
diborane, aluminum halide [e.g. aluminum chloride, etc.], phosphorus 
trihalide [e.g. phosphorus trichloride, phosphorus tribromide, etc.], 
ferrous oxalate, a combination of metal [e.g. tin, zinc, iron, etc.]or 
metallic compound [e.g. chromium chloride, chromium acetate, etc.]and an 
organic or inorganic acid [e.g. formic acid, acetic acid, propionic acid, 
trifluoroacetic acid, p-toluenesulfonic acid, hydrochloric acid, 
hydrobromic acid, etc.]or the like. 
Suitable catalysts to be used in catalytic reduction are conventional ones 
such as platinum catalyst [e.g. platinum plate, spongy platinum, platinum 
black, colloidal platinum, platinum oxide, platinum wire, etc.], palladium 
catalyst [e.g. spongy palladium, palladium black, palladium oxide, 
palladium on carbon, colloidal palladium, palladium on barium sulfate, 
palladium on barium carbonate, etc.], nickel catalyst [e.g. reduced 
nickel, nickel oxide, Raney nikel, etc.], cobalt catalyst [e.g. reduced 
cobalt, Raney cobalt, etc.], iron catalyst [e.g. reduced iron, Raney iron, 
etc.], copper catalyst [e.g. reduced copper, Raney copper, Ullman copper, 
etc.]or the like. 
The reaction of this process is usually carried out in a solvent such as 
water, alcohol [e.g. methanol, ethanol, propanol, etc.], acetic acid, 
diethyl ether, dioxane, tetrahydrofuran, methylene chloride, chloroform, 
N,N-dimethylformamide, dimethylsulfoxide, or any other organic solvent 
which does not adversely influence the reaction, or a mixture thereof. 
The reaction is preferably carried out under somewhat milder conditions 
such as under cooling to warming. 
PROCESS 9 
The object compound (Ik) or a salt thereof can be prepared by subjecting 
the compound (Ij) or a salt thereof to elimination reaction of the amino 
protective group in R.sub.i.sup.3. 
Suitable salts of the compound (Ij) and (Ik) can be referred to the salts 
as exemplified for the compound (I). 
The present reaction can be carried out in a similar manner to that of 
Process 4 as mentioned above and therefore the reaction mode and reaction 
conditions can be referred to those of Process 4. 
PROCESS 10 
The object compound (Im) or a salt thereof can be prepared by reacting the 
compound (Il) or a salt thereof with the compund (VIII) in the presence of 
formaldehyde. 
Suitable salts of the compound (Il) and (Im) can be referred to the salts 
as exemplified for the compound (I). 
The present reaction is carried out by the method of so-called Mannich 
reaction. 
The reaction is usually carried out in a solvent such as water, methylene 
chloride, N,N-dimethylformamide, an alcohol (e.g. methanol, ethanol, 
etc.), tetrahydrofuran, dioxane, diethyl ether, a mixture thereof or any 
other solvent which does not adversely influence the reaction. A liquid 
acid can be also used as the solvent. 
The reaction may be carried out in the presence of a catalyst such as 
cuprous chloride. 
The reaction temperature is not critical and the reaction is usually 
carried out under cooling to heating. 
The object compounds (I) and their pharmaceutically acceptable salts of the 
present invention are novel and exhibit high inhibitory activity on ulcer. 
In order to illustrate the usefulness of the object compound (I), the 
pharmacological data of the representative compound of the object compound 
(I) are shown in the following. 
(A) Inhibition on ethanol ulcer 
Test Method 
Five male Sprague-Dawley rats, aged 7 weeks and weighing about 200 g, were 
used per group for the study on ethanol ulcer after the fast for 24 hours. 
Test compound was suspended in 0.1% methylcellulose aqueous solution, and 
the suspension (5 ml/kg) was orally given to each rat. 
The control group was given a vehicle, i.e. 0.1% methylcellulose aqueous 
solution (5 ml/kg), alone in the same way. 
Absolute ethanol (5 ml/kg) was orally administered 30 minutes after dosing 
with test compound, and one hour later, the rats were sacrificed and their 
stomachs were removed. The area of ulcers of each rat was measured. The 
mean area (mm) in the medicated group was compared with that in the 
control group. 
Test Compound 
(1) 
8-(2-Methoxycarbonylamino-6-methylbenzyloxy)-2methyl-3-(2-propynyl)imidazo 
[1,2-a]pyridine 
Test Result 
Inhibition % at the dose of 32 mg/kg: 
______________________________________ 
Test Compound Inhibition % 
______________________________________ 
(1) 93.2 
______________________________________ 
(B) Inhibition on Stress Ulcer 
Test Method 
Five Sprague-Dawley rats weighing about 200 g were used per group. Each 
animal was immobilized in a small cage and put in a water bath allowing to 
respire. The temperature of the water bath kept at 22.degree. C. The test 
compound was administered orally just before the immobilization. Seven 
hours later, the animals were sacrificed and their stomachs were removed. 
The stomach was then fixed with 2% formalin. The area of ulcers was 
measured for each animal. The mean area (mm.sup.2) in the medicated 
animals was compared with that in the control animals. 
Test Compounds 
(1) 
8-(2-Methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2-propynyl)imidaz 
o[1,2-a]pyridine 
(2) 
8-(2-Acetamido-6-methylbenzyloxy)-2-methyl-3(2-propynyl)imidazo[1,2-a]pyri 
dine 
(3) 
2-methyl-8-(2-methyl-6-ureidobenzyloxy)-3-(2propynyl)imidazo[1,2-a]pyridin 
(4) 
2-Methyl-8-(2-methyl-6-thioureidobenzyloxy)-3(2-propynyl)imidazo[1,2-a]pyr 
idine 
Test Result Inhibition % at the dose of 32 mg/kg: 
______________________________________ 
Test Compound Inhibition % 
______________________________________ 
(1) 100 
(2) 100 
(3) 100 
(4) 100 
______________________________________ 
As being apparent from the above test results, the object compound (I) of 
the present invention are useful as antiulcer medicines. 
For therapeutic purpose, the compounds according to the present invention 
can be used in a form of pharmaceutical preparation containing said 
compound as an active ingredient, in admixture with a pharmaceitically 
acceptable carrier such as an organic or inorganic solid or liquid 
excipient suitable for oral or parenteral administration. The 
pharmaceutical preparations may be capsules, tablets, dragees, solution, 
suspension, emulsion, and the like. If desired, there may be included in 
the above preparations auxiliary substances, stabilizing agents, wetting 
or emulsifying agents, buffers and other commonly used additives. 
While the dosage of the compounds will vary depending upon the age and 
condition of the patient, an average single dose of about 5 mg, 10 mg, 50 
mg, 100 mg, 250 mg, 500 mg, and 1000 mg of the compounds according to the 
present invention may be effective for treating ulcer. In general, amounts 
between 1 mg/body and about 2,000 mg/body or even more may be administered 
per day.