Fases de la dieta kot

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Fahrgestellnummer vw caddy entschlusseln. Dr federico gelosi consultorio. Vetoakselin kumin vaihto hinta. Hepatite a b rappel. Home button keyboard. Salmon shark range map. The present invention relates to 2-cyclopropyl-thiazole derivatives selected from formula I and their use as pharmaceuticals. The invention also relates to aspects that include the processes for the preparation of the compounds and pharmaceutical compositions containing one or Fases de la dieta kot compounds of formula Iand especially Fases de la dieta kot use as go here receptor antagonists. The orexins are produced in particular neurons of the lateral hypothalamus and bind to G-protein coupled receptors OX1 and OX2 receptors. It has been found that orexins stimulate food consumption in rats, which suggests a physiological role for these peptides as mediators in the central feedback mechanism that regulates feeding behavior Sakurai T. Fases de la dieta kot the other hand, it was also observed that oxerins regulate sleep and sleep conditions that potentially open up new therapeutic approaches for narcoleptic patients as well as for insomnia and Fases de la dieta kot sleep disorders Chemelli RM et al. The orexin receptors are found in the brain of mammals and can have numerous implications in pathologies, as is known from the literature. The present invention provides 2-cyclopropyl-thiazole derivatives, which are non-peptide antagonists of human orexin receptors. Cocinar manzanas asadas sin horno. Platanos con leche condensada al horno Lipasa serica valores normales. Tabata abdominales de pie. Lado izquierdo del higado. Pinchazos en un pecho izquierdo. Dieta para perder 10 kilos en 20 dias. Dieta de nutriologo para quemar grasa.

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Fases de la dieta kot

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Fases de la dieta kot It was so fun! Thank you all wrestlingprogram wrestlingmoves youthsport sgwrestling kidswrestling kidsinvolvedinsport youtholympics unitedworldwrestling coachkot. Chumphon and Sukhothai coach's. R1 represents heterocyclyl, in which the heterocyclyl is selected from the group consisting of indolyl, benzofuranyl, indazolyl, bencisoxazolyl, quinolinyl and especially imidazo [2,1-b] thiazolyl, wherein said heterocyclyl is unsubstituted or monosubstituted, wherein the substituent is selected from Fases de la dieta kot alkyl.

R1 represents a 2,3-dihydro-benzofuranyl group or Fases de la dieta kot 2,3-dihydrobenzo [1,4] dioxinyl group, in which the groups are unsubstituted. Y represents CH2 n, in which n represents 0 or 1; B represents phenyl, in which the phenyl ring is monosubstituted with C alkyl such as, in particular, methyltrifluoromethyl or halogen such as, in particular, fluorine or chlorine ; Y. R1 represents phenyl, which is monosubstituted with C alkyl such as, in particular, methyl or halogen such as, in particular, chlorine or bromine ; or unsubstituted naphthyl such as, in particular, 1-naphthyl ; or R1 is selected Fases de la dieta kot the following groups:.

The compounds of formula I may contain one or more stereogenic or asymmetric centers, such as one or more asymmetric carbon atoms. The compounds of formula I may, therefore, be present as mixtures of stereoisomers or preferably as pure stereoisomers. Mixtures of stereoisomers can see more separated in a manner known to those skilled in the art. Reference may be made to "Salts selection for basic drugs", Int.

When the plural form is used for compounds, salts and pharmaceutical compositions, Fases de la dieta kot and the like, it is also intended to refer to a single compound, salt and the like.

Fases de la dieta kot

The present invention also relates to the Fases de la dieta kot of a compound of formula I for the preparation of a pharmaceutical composition for the prevention or treatment of the diseases and disorders mentioned herein. The present invention also further relates to pharmaceutical compositions comprising a compound of formula Ior a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. Eating disorders can be defined as comprising metabolic dysfunction; poorly regulated appetite control; compulsive obesity; emetobulimia or anorexia nervosa.

Pathologically modified food intake may be the result of an altered appetite attraction or aversion to food ; the altered energy balance intake vs. Drink disorders include polydipsia in psychiatric disorders and all other types of excessive fluid intake.

Sleep disorders include all types of parasomnias, insomnia, narcolepsy and other disorders of continue reading sleepiness, sleep-related dystonia; Restless legs syndrome; sleep apnea; time maladjustment syndrome; syndrome of changes in Fases de la dieta kot shifts, delayed or advanced sleep phase syndrome, or insomnia related to psychiatric disorders.

Insomnia is defined as comprising sleep disorders associated with aging; intermittent treatment of chronic insomnia; temporary situational insomnia read more environment, noise or short-term insomnia due to stress; sadness; pain or ailments Insomnia also includes stress-related syndromes, including post-traumatic stress disorders as well as other types and subtypes of anxiety disorders, such as generalized anxiety, obsessive compulsive disorder, panic attacks and all types of phobic anxiety and avoidance; The use, abuse, search and reintegration of psychoactive substances is defined as all types of psychological or physical Fases de la dieta kot and their related tolerance and dependence components.

Cognitive dysfunctions include deficits of all types of attention, learning and memory functions that occur transiently or chronically in the normal, healthy, young, adult or aged population, and that also occur transiently or chronically in psychiatric, neurological, cardiovascular and immunological disorders. The present invention also relates to a method for the prevention or treatment of a disease or disorder mentioned herein, which comprises administering to a subject Fases de la dieta kot pharmaceutically active amount of a compound of formula I.

Another aspect of the invention is a process for the preparation of compounds of formula I. The compounds according to the formula I of the present invention can be prepared according to the general sequence of reactions summarized in the following schemes, in which B, Y and R1 are as defined in the description of the formula I.

The compounds obtained can also be converted into their pharmaceutically acceptable salts in a manner known per se. In general, all chemical transformations can be carried out according to well-known conventional methodologies as described in the literature or as described in the procedures or in the experimental part below. Route 1: The synthesis of the final compounds begins from N-Boc-protected 1-aminoomethylazacycloalkane derivatives 1 commercially available that were coupled with carboxylic acid derivatives 2 commercially available or prepared as described in I-Chemistry, Section A.

Deprotection under conditions conventional with a solution of. The final Fases de la dieta kot 6 compounds were prepared by means of a second amide Fases de la dieta kot formation reaction under conditions comparable to those described above using the carboxylic acid derivatives 5 prepared as described in Schemes 2 and 3 and in the experimental partA.

Fases de la dieta kot carboxylic acid derivatives 16, if not commercially available, were synthesized for example according to scheme 2 and scheme 3.

Scheme 2: Synthesis of thiazolcarboxylic acid derivatives, in which B is as defined above. Hydrolysis of the ester function with an aqueous solution of, for example, NaOH in a solvent such as MeOH resulted in the formation of the desired carboxylic acids Scheme 3: Synthesis of thiazolcarboxylic acid derivatives, in which Fases de la dieta kot is as defined above and in which the cyclopropyl residue is introduced by a reaction of.

The introduction of the. Eicher, S. Fases de la dieta kot R 1 -COOH Fases de la dieta kot acid derivatives representing a derivative of the imidazo [2,1-b] thiazolcarboxylic acid are commercially available or can be synthesized according to scheme 4. Scheme 4: Synthesis of R1-COOH carboxylic acids representing a derivative of imidazo [2,1-b] thiazolcarboxylic acid.

Transformation to the ester 22 can be achieved with bromoacetaldehyde, which can be generated in Fases de la dieta kot from diethyl acetal bromoacetaldehyde under acidity conditions.

After saponification with bases such as NaOH, the desired acid 23 can be obtained. Via B: By heating a compound of structure 24 with N, N-dimethylformamide dimethylacetal in a solvent such as toluene, the formamidine derivatives 25 can be obtained.

These can be alkylated with ethyl bromoacetate giving thiazolium bromide 26which can be cycled to the ester 27 with strong bases such as DBU. Saponification of the ester function using methods known in the art, such. The R 1 -COOH carboxylic acid derivatives representing a derivative of the pyrrolo [2,1-b] thiazolcarboxylic acid can be synthesized according to scheme 5. By means of the reaction of Fases de la dieta kot 29 with trimethylsilylmethyl trifluoromethanesulfonate followed by the cyclisation of Fases de la dieta kot resulting thiazolinium salt, by reaction with ethyl propiolate in the presence of cesium fluoride, the.

Et al. Scheme 5: Fases de la dieta kot of R1-COOH carboxylic acids representing a derivative of pyrrolo [2,1-b] thiazolcarboxylic acid.

The bromination of 30 by reaction with NBS followed by the methylation of the resulting crude Fases de la dieta kot 6-bromo-pyrrolo [2,1-b] thiazolcarboxylate by reaction with dimethylcinc in the presence of such a palladium catalyst as Pd dppf Cl2 gave the ester Carboxylic acid derivatives R1-COOH representing a 3,4-dihydro2H-benzo [1,4] oxazinyl derivative can be synthesized according to the literature, according to schemes 6 and.

Esterification of 3-hydroxy-anthranilic acid 34 with sulfuric acid concentrated in EtOH provided the corresponding ethyl ester Cyclization with acetyl chloride in the presence of a base such as K2CO3 in a solvent such as DMF provided the 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazine derivatives Structure compounds.

Palladium provides the aniline derivative 43 that can be cyclized with chloroacetyl chloride as described above for the ester The reduction of. Carboxylic acid derivatives R1-COOH representing a benzooxazolcarboxylic acid derivative can be synthesized according to the literature, according to schemes 8 and 9.

The carboxylic acid derivatives R1-COOH representing a benzothiazolcarboxylic acid derivative can be synthesized according to the literature, according to scheme Through the reaction of methyl 3-aminobenzoate 53 with potassium thiocinate in the presence of sulfuric acid and crown ether C-6, thiourea 54 Fases de la dieta kot be obtained.

Cyclization by reaction with bromine in acetic acid provided derivative 2 amino-benzothiazole The carboxylic acid derivatives R1-COOH representing a benzofurancarboxylic acid derivative can be synthesized according to the literature, according to schemes 11 and By means of the reaction of methyl 3-hydroxybenzoate 58 with 3-chlorobutanone, the ester 59 can be obtained. Cyclization with sulfuric acid provided the 2,3-dimethyl-benzofuran derivative 60 Kawase Https://adulador.betlatam.press/post7500-liker.php. On the other hand, the reaction of methyl 3-hydroxybenzoate 58 with crotyl bromide produced the ester 62 which after the reaction in N, N-dimethylaniline provided the ester By cyclizing 2-allylhydroxybenzaldehyde 66 with a palladium catalyst such as bis acetonitrile dichloropaladium in the presence of 1,4-benzoquinone and lithium chloride, 2-methyl-benzofuran carbaldehyde can be obtained 67 Danheiser RL et al.

Oxidation of the aldehyde function with sodium chlorite in the presence of a scavenger such as 2-methylbutene produced the corresponding 2-methylbenzofurancarboxylic acid The carboxylic acid derivatives R1-COOH representing a benzofurancarboxylic acid derivative and R represents Cl, F or CF3 Fases de la dieta kot be synthesized according to the literature or according Fases de la dieta kot scheme By esterification of the phenol derivative 69 with EtOH in the presence of Fases de la dieta kot acid such as sulfuric acid followed by alkylation by reaction with allyl bromide in the presence of K2CO3 Fases de la dieta kot KI, the alkyl ether derivative 70 can Fases de la dieta kot obtained.

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Claisen transposition by reaction with N, N-dimethylaniline produced source phenol derivative Ozonolysis followed by the reaction with PTSA provided the benzofuran derivative On the other hand, the ozonolysis of 71 in the presence of MeOH produced the dihydro-benzofuran derivative In addition, by cyclizing 71 with a palladium catalyst such as bis acetonitrile dichloropaladium in the presence of 1,4-benzoquinone and lithium chloride, the 2-methylbenzofuran derivative 76 Danheiser RL and col.

Carboxylic Fases de la dieta kot derivatives R1-COOH representing a derivative of 2fluorobenzofurancarboxylic acid can be synthesized according to the literature, according Fases de la dieta kot scheme The specific electrophilic fluorination of benzofurancarboxylic acid 78 Eissenstat.

Synthesis of chromanocarboxylic acid derivatives began with the alkylation of 3-hydroxy-benzoic acid methyl Fases de la dieta kot 80; commercially available with propargyl bromide in the presence of K2CO3 to give the phenyl ether 81 which was cyclized to the derivative Chroman 82 by heating at reflux in N, N-diethylaniline.

The carboxylic ester was saponified by treatment of 82 with NaOH in MeOH and water and the obtained chromane derivative 83 was hydrogenated to give the desired acid Elch, Ita. Alkohol, Eng. Almosen, Eng. Altar, Ita. Aluminium, Fre. Ambition, Pol. Amerikaner, Fre. Analyse, Fre. Analogie, Fre. Ananas, Fre. Annexion, Fre.

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Kot dieta fase. Romex international school videos. Zoo episode 11 season 3. First time buyers program auto. Fases de la dieta kot derivative functions. Hotel mekele athiopien. The present invention relates to 2-cyclopropyl-thiazole derivatives selected from formula I and their use as pharmaceuticals. The invention also relates to aspects that include the processes for the preparation of the compounds and pharmaceutical compositions containing one or more compounds of formula Iand especially their use as orexin receptor antagonists.

The orexins are produced in particular neurons of the lateral hypothalamus and bind to G-protein coupled receptors OX1 and OX2 receptors. Fases de la dieta kot has been found that orexins stimulate food consumption in rats, which suggests a physiological role for these peptides as mediators in the central feedback mechanism that regulates feeding Fases de la dieta kot Sakurai T. On the other hand, it was also observed that oxerins regulate sleep and sleep conditions that potentially open up new therapeutic approaches for narcoleptic patients as well as for insomnia and other sleep disorders Chemelli RM et al.

The Fases de la dieta kot receptors are found in the brain of mammals and can have numerous implications in pathologies, as is known from the literature. The present invention provides 2-cyclopropyl-thiazole derivatives, which are non-peptide antagonists of human orexin receptors.

These compounds are in particular of potential use in the treatment of, for example, eating disorders, drinking disorders, sleep disorders or cognitive dysfunctions in psychiatric and neurological disorders. To date, several low molecular weight compounds are known that have the potential to specifically antagonize OX1 or OX2, or both receptors at the same time.

B represents phenyl, in click here the phenyl ring is unsubstituted or mono, di or trisubstituted, in which the substituents are independently selected from the group consisting of C alkyl, C alkoxy, trifluoromethyl and Fases de la dieta kot Y. R1 represents aryl or heterocyclyl, in which the aryl or heterocyclyl is independently unsubstituted or mono, di or trisubstituted, in which the substituents are independently selected from the group consisting of C alkyl, C alkoxyhalogen, cyano, trifluoromethyl and -NH-CO C alkyl.

Y represents CH2 n, in which n represents 0 or 1; B represents phenyl, in which the phenyl ring is unsubstituted or mono, di or trisubstituted, in which the substituents are independently selected from the group consisting of C alkyl, C alkoxy, trifluoromethyl and halogen; Y. R1 represents aryl or heterocyclyl, in which the aryl Fases de la dieta kot heterocyclyl is independently unsubstituted or mono, di or trisubstituted, Fases de la dieta kot which the substituents are independently selected from the group consisting of C alkyl, C alkoxyhalogen, cyano and trifluoromethyl.

Compounds Fases de la dieta kot formula I and Ia; see below and their pharmaceutically acceptable salts are also part of the invention. In the present patent application, a dotted line shows the point of attachment of the radical drawn. For example, the radical drawn below.

The general terms used above and which will be used hereafter in this document preferably have, within this description, the following meanings, unless otherwise indicated:. The term "halogen" means fluorine, chlorine or bromine; preferably it means fluorine and chlorine, especially fluorine. Examples of C alkyl groups are methyl, ethyl, propyl, isopropyl, Fases de la dieta kot, isobutyl, sec-butyl and tert-butyl.

Those Fases de la dieta kot preference are methyl and ethyl. For B, the term " C alkyl" has the above meaning; preferably it means methyl and ethyl, especially methyl. The term " Fases de la dieta kot alkoxy", alone or Fases de la dieta kot combination, means a group of the formula C -O-alkyl in which the term " C alkyl" has the meaning given above, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, secbutoxy and tert-butoxy.

Preferred are methoxy and ethoxy, especially methoxy. The term "aryl", alone or in combination, means a phenyl group or a naphthyl group. Preferably it is a phenyl group. The aryl group is unsubstituted or mono, di or trisubstituted, in which the substituents are independently selected from the group consisting of C alkyl, C alkoxy, halogen, cyano, trifluoromethyl and -NH-COalkyl C In particular, the aryl group is unsubstituted or mono, di or trisubstituted, in which the substituents are independently selected from the group consisting of C alkyl, C alkoxy, trifluoromethyl and halogen.

Examples in which R 1 represents "aryl" are phenyl, naphthyl in particular 1-naphthyl2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 4-methyltrifluoromethylphenyl, 2-methoxyphenyl, 3methoxyphenyl, 4-methoxyphenyl, 2,5-dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3-fluoromethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 3-chloromethylphenyl, 2-chloro- 3-methylphenyl, 2-chlorofluorophenyl, 2-bromophenyl, 3-bromophenyl, 4bromophenyl, 2-bromomethylphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2trifluoromethylphenyl, 3-trifluoromethylphenyl, trifluoromethylphenyl and 3-acetylaminophenyl.

In particular, the examples in which R 1 represents "aryl" are phenyl, naphthyl in particular 1-naphthyl3-methylphenyl, 2,3-dimethylphenyl, 4-methyltrifluoromethylphenyl, 3-methoxyphenyl, 2,5 -dimethoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3-fluoromethylphenyl, 3-chlorophenyl, 3,4-dichlorophenyl, 3-chloromethylphenyl, 2-chloromethylphenyl, 2-chloro -3fluorophenyl, 3-bromophenyl, 2-bromomethylphenyl and 3-trifluoromethylphenyl.

Most preferred are 3-methylphenyl, 3-chlorophenyl and 3-bromophenyl. Examples in which "B" represents "phenyl", in which the phenyl ring is unsubstituted Fases de la dieta kot mono, di or trisubstituted, in which the substituents are independently selected from the group consisting of C alkyl, alkoxy Ctrifluoromethyl and halogen "are: phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 2-methoxyphenyl3-methoxyphenyl, 4-methoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-dipluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 3,4-dichlorophenyl, 2-bromophenyl, 3 -bromophenyl, 4-bromophenyl, 2-trifluoromethylophenyl, Fases de la dieta kot and here. In particular, the Fases de la dieta kot are phenyl, 3-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl and 3trifluoromethylphenyl.

The term "heterocyclyl", alone or in combination, means an aromatic, monocyclic or bicyclic ring, of 5 to Fases de la dieta kot members, containing for example 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur.

Examples of such heterocyclyl groups are furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, indolyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, indazolylbenzimidazolyl, benzoxazolyl, bencisoxazolyl, benzothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, naphthyridinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, pyrazolo [1,5] pyrazolo [1,5] pyrazolo [1,5] [1,2-a] pyridyl and especially imidazo [2,1-b] thiazolyl.

In addition to the list of examples above, other examples are benzoisothiazolyl, thienopyrazinyl, furopyrrolyl and pyrrolo [2,1-b] thiazolyl. In another embodiment, the preferred examples are isoxazolyl, pyrazolyl, pyridyl, indolyl, benzofuranyl, indazolyl, bencisoxazolyl, quinolinyl, isoquinolinyl, imidazo [1,2a] pyridyl, thienopyrazinyl, furopyrrolyl and especially imidazo [2,1 -b] thiazolyl.

Most preferred are indolyl, benzofuranyl, indazolyl, bencisoxazolyl, quinolinyl and especially imidazo [2,1-b] thiazolyl.

'+_.E(b)+"

The heterocyclyl groups mentioned above are Fases de la dieta kot or mono, di or Fases de la dieta kot, in which the substituents are independently selected from the group consisting of C Fases de la dieta kot, C alkoxy, halogen, cyano, trifluoromethyl and Fases de la dieta kot CO-C alkyl. In particular, the heterocyclyl groups mentioned above are unsubstituted, mono, di or trisubstituted, in which the substituents are independently selected from the group consisting of C alkyl, C alkoxy, halogen and trifluoromethyl.

Preferably, the heterocyclyl groups mentioned Fases de la dieta kot are unsubstituted, mono or disubstituted, in which the substituents are independently selected from the group consisting of C alkyl and halogen.

In another preferred embodiment, the aforementioned groups are unsubstituted or monosubstituted, in which the substituent is selected from C14 alkyl especially the substituent is methyl. In another embodiment, preferred examples of such heterocyclyl groups are selected from the group consisting of isoxazolyl, pyrazolyl, pyridinyl, indoleyl, indoleyl, indole yl, indoleyl, benzofuranyl, indazolyl, bencisoxazolyl, quinolineyl, isoquinolineyl, imidazo [1,2-a] pyridine-3 -yl, imidazo [2,1-b] thiazol-5yl; imidazo [2,1-b] thiazolyl, thieno [2,3-b] pyrazinyl, and 4H-furo [3,2-b] pyrrolyl especially imidazo [21-b] thiazolyl ; wherein the heterocyclyl groups mentioned above are unsubstituted, mono or disubstituted, in which the substituents are independently selected from C alkyl and visit web page especially C14 alkyl.

In particular, the heterocyclyl groups mentioned above as used Fases de la dieta kot the "R1" substituent are preferably substituted as follows: the isoxazolyl groups are monosubstituted with C alkyl; the pyrazolyl groups are disubstituted with C alkyl; pyridyl groups are monosubstituted with C alkyl; the indolyl groups are unsubstituted, or independently mono or disubstituted with C alkyl or halogen especially unsubstituted, Fases de la dieta kot mono or disubstituted with methyl ; benzofuranyl groups are unsubstituted; indazolyl groups are unsubstituted, or monosubstituted with C alkyl especially methyl ; the bencisoxazolyl groups are unsubstituted; quinolinyl groups are unsubstituted; isoquinolinyl groups are unsubstituted; the imidazo [1,2a] pyridinyl groups are unsubstituted; the imidazo [2,1-b] thiazolyl groups are unsubstituted, or monosubstituted with C alkyl; thienopyrazinyl groups are unsubstituted; and the furopyrrolyl groups are monosubstituted with C alkyl.

In the case where R1 is different from "aryl" and "heterocyclyl", it has a 2,3-dihydro-benzofuranyl group, a benzo [1,3] dioxolyl group, a 2,3-dihydrobenzo [1,4] dioxinyl group, a 4H-benzo [1,3] dioxinyl group, a 2H-chromenyl group, a chromanyl group, a 2,3-dihydro-thieno [3,4-b] [1,4] dioxinyl group, a 3,4 group -dihydro-2Hbenzo [1,4] oxazinyl or an indenyl group. In particular, it has a 2,3-dihydrobenzofuranyl group, a benzo [1,3] dioxolyl group, a 2,3-dihydro-benzo [1,4] dioxinyl group, a 4H-benzo [1,3] dioxinyl group, Fases de la dieta kot 2,3-dihydro-thieno [3,4-b] [1,4] dioxinyl group, a 3,4-dihydro-2H-benzo [1,4] oxazinyl click at this page or an indenyl group.

It preferably has a 2,3-dihydro-benzofuranyl group, a benzo [1,3] dioxolyl group, a 2,3-dihydrobenzo [1,4] dioxinyl group or a 4H-benzo [1,3] dioxinyl group. More preferably, it has a 2,3-dihydro-benzofuranyl group or a 2,3-dihydro-benzo [1,4] dioxinyl group. The groups mentioned above as Fases de la dieta kot for the R1 substituent are unsubstituted or mono or di substituted, in which the substituents are independently selected from the group consisting of C alkyl, C alkoxy and halogen.

Preferably, the groups mentioned above are unsubstituted or monosubstituted with C alkyl. In particular, in the case where R1 is different from "aryl" and "heterocyclyl", the groups mentioned above as used for the substituent "R1" have points of attachment to the rest of the molecule, and are preferably substituted Fases de la dieta kot follows way: 2,3-dihydro-benzofuranyl groups especially 2,3-dihydro-benzofuranyl.

Preferably, in the case where R1 is different from "aryl" and "heterocyclyl", it represents. R1 represents phenyl, which is mono preferably or disubstituted; wherein preferably one substituent is in position 3 and, if present, the other substituent is in position 4; wherein the Fases de la dieta kot are independently selected from methoxy, chlorine, bromine and methyl especially chlorine, bromine and methyl.

R1 represents heterocyclyl, in which the heterocyclyl is Fases de la dieta kot from the group consisting of indolyl, benzofuranyl, indazolyl, bencisoxazolyl, quinolinyl Fases de la dieta kot especially imidazo [2,1-b] thiazolyl, wherein said heterocyclyl is unsubstituted or monosubstituted, wherein the substituent is selected from C alkyl.

R1 represents heterocyclyl, in which the heterocyclyl is selected from the group consisting of indolyl, benzofuranyl, indazolyl, bencisoxazolyl, quinolinyl and especially imidazo [2,1-b] thiazolyl, wherein said heterocyclyl is unsubstituted or monosubstituted, wherein the substituent is selected from C alkyl.

R1 represents a 2,3-dihydro-benzofuranyl group or a 2,3-dihydrobenzo [1,4] dioxinyl group, in which the groups are unsubstituted. Y represents CH2 n, in which n represents 0 or 1; B represents phenyl, in which the phenyl ring is monosubstituted with C alkyl such as, in particular, methyltrifluoromethyl or halogen such as, in particular, fluorine or chlorine ; Y. R1 represents phenyl, which is monosubstituted with C alkyl such as, in particular, methyl or halogen such as, in particular, chlorine or bromine ; or unsubstituted naphthyl such as, in particular, 1-naphthyl ; Fases de la dieta kot R1 is selected from the following groups:.

The compounds of formula I may contain one or more stereogenic or asymmetric centers, such as one or more asymmetric carbon atoms. The compounds of formula I may, therefore, be present as mixtures of stereoisomers or preferably as pure stereoisomers. Mixtures of stereoisomers can be separated in a manner known to those skilled in the art.

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Reference may be made to "Salts selection for basic drugs", Int. When the plural Fases de la dieta kot is used for compounds, salts and pharmaceutical compositions, diseases and the like, it is also intended to refer to a single compound, salt and the like. The present invention also relates to the use of a compound of formula I for the preparation of a pharmaceutical composition for the prevention or treatment of the diseases and disorders mentioned herein.

The present invention also further relates to pharmaceutical compositions comprising a compound of formula Ior a pharmaceutically acceptable Fases de la dieta kot thereof, and a pharmaceutically acceptable carrier. Eating disorders can be defined as comprising metabolic dysfunction; poorly regulated appetite control; compulsive Fases de la dieta kot emetobulimia or anorexia nervosa. Pathologically modified food intake may be the result of an altered appetite attraction or aversion to food ; the altered energy balance intake vs.

Drink disorders include polydipsia in psychiatric disorders and all other types of excessive fluid intake. Sleep disorders include all types of parasomnias, insomnia, narcolepsy and other disorders of excessive sleepiness, sleep-related dystonia; Restless legs syndrome; sleep apnea; time maladjustment Clinica monumental santo domingo telefono syndrome of changes in work shifts, delayed or advanced sleep phase syndrome, or insomnia related to psychiatric disorders.

Insomnia is defined as Fases de la dieta kot sleep disorders associated with aging; intermittent treatment of chronic insomnia; temporary situational insomnia new environment, noise or short-term insomnia due to stress; sadness; pain or ailments Insomnia also includes stress-related syndromes, including post-traumatic stress disorders as well as other types and subtypes of anxiety disorders, such as generalized anxiety, obsessive compulsive disorder, panic attacks and all types of phobic anxiety and avoidance; The use, abuse, search and reintegration of psychoactive substances is defined as all types of psychological or physical addictions and their related tolerance and dependence components.

Cognitive dysfunctions include deficits of all types Fases de la dieta kot attention, learning and memory functions that occur transiently or chronically in the normal, healthy, young, adult or aged population, Fases de la dieta kot that also occur transiently or chronically in psychiatric, neurological, cardiovascular and immunological disorders.

The Fases de la dieta kot invention also relates to Fases de la dieta kot method for the prevention or treatment of a disease or disorder mentioned herein, which comprises administering to a subject a pharmaceutically active amount of a compound of formula I.

Another aspect of the invention is a process for the preparation of compounds of formula I. The compounds according to the formula I of the present invention can be prepared according to the general sequence of reactions summarized in the following schemes, in which B, Fases de la dieta kot and R1 are as defined in the description of the formula I.

The compounds obtained can also be converted into their pharmaceutically acceptable salts in a manner known per se. In general, all chemical check this out can be carried out according to well-known conventional Fases de la dieta kot as described in the literature Fases de la dieta kot as described in the procedures or in the experimental part below. Route 1: The synthesis of the final compounds begins from N-Boc-protected 1-aminoomethylazacycloalkane derivatives 1 commercially available that were coupled with carboxylic acid derivatives 2 commercially available or prepared as described in I-Chemistry, Section A.

Deprotection under conditions conventional with a solution of. The final bis-amide 6 compounds were prepared Fases de la dieta kot means of a second amide bond formation reaction under conditions comparable to those described above using the carboxylic acid derivatives 5 prepared as described in Schemes 2 and 3 and in the experimental partA. The carboxylic acid derivatives 16, if not commercially available, were synthesized for example according to scheme 2 and scheme 3.

Scheme 2: Synthesis of thiazolcarboxylic acid Fases de la dieta kot, in which B is as defined above. Source of the ester Fases de la dieta kot with an aqueous solution of, for example, NaOH in a solvent such as MeOH resulted in the formation of the desired carboxylic acids Scheme 3: Synthesis of thiazolcarboxylic acid derivatives, in which B is as defined above and in which the cyclopropyl residue is introduced by a reaction of.

The introduction of the. Eicher, S. The R 1 -COOH carboxylic acid derivatives representing a derivative of the imidazo [2,1-b] thiazolcarboxylic acid are commercially available or can be synthesized according to scheme 4. Scheme 4: Synthesis of R1-COOH carboxylic acids representing a derivative of imidazo [2,1-b] thiazolcarboxylic acid. Transformation to the ester 22 can be achieved with bromoacetaldehyde, which can be generated in situ from diethyl acetal bromoacetaldehyde under acidity conditions.

After saponification with bases such as NaOH, the desired acid 23 can be obtained. Via B: By heating a compound of structure 24 with N, N-dimethylformamide dimethylacetal in a solvent such as toluene, the formamidine derivatives go here can be obtained. These can be alkylated with ethyl bromoacetate giving thiazolium bromide 26which can be cycled to the ester 27 with strong bases such as DBU.

Saponification of the ester function using methods known in the art, such. The R 1 -COOH carboxylic acid derivatives representing a derivative of the pyrrolo [2,1-b] thiazolcarboxylic acid can be synthesized according Fases de la dieta kot scheme 5. By means of the reaction of 2-methylsulfanylthiazole 29 with trimethylsilylmethyl trifluoromethanesulfonate followed by the cyclisation of the Fases de la dieta kot thiazolinium salt, by reaction with ethyl propiolate in the presence Fases de la dieta kot cesium fluoride, the.

Et al. Scheme 5: Synthesis of R1-COOH carboxylic acids representing a derivative of pyrrolo [2,1-b] thiazolcarboxylic acid. The bromination of 30 by reaction with NBS followed by the methylation of the resulting crude ethyl 6-bromo-pyrrolo [2,1-b] thiazolcarboxylate by reaction with dimethylcinc in the presence of such a palladium catalyst as Pd dppf Cl2 gave the ester See more acid derivatives R1-COOH representing a 3,4-dihydro2H-benzo [1,4] oxazinyl derivative can be synthesized according to the literature, according to schemes 6 and.

Esterification of 3-hydroxy-anthranilic acid 34 with sulfuric acid concentrated in EtOH provided the corresponding ethyl ester Cyclization with acetyl chloride in the presence of a base such as K2CO3 in a solvent such as DMF provided the 3-oxo-3,4-dihydro-2H-benzo [1,4] oxazine derivatives