Indian Patents. 252351:IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AND COMPOSITIONS

Title of Invention	IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AND COMPOSITIONS
Abstract	The present invention relates to novel imidazo[1,2- a]pyridine compounds of general formula (I) as well as pharmaceutically acceptable salts thereof; wherein R1, R2, R3 and R4 are as defined in the claims. The compounds have specific affinity for GABAA receptor and are therefore useful in the treatment and prevention of diseases modulated by α1- and α2-GABAA receptors.

Full Text	Technical field This invention is directed to agents with affinity for GABAA receptor, specifically to imidazo[1,2-a]pyridine compounds. Background of the invention GABAA receptor (γ-aminobutyric acidA) is a pentameric protein which forms a membrane ion channel. GABAA receptor is implicated in the regulation of sedation, anxiety, muscle tone, epileptogenic activity and memory functions. These actions are due to defined subunits of GABAA receptor, particularly the α1- and α2-subunits. Sedation is modulated by the α1-subunit. Zolpidem is characterized by a high affinity for the α1-receptors and its sedative and hypnotic action is mediated by these receptors in vivo. Similarly, the hypnotic action of zaleplon is also mediated by the α1-receptors. The anxiolytic action of diazepam is mediated by the enhancement of GABAergic transmission in a population of neurons expressing the α2-receptors. This indicates that the α2-receptors are highly specific targets for the treatment of anxiety. Muscle relaxation in diazepam is mainly mediated by α2- receptors, since these receptors exhibit a highly specific expression in spinal cord. The anticonvulsant effect of diazepam is partly due to α1-receptors. In diazepam, a memory-impairing compound, anterograde amnesia is mediated by α1-receptors. GABAA receptor and its α1- and α2-subunits have been widely reviewed by H. Mohler et al.(J. Pharmacol. Exp. Ther., 300, 2-8, 2002); H. Mohler et al.(Curr. Opin. Pharmacol., 1, 22-25, 2001); U. Rudolph et al.(Nature, 401, 796-800, 1999); and D.J. Nutt et al. (Br. J. Psychiatry, 179, 390-396, 2001) . Diazepam and other classical benzodiazepines are extensively used as anxiolytic agents, hypnotic agents, anticonvulsants and muscle relaxants. Their side effects include anterograde amnesia, decrease in motor activity and potentiation of ethanol effects. In this context, the compounds of this invention are ligands of α1- and α2-GABAA receptor for their clinical application in sleep disorders, preferably insomnia, anxiety and epilepsy. Insomnia is a highly prevalent disease. Its chronicity affects 10% of the population and 30% when transitory insomnia is computed as well. Insomnia describes the trouble in falling asleep, staying asleep or waking up too early, experiencing a non-refreshing sleep, and is associated with next-day hangover effects such as weariness, lack of energy, low concentration and irritability. The social and health impact of this complaint is important and results in evident socioeconomic repercussions. Pharmacological therapy in the management of insomnia firstly included barbiturates and chloral hydrate, but these drugs elicit numerous known adverse effects, for example, overdose toxicity, metabolic induction, and enhanced dependence and tolerance. In addition, they affect the architecture of sleep by decreasing above all the duration and the number of REM sleep stages. Later, benzodiazepines meant an important therapeutic advance because of their lower toxicity, but they still showed serious problems of dependence, muscle relaxation, amnesia and rebound insomnia following discontinuation of medication. The latest known therapeutic approach has been the introduction of non-benzodiazepine hypnotics, such as pyrrolo [3, 4-b]pyrazines (zopiclone), imidazo[1,2-a] pyridines (Zolpidem) and, finally, pyrazolo[1,5-a] pyrimidines (zaleplon). Later, two new pyrazolo[1,5-a] pyrimidines, indiplon and ocinaplon, have entered into development, the latter with rather anxiolytic action. All these compounds show a rapid sleep induction and have less next-day hangover effects, lower potential for abuse and lower risk of rebound insomnia than benzodiazepines. The mechanism of action of these compounds is the alosteric activation of GABAA receptor through its binding to benzodiazepine binding site (C. F. P. George, The Lancet, 358, 1623-1626, 2001). While benzodiazepines are unspecific ligands at GABAA receptor binding site, Zolpidem and zaleplon show a greater selectivity for α1-subunit. Notwithstanding that, these drugs still affect the architecture of sleep and may induce dependence in long-term treatments. Zolpidem is disclosed in US 4382938. Some other related hypnotic imidazo[1,2-a]pyridines have been disclosed in FR 2593818, US 4650796 and EP 172096. In US 4626538 (zaleplon), US 4654347, US 6399621 (indiplon) and EP 129847 (ocinaplon) hypnotic pyrazolo[1,5-a]pyrimidines are disclosed. The use of N-[[(ethyl-4-phenyl)-2- imidazo[1,2-a]pyridinyl-3]methyl-N,3-dimethyl- butanamide, a compound previously disclosed in EP 172096, has been claimed in the manufacturing of anesthetic medicaments in EP 430738. Research for new active compounds in the management of insomnia answers an underlying health need, because even recently introduced hypnotics still affect the architecture of sleep and may induce dependence in long-term treatments. It is therefore desirable to focus on the development of new hypnotic agents with a lower risk of side effects. Thus, the present invention is directed to new imidazo[1,2-a]pyridine compounds which are active versus GABAA and, particularly, versus its α1- and α2- subunits. Consequently, the compounds of this invention are useful in the treatment and prevention of all those diseases mediated by GABAA receptor α1- and α2-subunits. Non-limitative examples of such diseases are sleep disorders, preferably insomnia, anxiety and epilepsy. Non-limitative examples of the relevant indications of the compounds of this invention are all those diseases or conditions, such as insomnia or anesthesia, in which an induction of sleep, an induction of sedation or an induction of muscle relaxation are needed. Detailed description of the invention The present invention relates to novel imidazo[1,2- a]pyridine compounds of general formula (I): as well as pharmaceutically acceptable salts thereof; wherein R1 and R2 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1- C6), alkenyl (C2-C6) , alkynyl (C2-C6) , haloalkyl (C1-C6) , - O-alkyl(C1-C6), fluoro, chloro and bromo; R3 is selected from the group consisting of hydrogen, linear or branched alkyl (C1-C6) , cycloalkyl (C3-C6) , cycloalkyl (C3-C6) alkyl (C1-C6) , alkenyl (C2-C6) , alkenyl (C2-C6) alkyl (d-C6) , alkynyl (C2-C6) , alkynyl (C2- C6) alkyl (C1-C6) ; R4 is selected from the group consisting of hydrogen, haloalkyl (C2-C6) , cycloalkyl (C3-C5) , cycloalkyl (C3- C6) alkyl (d-C6) , alkynyl (C2-C6) alkyl (C1-C6) , alkyl (C1-C6)- O-alkyl (C1-C6) , alkyl (C1-C6) -NH-alkyl (C1-C6) , alkyl (C1- C6) -N (dialkyl (C1-C6) ) , -OR5, -NHR5, -NR5R6, phenylalkyl (C2-C6) , phenylalkenyl (C2-C6) , naphthyl, monosubstituted naphthyl, disubstituted naphthyl, naphthylalkyl (C1-C6) , naphthylalkenyl (C2-C6) , furyl, substituted furyl, benzofuryl, substituted benzofuryl, pyrrolyl, substituted pyrrolyl, isoxazolyl, substituted isoxazolyl, benzoisoxazolyl, substituted benzoisoxazolyl, imidazolyl, substituted imidazolyl, benzimidazolyl, substituted benzimidazolyl, indolyl, substituted indolyl, pyrazolyl, substituted pyrazolyl, thienyl, substituted thienyl, benzothienyl, substituted benzothienyl, thiazolyl, substituted thiazolyl, benzothiazolyl, substituted benzothiazolyl, quinolinyl, substituted quinolinyl, isoquinolinyl, substituted isoquinolinyl, pyridyl, substituted pyridyl, pyrazinyl, substituted pyrazinyl, 6-oxo-1,4,5,6- tetrahydropyridazinyl, substituted 6-oxo-1,4,5,6- tetrahydropyridazinyl, thiadiazolyl, substituted thiadiazolyl, isothiazolyl, substituted isothiazolyl, thienylmethyl, 2-oxochromenyl, substituted 2- oxochromenyl, 2-(furan-2-yl)vinyl, oxazolyl, substituted oxazolyl, and benzisoxazolyl; Rs and R6 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1- C6) , phenylalkyl (C1-C6) , haloalkyl (C1-C6) , cycloalkyl(C3- C6) , cycloalkyl (C3-C6) alkyl (C1-C6) , alkenyl (C2-C6) and alkynyl (C2-C6) , alkenyl (C2-C6) alkyl (C1-C6) , alkynyl (C2- C6) alkyl (C1-C6), phenyl, substituted phenyl, heteroaryl, substituted heteroaryl; and R7 and R8 are independently selected from the group consisting of linear or branched alkyl (C2_C6), cycloalkyl (C3-C6) , alkenyl (C2-C6) , alkynyl (C2-C6) , -OH, - O-alkyl (C1-C6) , -SH, -S-alkyl (C1-C6) , halo-alkyl (C1-C6) , ω,ω,ω-trifluoroalkyl (C1-C6) , -NHalkyl (C1-C6) , Ndialkyl(C1-C6) , -NO2, -CN, -SO2alkyl (C1-C6) , COalkyl (C1-C6) , -COOalkyl (C1-C6) , -CO-NHalkyl (C1-C6), - CONdialkyl(C1-C6), phenyl, substituted phenyl, heteroaryl and substituted heteroaryl. The term "pharmaceutically acceptable salt" used herein encompasses any salt formed from organic and inorganic acids, such as hydrobromic, hydrochloric, phosphoric, nitric, sulfuric, acetic, adipic, aspartic, benzenesulfonic, benzoic, citric, ethanesulfonic, formic, fumaric, glutamic, lactic, maleic, malic, malonic, mandelic, methanesulfonic, 1,5- naphthalendisulfonic, oxalic, pivalic, propionic, p- toluenesulfonic, succinic, tartaric acids and the like. The term "substituted" used herein refers to the substitution of the corresponding radical or compound with at least one suitable substituent preferably selected from the group consisting of linear or branched alkyl (C2-C6) , cycloalkyl (C3-C6) , alkenyl (C2-C6) , alkynyl (C2-C6) , -OH, -O-alkyl (C1-C6) , -SH, -S-alkyl (C1- C6) , halo-alkyl (C1-C6) , ω, ω, ω-trifluoroalkyl (C1-C6), NHalkyl (C1-C6) , -Ndialkyl (C1-C6) , -NO2, -CN, SO2alkyl(C1-C6) , -COalkyl (C1-C6) , -COOalkyl (C1-C6) , -CO- NHalkyl (C1-C6) , -CONdialkyl (C1-C6), phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, fluoro, chloro and bromo. The preferred compounds of the present invention are shown below: Furan-2-carboxylic acid (6-methyl-2-p-tolyl- imidazo[1,2-a] pyridin-3-ylmethyl)-amide; Pyridine-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo [1,2-a]pyridin-3-ylmethyl)-amide; Thiophene-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo [1,2-a]pyridin-3-ylmethyl)-amide; Cyclopropanecarboxylic acid (6-methyl-2-p-tolyl-imidazo [1,2-a]pyridin-3-ylmethyl)-amide; 5-Nitro-furan-2-carboxylic acid (6-methyl-2-p-tolyl- imidazo [1,2-a]pyridin-3-ylmethyl)-amide; 3,5-Difluoro-pyridine-2-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 6-Methoxy-benzothiazole-2-carboxylic acid(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 4-Dimethylamino-N-methyl-N-(6-methyl-2-p-tolyl-imidazo [1,2-a]pyridin-3-ylmethyl)-benzamide; Cyclopropanecarboxylic acid methyl-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-amide; Pyridine-2-carboxylic acid methyl-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-amide; Thiophene-2-carboxylic acid methyl-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 5-Nitro-furan-2-carboxylic acid methyl-(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 2-Chloro-N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-isonicotinamide; Cyclobutanecarboxylic acid (6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 5-Methyl-pyrazine-2-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 6-Oxo-1,4,5,6-tetrahydro-pyridazine-3-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide; [1,2,3]Thiadiazole-4-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1, 2-a]pyridin-3-ylmethyl)-amide; N-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-2-thiophen-2-yl-acetamide; 1-Methyl-1H-imidazole-2-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; Thiazole-4-carboxylic acid (6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 2,5-Dimethyl-oxazole-4-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 3,5-Dimethyl-isoxazole-4-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; Thiazole-4-carboxylic acid methyl-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 1-(4-Dimethylamino-phenyl)-3-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-urea; 1-Ethyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-urea; 1-Isopropyl-3-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin- 3-ylmethyl)-urea; 1-Cyclopentyl-3-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-urea; 1-Cyclohexyl-3-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-urea; 1-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-3-phenyl-urea; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid p-tolyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid prop-2-ynyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid methyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid benzyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid 4-methoxy-phenyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid ethyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid phenyl ester; and (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- carbamic acid isopropyl ester. Another aspect of the present invention is to provide a process for preparing the compounds of formula (I) and their pharmaceutically acceptable salts. Another aspect of the present invention is to provide a method for treating or preventing diseases associated with GABAA receptor modulation in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for treating or preventing diseases associated with Α1-GABAA receptor modulation in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for treating or preventing diseases associated with α2-GABAA receptor modulation in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for treating or preventing anxiety in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for treating or preventing epilepsy in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for treating or preventing sleep disorders in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for treating or preventing insomnia in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for inducing sedation-hypnosis in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for inducing anesthesia in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for modulating the necessary time to induce sleep and its duration in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a method for inducing muscle relaxation in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. Another aspect of the present invention is to provide a pharmaceutical composition containing a compound of formula (I) or a pharmaceutically acceptable salt thereof in association with therapeutically inert carriers. Another aspect of the present invention is to provide the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for preparing a medicament for treating or preventing diseases associated with GABAA receptor modulation. Another aspect of the present invention is to provide the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for preparing a medicament for treating or preventing diseases associated with α1-GABAA or α2-GABAA receptor modulation. Another aspect of the present invention is to provide the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for preparing a medicament for treating or preventing anxiety, epilepsy, sleep disorders, insomnia, for inducing sedation-hypnosis, anesthesia or muscle relaxation or for modulating the necessary time to induce sleep and its duration. The compounds of general formula (I) wherein R3 is hydrogen and R4 is a carbon group can be obtained following the synthetic strategy showed in Scheme 1. The imidazopyridine (IV) is obtained by cyclization between the corresponding aminopyridine (VII) and the bromoacetophenone (VIII). This reaction is carried out by heating both components at reflux for 2-8 hours, using a polar solvent such as methanol, ethanol, butanol and the like. The final product (IV) is obtained by evaporation of the crude and crystallization of the residue with the adequate solvent. The Mannich reaction between this imidazopyridine (IV) and formaldehyde in an acidic moiety, such as diluted acetic acid, yields the alcohol (II). The reaction is carried out by heating the mixture at 55°C for a period of 2-6 h. The solvent is removed and the residue thus obtained is suspended in dichloromethane, and stirred for 12 hours. The alcohol (II) is washed and dried. Finally, the condensation of the alcohol (II) and the appropriate nitrile (IX) yields compounds of general formula (I) , when R3 is hydrogen and R4 is a carbon group, by using sulphuric acid as catalyst and a polar solvent, such as acetic acid, acetonitrile, tetrahydrofurane and the like. The components are stirred and heated at reflux for 2-6 hours. The crude thus obtained is basified with ammonia and extracted with dichloromethane to yield the corresponding amide (I, R3 = H, R4 = carbon group). Once the amides (I, R3 = H, R4 = carbon group) are obtained, the nitrogen present in this functional group can be alkylated according to a procedure which is well known by an expert skilled in organic chemistry. The reaction is shown in Scheme 2. The reaction is done by using sodium hydride as base and dimethylformamide as solvent under inert atmosphere. The mixture is stirred at room temperature for 1 hour, and the crude thus obtained is removed with dichloromethane. The procedure yields the corresponding N-alkylated amides (I, R3 = carbon group, R4 = carbon group). We also report the preparation of urea compounds of general formula (I) when R3 is hydrogen and R4 is -NHR5. The synthetic strategy is shown in Scheme 3. In this case, the imidazopyridine (IV) described above is treated with (V) to yield the corresponding acetamide (VI). Q is selected from the group consisting of -OH, -Oalkyl (C1-C3) , -N+ (alkyl (C1-C3))3Cl-, N+(alkyl(C1-C3) )3Br-, -N+(alkyl (C1-C3))3I-, preferably OH. This reaction is carried out by using an acidic solvent such as acetic acid and an acid as catalyst. The reaction takes place at room temperature for 1-3 hours and then at reflux for 2-4 hours. An extraction with an organic solvent yields the corresponding acetamide (VI). The hydrolysis of acetamides (VI) in acidic media leads to amines (III). The reaction takes place at reflux using a protic solvent such as methanol, ethanol, propanol, and the like, for a period of 30-90 min. The solvent is removed and the crude is neutralized and extracted with an organic solvent to obtain amines (III) . These amines are the precursors of urea compounds (I, R3 = H, R4 = -NHR5) . Finally, the coupling between amines (III) and isocyanates R5NCO yields the corresponding urea compounds (I, R3 = H, R4 = -NHR5) as mentioned above. The reaction is carried out by using the appropriate isocyanate, stirring at room temperature for 20-30 hours, and using a basic solvent such as pyridine. The solvent is removed and the products are crystallized with the appropriate solvent. In parallel, amines (III) react with chloroformiates to yield carbamates of general formula (I) when R3 is hydrogen and R4 is -OR5, as shown in Scheme 4. The reaction takes place at room temperature for a period of 20-30 hours. The appropriate chloroformiate reacts by using a basic solvent such as pyridine. The solvent is removed and the products are crystallized with water, and filtered off. Thus, carbamates (I, R3 = H, R4 = -OR5) are obtained in good yields. From the compounds of general formula (I) it is possible to obtain their pharmaceutically acceptable salts by treatment with the corresponding acids. The applicants have discovered that the compounds of the present invention have a high affinity for α1- and α2- GABAA receptors as shown in Tables 1 and 2. These in vitro results are consistent with those in vivo results obtained in sedation-hypnosis tests (Table 3). In accordance with the results obtained, certain compounds of the present invention have surprisingly evidenced high affinity for α1-GABAA receptors and interesting pharmacological activity in vivo, which have been similar to or higher than those of prior-art compounds. Moreover, some of them displayed lower affinity for α2-GABAA receptors, indicating increased selectivity for α1-GABAA versus α2-GABAA receptors. All these results support their use in diseases or conditions, in which preferential activity on α1-GABAA is desirable, such as insomnia or anesthesia, in which an induction of sleep and an induction of sedation are needed. Furthermore, lost of righting reflex has been detected in some animals administered with certain compounds of the present invention, supporting their use as anesthetic agents. Indeed, certain compounds of the present invention have demonstrated interesting affinity for α2-GABAA receptors, which has been similar to or higher than that of prior-art compounds. These results support their use in diseases or conditions in which preferential activity on α2-GABAA receptors is desirable, such as anxiety or in which an induction of muscle relaxation is needed. The pharmacological activity of the compounds of the present invention has been determined as shown below. Ligand-binding assays. Determination of the affinity of test compounds for α1- and α2-GABAA receptor. Male Sprague-Dawley rats weighing 200-250 g at the time of experiment were used. After decapitation of the animal, the cerebellum (tissue that mostly contains α1- GABAA receptor) and spinal cord (tissue that mostly contains α2-GABAA receptor) were removed. The membranes were prepared according to the method by J. Lameh et al.(Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 24, 979-991, 2000) and H. Noguchi et al. (Eur. J. Pharm., 434, 21-28, 2002). Once the tissues weighed, they were suspended in 50 mM Tris HCl (pH 7.4), 1:40 (w/v) , or sucrose 0.32 M in the case of spinal cord, homogenized and then centrifuged at 20,000 g for 10 min at 7°C twice. The resulting pellet was resuspended under the same conditions and centrifuged again. The pellet was finally resuspended on a minimum volume and kept at - 80°C overnight. On the next day, the process was repeated until the final pellet was resuspended at a ratio of 1:10 (w/v) in the case of cerebellum and at a ratio of 1:5 (w/v) in the case of spinal cord. Affinity was determined by competitive tests using radiolabeled flumazenil as ligand. The tests were performed according to the methods described by S. Arbilla et al. (Eur. J. Pharmacol., 130, 257-263, 1986); and Y. Wu et al. (Eur. J. Pharmacol., 278, 125- 132, 1995) using 96-well microtiter plates. The membranes containing the study receptors, flumazenil (radiolabeling at a final concentration of 1 nM) and ascending concentrations of test compounds (in a total volume of 230 µL in 50 mM [ph 7.4] Tris.HCl buffer) were incubated. Simultaneously, the membranes were only incubated with the radiolabeled flumazenil, (total binding, 100%) and in the presence of an elevated concentration of unradiolabeled flumazenil (non- specific binding, % estimation of radiolabeled ligand). The reactions started on adding the radiolabeled ligand followed by incubation for 60 minutes at 4°C. At the end of the incubation period, 200 µL of reaction were transferred to a multiscreen plate (Millipore) and filtered using a vacuum manifold and then washed three times with cold test buffer. The multiscreen plates were equipped with a GF/B filter that retained the membranes containing the receptors and the radiolabeled ligand which has been bound to the receptors. After washing, the plates were left till dry. Once dried, scintillation liquid was added and left under stirring overnight. The next day the plates were counted using a Perkin-Elmer Microbeta scintillation counter. For analysis of the results the percentage of specific binding for every concentration of test compound was calculated as follows: % specific binding = (X-N/T-N) x 100 where, X: amount of bound ligand for every concentration of compound. T: total binding, maximum amount bound to the radiolabeled ligand. N: non-specific binding, amount of radiolabeled ligand bound in a non-specific way irrespective of the receptor used. Every concentrations of compound were tested in triplicate and their mean values were used to determine the experimental values of % specific binding versus the concentration of compound. Affinity data are expressed as % inhibition at 10-5M and 10-7M concentrations. The results of these tests are given in Tables 1 and 2. In vivo determination of predictive sedative-hypnotic action. The in vivo effects of these compounds were assessed by a predictive sedation-hypnosis test in mice (D. J. Sanger et al., Eur.J.Pharmacol., 313, 35-42, 1996/ and G. Griebel et al., Psychopharmacology, 146, 205-213, 1999). Groups of 5-8 male CD1 mice, weighing 22-26 g at the time of test, were used. The test compounds were administered in single equimolecular intraperitoneal doses, suspended in 0.25% agar with one drop of Tween in a volume of 10 mL/kg. Control animals received the vehicle alone. Using a Smart System (Panlab,S.L., Spain) the traveled distance in cm is recorded for each mouse at 5-min intervals during a period of 30 minutes after dosing. The inhibition percentage of traveled distance of treated animals versus control animals (the first 5 min were discarded) was calculated. The results of this test are given in Table 3. Table 3. Determination of in vivo sedative-hypnotic activity in mice. The following non-limiting examples illustrate the scope of the present invention. Example 1: 6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-4- ium bromide A solution of 11.53 g (106.7 mmol) of 5-methyl-pyridin- 2-ylamine in 150 mL of ethanol is added to a solution of 25 g (117.3 mmol) of 2-bromo-1-p-tolyl-ethanone in 150 mL of ethanol. The resulting solution is stirred at reflux for 4 hours. The reaction is allowed to cool, and the solvent is removed in vacuo. The yellow solid obtained is dissolved in 30 mL of hot ethanol, and 40 mL of acetone are added. The solid obtained is filtered off, washed with acetone and dried over calcium chloride to give 20.0 g (65.9 mmol, yield: 62%) of 6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-4-ium bromide as a white solid. 1H NMR (400 MHz, DMSO-d6) : δ 8.31-7.10 (Ar, 8H, m) , 2.36 (Ph-Me, 3H, s), 2.31 (Me, 3H, s). MS (ES) m/z = 223 (MH+) HPLC = 100% Example 2: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- yl)-methanol A solution of 6 mL (81 mmol) of formaldehyde in water (37%) is added to a solution of 4 g (18 mmol) of 6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-4-ium bromide in 30 mL of acetic acid. The reaction is heated at 55°C for 4 h. The resulting solution is allowed to cool, and the solvent is removed in vacuo. To the corresponding residue are added 20 mL of ammonia (25%) and 30 mL of dichloromethane, and the suspension is stirred overnight. The solid obtained is filtered off, washed with dichloromethane and water and dried over calcium chloride, to yield 2.8 g (11 mmol, 62%) of (6-methyl-2- p-tolyl-imidazo[1,2-a]pyridin-3-yl)-methanol as a white solid. 1H NMR (400 MHz, DMSO-d6) : δ 8.23-7.13 (Ar, 7H, m) , 5.33 (OH, 1H, t, J= 5.2 Hz), 4.85 (CH2, 2H, d, J= 5.2 Hz), 2.35 (Ph-Me, 3H, s), 2.33 (Me, 3H, s). MS (ES) m/z = 253 (MH+) HPLC = 98.3% Example 3: 4-Dimethylamino-N-(6-methyl-2-p-tolyl- imidazo [1,2-a]pyridin-3-ylmethyl)-benzamide To a solution of 1 eq of (6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-yl)-methanol in acetic acid is added a solution of 4-dimethylaminobenzonitrile (2 eq) in acetic acid. Then, 4 eq of sulphuric acid are added slowly. The mixture is heated at room temperature for 1.5 h, and then at reflux for 2 h. The reaction is allowed to cool and is basified with ammonia (25%). The suspension is extracted with dichloromethane. The organic phase is dried over magnesium sulphate and filtered off. The solvent is removed in vacuo to give 0.96 eq of 4-Dimethylamino-N-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide. 1H NMR (400 MHz, DMSO-d6) : δ 8.58 (NH, 1H, t, J= 5.2 Hz), 8.29-6.65 (Ar, 11H, m) , 4.87 (CH2, 2H, d, J= 5.2 Hz), 2.94 (N-Me, 6H, s), 2.34 (Ph-Me, 3H, s). MS (ES) m/z = 399 (MH+) HPLC = 97.1% The compounds of examples 4-21 were prepared according to this procedure starting from (6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-yl)-methanol and the corresponding nitrile. Example 4: Furan-2-carboxylic acid (6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-amide Yield: 47% 1H NMR (400 MHz, DMSO-d6) : δ 8.17 (NH, 1H, m) , 7.65- 6.11 (Ar, 10H, m) , 4.51 (CH2, 2H, m) , 2.33 (Ph-Me, 3H, s), 2.29 (Me, 3H, s). MS (ES) m/z = .346 (MH+) HPLC = 82.7% Example 5: Pyridine-2-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide Yield: 17% 1H NMR (400 MHz, DMSO-d6) : 5 9.36 (NH, 1H, t, J= 5.6 Hz), 8.61-7.12 (Ar, 14H, m) , 4.95 (CH2, 2H, d, J= 5.6 Hz), 2.34 (Ph-Me, 3H, s), 2.29 (Me, 3H, s). MS (ES) m/z = 357 (MH+) HPLC = 96.7% Example 6: 1,5-Dimethyl-1H-pyrrole-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 14% 1H NMR (400 MHz, DMSO-d6) : 8 8.31 (NH, 1H, m) , 7.66- 6.99 (Ar, 9H, m) , 4.64 (CH2, 2H, m) , 3.28 (N-Me, 3H, s), 2.34 (Ph-Me, 3H, s) , 2.17 (Me, 3H, s) , 1.34 (Me- pyrrole, 3H, s). MS (ES) m/z = 373 (MH+) HPLC = 97.9% Example 7: N-(6-Methyl-2-p-tolyl-imidazo[1, 2-a]pyridin- 3-ylmethyl)-isonicotinamide Yield: 19% 1H NMR (400 MHz, DMSO-d6): 8 9.23 (NH, 1H, t, J= 4.8 Hz), 8.70-7.14 (Ar, 11H, m) , 4.93 (CH2, 2H, d, J= 4.8 Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 357 (MH+) HPLC = 92.9% Example 8: N-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin- 3-ylmethyl)-4-nitro-benzamide Yield: 29% 1H NMR (400 MHz, DMSO-d6) : δ 9.28 (NH, 1H, t, J= 3.6 Hz), 8.29-7.14 (Ar, 11H, m) , 4.94 (CH2, 2H, d, J= 3.6 Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 401 (MH+) HPLC = 98.8% Example 9: Thiophene-2-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide Yield: 8% 1H NMR (400 MHz, DMSO-d6) : δ 8.94 (NH, 1H, t, J= 5.2 Hz), 8.26-7.10 (Ar, 10H, m) , 4.89 (CH2, 2H, d, J= 5.2 Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 362 (MH+) HPLC = 92.1% Example 10: N-(6-Methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide Yield: 89% 1H NMR (400 MHz, DMSO-d6) : δ 9.18 (NH, 1H, t, J= 5.2 Hz), 8.27-7.14 (Ar, 11H, m) , 4.94 (CH2, 2H, d, J= 5.2 Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 424 (MH+) HPLC = 98.5% Example 11: 4-Methoxy-N-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide Yield: 14% 1H NMR (400 MHz, DMSO-d6) : δ 8.8 (NH, 1H, t, J= 5.2 Hz), 8.28-6.95 (Ar, 11H, m) , 4.89 (CH2, 2H, d, J= 5.2 Hz), 3.78 (MeO, 3H, s), 2.34 (Ph-Me, 3H, s), 2.29 (Me, 3H, s) . MS (ES) m/z = 386 (MH+) HPLC = 98.3% Example 12: 4-Acetyl-N-(6-methyl-2-p-tolyl-imidazo[1,2- a] pyridin-3-ylmethyl)-benzamide Yield: 17% 1H NMR (400 MHz, DMSO-d6) : δ 9.14 (NH, 1H, t, J= 4.8 Hz), 8.28-7.14 (Ar, 11H, m) , 4.93 (CH2, 2H, d, J= 4.8 Hz), 2.6 (Me-CO, 3H, s), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s) . MS (ES) m/z = 398 (MH+) HPLC = 94.9% Example 13: Cyclopropanecarboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide Yield: 60% 1H NMR (400 MHz, DMSO-d6) : δ 8.6 (NH, 1H, t, J= 5.2 Hz), 8.16-7.13 {Ar, 7H, m) , 4.72 (CH2, 2H, d, J= 5.2 Hz), 2.35 (Ph-Me, 3H, s) , 2.3 (Me, 3H, s), 1.59 (CH, 1H, m), 0.76 (CH2CH2, 4H, m). MS (ES) m/z = 320 (MH+) HPLC = 99.3% Example 14: 5-Nitro-furan-2-carboxylic acid (6-methyl- 2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide Yield: 27% 1H NMR (400 MHz, DMSO-d6) : δ 9.38 (NH, 1H, m) , 8.25- 7.15 (Ar, 9H, m), 4.91 (CH2, 2H, d, J= 4 Hz), 2.34 (Ph- Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 391 (MH+) HPLC = 97.9% Example 15: 3-Methyl-furan-2-carboxylic acid (6-methyl- 2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide Yield: 3% 1H NMR (400 MHz, DMSO-d6) : δ 8.74 (NH, 1H, t, J= 5.2 Hz), 8.25-6.21 (Ar, 9H, m) , 5.85 {CH2, 2H, d, J= 5.2 Hz), 2.34 (Ph-Me, 3H, s) , 2.29 (Me, 3H, s) , 1.03 (Me- furane, 3H, s). MS (ES) m/z = 360 (MH+) HPLC = 93.7% Example 16: 3-Methyl-thiophene-2-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 29% 1H NMR (400 MHz, DMSO-d6) : δ 8.6 (NH, 1H, m) , 8.3-6.9 (Ar, 9H, m) , 4.87 (CH2, 2H, d, J= 5.2 Hz), 2.37 (Me, 3H, s), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). HPLC = 87.1% Example 17: 2-Chloro-N-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-isonicotinamide Yield: 15% 1H NMR (400 MHz, DMSO-d6) : δ 9.29 (NH, 1H, m) , 8.56- 7.16 (Ar, 10H, m) , 4.92 (CH2, 2H, d, J= 4.4 Hz), 2.34 (Ph-Me, 3H, s), 2.31 (Me, 3H, s). HPLC = 99.2% Example 18: 2,3,5,6-Tetrafluoro-N-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-isonicotinamide Yield: 13% 1H NMR (400 MHz, DMSO-d6) : δ 9.65 (NH, 1H, m) , 8.19 (Ar, 7H, m) , 4.99 (CH2, 2H, m) , 2.36 (Ph-Me, 3H, s) , 2.32 (Me, 3H, s). HPLC = 96.9% Example 19: Quinoline-2-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide Yield: 17% 1H NMR (400 MHz, DMSO-d6) : δ 9.47 Hz), 8.57-7.13 (Ar, 13H, m) , 5.05 (CH2, 2H, d, J= 4.8 Hz), 2.34 (Ph-Me, 3H, s), 2.29 (Me, 3H, s). MS (ES) m/z = 407 (MH+) HPLC = 90.5% Example 20: 3,5-Difluoro-pyridine-2-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 86% 1H NMR (400 MHz, DMSO-d6) : δ 9.28 (NH, 1H, t, J= 5.2 Hz), 8.54-7.14 (Ar, 9H, m) , 4.92 (CH2, 2H, d, J= 5.2 Hz), 2.35 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 393 (MH+) HPLC = 96.6% Example 21: 6-Methoxy-benzothiazole-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 10% 1H NMR (400 MHz, DMSO-d6) : δ 8.18 (NH, 1H, m) , 8.02- 7.12 (Ar, 10H, m) , 4.67 (CH2, 2H, m) , 4.06 (MeO, 3H, s), 2.27 (Ph-Me, 3H, s), 2.17 (Me, 3H, s). MS (ES) m/z = 443 (MH+) HPLC = 100% Example 22: 4-Dimethylamino-N-methyl-N-(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide To a solution of 4-dimethylamino-N-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide (1 eq) in dry DMF are added 1.2 eq of NaH (60%) under argon. The suspension is stirred for 10 min at room temperature. Then 1.1 eq of Mel are added and the corresponding mixture is stirred for 1 h at room temperature. After this period, 0.5 N NaOH is added. The mixture is extracted with dichloromethane. The organic layer is dried over magnesium sulphate and the solvent is removed in vacuo to obtain 0.58 eq of 4-dimethylamino- N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-benzamide. 1H NMR (400 MHz, DMSO-d6) : δ 8.23-6.67 (Ar, 11H, m) , 5.19 (CH2, 2H, s), 2.92 (NMe2, 6H, s) , 2.58 (N-Me, 3H, s), 2.34 (Ph-Me, 3H, s), 2.28 (Me, 3H, s). MS (ES) m/z = 413 (MH+) HPLC = 90.8% The compounds of examples 23-36 were prepared following this procedure starting from the corresponding N- dealkylated amides. Example 23: 4-Isobutyryl-N-methyl-N-(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide Yield: 20% 1H NMR (400 MHz, DMSO-d6) : δ 8.31-7.18 (Ar, 11H, m) , 5.27 (CH2, 2H, s), 3.64 (CH, 1H, hept, J= 6.8 Hz), 2.46 (N-Me, 3H, s), 2.35 (Ph-Me, 3H, s) , 2.32 (Me, 3H, s), 1.09 (Me, 6H, d, J= 6.8 Hz). MS (ES) m/z = 440 (MH+) HPLC = 83.7% Example 24: Cyclopropanecarboxylic acid methyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 100% 1H NMR (400 MHz, DMSO-d6) : δ 8.08-7.14 (Ar, 7H, m) , 5.09 (CH2, 2H, s), 2.72 (N-Me, 3H, s), 2.35 (Ph-Me, 3H, s), 2.25 (Me, 3H, s) , 1.89 (CH, 1H, m) , 0.8 (CH2, 4H, m) . MS (ES) m/z = 334 (MH+) HPLC = 98.6% Example 25: 4-Methoxy-N-methyl-N-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide Yield: 93% 1H NMR (400 MHz, DMSO-d6) : δ 9.45-7.68 (Ar, 11H, m) , 5.2 (CH2, 2H, s), 3.77 (MeO, 3H, s), 2.55 (N-Me, 3H, s), 2.35 (Ph-Me, 3H, s), 2.3 (Me, 3H, m). MS (ES) m/z = 400 (MH+) HPLC = 95% Example 26: N-Methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2- a] pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide Yield: 100% 1H NMR (400 MHz, DMSO-d6) : δ 8.30-7.18 (Ar, 11H, m) , 5.27 (CH2, 2H, s), 2.5 (N-Me, 3H, s) , 2.35 (Ph-Me, 3H, s), 2.32 (Me, 3H, s). MS (ES) m/z = 438 (MH+) HPLC = 95.9% Example 27: N-Methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2- a] pyridin-3-ylmethyl)-isonicotinamide Yield: 22% 1H NMR (400 MHz, DMSO-d6) : δ 8.63-7.19 (Ar, 11H, m) , 5.25 (CH2, 2H, s), 2.46 (N-Me, 3H, s), 2.35 (Ph-Me, 3H, s) , 2.32 (Me, 3H, s) . MS (ES) m/z = 371 (MH+) HPLC = 94.6% Example 28: Pyridine-2-carboxylic acid methyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 77% 1H NMR (400 MHz, DMSO-d6) : δ 8.53-7.18 (Ar, 11H, m) , 5.27 (CH2, 2H, s), 2.54 (N-Me, 3H, s), 2.33 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 371 (MH+) HPLC = 80.6% Example 29: Thiophene-2-carboxylic acid methyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 100% 1H NMR (400 MHz, DMSO-d6) : δ 8.22-7.09 (Ar, 10H, m) , 5.26 (CH2, 2H, s), 2.77 (N-Me, 3H, s), 2.34 (Ph-Me, 3H, s), 2.28 (Me, 3H, s). MS (ES) m/z = 376 (MH+) HPLC = 87% Example 30: 4,N-Dimethyl-N-(6-methyl-2-p-tolyl-imidazo [1,2-a]pyridin-3-ylmethyl)-benzamide Yield: 83% 1H NMR (400 MHz, DMSO-d6) : δ 7.67-7.16 (Ar, 11H, m) , 5.22 (CH2, 2H, s), 2.52 (N-Me, 3H, s) , 2.34 (Ph-Me, 3H, s), 2.31 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 384 (MH+) HPLC = 99% Example 31: N-Methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2- a] pyridin-3-ylmethyl)-4-nitro-benzamide Yield: 48% 1H NMR (400 MHz, DMSO-d6) : δ 8.30-7.19 (Ar, 11H, m) , 5.27 (CH2, 2H, s), 2.49 (N-Me, 3H, s), 2.34 (Ph-Me, 3H, s), 2.32 (Me, 3H, s). MS (ES) m/z = 415 (MH+) HPLC = 100% Example 32: 5-Nitro-furan-2-carboxylic acid methyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 42% 1H NMR (400 MHz, DMSO-d6) : δ 8.26-7.19 (Ar, 9H, m) , 5.26 (CH2, 2H, s), 2.82 (N-Me, 3H, s), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s). MS (ES) m/z = 405 (MH+) HPLC = 98.8% Example 33: 3,5-Difluoro-pyridine-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide Yield: 27% 1H NMR (400 MHz, DMSO-d6) : δ 8.55-7.20 (Ar, 9H, m) , 5.3 (CH2, 2H, s), 2.46 (N-Me, 3H, s) , 2.34 (Ph-Me, 3H, s) , 2.3 (Me, 3H, s). MS (ES) m/z = 407 (MH+) HPLC = 96.6% Example 34: 2-Chloro-N-methyl-N-(6-methyl-2-p-tolyl- imidazo [1,2-a]pyridin-3-ylmethyl)-isonicotinamide Yield: 61% 1H NMR (400 MHz, DMSO-d6) : δ 8.51-7.22 (Ar, 10H, m) , 5.26 (CH2, 2H, s), 2.48 (N-Me, 3H, s), 2.38 (Ph-Me, 3H, s), 2.36 (Me, 3H, s). MS (ES) m/z = 405 (MH+) HPLC = 83.6% Example 35: Quinoline-2-carboxylic acid methyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 60% 1H NMR (400 MHz, DMSO-d6) : δ 8.77-7.16 (Ar, 13H, m) , 5.35 (CH2, 2H, s), 2.65 (N-Me, 3H, s), 2.36 (Ph-Me, 3H, s), 2.33 (Me, 3H, s). MS (ES) m/z = 421 (MH+) HPLC = 96.6% Example 36: 6-Methoxy-3-methyl-2-[methyl-(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamoyl]- benzothiazol-3-ium iodide Yield: 85% 1H NMR (400 MHz, DMSO-d6) : δ 8.53-7.29 (Ar, 10H, m) , 4.73 (CH2, 2H, s), 3.94 (MeO, 3H, s) , 3.44 (Me- thiazole, 3H, s), 2.97 (N-Me, 3H, s), 2.37 (Ph-Me, 3H, s), 2.32 (Me, 3H, s). MS (ES) m/z = 471 (MH+) HPLC = 97.6% Example 37: N-Ethyl-N-(6-methyl-2-p-tolyl-imidazo[1,2- a] pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide To a solution of N-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide (1 eq) in dry DMF are added 1.2 eq of NaH (60%) under argon. The suspension is stirred for 10 min at room temperature. Then 1.1 eq of EtI are added and the corresponding mixture is stirred for 1 h at room temperature. After this period, 0.5 N NaOH is added. The mixture is extracted with dichloromethane. The organic layer is dried over magnesium sulphate and the solvent is removed in vacuo to obtain 0.47 eq of N- ethyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-4-trifluoromethyl-benzamide. Yield: 47% 1H NMR (400 MHz, DMSO-d6) : δ 8.26-7.19 (Ar, 11H, m) , 5.32 (CH2, 2H, s), 2.7 (CH2-Me, 2H, m) , 2.36 (Ph-Me, 3H, s), 2.33 (Me, 3H, s), 0.55 (Me-CH2, 3H, m) . MS (ES) m/z = 452 (MH+) HPLC = 99.8% The compound of example 38 was prepared according to this procedure starting from the corresponding N- dealkylated amide. Example 38: Cyclopropanecarboxylic acid ethyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide Yield: 41% 1H NMR (400 MHz, DMSO-d6) : δ 8.07-7.14 (Ar, 7H, m) , 5.12 (CH2, 2H, s), 3.08 (CH2-Me, 2H, q, J= 7.2 Hz), 2.36 (Ph-Me, 3H, s) , 2.25 (Me, 3H, s) , 1.85 (CH, 3H, m) , 0.81 (Me-CH2, 3H, t, J= 7.2 Hz), 0.73 (CH2, 4H, m) . MS (ES) m/z = 348 (MH+) HPLC = 92.3% Example 39: N-(6-Methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-N-propyl-4-trifluoromethyl- benzamide To a solution of N-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide (1 eq) in dry DMF are added 1.2 eq of NaH (60%) under argon. The suspension is stirred for 10 min at room temperature. Then 1.1 eq of PrI are added and the corresponding mixture is stirred for 1h at room temperature. After this period, 0.5 N NaOH is added. The mixture is extracted with dichloromethane. The organic layer is dried over magnesium sulphate and the solvent is removed in vacuo to obtain 0.17 eq of N-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-N- propyl-4-trifluoromethyl-benzamide. Yield: 17% MS (ES) m/z = 466 (MH+) HPLC = 83.9% The compound of example 40 was prepared according to this procedure starting from the corresponding N- dealkylated amide. Example 40: Cyclopropanecarboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-propyl-amide Yield: 35% MS (ES) m/z = 362 (MH+) HPLC = 89.8% Example 41: N-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-N-prop-2-ynyl-4-trifluoromethyl- benzamide To a solution of N-(6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide (1 eq) in dry DMF are added 1.2 eq of NaH (60%) under argon. The suspension is stirred for 10 min at room temperature. Then 1.1 eq of 3-bromo-propyne are added and the corresponding mixture is stirred for lh at room temperature. After this period, NaOH 0.5 N is added. The mixture is extracted with dichloromethane. The organic layer is dried under magnesium sulphate and the solvent is removed in vacuo to obtain 0.16 eq of N-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-N- prop-2-ynyl-4-trifluoromethyl-benzamide. MS (ES) m/z = 462 (MH+) HPLC = 84% The compound of example 42 was prepared according to this procedure starting from the corresponding N- dealkylated amide. Example 42: Cyclopropanecarboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-prop-2-ynyl- amide Yield: 29% MS (ES) m/z = 358 (MH+) HPLC = 84.7% Example 43: C-(6-Methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-yl)-methylamine A solution of 3 g (13 mmol) of bromide of 6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-4-ium in 50 mL of acetic acid is added to a solution of 1 g (13 mmol) N- methanolacetamide in 50 mL of acetic acid. To the resulting solution are added slowly 5 g (54 mmol) of concentrated sulphuric acid. The crude is stirred at room temperature for 1.5 hours and after at reflux for 2 hours. The reaction is allowed to cool, and 50 mL of water are added. The crude is basified with ammonia 25% and extracted with dichloromethane. The organic layer is dried, filtered off and the solvent is removed in vacuo, to obtain 3.86 g (13.2 mmol, yield: 97%) of the corresponding amide. This amide is dissolved in 150 mL of ethanol and 50 mL of concentrated hydrochloric acid are added. The mixture is heated at reflux for 30 min. The crude is neutralized and the solvent is removed. The residue is extracted with DCM-water, and the organic layer is dried, filtered off and evaporated, to obtain 3.2 g (12.8 mmol, 97%) of C-(6-Methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-yl)-methylamine as a white solid. MS (ES) m/z = 252 (MH+) HPLC = 90% Example 44: 1-(4-Dimethylamino-phenyl)-3-(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea To a solution of 1 eq of C-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-yl)-methylamine in pyridine is added a solution of 1-(4-Dimethylamino-phenyl)- isocyanate (1 eq) in pyridine. The mixture is stirred at room temperature for 2 4 hours. The solvent is removed and water is added to the residue. The solid thus obtained is filtered off, washed with water and dried over calcium chloride to give 1-(4-Dimethylamino- phenyl) -3- (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-urea. Yield: 27% 1H NMR (400 MHz, DMSO-d6) : δ 8.78 (NH, 1H, s) , 8.45 (NH, 1H, m) , 7.80-6.80 (Ar, 11H, m) , 4.76 (CH2, 2H, d, J= 5.6 Hz), 2.85 (Me2N, 6H, s) , 2.43 (Ph-Me, 3H, s) , 2.4 (Me, 3H, s). MS (ES) m/z = 414 (MH+) HPLC =94% The compounds of examples 45-4 9 were prepared according to this procedure starting from the corresponding isocyanates. Example 45: 1-Ethyl-3-(6-methyl-2-p-tolyl-imidazo[1,2- a] pyridin-3-ylmethyl)-urea Yield: 27% 1H NMR (400 MHz, DMSO-d6) : δ 8.84-7.41 (Ar, 7H, m) , 6.78 (NH, 1H, m) , 6.08 (NH, 1H, m) , 4.67 (CH2, 2H, d, J= 5.2 Hz), 3.01 (CH2, 2H, quint, J= 6.8 Hz), 2.44 (Ph- Me, 3H, s), 2.4 (Me, 3H, s) , 0.97 (Me-CH2, 3H, t, J= 6.8 Hz). MS (ES) m/z = 323 (MH+) HPLC = 100% Example 46: 1-Isopropyl-3-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-urea Yield: 28% 1H NMR (400 MHz, DMSO-d6) : δ 8.83-7.42 (Ar, 7H, m) , 6.61 (NH, 1H, m) , 5.93 (NH, 1H, d, J= 8 Hz), 4.68 (CH2, 2H, d, J= 5.2 Hz), 3.67 (CH-Me2, 1H, m) , 2.43 (Ph-Me, 3H, s), 2.41 (Me, 3H, s) , 1.00 (Me2-CH, 6H, d, J= 6 Hz) . MS (ES) m/z = 337 (MH+) HPLC = 100% Example 47: 1-Cyclopentyl-3-(6-methyl-2-p-tolyl-imidazo [1,2-a]pyridin-3-ylmethyl)-urea Yield: 36% 1H NMR (400 MHz, DMSO-d6) : δ 8.79-7.40 (Ar, 7H, m), 6.52 (NH, 1H, m) , 6.05 (NH, 1H, d, J= 7.6 Hz), 4.68 (CH2, 2H, d, J= 5.2 Hz), 3.85 (CH, 1H, m), 2.42 (Ph-Me, 3H, s), 2.4 (Me, 3H, s), 1.76-1.22 ((CH2)4, 8H, m) . MS (ES) m/z = 363 (MH+) HPLC = 99% Example 48: 1-Cyclohexyl-3-(6-methyl-2-p-tolyl-imidazo [1,2-a]pyridin-3-ylmethyl)-urea Yield: 46% 1H NMR (400 MHz, DMSO-d6) : δ 8.75-7.40 (Ar, 7H, m) , 6.54 (NH, 1H, m) , 5.94 (NH, 1H, d, J= 6.8 Hz), 4.68 (CH2, 2H, d, J= 5.2 Hz), 3.9 (CH, 1H, m) , 2.42 (Ph-Me, 3H, s), 2.4 (Me, 3H, s), 1.72-1.04 ((CH2)5, 10H, m) . MS (ES) m/z = 377 (MH+) HPLC = 98% Example 49: 1-(6-Methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-3-phenyl-urea Yield: 30% 1H NMR (400 MHz, DMSO-d6) : δ 8.43 (NH, 1H, s), 8.34- 6.88 (Ar, 12H, m) , 6.83 (NH, 1H, t, J= 5.6 Hz), 4.74 (CH2, 2H, d, J= 5.6 Hz), 2.35 (Ph-Me, 3H, s), 2.31 (Me, 3H, s). MS (ES) m/z = 371 (MH+). HPLC =92% Example 50: (6-Methyl-2-p-tolyl-imidazo[1, 2-a]pyridin- 3-ylmethyl)-carbamic acid p-tolyl ester To a solution of 1 eq of C-(6-Methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-yl)-methylamine in pyridine is added a solution of p-tolyl-chloroformiate (1 eq) in pyridine. The mixture is stirred at room temperature for 2 4 hours. The solvent is removed and water is added to the residue. The solid thus obtained is filtered off, washed with water and dried over calcium chloride to give (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-carbamic acid p-tolyl ester. Yield: 16% 1H NMR (400 MHz, DMSO-d6) : δ 8.41-6.93 (Ar, 11H, m) , 6.62 (NH, 1H, t, J= 5.6 Hz), 4.71 (CH2, 2H, d, J= 5.6 Hz), 2.35 (impy-Ph-Me, 3H, s), 2.3 (Ph-Me, 3H, s), 2.28 (Me, 3H, s). MS (ES) m/z = 386 (MH+) HPLC = 80% The compounds of examples 51-57 were prepared according to this procedure starting from the corresponding chloroformiates. Example 51: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin- 3-ylmethyl)-carbamic acid prop-2-ynyl ester Yield: 5% 1H NMR (400 MHz, DMSO-d6) : δ 8.21-7.15 (Ar, 7H, m) , 8.05 (NH, 1H, t, J= 5.2 Hz), 4.66 (CH2-C, 2H, d, J= 2.4 Hz), 4.64 (CH2, 2H, d, J= 5.2 Hz), 3.5 (CH, 1H, t, J= 2.4 Hz), 2.34 (Ph-Me, 3H, s), 2.31 (Me, 3H, s). MS (ES) m/z = 334 (MH+) HPLC = 98% Example 52: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin- 3-ylmethyl)-carbamic acid methyl ester Yield: 30% 1H NMR (400 MHz, DMSO-d6) : δ 8.23-7.14 (Ar, 7H, m) , 7.83 (NH, 1H, m) , 4.61 (CH2, 2H, d, J= 5.2 Hz), 3.56 (MeO, 3H, s), 2.34 (Ph-Me, 3H, s) , 2.31 (Me, 3H, s). MS (ES) m/z = 310 (MH+) HPLC = 100% Example 53: (6-Methyl-2-p-tolyl-imidazo[1, 2-a]pyridin- 3-ylmethyl)-carbamic acid benzyl ester Yield: 15% 1H NMR (400 MHz, DMSO-d6) : δ 8.21-7.14 (Ar, 12H, m) , 7.98 (NH, 1H, m) , 5.08 (CH2-Ph, 2H, s) , 4.65 (CH2, 2H, d, J= 5.6 Hz), 2.34 (Ph-Me, 3H, s), 2.28 (Me, 3H, s). MS (ES) m/z = 386 (MH+) HPLC =86% Example 54: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin- 3-ylmethyl)-carbamic acid 4-methoxy-phenyl ester Yield: 41% 1H NMR (400 MHz, DMSO-d6) : δ 8.70-6.89 (Ar, 11H, m) , 8.50 (NH, 1H, m) , 4.74 (CH2, 2H, d, J= 5.2 Hz), 3.73 (MeO, 3H, s), 2.45 (Ph-Me, 3H, s), 2.39 (Me, 3H, s). MS (ES) m/z = 402 (MH+) HPLC = 88% Example 55: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin- 3-ylmethyl)-carbamic acid ethyl ester Yield: 23% 1H NMR (400 MHz, DMSO-d6) : δ 8.46-7.32 (Ar, 7H, m) , 4.63 (CH2, 2H, d, J= 4.4 Hz), 4.02 (CH2-Me, 2H, m) , 2.49 (Ph-Me, 3H, s), 2.37 (Me, 3H, s) , 1.15 (Me, 3H, t, J= 6.8 Hz). MS (ES) m/z = 324 (MH+) HPLC = 81% Example 56: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin- 3-ylmethyl)-carbamic acid phenyl ester Yield: 22% 1H NMR (400 MHz, DMSO-d6) : δ 8.70-6.72 (Ar, 12H, m) , 8.56 (NH, 1H, m) , 4.76 (CH2, 2H, d, J= 5.6 Hz), 2.45 (Ph-Me, 3H, s), 2.39 (Me, 3H, s). MS (ES) m/z = 372 (MH+) HPLC = 90% Example 57: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin- 3-ylmethyl)-carbamic acid isopropyl ester Yield: 16% 1H NMR (400 MHz, DMSO-d6) : δ 8.25-7.14 (Ar, 7H, m) , 7.75 (NH, 1H, d, J= 5.6 Hz), 4.81 (CH, 1H, m) , 4.62 (CH2, 2H, d, J= 5.6 Hz), 2.34 (Ph-Me, 3H, s) , 2.31 (Me, 3H, s), 1.17 (Me2CH, 6H, d, J= 6.4 Hz). MS (ES) m/z = 338 (MH+) HPLC = 98% The compounds of examples 58-90 were prepared according to the procedure described for example 44, starting from C-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)- methylamine and the corresponding acid chlorides. Example 58: Cyclobutanecarboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 334 (MH+) HPLC = 99% Example 59: Cyclopentanecarboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 348 (MH+) HPLC = 99% Example 60: Benzo[b]thiophene-3-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 413 (MH+) HPLC = 97% Example 61: 5-Methyl-pyrazine-2-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 372 (MH+) HPLC = 90% Example 62: 1-Methyl-1H-pyrrole-2-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 359 (MH+) HPLC = 90% Example 63: N-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin -3-ylmethyl)-nicotinamide MS (ES) m/z = 357 (MH+) HPLC =92% Example 64: 5-Chloro-4-methoxy-thiophene-3-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 427 (MH+) HPLC = 98% Example 65: 6-Oxo-1,4,5,6-tetrahydro-pyridazine-3- carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 376 (MH+) HPLC = 99% Example 66: Benzo[c]isoxazole-3-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 397 (MH+) HPLC = 97% Example 67: 1,5-Dimethyl-1H-pyrazole-3-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 374 (MH+) HPLC = 99% Example 68: 1-Methyl-1H-indole-3-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 410 (MH+) HPLC = 98% Example 69: 2-Methyl-thiazole-4-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 377 (MH+) HPLC = 99% Example 70: [1,2,3]Thiadiazole-4-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 364 (MH+) HPLC = 99% Example 71: N-(6-Methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-2-thiophen-2-yl-acetamide MS (ES) m/z = 376 (MH+) HPLC = 98% Example 72: 5-Methyl-isoxazole-3-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 361 (MH+) HPLC = 97% Example 73: N-(6-Methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-6-(2,2,2-trifluoro-ethoxy)- nicotinamide MS (ES) m/z = 455 (MH+) HPLC = 91% Example 74: 1-Methyl-1H-imidazole-4-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 360 (MH+) HPLC = 99% Example 75: 6-Methoxy-2-oxo-2H-chromene-3-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 454 (MH+) HPLC = 89% Example 76: 4-Methoxy-thiophene-3-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 392 (MH+) HPLC = 93% Example 77: 5-Methoxy-thiophene-2-carboxylic acid (6- methyl-2-p-tolyl-imidazo [1, 2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 392 (MH+) HPLC = 91% Example 78: 1-Methyl-1H-imidazole-2-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 360 (MH+) HPLC = 90% Example 79: 4-Methyl-[1,2,3]thiadiazole-5-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1, 2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 378 (MH+) HPLC = 91% Example 80: 3-Furan-2-yl-N-(6-methyl-2-p-tolyl- imidazo[1,2-a]pyridin-3-ylmethyl)-acrylamide MS (ES) m/z = 372 (MH+) HPLC = 96% Example 81: Thiazole-4-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 363 (MH+) HPLC = 98% Example 82: Thiophene-3-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 362 (MH+) HPLC = 95% Example 83: 2,5-Dimethyl-oxazole-4-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 375 (MH+) HPLC = 98% Example 84: 1-Cyclopropyl-2,5-dimethyl-1H-pyrrole-3- carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2- a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 414 (MH+) HPLC = 95% Example 85: 4,5-Dichloro-isothiazole-3-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 432 (MH+) HPLC =92% Example 86: 1,2,5-Trimethyl-1H-pyrrole-3-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 387 (MH+) HPLC = 96% Example 87: 2,4-Dichloro-5-fluoro-N-(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide MS (ES) m/z = 443 (MH+) HPLC = 91% Example 88: 5-Nitro-thiophene-3-carboxylic acid (6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 407 (MH+) HPLC = 97% Example 89: Pyrazine-2-carboxylic acid (6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 358 (MH+) HPLC = 97% Example 90: 3,5-Dimethyl-isoxazole-4-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 375 (MH+) HPLC = 93% The compounds of examples 91-100 were prepared according to the procedure described for example 22. Example 91: 2-Methyl-thiazole-4-carboxylic acid methyl- (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 392 (MH+) HPLC = 99% Example 92: 1,5-Dimethyl-1H-pyrazole-3-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 388 (MH+) HPLC = 90% Example 93: 1-Methyl-6-oxo-1,4,5,6-tetrahydro- pyridazine-3-carboxylic acid methyl-(6-methyl-2-p- tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide MS (ES) m/z = 404 (MH+) HPLC = 90% Example 94: Thiazole-4-carboxylic acid methyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 377 (MH+) HPLC = 99% Example 95: 2,5-Dimethyl-oxazole-4-carboxylic acid methyl-{6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 389 (MH+) HPLC = 91% Example 96: Pyrazine-2-carboxylic acid methyl-(6- methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)- amide MS (ES) m/z = 372 (MH+) HPLC = 98% Example 97: 1-Methyl-1H-imidazole-4-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 374 (MH+) HPLC = 95% Example 98: 1-Methyl-1H-imidazole-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 374 (MH+) HPLC = 99% Example 99: 5-Methyl-isoxazole-4-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 375 (MH+) HPLC =99% Example 100: 5-Nitro-thiophene-3-carboxylic acid methyl-(6-methyl-2-p-tolyi-imidazo[1,2-a]pyridin-3- ylmethyl)-amide MS (ES) m/z = 421 (MH+) HPLC = 90% We claim : 1, An imidazo[1,2-a] pyridine compound of formula (I): as well as pharmaceutically acceptable salts thereof; wherein R1 and R2 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1-C6), alkenyl (C2-C6), alkynyl(C2-C6), haloalkyl (C1-C6),-O-alkyl(C1-C6), fluoro, chioro and bromo; R3 is selected from the group consisting of hydrogen, linear orbranched alkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl (C3-C6) alkyl (C1-C6), alkenyl (C1-C6), alkynyl (C2-C6) alkyl (C1-C6), alkynyl (C2-C5), alkynyl (C2-C6) alkyl (C1-C6); R4 is selected from the group consisting of haioalkyl (C2-C6) cycloalkyl (C3-C5), cycloalkyl (C3-C6)alkyl(C1-C6), alkynyl (C2-C6) alkyl (C1-C6), alkyl(C1-C6)-O-alkyl (C1-C6), alkyl (C1-C6)-NH-alkyl (C1-C6), alkyl (C1-C6)-N(dialkyl (C1-C6)), -OR5, -NHR5,-NR5R6, phenylalkyl (C2-C6), Phenylalkenyl (C2-C6), naphthyl, monosubstituted naphthyl, disubstituted naphthyl, naphthy- lalkyl(C1-C6), naphthylalkenyl (C2-C6) furyl, substituted furyl, benzofuryl, substituted benzofuryl, pyrrolyl, substituted pyrrolyl, isoxazolyl, substituted isoxazolyl, benzoisoxazolyl, substituted benzoisoxazolyl, imidazolyl, substituted im- idazolyl, benzimidazolyl, substituted benzimidazolyl, indolyl, substituted indolyl, pyrazolyl, substituted pyrazolyl, thienyl, substituted thienyl, benzothienyl, substituted benzothienyl, thiazolyl, substituted thiazolyl, benzothiazolyl, substituted benzothiazolyl, quinolinyl, substituted quinolinyl, isoquinolinyl, substituted isoquinoiinyl, pyridyl, substi- tuted pyridyl, pyrazinyl, substituted pyrazinyl, 6-oxo-1,4,5,6-tetrahydropyridazinyl, substituted 6-oxo-1,4,5,6-tetrahy- dropyridazinyl, thiadiazolyl, substituted thiadiazolyl, isothiazolyl, substituted isothiazolyl, thienylmethyl, 2-oxo- chromenyl, substituted 2-oxochromenyl, 2-(furan-2-yl)vinyl; oxazolyl, substituted oxazolyl, and benzisoxazolyl; R5 and R6 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1-C6), phenylalkyl (C1-C6), haloalkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl(C3-C6)alkyl(C1-C6), alkenyl(C2-C6) and alky- nyl(C2-C6), alkenyl(C2-C5)alkyl(C1-C6), alkynyl(C2-C6)-alkyl(C1-C6), phenyl, substituted phenyl, heteroaryl, substi- tuted heteroaryl; and R7 and R8 are independently selected from the group consisting of linear or branched alkyl(C2-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), alkynyl(C2-C6), -OH, - O-alkyl(C1-C6), -SH, -S-alkyl(C1-C6), halo-alkyl (C1-C6), ω,ω,ω-trifluoroalkyl (C1-C6), -NHalkyl(C1-C6), - Ndialkyl(C1-C6), -NO2, -CN, -SO2alkyl(C1-C6), - Coalkyl(C1-C6), -COOalkyl(C1-C6 , -CO-NHalkyl(C1-C6), CONdialkyl (C1-C6), phenyl, substituted phenyl, heteroaryl, and substituted heteroaryl and wherein the substituents of the radicals that are substituted are selected from the group consisting of linear or branched alkyl (C2-C6), cycloalkyl (C3-C6), alkenyl(C2-C6), alkynyl (C2-C6), -OH, -O-alkyI (C1-C6), -SH, S-alkyl (C1-C5), halo-alkyl(C1-C6), ω,ω,ω-trifluoroalkyl (C1-C6), -NHalkyl(C2-C6), -Ndialkyl (C1-C6),-NO2, -CN, -SO2alkyl (C1-C6),-COalkyl(C1-C6),-COOalkyl(C1-C6),-CO-NHalkyl(C1-C6), -CONdialkyl(C1-C6), phenyl, substituted phenyl, heteroaryl, substituted heteroaryl, fluoro, chloro and bromo. 2. An imidazo [1,2-a] pyridine compound of formula (I): as well as pharmaceutically acceptable salts thereof; wherein R1 and R2 are independently selected from the group consisting of hydrogen, linear or branched alkyl (C1-C6), alkenyl (C2-C6), alkynyl (C2-C6), haloalkyl (C1-C6), -O-alkyl(C1-C6), fluoro, chloro and bromo; R3 is selected from the group consisting of hydrogen, linear or branched alkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl (C3-C6) alkyl (C1-C6), alkynyl (C2-C6), alkenyl(C2-C6)alkyl(C1-C6), alkynyl (C2-C6), alkynyl (C2-C6) alkyl (C1-C6); R4 is selected from the group consisting of haioalkyl(C2-C6), cycloalkyl (C3-C5), cycloalkyl (C3-C6) alkyl (C1-C6), alkynyl (C2-C6) alkyl (C1-C6), alkyl (C1-C6) - O-alkyl (C1-C6), alkyl (C1-C6) -NH-alkyl (C1-C6), alkyl (C1-C6)-N(dialkyl (C1-C6)), -OR5, -NHR5, -NR5R6, phenylalkyl (C2-C6), phenylalkenyl (C2-C6), naphthyl, monosubstituted naphthyl, disubstituted naphthyl, naphthyl- alkyl(C1-C6), naphthylalkenyl (C2-C6), furyl, substituted furyl, benzofuryl, substituted benzofuryt, pyrrolyl, substituted pyrrolyl, isoxazolyl, substituted isoxazolyl, benzoisoxazolyl, substituted benzoisoxazolyl, imidazolyl, substituted im- idazolyl, benzimldazolyl, substituted benzimidazolyl, indolyl, substituted indolyl, pyrazolyl, substituted pyrazolyl, thienyl substituted thienyl, benzothienyl, substituted benzothtenyl, thiazoiyl, substituted thiazolyl, benzothiszolyl, substituted benzothiazolyl, quinolinyl, substituted quolinyl, isoquinolinyl, substituted isoquinolinyl, pyridyl, and sub- stituted pyridyl; R5 and R6 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1-C6), phenylalkyl (C1-C6), haloalkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl (C3-C5) alkyl (C1-C6), alkenyl (C2-C6) and alkynyl (C2-C6), alkenyl(C2-C6) alkyl (C1-C6), alkynyl (C2-C6)alkyl(C1-C6), phenyl, substituted phenyl, heteroaryl, substituted heteroaryl; and R7 and R8 are independently selected from the group consisting of linear or branched alkyl(C2-C6), cycloalkyl(C3-C6), alkenyl(C2-C6),alkynyl(C2-C6), -OH,-O-alkyl(C1-C6),-SH, -S-alkyl (C1-C6), halo-alkyl (C1-C6), ω,ω,ω-trifluoroalkyl (C1-C6), -NHalkyl (C1-C6), - Ndialkyl (C1-C6), -NO2, -CN, -SO2alkyl (C1-C6), - COalkyl (C1-C6), -COOalkyl (C1-C6), -CO-NHalkyl(C1-C6). - CONdialkyl(C1-C6),- phenyl, substituted phenyl, heteroaryl and substituted heteroaryl. 3. A compound as claimed in claim 1, wherein R1 is a methyl group and R2 is a methyl group in para-position; and R3 is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, i-propyl, cyclopropyl and 2-propynyl. 4. A compound as claimed in claim 3, wherein R4 is selected from the group consisting of cyclopropyl, cyclobutyl, 2- propynyl, N,N-dimethyl-4-aminophenyl, 2-furyl, 5-NO2-2-furyl, 2-pyrrolyl, 2-thienyl, 2-pyridyl, 4,6-difiuoro-2-pyridyl, 2-chloro-4-pyridyl, 4-pyridyl, 5-methyl-2-pyrazinyl, 6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl, [1,2,3]thiadiazol-4-yI, 2- thienylmethyl, 1-methyl-1H-imidazol-2-yl, 4-thiazolyl, 2,5-dimethyl-4-oxazolyl and 3,5-dimethyl-4-isoxazolyl. 5. A compound as claimed in claim 4, wherein R4 is selected from the group consisting of cyclopropyl, 2-propynyl, N, N-dimethyl-4-aminophenyl, 2-furyl, 5-NO2-2-furyl, 2-pyrrolyl, 2-thienyl, 2-pyridyl, 4,6-difluoro-2-pyridyl, 2-chioro-4- pyridyf and 4-pyridyl. 6. A compound as claimed in claim 3, wherein R4 is -NR5R6. 7. A compound as claimed in claim 5, wherein R5 is hydrogen or methyl; and R6 is selected from the group consisting of methyl, ethyl, n-propyi, i-propyl, cyclopropyi, cyclopentyl, cyclohexyl, 2-propinyl and phenyl. 6. A compound as claimed in claim 3, wherein R4 is -OR5. 9. A compound as claimed in claim 8, wherein R5 is selected from the group consisting of methyl, ethyl, n-propyl, i- propyl, cyclopropyi, cyclopentyl, cyclohexyl, 2-propinyl, 4-methyl-phenyl, 4-methoxy-phenyl and phenyl. 10. A compound as claimed in claim 4, wherein said compound is selected from the group consisting of: Furan-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yImethyl)-amide; Pyridine-2-carboxylic acid (S-methyl-2-p-tolyl-imidazo[1,2-alpyridin-3-yimethyl)-amide; Thiophene-2-carboxylic acid (S-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; Cyclopropanecarboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 5-Nitro-furan-2-carboxylic acid (S-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 3,5-Difluoro-pyridine-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 6-Methoxy-benzothiazole-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 4-Dimethylamino-N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide; cyclopropanecarboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; Pyridine-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; Thiophene-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 5-Nitro-furan-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 2-Chloro-N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-isonicotinamide; Cyclobutanecarboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yimethyl)-amide; 5-Methyl-pyrazine-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 6-Oxo-1,4,5,6-tetrahydro-pyridazine-3-carboxylic acid (8-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylme- thyl)-amide; [1,2,3]Thiadiazole-4-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide: N-(6-yethyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-2-thiophen-2-yl-acetamide; 1-methyl-1H-imidazole-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-alpyridin-3-ylmethyl)-amide; Thiazoie-4-carboxylic acid (16-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 2,5-Dimethyl-Qxazole-4-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; 3,5-Dimethyl-isoxazole-4-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; and Thiazole-4-carboxylic add methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide. 11. A compound as claimed in claims 6 and 7, wherein said compound is selected from the group consisting of: 1-(4-Dimethylamino-phenyl)-3-(6-methyl-2-p-tolyI-imidazo[1,2-a]pyridin-3-ylmethyl)-urea: 1-Ethyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea: 1-lsopropyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea: 1-Cyclopentyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea: 1-Cyclohexyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea; and 1-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-3-phenyl-urea. 12. A compound as claimed in claims 8 and 9, wherein said compound is selected from the group consisting of: (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid p-tolyl ester; (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid prop-2-ynyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid methyl ester; (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid benzyl ester; (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yimefbyl)-carbamic acid 4-methoxy-phenyl ester; (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid ethyl ester; (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid phenyl ester, and (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid isopropyl ester. 13. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof, as claimed in claim 1, comprising reacting intermediate (II): with the nitrile of the formula R4-CN wherein R1, R2 and R4 are as defined in (I). 14. A process for preparing a compound of formula (I) or a pharmaceuticaliy acceptable saltthereof, as claimed in claim 1, comprising reacting intermediate (III): with an acyl chloride of the formula R4-COCI, an isocyanate of the formula R4-CNO or a chloroformiate of the formula R4-OCOCI, wherein R1, R2 and R4 are as defined in (I). 15. A process as claimed in claim 14, comprising reacting previously in the adequate acid conditions, an intermediate of formula (IV) with an intermediate of formula (V); CH3CONHCH2Q (V) wherein Q is selected from the group consisting of -OH, -Oalkyl (C1-C3), -N+(alkyl(C1-C3)3Cl-, -N+(alkyl(C1-C3)) 38r-, -N+(alkyl(C1-C3)) 3I-, and then hydrolyzing the obtained intermediate (VI): to obtain said intermediate (Ill). 16. A process as claimed in claim 15, comprising utilizing the intermediate of formula (V) wherein Q is -OH. 17. A composition comprising a compound as claimed in claim 1 in association with a therapeutically inert carrier. 18. A compound as claimed in claim 1 for preparing a medicament for treating or preventing diseases associated with GABAA receptor modulation. The present invention relates to novel imidazo[1,2- a]pyridine compounds of general formula (I) as well as pharmaceutically acceptable salts thereof; wherein R1, R2, R3 and R4 are as defined in the claims. The compounds have specific affinity for GABAA receptor and are therefore useful in the treatment and prevention of diseases modulated by α1- and α2-GABAA receptors.

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Technical field
This invention is directed to agents with affinity for
GABAA receptor, specifically to imidazo[1,2-a]pyridine
compounds.
Background of the invention
GABAA receptor (γ-aminobutyric acidA) is a pentameric
protein which forms a membrane ion channel. GABAA
receptor is implicated in the regulation of sedation,
anxiety, muscle tone, epileptogenic activity and memory
functions. These actions are due to defined subunits of
GABAA receptor, particularly the α1- and α2-subunits.
Sedation is modulated by the α1-subunit. Zolpidem is
characterized by a high affinity for the α1-receptors
and its sedative and hypnotic action is mediated by
these receptors in vivo. Similarly, the hypnotic action
of zaleplon is also mediated by the α1-receptors.
The anxiolytic action of diazepam is mediated by the
enhancement of GABAergic transmission in a population
of neurons expressing the α2-receptors. This indicates
that the α2-receptors are highly specific targets for
the treatment of anxiety.

Muscle relaxation in diazepam is mainly mediated by α2-
receptors, since these receptors exhibit a highly
specific expression in spinal cord.
The anticonvulsant effect of diazepam is partly due to
α1-receptors. In diazepam, a memory-impairing compound,
anterograde amnesia is mediated by α1-receptors.
GABAA receptor and its α1- and α2-subunits have been
widely reviewed by H. Mohler et al.(J. Pharmacol. Exp.
Ther., 300, 2-8, 2002); H. Mohler et al.(Curr. Opin.
Pharmacol., 1, 22-25, 2001); U. Rudolph et al.(Nature,
401, 796-800, 1999); and D.J. Nutt et al. (Br. J.
Psychiatry, 179, 390-396, 2001) .
Diazepam and other classical benzodiazepines are
extensively used as anxiolytic agents, hypnotic agents,
anticonvulsants and muscle relaxants. Their side
effects include anterograde amnesia, decrease in motor
activity and potentiation of ethanol effects.
In this context, the compounds of this invention are
ligands of α1- and α2-GABAA receptor for their clinical
application in sleep disorders, preferably insomnia,
anxiety and epilepsy.
Insomnia is a highly prevalent disease. Its chronicity
affects 10% of the population and 30% when transitory
insomnia is computed as well. Insomnia describes the
trouble in falling asleep, staying asleep or waking up
too early, experiencing a non-refreshing sleep, and is

associated with next-day hangover effects such as
weariness, lack of energy, low concentration and
irritability. The social and health impact of this
complaint is important and results in evident
socioeconomic repercussions.
Pharmacological therapy in the management of insomnia
firstly included barbiturates and chloral hydrate, but
these drugs elicit numerous known adverse effects, for
example, overdose toxicity, metabolic induction, and
enhanced dependence and tolerance. In addition, they
affect the architecture of sleep by decreasing above
all the duration and the number of REM sleep stages.
Later, benzodiazepines meant an important therapeutic
advance because of their lower toxicity, but they still
showed serious problems of dependence, muscle
relaxation, amnesia and rebound insomnia following
discontinuation of medication.
The latest known therapeutic approach has been the
introduction of non-benzodiazepine hypnotics, such as
pyrrolo [3, 4-b]pyrazines (zopiclone), imidazo[1,2-a]
pyridines (Zolpidem) and, finally, pyrazolo[1,5-a]
pyrimidines (zaleplon). Later, two new pyrazolo[1,5-a]
pyrimidines, indiplon and ocinaplon, have entered into
development, the latter with rather anxiolytic action.
All these compounds show a rapid sleep induction and
have less next-day hangover effects, lower potential
for abuse and lower risk of rebound insomnia than
benzodiazepines. The mechanism of action of these
compounds is the alosteric activation of GABAA receptor

through its binding to benzodiazepine binding site (C.
F. P. George, The Lancet, 358, 1623-1626, 2001). While
benzodiazepines are unspecific ligands at GABAA
receptor binding site, Zolpidem and zaleplon show a
greater selectivity for α1-subunit. Notwithstanding
that, these drugs still affect the architecture of
sleep and may induce dependence in long-term
treatments.
Zolpidem is disclosed in US 4382938. Some other related
hypnotic imidazo[1,2-a]pyridines have been disclosed in
FR 2593818, US 4650796 and EP 172096. In US 4626538
(zaleplon), US 4654347, US 6399621 (indiplon) and EP
129847 (ocinaplon) hypnotic pyrazolo[1,5-a]pyrimidines
are disclosed. The use of N-[[(ethyl-4-phenyl)-2-
imidazo[1,2-a]pyridinyl-3]methyl-N,3-dimethyl-
butanamide, a compound previously disclosed in EP
172096, has been claimed in the manufacturing of
anesthetic medicaments in EP 430738.
Research for new active compounds in the management of
insomnia answers an underlying health need, because
even recently introduced hypnotics still affect the
architecture of sleep and may induce dependence in
long-term treatments.
It is therefore desirable to focus on the development
of new hypnotic agents with a lower risk of side
effects.

Thus, the present invention is directed to new
imidazo[1,2-a]pyridine compounds which are active
versus GABAA and, particularly, versus its α1- and α2-
subunits. Consequently, the compounds of this invention
are useful in the treatment and prevention of all those
diseases mediated by GABAA receptor α1- and α2-subunits.
Non-limitative examples of such diseases are sleep
disorders, preferably insomnia, anxiety and epilepsy.
Non-limitative examples of the relevant indications of
the compounds of this invention are all those diseases
or conditions, such as insomnia or anesthesia, in which
an induction of sleep, an induction of sedation or an
induction of muscle relaxation are needed.
Detailed description of the invention
The present invention relates to novel imidazo[1,2-
a]pyridine compounds of general formula (I):

as well as pharmaceutically acceptable salts thereof;
wherein
R1 and R2 are independently selected from the group
consisting of hydrogen, linear or branched alkyl(C1-

C6), alkenyl (C2-C6) , alkynyl (C2-C6) , haloalkyl (C1-C6) , -
O-alkyl(C1-C6), fluoro, chloro and bromo;
R3 is selected from the group consisting of hydrogen,
linear or branched alkyl (C1-C6) , cycloalkyl (C3-C6) ,
cycloalkyl (C3-C6) alkyl (C1-C6) , alkenyl (C2-C6) ,
alkenyl (C2-C6) alkyl (d-C6) , alkynyl (C2-C6) , alkynyl (C2-
C6) alkyl (C1-C6) ;
R4 is selected from the group consisting of hydrogen,
haloalkyl (C2-C6) , cycloalkyl (C3-C5) , cycloalkyl (C3-
C6) alkyl (d-C6) , alkynyl (C2-C6) alkyl (C1-C6) , alkyl (C1-C6)-
O-alkyl (C1-C6) , alkyl (C1-C6) -NH-alkyl (C1-C6) , alkyl (C1-
C6) -N (dialkyl (C1-C6) ) , -OR5, -NHR5, -NR5R6,

phenylalkyl (C2-C6) , phenylalkenyl (C2-C6) , naphthyl,
monosubstituted naphthyl, disubstituted naphthyl,
naphthylalkyl (C1-C6) , naphthylalkenyl (C2-C6) , furyl,
substituted furyl, benzofuryl, substituted benzofuryl,
pyrrolyl, substituted pyrrolyl, isoxazolyl, substituted
isoxazolyl, benzoisoxazolyl, substituted
benzoisoxazolyl, imidazolyl, substituted imidazolyl,
benzimidazolyl, substituted benzimidazolyl, indolyl,
substituted indolyl, pyrazolyl, substituted pyrazolyl,
thienyl, substituted thienyl, benzothienyl, substituted
benzothienyl, thiazolyl, substituted thiazolyl,
benzothiazolyl, substituted benzothiazolyl, quinolinyl,
substituted quinolinyl, isoquinolinyl, substituted
isoquinolinyl, pyridyl, substituted pyridyl, pyrazinyl,
substituted pyrazinyl, 6-oxo-1,4,5,6-
tetrahydropyridazinyl, substituted 6-oxo-1,4,5,6-

tetrahydropyridazinyl, thiadiazolyl, substituted
thiadiazolyl, isothiazolyl, substituted isothiazolyl,
thienylmethyl, 2-oxochromenyl, substituted 2-
oxochromenyl, 2-(furan-2-yl)vinyl, oxazolyl,
substituted oxazolyl, and benzisoxazolyl;
Rs and R6 are independently selected from the group
consisting of hydrogen, linear or branched alkyl(C1-
C6) , phenylalkyl (C1-C6) , haloalkyl (C1-C6) , cycloalkyl(C3-
C6) , cycloalkyl (C3-C6) alkyl (C1-C6) , alkenyl (C2-C6) and
alkynyl (C2-C6) , alkenyl (C2-C6) alkyl (C1-C6) , alkynyl (C2-
C6) alkyl (C1-C6), phenyl, substituted phenyl, heteroaryl,
substituted heteroaryl; and
R7 and R8 are independently selected from the group
consisting of linear or branched alkyl (C2_C6),
cycloalkyl (C3-C6) , alkenyl (C2-C6) , alkynyl (C2-C6) , -OH, -
O-alkyl (C1-C6) , -SH, -S-alkyl (C1-C6) , halo-alkyl (C1-C6) ,
ω,ω,ω-trifluoroalkyl (C1-C6) , -NHalkyl (C1-C6) ,
Ndialkyl(C1-C6) , -NO2, -CN, -SO2alkyl (C1-C6) ,
COalkyl (C1-C6) , -COOalkyl (C1-C6) , -CO-NHalkyl (C1-C6), -
CONdialkyl(C1-C6), phenyl, substituted phenyl,
heteroaryl and substituted heteroaryl.
The term "pharmaceutically acceptable salt" used herein
encompasses any salt formed from organic and inorganic
acids, such as hydrobromic, hydrochloric, phosphoric,
nitric, sulfuric, acetic, adipic, aspartic,
benzenesulfonic, benzoic, citric, ethanesulfonic,
formic, fumaric, glutamic, lactic, maleic, malic,
malonic, mandelic, methanesulfonic, 1,5-
naphthalendisulfonic, oxalic, pivalic, propionic, p-
toluenesulfonic, succinic, tartaric acids and the like.

The term "substituted" used herein refers to the
substitution of the corresponding radical or compound
with at least one suitable substituent preferably
selected from the group consisting of linear or
branched alkyl (C2-C6) , cycloalkyl (C3-C6) , alkenyl (C2-C6) ,
alkynyl (C2-C6) , -OH, -O-alkyl (C1-C6) , -SH, -S-alkyl (C1-
C6) , halo-alkyl (C1-C6) , ω, ω, ω-trifluoroalkyl (C1-C6),
NHalkyl (C1-C6) , -Ndialkyl (C1-C6) , -NO2, -CN,
SO2alkyl(C1-C6) , -COalkyl (C1-C6) , -COOalkyl (C1-C6) , -CO-
NHalkyl (C1-C6) , -CONdialkyl (C1-C6), phenyl, substituted
phenyl, heteroaryl, substituted heteroaryl, fluoro,
chloro and bromo.
The preferred compounds of the present invention are
shown below:
Furan-2-carboxylic acid (6-methyl-2-p-tolyl-
imidazo[1,2-a] pyridin-3-ylmethyl)-amide;
Pyridine-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo
[1,2-a]pyridin-3-ylmethyl)-amide;
Thiophene-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo
[1,2-a]pyridin-3-ylmethyl)-amide;
Cyclopropanecarboxylic acid (6-methyl-2-p-tolyl-imidazo
[1,2-a]pyridin-3-ylmethyl)-amide;
5-Nitro-furan-2-carboxylic acid (6-methyl-2-p-tolyl-
imidazo [1,2-a]pyridin-3-ylmethyl)-amide;
3,5-Difluoro-pyridine-2-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
6-Methoxy-benzothiazole-2-carboxylic acid(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;

4-Dimethylamino-N-methyl-N-(6-methyl-2-p-tolyl-imidazo
[1,2-a]pyridin-3-ylmethyl)-benzamide;
Cyclopropanecarboxylic acid methyl-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
Pyridine-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
Thiophene-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
5-Nitro-furan-2-carboxylic acid methyl-(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
2-Chloro-N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-isonicotinamide;
Cyclobutanecarboxylic acid (6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
5-Methyl-pyrazine-2-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
6-Oxo-1,4,5,6-tetrahydro-pyridazine-3-carboxylic acid
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide;
[1,2,3]Thiadiazole-4-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1, 2-a]pyridin-3-ylmethyl)-amide;
N-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-2-thiophen-2-yl-acetamide;
1-Methyl-1H-imidazole-2-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
Thiazole-4-carboxylic acid (6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
2,5-Dimethyl-oxazole-4-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
3,5-Dimethyl-isoxazole-4-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;

Thiazole-4-carboxylic acid methyl-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
1-(4-Dimethylamino-phenyl)-3-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-urea;
1-Ethyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-urea;
1-Isopropyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-
3-ylmethyl)-urea;
1-Cyclopentyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-urea;
1-Cyclohexyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-urea;
1-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-3-phenyl-urea;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid p-tolyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid prop-2-ynyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid methyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid benzyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid 4-methoxy-phenyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid ethyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid phenyl ester; and
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
carbamic acid isopropyl ester.

Another aspect of the present invention is to provide a
process for preparing the compounds of formula (I) and
their pharmaceutically acceptable salts.
Another aspect of the present invention is to provide a
method for treating or preventing diseases associated
with GABAA receptor modulation in a mammal which
comprises administering to said mammal an effective
amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
method for treating or preventing diseases associated
with Α1-GABAA receptor modulation in a mammal which
comprises administering to said mammal an effective
amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
method for treating or preventing diseases associated
with α2-GABAA receptor modulation in a mammal which
comprises administering to said mammal an effective
amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
method for treating or preventing anxiety in a mammal
which comprises administering to said mammal an
effective amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.

Another aspect of the present invention is to provide a
method for treating or preventing epilepsy in a mammal
which comprises administering to said mammal an
effective amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
method for treating or preventing sleep disorders in a
mammal which comprises administering to said mammal an
effective amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
method for treating or preventing insomnia in a mammal
which comprises administering to said mammal an
effective amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
method for inducing sedation-hypnosis in a mammal which
comprises administering to said mammal an effective
amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
method for inducing anesthesia in a mammal which
comprises administering to said mammal an effective
amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.

Another aspect of the present invention is to provide a
method for modulating the necessary time to induce
sleep and its duration in a mammal which comprises
administering to said mammal an effective amount of a
compound of formula (I) or a pharmaceutically
acceptable salt thereof.
Another aspect of the present invention is to provide a
method for inducing muscle relaxation in a mammal which
comprises administering to said mammal an effective
amount of a compound of formula (I) or a
pharmaceutically acceptable salt thereof.
Another aspect of the present invention is to provide a
pharmaceutical composition containing a compound of
formula (I) or a pharmaceutically acceptable salt
thereof in association with therapeutically inert
carriers.
Another aspect of the present invention is to provide
the use of a compound of formula (I) or a
pharmaceutically acceptable salt thereof for preparing
a medicament for treating or preventing diseases
associated with GABAA receptor modulation.
Another aspect of the present invention is to provide
the use of a compound of formula (I) or a
pharmaceutically acceptable salt thereof for preparing
a medicament for treating or preventing diseases
associated with α1-GABAA or α2-GABAA receptor
modulation.

Another aspect of the present invention is to provide
the use of a compound of formula (I) or a
pharmaceutically acceptable salt thereof for preparing
a medicament for treating or preventing anxiety,
epilepsy, sleep disorders, insomnia, for inducing
sedation-hypnosis, anesthesia or muscle relaxation or
for modulating the necessary time to induce sleep and
its duration.
The compounds of general formula (I) wherein R3 is
hydrogen and R4 is a carbon group can be obtained
following the synthetic strategy showed in Scheme 1.

The imidazopyridine (IV) is obtained by cyclization
between the corresponding aminopyridine (VII) and the
bromoacetophenone (VIII). This reaction is carried out

by heating both components at reflux for 2-8 hours,
using a polar solvent such as methanol, ethanol,
butanol and the like. The final product (IV) is
obtained by evaporation of the crude and
crystallization of the residue with the adequate
solvent.
The Mannich reaction between this imidazopyridine (IV)
and formaldehyde in an acidic moiety, such as diluted
acetic acid, yields the alcohol (II). The reaction is
carried out by heating the mixture at 55°C for a period
of 2-6 h. The solvent is removed and the residue thus
obtained is suspended in dichloromethane, and stirred
for 12 hours. The alcohol (II) is washed and dried.
Finally, the condensation of the alcohol (II) and the
appropriate nitrile (IX) yields compounds of general
formula (I) , when R3 is hydrogen and R4 is a carbon
group, by using sulphuric acid as catalyst and a polar
solvent, such as acetic acid, acetonitrile,
tetrahydrofurane and the like. The components are
stirred and heated at reflux for 2-6 hours. The crude
thus obtained is basified with ammonia and extracted
with dichloromethane to yield the corresponding amide
(I, R3 = H, R4 = carbon group).
Once the amides (I, R3 = H, R4 = carbon group) are
obtained, the nitrogen present in this functional group
can be alkylated according to a procedure which is well
known by an expert skilled in organic chemistry. The
reaction is shown in Scheme 2.

The reaction is done by using sodium hydride as base
and dimethylformamide as solvent under inert
atmosphere. The mixture is stirred at room temperature
for 1 hour, and the crude thus obtained is removed with
dichloromethane. The procedure yields the corresponding
N-alkylated amides (I, R3 = carbon group, R4 = carbon
group).
We also report the preparation of urea compounds of
general formula (I) when R3 is hydrogen and R4 is -NHR5.
The synthetic strategy is shown in Scheme 3.

In this case, the imidazopyridine (IV) described above
is treated with (V) to yield the corresponding
acetamide (VI). Q is selected from the group consisting
of -OH, -Oalkyl (C1-C3) , -N+ (alkyl (C1-C3))3Cl-,
N+(alkyl(C1-C3) )3Br-, -N+(alkyl (C1-C3))3I-, preferably
OH. This reaction is carried out by using an acidic
solvent such as acetic acid and an acid as catalyst.
The reaction takes place at room temperature for 1-3
hours and then at reflux for 2-4 hours. An extraction

with an organic solvent yields the corresponding
acetamide (VI).
The hydrolysis of acetamides (VI) in acidic media leads
to amines (III). The reaction takes place at reflux
using a protic solvent such as methanol, ethanol,
propanol, and the like, for a period of 30-90 min. The
solvent is removed and the crude is neutralized and
extracted with an organic solvent to obtain amines
(III) . These amines are the precursors of urea
compounds (I, R3 = H, R4 = -NHR5) .
Finally, the coupling between amines (III) and
isocyanates R5NCO yields the corresponding urea
compounds (I, R3 = H, R4 = -NHR5) as mentioned above.
The reaction is carried out by using the appropriate
isocyanate, stirring at room temperature for 20-30
hours, and using a basic solvent such as pyridine. The
solvent is removed and the products are crystallized
with the appropriate solvent.
In parallel, amines (III) react with chloroformiates to
yield carbamates of general formula (I) when R3 is
hydrogen and R4 is -OR5, as shown in Scheme 4.

The reaction takes place at room temperature for a
period of 20-30 hours. The appropriate chloroformiate
reacts by using a basic solvent such as pyridine. The
solvent is removed and the products are crystallized
with water, and filtered off. Thus, carbamates (I, R3 =
H, R4 = -OR5) are obtained in good yields.

From the compounds of general formula (I) it is
possible to obtain their pharmaceutically acceptable
salts by treatment with the corresponding acids.
The applicants have discovered that the compounds of
the present invention have a high affinity for α1- and
α2- GABAA receptors as shown in Tables 1 and 2. These
in vitro results are consistent with those in vivo
results obtained in sedation-hypnosis tests (Table 3).
In accordance with the results obtained, certain
compounds of the present invention have surprisingly
evidenced high affinity for α1-GABAA receptors and
interesting pharmacological activity in vivo, which
have been similar to or higher than those of prior-art
compounds. Moreover, some of them displayed lower
affinity for α2-GABAA receptors, indicating increased
selectivity for α1-GABAA versus α2-GABAA receptors. All
these results support their use in diseases or
conditions, in which preferential activity on α1-GABAA
is desirable, such as insomnia or anesthesia, in which
an induction of sleep and an induction of sedation are
needed. Furthermore, lost of righting reflex has been
detected in some animals administered with certain
compounds of the present invention, supporting their
use as anesthetic agents. Indeed, certain compounds of
the present invention have demonstrated interesting
affinity for α2-GABAA receptors, which has been similar
to or higher than that of prior-art compounds. These
results support their use in diseases or conditions in
which preferential activity on α2-GABAA receptors is

desirable, such as anxiety or in which an induction of
muscle relaxation is needed.
The pharmacological activity of the compounds of the
present invention has been determined as shown below.
Ligand-binding assays. Determination of the
affinity of test compounds for α1- and α2-GABAA
receptor.
Male Sprague-Dawley rats weighing 200-250 g at the time
of experiment were used. After decapitation of the
animal, the cerebellum (tissue that mostly contains α1-
GABAA receptor) and spinal cord (tissue that mostly
contains α2-GABAA receptor) were removed. The membranes
were prepared according to the method by J. Lameh et
al.(Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 24,
979-991, 2000) and H. Noguchi et al. (Eur. J. Pharm.,
434, 21-28, 2002). Once the tissues weighed, they were
suspended in 50 mM Tris HCl (pH 7.4), 1:40 (w/v) , or
sucrose 0.32 M in the case of spinal cord, homogenized
and then centrifuged at 20,000 g for 10 min at 7°C
twice. The resulting pellet was resuspended under the
same conditions and centrifuged again. The pellet was
finally resuspended on a minimum volume and kept at -
80°C overnight. On the next day, the process was
repeated until the final pellet was resuspended at a
ratio of 1:10 (w/v) in the case of cerebellum and at a
ratio of 1:5 (w/v) in the case of spinal cord.
Affinity was determined by competitive tests using
radiolabeled flumazenil as ligand. The tests were

performed according to the methods described by S.
Arbilla et al. (Eur. J. Pharmacol., 130, 257-263,
1986); and Y. Wu et al. (Eur. J. Pharmacol., 278, 125-
132, 1995) using 96-well microtiter plates. The
membranes containing the study receptors, flumazenil
(radiolabeling at a final concentration of 1 nM) and
ascending concentrations of test compounds (in a total
volume of 230 µL in 50 mM [ph 7.4] Tris.HCl buffer)
were incubated. Simultaneously, the membranes were only
incubated with the radiolabeled flumazenil, (total
binding, 100%) and in the presence of an elevated
concentration of unradiolabeled flumazenil (non-
specific binding, % estimation of radiolabeled ligand).
The reactions started on adding the radiolabeled ligand
followed by incubation for 60 minutes at 4°C. At the
end of the incubation period, 200 µL of reaction were
transferred to a multiscreen plate (Millipore) and
filtered using a vacuum manifold and then washed three
times with cold test buffer. The multiscreen plates
were equipped with a GF/B filter that retained the
membranes containing the receptors and the radiolabeled
ligand which has been bound to the receptors. After
washing, the plates were left till dry. Once dried,
scintillation liquid was added and left under stirring
overnight. The next day the plates were counted using a
Perkin-Elmer Microbeta scintillation counter.
For analysis of the results the percentage of specific
binding for every concentration of test compound was
calculated as follows:

% specific binding = (X-N/T-N) x 100
where,
X: amount of bound ligand for every concentration of
compound.
T: total binding, maximum amount bound to the
radiolabeled ligand.
N: non-specific binding, amount of radiolabeled
ligand bound in a non-specific way irrespective of the
receptor used.
Every concentrations of compound were tested in
triplicate and their mean values were used to determine
the experimental values of % specific binding versus
the concentration of compound. Affinity data are
expressed as % inhibition at 10-5M and 10-7M
concentrations. The results of these tests are given in
Tables 1 and 2.

In vivo determination of predictive sedative-hypnotic
action.
The in vivo effects of these compounds were assessed by
a predictive sedation-hypnosis test in mice (D. J.
Sanger et al., Eur.J.Pharmacol., 313, 35-42, 1996/ and
G. Griebel et al., Psychopharmacology, 146, 205-213,
1999).
Groups of 5-8 male CD1 mice, weighing 22-26 g at the
time of test, were used. The test compounds were
administered in single equimolecular intraperitoneal
doses, suspended in 0.25% agar with one drop of Tween
in a volume of 10 mL/kg. Control animals received the
vehicle alone. Using a Smart System (Panlab,S.L.,
Spain) the traveled distance in cm is recorded for each
mouse at 5-min intervals during a period of 30 minutes
after dosing. The inhibition percentage of traveled
distance of treated animals versus control animals (the
first 5 min were discarded) was calculated. The results
of this test are given in Table 3.
Table 3. Determination of in vivo sedative-hypnotic
activity in mice.

The following non-limiting examples illustrate the
scope of the present invention.
Example 1: 6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-4-
ium bromide

A solution of 11.53 g (106.7 mmol) of 5-methyl-pyridin-
2-ylamine in 150 mL of ethanol is added to a solution
of 25 g (117.3 mmol) of 2-bromo-1-p-tolyl-ethanone in
150 mL of ethanol. The resulting solution is stirred at
reflux for 4 hours. The reaction is allowed to cool,
and the solvent is removed in vacuo. The yellow solid
obtained is dissolved in 30 mL of hot ethanol, and 40

mL of acetone are added. The solid obtained is filtered
off, washed with acetone and dried over calcium
chloride to give 20.0 g (65.9 mmol, yield: 62%) of 6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-4-ium bromide as
a white solid.
1H NMR (400 MHz, DMSO-d6) : δ 8.31-7.10 (Ar, 8H, m) ,
2.36 (Ph-Me, 3H, s), 2.31 (Me, 3H, s).
MS (ES) m/z = 223 (MH+)
HPLC = 100%
Example 2: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
yl)-methanol

A solution of 6 mL (81 mmol) of formaldehyde in water
(37%) is added to a solution of 4 g (18 mmol) of 6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-4-ium bromide in
30 mL of acetic acid. The reaction is heated at 55°C
for 4 h. The resulting solution is allowed to cool, and
the solvent is removed in vacuo. To the corresponding
residue are added 20 mL of ammonia (25%) and 30 mL of
dichloromethane, and the suspension is stirred
overnight. The solid obtained is filtered off, washed
with dichloromethane and water and dried over calcium
chloride, to yield 2.8 g (11 mmol, 62%) of (6-methyl-2-
p-tolyl-imidazo[1,2-a]pyridin-3-yl)-methanol as a white
solid.

1H NMR (400 MHz, DMSO-d6) : δ 8.23-7.13 (Ar, 7H, m) ,
5.33 (OH, 1H, t, J= 5.2 Hz), 4.85 (CH2, 2H, d, J= 5.2
Hz), 2.35 (Ph-Me, 3H, s), 2.33 (Me, 3H, s).
MS (ES) m/z = 253 (MH+)
HPLC = 98.3%
Example 3: 4-Dimethylamino-N-(6-methyl-2-p-tolyl-
imidazo [1,2-a]pyridin-3-ylmethyl)-benzamide

To a solution of 1 eq of (6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-yl)-methanol in acetic acid is
added a solution of 4-dimethylaminobenzonitrile (2 eq)
in acetic acid. Then, 4 eq of sulphuric acid are added
slowly. The mixture is heated at room temperature for
1.5 h, and then at reflux for 2 h. The reaction is
allowed to cool and is basified with ammonia (25%). The
suspension is extracted with dichloromethane. The
organic phase is dried over magnesium sulphate and
filtered off. The solvent is removed in vacuo to give
0.96 eq of 4-Dimethylamino-N-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide.
1H NMR (400 MHz, DMSO-d6) : δ 8.58 (NH, 1H, t, J= 5.2
Hz), 8.29-6.65 (Ar, 11H, m) , 4.87 (CH2, 2H, d, J= 5.2
Hz), 2.94 (N-Me, 6H, s), 2.34 (Ph-Me, 3H, s).

MS (ES) m/z = 399 (MH+)
HPLC = 97.1%
The compounds of examples 4-21 were prepared according
to this procedure starting from (6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-yl)-methanol and the
corresponding nitrile.
Example 4: Furan-2-carboxylic acid (6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-amide

Yield: 47%
1H NMR (400 MHz, DMSO-d6) : δ 8.17 (NH, 1H, m) , 7.65-
6.11 (Ar, 10H, m) , 4.51 (CH2, 2H, m) , 2.33 (Ph-Me, 3H,
s), 2.29 (Me, 3H, s).
MS (ES) m/z = .346 (MH+)
HPLC = 82.7%
Example 5: Pyridine-2-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

Yield: 17%
1H NMR (400 MHz, DMSO-d6) : 5 9.36 (NH, 1H, t, J= 5.6
Hz), 8.61-7.12 (Ar, 14H, m) , 4.95 (CH2, 2H, d, J= 5.6
Hz), 2.34 (Ph-Me, 3H, s), 2.29 (Me, 3H, s).
MS (ES) m/z = 357 (MH+)
HPLC = 96.7%
Example 6: 1,5-Dimethyl-1H-pyrrole-2-carboxylic acid
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 14%
1H NMR (400 MHz, DMSO-d6) : 8 8.31 (NH, 1H, m) , 7.66-
6.99 (Ar, 9H, m) , 4.64 (CH2, 2H, m) , 3.28 (N-Me, 3H,
s), 2.34 (Ph-Me, 3H, s) , 2.17 (Me, 3H, s) , 1.34 (Me-
pyrrole, 3H, s).
MS (ES) m/z = 373 (MH+)
HPLC = 97.9%
Example 7: N-(6-Methyl-2-p-tolyl-imidazo[1, 2-a]pyridin-
3-ylmethyl)-isonicotinamide

Yield: 19%
1H NMR (400 MHz, DMSO-d6): 8 9.23 (NH, 1H, t, J= 4.8
Hz), 8.70-7.14 (Ar, 11H, m) , 4.93 (CH2, 2H, d, J= 4.8
Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s).
MS (ES) m/z = 357 (MH+)
HPLC = 92.9%
Example 8: N-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-
3-ylmethyl)-4-nitro-benzamide

Yield: 29%
1H NMR (400 MHz, DMSO-d6) : δ 9.28 (NH, 1H, t, J= 3.6
Hz), 8.29-7.14 (Ar, 11H, m) , 4.94 (CH2, 2H, d, J= 3.6
Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s).
MS (ES) m/z = 401 (MH+)
HPLC = 98.8%
Example 9: Thiophene-2-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

Yield: 8%
1H NMR (400 MHz, DMSO-d6) : δ 8.94 (NH, 1H, t, J= 5.2
Hz), 8.26-7.10 (Ar, 10H, m) , 4.89 (CH2, 2H, d, J= 5.2
Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s).
MS (ES) m/z = 362 (MH+)
HPLC = 92.1%
Example 10: N-(6-Methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide

Yield: 89%
1H NMR (400 MHz, DMSO-d6) : δ 9.18 (NH, 1H, t, J= 5.2
Hz), 8.27-7.14 (Ar, 11H, m) , 4.94 (CH2, 2H, d, J= 5.2
Hz), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s).
MS (ES) m/z = 424 (MH+)
HPLC = 98.5%
Example 11: 4-Methoxy-N-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide

Yield: 14%
1H NMR (400 MHz, DMSO-d6) : δ 8.8 (NH, 1H, t, J= 5.2
Hz), 8.28-6.95 (Ar, 11H, m) , 4.89 (CH2, 2H, d, J= 5.2
Hz), 3.78 (MeO, 3H, s), 2.34 (Ph-Me, 3H, s), 2.29 (Me,
3H, s) .
MS (ES) m/z = 386 (MH+)
HPLC = 98.3%
Example 12: 4-Acetyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-
a] pyridin-3-ylmethyl)-benzamide

Yield: 17%
1H NMR (400 MHz, DMSO-d6) : δ 9.14 (NH, 1H, t, J= 4.8
Hz), 8.28-7.14 (Ar, 11H, m) , 4.93 (CH2, 2H, d, J= 4.8
Hz), 2.6 (Me-CO, 3H, s), 2.34 (Ph-Me, 3H, s), 2.3 (Me,
3H, s) .
MS (ES) m/z = 398 (MH+)
HPLC = 94.9%
Example 13: Cyclopropanecarboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

Yield: 60%
1H NMR (400 MHz, DMSO-d6) : δ 8.6 (NH, 1H, t, J= 5.2
Hz), 8.16-7.13 {Ar, 7H, m) , 4.72 (CH2, 2H, d, J= 5.2
Hz), 2.35 (Ph-Me, 3H, s) , 2.3 (Me, 3H, s), 1.59 (CH,
1H, m), 0.76 (CH2CH2, 4H, m).
MS (ES) m/z = 320 (MH+)
HPLC = 99.3%
Example 14: 5-Nitro-furan-2-carboxylic acid (6-methyl-
2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

Yield: 27%
1H NMR (400 MHz, DMSO-d6) : δ 9.38 (NH, 1H, m) , 8.25-
7.15 (Ar, 9H, m), 4.91 (CH2, 2H, d, J= 4 Hz), 2.34 (Ph-
Me, 3H, s), 2.3 (Me, 3H, s).
MS (ES) m/z = 391 (MH+)
HPLC = 97.9%

Example 15: 3-Methyl-furan-2-carboxylic acid (6-methyl-
2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

Yield: 3%
1H NMR (400 MHz, DMSO-d6) : δ 8.74 (NH, 1H, t, J= 5.2
Hz), 8.25-6.21 (Ar, 9H, m) , 5.85 {CH2, 2H, d, J= 5.2
Hz), 2.34 (Ph-Me, 3H, s) , 2.29 (Me, 3H, s) , 1.03 (Me-
furane, 3H, s).
MS (ES) m/z = 360 (MH+)
HPLC = 93.7%
Example 16: 3-Methyl-thiophene-2-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 29%
1H NMR (400 MHz, DMSO-d6) : δ 8.6 (NH, 1H, m) , 8.3-6.9
(Ar, 9H, m) , 4.87 (CH2, 2H, d, J= 5.2 Hz), 2.37 (Me,
3H, s), 2.34 (Ph-Me, 3H, s), 2.3 (Me, 3H, s).
HPLC = 87.1%

Example 17: 2-Chloro-N-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-isonicotinamide

Yield: 15%
1H NMR (400 MHz, DMSO-d6) : δ 9.29 (NH, 1H, m) , 8.56-
7.16 (Ar, 10H, m) , 4.92 (CH2, 2H, d, J= 4.4 Hz), 2.34
(Ph-Me, 3H, s), 2.31 (Me, 3H, s).
HPLC = 99.2%
Example 18: 2,3,5,6-Tetrafluoro-N-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-isonicotinamide

Yield: 13%
1H NMR (400 MHz, DMSO-d6) : δ 9.65 (NH, 1H, m) , 8.19
(Ar, 7H, m) , 4.99 (CH2, 2H, m) , 2.36 (Ph-Me, 3H, s) ,
2.32 (Me, 3H, s).
HPLC = 96.9%
Example 19: Quinoline-2-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

Yield: 17%
1H NMR (400 MHz, DMSO-d6) : δ 9.47 Hz), 8.57-7.13 (Ar, 13H, m) , 5.05 (CH2, 2H, d, J= 4.8
Hz), 2.34 (Ph-Me, 3H, s), 2.29 (Me, 3H, s).
MS (ES) m/z = 407 (MH+)
HPLC = 90.5%
Example 20: 3,5-Difluoro-pyridine-2-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
Yield: 86%
1H NMR (400 MHz, DMSO-d6) : δ 9.28 (NH, 1H, t, J= 5.2
Hz), 8.54-7.14 (Ar, 9H, m) , 4.92 (CH2, 2H, d, J= 5.2
Hz), 2.35 (Ph-Me, 3H, s), 2.3 (Me, 3H, s).
MS (ES) m/z = 393 (MH+)
HPLC = 96.6%

Example 21: 6-Methoxy-benzothiazole-2-carboxylic acid
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 10%
1H NMR (400 MHz, DMSO-d6) : δ 8.18 (NH, 1H, m) , 8.02-
7.12 (Ar, 10H, m) , 4.67 (CH2, 2H, m) , 4.06 (MeO, 3H,
s), 2.27 (Ph-Me, 3H, s), 2.17 (Me, 3H, s).
MS (ES) m/z = 443 (MH+)
HPLC = 100%
Example 22: 4-Dimethylamino-N-methyl-N-(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide

To a solution of 4-dimethylamino-N-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide (1 eq) in
dry DMF are added 1.2 eq of NaH (60%) under argon. The
suspension is stirred for 10 min at room temperature.
Then 1.1 eq of Mel are added and the corresponding

mixture is stirred for 1 h at room temperature. After
this period, 0.5 N NaOH is added. The mixture is
extracted with dichloromethane. The organic layer is
dried over magnesium sulphate and the solvent is
removed in vacuo to obtain 0.58 eq of 4-dimethylamino-
N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-benzamide.
1H NMR (400 MHz, DMSO-d6) : δ 8.23-6.67 (Ar, 11H, m) ,
5.19 (CH2, 2H, s), 2.92 (NMe2, 6H, s) , 2.58 (N-Me, 3H,
s), 2.34 (Ph-Me, 3H, s), 2.28 (Me, 3H, s).
MS (ES) m/z = 413 (MH+)
HPLC = 90.8%
The compounds of examples 23-36 were prepared following
this procedure starting from the corresponding N-
dealkylated amides.
Example 23: 4-Isobutyryl-N-methyl-N-(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide

Yield: 20%
1H NMR (400 MHz, DMSO-d6) : δ 8.31-7.18 (Ar, 11H, m) ,
5.27 (CH2, 2H, s), 3.64 (CH, 1H, hept, J= 6.8 Hz), 2.46
(N-Me, 3H, s), 2.35 (Ph-Me, 3H, s) , 2.32 (Me, 3H, s),
1.09 (Me, 6H, d, J= 6.8 Hz).

MS (ES) m/z = 440 (MH+)
HPLC = 83.7%
Example 24: Cyclopropanecarboxylic acid methyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 100%
1H NMR (400 MHz, DMSO-d6) : δ 8.08-7.14 (Ar, 7H, m) ,
5.09 (CH2, 2H, s), 2.72 (N-Me, 3H, s), 2.35 (Ph-Me, 3H,
s), 2.25 (Me, 3H, s) , 1.89 (CH, 1H, m) , 0.8 (CH2, 4H,
m) .
MS (ES) m/z = 334 (MH+)
HPLC = 98.6%
Example 25: 4-Methoxy-N-methyl-N-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide

Yield: 93%
1H NMR (400 MHz, DMSO-d6) : δ 9.45-7.68 (Ar, 11H, m) ,
5.2 (CH2, 2H, s), 3.77 (MeO, 3H, s), 2.55 (N-Me, 3H,
s), 2.35 (Ph-Me, 3H, s), 2.3 (Me, 3H, m).

MS (ES) m/z = 400 (MH+)
HPLC = 95%
Example 26: N-Methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-
a] pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide

Yield: 100%
1H NMR (400 MHz, DMSO-d6) : δ 8.30-7.18 (Ar, 11H, m) ,
5.27 (CH2, 2H, s), 2.5 (N-Me, 3H, s) , 2.35 (Ph-Me, 3H,
s), 2.32 (Me, 3H, s).
MS (ES) m/z = 438 (MH+)
HPLC = 95.9%
Example 27: N-Methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-
a] pyridin-3-ylmethyl)-isonicotinamide

Yield: 22%
1H NMR (400 MHz, DMSO-d6) : δ 8.63-7.19 (Ar, 11H, m) ,
5.25 (CH2, 2H, s), 2.46 (N-Me, 3H, s), 2.35 (Ph-Me, 3H,
s) , 2.32 (Me, 3H, s) .

MS (ES) m/z = 371 (MH+)
HPLC = 94.6%
Example 28: Pyridine-2-carboxylic acid methyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 77%
1H NMR (400 MHz, DMSO-d6) : δ 8.53-7.18 (Ar, 11H, m) ,
5.27 (CH2, 2H, s), 2.54 (N-Me, 3H, s), 2.33 (Ph-Me, 3H,
s), 2.3 (Me, 3H, s).
MS (ES) m/z = 371 (MH+)
HPLC = 80.6%
Example 29: Thiophene-2-carboxylic acid methyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 100%
1H NMR (400 MHz, DMSO-d6) : δ 8.22-7.09 (Ar, 10H, m) ,
5.26 (CH2, 2H, s), 2.77 (N-Me, 3H, s), 2.34 (Ph-Me, 3H,
s), 2.28 (Me, 3H, s).

MS (ES) m/z = 376 (MH+)
HPLC = 87%
Example 30: 4,N-Dimethyl-N-(6-methyl-2-p-tolyl-imidazo
[1,2-a]pyridin-3-ylmethyl)-benzamide

Yield: 83%
1H NMR (400 MHz, DMSO-d6) : δ 7.67-7.16 (Ar, 11H, m) ,
5.22 (CH2, 2H, s), 2.52 (N-Me, 3H, s) , 2.34 (Ph-Me, 3H,
s), 2.31 (Ph-Me, 3H, s), 2.3 (Me, 3H, s).
MS (ES) m/z = 384 (MH+)
HPLC = 99%
Example 31: N-Methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-
a] pyridin-3-ylmethyl)-4-nitro-benzamide
Yield: 48%
1H NMR (400 MHz, DMSO-d6) : δ 8.30-7.19 (Ar, 11H, m) ,
5.27 (CH2, 2H, s), 2.49 (N-Me, 3H, s), 2.34 (Ph-Me, 3H,
s), 2.32 (Me, 3H, s).

MS (ES) m/z = 415 (MH+)
HPLC = 100%
Example 32: 5-Nitro-furan-2-carboxylic acid methyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 42%
1H NMR (400 MHz, DMSO-d6) : δ 8.26-7.19 (Ar, 9H, m) ,
5.26 (CH2, 2H, s), 2.82 (N-Me, 3H, s), 2.34 (Ph-Me, 3H,
s), 2.3 (Me, 3H, s).
MS (ES) m/z = 405 (MH+)
HPLC = 98.8%
Example 33: 3,5-Difluoro-pyridine-2-carboxylic acid
methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

Yield: 27%

1H NMR (400 MHz, DMSO-d6) : δ 8.55-7.20 (Ar, 9H, m) , 5.3
(CH2, 2H, s), 2.46 (N-Me, 3H, s) , 2.34 (Ph-Me, 3H, s) ,
2.3 (Me, 3H, s).
MS (ES) m/z = 407 (MH+)
HPLC = 96.6%
Example 34: 2-Chloro-N-methyl-N-(6-methyl-2-p-tolyl-
imidazo [1,2-a]pyridin-3-ylmethyl)-isonicotinamide

Yield: 61%
1H NMR (400 MHz, DMSO-d6) : δ 8.51-7.22 (Ar, 10H, m) ,
5.26 (CH2, 2H, s), 2.48 (N-Me, 3H, s), 2.38 (Ph-Me, 3H,
s), 2.36 (Me, 3H, s).
MS (ES) m/z = 405 (MH+)
HPLC = 83.6%
Example 35: Quinoline-2-carboxylic acid methyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 60%
1H NMR (400 MHz, DMSO-d6) : δ 8.77-7.16 (Ar, 13H, m) ,
5.35 (CH2, 2H, s), 2.65 (N-Me, 3H, s), 2.36 (Ph-Me, 3H,
s), 2.33 (Me, 3H, s).
MS (ES) m/z = 421 (MH+)
HPLC = 96.6%
Example 36: 6-Methoxy-3-methyl-2-[methyl-(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamoyl]-
benzothiazol-3-ium iodide

Yield: 85%
1H NMR (400 MHz, DMSO-d6) : δ 8.53-7.29 (Ar, 10H, m) ,
4.73 (CH2, 2H, s), 3.94 (MeO, 3H, s) , 3.44 (Me-
thiazole, 3H, s), 2.97 (N-Me, 3H, s), 2.37 (Ph-Me, 3H,
s), 2.32 (Me, 3H, s).
MS (ES) m/z = 471 (MH+)
HPLC = 97.6%
Example 37: N-Ethyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-
a] pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide

To a solution of N-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide (1
eq) in dry DMF are added 1.2 eq of NaH (60%) under
argon. The suspension is stirred for 10 min at room
temperature. Then 1.1 eq of EtI are added and the
corresponding mixture is stirred for 1 h at room
temperature. After this period, 0.5 N NaOH is added.
The mixture is extracted with dichloromethane. The
organic layer is dried over magnesium sulphate and the
solvent is removed in vacuo to obtain 0.47 eq of N-
ethyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-4-trifluoromethyl-benzamide.
Yield: 47%
1H NMR (400 MHz, DMSO-d6) : δ 8.26-7.19 (Ar, 11H, m) ,
5.32 (CH2, 2H, s), 2.7 (CH2-Me, 2H, m) , 2.36 (Ph-Me,
3H, s), 2.33 (Me, 3H, s), 0.55 (Me-CH2, 3H, m) .
MS (ES) m/z = 452 (MH+)
HPLC = 99.8%
The compound of example 38 was prepared according to
this procedure starting from the corresponding N-
dealkylated amide.

Example 38: Cyclopropanecarboxylic acid ethyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

Yield: 41%
1H NMR (400 MHz, DMSO-d6) : δ 8.07-7.14 (Ar, 7H, m) ,
5.12 (CH2, 2H, s), 3.08 (CH2-Me, 2H, q, J= 7.2 Hz),
2.36 (Ph-Me, 3H, s) , 2.25 (Me, 3H, s) , 1.85 (CH, 3H,
m) , 0.81 (Me-CH2, 3H, t, J= 7.2 Hz), 0.73 (CH2, 4H, m) .
MS (ES) m/z = 348 (MH+)
HPLC = 92.3%
Example 39: N-(6-Methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-N-propyl-4-trifluoromethyl-
benzamide

To a solution of N-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide (1
eq) in dry DMF are added 1.2 eq of NaH (60%) under
argon. The suspension is stirred for 10 min at room
temperature. Then 1.1 eq of PrI are added and the
corresponding mixture is stirred for 1h at room

temperature. After this period, 0.5 N NaOH is added.
The mixture is extracted with dichloromethane. The
organic layer is dried over magnesium sulphate and the
solvent is removed in vacuo to obtain 0.17 eq of N-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-N-
propyl-4-trifluoromethyl-benzamide.
Yield: 17%
MS (ES) m/z = 466 (MH+)
HPLC = 83.9%
The compound of example 40 was prepared according to
this procedure starting from the corresponding N-
dealkylated amide.
Example 40: Cyclopropanecarboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-propyl-amide

Yield: 35%
MS (ES) m/z = 362 (MH+)
HPLC = 89.8%
Example 41: N-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-N-prop-2-ynyl-4-trifluoromethyl-
benzamide

To a solution of N-(6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-4-trifluoromethyl-benzamide (1
eq) in dry DMF are added 1.2 eq of NaH (60%) under
argon. The suspension is stirred for 10 min at room
temperature. Then 1.1 eq of 3-bromo-propyne are added
and the corresponding mixture is stirred for lh at room
temperature. After this period, NaOH 0.5 N is added.
The mixture is extracted with dichloromethane. The
organic layer is dried under magnesium sulphate and the
solvent is removed in vacuo to obtain 0.16 eq of N-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-N-
prop-2-ynyl-4-trifluoromethyl-benzamide.
MS (ES) m/z = 462 (MH+)
HPLC = 84%
The compound of example 42 was prepared according to
this procedure starting from the corresponding N-
dealkylated amide.
Example 42: Cyclopropanecarboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-prop-2-ynyl-
amide

Yield: 29%
MS (ES) m/z = 358 (MH+)
HPLC = 84.7%
Example 43: C-(6-Methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-yl)-methylamine

A solution of 3 g (13 mmol) of bromide of 6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-4-ium in 50 mL of acetic
acid is added to a solution of 1 g (13 mmol) N-
methanolacetamide in 50 mL of acetic acid. To the
resulting solution are added slowly 5 g (54 mmol) of
concentrated sulphuric acid. The crude is stirred at
room temperature for 1.5 hours and after at reflux for
2 hours. The reaction is allowed to cool, and 50 mL of
water are added. The crude is basified with ammonia 25%
and extracted with dichloromethane. The organic layer
is dried, filtered off and the solvent is removed in
vacuo, to obtain 3.86 g (13.2 mmol, yield: 97%) of the
corresponding amide. This amide is dissolved in 150 mL
of ethanol and 50 mL of concentrated hydrochloric acid
are added. The mixture is heated at reflux for 30 min.

The crude is neutralized and the solvent is removed.
The residue is extracted with DCM-water, and the
organic layer is dried, filtered off and evaporated, to
obtain 3.2 g (12.8 mmol, 97%) of C-(6-Methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-yl)-methylamine as a white
solid.
MS (ES) m/z = 252 (MH+)
HPLC = 90%
Example 44: 1-(4-Dimethylamino-phenyl)-3-(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea

To a solution of 1 eq of C-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-yl)-methylamine in pyridine is
added a solution of 1-(4-Dimethylamino-phenyl)-
isocyanate (1 eq) in pyridine. The mixture is stirred
at room temperature for 2 4 hours. The solvent is
removed and water is added to the residue. The solid
thus obtained is filtered off, washed with water and
dried over calcium chloride to give 1-(4-Dimethylamino-
phenyl) -3- (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-urea.
Yield: 27%

1H NMR (400 MHz, DMSO-d6) : δ 8.78 (NH, 1H, s) , 8.45
(NH, 1H, m) , 7.80-6.80 (Ar, 11H, m) , 4.76 (CH2, 2H, d,
J= 5.6 Hz), 2.85 (Me2N, 6H, s) , 2.43 (Ph-Me, 3H, s) ,
2.4 (Me, 3H, s).
MS (ES) m/z = 414 (MH+)
HPLC =94%
The compounds of examples 45-4 9 were prepared according
to this procedure starting from the corresponding
isocyanates.
Example 45: 1-Ethyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-
a] pyridin-3-ylmethyl)-urea

Yield: 27%
1H NMR (400 MHz, DMSO-d6) : δ 8.84-7.41 (Ar, 7H, m) ,
6.78 (NH, 1H, m) , 6.08 (NH, 1H, m) , 4.67 (CH2, 2H, d,
J= 5.2 Hz), 3.01 (CH2, 2H, quint, J= 6.8 Hz), 2.44 (Ph-
Me, 3H, s), 2.4 (Me, 3H, s) , 0.97 (Me-CH2, 3H, t, J=
6.8 Hz).
MS (ES) m/z = 323 (MH+)
HPLC = 100%
Example 46: 1-Isopropyl-3-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-urea

Yield: 28%
1H NMR (400 MHz, DMSO-d6) : δ 8.83-7.42 (Ar, 7H, m) ,
6.61 (NH, 1H, m) , 5.93 (NH, 1H, d, J= 8 Hz), 4.68 (CH2,
2H, d, J= 5.2 Hz), 3.67 (CH-Me2, 1H, m) , 2.43 (Ph-Me,
3H, s), 2.41 (Me, 3H, s) , 1.00 (Me2-CH, 6H, d, J= 6
Hz) .
MS (ES) m/z = 337 (MH+)
HPLC = 100%
Example 47: 1-Cyclopentyl-3-(6-methyl-2-p-tolyl-imidazo
[1,2-a]pyridin-3-ylmethyl)-urea

Yield: 36%
1H NMR (400 MHz, DMSO-d6) : δ 8.79-7.40 (Ar, 7H, m),
6.52 (NH, 1H, m) , 6.05 (NH, 1H, d, J= 7.6 Hz), 4.68
(CH2, 2H, d, J= 5.2 Hz), 3.85 (CH, 1H, m), 2.42 (Ph-Me,
3H, s), 2.4 (Me, 3H, s), 1.76-1.22 ((CH2)4, 8H, m) .
MS (ES) m/z = 363 (MH+)
HPLC = 99%

Example 48: 1-Cyclohexyl-3-(6-methyl-2-p-tolyl-imidazo
[1,2-a]pyridin-3-ylmethyl)-urea

Yield: 46%
1H NMR (400 MHz, DMSO-d6) : δ 8.75-7.40 (Ar, 7H, m) ,
6.54 (NH, 1H, m) , 5.94 (NH, 1H, d, J= 6.8 Hz), 4.68
(CH2, 2H, d, J= 5.2 Hz), 3.9 (CH, 1H, m) , 2.42 (Ph-Me,
3H, s), 2.4 (Me, 3H, s), 1.72-1.04 ((CH2)5, 10H, m) .
MS (ES) m/z = 377 (MH+)
HPLC = 98%
Example 49: 1-(6-Methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-3-phenyl-urea

Yield: 30%
1H NMR (400 MHz, DMSO-d6) : δ 8.43 (NH, 1H, s), 8.34-
6.88 (Ar, 12H, m) , 6.83 (NH, 1H, t, J= 5.6 Hz), 4.74
(CH2, 2H, d, J= 5.6 Hz), 2.35 (Ph-Me, 3H, s), 2.31 (Me,
3H, s).

MS (ES) m/z = 371 (MH+).
HPLC =92%
Example 50: (6-Methyl-2-p-tolyl-imidazo[1, 2-a]pyridin-
3-ylmethyl)-carbamic acid p-tolyl ester

To a solution of 1 eq of C-(6-Methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-yl)-methylamine in pyridine is
added a solution of p-tolyl-chloroformiate (1 eq) in
pyridine. The mixture is stirred at room temperature
for 2 4 hours. The solvent is removed and water is added
to the residue. The solid thus obtained is filtered
off, washed with water and dried over calcium chloride
to give (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-carbamic acid p-tolyl ester.
Yield: 16%
1H NMR (400 MHz, DMSO-d6) : δ 8.41-6.93 (Ar, 11H, m) ,
6.62 (NH, 1H, t, J= 5.6 Hz), 4.71 (CH2, 2H, d, J= 5.6
Hz), 2.35 (impy-Ph-Me, 3H, s), 2.3 (Ph-Me, 3H, s), 2.28
(Me, 3H, s).
MS (ES) m/z = 386 (MH+)
HPLC = 80%

The compounds of examples 51-57 were prepared according
to this procedure starting from the corresponding
chloroformiates.
Example 51: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-
3-ylmethyl)-carbamic acid prop-2-ynyl ester

Yield: 5%
1H NMR (400 MHz, DMSO-d6) : δ 8.21-7.15 (Ar, 7H, m) ,
8.05 (NH, 1H, t, J= 5.2 Hz), 4.66 (CH2-C, 2H, d, J= 2.4
Hz), 4.64 (CH2, 2H, d, J= 5.2 Hz), 3.5 (CH, 1H, t, J=
2.4 Hz), 2.34 (Ph-Me, 3H, s), 2.31 (Me, 3H, s).
MS (ES) m/z = 334 (MH+)
HPLC = 98%
Example 52: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-
3-ylmethyl)-carbamic acid methyl ester

Yield: 30%

1H NMR (400 MHz, DMSO-d6) : δ 8.23-7.14 (Ar, 7H, m) ,
7.83 (NH, 1H, m) , 4.61 (CH2, 2H, d, J= 5.2 Hz), 3.56
(MeO, 3H, s), 2.34 (Ph-Me, 3H, s) , 2.31 (Me, 3H, s).
MS (ES) m/z = 310 (MH+)
HPLC = 100%
Example 53: (6-Methyl-2-p-tolyl-imidazo[1, 2-a]pyridin-
3-ylmethyl)-carbamic acid benzyl ester

Yield: 15%
1H NMR (400 MHz, DMSO-d6) : δ 8.21-7.14 (Ar, 12H, m) ,
7.98 (NH, 1H, m) , 5.08 (CH2-Ph, 2H, s) , 4.65 (CH2, 2H,
d, J= 5.6 Hz), 2.34 (Ph-Me, 3H, s), 2.28 (Me, 3H, s).
MS (ES) m/z = 386 (MH+)
HPLC =86%
Example 54: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-
3-ylmethyl)-carbamic acid 4-methoxy-phenyl ester

Yield: 41%
1H NMR (400 MHz, DMSO-d6) : δ 8.70-6.89 (Ar, 11H, m) ,
8.50 (NH, 1H, m) , 4.74 (CH2, 2H, d, J= 5.2 Hz), 3.73
(MeO, 3H, s), 2.45 (Ph-Me, 3H, s), 2.39 (Me, 3H, s).
MS (ES) m/z = 402 (MH+)
HPLC = 88%
Example 55: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-
3-ylmethyl)-carbamic acid ethyl ester

Yield: 23%
1H NMR (400 MHz, DMSO-d6) : δ 8.46-7.32 (Ar, 7H, m) ,
4.63 (CH2, 2H, d, J= 4.4 Hz), 4.02 (CH2-Me, 2H, m) ,
2.49 (Ph-Me, 3H, s), 2.37 (Me, 3H, s) , 1.15 (Me, 3H, t,
J= 6.8 Hz).
MS (ES) m/z = 324 (MH+)
HPLC = 81%
Example 56: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-
3-ylmethyl)-carbamic acid phenyl ester

Yield: 22%
1H NMR (400 MHz, DMSO-d6) : δ 8.70-6.72 (Ar, 12H, m) ,
8.56 (NH, 1H, m) , 4.76 (CH2, 2H, d, J= 5.6 Hz), 2.45
(Ph-Me, 3H, s), 2.39 (Me, 3H, s).
MS (ES) m/z = 372 (MH+)
HPLC = 90%
Example 57: (6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-
3-ylmethyl)-carbamic acid isopropyl ester

Yield: 16%
1H NMR (400 MHz, DMSO-d6) : δ 8.25-7.14 (Ar, 7H, m) ,
7.75 (NH, 1H, d, J= 5.6 Hz), 4.81 (CH, 1H, m) , 4.62
(CH2, 2H, d, J= 5.6 Hz), 2.34 (Ph-Me, 3H, s) , 2.31 (Me,
3H, s), 1.17 (Me2CH, 6H, d, J= 6.4 Hz).
MS (ES) m/z = 338 (MH+)
HPLC = 98%
The compounds of examples 58-90 were prepared according
to the procedure described for example 44, starting
from C-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yl)-
methylamine and the corresponding acid chlorides.
Example 58: Cyclobutanecarboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 334 (MH+)
HPLC = 99%
Example 59: Cyclopentanecarboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 348 (MH+)
HPLC = 99%
Example 60: Benzo[b]thiophene-3-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 413 (MH+)
HPLC = 97%

Example 61: 5-Methyl-pyrazine-2-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
MS (ES) m/z = 372 (MH+)
HPLC = 90%
Example 62: 1-Methyl-1H-pyrrole-2-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
MS (ES) m/z = 359 (MH+)
HPLC = 90%
Example 63: N-(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin
-3-ylmethyl)-nicotinamide

MS (ES) m/z = 357 (MH+)
HPLC =92%

Example 64: 5-Chloro-4-methoxy-thiophene-3-carboxylic
acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 427 (MH+)
HPLC = 98%
Example 65: 6-Oxo-1,4,5,6-tetrahydro-pyridazine-3-
carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 376 (MH+)
HPLC = 99%
Example 66: Benzo[c]isoxazole-3-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 397 (MH+)
HPLC = 97%
Example 67: 1,5-Dimethyl-1H-pyrazole-3-carboxylic acid
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 374 (MH+)
HPLC = 99%
Example 68: 1-Methyl-1H-indole-3-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 410 (MH+)
HPLC = 98%
Example 69: 2-Methyl-thiazole-4-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
MS (ES) m/z = 377 (MH+)
HPLC = 99%
Example 70: [1,2,3]Thiadiazole-4-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 364 (MH+)
HPLC = 99%
Example 71: N-(6-Methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-2-thiophen-2-yl-acetamide

MS (ES) m/z = 376 (MH+)
HPLC = 98%
Example 72: 5-Methyl-isoxazole-3-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
MS (ES) m/z = 361 (MH+)
HPLC = 97%
Example 73: N-(6-Methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-6-(2,2,2-trifluoro-ethoxy)-
nicotinamide

MS (ES) m/z = 455 (MH+)
HPLC = 91%

Example 74: 1-Methyl-1H-imidazole-4-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
MS (ES) m/z = 360 (MH+)
HPLC = 99%
Example 75: 6-Methoxy-2-oxo-2H-chromene-3-carboxylic
acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 454 (MH+)
HPLC = 89%
Example 76: 4-Methoxy-thiophene-3-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 392 (MH+)
HPLC = 93%
Example 77: 5-Methoxy-thiophene-2-carboxylic acid (6-
methyl-2-p-tolyl-imidazo [1, 2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 392 (MH+)
HPLC = 91%
Example 78: 1-Methyl-1H-imidazole-2-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 360 (MH+)
HPLC = 90%
Example 79: 4-Methyl-[1,2,3]thiadiazole-5-carboxylic
acid (6-methyl-2-p-tolyl-imidazo[1, 2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 378 (MH+)
HPLC = 91%
Example 80: 3-Furan-2-yl-N-(6-methyl-2-p-tolyl-
imidazo[1,2-a]pyridin-3-ylmethyl)-acrylamide

MS (ES) m/z = 372 (MH+)
HPLC = 96%
Example 81: Thiazole-4-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 363 (MH+)
HPLC = 98%

Example 82: Thiophene-3-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 362 (MH+)
HPLC = 95%
Example 83: 2,5-Dimethyl-oxazole-4-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
MS (ES) m/z = 375 (MH+)
HPLC = 98%
Example 84: 1-Cyclopropyl-2,5-dimethyl-1H-pyrrole-3-
carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-
a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 414 (MH+)
HPLC = 95%
Example 85: 4,5-Dichloro-isothiazole-3-carboxylic acid
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide
MS (ES) m/z = 432 (MH+)
HPLC =92%
Example 86: 1,2,5-Trimethyl-1H-pyrrole-3-carboxylic
acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 387 (MH+)
HPLC = 96%
Example 87: 2,4-Dichloro-5-fluoro-N-(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide

MS (ES) m/z = 443 (MH+)
HPLC = 91%
Example 88: 5-Nitro-thiophene-3-carboxylic acid (6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 407 (MH+)
HPLC = 97%
Example 89: Pyrazine-2-carboxylic acid (6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 358 (MH+)
HPLC = 97%

Example 90: 3,5-Dimethyl-isoxazole-4-carboxylic acid
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 375 (MH+)
HPLC = 93%
The compounds of examples 91-100 were prepared
according to the procedure described for example 22.
Example 91: 2-Methyl-thiazole-4-carboxylic acid methyl-
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 392 (MH+)
HPLC = 99%
Example 92: 1,5-Dimethyl-1H-pyrazole-3-carboxylic acid
methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 388 (MH+)
HPLC = 90%
Example 93: 1-Methyl-6-oxo-1,4,5,6-tetrahydro-
pyridazine-3-carboxylic acid methyl-(6-methyl-2-p-
tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide

MS (ES) m/z = 404 (MH+)
HPLC = 90%
Example 94: Thiazole-4-carboxylic acid methyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 377 (MH+)
HPLC = 99%
Example 95: 2,5-Dimethyl-oxazole-4-carboxylic acid
methyl-{6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 389 (MH+)
HPLC = 91%
Example 96: Pyrazine-2-carboxylic acid methyl-(6-
methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-
amide

MS (ES) m/z = 372 (MH+)
HPLC = 98%

Example 97: 1-Methyl-1H-imidazole-4-carboxylic acid
methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 374 (MH+)
HPLC = 95%
Example 98: 1-Methyl-1H-imidazole-2-carboxylic acid
methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 374 (MH+)
HPLC = 99%
Example 99: 5-Methyl-isoxazole-4-carboxylic acid
methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 375 (MH+)
HPLC =99%
Example 100: 5-Nitro-thiophene-3-carboxylic acid
methyl-(6-methyl-2-p-tolyi-imidazo[1,2-a]pyridin-3-
ylmethyl)-amide

MS (ES) m/z = 421 (MH+)
HPLC = 90%

We claim :
1, An imidazo[1,2-a] pyridine compound of formula (I):

as well as pharmaceutically acceptable salts thereof;
wherein
R1 and R2 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1-C6), alkenyl
(C2-C6), alkynyl(C2-C6), haloalkyl (C1-C6),-O-alkyl(C1-C6), fluoro, chioro and bromo;
R3 is selected from the group consisting of hydrogen, linear orbranched alkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl
(C3-C6) alkyl (C1-C6), alkenyl (C1-C6), alkynyl (C2-C6) alkyl (C1-C6), alkynyl (C2-C5), alkynyl (C2-C6) alkyl (C1-C6);
R4 is selected from the group consisting of haioalkyl (C2-C6) cycloalkyl (C3-C5), cycloalkyl (C3-C6)alkyl(C1-C6),
alkynyl (C2-C6) alkyl (C1-C6), alkyl(C1-C6)-O-alkyl (C1-C6), alkyl (C1-C6)-NH-alkyl (C1-C6), alkyl (C1-C6)-N(dialkyl
(C1-C6)), -OR5, -NHR5,-NR5R6,

phenylalkyl (C2-C6), Phenylalkenyl (C2-C6), naphthyl, monosubstituted naphthyl, disubstituted naphthyl, naphthy-
lalkyl(C1-C6), naphthylalkenyl (C2-C6) furyl, substituted furyl, benzofuryl, substituted benzofuryl, pyrrolyl, substituted
pyrrolyl, isoxazolyl, substituted isoxazolyl, benzoisoxazolyl, substituted benzoisoxazolyl, imidazolyl, substituted im-
idazolyl, benzimidazolyl, substituted benzimidazolyl, indolyl, substituted indolyl, pyrazolyl, substituted pyrazolyl,
thienyl, substituted thienyl, benzothienyl, substituted benzothienyl, thiazolyl, substituted thiazolyl, benzothiazolyl,
substituted benzothiazolyl, quinolinyl, substituted quinolinyl, isoquinolinyl, substituted isoquinoiinyl, pyridyl, substi-
tuted pyridyl, pyrazinyl, substituted pyrazinyl, 6-oxo-1,4,5,6-tetrahydropyridazinyl, substituted 6-oxo-1,4,5,6-tetrahy-
dropyridazinyl, thiadiazolyl, substituted thiadiazolyl, isothiazolyl, substituted isothiazolyl, thienylmethyl, 2-oxo-
chromenyl, substituted 2-oxochromenyl, 2-(furan-2-yl)vinyl; oxazolyl, substituted oxazolyl, and benzisoxazolyl;
R5 and R6 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1-C6),
phenylalkyl (C1-C6), haloalkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl(C3-C6)alkyl(C1-C6), alkenyl(C2-C6) and alky-
nyl(C2-C6), alkenyl(C2-C5)alkyl(C1-C6), alkynyl(C2-C6)-alkyl(C1-C6), phenyl, substituted phenyl, heteroaryl, substi-
tuted heteroaryl; and
R7 and R8 are independently selected from the group consisting of linear or branched alkyl(C2-C6), cycloalkyl(C3-C6),
alkenyl(C2-C6), alkynyl(C2-C6), -OH, - O-alkyl(C1-C6), -SH, -S-alkyl(C1-C6), halo-alkyl (C1-C6), ω,ω,ω-trifluoroalkyl
(C1-C6), -NHalkyl(C1-C6), - Ndialkyl(C1-C6), -NO2, -CN, -SO2alkyl(C1-C6), - Coalkyl(C1-C6), -COOalkyl(C1-C6 ,
-CO-NHalkyl(C1-C6), CONdialkyl (C1-C6), phenyl, substituted phenyl, heteroaryl, and substituted heteroaryl
and wherein the substituents of the radicals that are substituted are selected from the group consisting of linear or
branched alkyl (C2-C6), cycloalkyl (C3-C6), alkenyl(C2-C6), alkynyl (C2-C6), -OH, -O-alkyI (C1-C6), -SH, S-alkyl
(C1-C5), halo-alkyl(C1-C6), ω,ω,ω-trifluoroalkyl (C1-C6), -NHalkyl(C2-C6), -Ndialkyl (C1-C6),-NO2, -CN, -SO2alkyl
(C1-C6),-COalkyl(C1-C6),-COOalkyl(C1-C6),-CO-NHalkyl(C1-C6), -CONdialkyl(C1-C6), phenyl, substituted phenyl,
heteroaryl, substituted heteroaryl, fluoro, chloro and bromo.

2. An imidazo [1,2-a] pyridine compound of formula (I):

as well as pharmaceutically acceptable salts thereof;
wherein
R1 and R2 are independently selected from the group consisting of hydrogen, linear or branched alkyl (C1-C6),
alkenyl (C2-C6), alkynyl (C2-C6), haloalkyl (C1-C6), -O-alkyl(C1-C6), fluoro, chloro and bromo;
R3 is selected from the group consisting of hydrogen, linear or branched alkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl
(C3-C6) alkyl (C1-C6), alkynyl (C2-C6), alkenyl(C2-C6)alkyl(C1-C6), alkynyl (C2-C6), alkynyl (C2-C6) alkyl (C1-C6);
R4 is selected from the group consisting of haioalkyl(C2-C6), cycloalkyl (C3-C5), cycloalkyl (C3-C6) alkyl (C1-C6),
alkynyl (C2-C6) alkyl (C1-C6), alkyl (C1-C6) - O-alkyl (C1-C6), alkyl (C1-C6) -NH-alkyl (C1-C6), alkyl (C1-C6)-N(dialkyl
(C1-C6)), -OR5, -NHR5, -NR5R6,

phenylalkyl (C2-C6), phenylalkenyl (C2-C6), naphthyl, monosubstituted naphthyl, disubstituted naphthyl, naphthyl-
alkyl(C1-C6), naphthylalkenyl (C2-C6), furyl, substituted furyl, benzofuryl, substituted benzofuryt, pyrrolyl, substituted
pyrrolyl, isoxazolyl, substituted isoxazolyl, benzoisoxazolyl, substituted benzoisoxazolyl, imidazolyl, substituted im-
idazolyl, benzimldazolyl, substituted benzimidazolyl, indolyl, substituted indolyl, pyrazolyl, substituted pyrazolyl,
thienyl substituted thienyl, benzothienyl, substituted benzothtenyl, thiazoiyl, substituted thiazolyl, benzothiszolyl,
substituted benzothiazolyl, quinolinyl, substituted quolinyl, isoquinolinyl, substituted isoquinolinyl, pyridyl, and sub-
stituted pyridyl;
R5 and R6 are independently selected from the group consisting of hydrogen, linear or branched alkyl(C1-C6),
phenylalkyl (C1-C6), haloalkyl (C1-C6), cycloalkyl (C3-C6), cycloalkyl (C3-C5) alkyl (C1-C6), alkenyl (C2-C6) and
alkynyl (C2-C6), alkenyl(C2-C6) alkyl (C1-C6), alkynyl (C2-C6)alkyl(C1-C6), phenyl, substituted phenyl, heteroaryl,
substituted heteroaryl; and
R7 and R8 are independently selected from the group consisting of linear or branched alkyl(C2-C6), cycloalkyl(C3-C6),
alkenyl(C2-C6),alkynyl(C2-C6), -OH,-O-alkyl(C1-C6),-SH, -S-alkyl (C1-C6), halo-alkyl (C1-C6), ω,ω,ω-trifluoroalkyl
(C1-C6), -NHalkyl (C1-C6), - Ndialkyl (C1-C6), -NO2, -CN, -SO2alkyl (C1-C6), - COalkyl (C1-C6), -COOalkyl (C1-C6),
-CO-NHalkyl(C1-C6). - CONdialkyl(C1-C6),- phenyl, substituted phenyl, heteroaryl and substituted heteroaryl.
3. A compound as claimed in claim 1, wherein R1 is a methyl group and R2 is a methyl group in para-position; and R3
is selected from the group consisting of hydrogen, methyl, ethyl, n-propyl, i-propyl, cyclopropyl and 2-propynyl.
4. A compound as claimed in claim 3, wherein R4 is selected from the group consisting of cyclopropyl, cyclobutyl, 2-
propynyl, N,N-dimethyl-4-aminophenyl, 2-furyl, 5-NO2-2-furyl, 2-pyrrolyl, 2-thienyl, 2-pyridyl, 4,6-difiuoro-2-pyridyl,
2-chloro-4-pyridyl, 4-pyridyl, 5-methyl-2-pyrazinyl, 6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl, [1,2,3]thiadiazol-4-yI, 2-
thienylmethyl, 1-methyl-1H-imidazol-2-yl, 4-thiazolyl, 2,5-dimethyl-4-oxazolyl and 3,5-dimethyl-4-isoxazolyl.

5. A compound as claimed in claim 4, wherein R4 is selected from the group consisting of cyclopropyl, 2-propynyl, N,
N-dimethyl-4-aminophenyl, 2-furyl, 5-NO2-2-furyl, 2-pyrrolyl, 2-thienyl, 2-pyridyl, 4,6-difluoro-2-pyridyl, 2-chioro-4-
pyridyf and 4-pyridyl.
6. A compound as claimed in claim 3, wherein R4 is -NR5R6.
7. A compound as claimed in claim 5, wherein R5 is hydrogen or methyl; and R6 is selected from the group consisting
of methyl, ethyl, n-propyi, i-propyl, cyclopropyi, cyclopentyl, cyclohexyl, 2-propinyl and phenyl.
6. A compound as claimed in claim 3, wherein R4 is -OR5.
9. A compound as claimed in claim 8, wherein R5 is selected from the group consisting of methyl, ethyl, n-propyl, i-
propyl, cyclopropyi, cyclopentyl, cyclohexyl, 2-propinyl, 4-methyl-phenyl, 4-methoxy-phenyl and phenyl.
10. A compound as claimed in claim 4, wherein said compound is selected from the group consisting of:
Furan-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yImethyl)-amide;
Pyridine-2-carboxylic acid (S-methyl-2-p-tolyl-imidazo[1,2-alpyridin-3-yimethyl)-amide;
Thiophene-2-carboxylic acid (S-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
Cyclopropanecarboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
5-Nitro-furan-2-carboxylic acid (S-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
3,5-Difluoro-pyridine-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
6-Methoxy-benzothiazole-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
4-Dimethylamino-N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-benzamide;
cyclopropanecarboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
Pyridine-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
Thiophene-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
5-Nitro-furan-2-carboxylic acid methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
2-Chloro-N-methyl-N-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-isonicotinamide;
Cyclobutanecarboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yimethyl)-amide;
5-Methyl-pyrazine-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
6-Oxo-1,4,5,6-tetrahydro-pyridazine-3-carboxylic acid (8-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylme-
thyl)-amide;
[1,2,3]Thiadiazole-4-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide:
N-(6-yethyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-2-thiophen-2-yl-acetamide;
1-methyl-1H-imidazole-2-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-alpyridin-3-ylmethyl)-amide;
Thiazoie-4-carboxylic acid (16-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
2,5-Dimethyl-Qxazole-4-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide;
3,5-Dimethyl-isoxazole-4-carboxylic acid (6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide; and
Thiazole-4-carboxylic add methyl-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-amide.
11. A compound as claimed in claims 6 and 7, wherein said compound is selected from the group consisting of:
1-(4-Dimethylamino-phenyl)-3-(6-methyl-2-p-tolyI-imidazo[1,2-a]pyridin-3-ylmethyl)-urea:
1-Ethyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea:
1-lsopropyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea:
1-Cyclopentyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea:
1-Cyclohexyl-3-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-urea; and
1-(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-3-phenyl-urea.

12. A compound as claimed in claims 8 and 9, wherein said compound is selected from the group consisting of:
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid p-tolyl ester;
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid prop-2-ynyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid methyl ester;
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid benzyl ester;
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-yimefbyl)-carbamic acid 4-methoxy-phenyl ester;
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid ethyl ester;
(6-methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid phenyl ester, and
(6-Methyl-2-p-tolyl-imidazo[1,2-a]pyridin-3-ylmethyl)-carbamic acid isopropyl ester.
13. A process for preparing a compound of formula (I) or a pharmaceutically acceptable salt thereof, as claimed in claim
1, comprising reacting intermediate (II):

with the nitrile of the formula R4-CN wherein R1, R2 and R4 are as defined in (I).
14. A process for preparing a compound of formula (I) or a pharmaceuticaliy acceptable saltthereof, as claimed in claim
1, comprising reacting intermediate (III):

with an acyl chloride of the formula R4-COCI, an isocyanate of the formula R4-CNO or a chloroformiate of the formula
R4-OCOCI, wherein R1, R2 and R4 are as defined in (I).
15. A process as claimed in claim 14, comprising reacting previously in the adequate acid conditions, an
intermediate of formula (IV)

with an intermediate of formula (V);
CH3CONHCH2Q (V)
wherein Q is selected from the group consisting of -OH, -Oalkyl (C1-C3), -N+(alkyl(C1-C3)3Cl-, -N+(alkyl(C1-C3))
38r-, -N+(alkyl(C1-C3)) 3I-, and then hydrolyzing the obtained intermediate (VI):

to obtain said intermediate (Ill).
16. A process as claimed in claim 15, comprising utilizing the intermediate of formula (V) wherein Q is -OH.
17. A composition comprising a compound as claimed in claim 1 in association with a therapeutically inert carrier.
18. A compound as claimed in claim 1 for preparing a medicament for treating or preventing diseases associated with
GABAA receptor modulation.

The present invention relates to novel imidazo[1,2- a]pyridine compounds
of general formula (I) as well as pharmaceutically acceptable salts thereof;
wherein R1, R2, R3 and R4 are as defined in the claims. The compounds have specific
affinity for GABAA receptor and are therefore useful in the treatment and prevention
of diseases modulated by α1- and α2-GABAA receptors.

IMIDAZO[1,2-A]PYRIDINE COMPOUNDS AND COMPOSITIONS

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