IMIDAZOHETEROCYCLIC COMPOUNDS PROCESSES FOR PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM

Abstract: Imidazoheterocyclic compounds of the formula: wherein R¹ is lower alkenyl, lower alkynyl, lower alkadienyl, lower alkenyloxy (lower) alkyl, lower alkynyloxy(lower)alkyl, carboxy(lower)alkynyloxy(loweralkyl or protected carboxy­ (lower)alkynyloxy(lower)alkyl, R² is hydrogen, lower alkyl or aryl, R³ is ar(lower)alkyl which may have one or more suitable substituent(s), ar(lower)alkenyl, condensed bicyclic hydro­ carbon group, lower alkyl having cyclo(lower)alkyl or lower alkyl, X is O or NH, and Y is CH or N and a pharmaceutical acceptable salt thereof, processes for their preparation and pharmaceutical compositions compris­ ing them as an active ingredient.

Description: The present invention relates to novel imidazoheterocyclic compounds and pharmaceutically acceptable salt thereof. More particularly, it relates to novel imidazoheterocyclic compounds and pharmaceutically acceptable salts thereof which have antiulcerative activity, to processes for preparation thereof, to a pharmaceutical composition comprising the same. EP-A-0 033 094 discloses imidazo[1,2-a]pyridines and 2,3-dihydro-, 5,6,7,8-tetrahydro-, 2,3,5,6,7,8-hexahydro-analogues and salts of such compounds. Also the process for preparing the compounds and pharmaceutical compositions containing them are disclosed. It is described that the compounds are antisecretory and cytoprotective agents and are particularly useful in the treatment of ulcer diseases. Accordingly, one object of the present invention is to provide novel imidazoheterocyclic compounds and pharmaceutically acceptable salt thereof, which are useful as an antiulcerative agent. Another object of the present invention is to provide processes for preparation of said imidazoheterocyclic compounds and salts thereof. A further object of the present invention is to provide a pharmaceutical composition comprising, as an active ingredient, said imidazoheterocyclic compound or its pharmaceutically acceptable salt. Still further object of the present invention is to provide a method of using said imidazoheterocyclic compound or its pharmaceutically acceptable salt in the treatment of ulcer in human or animals. The imidazoheterocyclic compounds of the present invention are novel and can be represented by the formula (I): wherein R¹ is (C₂ - C₆) alkenyl, (C₂ - C₆) alkynyl, (C₃ - C₆) alkadienyl, (C₂ - C₆) alkenyloxy (C₁ - C₆) alkyl, (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl, carboxy (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl or (C₁ - C₆) alkoxycarbonyl (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl; R² is hydrogen, (C₁ - C₆) alkyl or aryl selected from a group consisting of phenyl, tolyl, xylyl, 1-naphthyl, 2-naphthyl, 1-anthryl, and 2-anthryl, R³ is ar (C₁ - C₆) alkyl which has one or more suitable substituent(s) selected from a group consisting of (C₁ - C₆)-alkyl and halogen, ar (C₂ - C₆) alkenyl, benzene-condensed cyclo (C₅ - C₆) alkyl, (C₁ - C₆) alkyl having cyclo (C₃ - C₆) alkyl or (C₁ - C₆) alkyl, and X is O or NH. According to the present invention, the object compounds (I) can be prepared by the following processes. wherein R¹, R², R³, X and Y are each as defined above, R 1 / a is (C₂ - C₆) alkynyl, R 1 / b is cumulated (C₃ - C₆) alkadienyl, R 1 / c is (ω-(C₂ - C₆) alkynyloxy) (C₁ - C₆) alkyl, R 1 / d is (ω-carboxy-ω-(C₂ - C₆) alkynyloxy) (C₁ - C₆) alkyl or (ω-(C₁ - C₆) alkoxycarbonyl-ω-(C₂ - C₆) alkynyloxy)-(C₁ - C₆) alkyl, R⁴ is (C₁ - C₆) alkylene, R⁵ is (C₂ - C₆) alkenyl, (C₂ - C₆) alkynyl, carboxy (C₂ - C₆) alkynyl or (C₁ - C₆) alkoxycarbonyl (C₂ - C₆) alkynyl, Z¹ is an acid residue selected from a group consisting of halogen and acyloxy, and Z² is a leaving group. As to the starting compounds (II), (III) and (IV), some of them are novel and can be prepared by the procedures disclosed in the Preparations as mentioned later. Especially, some of said novel starting compound (II) can be represented by the following general formula: wherein R 3 / a is (C₁ - C₆) alkyl having cyclo (C₃ - C₆) alkyl or ar (C₁ - C₆) alkyl which has one or more suitable substituent(s) selected from the group consisting of (C₁ - C₆) alkyl and halogen, X is O or NH. Suitable pharmaceutically acceptable salts of the object compounds (I) are conventional non-toxic salts and include a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g. sodium salt or potassium salt), an alkaline earth metal salt (e.g. calcium salt or magnesium salt), an ammonium salt; a salt with an organic base, for example, or an organic amine salt (e.g. triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, or N,N'-dibenzylethylenediamine salt); an organic acid addition salt (e.g. acetate, maleate, tartrate, methanesulfonate, benzenesulfonate, formate, or toluenesulfonate), an inorganic acid addition salt (e.g. hydrochloride, hydrobromide, sulfate, or phosphate), or a salt with an amino acid (e.g. arginine, aspartic acid, glutamic acid). In the above and subsequent descriptions of the present specification, suitable examples and illustrations of the various definitions which the present invention includes within the scope thereof are explained in detail as follows. Suitable (C₁ - C₆) alkyl may include methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, pentyl or hexyl, in which the preferred one may be C₁-C₄alkyl and the more preferred one may be methyl and ethyl. Suitable (C₂-C₆) alkenyl'' may include vinyl, allyl, isopropenyl, 1(or 2 or 3)-butenyl, 1(or 2 or 3 or 4)-pentenyl, or 1(or 2 or 3 or 4 or 5)-hexenyl, in which the preferred one may be C₂-C₄alkenyl and the more preferred one may be allyl. Suitable (C₂-C₆) alkynyl'' may include ethynyl, 1(or 2)-propynyl, 1(or 2 or 3)-butynyl, 1-methyl-2-propynyl, 1(or 2 or 3 or 4)-pentynyl, or 1(or 2 or 3 or 4 or 5)-hexynyl, in which the preferred one may be C₂-C₄alkynyl and the more preferred one may be 2-propynyl. Suitable (C₃-C₆) alkadienyl'' may include 1,2-propadienyl, 1,2-butadienyl, 1,3-butadienyl, 2,3-pentadienyl, 1,4-pentadienyl, 1,2-hexadienyl, 1,3-hexadienyl, or 1,4-hexadienyl, in which the preferred one may be C₃-C₅ alkadienyl and the more preferred one may be 1,2-propadienyl. "Cumulated (C₃-C₆) alkadienyl" means the above-defined (C₃-C₆) alkadienyl" group in which two double bonds are adjacent to each other through one carbon atom, and suitable examples of such "cumulated (C₃-C₆)-alkadienyl" may include 1,2-propadienyl, 1,2-butadienyl, 2,3-pentadienyl, or 1,2-hexadienyl, in which the preferred one may be cumulated C₃-C₅alkadienyl and the more preferred one may be 1,2-propadienyl. In the term (C₂-C₆) alkenyloxy (C₁-C₆) alkyl'', suitable (C₂-C₆) alkenyl'' moiety and (C₁-C₆) alkyl'' moiety can be referred to the ones as mentioned above, respectively, and suitable examples of such "(C₂-C₆) alkenyloxy (C₁-C₆)alkyl" may include vinyloxymethyl, allyloxymethyl, 1-allyloxyethyl, 1-allyloxypropyl, 3-allyloxybutyl, 3-(2-butenyloxy)butyl, 5-(3-pentenyloxy)pentyl, or 1-(2-hexenyloxy)hexyl, in which the preferred one may be (C₂-C₄)alkenyloxy(C₁-C₄)alkyl and the more preferred one may be allyloxymethyl. In the term (C₂-C₆) alkynyloxy (C₁-C₆) alkyl'', suitable (C₂-C₆) alkynyl'' moiety and (C₁-C₆) alkyl'' moiety can be referred to the ones as mentioned above, respectively, and suitable examples of such (C₂-C₆) alkynyloxy (C₁-C₆)alkyl'' may include ethynyloxymethyl, 2-propynyloxymethyl, 2-(2-propynyloxy)ethyl, 1-(2-butynyloxy)propyl, 1-(3-butynyloxy)propyl, 2-(3-butynyloxy)butyl, 3-(3-butynyloxy)butyl, 4-(1-pentynyloxy)pentyl, 4-(4-pentynyloxy)pentyl, 5-(5-hexynyloxy)hexyl, or 6-(5-hexynyloxy)hexyl, in which the preferred one may be (C₂-C₄)alkynyloxy(C₁-C₄)alkyl and the more preferred one may be 2-propynyloxymethyl. "Carboxy (C₂-C₆) alkynyloxy (C₁-C₆) alkyl" means the above-defined (C₂-C₆) alkynyloxy (C₁-C₆) alkyl group which is substituted with carboxy, and suitable examples of such "carboxy (C₂-C₆) alkynyloxy (C₁-C₆) alkyl" may include carboxyethynyloxymethyl, 3-carboxy-2-propynyloxymethyl, 1-carboxy-2-propynyloxymethyl, 2-(3-carboxy-2-propynyloxy)ethyl, 1-(1-carboxy-2-butynyloxy)propyl, 1-(4-carboxy-3-butynyloxy)propyl, 2-(4-carboxy-3-butynyloxy)butyl, 3-(4-carboxy-3-butynyloxy)butyl, 4-(3-carboxy-1-pentynyloxy)pentyl, 4-(5-carboxy-4-pentynyloxy)pentyl, 5-(1-carboxy-5-hexynyloxy)hexyl, or 6-(6-carboxy-5-hexynyloxy)hexyl, in which the preferred one may be carboxy(C₂-C₄)alkynyloxy(C₁-C₄)alkyl and the more preferred one may be 3-carboxy-2-propynyloxymethyl. Suitable examples of (C₁-C₆) alkoxycarbonyl (C₂-C₆) alkynyloxy (C₁-C₆)alkyl may be methoxycarbonylethynyloxymethyl, 3-ethoxycarbonyl-2-propynyloxymethyl, 1-ethoxycarbonyl-2-propynyloxymethyl, 2-(3-ethoxycarbonyl-2-propynyloxy)ethyl, 1-(1-propoxycarbonyl-2-butynyloxy)propyl, 1-(4-ethoxycarbonyl-3-butynyloxy)propyl, 2-(4-butoxycarbonyl-3-butynyloxy)butyl, 3-(4-tert-butoxycarbonyl-3-butynyloxy)butyl, 4-(3-pentyloxycarbonyl-1-pentynyloxy)pentyl, 4-(5-ethoxycarbonyl-4-pentynyloxy)pentyl, 5-(1-hexyloxycarbonyl-5-hexynyloxy)hexyl, or 6-(6-hexyloxycarbonyl-5-hexynyloxy)hexyl, in which the preferred one may be (C₁-C₄)alkoxycarbonyl(C₂-C₄)alkynyloxy(C₁-C₄)alkyl and the more preferred one may be 3-ethoxycarbonyl-2-propynyloxymethyl. Suitable "carboxy (C₂-C₆) alkynyl" may be the same as that in the terms of "carboxy (C₂-C₆))alkynyloxy (C₁-C₆))-alkyl" and may include carboxyethynyl, 3-carboxy-2-propynyl, 1-carboxy-2-propynyl, 1-carboxy-2-butynyl, 4-carboxy-3-butynyl, 3-carboxy-1-pentynyl, 1-carboxy-5-hexynyl, or 6-carboxy-5-hexynyl, in which the preferred one may be carboxy(C₂-C₄)alkynyl and the more preferred one may be 3-carboxy-2-propynyl. Suitable (C₁-C₆) alkoxycarbonyl (C₂-C₆))alkynyl may include methoxycarbonylethynyl, 3-ethoxycarbonyl-2-propynyl, 1-ethoxycarbonyl-2-propynyl, 1-propoxycarbonyl-2-butynyl, 4-ethoxycarbonyl-3-butynyl, 4-butoxycarbonyl-3-butynyl, 4-tert-butoxycarbonyl-3-butynyl, 3-pentyloxycarbonyl-1-pentynyl, 1-hexyloxycarbonyl-5-hexynyl, or 6-hexyloxycarbonyl-5-hexynyl, in which the preferred one may be (C₁-C₄)alkoxycarbonyl(C₂-C₄)alkynyl and the more preferred one may be 3-ethoxycarbonyl-2-propynyl. "(ω-(C₂-C₆)Alkynyloxy)(C₁-C₆))alkyl" means the above-defined lower alkynyloxy(C₁-C₆))alkyl group, in which the triple bond always exists on the terminal carbon atom of the (C₂-C₆) alkynyl moiety, and suitable examples of such "(ω-(C₂-C₆)alkynyloxy) (C₁-C₆) alkyl" may include ethynyloxymethyl, 2-propynyloxymethyl, 2-(2-propynyloxy)ethyl, 1-(3-butynyloxy)propyl, 2-(3-butynyloxy)butyl, 4-(4-pentynyloxy)pentyl, or 6-(5-hexynyloxy)hexyl, in which the preferred one may be [ω-(C₂-C₄)alkynyloxy](C₁-C₄)alkyl and the more preferred one may be 2-propynyloxymethyl. "(ω-Carboxy-ω-(C₂-C₆ alkynyloxy) (C₁-C₆) alkyl" means the above-defined ω-(C₂-C₆)alkynyloxy(C₁-C₆) alkyl group which is substituted with carboxy on the terminal carbon atom of the (C₂-C₆) alkynyl moiety, and suitable examples of such "(ω-carboxy-ω-(C₂-C₆)alkynyloxy)(C₁-C₆) alkyl" may include carboxyethynyloxymethyl, 3-carboxy-2-propynyloxymethyl, 2-(3-carboxy-2-propynyloxy)ethyl, 1-(4-carboxy-3-butynyloxy)propyl, 2-(4-carboxy-3-butynyloxy)butyl, 4-(5-carboxy-4-pentynyloxy)pentyl, or 6-(6-carboxy-5-hexynyloxy)hexyl, in which the preferred one may be [ω-carboxy-ω-(C₂-C₄)alkynyloxy](C₁-C₄)alkyl and the more preferred one may be 3-carboxy-2-propynyloxymethyl. "(ω-(C₁-C₆)Alkoxycarbonyl-ω-(C₂-C₆) alkynyloxy (C₁-C₆)-alkyl" means the above-defined ω-(C₁-C₆)alkoxycarbonyl (C₁-C₆)-alkyl-group which is substituted with (C₁-C₆)alkoxycarbonyl as mentioned above on the terminal carbon atom of the (C₂-C₆) alkynyl moiety, and suitable examples of such (ω-(C₁-C₆) alkoxycarbonyl-ω-(C₂-C₆) alkynyloxy) (C₁-6₆) alkyl may be such as methoxycarbonylethynyloxymethyl, 3-ethoxycarbonyl-2-propynyloxymethyl, 2-(3-ethoxycarbonyl-2-propynyloxy)ethyl, 1-(4-propoxycarbonyl-3-butynyloxy)propyl, 3-(4-tert-butoxycarbonyl-3-butynyloxy)butyl, 4-(5-pentyloxycarbonyl-4-pentynyloxy)pentyl, or 5-(6-hexyloxycarbonyl-5-hexynyloxy)hexyl, in which the preferred one may be [ω-(C₁-C₄)alkoxycarbonyl-ω-(C₂-C₄)alkynyloxy](C₁-C₄)alkyl and the more preferred one may be 3-ethoxycarbonyl-2-propynyloxymethyl. Suitable "aryl" may include phenyl, tolyl, xylyl, 1-naphthyl, 2-naphthyl, 1-anthryl, or 2-anthryl, in which the preferred one may be phenyl. Suitable "ar (C₁-C₆) alkyl" may include mono-(or di- or tri-)phenyl (C₁-C₆)alkyl such as benzyl, 1-phenylethyl, 2-phenylethyl, 2-phenylpropyl, 3-phenylbutyl, 1-methyl-2-phenylpropyl, 5-phenylpentyl, 4-phenylhexyl, benzhydryl, 2,3-diphenylpropyl, trityl, or 1,2,3-triphenylbutyl or naphthyl (C₁-C₆) alkyl such as 1-naphthylmethyl, 2-naphthylmethyl, 1-(2-naphthyl)ethyl, 3-(1-naphthyl)propyl, 2-(2-naphthyl)butyl, 5-(1-naphthyl)pentyl, or 4-(2-naphthyl)hexyl ; in which the preferred one may be phenyl(C₁-C₄)alkyl and naphthyl(C₁-C₄)alkyl, and the more preferred one may be benzyl, 1-phenylethyl, 2-phenylethyl, 1-naphthylmethyl and 2-naphthylmethyl. Said "ar (C₁-C₆)alkyl" may have one or more (preferably 1 to 3) suitable substituent(s) selected from a group consisting of (C₁-C₆) alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, pentyl, or hexyl) and halogen (e.g. fluoro, chloro, bromo, iodo), and the preferred examples of said substituted ar(C₁-C₆)alkyl may be mono or di halophenyl(lower)alkyl (e.g. 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-bromobenzyl, 4-bromobenzyl, 2-fluorobenzyl, 4-fluorobenzyl, 4-iodobenzyl, 2-chlorophenethyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 2-chloro-4-fluorobenzyl, mono or di (C₁-C₆) alkylphenyl (C₁-C₆) alkyl (e.g. 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2-methylphenethyl, 2-ethylbenzyl, 2-propylbenzyl, 2-isopropylbenzyl, 3-butylbenzyl, 4-pentylbenzyl, 2-hexylbenzyl, 2,3-dimethylbenzyl, 2,6-dimethylbenzyl, 2,4-diethylbenzyl, or 2-methyl-4-propylbenzyl , and the more preferred one may be mono or dihalophenyl(C₁-C₄)alkyl and mono or di(C₁-C₄)alkyl phenyl(C₁-C₄)alkyl, and the most preferred one may be 2-chlorobenzyl, 3-chlorobenzyl, 2-bromobenzyl, 2-fluorobenzyl, 2,4-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 2-methylbenzyl, 2-ethylbenzyl, 2-isopropylbenzyl and 2,6-dimethylbenzyl. Suitable "ar (C₂-C₆) alkenyl" may include mono (or di or tri)-phenyl(C₂-C₆) alkenyl such as styryl, cinnamyl, phenylbutenyl (e.g. 4-phenyl-2-butenyl, or 2-phenyl-3-butenyl, phenylpentenyl (e.g. 1-phenyl-1-pentenyl, phenylhexenyl (e.g. 4-phenyl-2-hexenyl, 2,3-diphenyl-1-butenyl, or 2,3,4-triphenyl-4-pentenyl, in which the preferred one may be phenyl(C₂-C₄)alkenyl and the more preferred one may be cinnamyl. Suitable "benzene-condensed cyclo (C₅-C₆)alkyl" may include naphthyl, 1,4-dihydronaphthyl, indenyl, benzene-condensed cyclo (C₅-C₆) alkyl (e.g. 1,2,3,4-tetrahydronaphthyl, 2,3-dihydroindenyl, or perhydroindenyl in which the preferred one may be benzene-condensed cyclo(C₅-C₆)alkyl and the more preferred one may be 1,2,3,4-tetrahydronaphthyl. Suitable "(C₁-C₆)alkyl having cyclo (C₃-C₆)alkyl" may include cyclopropylmethyl, cyclobutylmethyl, cyclopentylethyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl, or cyclohexylhexyl, in which the preferred one may be cyclo(C₅-C₆)alkyl(C₁-C₄)alkyl and the more preferred one may be cyclohexylmethyl. Suitable "(C₁-C₆)alkylene" may include methylene, ethylene, trimethylene, propylene, tetramethylene, pentamethylene, or hexamethylene in which the preferred one may be C₁-C₄alkylene and the more preferred one may be methylene. Suitable "an acid residue" may include halogen (e.g. fluorine, chlorine, bromine, iodine), or acyloxy (e.g. acetoxy, tosyloxy, mesyloxy, etc.). Suitable "a leaving group" may include an acid residue as mentioned above, a group of the formula: wherein R⁶, R⁷ and R⁸ are each (C₁-C₆) alkyl as mentioned above, and Z³ is an acid residue as mentioned above . The processes for preparing the object compounds of the present invention are explained in detail in the following. Process 1 The object compound (I) or a salt thereof can be prepared by reacting the compound (II) or a salt thereof with the compound (III) or a salt thereof. Suitable salts of the compound (II) can be referred to the acid addition salt as exemplified for the compound (I) and those of the compound (III) can be referred to the salt with a base for the same. This reaction is usually carried out in a solvent such as alcohol [e.g. methanol, or ethanol, benzene, N,N-dimethylformamide, tetrahydrofuran, diethyl ether or any other solvent which does not adversely affect the reaction. The reaction may be carried out in the presence of an inorganic or an organic base such as an alkali metal hydroxide [e.g. sodium hydroxide, or potassium hydroxide], an alkali metal carbonate [e.g. sodium carbonate, or potassium carbonate], an alkali metal bicarbonate [e.g. sodium bicarbonate, or potassium bicarbonate], tri (C₁-C₆)alkylamine [e.g. trimethylamine, or triethylamine], pyridine or its derivative [e.g. picoline, lutidine, or 4-dimethylaminopyridine], In case that the base to be used is liquid, it can also be used as a solvent. The reaction temperature is not critical, and the reaction can be carried out under cooling, at ambient temperature or under warming or heating. Process 2 The object compound (Ib) or a salt thereof can be prepared by subjecting the compound (Ia) or a salt thereof to isomerization reaction of (C₂-C₆) alkynyl into cumulated (C₃-C₆) alkadienyl. Suitable salts of the compounds (Ia) and (Ib) can be referred to the acid addition salts as exemplified for the compound (I). This reaction is usually carried out in the presence of a base such as an alkali metal hydroxide (e.g. sodium hydroxide, or potassium hydroxide, or an alkali metal carbonate (e.g. sodium carbonate, potassium carbonate). This reaction is usually carried out in a solvent such as alcohol (e.g. methanol, or ethanol). N,N-dimethylformamide or any other solvent which does not adversely affect the reaction. The reaction temperature is not critical, and the reaction can be carried out at ambient temperature or under warming or heating. Process 3 The object compound (Ic) or a salt thereof can be prepared by reacting the compound (IV) or a salt thereof with the compound (V) or a salt thereof. Suitable salts of the compound (IV) can be referred to the acid addition salts as exemplified for the object compound (I). Suitable salts of the compound (Ic) can be referred to the ones as exemplified for the object compound (I). Suitable salts of the compound (V) are salts with a base such as an alkali metal salt (e.g. sodium salt, potassium salt, or lithium salt). This reaction is usually carried out in the presence of a base such as alkali metal hydride (e.g. sodium hydride, potassium hydride, or lithium hydride), alkali metal alkoxide (e.g. potassium t-butoxide or an alkali metal (e.g. sodium, or potassium, lithium ). This reaction is usually carried out in a solvent such as alcohol [e.g. methanol, or ethanol], dimethyl sulfoxide, benzene, N,N-dimethylformamide, tetrahydrofuran, diethyl ether or any other solvent which does not adversely affect the reaction. In case that the compound (V) or a salt thereof to be used is liquid, it can also be used as a solvent. The reaction temperature is not critical, and the reaction can be carried out under cooling, at ambient temperature or under warming or heating. Process 4 The object compound (Ie) or a salt thereof can be prepared by subjecting the compound (Id) or a salt thereof to acylation reaction. Suitable salts of the compound (Id) can be referred to the acid addition salts as exemplified for the compound (I). Suitable salts of the compound (Ie) can be referred to the ones as exemplified for the compound (I). The acylation reaction of this process can be carried out by reacting the compound (Id) or a salt thereof with a conventional agent which can introduce a carboxy or a protected carboxy group into a terminal carbon atom of (C₂-C₆) alkynyl such as carbon dioxide gas, dry ice, (C₁-C₆)alkoxy(halo)formate (e.g. ethyl chloroformate, di(C₁-C₆))alkyl carbonate (e.g. dimethyl carbonate, or diethyl carbonate), di(C₁-C₆))alkyl oxalate (e.g. diethyl oxalate) or tri (C₁-C₆) alkyl phosphonoacetate (e.g. triethyl phosphonoacetate ). This reaction is usually carried out in the presence of a base such as metalated (C₁-C₆) alkyl (e.g. methyl lithium, or n-butyl lithium , metalated aryl (e.g. phenyl lithium), or alkali metal hydride (e.g. sodium hydride, or potassium hydride). This reaction is usually carried out in a solvent such as diethyl ether, tetrahydrofuran, N,N-dimethylformamide, n-hexane or any other solvent which does not adversely affect the reaction. The reaction temperature is not critical, and the reaction can be carried out under cooling or at ambient temperature. The object compounds (I) and their pharmaceutically acceptable salts of the present invention are novel and exhibit high antiulcerative activity. In order to illustrate the usefulness of the object compounds (I), the pharmacological data of some representative compounds of the object compounds (I) are shown in the following. (A) Inhibition on ethanol ulcer Test Method : Five male Sprague-Dawley rats, aged 7 weeks and weighing about 200 g, were used per group for the study on ethanol ulcer after the fast for 24 hours. Test compound was suspended in 0.1% methylcellulose aqueous solution, and the suspension (5 ml/kg) was orally given to each rat. The control group was given a vehicle, i.e. 0.1% methylcellulose aqueous solution (5 ml/kg), alone in the same way. Absolute ethanol (5 ml/kg) was orally administered 30 minutes after dosing with test compound, and one hour later, the rats were sacrificed and their stomachs were removed. The area of ulcers of each rat was measured. The mean area (mm) in the medicated group was compared with that in the control group. Test compounds (1) 8-(2-Methylbenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a] pyridine (2) 8-(2-Chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (3) 8-(2-Methylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine Test Results A) Inhibition % at the dose of 32 mg/kg : Test Compound Inhibition % (1) 94.4 (2) 98.2 (3) 91.8 B) The ED₅₀ value of the Test Compound (1) : 1.1 mg/kg (B) Inhibition on stress ulcer Test Method : Five Sprague-Dawley rats weighing about 200 g were used per group. Each animal was immobilized in a small cage and put in a water bath allowing to respire. The temperature of the water bath kept at 22°C. The test compound was administered orally just before the immobilization. Seven hours later, the animals were sacrificed and their stomachs were removed. The stomach was then fixed with 2% formalin. The area of ulcers was measured for each animal. The mean area (mm²) in the medicated animals was compared with that in the control animals. Test Compounds (1) 8-(2-Methylbenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (2) 8-(2-Chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (3) 8-(2-Methylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine Test Results A) Inhibition % at the dose of 32 mg/kg : Test Compound Inhibition % (1) 100 (2) 100 (3) 100 B) The ED₅₀ value of the Test Compound (1) : 0.15 mg/kg As being apparent from the above test results, the object compound (I) of the present invention are useful as an antiulcerative agent. For therapeutic purpose, the compounds according to the present invention can be used in a form of pharmaceutical preparation containing said compound as an active ingredient, in admixture with a pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient suitable for oral or parenteral administration. The pharmaceutical preparations may be capsules, tablets, dragees, solution, suspension, emulsion, and the like. If desired, there may be included in the above preparations auxiliary substances, stabilizing agents, wetting or emulsifying agents, buffers and other commonly used additives. While the dosage of the compounds will vary depending upon the age and condition of the patient, an average single dose of about 5 mg, 10 mg, 50 mg, 100 mg, 250 mg, 500 mg, and 1000 mg of the compounds according to the present invention may be effective for treating ulcer. In general, amounts between 1 mg/body and about 2,000 mg/body or even more may be administered per day. The following preparations and examples are given for the purpose of illustrating the present invention. Preparation 1 A solution of 5-hexen-2-one (3.92 g) in N,N-dimethylformamide (4 ml) was added to mixture of cupric chloride dihydrate (13.636 g) and lithium chloride (3.392 g) in N,N-dimethylformamide (20 ml) at 80°C. After being stirred at 80-90°C for 1 hour, the mixture was poured into cold water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo to give a crude oil of 3-chloro-5-hexen-2-one (3.01 g) which was used for the next step without purification. Preparation 2 Tosyl chloride (3.81 g) was added to a solution of 3-hydroxy-5-hexyn-2-one (2.24 g) and triethylamine (2.424 g) in methylene chloride (20 ml) under ice-cooling. After being stirred for 2.5 hours, the mixture was washed with water, dried over magnesium sulfate and evaporated in vacuo. The oily residue was purified by column chromatography on silica gel (60 g) using methylene chloride as an eluent to give an oil of 3-tosyloxy-5-hexyn-2-one (2.94 g). IR (film/NaCl) : 3280, 1720, 1590, 1360 (broad) cm⁻¹ NMR (CCl₄, δ) : 1.79 (1H, t, J=2Hz), 2.25 (3H, s), 2.43 (3H, s), 2.3-2.6 (2H, m), 4.66 (1H, t, J=5Hz), 7.31 (2H, d, J=8Hz), 7.78 (2H, d, J=8Hz). Preparation 3 Mesyl chloride (1.73 ml) was added dropwise to a solution of 3-hydroxy-2-methoxy-1-hexen-5-yne (2 g) and triethylamine (3.32 ml) in methylene chloride (20 ml) under ice-cooling over a period of 10 minutes. After being stirred for 48 hours at room temperature the mixture was washed successively with water, aqueous sodium bicarbonate solution, and brine, dried over magnesium sulfate, and evaporated in vacuo to give 3-mesyloxy-2-methoxy-1-hexen-5-yne (3.45 g). IR (film/NaCl) : 3280, 2110 cm⁻¹ NMR (CCl₄, δ) : 1.96 (1H, t, J=3Hz), 2.63-2.80 (2H, m), 2.95 (3H, s), 3.62 (3H, s), 4.22 (1H, d, J=3Hz), 4.40 (1H, d, J=3Hz), 4.93 (1H, t, J=6Hz) Preparation 4 To a solution of 3-mesyloxy-2-methoxy-1-hexen-5-yne (0.5 g) in acetone (1.5 ml) was added 20% sulfuric acid (1.5 ml) under ice-cooling and the mixture was stirred for 1.5 hours under the same conditions and then for 1.5 hours at room temperature. Acetone was evaporated in vacuo and the residue was extracted with methylene chloride. The extract was washed successively with water, aqueous sodium bicarbonate solution, and brine, dried over magnesium sulfate, and evaporated in vacuo to give 3-mesyloxy-5-hexyn-2-one (0.41 g). IR (film/NaCl) : 3290, 2120, 1720 cm⁻¹ NMR (CCl₄, δ) : 2.03 (1H, t, J=3Hz), 2.31 (3H, s) 2.70-2.86 (2H, m), 3.11 (3H, s), 4.92 (1H, t, J=6Hz) Preparation 5 To a mixture of 2-amino-3-hydroxypyridine (7 g) and Adogen 464 (Trademark : prepared by Aldrich Chemical Co.) (0.4 g) in 40% aqueous sodium hydroxide (32 ml) and methylene chloride (32 ml) was added 2-methylbenzyl chloride (8.42 ml) at ambient temperature. After being stirred for 24 hours, the organic layer was separated and the aqueous layer was extracted with methylene chloride. The combined extracts were washed with saturated sodium chloride aqueous solution, dried over magnesium sulfate, and evaporated in vacuo. The crystalline residue was recrystallized from ethyl acetate to give 2-amino-3-(2-methylbenzyloxy)pyridine (7.56 g). mp : 100 to 101°C IR (Nujol) : 3450, 3275, 3125, 1625 cm⁻¹ NMR (CDCl₃, δ) : 2.40 (3H, s), 4.68 (2H, s), 5.05 (2H, s), 6.43-6.73 (1H, m), 6.98 (1H, dd, J=2Hz and 8Hz), 7.10-7.46 (4H, m), 7.66 (1H, dd, J=2Hz and 5Hz) Preparation 6 The following compounds were prepared according to a similar manner to that of Preparation 5. (1) 2-Amino-3-(2-ethylbenzyloxy)pyridine mp : 93 to 95°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3475, 3275, 3130, 1620 cm⁻¹ NMR (CDCl₃, δ) : 1.27 (3H, t, J=8Hz), 2.73 (2H, q, J=8Hz), 4.68 (2H, broad s), 5.07 (2H, s), 6.43-6.73 (1H, m), 6.99 (1H, d, J=7Hz), 7.12-7.50 (4H, m), 7.66 (1H, dd, J=2Hz and 5Hz) (2) 2-Amino-3-(2-isopropylbenzyloxy)pyridine mp : 106 to 107°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3450, 3275, 3120, 1620 cm⁻¹ NMR (CDCl₃, δ) : 1.25 (6H, d, J=6Hz), 2.50-3.45 (1H, m), 4.63 (2H, broad s), 5.05 (2H, s), 6.43-6.75 (1H, m), 7.02 (1H, d, J=8Hz), 7.15-7.48 (4H, m), 7.66 (1H, dd, J=2Hz and 5Hz) (3) 2-Amino-3-(2-chlorobenzyloxy)pyridine mp : 100 to 101°C (recrystallized from methylene chloride) IR (Nujol) : 3465, 3275, 3120, 1620 cm⁻¹ NMR (CDCl₃, δ) : 4.73 (2H, broad s), 5.15 (2H, s), 6.40-6.70 (1H, m), 6.92 (1H, dd, J=2Hz and 8Hz), 7.10-7.50 (4H, m), 7.65 (1H, dd, J=2Hz and 5Hz) (4) 2-Amino-3-(3-chlorobenzyloxy)pyridine mp : 87.5 to 89°C (recrystallized from a mixture of methylene chloride and n-hexane) IR (Nujol) : 3480, 3275, 3100, 1622 cm⁻¹ NMR (CDCl₃, δ) : 4.88 (2H, broad s), 4.97 (2H, s), 6.40-6.63 (1H, m), 6.89 (1H, d, J=8Hz), 7.27 (3H, s), 7.38 (1H, s), 7.65 (1H, dd, J=2Hz and 5Hz) (5) 2-Amino-3-(2-bromobenzyloxy)pyridine mp : 107 to 108°C (recrystallized from ethyl acetate) IR (Nujol) : 3440, 3270, 3125, 1617 cm⁻¹ NMR (CDCl₃, δ) : 4.80 (2H, broad s), 5.11 (2H, s), 6.46-6.70 (1H, m), 6.94 (1H, dd, J=1.5Hz and 7.5Hz), 7.06-7.76 (5H, m) (6) 2-Amino-3-(2,6-dimethylbenzyloxy)pyridine mp : 151 to 155°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3470, 3280, 3145, 1620 cm⁻¹ NMR (CDCl₃, δ) : 2.47 (6H, s), 4.68 (2H, broad s), 5.01 (2H, s), 6.48-6.71 (1H, m), 6.97-7.28 (4H, m), 7.68 (1H, dd, J=2Hz and 5Hz) (7) 2-Amino-3-(2,6-dichlorobenzyloxy)pyridine mp : 146 to 148°C (recrystallized from methanol) IR (Nujol) : 3455, 3270, 3125, 1620 cm⁻¹ NMR (CDCl₃, δ) : 4.70 (2H, broad s), 5.28 (2H, s), 6.45-6.73 (1H, m), 7.02-7.53 (4H, m), 7.67 (1H, dd, J=2Hz and 5Hz) (8) 2-Amino-3-(2-naphthylmethoxy)pyridine mp : 138 to 139°C NMR (CDCl₃, δ) : 4.73 (2H, broad s), 5.22 (2H, s), 6.40-6.70 (1H, m), 6.96 (1H, dd, J=2Hz and 7Hz), 7.30-8.0 (8H, m) (9) 2-Amino-3-(1-naphthylmethoxy)pyridine mp : 146 to 148°C (recrystallized from ethyl acetate) NMR (CDCl₃, δ) : 4.72 (2H, broad s), 5.38 (2H, s), 6.36 (1H, dd, J=5Hz and 8Hz), 7.02 (1H, d, J=8Hz), 7.30-8.13 (8H, m) (10) 2-Amino-3-cinnamyloxypyridine (trans isomer) mp : 127 to 129°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3475, 3275, 3120, 1620 cm⁻¹ NMR (CDCl₃, δ) : 4.66 (2H, d, J=5Hz), 4.79 (2H, broad s), 6.14-7.02 (4H, m), 7.20-7.48 (5H, m), 7.66 (1H, dd, J=2Hz and 5Hz) (11) 2-Amino-3-(1,2,3,4-tetrahydro-1-naphthyloxy)pyridine mp : 106.5 to 107°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3475, 3300, 3140, 1626 cm⁻¹ NMR (CDCl₃, δ) : 1.60-2.36 (4H, m), 2.63-3.06 (2H, m), 4.63 (2H, broad s), 5.20-5.46 (2H, m), 6.46-6.75 (1H, m), 6.98-7.50 (5H, m), 7.65 (1H, dd, J=1Hz and 5Hz) (12) 2-Amino-3-cyclohexylmethoxypyridine mp : 110 to 112°C NMR (CDCl₃, δ) : 0.63-2.10 (11H, m), 3.78 (2H, d, J=6Hz), 4.69 (2H, broad s), 6.43-6.73 (1H, m), 6.90 (1H, dd, J=2Hz and 8Hz), 7.64 (1H, dd, J=2Hz and 5Hz) Preparation 7 Molecular Sieves (16 g) was added to a solution of 2,3-diaminopyridine (8 g), 2-methylbenzaldehyde (8.81 g), and acetic acid (4.2 ml) in methanol (160 ml) and the mixture was stirred for 96 hours at room temperature. Sodium cyanoborohydride (4.61 g) was added portionwise to the mixture with stirring under ice-cooling over a period of 20 minutes. After being stirred for 3 hours, the mixture was made alkaline with aqueous sodium bicarbonate solution and filtered by suction. The filtrate was evaporated in vacuo, and to the residue was added water and then extracted with methylene chloride. The extract was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The crystalline residue was recrystallized from a mixture of ethyl acetate and n-hexane to give 2-amino-3-(2-methylbenzylamino)pyridine (5.38 g). mp : 135 to 140°C NMR (CDCl₃, δ) : 2.36 (3H, s), 3.20-3.63 (1H, broad s), 4.20 (2H, broad d, J=4Hz), 4.40-5.20 (2H, broad s), 6.50-6.93 (2H, m), 7.0-7.63 (5H, m) Preparation 8 2-Amino-3-(2-chlorobenzylamino)pyridine was obtained according to a similar manner to that of Preparation 7. mp : 144 to 147°C NMR (CDCl₃, δ) : 3.60-4.60 (3H, m), 4.36 (2H, d, J=6Hz), 6.43-6.83 (2H, m), 6.96-7.86 (5H, m) Preparation 9 To a solution of 2-methylbenzyl alcohol (0.985 g) in N,N-dimethylformamide (10 ml) was added 62.8% sodium hydride (0.308 g) under a nitrogen atmosphere and then stirred for 30 minutes. 2-Amino-3-chloropyrazine (0.87 g) was added to the solution and the mixture was heated at 65°C for 2 hours and poured onto crushed ice. The resulting precipitates were collected by filtration, washed with n-hexane, and dried in a desiccator to give 2-amino-3-(2-methylbenzyloxy)pyrazine (0.6 g). mp : 70 to 72°C NMR (CDCl₃, δ) : 2.37 (3H, s), 4.40-5.00 (2H, broad s), 5.34 (2H, s), 7.00-7.45 (4H, m), 7.35 (1H, d, J=3Hz), 7.48 (1H, d, J=3Hz) Preparation 10 A mixture of 2-amino-3-chloropyrazine (4.3 g), 2-methylbenzylamine (4.6 g), potassium carbonate (5.5 g), and potassium iodide (0.4 g)) in N,N-dimethylformamide (43 ml) was refluxed for 24 hours under a nitrogen atmosphere and allowed to stand at room temperature. The mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (110 g) with a mixture of chloroform and methanol (100:3) as an eluent to give 2-amino-3-(2-methylbenzylamino)pyrazine (1.4 g). NMR (CDCl₃, δ) : 2.33 (3H, s), 3.80-4.50 (3H, broad s), 4.50 (2H, d, J=5Hz), 6.95-7.35 (4H, m), 7.30 (1H, d, J=3Hz), 7.50 (1H, d, J=3Hz) Preparation 11 A 60% dispersion of sodium hydride in mineral oil (1.87 g) was added portionwise to a suspension of 8-hydroxy-2-methylimidazo[1,2-a]pyridine (6.3 g) in dimethyl sulfoxide (63 ml) at room temperature over a period of 15 minutes. After being stirred for 30 minutes, 2-chlorobenzyl chloride (7.54 g) was added in one portion to the mixture and then the resultant mixture was stirred for 24 hours at room temperature. The mixture was poured into water and the resulting precipitate was collected by filtration. The crude product was purified by column chromatography on silica gel (30 g) with methylene chloride as an eluent to afford a solid, which was recrystallized from a mixture of diethyl ether and n-hexane to give 8-(2-chlorobenzyloxy)-2-methylimidazo[1,2-a]pyridine (7.75 g). mp : 97 to 98°C IR (Nujol) : 1535, 1280, 1260, 1100 cm⁻¹ NMR (CDCl₃, δ) : 2.46 (3H, s), 5.41 (2H, s), 6.26-6.73 (2H, m), 7.05-7.50 (4H, m), 7.52-7.83 (2H, m) Preparation 12 The following compounds were obtained according to a similar manner to that of Preparation 11. (1) 8-(2-Methylbenzyloxy)-2-methylimidazo[1,2-a]pyridine mp : 101 to 103°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 1530, 1485, 1275, 1260, 1095 cm⁻¹ NMR (CDCl₃, δ) : 2.36 (3H, s), 2.43 (3H, s), 5.23 (2H, s), 6.28-6.63 (2H, m), 7.0-7.53 (5H, m), 7.59 (1H, dd, J=1.5HZ and 6HZ) (2) 8-(1-Phenylethoxy)-2-methylimidazo[1,2-a]pyridine NMR (CDCl₃, δ) : 1.80 (3H, d, J=7Hz), 2.52 (3H, s), 5.50 (1H, q, J=7Hz), 6.06-6.56 (2H, m), 6.93-7.66 (7H, m) (3) 8-(3-Chlorobenzyloxy)-2-methylimidazo[1,2-a]pyridine mp : 108 to 110°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 1590, 1530, 1490, 1275, 1260, 1160, 1100 cm⁻¹ NMR (CDCl₃, δ) : 2.46 (3H, s), 5.26 (2H, s), 6.25-6.75 (2H, m), 7.15-7.45 (4H, m), 7.50 (1H, s), 7.63 (1H, dd, J=2Hz and 6Hz) (4) 8-(2-Bromobenzyloxy)-2-methylimidazo[1,2-a]pyridine mp : 113 to 114°C (recrystallized from diethyl ether) NMR (CDCl₃, δ) : 2.54 (3H, s), 5.43 (2H, s), 6.29-6.76 (2H, m), 7.10-7.80 (6H, m) (5) 8-(2,6-Dichlorobenzyloxy)-2-methylimidazo[1,2-a]pyridine mp : 157 to 160°C NMR (CDCl₃, δ) : 2.43 (3H, s), 5.45 (2H, s), 6.46-6.76 (2H, m), 7.13-7.46 (4H, m), 7.56-7.76 (1H, m) (6) 8-(2,4-Dichlorobenzyloxy)-2-methylimidazo[1,2-a]pyridine mp : 140 to 141°C (recrystallized from ethyl acetate) IR (Nujol) : 1280, 1100 cm⁻¹ NMR (CDCl₃, δ) : 2.50 (3H, s), 5.36 (2H, s), 6.20-6.73 (2H, m), 7.10-7.80 (5H, m) Preparation 13 A solution of 2-amino-3-(2-methylbenzylamino)-pyridine (3.25 g) and chloroacetone (1.26 ml) in ethanol (65 ml) was refluxed for 18 hours and then evaporated in vacuo. To the residue was added aqueous sodium bicarbonate solution and the mixture was extracted with methylene chloride. The extract was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The oily residue was purified by column chromatography on silica gel (40 g) with a mixture of methylene chloride and ethyl acetate (10:1) as an eluent to give 8-(2-methylbenzylamino)-2-methylimidazo[1,2-a]pyridine (1.80 g). NMR (CDCl₃, δ) : 2.38 (3H, s), 2.42 (3H, s), 4.40 (2H, d, J=6Hz), 5.06-5.46 (1H, broad s), 6.04 (1H, d, J=7.5Hz), 6.56 (1H, t, J=7Hz), 7.10-7.56 (6H, m) Preparation 14 8-(2-Chlorobenzylamino)-2-methylimidazo[1,2-a]pyridine was obtained according to a similar manner to that of Preparation 13. NMR (CDCl₃ δ) : 2.43 (3H, s), 4.56 (2H, d, J=6Hz), 5.36-5.76 (1H, m), 5.96 (1H, d, J=7Hz), 6.52 (1H, t, J=7Hz), 7.06-7.63 (6H, m) Preparation 15 To a solution of 37% aqueous formaldehyde (2.38 g) in acetic acid (38 ml) was added dropwise 50% aqueous dimethylamine (2.63 g) with ice-cooling over a period of 10 minutes and the mixture was stirred for an additional 10 minutes. The mixture was heated at 50-55°C for 2 hours after an addition of 8-(2-chlorobenzyloxy)-2-methylimidazo[1,2-a]pyridine (7.6 g) thereto and then evaporated in vacuo. The residue was basified with aqueous sodium hydroxide and extracted with methylene chloride. The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residual solid was recrystallized from a mixture of diethyl ether and n-hexane to give 8-(2-chlorobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine (7.85 g). mp : 100 to 101°C IR (Nujol) : 1550, 1295, 1285 cm⁻¹ NMR (CDCl₃, δ) : 2.26 (6H, s), 2.50 (3H, s), 3.63 (2H, s), 5.43 (2H, s), 6.30-6.80 (2H, m), 7.10-7.46 (3H, m), 7.50-7.93 (2H, m) Preparation 16 The following compounds were obtained according to a similar manner to that of Preparation 15. (1) 8-(2-Methylbenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine mp : 65 to 67°C (recrystallized from petroleum ether) IR (Nujol) : 1535, 1270, 1085, 1010 cm⁻¹ NMR (CDCl₃, δ) : 2.21 (6H, s), 2.40 (3H, s), 2.45 (3H, s), 3.60 (2H, s), 5.26 (2H, s), 6.30-6.77 (2H, m), 7.07-7.56 (4H, m), 7.81 (1H, dd, J=1.5Hz and 6Hz) (2) 8-(1-Phenylethoxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine NMR (CDCl₃, δ) : 1.80 (3H, d, J=7Hz), 2.23 (6H, s), 2.50 (3H, s), 3.60 (2H, s), 5.50 (1H, q, J=7Hz), 6.25 (1H, dd, J=1Hz and 6Hz), 6.46 (1H, t, J=6Hz), 7.16-7.56 (5H, m), 7.71 (1H, dd, J=1Hz and 6Hz) (3) 8-(3-Chlorobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine mp : 71 to 72°C (recrystallized from a mixture of of diethyl ether and n-hexane) IR (Nujol) : 1540, 1290, 1275 cm⁻¹ NMR (CDCl₃, δ) : 2.22 (6H, s), 2.46 (3H, s), 3.63 (2H, s), 5.29 (2H, s), 6.30-6.79 (2H, m), 7.16-7.46 (3H, m), 7.52 (1H, s), 7.83 (1H, dd, J=2Hz and 6Hz) (4) 8-(4-Chlorobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine mp : 132 to 134°C NMR (DMSO-d₆, δ) : 2.12 (6H, s), 2.30 (3H, s), 3.6 (2H, s), 5.25 (2H, s), 6.60-6.80 (2H, m), 7.45 (4H, s), 7.76-7.96 (1H, m) (5) 8-(2-Bromobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine mp : 107 to 108°C (recrystallized from petroleum ether) NMR (CDCl₃, δ) : 2.22 (6H, s), 2.46 (3H, s), 3.60 (2H, s), 5.37 (2H, s), 6.27-6.73 (2H, m), 6.93-7.73 (4H, m), 7.80 (1H, dd, J=2Hz and 6Hz) (6) 8-(2,6-Dichlorobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine mp : 141 to 145°C NMR (CDCl₃, δ) : 2.25 (6H, s), 2.45 (3H, s), 3.63 (2H, s), 5.50 (2H, s), 6.53-6.83 (2H, m), 7.16-7.50 (3H, m), 7.85 (1H, dd, J=3Hz and 5Hz) (7) 8-(3,4-Dichlorobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine mp : 96 to 98°C NMR (CDCl₃, δ) : 2.23 (6H, s), 2.46 (3H, s), 3.60 (2H, s), 5.25 (2H, s), 6.36-6.80 (2H, m), 7.20-7.66 (3H, m), 7.83 (1H, dd, J=2Hz and 7Hz) (8) 8-(2,4-Dichlorobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine mp : 90 to 92°C NMR (CDCl₃, δ) : 2.23 (6H, s), 2.46 (3H, s), 3.63 (2H, s), 5.36 (2H, s), 6.26-6.76 (2H, m), 7.23 (1H, dd, J=2Hz and 8Hz), 7.40 (1H, d, J=2Hz), 7.56 (1H, d, J=8Hz), 7.80 (1H, dd, J=2Hz and 7Hz) (9) 8-Benzyloxy-3-dimethylaminomethylimidazo[1,2-a]pyridine mp : 86 to 87°C NMR (CDCl₃, δ) : 2.23 (6H, s), 3.66 (2H, s), 5.33 (2H, s), 6.36-6.76 (2H, m), 7.20-7.60 (6H, m), 7.90 (1H, dd, J=2Hz and 6Hz) (10) 8-Benzyloxy-3-dimethylaminomethyl-2-phenylimidazo[1,2-a]pyridine mp : 87 to 89°C (recrystallized from a mixture of ethyl acetate and n-hexane) NMR (CDCl₃, δ) : 2.23 (6H, s), 3.83 (2H, s), 5.40 (2H, s), 6.30-6.80 (2H, m), 7.20-8.13 (11H, m) (11) 8-(2-Methylbenzylamino)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine NMR (CDCl₃, δ) : 2.22 (6H, s), 2.38 (6H, s), 3.58 (2H, s), 4.36 (2H, d, J=6Hz), 5.0-5.43 (1H, broad s), 6.06 (1H, d, J=7Hz), 6.59 (1H, t, J=7Hz), 7.05-7.45 (4H, m), 7.55 (1H, d, J=7Hz) (12) 8-(2-Chlorobenzylamino)-3-dimethylaminomethyl-2-methylimidazo[1,2-a[pyridine NMR (CDCl₃, δ) : 2.25 (6H, s), 2.45 (3H, s), 3.62 (2H, s), 4.60 (2H, d, J=6Hz), 5.40-5.83 (1H, m), 6.03 (1H, d, J=7Hz), 6.60 (1H, t, J=7Hz), 7.07-7.56 (4H, m), 7.60 (1H, d, J=7Hz) Preparation 17 Methyl iodide (3.48 g) was added dropwise to a solution of 8-(2-chlorobenzyloxy)-3-dimethylaminomethyl-2-methylimidazo[1,2-a]pyridine (7.8 g) in acetone (100 ml) at room temperature and the mixture was stirred for 24 hours. The resulting precipitate was collected by filtration, washed with acetone, and dried in a desiccator to give 8-(2-chlorobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide (11.35 g). mp : > 165°C (decomp.) IR (Nujol) : 1540, 1400, 1360, 1290 cm⁻¹ NMR (DMSO-d₆, δ) : 2.50 (3H, s), 3.20 (9H, s), 5.10 (2H, s), 5.39 (2H, s), 6.98 (2H, broad d, J=4Hz), 7.30-7.86 (4H, m), 8.55 (1H, broad-t, J=4Hz). Preparation 18 The following compounds were obtained according to a similar manner to that of Preparation 17. (1) 8-(2-Methylbenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : >175°C (decomp.) IR (Nujol) : 1545, 1490, 1285, 1270 cm⁻¹ NMR (DMSO-d₆, δ) : 2.38 (3H, s), 2.46 (3H, s), 3.13 (9H, s), 5.02 (2H, s), 5.28 (2H, s), 6.9-7.6 (6H, m), 8.45 (1H, t, J=3.5Hz) (2) 8-(1-Phenylethoxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : 158°C (decomp.) NMR (DMSO-d₆, δ) : 1.63 (3H, d, J=6Hz), 2.49 (3H, s), 3.10 (9H, s), 4.96 (2H, s), 5.78 (1H, q J=6Hz), 6.53-7.0 (2H, m), 7.11-7.65 (5H, m), 8.35 (1H, broad d, J=6Hz) (3) 8-(3-Chlorobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : >153°C (decomp.) IR (Nujol) : 1540, 1290, 1080 cm⁻¹ NMR (DMSO-d₆, δ) : 2.49 (3H, s), 3.16 (9H, s), 5.06 (2H, s), 5.39 (2H, s), 6.86-7.1 (2H, m), 7.33-7.73 (4H, m), 8.40-8.63 (1H, m) (4) 8-(4-Chlorobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : >180°C (decomp.) NMR (DMSO-d₆, δ) : 2.52 (2H, s), 3.22 (9H, s), 5.10 (2H, s), 5.33 (2H, s), 6.80-7.10 (2H, m), 7.30-7.70 (4H, m), 8.54 (1H, broad t, J=3Hz) (5) 8-(2-Bromobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : >160°C (decomp.) NMR (DMSO-d₆, δ) : 2.47 (3H, s), 3.14 (9H, s), 5.01 (2H, s), 5.32 (2H, s), 6.86-7.06 (2H, m), 7.23-7.86 (4H, m), 8.36-8.63 (1H, m) (6) 8-(2,6-Dichlorobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : 270 to 275°C (decomp.) NMR (DMSO-d₆, δ) : 2.40 (3H, s), 3.10 (9H, s), 5.00 (2H, s), 5.40 (2H, s), 6.76-7.20 (2H, m), 7.40-7.70 (3H, m), 8.45 (1H, dd, J=2Hz and 6Hz) (7) 8-(3,4-Dichlorobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : 190°C (decomp.) NMR (DMSO-d₆, δ) : 2.43 (3H, s), 3.13 (9H, s), 5.00 (2H, s), 5.45 (2H, s), 6.46-6.76 (2H, m), 7.36-7.83 (3H, m), 8.45 (1H, dd, J=2Hz and 4Hz) (8) 8-(2,4-Dichlorobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : 187°C (decomp.) NMR (DMSO-d₆, δ) : 2.50 (3H, s), 3.20 (9H, s), 5.03 (2H, s), 5.35 (2H, s), 6.86-7.10 (2H, m), 7.50 (1H, dd, J=2Hz and 8Hz), 7.68 (1H, d, J=2Hz), 7.75 (1H, d, J=8Hz), 8.43-8.63 (1H, m) (9) 8-Benzyloxy-3-trimethylammoniomethylimidazo[1,2-a]pyridine iodide mp : 202°C (decomp.) NMR (DMSO-d₆, δ) : 3.16 (9H, s), 5.10 (2H, s), 5.36 (2H, s), 6.70-7.20 (2H, m), 7.26-7.73 (5H, m), 7.86 1H, s), 8.56 (1H, dd, J=2Hz and 6Hz) (10) 8-Benzyloxy-3-trimethylammoniomethyl-2-phenylimidazo[1,2-a]pyridine iodide mp : 159°C (decomp.) NMR (DMSO-d₆, δ) : 2.90 (9H, s), 5.23 (2H, s), 5.33 (2H, s), 6.90-7.10 (2H, m), 7.23-8.00 (10H, m), 8.56 (1H, dd, J=3Hz and 5Hz) (11) 8-(2-Methylbenzylamino)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : 190°C (decomp.) NMR (DMSO-d₆, δ) : 2.35 (3H, s), ca. 2.4-2.7 (3H, s), 3.12 (9H, s), 4.45 (2H, d, J=6Hz), 4.85 (2H, s), 6.08 (1H, d, J=8Hz), 6.35-6.95 (2H, m), 7.06-7.36 (4H, m), 8.03 (1H, d, J=7Hz) (12) 8-(2-Chlorobenzylamino)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide mp : >140°C (decomp.) NMR (DMSO-d₆, δ) : 2.53 (3H, s), 3.16 (9H, s), 4.55 (2H, d, J=6Hz), 4.98 (2H, s), 6.03 (1H, d, J=8Hz), 6.56-6.93 (2H, m), 7.10-7.63 (4H, m), 8.11 (1H, d, J=7Hz) Example 1 A solution of 2-amino-3-benzyloxypyridine (3 g) and 3-chloro-5-hexen-2-one (2.981 g) in ethanol (15 ml) was stirred and refluxed for 45 hours and then evaporated in vacuo. To the residue was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo. The oily residue was purified by column chromatography on silica gel (50 g) using methylene chloride and then chloroform as eluents. The eluate with chloroform was evaporated in vacuo and the residual solid was recrystallized from diisopropyl ether to give 8-benzyloxy-3-allyl-2-methylimidazo[1,2-a]pyridine (0.31 g). mp : 90.5 to 91.5°C IR (Nujol) : 1530, 1275 cm⁻¹ NMR (CDCl₃, δ) : 2.43 (3H, s), 3.43-3.66 (2H, m), 4.69-5.20 (2H, m), 5.30 (2H, s), ca. 5.4-6.2 (1H, m), 6.23-6.69 (2H, m), 7.13-7.58 (6H, m) Analysis Calcd. for C₁₈H₁₈N₂O : C: 77.67; H: 6.52; N: 10.06 Found : C: 78.06; H: 6.61; N: 9.94 Example 2 A solution of 2-amino-3-benzyloxypyridine (2 g) and 3-tosyloxy-5-hexyn-2-one (2.66 g) in ethanol (15 ml) was stirred and refluxed for 24 hours and then evaporated in vacuo. To the residue was added an aqueous solution of sodium bicarbonate and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo. The oily residue was purified by column chromatography on silica gel (50 g) using chloroform as an eluent to give a solid, which was recrystallized from a mixture of methylene chloride and diethyl ether to give 8-benzyloxy-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine (0.855 g). mp : 112 to 112.5°C IR (Nujol) : 3270, 1570, 1535, 1280, 1265, 1085, 1010 cm⁻¹ NMR (CDCl₃, δ) : 2.05 (1H, t, J=3Hz), 2.48 (3H, s), 3.73 (2H, d, J=3Hz), 5.33 (2H, s), 6.31-6.78 (2H, m), 7.20-7.76 (6H, m) Analysis Calcd. for C₁₈H₁₆N₂O : C: 78.24; H: 5.84: N: 10.14 Found : C: 78.40; H: 5.72; N: 10.30 Example 3 8-(2-Phenylethoxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine was obtained by reacting 2-amino-3-(2-phenylethoxy)pyridine with 3-mesyloxy-5-hexyn-2-one according to similar manners to those of Examples 1 and 2. mp : 114 to 116°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3295, 3095, 2100 cm⁻¹ NMR (CDCl₃, δ) : 2.07 (1H, t, J=3Hz), 2.49 (3H, s), 3.30 (2H, t, J=8Hz), 3.76 (2H, d, J=3Hz), 4.37 (2H, t, J=8Hz), 6.33-6.86 (2H, m), 7.30 (5H, s), 7.68 (1H, dd, J=1Hz and 7Hz) Analysis Calcd. for C₁₉H₁₈N₂O : C: 78.59; H: 6.25; N: 9.65 Found : C: 78.43; H: 6.11; N: 9.98 Example 4 A solution of 2-amino-3-(2-methylbenzyloxy)pyridine (5 g) and 3-tosyloxy-5-hexyn-2-one (7.45 g) in ethanol (35 ml) was heated under reflux for 28 hours and then evaporated in vacuo. The residue was dissolved in ethyl acetate and the solution was allowed to stand at ambient temperature. The resultant precipitate was collected by filtration and dissolved in a mixture of methylene chloride and aqueous sodium bicarbonate. The organic layer was separated, washed with saturated sodium chloride aqueous solution, treated with silica gel and activated charcoal successively, and evaporated in vacuo. The crystalline residue was recrystallized from ethyl acetate to give 8-(2-methylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine (1.44 g). mp : 138 to 140°C IR (Nujol) : 3270, 1570, 1535 cm⁻¹ NMR (CDCl₃, δ) : 2.04 (1H, t, J=3Hz), 2.38 (3H, s), 2.44 (3H, s), 3.75 (2H, d, J=3Hz), 5.28 (2H, s), 6.45 (1H, dd, J=1Hz and 8Hz), 6.66 (1H, t, J=8Hz), 7.06-7.30 (3H, m), 7.37-7.55 (1H, m), 7.70 (1H, dd, J=1Hz and 8Hz) Analysis, Calcd. for C₁₉H₁₈N₂O : C : 78.59; H: 6.25; N: 9.65 Found : C : 78.69; H: 6.11; N: 9.74 Example 5 The following compounds were prepared according to similar manners to those of Examples 1, 2, 3 and 4. (1) 8-(2-Ethylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 109 to 110°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3275 cm⁻¹ NMR (CDCl₃, δ) : 1.24 (3H, t, J=8Hz), 2.03 (1H, t, J=3Hz), 2.43 (3H, s), 2.76 (2H, q, J=8Hz), 3.74 (2H, d, J=3Hz), 5.31 (2H, s), 6.49 (1H, d, J=7Hz), 6.68 (1H, t, J=7Hz), 7.13-7.43 (3H, m), 7.49-7.66 (1H, m), 7.81 (1H, d, J=7Hz) Analysis Calcd. for C₂₀H₂₀N₂O : C: 78.92; H: 6.62; N: 9.20 Found : C: 79.13; H: 6.39; N: 9.23 (2) 8-(2-Isopropylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 108 to 109°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3280 cm⁻¹ NMR (CDCl₃, δ) : 1.26 (6H, d, J=7Hz), 2.03 (1H, t, J=3Hz), 2.43 (3H, s), 3.32 (1H, septet, J=7Hz), 3.74 (2H, d, J=3Hz), 5.36 (2H, s), 6.45 (1H, d, J=7Hz), 6.66 (1H, t, J=7Hz), 7.00-7.53 (4H, m), 7.69 (1H, d, J=7Hz) Analysis, Calcd. for C₂₁H₂₂N₂O : C: 79.21; H: 6.96; N: 8.80 Found : C: 79.32; H: 7.38; N: 8.68 (3) 8-(2-Chlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 130 to 131°C (recrystallized from ethyl acetate) IR (Nujol) : 3265, 1560, 1525 cm⁻¹ NMR (CDCl₃, δ) : 2.05 (1H, t, J=3Hz), 2.46 (3H, s), 3.76 (2H, d, J=3Hz), 5.42 (2H, s), 6.42 (1H, d, J=7Hz), 6.66 (1H, t, J=7Hz), 7.15-7.50 (3H, m), 7.53-7.70 (1H, m), 7.72 (1H, d, J=7Hz) Analysis, Calcd. for C₁₈H₁₅CℓN₂O : C: 69.57; H: 4.86; N: 9.01 Found : C: 69.58; H: 5.13; N: 9.06 (4) 8-(3-Chlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine. mp : 110 to 111°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3200, 1542 cm⁻¹ NMR (CDCl₃, δ) : 2.04 (1H, t, J=3Hz), 2.46 (3H, s), 3.76 (2H, d, J=3Hz), 5.29 (2H, s), 6.43 (1H, d, J=7Hz), 6.66 (1H, t, J=7Hz), 7.18-7.40 (3H, m), 7.49 (1H, s), 7.71 (1H, d, J=7Hz) Analysis Calcd. for C₁₈H₁₅CℓN₂O: C: 69.57; H: 4.86; N: 9.11 Found : C: 69.86; H: 4.79; N: 9.11 (5) 8-(4-Chlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 173 to 175°C (recrystallized from ethyl acetate) IR (Nujol) : 3295 cm⁻¹ NMR (CDCl₃, δ) : 2.05 (1H, t, J=3Hz), 2.48 (3H, s), 3.76 (2H, d, J=3Hz), 5.30 (2H, s), 6.32-6.83 (2H, m), 7.19-7.56 (4H, m), 7.72 (1H, dd, J=2Hz, 6Hz) Analysis Calcd. for C₁₈H₁₅CℓN₂O : C: 69.57; H: 4.86; N: 9.01 Found : C: 69.45; H: 4.55; N: 9.18 (6) 8-(2-Bromobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 156 to 157°C (recrystallized from ethyl acetate) IR (Nujol) : 3150, 2100, 1535 cm⁻¹ NMR (CDCl₃, δ) : 2.0-2.17 (1H, m), 2.46 (3H, s), 3.76 (2H, d, J=3Hz), 5.38 (2H, s), 6.40 (1H, d, J=7.5Hz), 6.65 (1H, t, J=7.5Hz), 7.03-7.40 (2H, m), 7.50-7.80 (3H, m) Analysis Calcd. for C₁₈H₁₅BrN₂O : C: 60.86; H: 4.26; N: 7.89 Found : C: 61.01; H: 4.45; N: 7.84 (7) 8-(2-Fluorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 123 to 125°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3300, 3275 cm⁻¹ NMR (CDCl₃, δ) : 2.06 (1H, t, J=3Hz), 2.49 (3H, s), 3.77 (2H, d, J=3Hz), 5.40 (2H, s), 6.52 (1H, d, J=7Hz), 6.69 (1H, t, J=7Hz), 6.92-7.63 (4H, m), 7.73 (1H, d, J=7Hz) Analysis, Calcd. for C₁₈H₁₅FN₂O : C: 73.45; H: 5.14; N: 9.52 Found : C: 73.72; H: 5.02; N: 9.45 (8) 8-(2,6-Dimethylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 165 to 168°C (recrystallized from a mixture of ethanol and n-hexane) IR (Nujol) : 3185 cm⁻¹ NMR (CDCl₃, δ) : 2.06 (1H, t, J=3Hz), 2.39 and 2.40 (each s, total 9H), 3.76 (2H, d, J=3Hz), 5.23 (2H, s), 6.53-6.87 (2H, m), 6.94-7.28 (3H, m), 7.73 (1H, dd, J=2Hz and 7Hz) Analysis Calcd. for C₂₀H₂₀N₂O : C: 78.92; H: 6.62; N: 9.20 Found : C: 78.95; H: 6.38; N: 9.06 (9) 8-(2,6-Dichlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 183 to 184°C (decomp.) (recrystallized from a mixture of methylene chloride and diisopropyl ether) IR (Nujol) : 3180, 1540 cm⁻¹ NMR (CDCl₃, δ) : 2.06 (1H, t, J=3Hz), 2.43 (3H, s), 3.75 (2H, d, J=3Hz), 5.47 (2H, s), 6.57-6.89 (2H, m), 7.17-7.43 (3H, m) 7.76 (1H, dd, J=2Hz and 7Hz) Analysis Calcd. for C₁₈H₁₄Cl₂N₂O : C: 62.62; H: 4.09; N: 8.11 Found : C: 63.14; H: 4.29; N: 8.17 (10) 8-(2-Naphthylmethoxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 138 to 139°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3290 cm⁻¹ NMR (CDCl₃, δ) : 2.04 (1H, t, J=3Hz), 2.50 (3H, s), 3.74 (2H, d, J=3Hz), 5.50 (2H, s), 6.33-6.78 (2H, m), 7.23-8.01 (8H, m) (11) 8-(1-Naphthylmethoxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 138 to 139°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3175, 2100 cm⁻¹ NMR (CDCl₃, δ) : 2.05 (1H, t, J=3Hz), 2.46 (3H, s), 3.75 (2H, d, J=3Hz), 5.80 (2H, s), 6.42-6.82 (2H, m), 7.22-8.26 (8H, m) Analysis Calcd. for C₂₂H₁₈N₂O : C: 80.96; H: 5.56; N: 8.58 Found : C: 80.86; H: 5.62; N: 8.86 (12) 8-(1,2,3,4-Tetrahydro-1-naphthyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 139 to 141°C (recrystallized from a mixture of ethanol and n-hexane) IR (Nujol) : 3180 cm⁻¹ NMR (CDCl₃, δ) : 1.67-2.34 (5H, m), 2.44 (3H, s), 2.83-2.97 (2H, m), 3.78 (2H, d, J=3Hz), 5.79 (1H, broad t, J=4Hz), 6.57-6.89 (2H, m), 7.01-7.30 (3H, m), 7.36-7.54 (1H, m), 7.74 (1H, dd, J=2Hz and 7Hz) Analysis Calcd. for C₂₁H₂₀N₂O·1/2H₂O : C: 77.51; H: 6.50; N: 8.61 Found : C: 78.08; H: 6.46; N: 8.66 (13) 8-(Cinnamyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine (trans isomer) mp : 130 to 131°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3280 cm⁻¹ NMR (CDCl₃, δ) : 2.04 (1H, t, J=3Hz), 2.44 (3H, s), 3.75 (2H, d, J=3Hz), 4.91 (2H, d, J=5Hz), 6.28-6.90 (4H, m), 7.14-7.44 (5H, m), 7.71 (1H, d, J=7.5Hz) Analysis Calcd. for C₂₀H₁₈N₂O : C: 79.44; H: 6.00; N: 9.26 Found : C: 79.26; H: 6.10; N: 9.24 (14) 8-Cyclohexylmethoxy-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 118 to 119.5°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3200, 2100 cm⁻¹ NMR (CDCl₃, δ) : 0.83-2.26 (11H, m), 2.03 (1H, t, J=3Hz), 2.46 (3H, s), 3.80 (2H, d, J=3Hz), 3.98 (2H, d, J=6Hz), 6.48 (1H, d, J=7Hz), 6.73 (1H, t, J=7Hz), 7.71 (1H, dd, J=1Hz and 7Hz) Analysis Calcd. for C₁₈H₂₂N₂O : C: 76.56; H: 7.85; N: 9.92 Found : C: 77.05; H: 7.54; N: 9.80 (15) 8-Ethoxy-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine mp : 163 to 165°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3190, 2100 cm⁻¹ NMR (CDCl₃, δ) : 1.53 (3H, t, J=7Hz), 2.03 (1H, t, J=3Hz), 2.44 (3H, s), 3.73 (2H, d, J=3Hz), 4.20 (2H, q, J=7Hz), 6.40 (1H, d, J=7Hz), 6.66 (1H, t, J=7Hz), 7.65 (1H, dd, J=1Hz and 7Hz) Analysis Calcd. for C₁₃H₁₄N₂O : C: 72.87; H: 6.59; N: 13.07 Found : C: 73.04; H: 6.48; N: 13.26 (16) 8-(2-Methylbenzyloxy)-3-(1,2-propadienyl)-2-methylimidazo[1,2-a]pyridine mp : 88 to 89°C (recrystallized from a mixture of diethyl ether and petroleum ether) IR (Nujol) : 1930 cm⁻¹ (17) 8-Benzyloxy-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride mp : 167 to 169°C IR (Nujol) : 3180, 2560 (broad), 2125, 1675, 1580, 1090 cm⁻¹ (18) 8-Benzyloxy-3-(2-propynyloxymethyl)-2-methylimidazo-[1,2-a]pyridine mp : 103 to 104°C IR (Nujol) : 3250, 2125, 1545, 1470, 1075 cm⁻¹ (19) 8-(1-Phenylethoxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine IR (film/NaCl) : 2100 cm⁻¹ (20) 8-(2-Methylbenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 87 to 89°C IR (Nujol) : 3225, 2125, 1530, 1060, 1050 cm⁻¹ (21) 8-(2-Chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 95 to 95.5°C IR (Nujol) : 3280, 2120, 1575, 1545, 1295, 1070 cm⁻¹ (22) 8-(3-Chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 81 to 83°C (recrystallized from petroleum ether) IR (Nujol) : 3130, 2095, 1570, 1540, 1285, 1055 cm⁻¹ (23) 8-(4-Chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 130 to 131°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3240, 2100, 1530, 1490, 1360, 1275, 1265 cm⁻¹ (24) 8-(2-Bromobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 103 to 104°C (recrystallized from a mixture of methylene chloride and diethyl ether) (25) 8-(2,6-Dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 129 to 130°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3290 cm⁻¹ (26) 8-(3,4-Dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 105 to 107°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3260, 2110, 1280, 1160 cm⁻¹ (27) 8-(2,4-Dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 123 to 124°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3250, 2110, 1280, 1060 cm⁻¹ (28) 8-Benzyloxy-3-(2-propynyloxymethyl)imidazo[1,2-a]pyridine mp : 84 to 85°C (recrystallized from diisopropyl ether) IR (Nujol) : 3170, 2100 cm⁻¹ (29) 8-Benzyloxy-3-(2-propynyloxymethyl)-2-phenylimidazo[1,2-a]pyridine NMR (CDCl₃, δ) : 2.40 (1H, t, J=1Hz), 4.20 (2H, d, J=1Hz), 4.96 (2H, s), 5.33 (2H, s), 6.40-6.80 (2H, m), 7.20-7.70 (8H, m), 7.76-7.96 (3H, m) (30) 8-(2-Methylbenzylamino)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride mp : 159 to 161°C (recrystallized from a mixture of ethanol and n-hexane) (31) 8-(2-Chlorobenzylamino)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride mp : 169°C (decomp.) (recrystallized from a mixture of ethanol and diethyl ether) (32) 8-Benzyloxy-3-allyloxymethyl-2-methylimidazo[1,2-a]pyridine mp : 70 to 71°C IR (Nujol) : 1535, 1280, 1265, 1195, 1100, 1050, 1015 cm⁻¹ (33) 8-Benzyloxy-3-(3-carboxy-2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 151°C (decomp.) (34) 8-Benzyloxy-3-(3-ethoxycarbonyl-2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine NMR (CDCl₃, δ) : 1.33 (3H, t, J=5Hz), 2.53 (3H, s), 4.20 (2H, s), 4.27 (2H, q, J=5Hz), 4.90 (2H, s), 5.30 (2H, s), 6.50 (1H, dd, J=1Hz and 5Hz), 6.65 (1H, t, J=5Hz), 7.26-7.60 (5H, m), 7.75 (1H, dd, J=1Hz and 5Hz) Example 6 A solution of 2-amino-3-(2-methylbenzylamino)pyridine (2 g) and 3-mesyloxy-5-hexyn-2-one (1.78 g) in ethanol (40 ml) was refluxed for 31.5 hours and then evaporated in vacuo. The residue was treated with aqueous sodium bicarbonate solution and extracted with methylene chloride. The extract was washed with water, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (40 g) with a mixture of methylene chloride and ethyl acetate (50:1 to 10:1) as an eluent to give 8-(2-methylbenzylamino)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine (0.82 g). mp : 126 to 128°C (recrystallized from diisopropyl ether) NMR (CDCl₃, δ) : 2.04 (1H, t, J=3Hz), 2.38 (3H, s), 2.40 (3H, s), 3.73 (2H, d, J=3Hz), 4.39 (2H, d, J=5Hz), 5.13-5.43 (1H, broad s), 6.08 (1H, d, J=8Hz), 6.66 (1H, t, J=7Hz), 7.0-7.43 (4H, m), 7.45 (1H, d, J=6Hz) Example 7 8-(2-Chlorobenzylamino)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine was obtained according to a similar manner to that of Example 6. mp : 115 to 116.5°C (recrystallized from a mixture of ethyl acetate and n-hexane) NMR (CDCl₃, δ) : 2.03 (1H, t, J=3Hz), 2.40 (3H, s), 3.68 (2H, d, J=3Hz), 4.52 (2H, d, J=6Hz), 5.55 (1H, broad t, J=6Hz), 5.95 (1H, d, J=7Hz), 6.55 (1H, t, J=7Hz), 6.96-7.55 (5H, m) Analysis Calcd. for C₁₈H₁₆ClN₃ : C: 69.79; H: 5.21; N: 13.56 Found : C: 69.97; H: 5.48; N: 13.62 Example 8 Sodium bicarbonate (2.73 g) was added to a solution of 2-amino-3-(2-methylbenzyloxy)pyrazine (3.5 g) and 3-mesyloxy-5-hexyn-2-one (6.18 g) in ethanol (35 ml) and the mixture was refluxed for 12 hours. The mixture was poured into an aqueous solution of sodium bicarbonate and extracted with chloroform. The extract was washed with water, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (200 g) with a mixture of chloroform and methanol (50:1) as an eluent to give 8-(2-methylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyrazine (0.182 g). mp : 123 to 124°C NMR (CDCl₃, δ) : 2.08 (1H, t, J=3Hz), 2.42 (3H, s), 2.45 (3H, s), 3.72 (2H, d, J=3Hz), 5.55 (2H, s), 7.00-7.55 (4H, m), 7.35 (1H, d, J=5Hz), 7.63 (1H, d, J=5Hz) Example 9 8-(2-Methylbenzylamino)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyrazine hydrochloride was obtained according to a similar manner to that of Example 8. mp : 184 to 186°C (decomp.) Analysis Calcd. for C₁₈H₁₈N₄·HCl : C: 66.19; H: 5.95; N: 17.38; Cl: 10.90 Found : C: 66.15; H: 5.86; N: 17.14; Cl: 10.52 IR (Nujol) : 3350, 3180, 2560, 1660, 1635, 1525 cm⁻¹ NMR (DMSO-d₆, δ) : 2.37 (3H, s), ca. 2.3-2.7 (3H, s), 3.13 (1H, t, J=3Hz), 4.08 (2H, d, J=3Hz), 4.90 (2H, d, J=6Hz), 7.00-7.50 (4H, m), 7.42 (1H, d, J=5Hz), 7.92 (1H, d, J=5Hz), 9.70-10.2 (1H, broad) Example 10 A solution of 8-(2-methylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine (0.99 g) and 1N-sodium hydroxide solution (5.65 ml) in methanol (50 ml) was stirred for 72 hours at room temperature. The mixture was evaporated in vacuo and the residue was dissolved in chloroform. The solution was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (14 g) with a mixture of chloroform and ethyl acetate (15:1) as an eluent to give 8-(2-methylbenzyloxy)-3-(1,2-propadienyl)-2-methylimidazo[1,2-a]pyridine (0.27 g). mp : 88 to 89°C (recrystallized from a mixture of diethyl ether and petroleum ether). IR (Nujol) : 1930 cm⁻¹ NMR (CDCl₃, δ) : 2.40 (3H, s), 2.46 (3H, s), 5.26 (2H, s), 5.26-5.43 (2H, m), 6.40-6.76 (3H, m), 7.06-7.30 (3H, m), 7.33-7.53 (1H, m), 8.10 (1H, dd, J=1Hz and 7Hz) Analysis Calcd. for C₁₉H₁₈N₂O : C: 78.59; H: 6.25; N: 9.65 Found : C: 78.86; H: 6.02; N: 9.57 Example 11 To a solution of sodium hydride (61% in mineral oil dispersion) (7.39 g) in 2-propynyl alcohol (300 ml) was added 8-benzyloxy-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide (74.6 g), and the mixture was heated at 90-95°C with stirring for 2.5 hours. After being cooled, the mixture was evaporated in vacuo and the residue was dissolved in methylene chloride. The solution was washed with water, dried over magnesium sulfate, and evaporated in vacuo. The oily residue was purified by column chromatography on Silica gel (200 g) with methylene chloride as an eluent and the fractions containing the object compound were combined. The resultant solution was treated with a solution of hydrogen chloride in ethanol to give 8-benzyloxy-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride (37.5 g). mp : 167 to 169°C IR (Nujol) : 3180, 2560(broad), 2125, 1675, 1580, 1090 cm⁻¹ NMR (D₂O, δ) : 2.56 (3H, s), 3.03 (1H, t, J=2Hz), 4.31 (2H, d, J=2Hz), 4.96 (2H, s), 5.29 (2H, s), 7.13-7.56 (7H, m), 8.01-8.14 (1H, m) Analysis Calcd. for C₁₉H₁₉ClN₂O₂ : C: 66.57; H: 5.59; N: 8.17 Found : C: 66.37; H: 5.33; N: 8.06 Example 12 A solution of 8-benzyloxy-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride (35.5 g) in hot water (700 ml) was neutralized with aqueous sodium hydroxide solution and extracted with methylene chloride. The extract was washed with water, dried over magnesium sulfate, treated with activated charcoal, and evaporated in vacuo. The residual solid was recrystallized from a mixture of methylene chloride and n-hexane to give 8-benzyloxy-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (26.03 g). mp : 103 to 104°C IR (Nujol) : 3250, 2125, 1545, 1470, 1075 cm⁻¹ NMR (CDCl₃, δ) : 2.43-2.60 (1H, m), 2.53 (3H, s), 4.07 (2H, d, J=2Hz), 4.87 (2H, s), 5.33 (2H, s), 6.33-6.76 (2H, m), 7.20-7.60 (5H, m), 7.73 (1H, dd, J=2Hz and 6Hz) Example 13 To a solution of sodium hydride (63.6% in mineral oil dispersion, 0.285 g) in 2-propynyl alcohol (12 ml) was added 8-(2-methylbenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide (3 g) and the mixture was heated at 85-100°C for 1.5 hours. After being cooled, the mixture was poured into ice-water and the resulting precipitate was collected by filtration and dissolved in methylene chloride. The solution was treated successively with silica gel (4.5 g) and activated charcoal and evaporated in vacuo. The crystalline residue was recrystallized from a mixture of ethyl acetate and petroleum ether to give 8-(2-methylbenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (1.18 g). mp : 87 to 89°C IR (Nujol) : 3225, 2125, 1530, 1060, 1050 cm⁻¹ NMR (CDCl₃, δ) : ca. 2.3-2.6 (1H), 2.40 (3H, s), 2.50 (3H, s), 4.06 (2H, d, J=2Hz), 4.86 (2H, s), 5.29 (2H, s), 6.32-6.8 (2H, m), 7.0-7.56 (4H, m), 7.75 (1H, dd, J=2Hz, 5Hz), Analysis Calcd. for C₂₀H₂₀N₂O₂ : C: 74.98; H: 6.29; N: 8.74 Found : C: 74.98; H: 6.05; N: 8.71 Example 14 To a solution of sodium hydride (60% in mineral oil dispersion, 0.186 g) in 2-propynyl alcohol (8 ml) was added 8-(2-chlorobenzyloxy)-3-trimethylammoniomethyl-2-methylimidazo[1,2-a]pyridine iodide (2 g) and the mixture was heated at 90-95°C with stirring for 1 hour. After being cooled, the mixture was poured into ice-water and the resulting precipitate was collected by filtration and dissolved in methylene chloride. The solution was treated successively with silica gel (1 g) and activated charcoal and evaporated in vacuo. The crystalline residue was recrystallized from a mixture of methylene chloride and n-hexane to give 8-(2-chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (0.9 g). mp : 95 to 95.5°C IR (Nujol) : 3280, 2120, 1575, 1545, 1295, 1070 cm⁻¹ NMR (CDCl₃, δ) : ca. 2.4-2.7 (1H), 2.58 (3H, s), 4.13 (2H, d, J=2Hz), 4.94 (2H, s), 5.47 (2H, s), 6.39-6.85 (2H, m), 7.10-7.50 (3H, m), 7.50-7.92 (2H, m) Analysis Calcd. for C₁₉H₁₇ClN₂O₂ : C: 66.96; H: 5.03; N: 8.22 Found : C: 67.13; H: 4.93; N: 8.12 Example 15 The following compounds were obtained according to similar manners to those of Examples 11, 13 and 14. (1) 8-(1-Phenylethoxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine IR (film/NaCl) : 2100 cm⁻¹ NMR (CDCl₃, δ) : 1.80 (3H, d, J=6Hz), 2.40-2.60 (1H, m), 2.53 (3H, s), 4.05 (2H, d, J=2Hz), 4.85 (2H, s), 5.52 (1H, q, J=6Hz), 6.16-6.69 (2H, m), 7.11-7.56 (5H, m), 7.64 (1H, dd, J=1Hz and 6Hz) (2) 8-(3-Chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 81 to 83°C (recrystallized from petroleum ether) IR (Nujol) : 3130, 2095, 1570, 1540, 1285, 1055 cm⁻¹ NMR (CDCl₃, δ) : 2.43-2.60 (1H, m), 4.52 (3H, s), 4.08 (2H, d, J=2Hz), 4.88 (2H, s), 5.29 (2H, s), 6.32-6.80 (2H, m), 7.10-7.60 (4H, m), 7.75 (1H, dd, J=2Hz and 7Hz) Analysis Calcd. for C₁₉H₁₇ClN₂O₂ : C: 66.96; H: 5.03; N: 8.22 Found C: 67.23; H: 4.88; N: 8.15 (3) 8-(4-Chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 130 to 131°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3240, 2100, 1530, 1490, 1360, 1275, 1265 cm⁻¹ NMR (CDCl₃, δ) : 2.38-2.58 (1H, m), 2.52 (3H, s), 4.06 (2H, d, J=2Hz), 4.86 (2H, s), 5.26 (2H, s), 6.26-6.73 (2H, m), 7.13-7.56 (4H, m), 7.76 (1H, dd, J=2Hz and 7Hz) Analysis Calcd. for C₁₉H₁₇ClN₂O₂ : C: 66.96; H: 5.03; N: 8.22 Found : C: 66.91; H: 4.95; N: 8.08 (4) 8-(2-Bromobenzyloxy)-3-(2-propynyloxymethyl-2-methylimidazo[1,2-a]pyridine mp : 103 to 104°C (recrystallized from a mixture of methylene chloride and diethyl ether) NMR (CDCl₃, δ) : 2.43-2.63 (1H, m), 2.52 (3H, s), 4.08 (2H, d, J=2Hz), 4.88 (2H, s), 5.39 (2H, s), 6.33-6.81 (2H, n), 7.06-7.73 (4H, m), 7.75 (1H, dd, J=2Hz and 7Hz) (5) 8-(2,6-Dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 129 to 130°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3290 cm⁻¹ NMR (CDCl₃, δ) : 2.45-2.60 (1H, m), 2.46 (3H, s), 4.06 (2H, d, J=2Hz), 4.86 (2H, s), 5.43 (2H, s), 6.60-6.85 (2H, m), 7.06-7.45 (3H, m), 7.80 (1H, dd, J=2Hz and 3Hz) Analysis Calcd. for C₁₉H₁₆Cl₂N₂O₂ : C: 60.81; H: 4.30; N: 7.47 Found : C: 61.31; H: 4.33; N: 7.48 (6) 8-(3,4-Dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 105 to 107°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3260, 2110, 1280, 1160 cm⁻¹ NMR (CDCl₃, δ) : 2.40-2.60 (1H, m), 2.46 (3H, s), 4.05 (2H, d, J=2Hz), 4.83 (2H, s), 5.23 (2H, s), 6.26-6.80 (2H, m), 7.13-7.63 (3H, m), 7.75 (1H, dd, J=1Hz and 7Hz) Analysis Calcd. for C₁₉H₁₆Cl₂N₂O₂ : C: 60.81; H: 4.30; N: 7.47 Found : C: 61.26; H: 4.23; N: 7.55 (7) 8-(2,4-Dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 123 to 124°C (recrystallized from a mixture of ethyl acetate and n-hexane) IR (Nujol) : 3250, 2110, 1280, 1060 cm⁻¹ NMR (CDCl₃, δ) : 2.40-2.66 (1H, m), 2.50 (3H, s) 4.08 (2H, d, J=2Hz), 4.90 (2H, s), 5.36 (2H, s), 6.30-6.83 (2H, m), 7.20 (1H, dd, J=2Hz and 8Hz), 7.40 (1H, d, J=2Hz), 7.50 (1H, d, J=8Hz), 7.80 (1H, dd, J=1Hz and 7Hz) Analysis Calcd. for C₁₉H₁₆Cl₂N₂O₂ : C: 60.81; H: 4.30; N: 7.47 Found : C: 61.29; H: 4.25; N: 7.41 (8) 8-Benzyloxy-3-(2-propynyloxymethyl)imidazo[1,2-a]pyridine mp : 84 to 85°C (recrystallized from diisopropyl ether) IR (Nujol) : 3170, 2100 cm⁻¹ NMR (CDCl₃, δ) : 2.46 (1H, t, J=2Hz), 4.13 (2H, d, J=2Hz), 4.9 (2H, s), 5.33 (2H, s), 6.40-6.90 (2H, m), 7.23-7.60 (5H, m), 7.60 (1H, s), 7.83 (1H, dd, J=2Hz and 7Hz) Analysis Calcd. for C₁₈H₁₆N₂O₂ : C: 73.95; H: 5.52; N: 9.58 Found : C: 73.74; H: 5.30; N: 9.47 (9) 8-Benzyloxy-3-(2-propynyloxymethyl)-2-phenylimidazo[1,2-a]pyridine NMR (CDCl₃, δ) : 2.40 (1H, t, J=1Hz), 4.20 (2H, d, J=1Hz), 4.96 (2H, s), 5.33 (2H, s), 6.40-6.80 (2H, m), 7.20-7.70 (8H, m), 7.76-7.96 (3H, m) (10) 8-(2-Methylbenzylamino)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride mp : 159 to 161°C (recrystallized from a mixture of ethanol and n-hexane) NMR (DMSO-d₆, δ) : 2.39 (3H, s), ca. 2.4-2.7 (3H, s), 3.50 (1H, t, J=2Hz), 4.39 (2H, d, J=2Hz), 4.50 (2H, broad d, J=5HZ), 4.91 (2H, s), 6.73 (1H, d, J=8HZ), 7.06-7.80 (6H, m), 7.91 (1H, d, J=6Hz) Analysis Calcd. for C₂₀H₂₂ClN₃O : C: 67.50; H: 6.23; N: 11.81 Found : C: 67.87; H: 6.43; N: 11.87 (11) 8-(2-Chlorobenzylamino)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride mp : 169°C (decomp.) (crystallized from a mixture of ethanol and diethyl ether) NMR (DMSO-d₆, δ) : 2.56 (3H, s), 3.52 (1H, t, J=2Hz), 4.25 (2H, d, J=2Hz), 4.85 (2H, broad s), 4.95 (2H, s), 6.73 (1H, d, J=8Hz), 7.13-8.13 (7H, m) Analysis Calcd. for C₁₉H₁₉Cl₂N₃O : C: 60.65; H: 5.09; N: 11.17 Found : C: 60.71; H: 5.39; N: 10.98 (12) 8-Benzyloxy-3-allyloxymethyl-2-methylimidazo[1,2-a]pyridine mp : 70 to 71°C IR (Nujol) : 1535, 1280, 1265, 1195, 1100, 1050, 1015 cm⁻¹ NMR (CDCl₃, δ) : 2.50 (3H, s), 3.95 (2H, d, J=6Hz), 4.76 (2H, s), 5.0-5.5 (2H, m), 5.33 (2H, s), 5.6-6.3 (1H, m), 6.36-6.79 (2H, m), 7.20-7.62 (5H, m), 7.75 (1H, dd, J=2Hz and 6Hz) Analysis Calcd. for C₁₉H₂₀N₂O₂ : C: 74.00;H: 6.54; N: 9.08 Found : C: 74.35;H: 6.48; N: 9.04 (13) 8-Benzyloxy-3-(3-carboxy-2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine mp : 151°C (decomp.) (14) 8-Benzyloxy-3-(3-ethoxycarbonyl-2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine NMR (CDCl₃, δ) : 1.33 (3H, t, J=5Hz), 2.53 (3H, s), 4.20 (2H, s), 4.27 (2H, q, J=5Hz), 4.90 (2H, s), 5.30 (2H, s), 6.50 (1H, dd, J=1Hz and 5Hz), 6.65 (1H, t, J=5Hz), 7.26-7.60 (5H, m), 7.75 (1H, dd, J=1Hz and 5Hz) Example 16 To a solution of 8-benzyloxy-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (1 g) in tetrahydrofuran (10 ml) was added dropwise 10% solution of n-butyllithium in n-hexane (2.09 ml) at -60°C under a nitrogen atmosphere. After being stirred for 10 minutes the solution was treated with dry ice (1.4 g), allowed to warm to room temperature, and acidified with diluted acetic acid. The resulting precipitates were collected by filtration, washed with water, and recrystallized from methanol to give 8-benzyloxy-3-(3-carboxy-2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine (0.67 g). mp : 151°C (decomp.) NMR (DMSO-d₆, δ) : 2.36 (3H, s), 4.30 (2H, s), 4.85 (2H, s), 5.26 (2H, s), 5.93 (1H, broad s), 6.80-7.03 (2H, m), 7.26-7.63 (5H, m), 7.86-8.10 (1H, m) Analysis Calcd. for C₂₀H₁₈N₂O₄ : C: 65.04; H: 5.72; N: 7.36 Found : C: 65.07; H: 5.54; N: 7.35 Example 17 8-Benzyloxy-3-(3-ethoxycarbonyl-2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine was obtained by reacting 8-benzyloxy-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine with ethyl chloroformate according to a similar manner to that of Example 16. NMR (CDCl₃, δ) : 1.33 (3H, t, J=5Hz), 2.53 (3H, s), 4.20 (2H, s), 4.27 (2H, q, J=5Hz), 4.90 (2H, s), 5.30 (2H, s), 6.50 (1H, dd, J=1Hz and 5Hz), 6.65 (1H, t, J=5Hz), 7.26-7.60 (5H, m), 7.75 (1H, dd, J=1Hz and 5Hz)

Claims: Imidazoheterocyclic compounds of the formula: wherein R¹ is (C₂ - C₆) alkenyl, (C₂ - C₆) alkynyl, (C₃ - C₆) alkadienyl, (C₂ - C₆) alkenyloxy (C₁ - C₆) alkyl, (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl, carboxy (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl or (C₁ - C₆) alkoxycarbonyl (C₂ - C₆) alkynyloxy-(C₁ - C₆) alkyl, R² is hydrogen, (C₁ - C₆) alkyl or aryl selected from a group consisting of phenyl, tolyl, xylyl, 1-naphthyl, 2-naphthyl, 1-anthryl and 2-anthryl, R³ is ar (C₁ - C₆) alkyl which has one or more suitable substituent(s) selected from a group consisting of (C₁ - C₆) alkyl and halogen, ar (C₂ - C₆) alkenyl, benzene-condensed cyclo (C₅ - C₆) alkyl, (C₁ - C₆) alkyl having cyclo (C₃ - C₆) alkyl or (C₁ - C₆) alkyl, and X is O or NH, and a pharmaceutically acceptable salt thereof. A compound of claim 1, wherein R¹ is (C₂ - C₆) alkenyl, (C₂ - C₆) alkynyl, (C₃ - C₆) alkadienyl, (C₂ - C₆) alkenyloxy (C₁ - C₆) alkyl, (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl, carboxy (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl or (C₁ - C₆) alkoxycarbonyl (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl and R³ is ar (C₁ - C₆) alkyl which has one or more suitable substituent(s) selected from a group consisting of (C₁ - C₆) alkyl and halogen, ar (C₂ - C₆) alkenyl, benzene-condensed cyclo (C₅ - C₆) alkyl, (C₁ - C₆) alkyl having cyclo (C₃ - C₆) alkyl or (C₁ - C₆) alkyl. A compound of claim 2, wherein R³ is ar (C₁ - C₆) alkyl which has one or more suitable substituent(s) selected from a group consisting of (C₁ - C₆) alkyl and halogen. A compound of claim 3, wherein R³ is phenyl (C₁ - C₆) alkyl or naphthyl (C₁ - C₆) alkyl, each of which has 1 to 3 suitable substituent(s) selected from a group consisting of (C₁ - C₆) alkyl and halogen. A compound of claim 4, wherein R¹ is allyl, 2-propynyl, 1,2-propadienyl, allyloxymethyl, 2-propynyloxymethyl, 3-carboxy-2-propynyloxymethyl or 3-ethoxycarbonyl-2-propynyloxymethyl, R² is hydrogen, methyl or phenyl, and R³ is benzyl which has 1 or 2 suitable substituent(s) selected from a group consisting of methyl, ethyl, isopropyl, fluoro, chloro and bromo. A compound of claim 5, which is selected from a group consisting of: 8-(2-methylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]-pyridine, 8-(2-ethylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]-pyridine, 8-(2-isopropylbenzyloxy)-3-(2-propynyl)-2-methylimidazo-[1,2-a]-pyridine, 8-(2-chlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]-pyridine, 8-(3-chlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]-pyridine, 8-(4-chlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]-pyridine, 8-(2-bromobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]-pyridine, 8-(2-fluorobenzyloxy)-3-(2-propynyl)-2-methylimidazo-[1,2-a]pyridine, 8-(2,6-dimethylbenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine, 8-(2,6-dichlorobenzyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine, 8-(2-methylbenzylamino)-3-(2-propynyl)-2-methylimidazo[1,2a]pyridine, 8-(2-chlorobenzylamino)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine, 8-(2-methylbenzyloxy)-3-(1,2-propadienyl)-2-methylimidazo[1,2-a] pyridine, 8-(2-methylbenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(2-chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(3-chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(4-chlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(2-bromobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(2,6-dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(3,4-dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(2,4-dichlorobenzyloxy)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine, 8-(2-methylbenzylamino)-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride, 8-(2-chlorobenzylamino-3-(2-propynyloxymethyl)-2-methylimidazo[1,2-a]pyridine hydrochloride. A compound of claim 2, wherein R¹ is (C₂ - C₆) alkynyl, R² is (C₁ - C₆) alkyl, R³ is phenyl (C₂ - C₆) alkenyl, 1,2,3,4-tetrahydronaphthyl, (C₁ - C₆) alkyl having cyclo (C₃ - C₆) alkyl or (C₁ - C₆) alkyl, and X is O. A compound of claim 7, wherein R¹ is 2-propynyl, R² is methyl and R³ is cinnamyl, 1,2,3,4-tetrahydro-1-naphthyl, cyclohexylmethyl or ethyl. A compound of claim 8, which is selected from a group consisting of: 8-(cinnamyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine, 8-(1,2,3,4-tetrahydro-1-naphthyloxy)-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine, 8-cyclohexylmethoxy-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine, and 8-ethoxy-3-(2-propynyl)-2-methylimidazo[1,2-a]pyridine. A process for preparing imidazoheterocyclic compounds of the formula: wherein R¹ is (C₂ - C₆) alkenyl, (C₂ - C₆) alkynyl, (C₃ - C₆) alkadienyl, (C₂ - C₆) alkenyloxy (C₁ - C₆) alkyl, (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl, carboxy (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl or (C₁ - C₆) alkoxycarbonyl (C₂ - C₆) alkynyloxy-(C₁ - C₆) alkyl, R² is hydrogen, (C₁ - C₆) alkyl or aryl selected from a group consisting of phenyl, tolyl, xylyl, 1-naphthyl, 2-naphthyl, 1-anthryl and 2-anthryl, R³ is ar (C₁ - C₆) alkyl which has one or more suitable substituent(s) selected from a group consisting of (C₁ - C₆) alkyl and halogen, ar (C₂ - C₆) alkenyl, benzene-condensed cyclo (C₅ - C₆) alkyl, (C₁ - C₆) alkyl having cyclo (C₃ - C₆) alkyl or (C₁ - C₆) alkyl, and X is O or NH or a salt thereof, which comprises reacting a compound of the formula: wherein R³ and X are each as defined above, or a salt thereof, with a compound of the formula: wherein R¹ and R² are each as defined above, and Z¹ is an acid residue selected from a group consisting of halogen and acyloxy, or a salt thereof. A process for preparing imidazoheterocyclic compounds of the formula: wherein R², R³ and X are each as defined in claim 10, and R 1 / b is cumulated (C₃- C₆) alkadienyl, or a salt thereof, which comprises subjecting a compound of the formula: wherein R², R³ and X are each as defined in claim 10, and R 1 / a is (C₂ - C₆) alkynyl, or a salt thereof, to isomerization reaction. A process for preparing imidazoheterocyclic compounds of the formula: wherein R², R³ and X are each as defined in claim 10, R⁴ is (C₂ - C₆) alkylene, and R⁵ is (C₂ - C₆) alkenyl, (C₂ - C₆) alkynyl, carboxy (C₂ - C₆) alkynyl or (C₁ - C₆) alkoxycarbonyl-(C₂ - C₆) alkynyl, or a salt thereof, which comprises reacting a compound of the formula: wherein R², R³, R⁴ and X are each as defined above, Z² is a leaving group, or a salt thereof, with a compound of the formula: R⁵ -OH wherein R⁵ is as defined above, or a salt thereof. A process for preparing imidazoheterocyclic compounds of the formula: wherein R², R³ and X each as defined in claim 10, R' d is carboxy (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl, in which the triple bond always exists on the terminal carbon atom of the (C₂ - C₆) alkyl moiety and this (C₂ - C₆) alkynyloxy-(C₁ - C₆) alkyl is substituted with carboxy on the terminal carbon atom of the (C₂ - C₆) alkynyl moiety, or (C₁ - C₆) alkoxycarbonyl (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl, in which the triple bond always exists on the terminal carbon atom of the (C₂ - C₆) alkynyl moiety and this (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl is substituted with (C₁ - C₆) alkoxycarbonyl on the terminal carbon atom of the (C₂ - C₆) alkynyl moiety, or a salt thereof, which comprises subjecting a compound of the formula: wherein R², R³ and X are each as defined in claim 10, and R' c is (C₂ - C₆) alkynyloxy (C₁ - C₆) alkyl, in which the triple bond always exists on the terminal carbon atom of the (C₂ - C₆) alkynyl moiety, or a salt thereof, to acylation reaction. A pharmaceutical composition which comprises, as an active ingredient, a compound of claim 1 or a pharmaceutically acceptable salt thereof in admixture with pharmaceutically acceptable carriers. A compound of claim 1 or pharmaceutically acceptable salts thereof for use as a medicament. A compound of claim 1 or pharmaceutically acceptable salts thereof for use in treating ulcer. A compound of claim 1 or pharmaceutically acceptable salts thereof for the manufacture of a medicament for treating ulcer.

Inventors: ITANI, HIROMICHI, SHIOKAWA, YOUICHI, TAKE, KAZUHIKO, UEDA, IKUO
Applicants: FUJISAWA PHARMACEUTICAL CO., LTD.
Application year: 1986
Main classification: C07D471
IPC codes: C07D471, C07D487