UA79808C2 - 1,4-diazabicycloalkane derivatives, their preparation and use - Google Patents

Abstract

This invention relates to novel 1,4-diazabicy-cloalkane derivatives of formula (I): any of its enantiomers or any mixture of its enantiomers, or a pharmaceutically-acceptable addition salt thereof, or an N-oxide thereof, and their use in the manufacture of pharmaceutical compositions. The compounds of the invention are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

Description

Description of the invention

This invention relates to new 1,4-diazadicycloalkane derivatives and their use in the production of 2 pharmaceutical compositions. The compounds of the invention were found to be cholinergic ligands for nicotinic acetylcholine receptors and modulators of monoamine receptors and transporters.

Due to their pharmacological profile, the compounds of the invention may be useful in the treatment of diseases or disorders associated with the cholinergic system of the central nervous system, peripheral nervous system, diseases or disorders associated with smooth muscle contraction, endocrine diseases or disorders, diseases or 70 disorders associated with neurodegeneration, diseases or disorders associated with inflammation, pain, withdrawal symptoms caused by cessation of chemical abuse.

The endogenous cholinergic neurotransmitter, acetylcholine, manifests its biological effects through two types of cholinergic receptors, muscarinic acetylcholine receptors (tACsSNK) and nicotinic acetylcholine receptors (pASPs). 12 It is well established that muscarinic acetylcholine receptors quantitatively dominate nicotinic acetylcholine receptors in an area of the brain important for memory and cognition, and much research aimed at developing agents for the treatment of memory-related disorders has focused on the synthesis of modulators. muscarinic acetylcholine receptors.

Now, however, there is interest in the development of pASNK modulators. Several diseases are associated with degeneration of the cholinergic system, namely senile dementia of the Alzheimer type, vascular dementia, and cognitive impairment due to disease from organic brain damage associated with alcoholism. Indeed, several central nervous system disorders can be attributed to cholinergic deficiency, dopaminergic deficiency, adrenergic deficiency, or serotonergic deficiency.

IMUO 00/34279 (Zapoii-Zupipeiaro)| describes derivatives of 1,4-diazadicyclo|3,2,2|nonane, which have activity with regard to nicotinic receptors. Only six-membered heteroaryl derivatives are described. Five-membered heteroaryl (U derivatives of the present invention are not described.

IMUO 01/55150 (Zapoii-Zupipeiaro)| describes 1,4-diazadicyclo|3,2,2|nonane derivatives having activity against nicotinic receptors. Only dicyclic heteroaryl derivatives are described. Monocyclic heteroaryl derivatives of the present invention are not described. co

IMO 01/92259 (Zapoii-zupipeiaro)| describes derivatives of 1,4-diazadicyclo/3,2,2|nonane having "3" activity against nicotinic receptors. Only phenylisoxazole derivatives are described. Thiadiazole derivatives of the present invention are not described. co

IMO 01/92260 (Zapoii-5upipeiaro)| describes derivatives of 1,4-diazadicyclo|3,2,2|)nonane, which have Fu activity against nicotinic receptors. Thiadiazole derivatives of the present invention are not described. 30 (EP 1219622 (Rijheg Tsa)) describes derivatives of 1,4-diazadicyclo|3,2,2|nonane, which have activity against nicotinic receptors. Derivatives of monocyclic heteroaryls of the present invention are not described.

The presented invention is directed to new modulators of nicotinic and/or monoamine receptors, if these modulators are useful for the treatment of diseases or disorders associated with cholinergic receptors, and "in particular, nicotinic acetylcholine receptor (PNAC), monoamine receptors 5-NTK, SAC and MEK, Z and biogenic amine transporters for 5-HT, BA and ME. c As a result of their pharmacological profile, the compounds of the invention may be useful in the treatment of diseases or disorders related to the cholinergic system of the central nervous system, peripheral nervous system, diseases or disorders associated with contraction of smooth muscles, endocrine diseases or disorders, diseases or disorders associated with neurodegeneration, diseases or disorders associated with inflammation, pain, withdrawal symptoms caused by cessation of chemical abuse. 7 The compounds of the invention may also be useful as diagnostic tools for monitoring in various (se)diagnostic methods, and in particular for ip mimo receptor mapping (neuroimaging), and may be used in labeled or unlabeled form.

According to the first aspect, the invention relates to new 1,4-diazadicycloalkane derivatives of the formula

F! any of their enantiomers or any mixture of their enantiomers, or their pharmaceutically acceptable addition salt, or their M-oxide, where o n is 1, 2 or 3;

X represents 0, 5 or be; and 60 Ag represents a carbocyclic aromatic (aryl) group, or a heterocyclic aromatic (heteroaryl) group, which may optionally be substituted with one or more substituents selected from the group: alkyl, cycloalkyl, cycloalkyl-alkyl, alkenyl, alkynyl, alkyl . According to the second aspect, the invention relates to pharmaceutical compositions containing a therapeutically effective amount of a 1,4-diazadicycloalkane derivative of the invention, its enantiomer or a mixture of enantiomers,

or a pharmaceutically acceptable addition salt thereof, together with at least one pharmaceutically acceptable carrier or diluent.

In another aspect, the invention relates to the use of a 1,4-diazadicycloalkane derivative of the invention, or an enantiomer or mixture of enantiomers, or a pharmaceutically acceptable addition salt thereof, for the manufacture of a medicament for the treatment, prevention or amelioration of a disease, disorder or condition which is sensitive to modulation of cholinergic receptors and/or monoamine receptors.

According to yet another aspect, the invention relates to a method of treating, preventing, or ameliorating a disease, disorder, or condition in an animal, including a human, if the disease or disorder is responsive to modulation of 7/0 X-cholinergic receptors and/or monoamine receptors, the method comprising the step of administering to such an animal organism in need thereof, a therapeutically effective amount of a 1,4-diazadicycloalkane derivative of the invention, any of its enantiomers or any mixture of its enantiomers, or its pharmaceutically acceptable addition salt.

Other objects of the invention will be apparent to those skilled in the art from the following detailed description and examples.

According to the first aspect, the presented invention relates to new 1,4-diazadicycloalkane derivatives represented by the general formula and whether in

And c - any of their enantiomers or any mixture of their enantiomers, or their pharmaceutically acceptable c additive salt, or their M-oxide, where o n is equal to 1, 2 or 3;

X represents 0, 5 or be; and

Ag represents a carbocyclic aromatic (aryl) group, or a heterocyclic aromatic (heteroaryl) group, which may optionally be substituted with one or more substituents selected from the group: alkyl, cycloalkyl, (ee) cycloalkyl-alkyl, alkenyl, alkynyl, carboxyl, alkoxy-alkyl, alkoxy-alkyl, cycloalkyl, cycloalkyl-cycloalkyl, cycloalkyl-alkyl, halogen, CE3, CM, MO», MH», carboxyl, carbamoyl, amido, o-sulfamoyl, phenyl and benzyl. (uh)

In an even better embodiment, Ag represents a carbocyclic aromatic (aryl) group, or a heterocyclic aromatic (heteroaryl) group, which may, as an option, be substituted by one or more substituents, F selected from the group: alkyl, alkyl, halogen, CE5, CM, MO ", MN", and phenyl. -

In the first preferred embodiment, the compound of the invention is a derivative of 1,4-diazadicyclo|Z,2,2|nonane, represented by formula II. : with ;" where

X and Ag are defined above. In an even better embodiment, the compound of the invention is a derivative of 4-thiadiazolyl-1,4-diazadicyclo|Z,2,2Inonane,

Ge) is represented by the formula ЯЙ ki so Shk U. (av) 20 g:z du vu

IR f) where Ag is defined above.

In another preferred embodiment, the compound of the invention is a derivative of 4-oxadiazolyl-1,4-diazadicyclo|3,2,-|nonane, represented by the formula IM (F, where Ag is defined above. ka In the second preferred embodiment, the carbocyclic aromatic (aryl) group is optionally substituted with phenyl, indenyl, naphthyl, azulenyl, fluorenyl, or anthracenyl.In an even more preferred embodiment, the carbocyclic aromatic group is phenyl, optionally substituted with one or two substituents selected from the group consisting of alkyl, cycloalkyl, alkyl, and alkyl.

substituted with one or two substituents selected from the group: alkyl, cycloalkyl, cycloalkyl-alkyl, alkyl, cycloalkyl, halogen, CEz, CM, MO", MH", carboxyl, carbamoyl, amido, sulfamoyl, phenyl and benzyl.

In an even more preferred embodiment, the carbocyclic aromatic group is phenyl, optionally substituted with one or two substituents selected from the group consisting of alkyl, alkoxy, halogen, C3, CM, MO", MH", and phenyl.

In the best embodiment, the 4-thiadiazolyl-1,4-diazadicyclo!|3,2,2|nonane derivative of the invention is 4-(5-Phenyl-1,3,4-thiadiazol-2-yl)-1,4-diazadicyclo! |IZ,2,2Inonane; or an enantiomer thereof or a mixture of enantiomers thereof, or a pharmaceutically acceptable addition salt thereof, or an M-oxide thereof; 70 and the 4-oxadiazolyl-1,4-diazadicyclo|3,2,2|nonane derivative of the invention is 4-(5-Phenyl-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo|3, 2,2|nonane; 4-(5-(3-Methoxyphenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5--4-Methoxyphenyl)-1, 3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl|-1, 4-Diazadicyclo!|3,2,2Inonane; 4-N5-(4-Phenyl-phenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadiylcyclo[3,2,2|nonane; or 4-(5-(-2-Naphthyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; or an enantiomer thereof or a mixture of enantiomers thereof, or its pharmaceutically acceptable addition salt, or its M-oxide.

In a third preferred embodiment, the heterocyclic aromatic (heteroaryl) group is optionally a substituted 2o aromatic monocyclic heterocyclic group, or alternatively a substituted aromatic di- or poly-heterocyclic heterocyclic group, these heterocyclic groups include benzo-fused 5- and b- membered heterocyclic rings containing one or more heteroatoms selected from nitrogen (M), oxygen (0), sulfur (5) and/or selenium (5e).

In an even better embodiment, the aromatic monocyclic heterocyclic group is, alternatively, a disubstituted aromatic 95- or b-membered heterocyclic monocyclic group.

In an even better embodiment, alternatively, the substituted aromatic monocyclic heterocyclic group is i) furanyl, in particular 2-furanyl or 3-furanyl; thienyl, in particular 2-thienyl or 3-thienyl; selenophenyl, in particular 2-selenophenyl or 3-selenophenyl; pyrrolyl (azolyl), in particular 2-pyrrolyl or 3-pyrrolyl; oxazolyl, in particular oxazol-2-, 4- or b5-yl; thiazolyl, in particular thiazol-2-, 4- or b5-yl; imidazolyl, in particular 2-imidazolyl or iso-4-imidazolyl; pyrazolyl, in particular 3-pyrazolyl or 4-pyrazolyl; isoxazolyl, in particular isoxazol-3-, 4- or 5-yl; isothiazolyl, in particular isothiazol-3-, 4-or 5-yl; oxadiazolyl, in particular 1,2,3-oxadiazol-4- or 5-yl, or o 1,3,4-oxadiazol-2-yl; triazolyl, in particular 1,2,3-triazol-4-yl or 1,2,4-triazol-3-yl; thiadiazolyl, in particular with 1,2,3-thiadiazol-4- or 5-yl, or 1,3,4-thiadiazol-2-yl; o pyridinyl, in particular 2-, 3- or 4-pyridinyl; pyridazinyl, in particular 3- or 4-pyridazinyl; pyrimidinyl, in particular 2-, 4-or 5-pyrimidinyl; pyrazinyl, in particular (22) 2- or 3-pyrazinyl; and triazinyl, particularly 1,2,4- or 1,3,5-triazinyl. uh-

In another preferred embodiment, the compound of the invention is a 4-thiadiazolyl-1,4-diazadicyclo|3,2,2|nonane derivative of the formula

AI, where Ag represents, as an option, a substituted aromatic monocyclic heterocycle selected from the group: selenophenyl, in particular 2-selenophenyl or 3-selenophenyl; imidazolyl, in particular 2-imidazolyl, 4-imidazolyl or 5-imidazolyl; pyrazolyl, in particular 3-pyrazolyl, 4-pyrazolyl or 5B-pyrazolyl; thiazolyl, in particular 2-thiazolyl or "5-thiazolyl; isothiazolyl, in particular 3-isothiazolyl, 4-isothiazolyl or β-isothiazolyl; oxadiazolyl, in particular pts) with 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-b-yl or 1,3,4-oxadiazol-2-yl; furazanil, in particular Z-furazanil; . triazolyl, in particular 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, 1,2,4-riazol-3-yl or /1,2,4-triazol-5 -il; and? thiadiazolyl, in particular 1,3,4-thiadiazol-2-yl, 1,2,4-thiadiazol-3-yl or 1,2,4-thiadiazol-5-yl; pyridazinyl, in particular 3-pyridazinyl or 4-pyridazinyl; and triazinyl, particularly 1,3,5-triazin-2-yl.

In an even better embodiment, the aromatic 5- or β-linked monocyclic heterocycle is optionally substituted by -I with one or two substituents selected from the group: alkyl, alkoxy, halogen, CEz, CM, MO", MH", and phenyl.

In the best embodiment, the 4-thiadiazolyl-1,4-diazadicyclo!|3,2,2|nonane derivative of the invention is se) 4-(5--2-Selenophenyl)-1,3,4-thiadiazol-2-yl|- 1,4-diazadicyclo!|C,2,2Inonane;

Go! 4-(5-(3-Selenophenyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(2-imidazolyl)-1, 3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2A|nonane; o 4-(5-(4-imidazolyl)-1,3,4-thiadiazol-2-yl|- 1,4-diazadicyclo|3,2,2A|nonane; c 4-(5-(5-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2A |nonane; 4-(5-(1-Methyl-2-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5- (1-Methyl-4-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(1-Methyl-5-imidazolyl) )-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(3-Pyrazolyl)-1,3,4-thiadiazol-2- yl|-1,4-diazadicyclo!|3,2,2Inonane; (F) 4-(5-(4-Pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!III ,2,2Inonane; ka 4-(5-(5-Pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!III,2,2Inonane; 4-(5-(1- Methyl-3-pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; in 4-(5-(1-Methyl-4-pyrazolyl)-1 ,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1-Methyl-5-pyrazolyl)-1,3,4-thiadiazole-2- yl|-1,4-diazadicyclo!|Z,2,2Inone an 4-(5-(2-Thiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(4-Thiazolyl)-1 ,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(5-Thiazolyl)-1,3,4-thiadiazol-2-yl|- 1,4-diazadicyclo|3,2,2I|nonane; 65 4-(5-(3-isothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I |nonane; 4-(5-(4-isothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane;

4-(5-(5-isothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1,2,3- Oxadizol-4-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1,2,3-Oxadizol-5 -yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(1,3,4-oxadizol-2-yl)-1, 3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(3-Furazanyl)-1,3,4-thiadiazol-2-yl|-1 ,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1,2,3-Triazol-4-yl)-1,3,4-thiadiazol-2-ylI|-1,4-diazadicyclo !|3,2,2|nonane; 4-(5-(1,2,3-Triazol-5-yl)-1,3,4-thiadiazol-2-ylI|-1,4-diazadicyclo!|C ,2,2|nonane; 4-(5-(1-Methyl-1,2,3-triazol-4-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3 ,2,2I|nonane; 70 4-(5-(1-Methyl-1,2,3-triazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo| 3,2,2Nonane; 4-(5-(1,2,4-Triazol-3-yl)-1,3,4-thiadiazol-2-ylN-1,4-diazadicyclo!|C,2 ,2|nonane; 4-(5-(1,2,4-Triazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|C,2,2| nonane; 4-(5-(1-Methyl-1,2,4-triazol-3-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I| nonane; 4-(5-(1-Methyl-1,2,4-triazole-5 -yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1,3,4-Thiadiazol-2-yl)-1,3,4-thiadiazol-2-yl)-1,4-diazadicyclo!III,2,2Inonane; 4-(5-( 1,2,4-Thiadiazol-3-yl)-1,3,4-thiadiazol-2-yl)-1,4-diazadicyclo!3,2,2-inonane; 4-(5-(1,2,4- Thiadiazol-5-yl)-1,3,4-thiadiazol-2-yl]-1,4-diazadicyclo!3,2,2-inonane; 4-(5-(3-Pyridazinyl)-1,3,4-thiadiazole -2-yl|-1,4-diazadicyclo|312I2I|nonane; 4-I5-(4-Pyridazinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,A |nonane; or 4-(5-(1,3,5-Triazin-2-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|C,2,2|nonane or an enantiomer thereof or a mixture of enantiomers thereof, or a pharmaceutically acceptable addition salt thereof, or an M-oxide thereof.

In another preferred embodiment, the compound of the invention is a 4-oxadiazolyl-1,4-diazadicyclo|3,2,2|nonane derivative of the formula IM, where Ag represents, as an option, a substituted aromatic monocyclic heterocycle selected from the group: furyl, in particular 2-furyl or 3-furyl; pyridyl, in particular 2-pyridyl, 3-pyridyl or 4-pyridyl; thienyl, in particular 2-thienyl or 3-thienyl; pyrrolyl, in particular 2-pyrrolyl or 3-pyrrolyl; pyrimidinyl, in particular 2-pyrimidinyl, i) 4-pyrimidinyl or 5-pyrimidinyl; pyrazinil; selenophenyl, in particular 2-selenophenyl or 3-selenophenyl; oxazolyl, in particular 2-oxazolyl, 4-oxazolyl or 5-oxazolyl; isoxazolyl, in particular 3-isoxazolyl, 4-isoxazolyl or 5B-isoxazolyl; imidazolyl, in particular 2-imidazolyl, 4-imidazolyl or 5B-imidazolyl; pyrazolyl, in particular iso 3-pyrazolyl, 4-pyrazolyl or B-pyrazolyl; thiazolyl, in particular 2-thiazolyl, 4-thiazolyl or 5-thiazolyl; isothiazolyl, in particular C-isothiazolyl, 4-isothiazolyl or B-isothiazolyl; oxadiazolyl, in particular o 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-b-yl or 1,3,4-oxadiazol-2-yl; furazanil, in particular Z-furazanil; co triazolyl, in particular 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, 1,2,4--riazol-3-yl or /1,2,4-triazol- 5-il; thiadiazolyl, in particular 1,3,4-thiadiazol-2-yl, 1,2,4-thiadiazol-3-yl or 1,2,4-thiadiazol-5-yl; pyridazinyl, (22) especially 3-pyridazinyl or 4-pyridazinyl; tatriazinip, in particular 1,3,5-triazin-2-yl. uh-

In the best embodiment, the 4-oxadiazolyl-1,4-diazadicyclo|3,2,2|nonane derivative of the invention is 4-(5-(2-Furyl)-1,3,4-oxadiazol-2-yl|-1,4 -diazadicyclo!|3,2,2|nonane; 4-(5-(3-Furyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane 4-(5-(2-Pyridyl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane; « 4-(5-(3-Pyridyl) )-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; with c 4-(5-(4-Pyridyl)-1,3,4-oxadiazole -2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(2-Thienyl)-1,3,4-oxadiazol-2-yl|-1,4- 4-(5-(3-Thienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,A|nonane; 4-(5-(2-Pyrrolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(3-Pyrrolyl)-1, 3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane;-I 4-(5-(1-Methyl-2-pyrrolyl)-1,3,4-oxadiazole-2 -yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1-Methyl-3-pyrrolyl)-1,3,4-oxadiazol-2-yl|-1,4 -diazadicyclo!|3,2,2|nonane; se) 4-(5-(2-Pyrimidinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,A| nonane;

Go! 4-(5-(4-Pyrimidinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,A|nonane; 4-(5-(5-Pyrimidinyl)-1 ,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,A|nonane; o 4-(5-(Pyrazinyl)-1,3,4-oxadiazol-2-yl|-1 ,4-diazadicyclo!|3,2,2Inonane; c 4-(5--2-Selenophenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane 4-(5--3-Selenophenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(-2-Oxazolyl) -1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!III,2,2Inonane; 4-(5-(4-Oxazolyl)-1,3,4-oxadiazol-2-yl|- 1,4-diazadicyclo!III,2,2Inonane; 4-(5-(5-Oxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!III,2,2Inonane; (F ) 4-(5-(3-isoxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; ka 4-(5-(4-isoxazolyl) -1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(5-isoxazolyl)-1,3,4-oxadiazol-2-yl |-1,4-diazadicyclo|3,2,2|nonane; in 4-(5-(2-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|Z, 2,2|nonane; 4-(5-(4-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5- (5-imidazolyl)-1,3, 4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1-Methyl-2-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!III,2,2|nonane; 4-(5-(1- Methyl-4-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!III,2,2|nonane; 65 4-(5-(1-Methyl-5-imidazolyl)- 1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!III,2,2|nonane; 4-(5-(3-Pyrazolyl)-1,3,4-oxadiazol-2-yl| -1,4-diazadicyclo|3,2,2|nonane;

4-(5-(4-Pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(5-Pyrazolyl)-1 ,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-/1-Methyl-3-pyrazolyl)-1,3,4-oxadiazole-2 -yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(1-Methyl-4-pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4- diazadicyclo|3,2,2|nonane; 4-(5-(/1-Methyl-5-pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2 |nonane; 4-(5-(2-Thiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(4- Thiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(5-Thiazolyl)-1,3,4-oxadiazol- 2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 70 4-(5-(3-isothiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo 13,2,2|nonane; 4-(5-(4-isothiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!13,2,2|nonane; 4-( 5-(5-Isothiazolyl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!III,2,2-nonane; 4-(5-(1,2,3-Oxadizol-4 -yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|III,2,2Inonane; 4-(5-(1,2,3-Oxadiazol-5-yl)-1 ,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|III,2,2Inone N; 4-(5-(1,3,4-Oxadizol-2-yl)-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo!I3,2,2Inonane; 4-(5- (3-Furazanyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1,2,3-Triazol-4- yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1,2,3-Triazol-5-yl)-1, 3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1-Methyl-1,2,3-triazol-4-yl)-1,3 ,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1-Methyl-1,2,3-triazol-5-yl)-1, 3,4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1,2,4-Triazol-3-yl)-1,3,4 -oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1,2,4-Triazol-5-yl)-1,3,4-oxadiazol-2- yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1-Methyl-1,2,4-triazol-3-yl)-1,3,4-oxadiazol-2-yl) |-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1-Methyl-1,2,4-triazol-5-yl)-1,3,4-oxadiazol-2- yl|-1,4-diazadicyclo!|3,2,2|nonane; ch 4-(5-(1,3,4-Thiadiazol-2-yl)-1,3,4-oxadiazol-2-yl| -1,4-diazadicyclo|3,2,2|nonane; 4-(5-(1,2,4-Thiadiazol-3-yl)-1,3,4-oxadiazol-2-yl|-1,4 -diazadicyclo|3,2,2|nonane; (8) 4-(5-(1,2,4-Thiadiazol-5-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(3-Pyridazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl|III,212|nonane; 4-I5-(4-Pyridazinyl)-1,3, 4-oxadiazol-2-yl|-1,4-diazadicyclo/|3,2,2|nonane; or 4-(5-(1,3,5-Triazin-2-yl)-1,3, 4-oxadiazol-2-yl1-1,4-diazadicyclo[3,2,2-inonane, or its enantiomer or a mixture of its enantiomers, or its pharmaceutically acceptable addition salt, or its M-oxide.

In a fourth preferred embodiment, the optionally substituted dicyclic aromatic heterocyclic group is indolyl, in particular 2-indolyl or 3-indolyl; isoindolyl, in particular 1-isoindolyl or 3-isoindolyl; benzo|p|furanil, (22) c5 In particular 2-benzo|p|Ifuranil or Z-benzo|p|Ifuranil; benzo|Bb|thienyl, in particular 2-benzo|b|htienyl or cha

Z-benzo|B|thienyl; benzoimidazolyl, in particular 2-benzoimidazolyl; benzothiazolyl, in particular 2-benzothiazolyl; quinolinyl, in particular 2-quinolinyl, 3-quinolinyl or 4-quinolinyl; isoquinolinyl, in particular 1-isoquinolinyl,

C-isoquinolinyl or 4-isoquinolinyl; cinolinyl, in particular 3-cinolinyl or 4-cinolinyl; phthalazinyl, in particular 1-phthalazinyl or 4-phthalazinyl; quinazolinyl, in particular 2-quinazolinyl or 4-quinazolinyl; quinoxalinyl, in particular "2-quinoxalinyl or 3-quinoxalinyl. with с In an even better embodiment, the optionally substituted polycyclic aromatic heterocyclic group is . tricyclic heteroaryls, in particular 2-acridinyl, 3-acridinyl, b-acridinyl or 7-acridinyl; carbazolyl, in particular and? 2-carbazolyl, 3-carbazolyl, b-carbazolyl or 7-carbazolyl; phenazinyl, in particular 2-phenazinyl, 3-phenazinyl, 7-phenazinyl or 8-phenazinyl; phenothiazinyl, in particular 2-phenothiazinyl, 3-phenothiazinyl, 7-phenothiazinyl or 8-phenothiazinyl; and phenoxazinyl, particularly 2-phenoxazinyl, 3-phenoxazinyl, 7-phenoxazinyl or 8-phenoxazinyl. -I In an even better embodiment, the compound of the invention is a derivative of 4-thiadiazolyl-1,4-diazadicyclo|3,2,2|nonane of the formula I, where the polycyclic aromatic heterocyclic group is, as an option, a substituted dicyclic and heteroaryl selected from quinolinyl, in particular 2-quinolinyl or 3-quinolinyl; isoquinolinyl, in particular

Go! C-isoquinolinyl; cinolinyl, in particular Z-cinolinyl; indolizinyl, in particular 2-indolizinyl; benzimidazolyl, 5or In particular 2-benzimidazolyl; benzothiazolyl, in particular 2-benzothiazolyl; phthalazinyl, in particular 7-phthalazinyl; about quinazolinyl, in particular 2-quinazolinyl, quinoxalinyl, in particular 2-quinoxalinyl; naphthyridinyl, in particular c 1,8-naphthyridin-2-yl or 1,8-naphthyridin-3-yl; and acridinyl, in particular 2-acridinyl or 3-afidinyl.

In an even more preferred embodiment, the dicyclic heteroaryl is optionally substituted with one or two substituents selected from the group consisting of alkyl, alkoxy, halogen, C3, CM, MO", MH", and phenyl.

In the best embodiment, the 4-thiadiazolyl-1,4-diazadicyclo!|3,2,2|nonane derivative of the invention is 4-(5-(2-Quinolinyl)-1,3,4-thiadiazol-2-yl|-1, 4-diazadicyclo|3,2,2I|nonane; (F) 4-(5-(3-Quinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I |nonane; ka 4-(5-(3-isoquinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(3-Cinolinyl) )-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; in 4-(5-(2-indolizinyl)-1,3,4-thiadiazol-2- yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1-Methyl-2-indolyl)-1,3,4-thiadiazol-2-yl|-1,4- Diazadicyclo!|3,2,2Inonane; 4-(5-(2-Benzimidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-I5- (1-Methyl-2-benzimidazolyl)-1,3,4-thiadiazol-2-yl]-1,4-diazadicycloyl3,2,2-inonane; 4-(5-(2-Benzothiazolyl)-1,3,4- Thiadiazol-2-yl|-1,4-diazadicyclo!|3,212Inonane;65 4-(5-(7-Phthalazinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!| C,2,2|nonane; 4-(5-(2-Quinazolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|C,2,2|nonane;

4-(5-(2-Quinoxalinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-O1,8-Naphthyridin-2 -yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-O/1,8-Naphthyridin-3-yl)- 1,3,4-thiadiazol-2-yl1-1,4-diazadicyclo13,2,2-nonane 4-15-(2-Aphidinyl)-1,3,4-thiadiazol-2-yl -1,4-diazadicyclo|3,2,2|nonane; or 4-(5-(3-Acridinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|Z,2 ,2Inonane; or an enantiomer thereof or a mixture of enantiomers thereof, or a pharmaceutically acceptable addition salt thereof, or an M-oxide thereof.

In another preferred embodiment, the compound of the invention is a derivative of 4-oxadiazolyl-1,4-diazadicyclo|3,2,2|nonane 7/0 of the formula IM, where Ag represents, as an option, a substituted aromatic monocyclic heterocycle selected from the group: benzothienyl, in particular 2-benzothienyl, 3-benzothienyl, 5-benzothienyl or b-benzothienyl; benzofuryl, in particular 2-benzofuryl, 3-benzofuryl, 5-benzofuryl or b-benzofuryl; quinolinyl, in particular 2-benzofuryl, 5-benzofuryl or b-benzofuryl; quinolinyl, in particular 2-quinolinyl or 3-quinolinyl; isoquinolinyl, in particular

C-isoquinolinyl; cinolinyl, in particular Z-cinolinyl; indolizinyl, in particular 2-indolizinyl; indolyl, in particular 2-indolyl; benzimidazolyl, in particular 2-benzimidazolyl; benzothiazolyl, in particular 2-benzothiazolyl; phthalazinyl, in particular 7-phthalazinyl; quinazolinyl, in particular 2-quinazolinyl; quinoxalinil, in particular 2-quinoxalinil; naphthyridinyl, in particular 1,8-naphthyridin-2-yl or 1,8-naphthyridin-3-yl; acridinyl, in particular 2-acridinyl or 3-acridinyl; dibenzofuryl, in particular 2-dibenzofuryl, or 3-dibenzofuryl; dibenzothienyl, in particular 2-dibenzothienyl or

Z-dibenzothienil; phenoxazinyl, in particular 2-phenoxazinyl or 3-phenoxazinyl.

In an even more preferred embodiment, the aromatic monocyclic heterocyclic group is optionally substituted with one or two substituents selected from the group consisting of alkyl, alkoxy, halogen, CE3, CM, MO", MH", and phenyl.

In the best embodiment, the compound of the invention is 4-(5-(2-Benzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-( 3-Benzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; ch 4-(5-(5-Benzothienyl)-1,3,4- oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(6-Benzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo |3,2,2|nonane; (8) 4-(5--2-Benzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|III,2,2Inonane; 4 -(5-(3-Benzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(5-Benzofuryl)-1,3 ,4-oxadiazol-2-yl1-1,4-diazadicyclo13,2,2-inonane, 4-(5-(6-Benzofuryl)-1,3,4-oxadiazol-2-yl1-1 4-(5-(2-Quinolinyl)-1)3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; o 4-(5-(3-Quinolinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; co 4-(5-(3-isoquinolinyl) )-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2I2I|nonane; 4-(5-(3-Cinolinyl)-1,3,4-oxadiazol-2-yl| -1,4-diazadicyclo|3,2,2|nonane; (22) 4-(5-(2-indolizinyl)-1,3,4-oxadiazol-2-y 11-1,4-diazadicyclo!3,2,2-inonane; y- 4-(5-(2-indolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1-Methyl-2 -indolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,A|nonane; 4-(5-(-2-Benzimidazolyl)-1,3,4- oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-15-(1-Methyl-2-benzimidazolyl)-1,3,4-oxadiazol-2-yl|-1, 4-diazadicyclo[3,2,2-nonane; "4-(5-(2-Benzothiazolyl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo[3,2,2]nonane; with 4-(5-(7-Phthalazinolinyl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!III,2,2Inonane; 4-(5-(2-Quinazolinyl)-1, 3,4-oxadiazol-2-yl1-1,4-diazadicyclo[3,2,2-inonane] 4-(5-(2-Quinoxalinyl)-1,3,4-oxadiazol-2-yl1-1 ,4-diazadicyclo!|3,2,2|nonane; 4-(5-031,8-Naphthyridin-2-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!| C,2,2Inonane; 4-(5-O31,8-Naphthyridin-3-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|C,2,2Inonane; -I 4-(5-(2-Acridinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(3-Acridinyl)-1, 3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; |-1,4-diazadicycloiZ3,2,2Inonane;

Go! 4-15-(3-Dibenzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl3,2,2-inonane; 4-15-(2-Dibenzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!/|3,2,nonane; o 4-15-(3-Dibenzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!/|3,2,nonane; c 4-15-(2-Phenoxazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; or 4-(5-(3-Phenoxazinyl) -1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; or an enantiomer thereof or a mixture of enantiomers thereof, or a pharmaceutically acceptable addition salt thereof, or 5B its M-oxide.

Any combination of two or more embodiments described herein is intended to be included within the scope of the present disclosure

F) invention. In the context of the present invention, alkyl denotes a monovalent saturated, linear or branched hydrocarbon chain. The hydrocarbon chain preferably has from one to eighteen carbon atoms (Ci-alkyl), preferably from one to six carbon atoms (Ci-C alkyl; lower alkyl) including pentyl, isopentyl, neopentyl, tertiary pentyl, hexyl and isohexyl. In a preferred embodiment, alkyl is C 1-4 alkyl, including butyl, isobutyl, secondary butyl, and tertiary butyl. In another preferred embodiment of the present invention, alkyl is C. alkyl, which can be, in particular, methyl, ethyl, propyl or isopropyl.

In the context of the present invention, cycloalkyl refers to a cyclic alkyl containing preferably from three to seven 65 carbon atoms (C3 dicycloalkyl), including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

In the context of the present invention, cycloalkyl-alkyl denotes cycloalkyl, as defined above, which is substituted by alkyl, as also defined above. Examples of preferred cycloalkyl-alkyls of the invention include cyclopropylmethyl and cyclopropylethyl.

In the context of the present invention, alkenyl denotes a carbon chain containing one or more double bonds, including dienes, trienes, and polyenes. In the best embodiment, the alkenyl of the invention contains from two to eight carbon atoms (alkenyl), preferably from two to six carbon atoms (Co. v-alkenyl), involving at least one double bond, in the best embodiment, the alkenyl of the invention is ethenyl; 1- or 2-propenyl (allyl); 1-, 2- or 3-butenyl, or 1,3-butadienyl; 1-, 2-, 3-, 4- or bB-hexenyl, or 1,3-hexadienyl, or 1,3,5-hexatrienyl; 1-, 2-, 3-, 4-, 5-, 6-, or 7-octenyl, or 1,3-octadienyl, or 1,3,5-octatrienyl, or 70 1,3,5,7-octatetraenyl .

In the context of the present invention, alkynyl denotes a carbon chain containing one or more triple bonds, including di-ynes, tri-ynes and poly-ynes. In the best embodiment, the alkynyl of the invention contains from two to eight carbon atoms (Co-alkynyl), preferably from two to six carbon atoms (C»ov-alkynyl), involving at least one triple bond, in the best embodiment, the alkynyl is ethynyl; 1- or 2-propynyl; 1-, 2-, or

C-butynyl, or 1,3-butadiinyl; 1-, 2-, 3-, 4-pentynyl, or 1,3-pentadiinyl; 1-, 2-, 3-, 4-, or b5B-hexenyl, or 1,3-hexadienyl or 1,3,5-hexatrienyl; 1-, 2-, 3-, 4-, 5- or b-heptynyl, or 1,3-heptadiynyl, or 1,3,5-heptatriynyl; 1-, 2-, 3-, 4-, 5-, 6- or 7-octynyl, or 1,3-octadiinyl, or 1,3,5-octatriynyl, or 1,3,5,7-ocgatetraynyl.

In the context of the present invention, alkyl denotes the group "alkyl-O-", where alkyl is defined above. Examples of preferred alkyl oxyls of the invention include methoxyl and ethoxyl.

In the context of the present invention, alkoxy-alkyl denotes the group "alkyl-O-alkyl--" where alkyl is defined above.

Examples of preferred alkoxy-alkyls of the invention include methoxy-methyl, methoxy-ethyl, ethoxy-methyl, and ethoxy-ethyl.

In the context of the present invention, alkoxy-alkyl refers to the group "alkyl-O-alkyl-O-", where alkyl is defined above. high school

Examples of preferred alkoxy-alkyls of the invention include methoxy-methoxy, methoxy-ethoxy, ethoxy-methoxy, o and ethoxy-ethoxy.

In the context of the present invention, cycloalkyl refers to the group "cycloalkyl-O-", where cycloalkyp is defined above.

In the context of the present invention, cycloalkyl-alkyl refers to the group "cycloalkyl-O-alkyl", where cycloalkyl and alkyl are defined above. In the context of the present invention, cycloalkyl-aluoxy refers to the group "cycloalkyl-O-alkyl-O", where cycloalkyl and alkyl are defined above. at

In the context of the present invention, halogen is fluorine, chlorine, bromine or iodine. Thus, trihalomethyl co represents, for example, trifluoromethyl, trichloromethyl and similar trihalo-substituted methyls.

In the context of the present invention, acyl means carboxyl (-COOH) or alkyl-carbonyl groups (alkyl-CO-), where alkyl is defined above. Examples of preferred acyls of the invention include carboxyl, acetyl, and propionyl. Cha

Pharmaceutically acceptable salts

The chemical compound of the invention can be presented in any form suitable for the intended use.

Suitable forms include pharmaceutically (ie, physiologically) acceptable salts, and pre- or pro-pharmaceutical forms of the chemical compound of the invention. "

Examples of pharmaceutically acceptable addition salts include, without limitation, non-toxic inorganic and organic acid addition salts such as chloride, hydrochloric acid derivative, bromide, bromic acid derivative, . nitrate, derivative of nitric acid, perchlorate, derivative of perchloric acid, phosphate, derivative of phosphate and? acid, sulfate, derivative of sulfuric acid, formate, derivative of formic acid, acetate, derivative of acetic acid, aconate, derivative of aconitic acid, ascorbate, derivative of ascorbic acid, benzenesulfonate, derivative of benzenesulfonic acid, benzoate, derivative of benzoic acid, cinnamate, derivative of cinnamic acid, citrate, -I derivative of citric acid, embonate, derivative of embonic acid, enanthate, derivative of enanthic acid, fumarate, derivative of fumaric acid, glutamate, derivative of glutamic acid, glycolate, derivative of glycolic acid, se) lactate, derivative of lactic acid, maleate, derivative of maleic acid acid, malonate, malonic acid derivative,

Go! mandelate, a derivative of mandelic acid, methanesulfonate, a derivative of methanesulfonic acid, 5-naphthalene-2-sulfonate, a derivative of naphthalene-2-sulfonic acid, phthalate, a derivative of phthalic acid, salicylate, a derivative of salicylic acid, sorbate, a derivative of sorbic acid, stearate, a derivative of stearic acid acids, succinate, a derivative of succinic acid, tartrate, a derivative of tartaric acid, p-toluenesulfonate, a derivative of p-toluenesulfonic acid, etc. Such salts can be formed by methods well known and described in the art. 5B Other acids, such as oxalic acid, which cannot be considered pharmaceutically acceptable, may be useful in the preparation of salts useful as intermediates in the preparation of a chemical compound. (F) Metal salts of the 1,4-diazadicycloalkane derivative of the invention include alkali metal salts such as the sodium salt of the carboxyl-containing chemical compound of the invention.

In the context of the present invention, "onium salts" of M-containing compounds are also considered as pharmaceutically acceptable salts. Preferred "onium salts" include alkyl onium salts, particularly methyl onium salts, cycloalkyl onium salts, and cycloalkylalkyl onium salts.

Steric isomers 1,4-diazadicycloalkane derivative of the present invention can exist in (g) and (-) forms, as well as racemic forms (i-4). The racemates of these isomers and the individual isomers themselves are within the scope of the present 65 invention.

Racemic forms can be separated into optical antipodes by known methods. One way to separate the diisomeric salts is to use an optically active acid and isolate the optically active amine compound by treatment with a base. Another method of separating racemates into optical antipodes is chromatography on an optically active matrix. The racemic compounds of the present invention can thus be separated into their optical antipodes, for example, by fractional crystallization of 4- or 1-(for example, tartrates, mandelates or camphorsulfonates). The 1,4-diazadicycloalkane derivative of the present invention can also be separated by the formation of diastereomeric amides by the reaction of chemical compounds of the present invention with optically active activated carboxylic acids, such as derivatives (t) or (-) phenylalanine, (y) or (-) phenylglycine, (y) or (-) /o Kcamphanic acid, or by the formation of diastereomeric carbamates by the reaction of the chemical compound of the present invention with optically active chloroformate or the like.

Additional methods for separating optical isomers are known in the art. Such methods include those described

Madnez U, SoiPeg( A, 5 UMiep 5 in "Epapiotegv, Kasegpayev. and KezvoiYishiopvg". dopp UMieu and Zopv, Mem Hogk (1981)).

Optically active compounds can also be obtained from optically active starting materials.

Methods of obtaining 1,4-diazadicycloalkane derivative of the invention can be obtained by conventional methods of chemical synthesis, for example, described in the examples. The starting materials described in the presented application are known or can be easily obtained by conventional methods from commercially available reagents.

Also, one compound of the invention can be converted into another compound of the invention using conventional methods.

The end products of the reactions described here can be isolated by conventional methods, such as extraction, crystallization, distillation, chromatography, etc.

Biological activity

The presented invention relates to new 1,4-diazadicycloalkane derivatives discovered as cholinergic ligands for nicotinic acetylcholine receptors (NACs) and modulators of monoamine receptors, in particular, transporters of biogenic amines 5-HT, BA and ME. Moreover, the preferred compounds of the invention show selective α7-activity. and)

In the context of the present invention, the term "modulator" includes agonists, partial agonists, antagonists and allosteric modulators of the receptor.

Due to their pharmacological profile, the 1,4-diazadicycloalkane derivatives of the invention may be useful in

For the treatment of diseases or conditions, such as those related to diseases of the central nervous system, diseases related to the peripheral nervous system, diseases related to smooth muscle contraction, endocrine disorders, diseases related to with neurodegeneration, diseases associated with inflammation, pain, with withdrawal symptoms caused by cessation of chemical abuse.

In the best embodiment, 1,4-diazadicycloalkane derivatives of the invention are used for the treatment of diseases, disorders and

With OR conditions affecting the central nervous system. Such diseases or disorders include anxiety, cognitive disorders, learning disabilities, memory deficits and dysfunctions, Alzheimer's disease, attention deficit disorder, attention deficit hyperactivity disorder, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Gilles de la Tourette syndrome , depression, mania, manic depression, schizophrenia, obsessive-compulsive disorder (OCD), panic disorders, eating disorders such as anorexia nervosa, bulimia and obesity, narcolepsy, pain perception, AIDS dementia, senile dementia , peripheral neuropathy, autism, dyslexia, tardive dyskinesia, hyperkinesia, epilepsy, bulimia, post-traumatic syndrome. social phobia, sleep disorders, pseudodementia, Hanser's syndrome, premenstrual syndrome, late-life syndrome? luteal phase, chronic fatigue syndrome, mutism, trichotillomania, and circadian rhythm disorders.

In another preferred embodiment, the 1,4-diazadicycloalkane derivatives of the invention may be useful in the treatment of diseases, disorders or conditions associated with smooth muscle contraction, including convulsive disorders, angina pectoris, premature labor, convulsions, diarrhea, asthma, epilepsy, late dyskinesia, hyperkinesia, premature ejaculation and difficulty with erection. ik In yet another preferred embodiment, the 1,4-diazadicycloalkane derivatives of the invention may be useful for

Go! treatment of endocrine disorders such as thyrotoxicosis, pheochromocytoma, hypertension and arrhythmia.

In yet another preferred embodiment, the 1,4-diazadicycloalkane derivatives of the invention may be useful in the treatment of neurodegenerative disorders, including transient anoxia and induced neurodegeneration. c In an even more preferred embodiment, the 1,4-diazadicycloalkane derivatives of the invention may be useful in the treatment of inflammatory diseases, disorders or conditions, including inflammatory skin disorders such as acne and erythema, Crohn's disease, inflammatory bowel disease, ulcerative colitis, and diarrhea .

In yet another preferred embodiment, the 1,4-diazadicycloalkane derivatives of the invention may be useful in the treatment of mild, moderate, or even severe pain of an acute, chronic, or recurrent nature, as well as

F) migraine-induced pain, post-operative pain, and phantom limb pain. Finally, the 1,4-diazadicycloalkane derivatives of the invention may be useful in the treatment of withdrawal symptoms caused by cessation of the abuse of addictive substances. Addictive substances include nicotine-containing products such as tobacco, opioids such as heroin, cocaine and morphine, benzodiazepines and benzodiazepine-like drugs, and alcohol. Withdrawal from addictive substances is generally a traumatic event characterized by anxiety and frustration, anger, anxiety, difficulty concentrating, dysphoria, decreased heart rate, and increased appetite and weight gain. 65 In this context, "treatment" includes the treatment, prevention, prevention and relief of withdrawal symptoms, as well as the treatment of the volunteer's reduced use of addictive substances.

In another aspect, the 1,4-diazadicycloalkane derivatives of the invention are used as diagnostic tools, for example, to identify and localize nicotine receptors in various tissues.

Pharmaceutical compositions

In another aspect, the invention relates to novel pharmaceutical compositions containing a therapeutically effective amount of a 1,4-diazadicycloalkane derivative of the invention.

Although the 1,4-diazadicycloalkane derivative of the invention for use in therapy can be used in the form of a crude chemical compound, it is preferable to administer the active ingredient, alternatively, in the form of a physiologically acceptable salt in a pharmaceutical composition together with one or more adjuvants, excipients, carriers, buffers , /o diluents, and/or other usual pharmaceutical excipients.

In a preferred embodiment, the invention relates to pharmaceutical compositions containing a 1,4-diazadicycloalkane derivative of the invention, or a pharmaceutically acceptable salt or derivative thereof, together with one or more pharmaceutically acceptable carriers and, optionally, other therapeutic and/or prophylactic ingredients known and used in the state of the art. Noses must be "acceptable" in the sense of 7/5 compatibility with other ingredients of the composition and harmless to their recipient.

The pharmaceutical compositions of the invention can be used in any convenient way suitable for the desired therapy. Preferred routes of administration include oral administration, particularly in tablet, capsule, dragee, powder or liquid form, and parenteral administration, particularly dermal, subcutaneous, intramuscular, or intravenous injection. The pharmaceutical composition of the invention can be produced by any expert using standard methods and conventional methods acceptable for the desired composition. If desired, compositions with continuous release of the active ingredient can be used.

The following details of the methods of formation and application can be found in (the latest edition

Ketipdiopye Rpaptaseciisa! Zsiepsez (Maask Rybiizpipd So., Eaviop, RA)).

The actual dosage depends on the nature and severity of the disease being treated, and is within the competence of the doctor, and can be differentiated by titration of the dosage for individual conditions of the present invention to obtain the desired therapeutic effect. However, pharmaceutical compositions containing from about 0.1 to (8) about 50Omg of active ingredient per single dose, preferably from about 1 to about 10OmgH, most preferably from about 1 to about 1Omg, are expected to be suitable for therapeutic treatment.

The active ingredient can be used in one or several doses per day. Satisfactory results can, in some cases, be obtained at low dosages, such as 0.mcg/kg IV and 1mcg/kg PO.

Preferred ranges are from about 0.1 µg/kg to about 1 µg/kg/day intravenously, and from about µg/kg SC to about 10 µg/kg/day orally.

Methods of therapy me) 1,4-diazadicycloalkane derivatives of the present invention are important modulators of nicotinic and monoamine receptors, and therefore useful for the treatment of a number of ailments involving cholinergic dysfunction, as well as a number of disorders sensitive to the action of PASNK modulators.

In another aspect, the invention relates to a method of treating, preventing, or ameliorating a disease, disorder, or condition of an animal organism, including a human, that is sensitive to modulation of cholinergic receptors and/or Monoamine receptors, the method includes application to such an animal organism in need thereof, in an effective amount of 1,4-diazadicycloalkane derivative of the invention. . In a preferred embodiment, the disease, disorder or condition involves the central nervous system. and?" In a preferred embodiment, the disease, disorder or condition is anxiety, cognitive disorders, learning disabilities, memory deficits and dysfunctions, Alzheimer's disease, attention deficit hyperactivity disorder and deficit hyperactivity disorder

Attention, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Gilles de la Tourette syndrome, -I depression, mania, manic depression, schizophrenia, obsessive-compulsive disorder (OC), panic disorder, eating disorder, somehow nervous- anorexia nervosa, bulimia and obesity, narcolepsy, pain perception, se) AIDS dementia, senile dementia, peripheral neuropathy, autism, dyslexia, tardive dyskinesia, hyperkinesia,

Go! epilepsy, bulimia, post-traumatic syndrome, social phobia, sleep disorders, pseudodementia, Hanser's syndrome, premenstrual syndrome, late luteal phase syndrome, chronic fatigue syndrome, mutism, trichotillomania, and circadian rhythm disorders. c In another preferred embodiment, the disease, disorder, or condition is associated with smooth muscle contraction, including convulsive disorders, angina pectoris, premature labor, convulsions, diarrhea, asthma, epilepsy, tardive dyskinesia, hyperkinesia, premature ejaculation, and erectile dysfunction. 5B In a third preferred embodiment, the disease, disorder or condition related to the endocrine system is thyrotoxicosis, pheochromocytoma, hypertension and arrhythmia. (F, In a fourth preferred embodiment, the disease, disorder or condition is a neurodegenerative disorder, including transient anoxia and induced neurodegeneration.

In a fifth preferred embodiment, the disease, disorder or condition is an inflammatory disorder, including inflammatory disorders of the skin such as acne and erythema, Crohn's disease, inflammatory bowel disease, ulcerative colitis, and diarrhea.

In a sixth preferred embodiment, the disease, disorder, or condition is mild, moderate, or even severe acute, chronic, or recurrent pain, as well as migraine pain, post-operative pain, and phantom limb pain.

In a seventh preferred embodiment, the disease, disorder or condition is associated with withdrawal symptoms caused by 65 stopping the use of addictive substances, including nicotine containing products such as tobacco, opioids such as heroin, cocaine and morphine, benzodiazepines and benzodiazepine - similar drugs and alcohol.

It can be expected that suitable dosage limits are 0.1-100Omg/day, 10-500mg/day, and especially 30-100mg/day, depending as usual on the correct mode of application, the form in which it is used, the indication for which application it is directed, the subject involved and the body weight of the subject involved, and in addition the choice and experience of the physician or veterinarian.

Satisfactory results can, in some cases, be obtained with a low dosage, such as 0.0005 mg/kg IV and 0.01 mg/kg orally. up to about mg/kg IV and about 0.1 to about 1Omg/kg orally 70 Examples

The invention is further illustrated by the following examples, which do not limit the scope of the invention.

Example 1

An example of receiving

All reactions involving air-sensitive reagents or intermediates are carried out under nitrogen and in /5 anhydrous solvents. Magnesium sulfate is used as a drying agent during preparation, and the solvents are evaporated under reduced pressure. 1,4-Diazadicyclo|3,2,2|nonane (Intermediate) is obtained according to |). May Spent 1993 36 2311-2320), and according to the following slightly modified method.

PAN (4.9 g, 130 mmol) was added to a solution of 1,4-diazadicyclo|3,2,2|nonan-Z-one (15.8 g, 113 mmol) in absolute dioxane (13 Oml) under argon. The mixture is heated at reflux for 6 hours and then allowed to reach room temperature. Water (5 ml in 10 ml of dioxane) is added dropwise to the reaction mixture, the mixture is stirred for 0.5 hours and then filtered through a glass filter. The solvent was evaporated and the residue was distilled using a Kugelrohr apparatus at 90 9 (0 mbar) to give 1,4-diazadicyclo!|3,2,2I|nonane (11.1g, 7890) as a colorless hygroscopic material. c 1,4-Diazadicyclo!|Z,2,2|nonan-3-one (Intermediate)

Hydroxylamine chloride (21g, o

302mmol) and sodium acetate (СНУСООН.ЗН.ОО, 83g, 610mmol), the mixture is stirred at 702 for 1 hour and then cooled to 02С. The separated crystalline material is filtered (without washing!) and dried in a vacuum, obtaining 40.0 g of oxime. (uh)

Z-Quinuclidinonone oxime (40.0 g) is added over 2 hours in small portions to polyphosphate acid" (190 g, obtained as described below"), preheated to 1202C. The temperature of the solution during the reaction is kept at 1302. After adding all the oxime, the solution is stirred for 20 minutes at the same (ee) temperature, then transferred to an enamel vessel and allowed to reach room temperature. The acidic mixture Fo is neutralized with a solution of potassium carbonate (500 g in 10 ml of water), transferred to a 2000 ml flask, diluted

ZbOml of water and extracted with chloroform (3xbOOml). The combined organic extracts were dried over sodium sulfate, the solvent was evaporated and the solid residue was dried in vacuo to give 30.0g (7790) of a mixture of lactams.

Crystallization of the obtained mixture of Kk) 1,4-dioxane (220 ml) gives 15.6 g (40.596) of 1,4-diazadicycloi|3,2,2|nonan-3-one as colorless large crystals with m.p. 211-21296. "

The filtrate is evaporated and the residue is chromatographed on silica gel (Megsk, 9385, 230-4000mesh) with acetone as an eluent. The solvent was evaporated and the residue was recrystallized from ethyl ethanoate to give c)c 1,3-diazadicycloyl3,2,2|nonan-4-one (10.2 g, 2695) as colorless small crystals with m.p. 125-12626. "from Polyphosphate acid" " 8596 Orthophosphate acid (500g, 294ml, 4.337mol) is placed in a 2000ml flask and then phosphorus pentoxide (750g, 5.284mol) is added at room temperature (acid-pentoxide ratio, 2:3). The mixture is stirred. at 200-2202C for 2 hours, yielding 1250g of polyphosphate acid containing 8095 ROB, ie 2-Chloro-5-Phenyl-1,3,4-thiadiazole (Intermediate) (se) 2-Amino-5-phenyl-1 ,3,4-thiadiazole sulfate (25.12g, 142mmol) was stirred in concentrated hydrochloric acid (300ml) at 02C. Sodium nitrite (12.7g, 184mmol) was added over 10 minutes. The reaction mixture was stirred at 502 for 15 hours. the acid is evaporated. Aqueous sodium hydroxide (4M, 250ml) is added and the precipitate (a) 50 is filtered off. Chromatography on silica gel with ethyl acetate as solvent gives the pure product. Yield 15.5g (5696). so Method A. 4-(5-Phenyl- 1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|Z,2,2|nonane fumarate (Compound AT)

A mixture of 1,4-diazadicyclo!|3,2,2|nonane (1.28g, 10.2mmol), 2-chloro-5-phenyl-1,3,4-thiadiazole (2.00g, y y y y, 10.2 mmol), triethylamine (2.833 ml, 20.3 mmol) and dioxane (200 ml) are stirred under reflux

GF) in the refrigerator for 70 hours. Aqueous sodium hydroxide (1M, 25ml) was added and the mixture was extracted twice with 7 ethyl acetate (2x20ml). Chromatography on silica gel with dichloromethane, 1095 methanol and 195 aqueous ammonia as eluent gave the title compound as an oil. The corresponding salt is obtained by adding a mixture of diethyl ether and methanol (9:1), saturated with fumaric acid. Output 0.95g, 2395. T. pl. 150,990, because the following compounds are obtained in a similar way: 4-(5--2-Selenophenyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound A) ; 4-(5--3-Selenophenyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound AZ); 4-(5-(2-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!/3,2,2|nonane (Compound A4); c5 4-(5-( 4-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound AB); 4-(5-(5-imidazolyl)-1, 3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound Ab);

4-(5-(1-Methyl-2-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A?7); 4 -(5-(1-Methyl-4-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound AB); 4-(5 -(1-Methyl-5-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound AZ); 4-(5-(3 -Pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A10); 4-(5-(4-Pyrazolyl)-1,3 ,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A11); 4-(5-(5-Pyrazolyl)-1,3,4-thiadiazole-2- yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A12); 4-(5-(1-Methyl-3-pyrazolyl)-1,3,4-thiadiazol-2-yl|- 1,4-diazadicyclo|3,2,2|nonane (Compound A13); 4-(5-(1-Methyl-4-pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4- diazadicyclo|3,2,2|nonane (Compound A14);70 4-(5-(1-Methyl-5-pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!| C,2,2|nonane (Compound A15); 4-(5-(2-Thiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|C,2,2|nonane (Compound A16); 4-(5-(4-Thiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A17); 4- (5-( 5-thiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A18); 4-(5-(3-isothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A19); 4-(5-(4 -isothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound A20); 4-(5-(5-isothiazolyl)-1,3, 4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A21); 4-(5-(1,2,3-oxadizol-4-yl)-1,3 ,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound A22); 4-(5-(1,2,3-Oxadizol-5-yl)-1,3 ,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound A23); 4-(1,3,4-oxadizol-2-yl)-1,3,4- Thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound AZ24); 4-(5-(3-Furazanyl)-1,3,4-thiadiazol-2-yl|- 1,4-diazadicyclo|3,2,2|nonane (Compound A25); 4-(5-(1,2,3-Triazol-4-yl)-1,3,4-thiadiazol-2-yl|- 1,4-diazadicycloyl3,2,2-nonane (Compound A2b); 4-(5-(1,2,3-Triazol-5-yl)-1,3,4-thiadiazol-2-yl)-1, 4-Diazadicycloyl3,2,2|nonane (Compound A27); 4-(5-(1-Methyl-1,2,3-triazol-4-yl)-1,3,4-thiadiazol-2-yl|- 1,4-diazadicyclo!|3,2,2|nonane (Compound A28); 4-(5-(1-Methyl-1,2,3-triazol-5-yl)-1,3,4-thiadiazol- 2-yl|-1,4-diazadicyclo!|3,2,2|no nan (Compound A29); 4-(5-(1,2,4-Triazol-3-yl)-1,3,4-thiadiazol-2-yl)-1,4-diazadicycloyl3,2,2-nonane (AZO compound); 4 -(5-(1,2,4-Triazol-5-yl)-1,3,4-thiadiazol-2-yl)-1,4-diazadicycloyl3,2,2-nonane (Compound AZI1); (8) 4-(5-(1-Methyl-1,2,4-triazol-3-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound AZ2); 4-(5-(1-Methyl-1,2,4-triazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2 ,2|nonane (Compound AZZ); 4-(5-(1,3,4-Thiadiazol-2-yl)-1,3,4-thiadiazop-2-yl|-1,4-diazadicyclo|3,2 ,2|nonane (Compound AZ4);so 4-(5-(1,2,4-Thiadiazol-3-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!| C,2,2|nonane (Compound AZB5B); 4-(5-(1,2,4-Thiadiazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo! |Z,2,2|nonane (Compound AZb); o 4-(5-(3-Pyridazinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|Z,2,2| nonane (Compound AZ7); co 4-(5-(4-Pyridazinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound AZV); 4 -(5-(1,3,5-Triazin-2-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicycloyl3,2,2|nonane (Compound AZ9); (22) 4-(5-(2-Quinolinyl)-1,3,4-thiadiazole -2-yl|-1,4-diazadicyclo!/3,2,2|nonane (Compound A40); y- 4-(5-(3-Quinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound A41); 4-(5- (3-Isoquinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!/3,2,2|Inonane (Compound A42); 4-(5-(3-Cinolinyl)-1 ,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!/3,2,2|nonane (Compound A43); 4-(5-(2-indolizinyl)-1,3,4-thiadiazole- 2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound A44); "4-(5-(2-isodolyl)-1,3,4-thiadiazol-2-yl|-1, 4-Diazadiylcycloyl3,2,2|nonane (Compound A45); with c 4-(5-(/1-Methyl-2-indolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicycloyl |III3,2,2|nonane (Compound A46); nonane (Compound A47); 4-N5-(1-Methyl-2-benzimidazolyl)-1,3,4-thiadiazol-2-yl]-1,4-diazadicycloyl3,2,2-nonane (Compound A48) 4-(5-(2-Benzothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!/3,2,2|nonane (Compound A49); 4-(5-( 7-Phthalazinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound OR); -I 4-(5-(2-Quinazolinyl)-1 ,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound AB); 4-(5-(2-Quinoxalinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound A5B2); ik 4-(5-(1 ,8-Naphthyridin-2-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|Z,2,2|nonane (Compound ABZ);

Go! 4-(5-(1,8-Naphthyridin-3-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound A5A4); 4- (5-(2-Acridinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicycloyl|3,2,2|nonane (Compound A55); and o 4-(5-(3- Acridinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicycloil|3,2,2|nonane (Compound A5Bb). c Method B 2-Mercaptobenzyl-5-Phenyl-1,3,4 -oxadiazole (Intermediate)

Benzyl bromide (16.vml, 141mmol) was added over 10 minutes to a mixture of 5-phenyl-1,3,4-oxadiazole-2-thiol (commercially available) (25.2g, 141mmol), triethylamine (19.7ml, 141mmol) and of ethanol (250 ml) at room temperature.

F) The mixture is stirred at room temperature for 3 hours. Aqueous sodium hydroxide (1M, 250ml) was added and the mixture was extracted twice with dichloromethane (2x200ml). Chromatography on silica gel with dichloromethane, 1095 methanol and 195 aqueous ammonia as eluent gave the title compound as an oil. Output 34.2g (90960). 60 Method C 5-(2-Furyl)-1,3,4-oxadiazole-2-thiol (Intermediate)

Carbon disulfide (16.5g, 21bmmol) was added to a mixture of 2-furancarbon hydrazide (13.6g, 108mmol), potassium hydroxide (6.68g, 119mmol) and methanol (125ml). The mixture is stirred at room temperature during

30 minutes, and then heated under reflux for 8 hours. Methanol is evaporated. The aqueous 65 phase is acidified to pH-4 with concentrated hydrochloric acid. The product is isolated by filtration. Yield 12.9g (7296).

Method O 4-(5-Phenyl-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo|Z,2,2|nonane fumarate (Compound 01)

A mixture of 2-mercaptobenzyl-5-phenyl-1,3,4-oxadiazole (Method B) (1.Og, C.7mmol), 1,4-diazadicyclo|3,2,2|nonane (0.47g, C, /mmol) and diisopropylethylamine (1.3 ml, 7.4 mmol) are stirred for 4 days at 100 92C. Aqueous sodium hydroxide (1M, 25bml) was added and the mixture was extracted twice with dichloromethane (2x20ml). Chromatography on silica gel with dichloromethane, 1095 methanol and 195 aqueous ammonia as eluent gave the title compound as an oil. The corresponding salt is obtained by adding a mixture of diethyl ether and methanol (9:1) saturated with fumaric acid. Output 0.47g, 3390. T. pl. 176.6-178.820.

The following compounds are obtained in a similar manner: 4-(5-(2-Furyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl|III3,2,2|nonane fumarate (Compound 02)

Obtained by method 0. T. pl. 175960. 4-(5--4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane fumarate (Compound 03)

Obtained by method 0. T. pl. 190.1-191.296. 4-I5-(4-pyridyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane fumarate (Compound 04)

Obtained by method 0. T. pl. 165.9-166.8260. 4-(5-(2-Thienyl)-1,3,4-oxadiazol-2-yl)-1,4-diazadicycloyl,2,2-nonane fumarate (Compound O5)

Obtained by method 0. T. pl. 161.8-162.796. 4-(5-(3-Pyridyl)-1,3,4-osadiazol-2-yl|-1,4-diazadicyclo|Z3,2,2|Inonane fumarate (Compound Ob)

Obtained by method 0. T. pl. 176.8-177.596. 4-(5-(4-Chlorophenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane fumarate (Compound 07)

Obtained by method 0. T. pl. 184.3-185.8260. 4-(5-(3-Methoxyphenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane fumarate (Compound 08)

Obtained by method 0. T. pl. 126-16496, p. 29 4-(5-(4-Phenyl-phenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|III,2,2|nonane fumarate (Compound 09) Gee)

Obtained by method 0. T. pl. 238-239, 4-(5-(-2-Naphthyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2)nonane fumarate (Compound Y10)

Obtained by method 0. T. pl. 194.6-195.796. co 20 The following compounds are similarly obtained: 4-(5-(3-Furyl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicycloyl3,2,2-nonane (Compound 011); (ab) 4-(5-(3-Thienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 012); so 4-(5-(2 -Pyridyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 013); 4-(5-(2-Pyrrolyl)-1,3, 4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane (Compound O14); (o) from 4-(5-(3-Pyrrolyl)-1,3,4-oxadiazole -2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound O15); M 4-(5-(1-Methyl-2-pyrrolyl)-1,3,4-oxadiazole-2 -ylI|-1,4-diazadicyclo|3,2,2|nonane (Compound O16); 4-(5-(1-Methyl-3-pyrrolyl)-1,3,4-oxadiazol-2-ylI|- 1,4-diazadicyclo|3,2,2|nonane (Compound 017); 4-(5-(2-Pyrimidinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3, 2,2|nonane (Compound O18); 4-(5-(4-Pyrimidinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound O19 ); " 20 4-(5-(5-Pyrimidinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound OХ20); -in 4- (5-(Pyrazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo! |Z,2,2|nonane (Compound 021); c 4-(5--2-Selenophenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 022); :z» 4-(5-"3-Selenophenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 023); 4-(5- (2-Oxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound O24); 15 4-(5-(4-Oxazolyl)- 1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane (Compound U25);-1 4-(5-(5-Oxazolyl)-1,3,4 -oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound U26); 4-(5-(3-isoxazolyl)-1,3,4-oxadiazol-2-yl| -1,1-diazadicyclo!3,2,2|nonane (Compound 027); (Ce) 4-(5-(4-isoxazolyl)-1,3,4-oxadiazol-2-yl|-1,4- diazadicyclo|3,2,2|nonane (Compound 028); co 4-(5-(5-isoxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2, 2|nonane (Compound 29); 4-(5-(2-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound Y30); (ab) 4-(5-(4-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 031); so 4-(5 -(5-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound Y32); 4-(5-(1-Methyl-2- imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2)nonane (Compound YZ33); 4-(5-(1-Methyl-4-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2)|nonane (Compound YZ34); 5 4-(5-(1-Methyl-5-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2)nonane (Compound YZ5); 4-(5-(3-Pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|)nonane (Compound YZ6b); (F) 4-(5-(4-Pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound OJ37);

Ge 4-(5-(5-Pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound YZ38); 4-(5-(1 -Methyl-3-pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound OYUZ39); in 4-(5-(1-Methyl- 4-pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 040); 4-(5-(1-Methyl-5-pyrazolyl) -1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 041); 4-(5-(2-Thiazolyl)-1,3,4-oxadiazole -2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 042); 4-(5-(4-Thiazolyl)-1,3,4-oxadiazol-2-yl|-1, 4-diazadicyclo|3,2,2|nonane (Compound 043); 4-(5-(5-Thiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2, 2|nonane (Compound 044); b5 4-(5-(3-isothiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloil|3,2,2|nonane (Compound 045) 4-(5-(4-isothiazolyl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicycloyl|3,2,2|nonane (Compound O46);

4-(5-(5-isothiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl|3,2,2|nonane (Compound 047); 4-(5-(1, 2,3-Oxadizol-4-yl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicycloyl|III3,2,2|nonane (Compound 048); 4-(5-(1, 2,3-Oxadizol-5-yl)-1,3,4xadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 049); 4-(5-(1,3, 4-Oxadizol-2-yl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo[III,2,2]nonane (Compound OY50); 4-(5-(3-Furazanil) -1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|III,2,2|nonane (Compound O51); 4-(5-(1,2,3-Triazol-4-yl) -1,3,4-oxadiazol-2-yl|-1,4-diazadiyl-4-cyclo!|3,2,2|nonane (Compound 052); 4-(5-(1,2,3-Triazol-5-yl) )-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound O53); 4-(5-(1-Methyl-1,2,3-triazole) -4-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl|III3,2,2|nonane (Compound O54); 70 4-(5-(1-Methyl-1, 2,3-triazol-5-yl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo[13,2,2]nonane (Compound O55); 4-(5-(1, 2,4-Triazol-3-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound O56); 4-(5-(1, 2,4-Triazol-5-yl)-1,3,4-oxa diazol-2-yl1-1,4-diazadicyclo3,2,2-nonane (Compound 057); 4-(5-(1-Methyl-1,2,4-triazol-3-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl|III,2,2|nonane ( Compound O58); 4-(5-(1-Methyl-1,2,4-triazol-5-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl|III,2, 2|nonane (Compound O59); 4-(5-(1,3,4-Thiadiazol-2-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2, 2|nonane (Compound YubO); 4-(5-(1,2,4-Thiadiazol-3-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2, 2|nonane (Compound 061); 4-(5-(1,2,4-Thiadiazol-5-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2, 2|nonane (Compound 062); 4-(5-(3-Pyridazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound Oyub3) 4-(5-(4-Pyridazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound Ob4); 4-(5-( 1,3,5-Triazin-2-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound Oyub65); 4-(5-( 2-Benzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound Jubb); 4-(5-(3-Benzothienyl)-1,3 ,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 067); 4-(5-(5-Benzothienyl)-1,3,4-oxadiazol-2-yl |-1,4-diazad icyclo|3,2,2|nonane (Compound Ob8); 4-(5-(6-Benzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound Ob); ch 4-(5-(- 2-Benzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound U70); 4-(5-(3-Benzofuryl)-1,3 ,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound Y71); i) 4-(5-(5-Benzofuryl)-1,3,4-oxadiazole- 2-yl[1,4-diazadicyclo[3,2,2]nonane (Compound 072); 4-(5-(6-Benzofuryl)-1,3,4-oxadiazol-2-yl[1], 4-diazadicyclo|Z,2,2|nonane (Compound Y73); 4-(5-(2-Quinolinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|Z,2, 2|nonane (Compound Y74); cozo 4-(5-(3-Quinolinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound Y75 ); 4-(5-(3-isoquinolinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 076); o 4-(5- (3-Cinolinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 077); co 4-(5-(2-indolizinyl)-1 ,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound 078); 4-(5-(2-indolyl)-1,3,4-oxadiazole- 2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 079); (22) 4-(5-(1-Methyl-2 -indolyl)-1,3,4-oxadiazol-2-yl|-yi Phdiazadicycloi!Z.g.gZnonane (Compound Y80); i- 4-(5-(2-Benzimidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound 081); 4-I5-(1 -Methyl-2-benzimidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound 082); 4-(5-(2-Benzothiazolyl) -1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound U83); 4-(5-(7-Phthalazinolinyl)-1,3,4-oxadiazole -2-yl|-1,4-diazadicyclo|3,2,2|nonane (Compound Y84); "4-(5-(2-Quinazolinyl)-1,3,4-oxadiazol-2-yl|-1 ,4-diazadicyclo!|3,2,2|nonane (Compound U85); with c 4-(5-(2-Quinoxalinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo| 3,2,2-nonane (Compound Y86); ,2,2|nonane (Compound 087); !|!3,2,2|nonane (Compound 088); 4-(5-(2-Acridinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2, 2|Inonane (Compound 089); 4-(5-(3-Acridinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|Inonane (Compound 090) ; -I 4-I5--2-Dibenzofuryl)-1,3,4-oxadiazol-2-ylI|-1,4-diaza dicyclo!|3,2,2|nonane (Compound 091); 4-15-(3-Dibenzofuryl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane (Compound 092); ik 4-I5-(2-Dibenzothienyl)-1,3,4-oxadiazol-2-ylI|-1,4-diazadicyclo|3,2,2|nonane (Compound 093);

Go! 4-I5-(3-Dibenzothienyl)-1,3,4-oxadiazol-2-ylI|-1,4-diazadicyclo|3,2,2|nonane (Compound 094); 4-(5-(-2-Phenoxazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound 095); and o 4-(5 -(3-Phenoxazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane (Compound Ob). c Example 2

Inhibition of the binding of ip mygo ZN-o-bungarotoxin in the brain of the rat. In this example, the affinity of the compounds of the invention in relation to the binding of nicotinic receptors of the o,-subtype is determined. o-Bungarotoxin is a peptide isolated from the venom of the Eiaridae snake Vypdagis tiyipsii5. It has a high affinity for neuronal and neuromuscular nicotinic receptors, where it acts as a potent antagonist.

ZH-a-Bungarotoxin marks nicotinic acetylcholine receptors formed by the o-subunit isoform, found in the brain, and the o.-isoform in the neuromuscular junction.

Obtaining tissues 60 Obtaining is carried out at 0-4 "С. Cerebral cortex from male MUiviag rats (150-250 g) is homogenized for 10 seconds in 15 ml of 20 mM Hepes buffer containing 118 mM Masi, 4.8 mM KSI, 1.2 mM Mo5O, and 2.5 mM Sasi" (pH 7.5), using Shga-Tytakh homogenizer. The tissue suspension is centrifuged at 27,000 rpm for 10 minutes. The supernatant is discarded and the pellet is washed twice by centrifugation at 27,000 x d for 10 minutes in 20 ml of fresh buffer, and the final pellet is then resuspended in fresh buffer containing 0.0190 65 bovine serum albumin (35 ml per g of starting tissue) and used for binding analysis.

Analysis

Aliquots of 500 μl of the homogenate are added to 25 μl of test solution and 25 μl of ZN-o-bungarotoxin (2NM, final concentration) and mixed and incubated for 2 hours at 37 C. Nonspecific binding is determined using (-)-nicotine (1 mM, final concentration). After incubation, the samples are added to 5 ml of ice-cooled Hepes buffer containing 0.0596 PE! and poured directly onto MUpaytap SR/C glass filters (pre-impregnated with 0.195 PE! for at least E hours) with suction and immediately washed with 2 x 5 mL of ice-cold buffer.

The amount of radioactivity on the filters is determined by conventional scintillation counting in the liquid. Specific binding is total binding minus non-specific binding.

The results are presented as IC 50 (the concentration of the test substance that inhibits the specific binding of ZN-o-bungarotoxin to 5096).

The results of these experiments are presented in the table below. and I

Claims (33)

The formula of the invention Ge! at 1. 1,4-diazadicycloalkane derivative of formula I: МА - Мярій m- Мх Аг , (Z o (sna p that: (22) any of its enantiomers or any mixture of its enantiomers, or its pharmaceutically acceptable salt addition salt, or its M-oxide, where n is 1, 2 or 3; X represents 0, 5 or be; and Ag represents a carbocyclic aromatic group (aryl) or a heterocyclic aromatic group (heteroaryl), " 70 Whose aromatic group may optionally be substituted with one or more substituents selected from the group: alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, alkoxyl, alkoxyalkyl, alkyloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkyloxy, halogen, CE3, CM, MO », MH»o, carboxyl, carbamoyl, amido, :z» sulfamoyl, phenyl and benzyl. 2. The compound according to claim 71, where Ag represents a carbocyclic aromatic group (aryl) or a heterocyclic aromatic group (heteroaryl), this aromatic group may, as an option, be substituted by one or more -I substituents selected from the group: alkyl, alkyl , halogen, SEz, SM, MO», MN» and phenyl. 3. The compound according to any of claims 1, 2, which is a derivative of 1,4-diazadicyclo|3,2,2|nonane, represented by the formula II and, MA - M and Z about 50 ahm Ag (IZ I where X and Ag is defined in claim 1. 4. The compound according to any of claims 1-3, which is a derivative of 4-thiadiazolyl-1,4-diazadicyclo|3,2,2I|Inonane, represented by the formula defined in claim 1. 5. The compound according to any of claims 1-3, which is a derivative of 4-oxadiazolyl-1,4-diazadicycloi|3,2,2|nonane, represented by the formula IM MA - M / ra vy M SU o AG, (M) 70 where Ag is defined in claim 1. 6. A compound according to any one of claims 1-5, where the carbocyclic aromatic group (aryl) is optionally substituted with phenyl, indenyl, naphthyl, azulenyl, fluorenyl or anthracenyl. 7. The compound according to claim 6, where the carbocyclic aromatic group is phenyl, optionally substituted with one or two substituents selected from the group: alkyl, cycloalkyl, cycloalkylalkyl, alkyl, cycloalkyl, halogen, CEz, 75 CM, MO», MH». carboxyl, carbamoyl, amido and sulfamoyl. 8. The compound according to claim 4, which is 4-(5-phenyl-1,3,4-thiadiazol-2-yl)-1,4-diazadicyclo|3,2,A|nonane; or an enantiomer or mixture of enantiomers thereof, or a pharmaceutically acceptable addition salt, or M-oxide. 9. The compound according to claim 5, which is: 4-(5-phenyl-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo!III,2,2Inonane; 4-(5-(3-methoxyphenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(4-methoxyphenyl)- 1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl |-1,4-diazadicyclo!|3,2,2Inonane; 4-15-(4-phenyl-phenyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2 2|nonane or 4-(5-(2-naphthyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; He! or its enantiomer or a mixture of enantiomers, or a pharmaceutically acceptable additive salt, or M-oxide 10. A compound according to any one of claims 1-5, where the heterocyclic aromatic group (heteroaryl) is optionally substituted aromatic monocyclic heterocyclic group, or optionally substituted aromatic di- or poly-heterocyclic heterocyclic group, these heterocyclic groups include benzofused 5- and b-membered heterocyclic rings containing one or more heteroatoms selected from nitrogen (M), oxygen (O), (ee) sulfur (5) and/or selenium (ze). 11. The compound according to claim 10, where the aromatic monocyclic heterocyclic group is optionally substituted with an aromatic 5- or 6b-linked heterocyclic monocyclic group. (uh) 12. The compound according to claim 11, where the optionally substituted aromatic monocyclic heterocyclic group is furanyl, in particular 2-furanyl or 3-furanyl; thienyl, in particular 2-thienyl or 3-thienyl; selenophenyl, in particular Ф 2-selenophenyl or З-selenophenyl; pyrrolyl (azolyl), in particular 2-pyrrolyl or 3-pyrrolyl; oxazolyl, in particular their oxazol-2-, 4- or b5-yl; thiazolyl, in particular thiazol-2-, 4- or b5-yl; imidazolyl, in particular 2-imidazolyl or 4-imidazolyl; pyrazolyl, in particular 3-pyrazolyl or 4-pyrazolyl; isoxazolyl, in particular isoxazol-3-, 4- or 5-yl; isothiazolyl, in particular isothiazol-3-, 4- or b5B-yl; oxadiazolyl, in particular 1,2,3-oxadiazol-4- or 5-yl, or "1,3,4-oxadiazol-2-yl; triazolyl, in particular 1,2,3-triazol-4-yl or 1,2,4-triazol-3-yl; thiadiazolyl, in particular 1,2,3-thiadiazol-4- or 5-yl, or 1,3,4-thiadiazol-2-yl; pyridinyl, in particular 2-pyridinyl, 3-pyridinyl or - 4-pyridinyl; pyridazinyl, in particular 3-pyridazinyl or 4-pyridazinyl; pyrimidinyl, in particular 2-pyrimidinyl, and 4-pyrimidinyl or β5B-pyrimidinyl; pyrazinyl, in particular 2-pyrazinyl or 3-pyrazinyl; and triazinyl, in particular, 1,2,4-triazinyl or 1,3,5-triazinyl. 13. The compound according to claim 4, where Ag represents a substituted, optionally, aromatic monocyclic heterocycle selected from the group: selenophenyl, in particular 2-selenophenyl or 3-selenophenyl; imidazolyl, in particular 2-imidazolyl, -| 4-imidazolyl or b5-imidazolyl; pyrazolyl, in particular 3-pyrazolyl, 4-pyrazolyl or 5-pyrazolyl; thiazolyl, in particular 2-thiazolyl or b5-thiazolyl; isothiazolyl, in particular 3-isothiazolyl, 4-isothiazolyl or β-isothiazolyl; oxadiazolyl, in particular 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl or 1,3,4-oxadiazol-2-yl; furazanil, in particular (ee) Z-furazanil; triazolyl, in particular 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, 1,2,4-triazol-3-yl or o 50 1,2,4-triazol-b -il; thiadiazolyl, in particular 1,3,4-thiadiazol-2-yl, 1,2,4-thiadiazol-3-yl or 1,2,4-thiadiazol-5-yl; pyridazinyl, in particular 3-pyridazinyl or 4-pyridazinyl; and triazinyl, particularly 1,3,5-triazin-2-yl. IR f) 14. The compound according to claim 13, which is: 4-(5-(2-selenophenyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane 4-(5-(3-selenophenyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(2-imidazolyl)- 1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2A|nonane; 4-(5-(4-imidazolyl)-1,3,4-thiadiazol-2-yl| -1,4-diazadicyclo|3,2,2A|nonane; IF) 4-(5-(5-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2 ,2A|nonane; ime) 4-(5-(1-methyl-2-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4- (5-(1-methyl-4-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 60 4-(5-(1-methyl- 5-imidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(3-pyrazolyl)-1,3,4-thiadiazol- 2-yl|-1,4-diazadicycloyl|3,2,2|nonane; 4-(5-(4-pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicycloyl|Z ,2,2|nonane; 4-(5-(5-pyrazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicycloi|3,2,2|nonane; 4-(5- (1-methyl-3-pyrazolyl)-1,3,4-thiadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane; 65 4-(5-(1-methyl-4 -pyrazolyl)-1,3,4-thiadia zol-2-yl|-1,4-diazadicyclo!|C,2,2|nonane; 4-(5-(1-methyl-5-pyrazolyl)-1,3,4-thiadiazol-2-yl)-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(2-thiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|III,2,2Inonane; 4-(5-(4-thiazolyl)-1, 3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|III,2,2Inonane; 4-(5-(5-thiazolyl)-1,3,4-thiadiazol-2-yl|-1, 4-diazadicyclo!|III,2,2Inonane; 4-(5-(3-isothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4 -(5-(4-isothiazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(5-isothiazolyl)-1, 3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1,2,3-oxadizol-4-yl)-1,3,4- Thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1,2,3-oxadizol-5-yl)-1,3,4-thiadiazol-2-yl |-1,4-diazadicyclo!|3,2,2Inonane; 70 4-(1,3,4-oxadizol-2-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo 13,2,2Inonane; 4-(5-(3-furazanyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5- (1,2,3-triazol-4-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1,2 ,3-triazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1-methyl-1,2 ,3-triazol-4-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4 -(5-(1-methyl-1,2,3-triazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1,2,4-triazol-3-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5 -(1,2,4-triazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1- methyl-1,2,4-triazol-3-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1-methyl -1,2,4-triazol-5-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1,3, 4-thiadiazol-2-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1,2,4-thiadiazole -3-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1,2,4-thiadiazol-5- yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(3-pyridazinyl)-1,3,4-thiadiazol- 2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-15-(4-pyridazinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|Z, 2,2|nonane or ch 4-(5-(1,3,5-triazin-2-yl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo|3,2,2I |nonane; or its enantiomer or a mixture of enantiomers, or a pharmaceutically acceptable additive salt, or M-oxide. i) 15. The compound according to claim 5, where Ag represents an optionally substituted aromatic monocyclic heterocycle selected from the group: furyl, in particular 2-furyl or 3-furyl; pyridyl, in particular 2-pyridyl, 3-pyridyl or 4-pyridyl; thienyl, in particular 2-thienyl or 3-thienyl; pyrrolyl, in particular 2-pyrrolyl or 3-pyrrolyl; pyrimidinyl, in particular, 2-pyrimidinyl, 4-pyrimidinyl or B5-pyrimidinyl; pyrazinil; selenophenyl, in particular 2-selenophenyl or 3-selenophenyl; oxazolyl, in particular 2-oxazolyl, 4-oxazolyl or 5-oxazolyl; isoxazolyl, in particular o3-isoxazolyl, 4-isoxazolyl or β5B-isoxazolyl; imidazolyl, in particular 2-imidazolyl, 4-imidazolyl or co 5-imidazolyl; pyrazolyl, in particular C-pyrazolyl, 4-pyrazolyl or B-pyrazolyl; thiazolyl, in particular 2-thiazolyl, 4-thiazolyl or b5-thiazolyl; isothiazolyl, in particular 3-isothiazolyl, 4-isothiazolyl or β-isothiazolyl; oxadiazolyl, (22) zv In particular 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl or 1,3,4-oxadiazol-2-yl; furazanil, in particular M. Z-furazanil; triazolyl, in particular 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, 1,2,4-triazol-3-yl or 1,2,4-triazol-5-yl ; thiadiazolyl, in particular 1,3,4-thiadiazol-2-yl, 1,2,4-thiadiazol-3-yl or 1,2,4-thiadiazol-b5-yl; pyridazinyl, in particular 3-pyridazinyl or 4-pyridazinyl; and triazinyl, particularly 1,3,5-triazin-2-yl. " 16. The compound according to claim 15, which is: c 4-(5-(2-furyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane ; . 4-(5-(3-furyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(2-pyridyl) )-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(3-pyridyl)-1,3,4-oxadiazol-2-yl |-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(4-pyridyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2, 2Inonane; -I 4-(5-(2-thienyl)-1,3,4-oxadiazol-2-ylI|-1,4-diazadicyclo!|III,2,2Inonane; 4-(5-(3-thienyl) )-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|III,2,2Inonane; se) 4-(5-(2-pyrrolyl)-1,3,4-oxadiazole-2 4-(5-(3-pyrrolyl)-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo !|3,2,2|nonane; 4-(5-(1-methyl-2-pyrrolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2| nonane; o 4-(5-(1-methyl-3-pyrrolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; c 4-(5 -(2-pyrimidinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(4-pyrimidinyl)-1,3,4- Oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane;4-(5-(5-pyrimidinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo! |3,2,2Inonane; 4-(5-(pyrazinyl)-1,3,4-oxa diazol-2-yl1-1,4-diazadicyclo!H3,2,2-nonane; 4-(5-(2-selenophenyl)-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo!III,2,2-nonane; (F) 4-(5-(3-selenophenyl) )-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!III,2,2|nonane;ka 4-(5-(2-oxazolyl)-1,3,4-oxadiazole-2 -yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(4-oxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3, 2,2|nonane; in 4-(5-(5-oxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5- (3-isoxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(4-isoxazolyl)-1,3,4- oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(5-isoxazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo |3,2,2|nonane; 4-(5-(2-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 65 4 -(5-(4-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(5-imidazolyl)-1 ,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1-methyl-2-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1- methyl-4-imidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(1-methyl-5-imidazolyl)-1 ,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2I|nonane; 4-(5-(3-pyrazolyl)-1,3,4-oxadiazol-2-yl|- 1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(4-pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(5-pyrazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(1-methyl-3-pyrazolyl) )-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo[13,2,2-inonane; 4-(5-(1-methyl-4-pyrazolyl)-1,3,4-oxadiazole 70 4-(5-(1-methyl-5-pyrazolyl)-1,3,4-oxadiazol-2-yl)-1, 4-diazadicyclo!|13,2,2Inonane; 4-(5-(2-thiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4- (5-(4-thiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(5-thiazolyl)-1,3, 4-oxadiazol-2-yl|-1,4-diazadicyclo!3,2,2Inonane; 4-(5-(3-isothiazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo !IZ,2, 2|nonane; 4-(5-(4-isothiazolyl)-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo!III,2,2-nonane; 4-(5-(5-isothiazolyl)-1 ,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!III,2,2|nonane; 4-(5-(1,2,3-oxadizol-4-yl)-1,3,4 -oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(1,2,3-oxadizol-5-yl)-1,3,4-oxadiazol-2 -yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(1,3,4-oxadizol-2-yl)-1,3,4-oxadiazol-2-yl|- 1,4-diazadicyclo|3,2,2|nonane; 4-(5-(3-furazanyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2 |nonane; 4-(5-(1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1,2,3-triazol-5-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-( 5-(1-methyl-1,2,3-triazol-4-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-( 5-(1-methyl-1,2,3-triazol-5-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; ch 4- (5-(1,2,4-triazol-3-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5- (1,2,4-triazol-5-yl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane; (8) 4-(5- (1-methyl-1,2,4-triazo 1-3-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(1-methyl-1,2,4-triazol-5-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(1,3,4-thiadiazol-2-yl)-1,3,4-oxadiazol-2-yl)-1,4-diazadicyclo!III,2,2-inonane; 4-(5 -(1,2,4-thiadiazol-3-yl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!3,2,2-inonane; 4-(5-(1,2, 4-thiadiazol-5-yl)-1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!3,2,2-inonane; o 4-(5-(3-pyridazinyl)-1,3, 4-oxadiazol-2-yl-1-1,4-diazadicyclo[3,2,2-nonane] 4-15-(4-pyridazinyl)-1,3,4-oxadiazol-2-yl-1, 4-diazadicyclo|3,2,2|nonane or 4-(5-(1,3,5-triazin-2-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo! |Z,2,2|nonane; (22) or its enantiomer or a mixture of enantiomers, or a pharmaceutically acceptable addition salt, or M-oxide. 17. The compound according to claim 10, where the optionally substituted dicyclic aromatic heterocyclic group is indolyl, in particular 2-indolyl or 3-indolyl; isoindolyl, in particular 1-isoindolyl or 3-isoindolyl; benzo|p|furanyl, in particular 2-benzo|p|furanyl or 3-benzo|b|furanyl; benzo|B|thienyl, in particular 2-benzo|b|thienyl or Z-benzo|b|hienyl; benzoimidazolyl, in particular 2-benzoimidazolyl; benzothiazolyl, in particular 2-benzothiazolyl; quinolinyl, in particular "2-quinolinyl, 3-quinolinyl or 4-quinolinyl; isoquinolinyl, in particular 1-isoquinolinyl, 3-isoquinolinyl or 3 with 4-isoquinolinyl; cinolinyl, in particular 3-cinolinyl or 4-cinolinyl; phthalazinyl, in particular 1-phthalazinyl or . 4-phthalazinil; quinazolinyl, in particular 2-quinazolinyl or 4-quinazolinyl; quinoxalinyl, in particular 2-quinoxalinyl or 3-quinoxalinyl. 18. The compound according to claim 10, where the optionally substituted polycyclic aromatic heterocyclic group is tricyclic heteroaryl, in particular 2-acridinyl, 3-acridinyl, b-acridinyl or 7-acridinyl; carbazolyl, in particular -I 2-carbazolyl, 3-carbazolyl, b-carbazolyl or 7-carbazolyl; phenazinyl, in particular 2-phenazinyl, 3-phenazinyl, 7-phenazinyl or 8-phenazinyl; phenothiazinyl, in particular 2-phenothiazinyl, 3-phenothiazinyl, 7-phenothiazinyl or 8-phenothiazinyl; and phenoxazinyl, particularly 2-phenoxazinyl, 3-phenoxazinyl, 7-phenoxazinyl or 8-phenoxazinyl. Go! 19. The compound according to claim 4, where the polycyclic aromatic heterocyclic group is, optionally, a substituted dicyclic heteroaryl selected from the group: quinolinyl, in particular 2-quinolinyl or 3-quinolinyl; isoquinolinyl, in particular 3-isoquinolinyl; cinolinyl, in particular Z-cinolinyl; indolizinyl, in particular 2-indolizinyl; benzimidazolyl, in particular 2-benzimidazolyl; benzothiazolyl, in particular 2-benzothiazolyl; phthalazinyl, in particular 7-phthalazinyl; quinazolinyl, in particular 2-quinazolinyl, quinoxalinyl, in particular 2-quinoxalinyl; naphthyridinyl, in particular 1,8-naphthyridin-2-yl or 1,8-naphthyridin-3-yl; and acridinyl, particularly 2-acridinyl or 3-acridinyl. 20. The compound according to claim 19, which is: 4-(5-(2-quinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; ( F) 4-(5-(3-quinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; ka 4-(5-(3- isoquinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(3-cinolinyl)-1,3,4-thiadiazol-2- yl|-1,4-diazadicyclo!III,2,2|nonane; in 4-(5-(2-indolizinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|Z ,2,2|nonane; 4-(5-(1-methyl-2-indolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-I5-(2-benzimidazolyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-I5-(1-methyl-2-benzimidazolyl )-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!/|3,2,2|nonane; 4-15-(2-benzothiazolyl)-1,3,4-thiadiazole-2 -yl|-1,4-diazadicyclo/|3,2,2|nonane; 65 4-(5-(7-phthalazinolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo| 3,2,2N|nonane; 4-(5-(2-quinazolinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|III,2,2Inonane; 4-(5-(2-quinoxalinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(1,8-naphthyridine) -2-yl)-1,3,4-thiadiazol-2-yl]-1,4-diazadicyclo!3,2,2-inonane; 4-(5-(1,8-naphthyridin-3-yl)-1, 3,4-thiadiazol-2-yl1-1,4-diazadicyclo13,2,2-inonane; 4-15-(2-acridinyl)-1,3,4-thiadiazol-2-yl1-1,4- diazadicyclo|3,2,2|nonane or 4-(5-(3-acridinyl)-1,3,4-thiadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; or its enantiomer or a mixture of enantiomers, or a pharmaceutically acceptable addition salt, or an M-oxide. 21. The compound according to claim 5, where Ag represents, as an option, a substituted aromatic monocyclic heterocycle selected from the group: benzothienyl, in particular 2-benzothienyl, 3-benzothienyl, 5-benzothienyl or b-benzothienyl; 7/0 benzofuryl, in particular 2-benzofuryl, 3-benzofuryl, 5-benzofuryl or b-benzofuryl; quinolinyl, in particular 2-quinolinyl or 3-quinolinyl; isoquinolinyl, in particular 3-isoquinolinyl; cinolinyl, in particular Z-cinolinyl; indolizinyl, in particular 2-indolizinyl; indolyl, in particular 2-indolyl; benzimidazolyl, in particular 2-benzimidazolyl; benzothiazolyl, in particular 2-benzothiazolyl; phthalazinyl, in particular 7-phthalazinyl; quinazolinyl, in particular 2-quinazolinyl; quinoxalinil, in particular 2-quinoxalinil; naphthyridinyl, in particular 1,8-naphthyridin-2-yl or 1,8-naphthyridin-3-yl; /5 acridinyl, in particular 2-acridinyl or 3-acridinyl; dibenzofuryl, in particular 2-dibenzofuryl or 3-dibenzofuryl; dibenzothienyl, in particular 2-dibenzothienyl or 3-dibenzothienyl; phenoxazinyl, in particular 2-phenoxazinyl or 3-phenoxazinyl. 22. The compound according to claim 21, which is: 4-15-(2-benzothienyl)-1,3,4-oxadiazol-2-yl1-1,4-diazadicycloyl3,2,2-inonane; 4-15-(3-benzothienyl)-1,3,4-oxadiazol-2-yl1-1,4-diazadicycloyl3,2,2-inonane; 4-15-(5-benzothienyl)-1,3,4-oxadiazol-2-yl1-1,4-diazadicycloyl3,2,2-inonane; 4-15-(6-benzothienyl)-1,3,4-oxadiazol-2-yl1-1,4-diazadicycloyl3,2,2-inonane; 4-I5-(2-benzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2I|nonane; 4-I5-(3-benzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2I|nonane; ch 4-I5-(5-benzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2I|nonane; 4-I5-(6-benzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2I|nonane; i) 4-(5-(2-quinolinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; 4-(5-(3-quinolinyl)- 1,3,4-oxadiazol-2-yl-1,4-diazadicyclo[3,2,2-inonane; 4-(5-(3-isoquinolinyl)-1,3,4-oxadiazol-2-yl]- 1,4-diazadicyclo|3,2,2|nonane;so 4-(5-(3-cinolinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2 ,2Inonane; 4-(5-(2-indolizinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; o 4-(5-(2-indolyl) )-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane; co 4-(5-(1-methyl-2-indolyl)-1,3,4- Oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2Inonane;4-15-(2-benzimidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!| C3,2,2|nonane; (22) 4-15-(1-methyl-2-benzimidazolyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!/|3,2, 2|nonane; 1-4-15-(2-benzothiazolyl)-1,3,4-oxadiazol-2-yl1|-1,4-diazadicycloyl33,2,2Inonane; 4-(5-(7-phthalazinolinyl)- 1,3,4-oxadiazol-2-yl]-1,4-diazadicyclo!|3,2,2|nonane; 4-(5-(2-quinazolinyl)-1,3,4-oxadiazol-2-yl |-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(2-quinoxalinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadi fang!|Z,2,2Inonan; « 4-(5-(1,8-naphthyridin-2-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; with c 4-( 5-(1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; . 4-(5-(2-acridinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-(5-(3-acridinyl) -1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo|3,2,2|nonane; 4-15-(2-dibenzofuryl)-1,3,4-oxadiazol-2-yl| -1,4-diazadicyclo!|3,2,2|nonane; 4-15-(3-dibenzofuryl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2, 2|nonane; -I 4-I5-(2-dibenzothienyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl33,2,2Inonane; 4-I5-(3-dibenzothienyl)-1 ,3,4-oxadiazol-2-yl|-1,4-diazadicycloyl|3,2,2Inonane; se) 4-15-(2-phenoxazinyl)-1,3,4-oxadiazol-2-yl|-1,4 -diazadicyclo|3,2,2|nonane or 4-(5-(3-phenoxazinyl)-1,3,4-oxadiazol-2-yl|-1,4-diazadicyclo!|3,2,2| nonane; or its enantiomer or a mixture of enantiomers, or a pharmaceutically acceptable additive salt, or M-oxide. o 23. A pharmaceutical composition containing a therapeutically effective amount of a compound according to any of clauses 1-22, any of its enantiomers or any mixture of enantiomers thereof, or a pharmaceutically acceptable addition salt thereof, together with at least one pharmaceutically acceptable carrier or solvent chewing gum 24. Use of a compound according to any of claims 1-22, any of its enantiomers or any mixture of its two enantiomers, or its pharmaceutically acceptable addition salt for the manufacture of a medicament for the treatment, prevention or alleviation of a disease, disorder or condition, which are sensitive to modulation of cholinergic F) receptors and/or monoamine receptors. ka 25. The use of claim 24, wherein the disease, disorder or condition involves the central nervous system. 26. Use according to claim 24, wherein the disease, disorder or condition is anxiety, cognitive disorders, learning disabilities, memory deficits and dysfunctions, Alzheimer's disease, attention deficit disorder, attention deficit hyperactivity disorder, Parkinson's disease, Huntington's disease, lateral amyotrophic sclerosis, Gilles de la Tourette syndrome, depression, mania, manic depression, schizophrenia, obsessive-compulsive disorder (OCD), panic disorder, eating disorder such as anorexia nervosa, bulimia and obesity, narcolepsy, pain perception , AIDS dementia, senile dementia, peripheral neuropathy, autism, dyslexia, tardive dyskinesia, 65 hyperkinesia, epilepsy, bulimia, post-traumatic syndrome, social phobia, sleep disorders, pseudodementia, Hanser syndrome, premenstrual syndrome, late luteal phase syndrome, chronic fatigue, mutism, trichotillomania and circadian rhythm disorders. 27. The use of claim 24, wherein the disease, disorder or condition is associated with smooth muscle contraction, including convulsive disorders, angina pectoris, premature labor, convulsions, diarrhea, asthma, epilepsy, tardive dyskinesia, hyperkinesia, premature ejaculation and erectile dysfunction. 28. The use of claim 24, wherein the disease, disorder or condition relates to the endocrine system, such as thyrotoxicosis, pheochromocytoma, hypertension and arrhythmia. 29. The use of claim 24, wherein the disease, disorder or condition is a neurodegenerative disorder comprising transient anoxia and induced neurodegeneration. 70 30. The use of claim 24, wherein the disease, disorder or condition is an inflammatory disorder, comprising inflammatory skin disorders such as acne and erythema, Crohn's disease, inflammatory bowel disease, ulcerative colitis and diarrhea. 31. The use of claim 24, wherein the disease, disorder or condition is mild, moderate or even severe pain of an acute, chronic or relapsing nature, as well as migraine pain, post-operative uv pain and phantom limb pain. 32. The use of claim 24, wherein the disease, disorder or condition is associated with withdrawal symptoms caused by stopping the use of addictive substances, including nicotine-containing products such as tobacco, opioids such as heroin, cocaine and morphine, benzodiazepines and benzodiazepine-like substances drugs and alcohol. 33. A method of treating, preventing or alleviating a disease, disorder or condition of an animal organism, 2o including a human, which is sensitive to the modulation of cholinergic receptors and/or monoamine receptors, this method involves introducing into such an animal organism, including a human in need, therapeutically an effective amount of the compound according to any of claims 1-22, any of its enantiomers or any mixture of its enantiomers, or its pharmaceutically acceptable addition salt. триигя я " : " " : : povs Official Bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated microcircuits", 2007, M 11, 25.07.2007. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine (ee) (av) (ee) Ge) - - a - and (se) (ee) (av) so ko bo b5