CA1041502A - Imidazo (4,5-b) pyridines - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE

This invention relates to new imidazo[4,5-b]pyridine having valuable physiological properties, in particular an activity on the blood pressure and heart force, a positive inotropic effect, an antiulcus activity, a platelet aggregation inhibiting effect and a prolonging activity on the bleeding time. Tests on certain of the new compounds with regard to their physiological properties are described. Processes for the preparation of the new compounds are described and exemplified and examples of pharmaceutical compositions containing the new compounds are given.

Description

~04150;~
The present invention relates to new imidazo ~4,5-b~pyridines having interesting physiological properties.
According to one feature of the present invention there are providedcompounds of general formula:

R

~ i ~ R3 (I) and isomers thereof of general formula:
R / Rl 5 ~ N ~ R (Ia) wherein Rl represents an alkylamino, dialkylamino, hydroxy, allyloxy, benzyloxy, alkylthio, alkylsulfinyl or alkylsulfonyl group, or an alkoxy group optionally substituted by a halogen atom or by a hydroxy, alkoxy~
alkylthio~ alkylsulfinyl~ alkylsulfonyl~ alkylamino~ dialkylamino~
piperidino, morpholino, thiomorpholino, 4-alkylpiperazino, 4-phenyl-piperazino, 4-methoxyphenylpiperazino, 4-phenylethylpiperazino, phenyl-20 ethylamino, N-methyl-phenylethylamino or N-methyl-dimethoxy-phenylethyl-amino group; ~
R2 represents a hydrogen or halogen atom or a hydroxy, methoxy, -ethoxy, methyl, methylthio, methylsulfinyl or methylsulfonyl group;
R3 represents a hydrogen atom or a methoxy group; or two of the groups Rl to R3 together represent a methylenedioxy group and the remaining Rl, R2 or R3 group is as hereinbefore defined;

R4 represents a hydrogen atom~ an alkyl group optionally substituted by a hydroxy, phenyl, dimethoxyphenyl, dialkylamino, piperidino, morpholino, 4 methylpiperazino or 4-phenylpiperazino group, or a phenyl .

1~)4150Z
group optionally substituted by a halogen atom or by one or two methoxy groups, whereby each of the above mentioned alkyl or alkoxy groups contain from 1 to 4 carbon atoms; and R5 represents a hydrogen atom, a halogen atom or a lower alkyl group and the corresponding imidazo ~4,5-b~ pyridine-~-oxides and isomers thereof and acid addition salts thereof.
According to another feature of the invention, there is also provided a process for the preparation of a compound of the general formula:
Rl R5 - ~ R ~ 2 (I) or an isomer thereof of the general formula: ~.

R5 ~ ~ ~ (Ia) wherein R1 represents an alkylamino, dialkylamino, hydroxy, allyloxy, benzyloxy, alkylthio, alkylsulfinyl or alkylsulfonyl group, or an alkoxy group optionally substituted by a halogen atom or by a hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, piperidino~ morpholino~ thiomorpholino~ 4-alkylpiperazino, 4-phenyl-piperazino, 4-methoxyphenylpiperazino, 4-phenylethylpiperazino, phenyl- :
ethylamino, N-methyl-phenylethylamino or N-methyl-dimethoxy-phenylethyl-amino group;
R2 represents a hydrogen or halogen atom or a hydroxy, methoxy, ethoxy, methyl, methylthio, methylsulfinyl or methylsulfonyl group;
R3 represents a hydrogen atom or a methoxy group; or two of the groups Rl to R3 together represent a methylenedioxy group and the ~ -3-,~, lU4150Z
remaining R1~ R2 or R3 group iS as hereinbefore defined;
R4 represents a hydrogen atom~ an alkyl group optionally substituted by a hydroxy~ phenyl~ dimethoxyphenyl~ dialkylamino~ piperidino~
morpholino~ 4-methylpiperazino or 4-phenylpiperazino groUp~ or a phenyl group optionally substituted by a halogen atom or by one or two methoxy groups~ whereby each of the above mentioned alkyl or alkoxy groups contain from 1 to 4 carbon atoms; and R5 represents a hydrogen atom~ a halogen atom or a lower alkyl group and the corresponding imidazo ~4~5b~pyridine-N-oxides and isomers thereof and pharmaceutically acceptable acid addition salts thereof, which comprises\either: -(a) reacting a compound of the formula:

~H2 , .

5 ~ (II) \Y ~ :

~ , -3a-~ .

104~ S~;~
wherein R5 is as hereinbefore defined and Y represents a group of the formula R4NH-, wherein R4 is as hereinbefore defined, with a compound of the formula X ---~
3 (III) wherein Rl, R2 and R3 are as hereinbefore defined and X represents a carboxyl, thiocarboxyl or dithiocarboxyl group, or functional derivative thereof; or (b) reacting a compound of the formula: -~H2 R ~ 1 (IIa) wherein R5 is as hereinbefore defined and Y represents a halogen atom, with a compound of the formula~

1 ~ R2 (IIIa) 3 ~ -wherein Rl, R2 and R3 are as hereinbefore defined and Xl represents an : .
appropriate -NR4 containing group which is derived from a carboxyl, thi-carboxyl or dithiocarboxyl group; and when a pharmaceutically acceptable acid addition salt is required converting a base of formula I obtained into such a salt.
In general the compounds of general formula I and isomers thereof of general formula Ia possess valuable physiological properties, in particular an activity on the blood pressure and heart force, a positive isotropic effect, an antiulcus activity, a platelet aggregation inhibiting effect and a prolong-ing activity on the bleeding time. --3b-Preferred compounds according to the invention by virtue of their particularly favourable physiological properties are those(wherein Rl, R4 and R5 represent hydrogen atoms and R2 and R3, which may be the same or different, each represents a halogen atom or a methyl, methoxy, ethoxy, alkylthio, alkylsulfinyl, dialkylamino- -alkoxy, morpholinoalkoxy, thiomorpholinoalkoxy, 4-methylpiperazinoalkoxy, 4-phenylpiperazinoalkoxy or alkylsulfinylalkoxy group (wherein each alkyl group contains from 1 to 3 carbon atoms and each alkoxy group :~contains 2 or 3 carbon atoms)and physiologically compatible acid addition salts thereof. Particularly preferred are the following compounds:-

2-(2,4-Dimethoxy-phenyl)-lH-imidazo~4,5-b]pyridine and physiologically compatible acid addition salts thereof, 2-(2-Methoxy-4-methylmercapto-phenyl)-lH-imidazo-[4,5-b] pyridine and physiologically compatible acid addition salts thereof~
2-(2-Methoxy-4-methylsu~lnyl-phenyl)lH-imidazo [4,5-b] pyridine and physiologically compatible acid addition salts thereof, 2-(2-Methoxy-4-methyl-phenyl)-lH-imidazo[4,5-b]
pyridine and physiologically compatible acid addition . ~. . .. . . . .

salts thereof, 2-(2-Methoxy-5-methylmercapto-phenyl)-lH-imidazo [4,5-b] pyridine and physiologically compatible acid addition salts thereof, and 2-(2-Ethoxy-4-methyl-phenyl)-lH-imidazo[4,5-b~
pyridine and physiologically compatible acid addition salts thereof.
The new compounds of general formula I and isomers thereof of general formula Ia as hereinbefore defined may be prepared by either of the following processes, which processes constitute further features of the invention:- :
a) Reaction of a compound of formula ~ 2 5 ~ (II) [wherein R5 is as hereinbefore defined and Y represents a group of formula R4NH-(wherein R4 is as hereinbefore defined)] with a compound of formula -2 (III)

3 ~
(wherein Rl to R3 are as hereinbefore defined and X :.
represents a carboxyl, thiocarboxyl or dithiocarboxyl .
- ; : .

1~)4150Z
group) or a functional derivative thereof, for example an acid halide, anhydride, ester or orthoester; and b) Reaction of a compound of formula R5 ~ 1 (II) (wherein R5 is as hereinbefore defined and Y represents a halogen-atom) with a compound of formula Rl 2 (III) -~wherein Rl to R3 are as hereinbefore defined and X
represents an appropriate -NR4 containing group (wherein R4 is as hereinbefore defined) which is derived from a carboxyl, thicarboxyl or dithiocarboxyl group, for example a nitrile, amide, amido ester, imido thioester, imido ~ .
halide or amidine group], In each case the reaction is preferably carried out in the presence of a solvent, suitable solvents including for example benzene, pyridine, glycol, toluene, acetone, diethylene glycol and triethylamine. However the reaction may also be performed in the absence of a solvent 104~S02 The reaction temperature used is determined by the reactivity of the group X in the compound of formula III used but generally the reaction is effected at temperatures-from -20 to 250C. If desired the re-action may be effected in the presence of an acidbinding agent, such as pyridine or triethylamine, or in the presence of a catalytic quantity of an acid, such as p-toluenesulfonic acid, or in the presence of a dehydrating agent,such as phosphorus oxychloride or thionyl chloride.
If for example a compound of formula III wherein X
represents a carboxyl or amide group is used the reaction ~ -if conveniently carried out in the presence of phosphorus oxychloride or thionyl chloride, if desired in the presence of a tertiary organic base such as pyridine or triethyl-amine, preferably at temperatures from -20C up to the boiling point of the solvent used, e.g. at 120C.
If for example a compound of formula III wherein X
represents a nitrile group is used, the reaction is conven~ently performed in the presence of a catalytic quantity of an acid, such as p-toluenesulfonic acid, preferably at temperatures from 120 to 180C, e.g. at 160C, optionally in the presence of a solvent. ~-~ : ' : ' . ~ . -'' :: ., ' : .

i~)4150Z
If for example a compound of formula III wherein X
represents a thioamide group is used, the reaction is conveniently effected in the presence of a solvent, such as glycol, and preferably at temperatures from 100 to 150C, e.g at 130C.
If a compound of formula II wherein Y represents a halogen atom, e.g. a chlorine atom is used, the reaction is preferably carried out via the corresponding amidine, which is cyclized at elevated temperatures, e.g. at temperatures from 100 to 200C, optionally without previous isolation.
The compounds of general formula I and isomers thereof of general formula Ia containing a reactive halogen atom obtained according to the processes of the present invention may, if desired, be subsequently converted into the corresponding amino compounds with amines, and/or compounds of general formula I and isomers thereof of general formula Ia containing reactive hydrogen atoms, may if desired be subsequently alkylated by means of an alkylating agent in the presence of a base.
In addition a compound of formula I or an isomer thereof of formula Ia may if desired be converted into the corresponding N-oxide, S-oxide or S,S-oxide compound by means of an oxidizing agent. Finally a compound of fo~mula I or an isomer thereof of formula Ia may if desired be converted into an acid addition salt thereof, S preferably into a physiologically compatible acid addition salt. Suitable acids include for example hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, tartaric acid, maleic acid and fumaric acid.
m e starting compounds used for the processes according to the invention are known from the literature, or they may be prepared according to known processes (see Examples).
As already mentioned above, the new compounds of general fonmula I and isomers thereof of general fonmula Ia in general show valuable pharmacological properties, those which have been tested showing especially an activity on the blood-pressure, a positive inotropic activity, an ~ - . . . ..
- antiulcus activity, a platlet aggregation inhibiting effect ~ -and a prolonging activity on the bleeding time.
m e following compounds have been tested with respect -to certain of their biological activities: ~-A - 2-(2,4-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride, _ 9 _ -~. ' :
- . : ,~ - -.

1043 S0;~
B = 2-[2-(2-Methylsulfinyl-ethoxy)-4-methoxy-phenyl]-lH-imidazo-[4,5-b]pyridine hydrochloride, C = 2-(2-Methoxy-4-methylmercapto-phenyl)-lH-imidazo - -[4,5-b]pyridine hydrochloride D = 2-(2-Methoxy-4-methylsulfinyl-phenyl)-lH-imidazo [4,5-b]pyridine hydrochloride, E = 2-(2-Methoxy-5-methylmercapto-phenyl)-lH-imidazo [4,5-b]pyridine hyrochloride F - 2-(2-Methoxy-4-methyl-phenyl)-lH-imidazo~4,5-b]
pyridine hydrochloride G = 2-(2-Ethoxy-4-methoxy-phenyl)-lH-imidazo~4,5-b]
pyridine hydrochloride, H = 2-(2-Ethoxy-4-methyl-phenyl)-lH-imidazo[4,5-b]
pyridine hydrochloride, I = 2-(2-Methoxy-4-chloro-phenyl)-lH-imidazo[4,5-b]
pyridine hydrochloride and J ~ 2-[2-(2-Methylsulfinyl-ethoxy)-4-methylmercapto-phenyl]-lH-imidazo~4,5-b]pyridine hydrochloride 1. Positive inotropic activity in the isolated auricle of the guinea-PiR:
Isolated auricles of guinea-pigs were put into an organ bath of 100 ml. The bath has been filled with a tyrode solution at a temperature of 30C. The tyrode solution was infused with carbogen (95% of 2 and 5% of C02). The spontaneous contractions of the auricles were registered isometrically with a Statham-Force-transducer on a Grass-polygraph. The auricles were charged with 1 g. Aftersufficient equilibrating time, the substances in question were added to the organ bath. The concentration of the substance in the bath was 1 x 10 5 g/ml in each case.
5 auricles were used for each solution.
The following Table gives the results:
Table I

Substance Increase of the contraction- ;-amplitude in %
, A 57.0 B 17.5 C 10.3 E 40.9 F 50.2 G 33.9 H 42.9 I 21.4 J 11.4 ~ .

' ~ ' - ~ ' ., .' '' . . - , ' ., . . ., :
- ~ . .
:
,~ - . - . . .

1~4~502 2. Circulation exPerimentS on the narcotized cat:
Cat were narcotized with 30 mg/kg of pentobarbital-sodium i.v. A plastic catheter was introduced into the arteria femoralis and into the left ventricle of the heart a steel catheter was introduced from the arteria carotis. With Statham-pressure-transducers of the type P23 AA and P23 Dc, the arterial blood-pressure and the pressure in the left ventricle was registered continuously.
From the ventricle-pressure-curve, the contractility parameters dp/dtmaX and VcE were continuously determined by means of an analogous computer. The heart frequency was ascertained from the ventricle-pressure-curve using a tachograph. In addition, the EKG was registered in the II derivation.
All registrations were effected on a Brush-direct-writer. The substances were injected over a vena cannula into the vena femoralis. At least three cats were used for the test on each substance.
The following Table gives the results:

+~ ~041S02 O Cl ~ 11~ N CJ~ O O In O O u~ O O ~J N 01~
~ . ++ ' ' ++ ++ ' I ++ I
~ 0 ~+~)~
+~ ~ h ;-~g 0~ ~ . .V, . .,' .) 0~ O-- ~ ~U~ ~ ~U~ ~ ~ U~U~ ~0 8 N ~ ~ N ;t U~ ~ U
+-'8++ ++ ++ ++ ++ ++ ++ ++ ++ ++ -:~
~ ~1 $~, :: ~.

~--IU~ ~ O O ~ O O ~ O U~ O U~ O ~ O ~ U~ U~ O U~ ~
~
~o I I ++ ++ I ++ ++ + ++ 1 1. ++ ~. . ' .

~ . . :' ~.YU~O U~O U~O U~O U~O U~O U~O U~O U~O U~O
a ~-i " '; ' " ~ ' ' ' " '~

H¦ ~ ~ ~~,~ ~., 14 ~ ~ , ' , ~1 ~

' ' .' ~ ~ '. .

1041S()2 None of the compounds showed any toxic side effects using the doses applied.
According to yet a further feature of the present invention there are provided pharmaceutical compositions comprisingas active ingredient at least one compound of formula I or isomer thereof of formula Ia or physologi-cally compatible acid addition salt thereof in association with a pharmaceutical carrier or excipient.
The compositions may for example be presented in a form suitable for oral, rectal or parenteral administration.
Thus for example compositions for oral administration may be solid or liquid and may take the form of tablets, coated tablets or drops, such compositions comprising carriers or excipients conventionally used in the pharmaceutical art.
For parenteral administration the carrier may be a parenterally acceptable liquid, such as sterile water or a parenterally acceptable oil, e.g. arachis oil, contained in ampoules. For rectal administration compositions may take the form of suppositories, the carrier comprising a suppository base.
Advantageously the compositions may be formulated as dosage units. Each dosage unit preferably contains from 35 to 200 mg, preferably from 50 to 100 mg, of active ingredient.

1()41SO~
The following Examples serve to illustrate the preparation of compounds according to the invention and of pharmaceutical compositions containing the same.

.

Example 1 2-(2,4-Dimethoxyphenvl)-lH-imidazo[4,5-b]pvridine hydrochloride 54.5 g of 2,3-diaminopyridine and 91.1 g of 2,4-dimethoxybenzoic acid were finely pulverized and added in small amounts to 1500 ml of phosphorus oxychloride whilst stirring. Afterwards, the mixture was refluxed for 2 hours, and the phosphorus oxychloride was distilled off in vacuo.
The residue was triturated with 2000 ml of 2N hydrochloric acid and the solid product obtained was suction filtered and recrystallized from water.
Yield: 121 g (85% of theory), m.p.: 238C
Example 2 2-(2,4-Dimethoxvphenyl)-lH-imidazo[4,5-b]pvridine hvdrochloride 360 mg of 2,4-dimethoxybenzoic acid were dissolved in 2 ml of pyridine and a solution of 220 mg of 2,3-diaminopyridine in 2 ml of pyridine was added, where-upon the corresponding salt precipitated out. Whilst ., .
,;

lOglSOZ ., stirring and ice-cooling, 0.38 ml of phosphorus oxychloride were added dropwise and the mixture was stirr-ed for a further hour at 0C and 1 hour at room temperature. Subsequently the excess of pyridine was removed in vacuo and the residue was dissolved by adding dilute hydrochloric acid. The mixture was neutralized with sodium hydroxide solution and extracted with ethyl acetate. The ethyl acetate layer was evaporated, the residue was treated with a small quantity of 2N hydrochloric acid, and the precipitate was suction filtered and recry-stallized from water.
M.p.: 238 to 239C.
Example 3 2-(2,4-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride Prepared analogously to Example 2 from 2,3-diaminopyridine, 2,4-dimethoxybenzoic acid and thionyl chloride.
M.p.: 238 to 239C.

' ' - '''~ ~ ' ', , :

104~5UZ
Example 4 2-(2,4-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride 900 mg of 2,4-dimethoxy-benzoic acid were converted into the acid chloride by heating in a mixture of 3 ml of benzene and 2 ml of thionyl chloride. Subsequently, the mixture was evaporated in vacuo and the residue obtained was taken up in 5 ml of benzene. This solution was dropped into a solution of 550 mg of 2,3-diamino-pyridine in 5 ml of pyridine whilst stirring. Afterwards, the mixture was heated for a short time at 60C, then cooled to room temperature, and 0.9 ml of phosphorus oxychloride were added dropwise. After the mixture had been stirred for a further 3 hours at room temperature, 2N hydrochloric acid was added. The mixture was then neutrallized and extracted with ethyl acetate. The ethyl acetate layers were evaporated and a small quantity of 2N hydrochloric acid was added to the residue. The crystals which precipitated were suction filtered and recrystallized - ~. . : . , -10415t~;~
from water.
M.p.: 237 to 238C.

Example 5 2-(2,4-Dimethoxv-phenvl)-lH-imidazo[4,5-b~pyridine hydrochloride a) 2-Amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hvdrochloride 530 mg of 2,4-dimethoxybenzoic acid were converted into the acid chloride analogously to Example 4 and this acid chloride was dissolved in 1 ml of benzene. The solution obtained was added dropwise to a mixture of 440 mg of 2,3-diamino-pyridine, 3 ml of pyridine and 2 ml of triethylamine. After the whole mixture had been stirred for a further 2 hours at room temperature, water was added, -the mixture was neutralized with concentrated hydrochloric acid and extracted with ethyl acetate. The ethyl acetate was removed, the residue was treated with dilute hydro-chloric acid, the precipitated crystals were suction filtered and recrystallized from ethanol.
M.p.: 172 to 174C.

; , .- '' :.

. ~

~ 041502 b) 2,4-Dimethoxy-phenvl)-lH-imidazo[4,5-b]pyridine hvdrochloride 155 mg of 2-amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hydrochloride were dissolved in 2 ml of pyridine.
0.2 ml of phosphorus oxychloride were dropped in whilst stirring at room temperature. After 2 hours the mixture was poured into water and worked up analogously to Example 4.
M.p.: 237 to 238C.
Example 6 2-(2,4-Dimethoxy-phenyl)-lH-imidazo~4,5-b]Pvridine hydrochloride 155 mg of 2-amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hydrochloride were heated for 5 minutes at 200 -210C. The mixture was treated with a small quantity of 2N hydrochloric acid, and the precipitate was filtered and recrystallized from water.
M.p.: 237 to 238C.

.
- - : . . ~ .': ' ' :

':

~041St~ ~
Example 7 2-(2 ,4-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride 155 mg of 2-amino-3-(2,4-dimethoxybenzoyl-amino)-pyridine hydrochloride were refluxed for 30 minutes in 2 ml of glycol. The mixture was then diluted with water, neutralized, extracted with ethyl acetate and processed analogously to Example 4.
M.p.: 238 to 239C.
Example 8 2-(2,4-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride 5.45 g of 2,3-diaminopyridine were added in small amounts to 150 ml of phosphorus oxychloride whilst stirring and 9.81 g of methyl 2,4-dimethoxybenzoate were also added dropwise. The mixture was then heated at 120C, After two hours the excess of phosphorus oxychloride was evaporated in vacuo, the residue was digested with 2N
hydrochloric acid and the solid product obtained was suction filtered and recrystallized from water.
M.p.: 238 to 239C.

- , ~
, ' 1~)41SOZ
Example 9 2-(2,4-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride 0.5 ml of morpholine were added whilst stirring to 470 mg of 2,4-dimethoxybenzoyl chloride in 6 ml of toluene.
After 20 minutes the toluene was ev~porated, the residue was treated with dilute hydrochloric acid and this mixture was extracted with ethyl acetate. After washing the ethyl acetate layer with sodium bicarbonate solution and evaporating off the solvent, crude 2,4-dimethoxybenzoyl-morpholine was obtained as oil. This oil was dissolved in S ml of pyridine, 250 mg of 2,3-diaminopyridine was added and finally 1 ml of phosphorus oxychloride was added dropwise whilst stirring and ice-cooling. After stirring for 5 hours at 0C, ice-water was added, the mixture was made alkaline with concentrated ammonia, heated for a short time on the steam bath and extracted with ethyl acetate. The ethyl acetate was removed, and the residue obtained was treated with 2N hydrochloric acid, suction ', ; . .

~ 04~SOZ
filtered and recrystallized from water.
M.p.: 238C.
Example 10 2-(2,4-Dimethoxyphenyl)-lH-imidazo[4,5-b]pyridine hvdrochloride 300 mg of 2,4-dimethoxybenzoyl-(4-chloro-anilide) and 110 mg of 2,3-diaminopyridine were mixed and added in small amounts to 3 ml of phosphorus oxychloride whilst stirring. Afterwards the mixture was refluxed for 8 hous.Then the phosphorus oxychloride was removed in vacuo, the residue was triturated with 2N hydrochloric acid and the solid product obtained was suction filtered and recrystal-lized from water.
M.p.: 237 to 238C.
Example 11 2-(2,4-Dimethoxy-Phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride 600 mg of 2,4-dimethoxybenzoyl-(4-chloro-anilide) in a mixture of 5 ml of benzene and 2 ml of thionyl ' - ' ' . ~ . :
- - ,.

1041~0Z
chloride were refluxed for 3 hours. After the mixture had been evaporated the crude 2,4-dimethyl-N-(4-chlorophenyl~-benzimidic acid chloride was obtained as an oil. This oil was dissolved in 9 ml of toluene and the solution was added to a solution of 200 mg of 2,3-di-aminopyridine in 10 ml of isopropanol. The mixture was heated for 10 minutes at 70C. The 2,4-dimethoxy-benzoic acid-N-(4-chlorophenyl)-N'-(2-amino-3-pyridyl)-amidine hydrochloride which formed was not isolated but was dissolved in 20 ml of glycol after removing the iso-propanol in vacuo. The glycol solution was refluxed for 10 minutes. Subsequently water was added, the mixture was made alkaline with concentrated ammonia, extracted with ethyl acetate and worked up as described in Example 4.
M.p.: 237 ~o 238C.
Example 12 2-(2,4-Dimethoxy-phenyl)-lH-imidazo~4,5-b~pyridine hydro-chloride 100 mg of 2,3-diaminopyridine, 200 mg of 2,4-dimethoxybenzonitrile and 400 mg of p-toluenesulfonic acid ;

'~

. . - ~

~ 041S0;~
monohydrate were mixed together and heated for 3~ hours at 160C The product was triturated with dilute ammonia and ethyl acetate until the whole product had dissolved. The aqueous layer wQs extracted with ethyl acetate. After some time, when the combined ethyl acetate layers had been extracted with a small quantity of 2N hydrochloric acid, the product crystallized out from the aqueous phase.
M.p.: 237 to 238C.
E~ample 13 2-(3,4,5-TrimethoxyPhenyl)-lH-imidazo[4,5-b]p~ridine 3.4 g of p-toluenesulfonic acid monohydrate and 15 ml of benzene were heated at 120C until all the benzene had evaporated. Subsequently 1.1 g of 2,3-diaminopyridine and 2 g of 3,4,5-trimethoxybenzoyl nitrile were added and the mixture was heated for 2 hours at 150C. After cooling, water was added, the mixture was extracted with ethyl acetate, the ethyl acetate layers were washed with dilute sodium hydroxide solution, evaporated and the residue was recrystallized from isopropanol/petroleum .

ether. 1041S02 M.p,: 226C.
Example 14 2-(3,4,5-Trimethoxy-phenyl)-lH-imidazo~4.5-b3pyridine A mixture of 4.2 g of 3,4,5-trimethoxybenzoic acid and 2.2 g of 2,3-diaminopyridine was refluxed for 2 hours in 40 ml of phosphorus oxychloride. Subsequently the excess of phosphorus oxychloride was distilled off, water was added to the residue and the precipitated solid product was suction filtered. The product was dissolved in hot water, made alkaline with concentrated ammonia, and the precipitate was suction filtered and recrystallized ~ --from a small qusntity of isopropanol.
M.p.: 225 to 226C. ~ -Example 15 2-(2,5-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pvridine a) 2,5-Dimethoxy-thiobenzoyl morPholide A mixture of 10 g of 2,5-dimethoxybenzaldehyde, 10 g of morpholine and 4 g of sulfur was heated st 130C for 3~ hours and subsequently dissolved in 300 ml of hot -~
ethanol. The product which precipitated out on cooling, , - : ' ' ""' - : ' ~' . -' ' - . - ~ , ~ 04~502 was recrystallized from ethanol.
M.p,: 127C.
b) S-Methyl-2,5-dimethoxy-thiobenzoyl morpholide iodide 6 g of 2,5-dimethoxy-thiobenzoyl morpholide, 6.5 g of methyl iodide and 30 ml of acetone were refluxed for ~ hours. Subse~uently the precipitated solid product was suction filtered and washed with ether. The product obtained was not purified further.
c? 2-(2,5-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine 2 g of S-methyl-2,5-dimethoxy-thiobenzoyl morpholide iodide and 1.1 g of 2,3-diaminopyridine were heated in 30 ml of glycol for 40 minutes at 130C. Subsequently the mixture was poured on ice-water, suction filtered and recrystallized from ethanol/water.
M.p.: 23S~.
Example 16 2-(4-HYdroxy-phenYl)-lH-imidazo[4,5-b]p~ridine a) 4-HYdroxy-thiobenzoYl morpholide Prepared analogously to Example 15a from 12.2 g of ~' .....
.~ ,.. .

4-hydroxy-benzaldehyde, 16 g of morpholine and 3,2 g of sulfur.
M.p.: 205C
~) S-Methyl-4-hydroxy-thiobenzyl morpholide iodide Prepared analogously to Example 15b from 14.4 g of 4-hydroxy-thiobenzyl morpholide and 2.1 g of methyl iodide in 100 ml of acetone.
M.p.: 181C.
c? 2-(4-Hydroxy-phenyl~-lH-imidazo[4,5-b]pyridine 1.84 g of S-methyl-4-hydroxy-thiobenzyl morpholide iodide were heated for 20 minutes at 130C with 1.1 g of 2,3-diaminopyridine in 30 ml of glycol. The product precipitated whilst cooling and was dissolved in sodium hydroxide solution and reprecipitated with an acid.
Analysis: Calculated: 65.87% C 5~13% H 16.46% N
Found: 65.90% C 5.16% H 16.47% N

- ~,, ~.. ..

. .

-104~SOZ
Example 17 2-[4-Methoxy-2-(3-chloropropoxy)-phenyl]-lH-imidazo [4,5-b~pyridine hydrochloride a) 4-Methox~-2-(3-chloro-propoxy)-benzoyl morpholide -21.9 g of 2-hydroxy-4-methoxy-benzoyl morpholide were dissolved in 200 ml of dimethylformamide and 11.2 g of potassium tert.-butoxide were added. After the whole product had dissolved, 50 g of 1-chloro-3-bromopropane were added and the mixture was heated for 2 hours at 130C.
Subsequently the mixture was evaporated in vacuo, the residue was dissolved in ethyl acetate, and the solution was washed with sodium hydroxide solution and water and evaporated.
b) 2-[4-Methoxy-2-(3-chloropropoxy)-phenyl]-lH-imidazo [4,5-b]Pvridine hydrochloride 20 g of 4-methoxy-2-(3-chloro-propoxy)-benzoyl -morpholide, 7 g of 2,3-diamino-pyridine and 170 ml of phosphorus oxychloride were refluxed for 2 hours. After lO~lSOZ
evaporation of the phosphorus oxychloride, the residue was mixed with water, neutralized with sodium hydroxide solution and extracted with ethyl acetate. The hydrochloride was precipitated with ethereal hydrochloric acid.
M.p.: 198C (decomp).
Example 18 2-[4-Methoxy-2-~2-chloroethoxy)-phenyl]-lH-imidazo [4,5-b]pyridine hydrochloride a) 4-Methoxy-2-(2-hydroxy-ethoxy)-benzoyl morpholide 23.7 g of 2-hydroxy-4-methoxy-benzoyl morpholide, 33.6 g of potassium tert.-butoxide and 37.4 g of ethylene bromohydrin were heated in 100 ml of dimethylformamide for 6 hours at 120C. After evaporation in vacuo, the residue was dissolved in chloroform and the solution was washed with sodium hydroxide solution and water and evaporated.
b) 2-[4-Methoxy-2-(2-chloroethoxy)-phenyl]-lH-imidazo L ,5-b]pyridine hvdrochloride 2.8 g of 4-methoxy-2-(2-hydroxy-ethoxy)-benzoyl morpholide, 1.1 g of 2,3-diaminopyridine and 20 ml of phosphorus oxychloride were refluxed for 2 hours. After ' :

.
, .

.

- ,. . . . .

1041S(~Z
evaporation w~ter was added, the mixture was neutralized, extracted with ethyl acetate and the hydrochloride was precipitated with ethereal hydrochloric acid from the organic layer.
M.p.: 110C (decomp.).
ExamPle 19 2-[4-Methoxy-2-(3-chloropropoxy)-phenyl]-lH-imidazo [4,5-b]pyridine hydrochloride a) 4-Methoxy-2-(3-chloropropoxy)-benzoyl anilide -2.5 g of 2-hydroxy-4-methoxy-benzoyl anilide, 5 ml of l-chloro-3-bromopropane, 1.12 g of potassium tert.-butoxide and 20 ml of dimethylformamide were heated for 2 hours at 130C. Subsequently the mixture was evaporated in vacuo, water was added and the mixture was suction filtered.
M.p.: 87 to 90C.
b) 2-[4-Methoxy-2-(3-chloropropoxy)-phenyl~-lH-imidazo [4,5-b]pyridine hydrochloride Prepared analogously to Example 17b from 4-methoxy-2-(3-chloropropoxy)-benzoyl anilide and 2,3-diamino-pyridine.
M.p.: 198C.
Example 20 2-[4-Methoxy-2-(3-morpholino-propoxy)-phenyl]-lH-imidazo [4,5-b]-pyridine 0.5 g of 2-[4-methoxy-2-(3-chloroproxy)-phenyl]-lH-imidazo[4,5-b]-pyridine hydrochloride were refluxed for 4~ hours in 5 ml of morpholine. Water was then added, the precipitate was suction filtered and recrystallized from water.
M.p.: 108 to 110C.
Example 21 2-[4-Methoxy-2-(2-(4-phenyl-1-piperazinyl)-ethoxy)-phenyl~-lH-imidazo[4,5-b]pvridine Prepared from 1.7 g of 2-[4-methoxy-2-(2-chloro-ethoxy)-phenyl]-lH-imidazo~4,5-b]pyridine and 3.2 g of 1-phenylpiperazine by boiling for 8 hours in ethanol.
M.p.: 164 to 165~C (from isopropanol) ~ ~- . .. .

1~41502 Example 22 2-[4-Methoxy-2-(3-dimethylamino-propoxy)-phenyl]-lH-imidazo[4,5-b~pyridine hydrochloride 1.8 g of 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-lH-imidazo[4,5-b]-pyridine hydrochloride and 20 ml of saturated dimethylamine solution in ethanoI were heated for 8 hours in a closed vessel at 100C. Subsequently the mixture was evaporated in vacuo and recrystallized from isopropanol.
M.p.: 209 - 210C
Example 23 2-[4-Methoxy-2-(3-dimethylamino-propoxy)-phenyl]-lH-imidazo-[4,5-b]pyridine dihydrochloride 1.64 g of 4-methoxy-2-(3-dimethylamino-propoxy)-thiobenzoyl morpholide were dissolved in a mixture of 17 ml of glacial acetic acid and 3 ml of acetic anhydride. 1 ml of dimethyl sulfate was added and the mixture was heated on the steam bath for 1 hour. Subsequently, the mixture was evaporated in vacuo. The crude S-methyl-4-methoxy-2-(3-dimethylamino-propoxy)-thiobenzoyl morpholide methyl .. .. . -, ,.

sulfate obtained was dissolved in 13 ml of glycol 0.7 g of 2,3-diaminopyridine was added and the mixture was heated for 2 hours at 160C. Subsequently, the mixture was poured into 50 ml of water, 5 ml of concentrated ammonia were added and the mixture was extracted with ethyl acetate. The ethyl acetate layers were evaporated, the residue was dissolved in ethanol, ethereal hydrochloric ~acid was added and it was again evaporated. The residue crystallized after trituration with toluene and a small quantity of ethanol. The product was suction filtered and recrystallized from isopropanol.
M.p.: of the dihydrochloride hydrate: 228 to 235C
(decomp.).
Example 24 2-(2,4-Dimethoxy-phenyl)-3-methyl-3H-imidazo[4,5-b]

pyridine _ 800 mg of 2,4-dimethoxybenzoyl methylamide were refluxed for 3 hours with 500 mg of 2-chloro-3-aminopyridine --in 10 ml of phosphorus oxychloride. Subsequently, the ~, : . . .

1041S0;~
mixture was poured into water, neutralized with concentrated ammonia and extracted with ethyl acetate.
After evaporation, the crude N-methyl-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine obtained was dissolved in 10 ml of 10% glycolic sodium hydroxide solution and heated for 4 hours at 180 to 190C. The mixture was poured into water and extracted with ethyl acetate. The compound obtained was purified by column chromatography (silica gel, eluent CHC13: MeOH = 19 : 1).
M.p. of the hydrochloride: 196 to 197C
Example 25 2-(2,4-Dimethoxy-phenyl)-3-(4-chlorophenyl~-lH-imidazo [4,5-b] pyridine 3 g of 2,4-dimethoxy-benzoyl (4-chloroanilide) and ;
1.3 g of 2-chloro-3-aminopyridine were refluxed for 2 hours in 16 ml of phosphorus oxychloride. Subsequently the mixture was poured into water, neutralized with concentrated ammonia and extracted with ethyl acetate. The ethyl acetate layer was extracted with 3N hydrochloric acid.

After neutralization of the aqueous layer, the mixture was again extracted with ethyl acetate. The solid ¦~
product remaining after evaporation of the organic layer was recrystallized from methanol.
M.p.: 176 to 178C.
Example 26 2-(2,4-Dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine ~y~ochloride 2.2 g of 2,3-diaminopyridine, 6.8 g of the imide chloride of 2,4-dimethoxy-benzoyl morpholide and 12 ml of triethylamine were heated for ~ hour at 120C in 10 ml of diethyleneglycol dimethyl ether. After cooling, water was added, the reaction mixture was extracted with chloro-form and the chloroform layer was extracted with 2N
sodium hydroxide solution. The yellow hydrochloride -which precipitated from the acidic solution was converted into the base with ammonia, and was purified by column chromatography. The hydrochloride was again precipitated from acetone with ethereal hydrochloric acid.
M.p.: 237 to 238C.

. . . :
.. . .
' ' . ~ ~ ' lO~lS~Z
Example 27 2-(2~4-Dimethoxy~phenyl)-lH-imidazo[4,5-b~pyridine hydrochloride Prepared from 1. 1 g of 2,3-diaminopyridine and 3.5 of 2,4-dimethoxybenzoyl anhydride by hea~ing for 5 hours at 180C The further processing was carried out as in Example 26.
M.p.: 236 to 238C.

rA~

~0415~Z
Example 28 2-(2-Methoxyphenyl)-lH-imidazo[4,5-b]pyridine-hydrochloride a) 2-Methoxy-thio-benzoic acid-morpholide 34 g of 2-methoxybenzaldehyde, 16 g of sulfur and 32,6 g of morpholine were heated for 3 hours up to 120C. The reaction mixture thus obtained was taken up in ethanol, filtered, cooled and the precipitated yellow crystals were suction filtered.

.. . . ..
Yield: 54,1 g (91 % of theory), m.p.: 80 to 82C. ~ ~ -b) 2-Methoxy-thio-benzoic acid-morPholide-methoidide 47,4 g of 2-methoxy-benzoic acid-thiomorpholide were refluxed for 1 hour in 150 ml of acetone with 25 ml of methyl iodide and the precipitated yellow crystals were suction filtered after cooling.
Yield: 64,4 g (85 % of theory), m.p.: 162 to 164C.
c) 2-(2-Methoxyphenyl)-lH-imidazo~4,5-b3pyridine ~ -19 g of 2-methoxy-thio-benzoic acid-morpholide-methoidide and 8,7 g of 2,3-diaminopyridine were heated for 3 hours at 120C
in 70 ml of glycol. After cooling, water was added, the mix-ture was made alkaline with ammonia and extracted with chloro-form. The organic layer was washed with water and subsequent-ly 2n hydrochloric acid was added. The precipitated product was suction filtered, the base was set free with ammonia~
taken up in chloroform and purified over a silica gel column.
The colorless hydrochloride was obtained from acetone by addition of ethereal hydrochloric acid.
M.p.: 233 to 234C.

. . . :

.. . - ~ , ~.~

amplc ~9 2-(2-~lethoxyphctlyl)-3-methyl-3H-i-nli-dazo/4~5 ~ pyridin~ h~drocllloride Prepared analogous to example 28 from 2-methylamino-3-amino-pyridine and 2-methoxy-thio-benzoic acid-morpholide-methoiodide.
M.p.: 208 to 210 C.

Example 30 2-~2-(2-Methoxy-ethoxy)-phellyl7-lH-imidazo~ ,5-b7pyridine-hydro--chloride Prepared analogous to example 28 from 2-(2-methoxy-ethoxy)-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 170 to 172 C.

Example 31 2-(4-Methoxyphenyl)-lH-imidazo/4,5-b7pyridine-hydrochloride prepared analogous to example 28 from 4~methoxy-thio-benzoic acid-morpholide-methoiodide (m.p.: 142 to 144 C) and 2,3-diamino-pyridine.
M.p.: 243 to 245 C.

Example 32 2-(3-~lethoxy-4-hydroxy-phenyl)-111-imidazo~4~5-b7pyridine-hydro-chloride Prepared analogous to example 28 from 3-methoxy-4-hydroxy-thio-benzoic acid-morpholide-methoiodide (m.p.: 178 to 180 C) and 2,3-diaminopyridine.
M.p.: 251 to 254 C.

;r~

1041S0;~
Examplc 33 2~(2~3-dimctho~y-pheny~ H-imidazo/4~s-b7pyridine-hydroch]oridc prepared analogous to example 28 from 2,3-dimethoxy-thio-benzoic acid-morpholide-methoiodide (m.p.: 138 to 140 C) and 2,3-diamino-pyridine .M.p.: 270 to 272 C.

Example 34 2-(2-Hydroxy-4-methoxy-phenyl)-~-imidazor4,5,-~ pyridine-hydro-chloride .
prepared analogous to example 28 from 2-hydroxy-4-methoxy-thio-benzoic acid-morpholide-methoiodide (m.p.: 180 to 181C) and 2,3-diPm;r opyridine.
M.p.: 190 to 192 C (decomp.).

N.p. of the free base: 292 to 293 C.
. .
le 35 2-(2,4-Dimethoxy-phenyl)-lH-im_dazo/4,5-b7pyridine-hydrochloride Prepared analogo~s to example 28 from 2,4-dimethoxy-thio-benzoic acid-morpholide-methoiodide (m.p.: 138 to 140 C (decomp.)) and 2,3-diaminopyridine.
M.p.: 238 C (from methanol) r~

.. ........ .

iO415U;~
E~ample ~6 2-(2~4-l~imethoxy-phellyl)-6-metllyl-lH-imidazo/4,5-b/pyridine-hydro-chloride Prepared allalogous to example 35 from 2,3-diamino-5-methyl-pyridine and 2~4-dimethoxy-thio-benzoic acid-morpholide-methoiodide.
M.p.: 260 to 261 C.

Example 37 2-(2,4-Dimethoxy-phenyl)-7-methyl-lH-imidazo~ ,5-b7pyridine-hydro-chloride Prepared analogous to example 35 from 2,3-diamino-4-methyl-pyridine 2nd 2,4-dime~hoxy-thio-benzoic acid-morpholide-methoiodide.
.p.: 230 to 23]. C.

Example 38 2-(2~4-Dimethoxy-phenyl)-5-methyl-lH-imidazo~ ,5-b7pyridire-hydro-chlori.de Prepared analogous to example 35 from 2,3-diamino-6-methyl-pyridine and 2~4-dimethoxj-th--o-benzoic acid-morpholide-methoiodide.
M.p.: 245 to 246 C.

Example 39 2-(2,4-Dimethoxy-ph~nyl)-6-chloro-lH-imi.dazo~4~5-b7pyridine-hydro-chloride _ Prepared analogous to example 35 from 2,3-diamino-5-chloro-pyridine ,~ .

.

,. . . . , , - - ; . . . : . .

104;1S(~Z
and 2,4-dimethox~-tllio-bcnzoic acid-morpholitle-methoiodidc.
M.p.: 253 to 255 C.

Example 40 2-(2-Ethoxy-4-methoxy-phenyl)-lH-imidazo/4~5-b7pyridine-hydrochloride Prepared analogous to example 28 from 2-ethoxy-4-methoxy-thio-benzoic -acid-morpholide-methoiodide (m.p.: 152 to 154C) and 2,3-diamino-pyridine.
M.p.: 228 to 230 C.

Example 41 2-(2-Methoxy-4-ethoxy-phenyl)-lH-imidazo ~ ,5-b/pyridine-hydro-chloride Prepared analogous to example 28 from 2-methoxy-4-ethoxy-thio-benzoic acid-morpholide-methoiodide and 2~3-diaminopyridine.
M.p.: 224 to 225 C (from methanol) Example 42 2-(2~4-Diethoxy-phenyl)-lH-imidazo/4,5-b7pyridine-hydrochloride Prepared analogous to example 28 from 2,4-diethoxy-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 224 to 226 C.

. . . ~ . .
r,~
'' ~04~SI~
Example 43 2-/2-(2-Hydroxy-ethoxy)-4-methoxy-pheny~7~ imidazo/4,5-b/-pyridine-hydroc2~.oride -prepared analogous to example 28 from 2-(2-hydroxy-ethoxy)-4-methoxy-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 237 to 239 C.

Example 44 2- ~ -(3-Hydroxy-propoxy)-4-methoxy-phenyl/-lH-imidazo~4,5-b/-pyridine-hydrochloride prepared analogous to example 28 from 2-l3-hydroxy-propoxy)-4-methoxy-thio-benzoic acid-morpholide-methoiodide and 2,3-diamino-pyridine.
N.p.: 170 C (whilst sirtering) .
Example 45 2-/2-(2-Methoxy-ethoxy)-4-methoxy-pheny ~ -lH-imidazo/4,5-b7-pyridine~hydrochloride Prepared analogous to example 28 from 2-(2-methoxy-cthoxy)-4-methoxy-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 191 to 193 C.

Example 46 2-~ -Methoxy-4-(2-methylmercapto-ethoxy)-phenyl7-lH-imidazo-/4,5-b7pyridine-hydrochloride ,~,~ , .
- - - , .. , . . .: : :

. . . ~ .
,: . ~. ~ - : - , 1041S0;~
a) 4-(2-Methylmercapto-ethoxy)-2-hydroxy-benzaldehyde 12 g of 2,4-dihydroxy-benzaldehyde and 9,6 g of potassium-tert.-butoxide were dissolved in 50 ml of ethyleneglycolmonomethylether, 9,6 g of methylmercaptoethylchloride were added and the reaction mixture was stirred for 8 hours at 80C (bath temperature). After removing the solvent, the residue was taken up in diluted sodium hydroxide solution, the mixture was extracted twice with chloro-form, the aqueous alkaline solution was separated, acidified and extracted with chloroform. The organic phase was dried and eva-porated. The residue was purified by column chromatography (silica gel). The oil thus obtained was processed directly.
b) 4-(2-Methylmercapto-ethoxy)-2-methoxy-benzaldehyde ~
9,? g of 4-~2-methylmercapto-ethoxy)-2-hydroxy-benzaldehyde ~ -were dissolved in ethanol together with 6,7 g of potassium-tert.-butoxide, 4,3 ml of dimethyl-sulfate were added and the mixture was refluxed for 3 hours. Then again 1 ml of dimethyl-sulfate was added and the mixture was heated for a further hour. After the ethanol had been distilled off, the residue was taken up in water/chloroform and 2n sodium hydroxide solution was added. The chloroform layer was separated, washed with water, dried and evaporated.
M.p.: 99 to 100C (from cyclohexane) c) 4-(2-Methylmercapto-ethoxy~-2-methoxy-thio-benzoic acid-morpholide Prepared analogous to example 28a from 4-(2-methylmercapto-ethoxy)-2-methoxy-benzaldehyde.
M.p.: 131 to 132C (from ethanol) d) 2-~2-Methoxy-~ (2-methylmercapto-ethoxy)-phenyl]-lH-imidazo-[4,5-b]-pyridine-hydrochloride

5,4 g of 4-(2-methylmercapto-ethoxy)-2-methoxy-thio-benzoic acid-- . . :

104150Z.
morpholide were rcfluxcd for 1 1/2 hours togctllcr with 1~2 ml of mcthyliodidc in 50 ml of acetone. After coolinc, thc solvent was removed and the obtained sirupy mcthoiodide was heated Witll 3,6 g of 2,3-diaminopyridine in 20 ml of glycol for 1 1/2 hours up to 120 C. The mixture was diluted with ~ater and extracted with chloroform. Subsequently, 2n hydroch~oric acid was added to the organic layer and the yellow precipitate was suction filtered.
M.p.: 197 to 199 C (from methanol) Example 47 2- ~ -Methoxy-4-(2-ethylmercapto-ethoxy)-phenyl/-lH-imidazo/4,5-b/-pyridine-hydrochloride prepared analogous to example ~6 from 4-(2-ethy~nercapto-ethox~)-2-metho~-thio-benzoic acid-morpholide and 2,3-diaminopyridine. ~he purification of the final product was effected by chromatography oYer silica gel and the preclpitation of the hydrochloride was effected by dissolving of the base in acetone and addition of an excess of ethereal hydrochloric acid.
M.p.: 195 to 196C.

Example 48 2- ~ -Methoxy-4-(3-methylmercapto-propoxy)-phenyl/-1~-imidazo-/4,5-b7pyridine-hydrochloridc prepared analo~ous to example 46 from 4-(3-methyln~ercapto-propo~)-2-methoxy-thio-bcn~ois acid~morpholide and 2~3-diaminopyridine.
M.p.: 189 to 191 C (decomp.).

. ~
'~''' ' ' ' .

. ~. , .

.

~04iSOZ

Examplc ~9 2-~2-Methoxy-~-(3-ethy]~ercapto-propox~)-phenyl/-lH-imida~o-/4,5-b7pyridine-hydrochloride Prepared analogous to example 46 from 4-(3-ethylmercapto-propoxy~
2-~ethoxy-thio-benzoic acid-morpholide and 2,3-diaminopyridine.
M.p.: 183 to 185 C (decomp.).

Example 50 2-~ -(2-Methylmercapto-ethoxy)-4-methoxy-phenyl/-lH-imida~o~ ,5-b7-Eyridine-hydrochloride Prep~red analogous to example 46 from 2-(2-methyl~ercapto-ethoxy)-4-methoxy-thio-benzoic acid-morpholide and 2,3-diamino-pyridine.
M.p.: 204 to 206 C (decomp.).

Example 51 2- ~ -(2-Ethylmercapto-ethoxy)-4-methoxy-phenyl/-lH-imidazor4, 5-b7-pyridine-hydrochloride prepared analogous to example 46 from 2-(2-ethylmercapto-ethoxy)-4-methoxy-thio-ben~oic acid-morpholide and 2,3-diaminopyridine.
M.p.: 193 to 195 C.

Example 52 2-/2-(3-llethylmercapto-propoxy)-4-methoxy-phenyl7-lH-imi.da~o-r4,5-b7pyridine-hydrochloride Prepared analogous to example 46 from 2-(3-methylmercapto-propoYy3-4-methoxy-thio-ben~oic acid-morpholidc and 2,3-diaminopyridine.
M.p.: ]91 to 193 C.

, . .

rAl , - '~ ' ~ , ; ' ;: ' 10~150'~
E~ _ ~Ic 53 2-/2-(3-~thylmercapto-propoxy)-4-methox~-phenyl/-1ll-imidazo-¦4,5-b/pyridine-h~drochloride prepared analogous to example 46 from 2-(3-ethylmercapto-propo~y)-4 methoxy-thio-benzoic acid-morpholide and 2,3-diaminopyridine.
M.p.: 187 to 189 C.

Example ~4 2-(2~3~4-Trimethoxy-phenyl)-lH-imidazo/4,5-b7-pyridine-hydro-chloride .
Prepared analo~ous to example 28 from 2,3,4-trimethoxy-thio-benzoic acid-morpholide-methoiodide (m.p. 147 to 150 C) and 2~3-diamino-pyridine.
M.p.: 231 to 233 C (decomp.).

Example 55 2-(2-Methoxy-3,4-mcthylenedioxy-phenyl)-lH-imidazo/4,5-b7pyridine-hydrochloride ' - .
~repared analogous to example 28 from 2-methoxy-3, 4 methylenedioxy-thio-benzoic acid-morpholide-methoiodide (m.p.: 109 to 111 C) ~nd 2,3-diaminopyridine.

M.p.: 266 to 268 C.

: , - . . . .

104iS02 Example 56 2-(2~4-Dimethoxy-3-hydroxy-phenyl)-lH-imidazo~4~5-b7pyridine-hydrochloride Prepared analogous to example 28 from 2,4-dimethoxy-3-hydro.Yy-thio-ben~oic acid-morphol_de-methoiodide and 2,3-diaminopyridine.
M.p.: 115 to 118 C.

Example 57 2-(2-Methoxy-4-chloro-phenyl)-lH-imidazo/~ pyridine-hydro-chloride Prepared analogous to example 28 from 2-methoxy-4-chloro-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 302 to 305 C.

Example 58 2-(2-Methoxy-4-methyl-phenyl)-lH-imidazo/4,5-b7pyridine-hydro-chloride ~. . .
Prepared analogous to example 28 from 2-methoxy-4-methyl-thio-ben70ic acid-morpholide and 2,3-diaminopyridine.

M .p .: 256 C (decomp.).

Examplc 5 2-(2-Ethoxy-4-methyl-phenyl)-1~l-imidazo/4~5-b7pyridine-hydrocllloridc Prepared analogous to example 28 from 2-ethoxy-4-mcthyl-thi.o-ben-oic rA~
, - 48 -- - .
. . - ~ . ~

lV41502 acid-morpholide-methoidide (m.p.: 142 to 144C) and 2,3-diamino-pyridine.
M.p.: 224 to 225C (decomp.).
xample 60 2-(2-Methoxy-4-methylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine-hydrochloride Prepared analogous to example 18b)from 2-methoxy-4-methylmercapto-benzoic acid-morpholide (m.p.: 124 to 129C) and 2,3-diamino-pyri-dine.
M.p.: 232 to 234C.
Example 61 2-(2-Methoxy-5-methylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine-hydrochloride Prepared analogous to example 18b)from 2-methoxy-5-methyLmercapto-benzoic acid-morpholide (m.p.: 106 to 108C) ard 2~3-diamino- --pyridine.
M.p.: 247 to 248C.
Example 62 2-(2-Methoxy-4-ethylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine-hydrochloride Prepared analogous to example 25 from 2-methoxy-4-ethylmercapto-benzoic acid-morpholide and 2~3-diaminopyridine.
M.p.: 215 to 217C.

, xample 63 ~04~502 2-(2-Methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine-hydrochloride Prepared analogous to example 28 from 2-methylmercapto-thio-benzoic acid-morpholide-methoiodide and 2~3-diaminopyridine.
M.p.: 185 to 187C.
xample 64 2-(2,4-Pismethylmercapto-phenyl-1H imidazo[4,5-b]pyridine-hydro-chloride Prepared analogous to example 28 from 2,4-bismethylmercapto-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 249 to 250C. `~
Example 65 2-[2-(2-Methylmercapto-ethoxy)-4-methylmercapto-phenyl]-lH-imidazo-[4.5-b]pyridine-hydrochloride Prepared analogous to example 28 from 2-(2-methylmercapto-ethoxy)-4-methylmercapto-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 180`to 182C.
Example 66 -2-~2-(2-Diethylamino-ethoxy)-4-methyl-phenyl]-1H-imidazo[4~5-b]-pryidine-hydrochloride Prepared analogous to example 28 from 2-(2-diethylamino-ethoxy)-4-methyl-thio-benzoic acid-morpholide-methoiodide-hydrochloride and -2,3-diaminopyridine.
M.p.: 221 to 223C.

`' ' ~ ~ .
.
.

r - ~

1041S0~

Example 67 2-(2-Allyloxr-4-methoxy-phenyl)-lH-imidazo[4,5-b]p~ridine ;
hydrochloride 16.5 g of 2-allyloxy-4-methoxy-benzoyl morpholide and 7.1 g of 2,3-diaminopyridine were powdered and ~ -intimately mixed and 30 ml of phosphorus oxychloride were added dropwise whilst stirring. Subsequently, the re~ction mixture was refluxed for 3 hours, the excess of phosphorus oxychloride was removed and the residue was decomposed with ice-water. The solu~ion, which had been made alkaline with ammonia, was extracted with chloro~orm.
The organic solution was extracted with 2N hydrochloric acid and the aqueous phase was made alkaline with c~mmonia and extracted with chlorofonm. The chl~rofol~ ~olution r ":IAl . .

1041S0;~
was dried, treated with charcoal/tonsil, filtered and evaporated. The residue was dissolved in acetone and the light yellow colored hydrochloride w~s precipitated with ethereal hydrochloric acid.
M.p.: 189 to 191C.
Example 68 2-(2~4,5-Trimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride a) 2-(2,4,5-Trimethoxy-phenyl)-1,3-dithiolanium-iodine 50 g of 1.2,4-trimethoxybenzene and 150 g of 2-methylmercapto-1,3-dithiolanium-methylsulfate were stirred in 600 ml of glacial acetic acid for 4 hours at 70~C bath temperature. Subsequently, the solvent was removet, the residue was dissolved in a mixture of chloroform and water and an excess of potassium iodide solution was added to the aqueous layer, whereby the product precipitated as orange-colored crystals.
b) 2-(2,4,5-Trimethoxy-phenyl)-lH-imidazo[4,5-b]
pyridine hydrochloride 3.8 g of 2-(2,4,5-trimethoxy-phenyl)-1,3-dithiolanium -iodide and 2.2 g of 2,3-diaminopyridine were heated for .

Al~ 3;~ -- 5~--~ ........
..... ~ .

1041S0~
10 minutes in 40 ml of glycol at 200C. After cooling the mixture was extracted with ether and then with chloroform. The chloroform layer was extracted with 2N
hydrochloric acid and the precipitated yellow hydrochloride was suction filtered and recrystallized from glycol.
M.p.: 278 to 280C
Example 69 2-(2-,4,6-Trimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride a) 2-(2~4,6-Trimethoxy-phenyl)-1,3-dithiolanium-iodide 33.6g of phloroglucinol-trimethyl ether and 105 g of 2-methylmercapto-1,3-dithiolanium-methylsulfate were held at 75C for 6 hours in 200 mI of glacial acetic acid and the crystals which precipitated after standing over-night were suction filtered, dissolved in w~ter and the iodide thereof was precipitated with potassium iodide solution.
M.p.: 153 to 154C.

rA~ ~

.

b) 2-(2,4,6-Trimethoxy-phenyl)-lH-imidazo[4,5-b]
pyridine hydrochloride 4 g of 2-(2,4,6-trimethoxy-phenyl)-1,3-dithiolanium-iodide, 2 2 g of 2,3-diaminopyridine and 5 g of lead acetate were heated for 10 minutes in 75 ml of glycol. Subse-quently the precipitated lead salt was filtered off, the filtrate was diluted with water and the precipitated product was suction filtered. After dissolving in methanolic hydrochloric acid, the product was purified by passage through a silica gel column (eluent: chloroform:
methanol s 9:1) M.p.: 241 to 244C (from ethanol) Example 70 2-(2,4-Dihydroxy-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride Prepared analogously to Example 69 from 3-hydroxy-4-[1',3'-dithiacyclopentylidene-(2')]-cyclohexadiene-(2,5)-one-(l) and 2,3-diaminopyridine.
M.p.: 298 to 301C.

. 5~G
r,A~

- ~ .

Example 71 2-(4-Dimethylamino-Phenyl)-lH-imidazo[4,5-b]Pyridine hydrochloride Prepared analogously to Example 69 from 2(4-dimethyl-amino-phenyl)-1,3-dithiolanium-iodide and 2,3-diamino-pyridine in n-propanol.
M.p.: 337 to 339C.
ExamPle 72 2-(2-Methoxy-4-dimethylamino-phenyl)-lH-imidazo[4,5-b]
pyridine hydrochloride a) 2-(2-Methoxy-4-dimethylamino-phenyl)-1,3-dithiolanium-iodide 22.6 g of 3-dimethylamino-anisole, 43.2 g of 2-methylmercapto-1,3-dithiolanium-methyl su~fate, 150 ml of glacial acetic acid and 22.5 ml of pyridine were refluxed for ~ hour. After cooling, the mixture was poured into an aqueous potassium iodide solution, the precipitated product wa8 suction filtered and dried.
M.p.: 189 to 195C (from dimethylformamide) .. - , . .. ..
'A~ 55~
'~'.

., - - . , ~ . : .

.. . : ,. .

~4lSO'~
b) 2-(2-Methoxy-4-dimethylamino-phenyl)-lH-imidazo [4,5-b~pyridine hydrochloride Prepared analogously to Example 42 from 2-(2-methoxy-4-dimethylamino-phenyl)-1,3-dithiolanium-iod~e and 2,3-diaminopyridine.
M.p.: 258 to 260C (from methanol~
Example 73 2-(2-Methylsulfinvl-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride 1.35 g of 2-(2-methylmercapto-phenyl)-lH-imidazo [4,5-b]pyridine were dissolved in 20 ml of glacial acetic -~
acid and 0.64 8 of 30% hydrogen peroxide dissolved in 5 ml of glacial acetic acid were added dropwise. After standing overnight, the mixture was diluted with water, neutralized with sodium bicarbonate and the precipitated product was suction filtered and dried. By addition of ethereal hydrochloric acid to a methanolic solution of the product the colorless hydrochloride was obtained.
M.p.: 205 to 210C.

5~ . .
_ ,~ _ 104150;~
Example 74 2-(2-Me ~ lsulfon~ phenyl)~ -imidazo~4,5-bJpyridine hydrochloride 450 mg of 2-(2-methylmercapto-phenyl)-lH-imidazo [4,5-b]pyridine hydrochloride and 370 mg of 300/D hydrogen peroxide were heated for 3 hours at 70C in 20 ml of glacial acetic acid. After evaporation and trituration with petroleum ether, the desired product crystallized~
M.p.: 259 to 262C (from isopropanol) Example 75 2- [2-(2-Methylsulfinyl-ethoxy)-phenyl]-lH-imidazo[~ ,s-b3 pyridine hydrvchloride a) 2-[2-(2-Methylmercapto-ethoxy)-phenyl~-lH-imidazo [~,5-b3pyridine hydrochloride .
.. ~1 . .

- . , , ~ . .

~04~SOZ
Prepared aralogous to example 28 from 2-(2-methylmercapto-ethoxy)-thio-benzoic acid-morpholide-methoiodide and 2,3-diaminopyridine.
M.p.: 138 to 140C.
b) 2-[2-(2-Nethylsulfinyl-ethoxy)-phenyl]-lH-imidazo[4,5-b]pyridine-hydrochloride 4,3 g of 2-[2-(2-methylmercapto-ethoxy)-phenyl]-lH-imidazo-[4,5-b]pyridine-hydrochloride and 1,5 g of 30 ~ hydrogen per-oxide were stirred for 2 hours at room temperature in 100 ml of glacial acetic acid. After standing over night, the mixture was diluted with water, neutralized with bicarbonate and ex-tracted with chloroform. The chloroform layer was evaporated, the residue was taken up in acetone and the hydrochloride was precipitated with methanolic hydrochloric acid.
.p.: 163 to 165C.
xample 76 2-[2-(2-Methylsulfinyl-ethoxy)-4-methoxy-phenyl]-lH-imidazo-[4~5-b]~yridine-hydrochloride Prepared analogous to example 75b from 2-~2-(2-methylmercapto-ethoxy)-4-methoxy-phenyl]-lH-imidazo[4,5-b]pyridine-hydrochloride.
M.p.: 231 to 232C.
xample 77 2-[2-(2-Ethylsulfinyl-ethoxy)-4-methoxy-phenyl]-lH-imidazo[4,5-b]-pYridine Prepared analogous to example 75b from 2-[2-(2-ethylmercapto-ethoxy)-~ methoxy-phenyl]-lH-imidazo~4,5-b3pyridine-hydrochloride.
M.p.: 188 to 189C.

1041~0Z

Example 78 2-[2-(3-Methylsulfinyl-propoxy~-4-methoxy~phenyl ~lH-.
Prepared analogously to Example 75b from 2-[2-[2- -(3-methylmercapto-prop~y~4-methoxy-pher,yl]-lH-imidazo ~4,5-b~pyridine hydrochloride M.p.: 132 to 133C
Example 79 ~ '' "' L4 ~ 5-b ]Pyri dine Prepared analogously to Example 75b from 2-~2-~3- .
ethylmercapto-propoxy)-4-methoxy-phenyl3-lH-imidazo[4,5-b3 : ;
pyridine hydrochloride. -;
p.: 126 to 127C.

- 59 - .
~, ..
~ r~

~ . . .

1~)41SO'~
Example 80 2-(2-Methoxy-4-methvlsulfinyl-phenyl)-lH-imidazo[4,5-b~
p~ridine hydrochloride

6.6 g of 2-(2-methoxy-4-methylmercapto-phenyl)-lH-imidazo[4,5-b]-pyridine were dissolved in 100 ml of chloro-form and a solution of 2.96 g of 3-chloro-perbenzoic acid in 600 ml of chloroform was dropped in at -15 to -20C
during 5 hours. Subsequently, the mixture was extracted with a dilute sodium carbonate solution and the chloroform layer was dried and evaporated. The residue was purified over a silica gel column (eluent: chloroform/methanol =
9:1) By addition of ethereal hydrochloric acid to a methanolic solution of the base the yellow hydrochloride was obtained.
M.p.: 154 to 155C.
ExamPle 81 2-(2-MethoxY-4-methYlsulfonYl-phenyl)-lH-imidazo[4~5-b~
pyridine hydrochloride Prepared analogously to Example 74 from 2-(2-methoxy -4-methylmercapto-phenyl)-lH-imidazo[4,5-b3pyridine hydrochloride.
M.p.: 240 to 242~G.

r 60 pj~ _ ~ _ Example 82 2-(2-Methoxy-4-ethylsulfinyl-phenyl)-lH-imidazo~4,5-b]
pyridine hydrochloride Prepared analogously to Example 80 from 2-(2-methoxy-4-ethylmerc~pto-phenyl)-lH-imidazo[4,5-b]pyridine M.p.: 121 to 123C
Example 83 2-[2-(2-Methylsulfinyl-ethoxy)-4-methylmercapto-phenvl]-lH-_idazo[4,5-b]pyridine Prepared analogously to Example 80 from 2-[2-methylmercapto-ethoxy)-4-methylmercapto-phenyl]-lH-imidazo [4,5-b]pyridine and an equimolar quantity of 3-chloro-perbenzoic acid.
M.p.: 191 to 192C (from acetone) ExamPle 84 2-[2-(2-MethylsulfinYl-ethoxy)-4-methylsulfinYl-phenyl]-lM-imidazo[4,5-b]pyridine Prçpared analogously to Example 80 from 2-[2-(2-methylsulfinyl-ethoxy)-4-methylmercapto-phenyl]-lH-imidazo ~4,5-b]pyridine and an equimolar quantity of 3-chloro-perbenzoic acid.
M.p.: 190 to 191C.

104~50'~
Example 85 2-[2-(2-Methylsulfinyl-ethoxy)-4-methYl-phenyl]-lH-imidazo [4,5-b~ pyridine hydrochloride Prepared analogously to Example 75b from 2-~2-(2-methylmercapto-ethoxy)-4-methyl-phenyl]-lH-imidazo[4,5-b]
pyridine hydrochloride.
M.p.: 191 to 192C (from acetone/ether).
Example 86 2-[2-(2-Methylsulfinyl-ethoxY)-4-chlorophen ~ H-imidazo [4,5-b] yridine hydrochloride Prepared analogously to Example 75b from 2-[2-(2-methymercapto-ethoxy)-4-chloro-phenyl]-lH-imidazo[4,5-b]
pyridine hydrochloride.
M.p.: 221 to 222C (from acetone/ether).
Example 87 2-[2-Methoxy-4-(2-methYlsulfinyl-ethoxy)-phenyl]-lH-imidazo [4,5-b]pyridine Prepared analogously to Example 75 b from 2-[2-methoxy-4-(2-methylmercapto-ethoxy)-phenyl]-lH-imidazo [4,5-b]pyridine hydrochloride.
M.p.: 204 to 205C.

rA~ ~ ~

~041S0~
Example 88 2-[2-Methoxv-4-(2-ethylsulfinyl-ethoxy)-phenyl]-lH-imidazo [4,5-b~ p~ridine Prepared analogously to Example 75b from 2-~2-methoxy-4-(2-ethyl-mercapto-ethoxy)-phenyl]-lH-imidazo [4,5-b]pyridine hydrochloride.

M.p.: 217 to 219C

Example 89 2-[2-Methoxv-4-(3-methylsulfinvl-propoxv)-phenyl]-lH-imidazo[4,5-b]pyridine Prepared analogously to Example 75b from 2-[2-methoxy-4-(3-methylmercapto-propoxy)-phenyl]-lH-imidazo [4,5-b]pyridine hydrochloride.

M.p.: 179 to 180C.

Example 90 2-[2-MethoxY-4-(3-ethvlsulfinvl-propoxY~-phenyl]-lH-imidazo [4,5-b] Pvridine hydrochloride .

Prepared analogously to Example 75b from 2-[2- ~-methoxy-4-(3-ethylmercapto-propoxy)-phenyl]-lH-imidazo [4,5-b]pyridine hydrochloride M.p.: 167 to 168C.

~3 , . .
--_&6~-- ' r~

104~50~
Example 91 2-(2-Methoxy-5-methylsulfinyl-phenyl)-lH-imidazo[4,5-b]
Pvridine Prepared analogously to Example 80 from 2-(2-methoxy-5-methylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride.
M.p.: 211 to 212C.
Example 92 2-(2-Methoxy-5-methylsulfonyl-phenyl)-lH-imidazo[4,5-b]
pyridine Prepared analogously to Example 74 from 2-(2-methoxy-5-methylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride M.p.: 240 to 241C.
Example 93 2-(2,4-Dimethoxy-phenyl-lH-imidazo[4,5-b~Pvridine-oxide-(4) 1 g of 2-(2,4-dimethoxy-phenyl)-lH-imidazo[4,5-b]
pyridine and 1.35 g of 3-chloroperbenzoic acid were stirred for 15 hours at 60C in 15 ml of glacial acetic acid. Subsequently, the mixture was recrystallized from 6y ~ ~ .' . ' -.
..

-~041502 2N acetic acid by addition of charcoal. The further purification was effected by boiling with acetone.
M.p.: 266 to 267C.
Example 94 2-(2,4-Dimethoxy-phenyl)-3-methyl-3H-imidazo[4~5-b~
Ey~idine hydrochloride 3.6 g of methyl iodide were added dropwise to a solution of 3.5 g of 2-(2,4-dimethoxy-phenyl)-lH-imidazo ~4,5-b]pyridine hydrochloride and 27 g of potassium tert.-butoxide in 40 ml of dimethylformamide. The mixture was stirred for 2 hours at room temperature and then evaporated. The residue was dissolved in chloroform4 water, the organic layer was separated, dried and evaporated.
The product was purified by column chromatography and subsequently precipitated from the solution in acetone with ethereal hydrochloric acid.
M.p.: 196 to 197C.

G~' ~ 'Al - ~

: . :
... , ' ' 104~50'~
Example 95 2-(2-Hydroxy-phenyl)-3-methyl-3H-imidazo~ [4,5-b]pyridine hydrochloride Prepared analogously to Example 94 from 2-(2-hydroxy-phenyl)-lH-imidazo[4,5-b]pyridine and methyl iodide.
M.p.: 215 to 216C.
Example 96 2-(2-Hvdroxy- 4-methoxy-phenyl)-3-(3-hydroxypropyl)-3H-i.midazo~4,5-b~pvridine hvdrochloride Prepared analogously to Example 94 from 2-(2-hydroxy-4-methoxy-phenyl)-lH-imidazo[4,5-b~pyridine and 3-bromo-propanol.
l~.p.: 154 to 155C.
Example 97 2-(2,4-Dimethoxy-phenYl)-3-benzyl-3H-imidazo[4,5-b]pyridine hydrochloride Prepared analogously to Example 94 from 2-(2,4-dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine and benzyl bromide.
M.p.: 148 to 150C.
Example 98 2-(2-Dimethoxy-phenyl)-3-(2-diethYlaminoethyl)-3H-imidazo~
[4,5-b]pyridine dihYdrochloride -. . .

;
-. .
.
, ~ :

~04~50'~
Prepared analogously to Example 94 from 2-(2-dimethoxy-phenyl)-lH-imidazo[4,5-b]pyridine and 2-diethylamino-ethyl chloride at 80C.
M.p.: 185C.
Example 99 2-(2,4-Dimethoxy-phenyl)-3-(3-dimethylaminopropyl)-3H
imidazo~4,5-b]pyridine dihydrochloride Prepared analogously to Example 94 from 2-(2,4-dimethoxy-phenyl)-lH-imidazo t 4,5-b]pyridine and 3-dimethylaminopropyl bromide at 70C.
M.p.: 190 to 192C (decomp.).
Example 100 2-(2-Methoxy-4-benzvloxy-phenyl)-lH-imidazot4,5-b]pyridine :
Prepared analogously to Example 10 from 2-methoxy-4-benzyloxy-benzoyl morpholide and 2,3-diamino-pyridinç.
M.p. of the hydrochloride: 218 to 219C (decomp.).
Example 101 Prepared analogously to Example 10 from 2,4-dimethoxy-benzoyl morpholide and 3-amino-2-butylamino-pyridine.
M.p. of the hydrochloride: 218 to 219C.
, ~1 - ~, ' rA~

., ,, ;
- : , -, ..... . -: :.......... .

Example 102 1041S02 2-(2-Methoxv-4-hydroxy-phenyl)-lH-imidazo[4,5-b]pyridine Prepared analogously to Example 10 from 2-methoxy-4-hydroxy-benzoyl morpholide and 2,3-diamino-pyridine.
M.p. of the hydrochloride: 230 to 231C.
Example 103 2-(2-Ethoxy-4-ethylmercapto-phenyl)-lH-imidazo~4,5-b~-pyridine Prepared analogously to Example 10 from 2-ethoxy-4-ethylmercapto-benzoyl morpholide and 2,3-diamino-pyridine.
M.p. of the hydrochloride: 198 to 199C (decomp.).
ExamPle 104 2~4-Methoxy-2-(3-(4-methvl-l-piPerazinyl)-propoxy)-phenvl]
lH-imidazo[4,5-b]pyridine Prepared analogously to Example 21 from 2-[4-methoxy-2-(3-chloro-propoxy)-phenyl]-lH-imidazo[4,5-~] pyridine and l-methylpiperazine.
M.p. of the trihydrochloride: 248C (decomp.) Example 105 2-r4-MethoxY-2-(2-thiomorPholine-ethoxy)-phenyl]-lH- , imidazo~4,5-b]Pyridine Prepared analogously to Ex~mple 21 from 2-[4-methoxy-2-(2-chloro-ethoxy)-phenyl]-lH-imidazo[4,5-b]-- ~1 ~~~

, .. . . .. . .

104~50Z
-pyridine and thiomorpholine.
M.p.: 158 to 160C.
ExamPle 106 2-(2-Fluoro-4-methoxy-phenyl)-lH-imidazo~ 5-b~pYridine Prepared analogously to Example 1 from 2-fluoro-4-methoxy-benzoic acid and 2,3-diamino-pyridine.
M.p. of the hydro~hloride: 237 to 238C (decomp.).
Example 107 2-(4-Fluoro-2-methoxy-phenyl)-lH-imidazo[4.5-b]pyridine Prepared analogously to Example 1 from 4-fluoro-2-methoxy-benzoic acid and 2,3-diamino-pyridine.
M.p. of the hydrochloride: 235 to 236C (decomp.) Example 108 2-(2-Hydroxy-4-methox~-phenyl)-3-phenyl-3H-imidazo-r4,5-b]pyridine 4.9 g of 2-hydroxy-4-methoxy-benzanilide and 2.6 g of 2-chloro-3-amino-pyridine were refluxed for 12 hours in 50 ml of phosphorus oxychloride. After distilling '. . . : ' ' ' ' - ' ' off the excess of phosphorus oxychloride the residue was boiled for 45 minutes with 2N hydrochloric acid, neutralized with ammonia and the precipitated product was recrystallized from isopropanol.
M.p.: 201C.
C Example ~
2-(2-Hvdroxy-4-methoxv-phenYl)-3-(2-methoxv-phenyl)-3H-imidazo~4,5-b]pyridine -/~
Prepared analogously to Example ~Q from N-(2-methoxy-phenyl)-2-hydroxy-4-methoxy-benzamide and 2-chloro-3-amino-pyridine.
M.p.: 197C.
~Q
Example l~L
2-(2-Hydroxv-4-methoxy-phenvl)-3-(4-methoxv-phenvl)-3H-imidazo~4,5~b]pvridine /o&
Prepared analogously to Example ~9R from N-(4-methoxy-phenyl)-2-hydroxy-4-methoxy-benzamide and 2-chloro-3-amino-pyridine.
M.p.: 175C.
:':
Exam~le 2-(2-HvdroxY-4-methoxY-PhenYl)-3-(2-phenvlethvl)-3H
imidazo~4,5-b~pyridlne /~&
Prepared analogously to ~xample ~Q from 5~1'. ~ ~ ....

. . -, .. . . .
.. : . : . -N-(2-phenylethyl)-2-hydroxy-4-methoxy-benzamide and 2-chloro-3-amino-pyridine.
M.p.: 155C.
Example 112 2- ~ 4 Dimethoxy-phenyl)-3-phenyl-3H-imidazo[4,5-b]pyridine Prepared from N-phenyl-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine by heating for 5 minutes with sodium hydride in dimethylformamide at 120C.
M.p.: 138C (from cyclohexane/isopropanol = 9/1). -ExamPle 113 2-(2,4 Dimethoxy-pheny1)-3-(2-methoxy-phenyl)-3H-imidazo-[4,5-b]pyridine Prepared analogously to Example 112 from N-(2-methoxy-phenyl)-N~-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine.
M.p.: 156C.

.
- : - - ~ , . : :

104~50Z
Y
Example r~
.

2-(2~4-Dimethoxy-phenyl)-3-(4-methoxy-phenyl)-3H-imidazo[4,5-b~pyridine ~/~
Prepared analogously to Example ~ from N-(4-methoxy-phenyl)-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine.
M.p.: 163C.
Example ~
2-(2,4-Dimet,hoxy-phenyl)-3-(3,4-dimethoxy-phenyl)-3H-imidazo[4,5-b~pyridine 11~
Prepared analogously to Example ~4~from N-(3,4-dimethoxy-phenyl)-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine.

M.p.: 190C.

Example ~9~
2-(3,4-Dimethoxy-phenyl)-3-(4-methoxy-phenyl)-3H-imidazo-[4,5-b]pyridine Prepared fron N-(4-methoxy-phenyl)-N'-(2-chloro-3-pyridyl)-2,4-dimethoxy-benzamidine analogously to Example ri~or by boiling in chlorobenzene.
M.p.: 181C.
Jl 1 2-(2,4-Dimethoxy-phenyl)-3-(3-morpholino-1-propYl)-3H-imidazo~4,5-b]pYridine 72, rAl - ~ - , , .

- . . ~ ~ . . ~
' " ~

11~
Prepared analogously to Example ~ from N-(3-morpholino-1-propyl)-N'~(2-chloro-3-pyridyl~-2,4-dimethoxy-benzamidine.
M.p.: 207C.
Example ~
2-(2,6-~imethoxyphenyl)-lH-imidazo[4,5-b]pyridine hvdrochloride 9.1 g of 2,6-dimethoxy-benzoic acid and 5.5 g of 2,3-diaminopyridine were refluxed for 3 hours in 100 ml of phosphorus oxychloride. Subsequently the excess of phosphorus oxychloride was distilled off and the residue was carefully decomposed with ice-water. The obt`ained solution was filtered, neutralized with potassium carbonate and made alkaline with concentrated ammonia. The suspension which formed was extracted three times with chloroform. The chloroform layer was dried over magnesium sulfate, filtered and the solvent was removed. The remaining residue was dissolved in 50 ml of methanolic hydrochloric acid, subsequently 100 ml of isoprqpanol were added and the product was kept in the deep freezer overnight. The precipitate was suction filtered and washed with ether.
M.p.: 250 to 254C.

-- 76 -- ' rAl 1041S0~

Example 2-(2-Propoxy-4-methyl-phenyl)-lH-imidazo[4,5-b]pvridine hydrochloride 1/~
Prepared analogously to Example ~Q from 2-propoxy-4-methyl-benzoyl morpholide.

M.p.: 221 to 223~. (decomp.).

Example ~Y~L

2-(2-Butoxy-4-methyl-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride Prepared analogously to Example ~ from 2-butoxy-4-methyl-benzoyl morpholide.
M.p.: 212 to 213C (decomp.).

/o~ I
Example ~X~
_ (4-Methylmercapto-phenyl)-lH-imidazo~4,5-b]pvridine hydrochloride Prepared analogously to Example ~Q from 4-mçthyl-mercaptobenzoic acid.
M.p.: 230 to 232C.
Example k~
2-[2-(2-Methvlmercapto-ethoxY)-5-methylmercapto-phenyl]-lH-imidazo r 4,5-b]pyridine hvdrochloride 50 g of S-methyl-~2-(2-methylmercapto-ethoxy)-5-methylmercapto]-thiobenzoyl morpholide iodide (obtained ~ -by reaction of [2-(2-methylmercapto-ethoxy)-5-methylmercapto]-r~ _ ~

. : , .

-thiobenzoyl morpholide with methyl iodide in methanol) and 15 g of 2,3-diaminopyridine were heated for 3 hours at 130C in 150 ml of glycol. After cooling, the mixture was diluted with water and 30 ml of concentrated ammonia were added. Subsequently, the mixture was extracted with chloroform, the organic layer was washed with ~ater -and 2N hydrochloric acid was added. The precipitate was suction filtered and recrystallized from methanol.

M~p.: 190 to 191C.
l~ 3 E~ample ~i 2-(2-Methoxy-4-propylmercapto-phenyl)-lH-i~midazo~4,5-b~- ;
pyridine hydrochloride Prepared analogously to Example ~ from 2-methoxy-4-propylmercapto-benzoyl morpholide.
M.p.: 203 to 204C (decomp.).
Example ~
2-(2-Ethoxy-4-propvlmercapto-phenyl)-lH-imidazo~4,5-b]-pyridine hydrochloride Prepared analogously to Example ~Q from 2-ethoxy-4-propylmercapto-benzoyl morpholide.
M.p.: 182 to 183C.

_ ~ _ . . .

. -Example ~2 1041S02 2-(2-Methoxv-4-butylmercapto-phenyl)-lH-imidazo~4,5-b]-pyridine hydrochloride 11~
Prepared analogously to Example r~Q from 2-methoxy-4-butylmercapto-benzoyl morpholide.

M.p.: 203 to 204C.
/~6 Example r~
2-(2-EthoxY-4-butylmercapto-phenyl)-H-imidazo[4,5-b~-pyridine hydrochloride Prepared analogously to Example ~ from 2-ethoxy-4-butylmercaptobenzoyl morpholide.
M.p.: 207 to 208C.
Example ~9 2-(4-Methylsulfinyl-phenyl)-lH-imidazo[4,5-b]pyridine 5.9 g of 2-(4-methylmercapto-phenyl)-lH-imidazo-[4,5-b]pyridine hydrochloride were dissolved in 100 ml of glacial acetic acid and 2.4 g of 30% hydrogen peroxide were added at 10C. Subsequently the mixture was stirred for 3 hours, and then left to stand over-night in the refrigerator and for 10 hours at laboratory temperature. The mixture was made alkaline with ammonia and was extracted several times with chloroform. The starting material was separated by column chromatography.
The residue was suspended in acetone and the crystals -: .
- ~6 Al ~ ,...... ..

~ ,.- . : , , which formed were suction filtered.

M.p.: 240 to 242C.

Example 13~

2-(2-Ethoxy-5-methylsulfinyl-phenyl)-lH-imidazo[4,5-b]-pyridine /~1 Prepared analogously to Example ~22 from 2-(2-ethoxy-5-methylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine.

M.p.: 197 to 198C.
I~q Example ~31 2-~2-(2-Methvlsulfinvl-ethoxy)-S-methylmercapto-phenyl]-lH-imidazo[4,5-b]pyridine Prepared analogously to Example ~ from 2-[2-(2-methylmercapto-ethoxy)-5-methylmercapto-phenyl]-lH-imidazo[4,5-b]pyridine hydrochloride.

M.p.: 189 to 190C.

Example 2-(2-Ethoxy-4-ethylsulfinyl-phenyl)-lH-imidazo~4~5-b]
pyridine Prepared analogously to Example 1~ from 2-(-2-ethoxy-4-ethylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride.
M.p.: 166 to 167C.

~ .
_ ~ _ rA~

... .. .

-~ 104~50Z
- ~ ~3, Example 1~
2-t2-Methoxy-4-propylsulfinyl-phenyl)-lH-imidazor4,5-b]-pyridine td~
Prepared analogously to Example ~ from 2-(2- :~
methoxy-4-propylmercapto-phenyl)-lH-imidazo[4,5-b~-pyridine hydrochloride, M.p.: 182 to 183C.
Example . 2-(2-Ethoxy-4-propvlsulfinyl-phenvl)-lH-imidazo[4,5-b~-pyridine ~ 7 Prepared analogously to Ex~mple ~a from 2-(2-ethoxy-4-propylmercapto-phenyl)-lH-imidazo~4,5-b~pyridine hydrochloride.

M.p.: 182 to 183C (decomp.).
t3 Example rg~
2-(2-Ethoxy-4-butyl'sulfinyl-phenyl)-lH-imidazo[4,5-b~-pyridine 1~1 Prepared analogously to Example r24~from 2-(2-ethoxy-4-butylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine . hydrochloride.
..
: M.p.: 185 to 186C.

'Al ~

. . . .
. . .
- .
. ~ ............ . . -. . . . .. . . .

~ Example ~
~J
2-(4-Methylsulfonyl-phenyl)-lH-imidazoC4,5-b]pyridine hydrochloride 6.95 g of 2-(4-methylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine hydrochloride were dissolved in 100 ml of glacial acetic acid, 8.5 g of 30% hydrogen peroxide were added and the mixture was left standing for 4 days at room temperature. After purification by passage through a silica gel column, the residue was dissolved in acetone and the hydrochloride was precipitated with methanolic hydrochloric acid.
M.p.: 286C.
/~
Example 137--2-(2-Ethoxy-4-ethylsulfonyl-phenyl)-lH-imidazo~4,5-b]-pvridine 400 mg of 2-(2-ethoxy-4-ethylmercapto-phenyl)-lH-imidazo[4,5-b] pyridine hydrochloride were dissolved in 30 ml of glacial acetic acid together with 0.5 ml of 30%
hydrogen peroxide. The mixture was allowed to stand overnight and was then heated for 1 hour at 90C.
After cooling, the mixture was diluted with water, neutralized with bicarbonate, extracted with chloroform and the organic layer was evaporated after drying. The residue was purified by column chromatography.
M.p.: 207 to 208C (from acetone).
-- ~7 , rAl - ~ ~

:

~041S02 f~l f3G
Example ~9_ 2-(2-Methoxy-4-propylsulfonyl-phenyl)-lH-imidazo[4,5-b~
pxridine ~3~
Prepared analogously to Example 137- from 2-(2-methoxy-4-propylmercapto-phenyl)-lH-imidazo[4,5-b]-pyridine.
M.p.: 219 to 220C.
/3'1 Example ~3a 2-(2-Ethoxy-4-butylsulfonyl-phenyl)-lH-imidazo[4,5-b]-pyridine Prepared analogously to Example r9~from 2-(2-ethoxy-4-butylmercapto-phenyl)-lH-imidazo~4,5-b]pyridine.
M.p.: 156 to 157C.
Example 2-r2-Methoxy-4-(2-dimethYlamino-ethoxY)-Phenyl]-lH
imidazo~4,5-b]pyridine dihydrochloride a) 2-[2-Methoxy-4-~2-chloroethoxy)-phenyl]-lH-imidazo-[4,5-b~pvridine hydrochloride ~ --v 14 g of 2-methoxy-4-(2-hydroxyethoxy)-benzoyl ! morpholide were refluxed for l~ hours with 7.1 g of 2,3-diaminopyridine in 100 ml of phosphorus oxychloride. L
Subsequently the mixture w~s decomposed with ice-w~ter.
The gradually crystallizing prec~pitate was suction _ ~- .

filtered and washed with acetone.
M.p.: 266 to 268C (decomp.).
b) 2 g of 2-[2-methoxy-4-(2-chloroethoxy)-phenyl]-lH-imidazo[4,5-b] pyridine hydrochloride were heated in a closed vessel for 12 hours at 120C with 5 g of dimethylamine in 100 ml of ethanol. After evaporation, the residue was purified by column chromatography.
The hydrochloride was precipitated from acetone with methanolic hydrochloric acid and subsequently recrystallized from methanol.

M.p.: ~ 250C.
~ 3q Example ~
2-[2-Methoxy-4-(3-dimeth~lamino-propoxy)-phenyl~-lH-imidazo~4,5-b~pyridine dihydrochloride Prepared analogously to Example 140 from 2-[2-methoxy-4-(3-chloropropoxy)-phenyl]-lH-imidazo[4,5-b~-pyridine hydrichloride.
M.p.: 238 to 242C.
; ' /Yo Example ~aL
2-r2-Methoxy-4-(3-diethylamino-propoxy)-phenYl~-lH-imidazo~4,5-b~ pyridine dihydrochloride -'A~

Prepared analogously to Example ~4Q from 2-~2-methoxy-4-(3-chloropropoxy)-phenyl]-lH-imidazo[4,5-b]-pyridine hydrochloride.
M.p.: 222 to 224C.
/'JI ' Example ~t~
2~2-Methoxy-4-(3-piperidino-propoxy)-phenyl]-lH-imidazo-~4,5-b]pyridine dihydrochloride /~q Prepared analogously to Example ~4L from 2-[2-methoxy-4-(3-chloropropoxy)-phenyl]-lH-imidazo-~4,5-b]pyridine hydrochloride.
M.p.: 225 to 226C ~decomp.).
Example ~
2-[2-Methoxy-4-(3-(4-phenyl-piperazin-1-yl)-propoxy)- v ~envl]-lH-imidazor4,5-b]pyridine dihydrochloride -~
Prepared analogously to Example ~ from 2-[2-methoxy-4-(3-chloro-propoxy)-phenyl]-lH-imidazo[4,5-b]- -pyridine hydrochloride.
M.p.: 197 to 200C.
/~
ExamPle 2-r2-Methox~,r-4-(3-(4-(2-methoxvphenYl)-piperzin-l-Yl)- '~

hvdrate g~2, , -, .

Prepared analogously to Example 139 from 2-[2-methoxy-4-(3-chloro-propoxy)-phenyl]-lH-imidazo[4,5-b]-pyridine hydrochloride.
M.p.: Sintering from 180C.
Example 144 2-(2-Methoxy-4-morpholino-phenyl)-lH-imidazo[4,5-b]-pyridine hydrochloride a) 2-(2-Methoxy-4-morpholino-phenyl)-1 3-di~hiolanium-iodide 10.5 g of 3-morpholino-anisole and 15.7 g of 2-methylmercapto-1,3-diethiolanium-methyl sulfate were boiled ~- in a mixture of 60 ml of glacial acetic acid and 8.3 ml of pyridine for 1 hour. After cooling, the mixture was poured into a saturated potassium iodide solution. The red precipitate was suction filtered and washed with water.
The product was used without further purification.

. . .
~. ' lO~:~SO;~
b) 22 g of 2-(2-methoxy-4-morpholino-phenyl)-1,3-dithiol-anium iodide,10.9 g of 2,3-diaminopyridine and 60 ml of glycol were heated for 2 hours at 130C. After cooling, water was added and the mixture was extracted with chloroform. After evaporation, the residue was purified by column chromatrography and the hydrochloride was precipitated from acetone with ether/hydrochloride acid.
M.p.: 207 to 209C (decomp.).
C Example ~ -v 2-~2-Methoxy-4-(4-methyl-piperazin-l-yl)-phenyl]-lH-imidazo~4,5-b] pyridine dihydrochloride ~yy - Prepared analogously to Example ~ from 3-(4-- ~ methyl-piperazin-l-yl~-anisole.
M.p.: 279 to 282C.
~C
Example 2-~2-Methoxy-4-(4-ethyl-piperazin-l-yl)-phenvl~-lH
imidazo[4,5-b]pyridine dihydrochloride Prepared analogously to Example ~4~from 3-(4-ethyl-piperazin-l~yl)-anisole.
M.p.: 218 to 222C.
~4 :;
- ~1~ :

. ._ .. __ . .
.:

. .

,~, ~ ~1 `~ Example ~ 1041SOZ

2-~2-Methoxy-4-(4-propyl-piperazin-1-yl)-phenyl]-lH-imidazo[4,5-b]pyridine dihydrochloride /Y~
Prepared analogously to Example ffiL from 3-(4-propyl-piperazin-1-yl)-anisole.

M.p.: 256 to 258C.
Example ~il 2-[2-Ethoxy-4-(4-methyl-piperazin-1-yl)-phenyl~-lH-imidazo[4,5-b]pyridine dihydrochloride /~J'J
Prepared analogously to Example ~L from 3-(4-methyl-piperazin-l-yl)-l-ethoxybenzene.

- M.p.: 269 to 271C.
)Y9 Example ~
2-(2-Ethoxy-4-(4-ethyl-piperazin-1-yl)-phenyl~-lH-imidazo[4,5-b ~-pyridine dihydrochloride lYS' Prepared analogously to Example 14~-from 3-( 4-ethyl-piperazin-1-yl)-1-ethoxybenzene.

M.p.: 257 to 259C.
lSo Example ~

2-[2-Methoxv- 4-( 4-phenyl-piperazin-1-vl)-phenvll-lH-imidazo[4,5-b]pyridine dihvdrochloride J~
Prepared analogously to Example 147 from 3-(4-phenyl-p~perazin-l-yl~anisole.
M.p.: 217 to 219C.

~, .
rAl - ~~

' 104~50Z

Example ~4 2-[4-Methoxy-2-(2-morpholino-ethoxy)-phenyl]-lH
imidazo[4,5-b]pyridine - Prepared from 6.3 g of 2-~4-methoxy-2-(2-chloro-ethoxy)-phenyl]-lH-imidazo[4,5-b]pyridine by refIuxing for 3 hours in 60 ml of morpholine, distilling off -~ ~ -the excess of morpholine in vacuo and recrystallizing the residue from isopropanol.
M.p.: 188 to 190C.
/,~ ,.
Example i~
2- r 4-Methoxy-2-(3-(4-phenyl-piperazin-1-yl)-propoxy)-Phenyl~-lH-imidazo[4~5-b]pyridine 10 g of 2-[4-methoxy -2-(3-chloropropoxy)-phenyl]- ;
lH-imidazo[4,5-b]pyridine, 10.2 g of l-phenyl-piperazine and 5 g of potassium carbonate were refluxed for 8 hours in 100 ml of ethanol. After distilling off the ethanol in vacuo, the mixture was recrystallized from ethanol/water 3:1.
M.p.: 162 to 163C.

Ex,amPle 2-~4-MethoxY-2-(3-(2-PhenYl-ethylamino)-propoxY)-phenyl]
lH-im~dazo~4,5-b~yridine dihvdrochloride ,' ~.r~l :. '' ' ' , : .
, - Prepared by heating 1.77 g of 2-[4-methoxy-2-(3-chloropropoxy)-phenylJ-lH-imidazo[4,5-b]pyridine in 10 ml of 2-phenyl-ethylamino for 1~ hours at 180C.
: The free base was converted into the dihydrochloride with methanolic hydrochloric acid. Recrystallization from isopropanol.

M.p.: 238C.

Example ~L
2-[4.methox~-2-(3-(N-meth~l-N-2-phenvlethyl-amino)-roPoxy)-Phenyl~-lH-imidazo[4,5-b]pyridine dihydrochloride Prepared from 3.2 g of 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-lH-imidazo[4,5-b]pyridine and 2.7 g of N-methyl-2-phenyl-ethylamine by heating for 6 hours in ethanol at 120C in a closed vessel. The dihydrochloride was precipitated with ethereal hydrochloric acid from an ethyl acetate solution of th~base, purified by column, chromatography and recrystallized from isopropsnol.
M.p.: 212 to 215C.
Example ~
2-[4-Methoxy-2-(3-(N-methyl-N-(2-(3,4-dimethox~phe~yl)-ethvl)-amino~-propoxy)-phenvl]-lH-imidazo~4,5-b]-pyridine dihydrochloride ~7 ~rp~ ~

. .

.~ -. .

Prepared from 5.0 g of 2-[4-methoxy-2-(3-chloro-propoxy)-phenyll-lH-imidazo[4,5-b]pyridine and 8.5 g of ~ v N-[2-(3,4-dimethoxy-phenyl)-ethyl]-methylamine by refluxing for 12 hours in ethylene glycol monomethyl ether. Precipitation of the dihydrochloride from ethyl acetate with ethereal hydrochloric acid.
M.p.: 169C.
Example ~
2-~4-Methoxv-2-(3-thiomorpholino-propoxy)-phenyl]-lH-imidazoc4~5-b]pyridine Pre~red analogously to Example 1,~ from 2-~4 methoxy-2-(3-chloropropoxy)-phenyl]-lH-imidazo[4,5-b]-pyridine and thiomorpholine by heating for 30 hours.
Purification was by precipitation of the maleate from ethyl acetate solution. The free base was obtained from the maleate with 2N ammonia.
M.p.: 111C
Example 2-~4-Methoxv-2-(2-(4-methYl-PiPerazin- 1-Y1) -ethoxv)-~he m ll-lH-imidazoc4,5-b~Pyridine Prepared from 3.0 g of 2-~4-methoxy-2-(2-chloro-etho~)-phenyl]-lH-imidazoC4,5-b]pyridine and 2.0 g of N-methylpiperazine by refluxing for 40 hours in ': , ~Ai~ g8 ~
.

. .
.
.

, . - . : : . :-`
. . . ~. i,., ,-:
.. .

ethanol. After purification by column chromatography , over silica gel, the product was recrystallized from water.
-~ M.p.: 136 to 137C.
C /S~
Example ~L
2-~4-Methoxy-2-(3-(4-(2-phenylethyl)-piperazin-1-yl)-propoxv)-phen,vl]-lH-imidazo~4,5-b]pyridine tri-hydrochloride lSy Prepared analogously to Example ~5~ from 2-[4-methoxy-2-(3-chloro-propoxy)-phenyl]-lH-imidazo[4,5-b~-pyridine and 1-(2-phenyl-ethyl)-piperazine.
M.p.: 236 to 238C.
~5'q Example K ~_ 2-r4-Metho ~-2-(3-methylamino-propoxy)-phenvl]-lH-imidazo[4,5-b]pyridine hydrochloride /SY
Prepared analogously to Example ~i from 2-[4-methoxy-2-(3-chloropropoxy)-phenyl]-lH-imidazo[4,5-b]-pyridine and methylamine.
M.p.: 215C.
Example K3L
2-r4-Methoxy-2-(2-dimethylamino-ethoxy)-phenYl]-lH-imidazo~4,5-b]pyridine dihydrochloride ~9 ~ ,. . , . . , . . . . . .. .. _ .

-... . . . . :. ., - :.. ,-- .. : : :- . . .. . ..
- . .. . . . . ..

t~ ~
Prepared analogously to Example 1,, from 2-[4-methoxy-2-(2-chloro-ethoxy)-phenyl]-lH-imidazo[4,5-b]-pyridine and dimethylamine.
M.p.: 240 to 242C.
Example K ~~

2-(2-MethYlamino-phenyl)-lH-imidazo[4,5-b]pyridine 1.77 g of N-methyl-isatinoyl anhydride and 1.09 g of 2,3-diaminopyridine were melted and heated for 10 minutes at 180C. Recrystallization from ethyl acetate, M.p.: 262 to 263C.

Example ~6 2-(2,4-Dimethoxy-phenvl)-3-(2-phenvl-ethyl)-3H-imida [4,5-b]p~ridine 0.17 g of 2-(2-hydroxy-4-methoxy-phenyl)-3-(2-phenyl-ethyl)-3H-imidazo[4,5-b]pyridine were dissolved in 7 ml of dimethylformamide. The mixture was s~irred for 5 minutes with 0.02 g of sodium hydride (80% suspension in oil) and reacted with 0.07 g of methyl iodide under ice-cooling. After 4 hours, water was .
adqed to the reaction mixture. The precipitated product was dissolved in ethyl acetate, and the organic layer was washed with 2N sodium hydroxide solution and water 9~
~rA~ , .. -- - - " , ., , ~
- ~ . - - ~. 1 - - , . .

and evaporated.
Recrystallization from ethanol/water.

M.p.: 157C.
~ 3 Example ~
2-(2,4-Dimethoxy-phenyl)-3-[2-(3,4-dimethoxv-phenyl)-ethyl]-3H-imidazo~4,5-b]pyridine hydrochloride Prepared analogously to Examp~e ~ from 3-amino-2-[2-(3,4-dimethoxy-phenyl)-ethylamino]pyridine and 2,4-dimethoxy-benzoic acid. The hydrochloride was precipitated from ether.
M.p.: 195C.

~Y
Example ~t~c 2-(2-Fluoro-5-methvlmercapto-phenlrl)-lH-imidazo~4,5-b]-E~ridine /~
Prepared analogously to Example ~ from 2,3-diaminopyridine and 2-fluoro-5-methylmercapto-benzoic acid.

M.p.: 195C.
/65' Example ~
2-(2-Fluoro-5-methylsulfinyl-phenvl~-lH-imidazo~4,5-bl-p~ridine Prepared from 2-(2-fluoro-5-methylmercapto-phenyl)-lH-imidazo~4,5-b]pyridi~e by oxidation with hydrogen 9~
` 'Al ~ :
,.
.
- .

- ~ . . . , . , , . ~ .
. ~ . . . .;
.-. - . ~- .- -, . . .

peroxide in glacial acetic acid at room temperature.
The purification was effected by column chromatography on silica gel with chloroform/methanol 19:1 as eluent.
M.p.: 190 to 192C.
Example 1~2 2-(2-Fluoro-5-methylsulfonyl-phenyl)-lH-imidazo[4,5-b]-pyridine Prepared from 2-(2-fluoro-5-methylmercapto-phenyl)-lH-imidazo[4,5-b]pyridine according to Example ~ , but at 40C.

M.p.: 242C.
/C~
Example 2-(3,4-Dimethoxyphenyl)-3-(3-morpholino-propvl)-3H-imida L4,5-b]pyridine dihydrochloride a) N-(2-Chloro-3-PYridYl)-N'-(3-morpholinoPropyl)-3~4 dimethoxy-benzamidine 4.9 g of N-(3-morpholinopro w 1)-3,4-dimethoxy-benzamide and 2.04 g of 2-chloro-3-aminopyridine were refl,uxed for 2 hours in ~5 ml of phosphorus oxychloride.
A~ter distilling off the excess of phosphorus oxychloride, the mixture was poured into water, The solution was made ~-alkaline and extracted with ethyl acetate. After 9~
. ~rAl -~-- . . . ..
.- . :
.
- .
-~041502 evaporation of the residue, the product remained as viscous oil.
b) 2-(3,4-Dimethoxyphenyl)-3-(3-morpholino-propyl)-3~-imidazo[4,5-b ~ dine dihydrochloride 5.2 8 Of N-(2-chloro 3-pyridyl)-N'-(3-morpholino-: propyl)-3,4-dimethoxy-benzamidine and 1.5 g of sodium hydride (80% suspension in oil) were heated in 100 ml of dimethylform.amide for 2 hours at 120C. The dihydrochloride was precipitated from ether with hydrochloric acid and recrystallized from ethanol/
cyclohexane.
C M-p-: 180C, Example l~Y~_ 2-(4-Methoxv-phenyl~-3-(3-morpholino-propoxy)-3H-imidazo-.

: ~4,5-b~pyridine dihYdrochloride /G ~
Prepared analogously to Ex~mple ~lQ fromN-(2-chloro-3-pyridyl)-N'-(3-morpholino-prop.yl)-5-methoxy-benzamidine.
M.p.:.218C.
~q Example : - 2,(4-Methoxv-phenYl)-3-r3-(4-phenYl-piperazin-l-yl)-propyl~-3H-imidazo[4,~-b~pyridine dihydrochloride hydrate . ~ .
. ~6 ~ :
Prepared an~logously to Example ~itt from N-(2-chloro-3-pyridyl)-N'- r 3-( 4 phenyl-piperazin-1-yl~-.

- . - . ' lSOZ
-pro W 1]-4-methoxy-benzamidine.

M.p.: 100C.

Example ~3L
2-(4-MetkoxY-phenvl)~3(2-morpholino-ethvl)-3H-imidazo-~4,S-b~Pyrldlne hvdrochloride /6 1 - Prep~red analogously to Example ~ from N-(2-cbloro-3-pyrldyl)-N'-(2-morpholino-ethyl)-4~methoxy-benzamldlne.
M.p.: 149C.

ÉxamPle ~
2-(4-Methoxv-~henvl) 3-~3-(4-methyl-piPerazin-l-yl~-propyl]-3H-imidazor4,5-blPYridine trihydrochloride /6~
Prepared analogously to Example ~ from N-(2-chloro-3-pyrldyl)-N'-~3-(4-methyl-pipeR~n-l-yl)-propyl]-4-methoxy-benzamidlne.
M.p.: 2S7C
ample ~r 2~ MethoxY-phenYl)-3- ~ (4-methYl-piperazin-l-yl)-ethyl]-3H-imidazo~4,5-b~Dvridine trlhYdrochloride /G ~
Prepared analogou~ly to Example ~7erfrom N-(2-chloro-3-pyrldyl)-N'-~-(4-methyl-piper~æin-1-yl)-ethyl~-4-methoxy-benzamld~ne.

M,p.: 225C.

7~v , . ............. .

.
. ' .
-Rxample 1732-~4-Methoxy-phenyl)-3-(3-dimethylamino-propyl)-3H-imidazo[4,5-b]pyridine dihydrochloride Prepared analogously to Example 167 from N-(2-chloro-3-pyridyl3-N'-(3-dimethylamino-propyl)-4-methoxy-benzamidine.
M.p.; 229C.
Example 174 2-(4 Methoxy-phenyl)-3-(3-piperidino-propyl~-3H-imidazo-C4~5-b]-pyridine dihydrochloride Prepared analogously to Example 167 from N-(2-chloro-3-pyridyl)-N'/(3-piperidino-propyl)-4-methoxy-benzamidine.
M.p.: 196C.
Example 175 2-(4-Methoxy-phenyl)-3-(4-morpholino-butyl)-3H-imidazo-[4,5~1py~1dine dihydrochlo~ide hydrate Prepared analogously to ~xample 167 from N-(2-- - ' _ 95 -.-, .. ~ .

, . .:. . . .. : -- .. . ., . , -, , ~ . . .

-~: .

chloro-3-pyridyl)-N~-(4-morpholino-butyl)-4-methoxy-benzamidine.
M.p.: 136C.
Example 176 2-(2-Fluoro-4-methylmercapto-phenyl)-lH-imidazo[4,5-b]-Pyridine hydrochloride Prepared analogously to ~xample 118 from 2-fluoro-4-methyl-mercapto-benzoic acid and 2,3-diaminopyridine.
M.p.: 257C. `~
Example 177 -~luoro-4-methylsulfinyl-Phen,yl)-lH-imidazol!,4,5-b]-pyridine Prepared analogously to Example 165 from 2-(2- ~ ~
,.
, ~

,~ , : .
: . ' ' ; `:

. i .

:' ' ' fluoro-4-methyl-mercapto-phenyl)-lH-imidazo[4~5-b]-pyridine. Crystallization by trituration in petroleum ether.
M.p.: 219C.
Example 178 2-(4-Methylmercapto-phenyl)-3-(3-morpholino-propyl)-3H
imidazo[4,5-b]pyridine Prepared analogously to Example 167 from N-(2-chloro-3-pyridyl)-N'-(3-morpholino-propyl)-4 methyl-mercapto-benzamidine. Recrystallized from ether/cyclohexane.
M.p.: 110C.
.

:~ .

:.

. . . :

~ 104150Z

2-[2-Propoxy-4-(4-methyl-piperazin-1-yl)-phenvl]-lH-imidazo[4,5-blpyridine dihYdrochloride Prepared analogously to Example ~ from 3-(4-methyl-piperazin-l-yl)-l-propoxy-benzene.
M.p.: 237 to 238C.
/~
Example ~L
Tablets containing 100 mg of 2-(2,4-dimethoxy-phenYl)-lH-imidazo[4,5-b]pyridine hydrochloride ~omposition:
1 tablet contains:
Active ingredient 100.0 mg lactose 50.0 mg polyvinyl pyrrolidone 5.0 mg carboxymethylcellulose 19.0 mg magnesium stearate 1.0 mg 175.0 mg moist screening: 1.5 mm Drying: in the circulating air drier at 50C.
Dry screening: 1 mm The dry granulate was admixed with the remaining auxiliary products and pressed into tablets.
Weight of tablet: 17S mg Punch: 8 mm 0 .. ~8 ' ~ ~ ~

.
, .

^~ -~ 04~S02 Example ~
Coated tablets containing 50 mg of 2-(2,4-dimethoxv-phenyl)-lH-imidazo~4,5-b]pyridine hydrochloride 1 coated tablet core contains:
Active ingredient 50.0 mg corn starch, dried 20.0 mg soluble starch 2.0 mg carboxymethylcellulose 7.0 mg magnesium stearate 1.0 mg 80.0 mg The active ingredient and corn starch were homogeneously moistened with the aqueous solution of the soluble starch.
Moist screening: 1.0 mm Dry screening: 1.0 mm Drying: at SO~C in the circulating air drier The granulate and the remaining auxiliary products were mixed and pressed to form coated tablet cores.
Weight of core: 80 mg Punch: 6 mm, arched (5 mm) The finished cores were covered with a coat consisting essentially of sugas and talcum in conventional manner. The finished coated tablets were polished with ~ .
. . --~2 --'Al 1041~0'~
beeswax.
Weight of the coated tablet: 120 mg Example ~
Suppositories containing 75 mg of 2-(2,4-dimethox -phenyl)- -lH-imidazo[4,5-b]pyridine hydrochloride 1 suppository contains:
Active ingredient 75.0 mg B - suppository mass ~.g. Witepsol~ Y
H 19 and Witepsol 45) 1 625.0 mg 1 700.0 mg Method of preparation:
The suppository mass was melted. At 38C the pulverized active ingredient was homogeneously dispersed in the melt. The suppository mass was cooled to 35C
and poured into pre-cooled moulds. ~ -Weight of suppository: 1.7 g Example ~g~3 Ampoules containing 50 mg of 2-(2,4-dimethoxy-phenyl)-- lH-imidazo~4,5-b]pyridine hydrochloride 1 ampoule contains:
Active ingredient 50.0 mg sorbitol 250.0 mg distilled water ad 5.0 ml ~r~ ~
4 ~Ra/e ~a~k . - : ' - ' ' : - ~
.

~04i5S)Z

Method of preparation:
The active ingredient and the sorbitol were dissolved in distilled water. The solution was made up to the given volumn and filtered sterile.
Filling: into ampoul.es of 5 ml capacity Sterilisation: 20 minutes at 120C.
Example ~
DroP solution containin~ 25 mg of 2-(2,4-dimethoxy-enyl)-lH-imidazo[4,5-b~pyridine hydrochloride per 5 ml Active ingredient 5.0 g methyl p-hydroxybenzoate 0.035 g propyl p-hydroxybenzoate 0.015 g aniseed oil 0.05 g menthol 0.06 g sodium saccharine 1.0 g glycerine 10.0 g ethanol . 40.0 g distilled water ad100.0 ml Method of preparation:
.
The benzoic acid esters were dissolved in ethanol and subsequently the aniseed oil and the menthol were added. Active ingredient, glycerine and sodium /0~
_ ~ _ io~

- saccharine were dissolved in water and added. The solution was filtered pure.

.
' ' ~ '' '' ` '' ' "'" '. , ,

Claims (47)

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 compound of the general formula:

(1) or an isomer thereof of the general formula:

(1a) wherein R1 represents an alkylamino, dialkylamino, hydroxy, allyloxy, benzyloxy, alkylthio, alkylsulfinyl or alkylsulfonyl group, or an alkoxy group optionally substituted by a halogen atom or by a hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, piperidino, morpholino, thiomorpholino, 4-alkylpiperazino, 4-phenyl-piperazino, 4-methoxyphenylpiperazino, 4-phenylethylpiperazino, phenyl-ethylamino, N-methyl-phenylethylamino or N-methyl-dimethoxyphenylethyl-amino group;
R2 represents a hydrogen or halogen atom or a hydroxy, methoxy, ethoxy, methyl, methylthio, methylsulfinyl or methylsulfonyl group;
R3 represents a hydrogen atom or a methoxy group; or two of the groups R1 to R3 together represent a methylenedioxy group and the remaining R1, R2 or R3 group is as hereinbefore defined;
R4 represents a hydrogen atom, an alkyl group optional b substituted by a hydroxy, phenyl, dimethoxyphenyl, dialkylamino, piperidino, morpholino, 4-methylpiperazino or 4-phenylpiperazino group, or a phenyl group optionally substituted by a halogen atom or by one or two methoxy groups, whereby each of the above mentioned alkyl or alkoxy groups contain from 1 to 4 carbon atoms; and R5 represents a hydrogen atom, a halogen atom or a lower alkyl group and the corresponding imidazo [4,5b]pyridine-N-oxides and isomers thereof and pharmaceutically acceptable acid addition salts thereof, which comprises either: -(a) reacting a compound of the formula:

(II) wherein R5 is as hereinbefore defined and Y represents a group of the formula R4NH-, wherein R4 is as hereinbefore defined, with a compound of the formula (III) wherein R1, R2 and R3 are as hereinbefore defined and X represents a carboxyl, thiocarboxyl or dithiocarboxyl group, or functional derivative thereof; or (b) reacting a compound of the formula:

(IIa) wherein R5 is as hereinbefore defined and Y represents a halogen atom, with a compound of the formula:

(IIIa) wherein R1, R2 and R3 are as hereinbefore defined and X1 represents an appropriate -NR4 containing group which is derived from a carboxyl, thio-carboxyl or dithiocarboxyl group; and when a pharmaceutically acceptable acid addition salt is required converting a base of formula I obtained into such a salt.

2. A compound of the general formula:

(I) or an isomer thereof of the general formula:

(Ia) wherein R1 represents an alkylamino, dialkylamino, hydroxy, allyloxy, benzyloxy, alkylthio, alkylsulfinyl or alkylsulfonyl group, or an alkoxy group optionally substituted by a halogen atom or by a hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, piperidino, morpholino, thiomorpholino, 4-alkylpiperazino, 4 phenyl-piperazino, 4-methoxyphenylpiperazino, 4-phenylethylpiperazino, phenyl-ethylamino, N-methyl-phenylethylamino or N-methyl-dimethoxyphenylethyl-amino group;

R2 represents a hydrogen or halogen atom or a hydroxy, methoxy, ethoxy, methyl, methylthio, methylsulfinyl or methylsulfonyl group;
R3 represents a hydrogen atom or a methoxy group; or two of the groups R1 to R3 together represent a methylenedioxy group and the remaining R1, R2 or R3 group is as hereinbefore defined;
R4 represents a hydrogen atom, an alkyl group optionally substituted by a hydroxy, phenyl, dimethoxyphenyl, dialkylamino, piperidino, morpholino, 4-methylpiperazino or 4-phenylpiperazino group, or a phenyl group optionally substituted by a halogen atom or by one or two methoxy groups, whereby each of the above mentioned alkyl or alkoxy groups contain from 1 to 4 carbon atoms; and R5 represents a hydrogen atom, a halogen atom or a lower alkyl group and the corresponding imidazo [4,5b]pyridine-N-oxides and isomers thereof and pharmaceutically acceptable acid addition salts thereof whenever prepared by the process of claim 1 or by an obvious chemical equivalent thereof.

3. A process according to claim 1 (a), in which the functional deri-vative is an acid halide, anhydride, ester or orthoester.

4. A process according to claim 1 (b), in which -NR4 is derived from a nitrile, amide, amidoester, imidothioester, imidohalide or amidine group.

5. A process according to claim 1, 3 or 4 in which R4 represents a hydrogen atom.

6. A process according to claim 1 in which R4 and R5 represent hydrogen atoms, R2 represents a halogen atom or a methyl, methoxy, ethoxy, methylthio, methylsulfinyl, and R3 represents a hydrogen atom or a methoxy group.

7. A process for the preparation of compounds of general formula I and isomers thereof of general formula Ia as defined in claim 1 which comprises reacting a compound of formula (II) wherein R5 and Y are as defined in claim 1 with a compound of formula (III) wherein R1 to R3 and X are as defined in claim 1 or a functional derivative thereof.

8. A process as claimed in claim 7 wherein the functional derivative is an acid halide, anhydride, ester or orthoester.

9. A process for the preparation of compounds of general formula I
and isomers thereof of general formula Ia as defined in claim 1 which comprises reacting a compound of formula (IIa) wherein R5 and Y1 are as defined in claim 1 with a compound of formula (IIIa) wherein X1 is as defined in claim 1 and wherein R1 represents a hydroxy, allyloxy, benzyloxy, alkylthio, alkylsulfinyl or alkylsulfonyl group; an alkylamino or dialkylamino group, or an alkoxy group containing from 1 to 4 carbon atoms optionally substituted by a halogen atom or by a hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, piperidino, morpholino, thiomorpholino, N-methylpiperazino or N-phenylpiperazino group; R2 represents a hydrogen or halogen atom;
or a hydroxy, methoxy or ethoxy group; and R3 represents a hydrogen atom or a methoxy group; or two of the groups R1 to R3 together represent a methylenedioxy group and the remaining R1, R2 or R3 group is as defined above; each of the above mentioned alkyl groups containing from 1 to 4 carbon atoms .

10. A compound of the general formula:

(I) or an isomer thereof of the general formula:

(Ia) wherein R1 represents a hydroxy, allyloxy, benzyloxy, alkylthio, alkyl-sulfinyl or alkylsulfonyl group, an alkylamino or dialkylamino group, or an alkoxy group containing from 1 to 4 carbon atoms optionally substituted by a halogen atom or by a hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, piperidino, morpholino, thio-morpholino, N-methylpiperazino or N-phenylpiperazino group; R2 represents a hydrogen or halogen atom; or a hydroxy, methoxy or ethoxy group; and R3 represents a hydrogen atom or a methoxy group; or two of the groups R1 to R3 together represent a methylenedioxy group and the remaining R1, R2 or R3 group is as defined above; each of the above mentioned alkyl groups containing from 1 to 4 carbon atoms; R4 represents a hydrogen atom; and alkyl group optionally substituted by a hydroxyl, dialkylamino, phenyl or morpholino group, whereby each of the above mentioned alkyl groups contains from 1 to 4 carbons; or a phenyl group optionally substituted by a halogen atom or a methoxy group; and R5 represents a hydrogen or halogen atom or a lower alkyl group and physiologically compatible acid addition salts thereof, whenever prepared by the process of claim 9 or by an obvious chemical equivalent thereof.

11. A process as claimed in claim 9 wherein the said -NR4- containing group is a nitrile, amide, amido ester, imido thioester, imido halide or amidine group.

12. A process as claimed in any of claims 7, 8 or 9 wherein the reaction is effected in the presence of a solvent.

13. A process as claimed in any of claims 7, 8 or 9 wherein the reaction is effected at temperatures from -20 to 250°C.

14. A process as claimed in either claim 7 or claim 9 wherein a compound of formula III or IIIa wherein X represents a carboxyl or an amide group is reacted with a compound of formula II or IIa as defined in claim 7 or claim 9 respectively in the presence of phosphorus oxychloride or thionyl chloride and in the presence of pyridine or triethylamine at temperatures from -20 to 120°C.

15. A process as claimed in claim 9 wherein a compound of formula IIIa wherein X represents a nitrile group is reacted with a compound of formula IIa as defined in claim 9 in the presence of a catalytic quantity of p-toluenesulfonic acid and at temperatures from 120 to 180°C.

16. A process as claimed in claim 9 wherein a compound of formula IIIa wherein X represents a thioamide group is reacted with a compound of formula IIa as defined in claim 9 at temperatures from 100 to 150°C.

17. A process as claimed in claim 9 wherein a compound of formula IIa wherein Y represents a chlorine atom is reacted with a compound of formula IIIa as defined in claim 9 at temperatures from 100 to 200°C.

18. A process for the preparation of compounds of general formula I
and isomers thereof of general formula Ia as defined in claim 10 which comprises reacting a compound of formula (II) wherein R5 is as defined in claim 10 and Y represents a group of formula R4NH- wherein R4 is as defined in claim 10 with a compound of formula (III) wherein R1 to R3 are as defined in claim 10 and X represents a carboxyl, thiocarboxyl or dithiocarboxyl group or with a functional derivative thereof.

19. A process for the preparation of a compound of the general formula:

(I) or an isomer thereof of the general formula:

(Ia) wherein R1 represents a methyl-amino group, a morpholino group or pipera-zino group substituted in the 4-position by a phenyl group or by an alkyl group containing from 1 to 3 carbon atoms, or an alkoxy group containing from 2 to 4 carbon atoms substituted by a dimethylamino, diethylamino, piperidino, morpholino or thiomorpholino group, phenylethylamino, N-methylphenylethylamino or N-methyldimethoxyphenylethylamino group or by a piperazino group substituted in the 4-position by a methyl, phenyl, methoxyphenyl or phenylethyl group, R2 represents a hydrogen, fluorine or chlorine atom, or a methoxy or ethoxy group; R3 represents a hydrogen atom or a methoxy group; R4 represents a hydrogen atom, an alkyl group containing from 2 to 4 carbon atoms substituted by a phenyl, dimethoxy-phenyl, piperidino, morpholino, 4-methylpiperazino or 4-phenylpiperazino group; and R5 represents a hydrogen atom and physiologically compatible acid addition salts thereof, which comprises reacting a compound of formula (II) wherein R5 represents a hydrogen atom and Y represents a group of formula R4NH- (wherein R4 is as defined above) with a compound of formula (III) wherein R1 to R3 are as defined above and X represen-bs a C~i'b~ b~
carboxy or dithiocarboxy group, or with a functional derivative thereof.

20. A compound of the general formula:

(I) or an isomer thereof of the general formula:

(Ia) wherein Rl represents a methyl-amino group, a morpholino group or piperazino group substituted in the 4-position by a phenyl group or by an alkyl group containing from 1 to 3 carbon atoms, or an alkoxy group containing from 2 to 4 carbon atoms substituted by a dimethylamino, diethylamino, piperidino, morpholino or thiomorpholino group, phenylethyl-amino, N-methylphenylethylamino or N-methyldimethoxyphenylethylamino group or by a piperazino group substituted in the 4-position by a methyl, phenyl, methoxyphenyl or phenylethyl group, R2 represents a hydrogen, fluorine or chlorine atom, or a methoxy or ethoxy group; R3 represents a hydrogen atom or a methoxy group; R4 represents a hydrogen atom, an alkyl group con-taining from 2 to 4 carbon atoms substituted by a phenyl, dimethoxyphenyl, piperidino, morpholino, 4-methylpiperazino or 4-phenylpiperazino group;
and Rs represents a hydrogen atom and physiologically compatible acid addition salts thereof whenever prepared by the process of claim 19 or by an obvious chemical equivalent thereof.

21. A process for the preparation of compounds of general formula I and isomers thereof of general formula Ia as defined in claim 10 which comprises reacting a compound of formula (II) wherein R5 is as defined in claim 10 and Y represents a halogen atom with a compound of formula (III) wherein R1 to R3 are as defined in claim 11 and X represents an appropriate -NR4- containing group (wherein R4 is as defined in claim 10) which is derived from a carboxyl, thiocarboxyl or dithiocarboxyl group.

22. A process for the preparation of compounds of general formula I and isomers thereof of general formula Ia as defined in claim 20 which comprises reacting a compound of formula (II) wherein R5 represents a hydrogen atom and Y represents a halogen atom with a compound of formula (III) wherein R to R3 are as defined in claim 20 and X represents an appropriate -NR4- containing group (wherein R4 is as defined in claim 1) which is derived from a carboxyl, thiocarboxyl or dithiocarboxyl group.

23. A process as claimed in any of claims 1, 7 or 9 wherein a compound of formula I or Ia containing a reactive halogen atom thereby obtained is subsequently converted into the corresponding amino compound by reaction with an amine.

24. A process as claimed in any of claims 1, 7 or 9 wherein a compound of formula I or Ia containing a reacting hydrogen atom thereby obtained is subsequently alkylated by reaction with an alkylating agent in the presence of a base.

25. A process as claimed in any of claims 1, 7 or 9 wherein a compound of formula I or Ia thereby obtained is subsequently converted into the corres-ponding N-oxide, S-oxide or S,S-dioxide compound by means of an oxidising agent.

26. A process according to claim 1 in which R1 and R2 are methoxy groups in the 2- and 4- positions and R3, R4 and R5 are hydrogen atoms.

27. A process according to claim 1 in which 2-(2,4-dimethoxyphenyl)-1H-imidazo[4,5-b]pyridine or its hydrochloride are prepared by either:-(a) reacting 2,3-diaminopyridine with 2,4-dimethoxybenzoic acid in phosphorus oxychloride, thionyl chloride, pyridine; or (b) reacting 2,4-dimethoxylbenzoyl chloride with 2,3-diaminopyridine; (c) heating 2-amino-3-(2,4-dimethoxybenzoyl-amino) pyridine hydrochloride alone or in a solvent or reacting it with phosphorus oxychloride and pyridine; or (d) reacting methyl 2,4-dimethoxyben-zoate with 2,3-diaminopyridine in phosphorus oxychloride; or (e) reacting 2,4-dimethoxybenzoylmorpholine with 2,3-diaminopyridine in pyridine containing phosphorus oxychloride, or (f) reacting 2,4-dimethoxylbenzoyl(4-chloroanilide) with 2,3-diaminopyridine in phosphorus oxychloride; or (g) reacting 2,4-dimethoxybenzoic acid-N-(4-chlorophenyl)-N1-(2-amino-3-pyridyl)amidine hydro-chloride; or (h) reacting 2,3-diaminopyridine with 2,4-dimethoxybenzonitrile and p-toluene sulfonic acid; or (i) reacting 2,3-diaminopyridine with 2,4-dimethoxybenzoyl morpholide and triethylamine; or (j) reacting 2,3-diamino-pyridine with 2,4-dimethoxybenzoyl anhydride; or (k) reacting 2,4-dimethoxy-thiobenzoic acid-morphalide-methiodide with 2,3-diaminopyridine.

28. 2-(2,4-Dimethoxy-phenyl)-1H-imidazo[4,5-b]pyridine or its hydro-chloride whenever prepared by the process of claim 27 or by an obvious chemical equivalent thereof.

29. A process according to claim 1 in which R1 is 2-methoxy, R2 is 4-methylmercapto and R3, R4 and R5 are hydrogen atoms.

30. A process according to claim 1 in which 2-(2-methoxy-4-methylmercapto-phenyl)-1H-imidazo[4,5-b] pyridine hydrochloride is prepared by reacting 2-methoxy-4-methylmercaptobenzoic acid morpholide with 2,3-diaminopyridine and phosphorus oxychloride.

31. 2-(2-Methoxy-4-methylmercapto-phenyl)-1H-imidazo-[4,5-b]pyridine hydrochloride whenever prepared by the process of claim 30 or by an obvious chemical equivalent thereof.

32. A process according to claim 1 in which R1 is 2-methoxy, R2 is 4-methylsulfinyl, R3, R4 and R5 are hydrogen atoms.

33. A process according to claim 25 in which 2-(2-methoxy-4-methyl-sulfinylphenyl)-lH-imidazo[4,5-b] pyridine and its hydrochloride are prepared by oxidising 2-(2-methoxy-4-methylmercaptophenyl)-1H-imidazo-[4,5-b]pyridine and when the hydrochloride is required, reacting the base so obtained with hydrogen chloride.

34. A process according to claim 33 in which the oxidation is effected by reaction with 3-chloroperbenzoic acid.

35. 2-(2-Methoxy-4-methylsulfinyl-phenyl)-1H-imidazo[4,5-b]pyridine and its hydrochloride whenever prepared by the process of claims 33 or 34 or by an obvious chemical equivalent thereof.

36. A process according to claim 1 in which R1 is 2-methoxy, R2 is 4-methyl and R3, R4 and R5 are hydrogen atoms.

37. A process according to claim 1 in which 2-(2-methoxy-4-methylphenyl) -1H-imidazo[4,5-b]pyridine and its hydrochloride are prepared by reacting 2-methoxy-4-methyl-thiobenzoic acid-morpholide and 2,3-diaminopyridine and when the hydrochloride is required reacting the base so obtained with hydrogen chloride.

38. 2-(2-Methoxy-4-methyl-phenyl)-1H-imidazo[4,5-b]pyridine and its hydrochloride whenever prepared by the process of claim 37 or by an obvious chemical equivalent thereof.

39. A process according to claim 1 in which R1 is 2-methoxy, R2 is 5-methylmercapto and R3, R4 and R5 are hydrogen atoms.

40. A process according to claim 1 in which 2-(2-methoxy-5-methylmercap-tophenyl)-1H-imidazo[4,5-b]pyridine and its hydrochloride are prepared by reacting 2-methoxy-5-methylmercaptobenzoic acid morpholide with 2,3-diamino-pyridine in phosphorus oxychloride, pouring into water and neutralising with a base and when the hydrochloride is required reacting the base so obtained with hydrogen chloride.

41. 2-(2-Methoxy-5-methylmercapto-phenyl)-1H-imidazo[4,5-b]pyridine and its hydrochloride whenever prepared by the process of claim 40 or by an obvious chemical equivalent thereof.

42. A process according to claim 1 in which R1 is 2-ethoxy, R2 is methyl and R3, R4 and R5 are hydrogen atoms.

43. A process according to claim 1 in which 2-(2-ethoxy-4-methylphenyl)-1H-imidazo[4,5-b]pyridine and its hydrochloride are prepared by reacting 2-ethoxy-4-methylthiobenzoic acid-morpholide-methiodide with 2,3-diamino-pyridine and when the hydrochloride is required reacting the base so obtained with hydrogen chloride.

44. 2-(2-Ethoxy-4-methyl-phenyl)-1H-imidazo[4,5-b]pyridine and its hydrochloride whenever prepared by the process of claim 43 or by an obvious chemical equivalent thereof.

45. A process according to claim 1 in which R1 is 2-ethoxy, R2 is 4-ethylpiperazine-1-yl and R3, R4 and R5 are hydrogen atoms.

46. A process according to claim 1 in which 2-[2-ethoxy-4-(4-ethyl-piperazin-1-yl)-phenyl]-1H-imidazo[4,5-b]-pyridine and its dihydrochloride are prepared by reacting 2-[2-ethoxy-4-(4-ethyl-piperazin-1-yl)-phenyl]-1,3-dithiolanium iodide with 2,3-diamincopyridine , and when the dihydrochloride is required converting the base so obtained with hydrogen chloride.

47. 2-[2-Ethoxy-4-(4-ethyl-piperazin-1-yl)-phenyl]-1H-imidazo[4,5-b]-pyridine and its dihydrochloride whenever prepared by the process of claim 46 or by an obvious chemical equivalent thereof.