An imidazole-indole derivative binding to 5-HT7 serotonin receptor, a pharmaceutical composition comprising the derivative, uses of the derivative and the composition, and an intermediate product for manufacturing the imidazole-indole derivative

Abstract

The subject matter of the invention is an imidazole-indole derivative of Formula (I): wherein R1 and R2 represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-C1-C3 alkylsulfanyl group, or R1 and R2 together form a C1-C3 alkylenedioxy group, or its pharmaceutically acceptable salt. The subject matter of the invention is also a pharmaceutical composition comprising an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as an active substance. The subject matter of the invention is an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt or a pharmaceutical composition comprising an imidazole- indole derivative of Formula (I) or its pharmaceutically acceptable salt, for use as a 5-HT7 serotonin receptor agonist or for use as a medicine, in particular in the treatment and / or prevention of a disease or disorder in which 5-HT7 serotonin receptor is involved. Moreover, the subject matter of the invention is a method for the treatment or prevention of a disease or disorder in which 5-HT7 serotonin receptor is involved in a subject. The subject matter of the invention is an intermediate product of Formula (II): wherein R1 and R2 substituents are as defined above for the Formula (I).

Description

[0001] AN IMIDAZOLE-INDOLE DERIVATIVE BINDING TO 5-HT7 SEROTONIN RECEPTOR, A PHARMACEUTICAL COMPOSITION COMPRISING THE DERIVATIVE, USES OF THE DERIVATIVE AND THE COMPOSITION, AND AN INTERMEDIATE PRODUCT FOR MANUFACTURING THE IMIDAZOLE-INDOLE DERIVATIVE

[0002] Field of the Invention

[0003] The invention relates to imidazole-indole derivatives and pharmaceutical compositions comprising these derivatives. The disclosed imidazole-indole derivatives exhibit agonist activity towards 5-HT? serotonin receptor. Therefore, the invention also relates to uses of the said imidazole-indole derivatives and their pharmaceutical compositions, which uses are associated with the said agonist activity. The invention further relates to intermediate products used for manufacturing the imidazole-indole derivative according to the invention.

[0004] Background of the Invention

[0005] The serotonergic system regulates many important physiological functions in human body, such as blood circulation, heart function, food intake, emotional states, sleep, memory, and pain. One of the known subtypes of serotonin receptors is 5-HT? receptor. This receptor, which is a representative of the family of G-protein coupled serotonin receptors, is expressed both in the central nervous system and in peripheral organs. Experiments conducted so far have shown that this receptor may be involved in many pathophysiological processes; therefore, it is an important therapeutic target.

[0006] Compounds that bind to 5-HT? serotonin receptor and exhibit agonist activity towards it are known in the prior art.

[0007] For example, patent specification EP 3 272 745 Bl and the specifications of related applications and patents WO 2018 / 015558 Al and US 10844046 B2 describe substituted indole derivatives able to activate 5-HT? serotonin receptor and their use for the treatment or prevention of disorders related to this receptor.

[0008] The publication by A.S. Hogendorf et al., “Low-basicity 5-HT? Receptor Agonists Synthesized Using the van Leusen Multicomponent Protocol”, Sci. Rep., 2017, 7, 1444, published online on 04 May 2017, describes 5- aryl- 1- alkylimidazole derivatives and methods of their production, as well as their agonist properties towards 5-HT? serotonin receptor.

[0009] Further, the publication by A.S. Hogendorf et al., “Fluorinated indole-imidazole conjugates: Selective orally bioavailable 5-HT? receptor low-basicity agonists, potential neuropathic painkillers”, Eur. J. Med. Chem. 2019, 170, 261 - 275, describes fluorinated indole- imidazole derivatives and their potential use for the treatment of neuropathic pain.

[0010] The publication by G. Latacz et al., “Search for a 5-CT alternative. In vitro and in vivo evaluation of novel pharmacological tools: 3-(l-alkyl-l / Z-imidazol-5-yl)-l / Z-indole-5- carboxamides, low-basicity 5-HT? receptor agonists”, Med. Chem. Commun. 2018, 9, 1882 - 1890 describes 3-(l-alkyl-l / Z-imidazol-5-yl)-l / Z-indole-5-carboxamide compounds and their biological properties.

[0011] The publication by E.T. L’Estrade et al., „Radiolabeling and in vivo evaluation of [nC]AGH-44: a potential lead structure to develop a positron emission tomography radioligand for the 5-HT7 receptor”, J. Radioanal. Nucl. Chem. 2019, 322, 847 - 851, published online on 3 August 2019, describes a substituted imidazole-indole compound and its potential use as a radioligand in positron emission tomography.

[0012] Purpose of the Invention

[0013] Despite the fact that compounds exhibiting agonist activity towards 5-HT? serotonin receptor are known in the prior art, there is still a need in this field for new compounds that will exhibit high selectivity towards this receptor and thus they will be effective and safe agents for the treatment of disorders related to this receptor.

[0014] Therefore, the purpose of this invention is to develop new compounds being 5-HT? serotonin receptor agonists which will exhibit high selectivity towards this receptor, and thus they will have a reduced potential for causing adverse effects, and which will also be characterized by good biological availability when administered by various routes and will show high efficacy in the treatment and prevention of disorders in which 5-HT? serotonin receptor is involved.

[0015] These purposes have been realized using the solutions presented in the appended claims. Unexpectedly, it has been turned out that these purposes can be realized using new imidazole-indole derivatives comprising appropriate substituents.

[0016] Summary of the Invention

[0017] The subject matter of the invention is an imidazole-indole derivative of Formula (I): Formula (I) wherein:

[0018] - R1and R2represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-Ci-C3 alkylsulfanyl group, or

[0019] - R1and R2together form a C1-C3 alkylenedioxy group, or its pharmaceutically acceptable salt.

[0020] Preferably, the substituted C1-C3 alkoxy group is selected from the group consisting of a halo-Ci-C3 alkoxy group and a phenyl-Ci-C3 alkoxy group, wherein the halo-Ci-C3 alkoxy group comprises at least one halogen atom selected from the group consisting of a bromine atom, a fluorine atom, a chlorine atom and an iodine atom.

[0021] Preferably, in the halo-Ci -C3 alkoxy group, all hydrogen atoms have been substituted with halogen atoms.

[0022] Preferably, the substituted C1-C4 alkyl group is selected from the group consisting of a halo-Ci-C4 alkyl group and a C1-C3 alkoxy-Ci-C4 alkyl group, wherein the halo-Ci-C4 alkyl group comprises at least one halogen atom selected from the group consisting of a bromine atom, a fluorine atom, a chlorine atom and an iodine atom.

[0023] Preferably, in the halo-Ci-C4 alkyl group, all hydrogen atoms have been substituted with halogen atoms.

[0024] Preferably, the halo-Ci-C3 alkylsulfanyl group comprises at least one halogen atom selected from the group consisting of a bromine atom, a fluorine atom, a chlorine atom and an iodine atom.

[0025] Preferably, in the halo-Ci -C3 alkylsulfanyl group, all hydrogen atoms have been substituted with halogen atoms. Preferably, R1and R2represent, independently of each other, a hydrogen atom, a chlorine atom, a bromine atom, an iodine atom, a fluorine atom, a hydroxy group, a methoxy group, a trifluoromethoxy group, a benzyloxy group, a methyl group, a tert-butyl group, a trifluoromethyl group, a methoxyethyl group, a methylsulfonyl group, an amide group, or a trifluoromethylsulfanyl group or R1and R2together form a methylenedioxy group, and more preferably, R1and R2represent, independently of each other, a hydrogen atom, a methoxy group, a chlorine atom, a bromine atom or an iodine atom.

[0026] Preferably, R1and / or R2are in the para and / or meta position relative to the oxygen atom of the phenoxy group.

[0027] Preferably, R1or R2is in the para position relative to the oxygen atom of the phenoxy group.

[0028] Preferably, the imidazole-indole derivative of Formula (I) is selected from the group consisting of the following compounds:

[0029] - 3-[l-(2-phenoxyethyl)-l / / -imidazol-5-yl]-l / / -indole-5-carboxamide,

[0030] - 3 - { 1 - [2-(4-methoxyphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,

[0031] - 3 - { 1 - [2-(4-methylphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide.

[0032] - 3-(l-{2-[4-(trifluoromethyl)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5- carboxamide,

[0033] - 3-{ l-[2-(4-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,

[0034] - 3 - { 1 - [2-(4-chlorophenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,

[0035] - 3-{ l-[2-(4-bromophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,

[0036] - 3-{ l-[2-(4-iodophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,

[0037] - 3 -( 1 - { 2- [4-(trifluoromethoxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 - carboxamide,

[0038] - 3 -( 1 - { 2- [4-(benzyloxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 -carboxamide,

[0039] - 3 - { 1 - [2-(4-hydroxyphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,

[0040] - 3-(l-{2-[4-(2-methoxyethyl)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5- carboxamide,

[0041] - 3 - { 1 - [2-(4-terZ-butylphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,

[0042] - 3-(l-{2-[4-(methanesulfonyl)phenoxy]ethyl]-l / / -imidazol-5-yl)-l / / -indole-5- carboxamide,

[0043] - 3 - [ 1 -(2- { 4- [(trifluoromethyl) sulfanyl] phenoxy } ethyl)- 1 H- imidazol-5 -yl] - l / Z-indole-5- carboxamide, - 3-{ l-[2-(4-carbamoylphenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,

[0044] - 3 - { 1 - [2-(3 -methoxyphenoxy)ethyl] - 1 / 7-i m i dazol -5 -yl } - 1 / / -indole-5 -carboxamide,

[0045] - 3 - { 1 - [2-(3 -methylphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,

[0046] - 3-{ l-[2-(3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,

[0047] - 3 - { 1 - [2-(3 -chlorophenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,

[0048] - 3-{ l-[2-(3-bromophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,

[0049] - 3 -( 1 - { 2- [3 -(trifluoromethoxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 - carboxamide,

[0050] - 3 -( 1 - { 2- [3 -(benzyloxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 -carboxamide,

[0051] - 3 - { 1 - [2-(3 -hydroxyphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,

[0052] - 3-{ l-[2-(4-chloro-3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5- carboxamide,

[0053] - 3-{ l-[2-(2 / / -l,3-benzodioxol-5-yloxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5- carboxamide,

[0054] - 3-{ l-[2-(3,4-dichlorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide, and their pharmaceutically acceptable salts.

[0055] Preferably, the pharmaceutically acceptable salt is a salt of an organic or inorganic acid.

[0056] Preferably, the organic or inorganic acid is selected from the group consisting of fumaric acid, citric acid, succinic acid, phosphoric acid, sulfuric acid and hydrochloric acid.

[0057] The subject matter of the invention is also a pharmaceutical composition comprising a therapeutically and / or prophylactically effective amount of an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as defined above as an active substance and at least one pharmaceutically acceptable excipient.

[0058] Preferably, the pharmaceutical composition is designed to be administered orally, parenterally, by inhalation, transdermally or transmucosally.

[0059] The subject matter of the invention is an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as defined above or a pharmaceutical composition as defined above, for use as a 5-HT? serotonin receptor agonist.

[0060] Moreover, the subject matter of the invention is an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as defined above or a pharmaceutical composition as defined above, for use as a medicine. The subject matter of the invention is an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as defined above or a pharmaceutical composition as defined above, for use in the treatment and / or prevention of a disease or disorder in which 5-HT? serotonin receptor is involved, preferably in the treatment and / or prevention of acute or chronic pain, and more preferably in the treatment and / or prevention of pain selected from the group comprising fibromyalgia, migraine, neuropathic pain, cancer pain, burning mouth syndrome, tension-type pain, vulvodynia, pain in irritable bowel syndrome, pain in the course of functional disorders of the gastrointestinal tract, pain in the course of Oddi’s sphincter dysfunction, back pain, psychogenic purpura, postoperative pain, post-traumatic pain, rheumatic pain, inflammatory pain, pain in the course of osteoarthritis, musculoskeletal pain in the course of neurological diseases, trigeminal neuralgia and pain of unknown origin.

[0061] The subject matter of the invention is also a method for the treatment or prevention of a disease or disorder in which 5-HT? serotonin receptor is involved in a subject, the method comprising administering to the subject in need thereof an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as defined above or a pharmaceutical composition as defined above, in an amount effective for the treatment or prevention of the disease or disorder in which 5-HT? serotonin receptor is involved.

[0062] Preferably, the disease or disorder in which 5-HT? serotonin receptor is involved is acute or chronic pain, and more preferably, the pain is selected from the group comprising fibromyalgia, migraine, neuropathic pain, cancer pain, burning mouth syndrome, tensiontype pain, vulvodynia, pain in irritable bowel syndrome, pain in the course of functional disorders of the gastrointestinal tract, pain in the course of Oddi’s sphincter dysfunction, back pain, psychogenic purpura, postoperative pain, post-traumatic pain, rheumatic pain, inflammatory pain, pain in the course of osteoarthritis, musculoskeletal pain in the course of neurological diseases, trigeminal neuralgia and pain of unknown origin.

[0063] Finally, the subject matter of the invention is an intermediate product of Formula (II):

[0064] Formula (II) wherein:

[0065] - R1and R2represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-Ci-C3 alkylsulfanyl group, or

[0066] - R1and R2together form a C1-C3 alkylenedioxy group.

[0067] Preferably, the intermediate product of Formula (II) is selected from the group consisting of the following compounds:

[0068] - 3 - [ 1 -(2-phenoxyethyl)- 177-imi dazol - 5 -yl ] - 177-indol e- 5 -carbonitrile ;

[0069] - 3-{l-[2-(4-methoxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0070] - 3-{l-[2-(4-methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0071] - 3-(l-{2-[4-(trifluoromethyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile;

[0072] - 3-{l-[2-(4-fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0073] - 3-{l-[2-(4-chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0074] - 3-{l-[2-(4-bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0075] - 3-{l-[2-(4-iodophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0076] 3-(l-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5- carbonitrile;

[0077] - 3 -( 1 - { 2- [4-(benzyloxy)phenoxy] ethyl } - 1 TZ-imidazol-5 -yl)-7 TZ-indole-5 -carbonitrile;

[0078] - 3-(l-{2-[4-(2-methoxyethyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile;

[0079] - 3-{l-[2-(4-tert-butylphenoxy)ethyl)-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile;

[0080] 3-(l-{2-[4-(methanesulfonyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5- carbonitrile;

[0081] 3-[ 1 -(2- { 4- [(trifluoromethyl) sulfanyl] phenoxy } ethyl)- 1 H- i m idazo 1 -5 -y 1 ] - 1H- indole-5 - carbonitrile;

[0082] - 3-{l-[2-(4-cyanophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0083] - 3-{l-[2-(3-methoxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0084] - 3-{l-[2-(3-methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0085] - 3-{l-[2-(3-fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0086] - 3-{l-[2-(3-chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile;

[0087] - 3-{l-[2-(3-bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile; 3-(l-{2-[3-(trifluoromethoxy)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5- carbonitrile;

[0088] - 3 -( 1 - { 2- [3 -(benzyloxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 -carbonitrile;

[0089] - 3-{ l-[2-(4-chloro-3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;

[0090] - 3-{ l-[2-(2 / / -l,3-benzodioxol-5-yloxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile; and

[0091] - 3 - { 1 - [2-(3 ,4-dichlorophenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carbonitrile.

[0092] Advantageous effects of the invention

[0093] As a result of the studies carried out, both in vitro and in vivo, it has been found that the imidazole-indole derivatives of Formula (I) according to the invention exhibit agonist activity towards 5-HT? serotonin receptor, and thus they can be used as medicines for the treatment and / or prevention of diseases and disorders in which this receptor is involved. The obtained derivatives exhibit high selectivity towards 5-HT? serotonin receptor and are also characterized by high bioactivity, which is associated with their higher analgesic activity. The above-mentioned advantageous properties of the derivatives according to the invention result from the introduction of an appropriately substituted phenoxyethyl group into the imidazole ring, with the simultaneous presence of the carboxamide moiety in position 5 of the indole system.

[0094] Brief description of the drawing

[0095] The results of studies concerning the properties of the derivatives of Formula (I) according to the invention are presented in Fig. 1, which shows a comparison of analgesic effects of the comparative compound described in US 10844046 B2 (Example 26) intraperitoneally administered once in the dose of 60 mg / kg and compound Bl according to the invention (Example 1) intraperitoneally administered once in the dose of 20 mg / kg in a model of neuropathic pain induced by sciatic nerve ligation in male mice.

[0096] Detailed description of the invention

[0097] The terms used herein relating to a derivative, such as “derivative of Formula (I)”, “ imidazole-indole derivative of Formula (I)”, “derivative according to the invention”, etc. include both the derivative (compound) as such and its pharmaceutically acceptable salt.

[0098] The subject matter of the invention is an imidazole-indole derivative (compound) of Formula (I) Formula (I) wherein:

[0099] - R1and R2represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-Ci-C3 alkylsulfanyl group, or

[0100] - R1and R2together from a C1-C3 alkylenedioxy group,

[0101] Below are presented detailed definitions of substituents: R1and R2.

[0102] The term “halogen atom” denotes a fluorine atom, a bromine atom, a chlorine atom and an iodine atom.

[0103] The term “C1-C4 alkyl group” refers to a straight-chain or branched alkyl group comprising 1 to 4 carbon atoms. In one embodiment, the C1-C4 alkyl group is unsubstituted. Examples of an unsubstituted C1-C4 alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group and a tert-butyl group. The methyl group and the tert-butyl group are preferred.

[0104] In other embodiments, the C1-C4 alkyl group is substituted by a C1-C3 alkoxy group (a C1-C3 alkoxy-Ci-C4 alkyl group) or by at least one halogen atom selected from a fluorine atom, a bromine atom, a chlorine atom and an iodine atom (a halo-Ci-C4 alkyl group). Therefore, the examples of a substituted C1-C4 alkyl group include a methoxy-Ci-C4 alkyl group, an ethoxy-Ci-C4 alkyl group, a propoxy-Ci-C4 alkyl group, a chloro-Ci-C4 alkyl group, a bromo-Ci-C4 alkyl group, an iodo-Ci-C4 alkyl group and a fluoro-Ci-C4 alkyl group, wherein the C1-C4 alkyl group represents a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group and a tert-butyl group. In the case of substitution with a halogen atom, the number of the halogen atoms depends on the length of the alkyl group, specifically on the number of hydrogen atoms that can be substituted with the halogen atom. In a halomethyl group, the number of halogen atoms is 1 to 3; in a haloethyl group, it is 1 to 5; in a halopropyl group, it is 1 to 7; whereas in a halobutyl group, it is 1 to 9. The preferred number of halogen atoms in the halo-Ci-C4 alkyl group is one, and particularly preferably, all hydrogen atoms in the halo-Ci-C4 alkyl group are substituted with halogen atoms. Preferred examples of the substituted C1-C4 alkyl group include a trifluoromethyl group and a methoxyethyl group.

[0105] The term “C1-C3 alkoxy group” refers to a straight-chain or branched alkoxy group comprising 1 to 3 carbon atoms. In one embodiment, the C1-C3 alkoxy group is unsubstituted. Examples of an unsubstituted C1-C3 alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group and an isopropoxy group. The methoxy group is preferred.

[0106] In other embodiments, the C1-C3 alkoxy group is substituted with phenyl (a phcnyl-Ci-Cs alkoxy group) or by at least one halogen atom selected from a fluorine atom, a bromine atom, a chlorine atom, and an iodine atom (a halo-C 1-C3 alkoxy group). Examples of a substituted C1-C3 alkoxy group include a phenyl-Ci-Cs alkoxy group, a chloro-Ci-Cs alkoxy group, a bromo-Ci-Cs alkoxy group, an iodo-Ci-Cs alkoxy group and a fluoro-Ci-Cs alkoxy group, wherein the C1-C3 alkoxy group represents a methoxy group, an ethoxy group, an n-propoxy group or an isopropoxy group. In the case of substitution with a halogen atom, the number of the halogen atoms depends on the length of the alkoxy group, specifically on the number of hydrogen atoms that can be substituted with the halogen atom. In a halomethoxy group, the number of halogen atoms is 1 to 3; in a haloethoxy group, it is 1 to 5; whereas in a halopropoxy group, it is 1 to 7. The preferred number of halogen atoms in the halo-C 1-C3 alkoxy group is one, and particularly preferably, all hydrogen atoms in the halo-C 1 -C3 alkoxy group are substituted with halogen atoms. The preferred examples of the substituted C1-C3 alkoxy group include a benzyloxy group (a phenylmethoxy group) and a trifluoromethoxy group.

[0107] The term “C1-C3 alkylsulfonyl group” relates to a sulfonyl group substituted with a C1-C3 alkyl group. Examples of the C1-C3 alkylsulfonyl group include a methylsulfonyl group, an ethylsulfonyl group, an n-propylsulfonyl group and an isopropylsulfonyl group. The methylsulfonyl group is preferred.

[0108] The term “halo-C 1-C3 alkylsulfanyl group” relates to a sulfanyl group bound with a C1-C3 alkyl group substituted with at least one halogen atom. Examples of the halo-C 1-C3 alkylsulfanyl group include a bromo-C 1 -C3 alkylsulfanyl group, a chloro-C 1 -C3 alkylsulfanyl group, a fluoro-Ci-Cs alkylsulfanyl group and an iodo-Ci-Cs alkylsulfanyl group, wherein the C1-C3 alkyl group represents a methyl group, an ethyl group, an n-propyl group or an isopropyl group. As in the case of the above-described C1-C4 alkyl group substituted with at least one halogen atom, also in the case of the halo-Ci-C3 alkylsulfanyl group, the number of halogen atoms depends on the length of the alkyl group, and specifically on the number of hydrogen atoms that can be substituted with the halogen atom. In a halomethylsulfanyl group, the number of halogen atoms is 1 to 3; in a haloethylsulfanyl group, it is 1 to 5; and in a halopropylsulfanyl group, it is 1 to 7. Preferably, all hydrogen atoms in the halo-Ci -C3 alkylsulfanyl group are substituted with halogen atoms. A trifluoromethylsulfanyl group is preferred.

[0109] The term “C1-C3 alkylenedioxy group” relates to a C1-C3 alkylene group comprising two oxygen atoms by means of which this group is connected to the benzene ring of the phenoxyethyl substituent of the derivative according to the invention. A methylenedioxy group is preferred.

[0110] The term “amide group” means -CONH2 group.

[0111] The term “hydroxy group” means -OH group.

[0112] Preferably, R1and R2represent, independently of each other, a hydrogen atom, a methoxy group, a chlorine atom, a bromine atom or an iodine atom.

[0113] The preferred positions of R1and R2substituents are the para and meta positions relative to the oxygen atom of the phenoxy group. Where one of the substituents (R1or R2) is present, it occupies the para or meta position, preferably the para position relative to the oxygen atom of the phenoxy group. Where both substituents (R1and R2) are present, one of them occupies the para position and the other one - the meta position.

[0114] Preferably, the derivatives according to the invention are selected from the group comprising the following compounds and their pharmaceutically acceptable salts:

[0115]

[0116] B7 B8 B9

[0117]

[0118] B16 B17 B18

[0119]

[0120] B27 A method of manufacturing the imidazole-indole derivatives according to the invention comprises producing 3-[l-(2-phenoxyethyl)-l / / -imidazol-5-yl]-l / / -indole-5-carbonitrile derivatives of Formula (II) as intermediate products which are subsequently hydrolyzed to the derivatives according to the invention.

[0121] Therefore, the invention also relates to the intermediate products of Formula (II):

[0122] Formula (II) wherein:

[0123] - R1and R2represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-Ci-C3 alkylsulfanyl group, or

[0124] - R1and R2together form a C1-C3 alkylenedioxy group.

[0125] The derivatives of Formula (I) according to the invention form salts as a result of a reaction with organic and inorganic acids, such as fumaric acid, citric acid, succinic acid, phosphoric acid(III) and phosphoric acid(V) (in particular phosphoric acid(V)), sulfuric acid(IV) and sulfuric acid(VI) (in particular sulfuric acid(VI)) and hydrochloric acid. These are pharmaceutically acceptable salts, i.e. they are permitted in the pharmacy field for administration to mammals, including humans. The pharmaceutically acceptable salts of the derivatives of Formula (I) according to the invention retain the biological activity of these derivatives. Therefore, the preferred pharmaceutically acceptable salts of the derivatives of Formula (I) according to the invention include fumarate, citrate, succinate, phosphate(III) and phosphate(V) (in particular phosphate(V)), sulfate(IV) and sulfate(VI) (in particular sulfate(VI)) and chloride, wherein phosphate includes phosphate, hydrogen phosphate and dihydrogen phosphate.

[0126] The subject matter of the invention is also a pharmaceutical composition comprising the imidazole-indole derivative of Formula (I) according to the invention or its pharmaceutically acceptable salt as an active substance and at least one pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient is such a substance that is accepted in the pharmacy field for the delivery of biologically active agents to mammals, including humans. The nature and type of excipient depend mainly on the form of the pharmaceutical composition. For example, the composition for oral administration in the form of a tablet or capsule may comprise excipients selected from the group comprising binders (e.g. pregelatinized corn starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose), fillers (e.g. lactose, sucrose, carboxymethyl cellulose, microcrystalline cellulose or calcium hydrogen phosphate), lubricants (e.g. magnesium stearate, talc or silica), disintegrating agents (e.g. crospovidone, corn starch or sodium starch glycolate) and wetting agents (e.g. sodium lauryl sulfate). The composition for oral administration in a liquid form such as a solution, syrup or suspension may comprise excipients selected from the group comprising suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible oils), emulsifying agents (e.g. lecithin or acacia gum), non-aqueous bases (e.g. almond oil, oil esters, ethyl alcohol or fractionated vegetable oils), preservatives (e.g. methyl p- hydroxybenzoate, propyl p-hydroxybenzoate or sorbic acid) and buffer systems. Furthermore, the composition for oral administration may comprise flavouring agents, colouring agents and sweetening agents. The composition for injection, on the other hand, may comprise, for example, water, physiological salt, dextrose, glycerol or ethanol. Apart from the above-mentioned exemplary excipients, the compositions according to the invention may also comprise other known agents commonly used in the pharmacy field. The selection of appropriate excipient(s) is within the skills of a person skilled in the art.

[0127] As indicated above, the derivatives of Formula (I) according to the invention exhibit agonist activity towards 5-HT? serotonin receptor; therefore, in another aspect, the invention relates to the derivatives of Formula (I) according to the invention and pharmaceutical compositions comprising them for use as 5-HT? serotonin receptor agonists.

[0128] Furthermore, the subject matter of the invention relates to the derivatives of Formula (I) according to the invention and pharmaceutical compositions comprising them for use as a medicine.

[0129] Considering the fact that 5-HT? serotonin receptor can be involved in many pathophysiological processes in an organism, the subject matter of the invention also relates to the derivatives of Formula (I) according to the invention and pharmaceutical compositions comprising them for use in the treatment and / or prevention of a disease or disorder in which 5-HT? serotonin receptor is involved, and a method for the treatment or prevention of the above-mentioned disease or disorder.

[0130] According to the invention, the method for the treatment or prevention of a disease or disorder in which 5-HT? serotonin receptor is involved in a subject comprises administering to the subject in need thereof a derivative of Formula (I) or its pharmaceutically acceptable salt or a pharmaceutical composition comprising a derivative of Formula (I) or its pharmaceutically acceptable salt, in an amount effective for the treatment or prevention of the disease or disorder in which 5-HT? serotonin receptor is involved.

[0131] Examples of diseases and disorders in which 5-HT? serotonin receptor is involved include conditions related to the nervous system, in particular pain and neuropathic pain, neurological disorders (e.g. depression, mood disorders, cognitive disorders), psychiatric disorders (schizophrenia, psychotic diseases, anxiety), neurodevelopmental diseases (autism, fragile X syndrome, Rett syndrome) and addictive disorders.

[0132] The derivatives of Formula (I) according to the invention and pharmaceutical compositions comprising them are particularly suitable for use in the treatment and / or prevention of acute or chronic pain, in particular pain selected from the group comprising fibromyalgia, migraine, neuropathic pain, cancer pain, burning mouth syndrome, tension-type pain, vulvodynia, pain in irritable bowel syndrome, pain in the course of functional disorders of the gastrointestinal tract, pain in the course of Oddi’s sphincter dysfunction, back pain, psychogenic purpura, postoperative pain, post-traumatic pain, rheumatic pain, inflammatory pain, pain in the course of osteoarthritis, musculoskeletal pain in the course of neurological diseases, trigeminal neuralgia and pain of unknown origin.

[0133] Therefore, the method for the treatment or prevention according to the invention is also particularly suitable for the treatment or prevention of acute or chronic pain, the examples of which are indicated above.

[0134] In the context of this invention, the term “prevention” means stopping the onset of a disease or disorder in a subject completely or almost completely or to an advantageously significant degree, especially when the subject is at risk of developing the disease or disorder.

[0135] In the context of the invention, the term “treatment” includes stopping, retarding or reversing the progress of a disease or disorder. This term also includes alleviating, improving or eliminating one or more symptoms of the disease or disorder, even if the disease or disorder is not actually eliminated and even if the progress as such is not stopped, retarded or reversed. In the above-described uses and method for the treatment or prevention, the derivatives of Formula (I) according to the invention can be administered as a chemical compound as such or as its pharmaceutically acceptable salt, or they may be used in the form of a pharmaceutical composition comprising, as an active substance, such a derivative of Formula (I) or its pharmaceutically acceptable salt in combination with at least one pharmaceutically acceptable excipient. For each of the applications, the amount of the active substance - the derivative of Formula (I) according to the invention or its pharmaceutically acceptable salt - is a therapeutically and / or prophylactically effective amount. The therapeutically and / or prophylactically effective amount is one that will induce a biological response or desired effect in a subject. The selection of the appropriate amount depends on many factors, such as the specific compound, use, method of administration, the age and general health condition of a subject, the selected dosage regimen, concomitant use of other medications and the like. Therefore, it will be obvious to a person skilled in the art that the exact amount will ultimately be determined by an attending physician using known techniques and considering the factors mentioned above.

[0136] Typically, a daily dose - in a single dose or divided doses - will contain, as the therapeutically and / or prophylactically effective amount, about 5 to about 4000 mg of the derivative of Formula (I) according to the invention or its pharmaceutically acceptable salt.

[0137] The derivatives of Formula (I) according to the invention and their pharmaceutically acceptable salts and pharmaceutical compositions comprising them can be administered by any route, including oral, parenteral, transdermal, by inhalation and transmucosal routes, and they will have a form appropriate for the intended route of administration. For example, the composition for oral administration may have a solid or liquid form, such as a tablet, capsule, solution, syrup, suspension or dry powder for reconstitution with water or another appropriate carrier before use. Moreover, tablets may be coated using methods that are well- known in the art, with ordinary coatings, release delaying / controlling coatings, or enteric coatings. On the other hand, the composition for parenteral administration may have a form of a solution, emulsion or suspension suitable for injection, e.g. subcutaneous, intravenous, intraperitoneal, intramuscular, etc. For transdermal or transmucosal administration, the composition may have a form of, e.g. a transdermal patch, gel, ointment, cream, drops, etc., and for administration by inhalation, it may have a form of an aerosol, solution for a nebulizer or microfine powder for insufflation. The selection of an appropriate form of the composition from among those mentioned above or others known in the pharmacy field depends on the route of administration of the composition and is within the skills of a person skilled in the art.

[0138] The invention is illustrated by the examples given below, which, however, do not limit the scope of protection defined in the claims.

[0139] Examples

[0140] The derivatives of Formula (I) according to the invention can be synthesized using the general procedure presented below, which consists of two steps.

[0141] I. General procedure of obtaining the derivatives of Formula (I) according to the invention (B)

[0142] Formula II Formula I

[0143] Step 1. Synthesis of 3-[l-(2-phenoxyethyl)-lH-imidazol-5-yl]-lH-indole-5-carbonitrile derivatives (A) from 3-formyl-lH-indole-5-carbonitrile and 2-phenoxyethyl-l-amine derivatives

[0144] 3-Formyl-l / / -indole-5-carbonitrile (10 mmol, 1.702 g) and methanol (20 ml) were added to a round-bottom flask. An appropriate 2-phenoxyethyl-l-amine derivative was added to the resulting suspension. Stirring was continued for 12 hours, and then anhydrous potassium carbonate (12 mmol, 1.2 equiv., 1.656 g) and tosylmethyl isocyanide (TosMIC, 12 mmol, 1.2 equiv., 2.341 g) were added. In most cases, LC-MS analysis showed the presence of unreacted imine in the reaction mixture. In these cases, additional portions of K2CO3 (138 mg, 1 mmol, 0.1 equiv.) and TosMIC (195 mg, 1 mmol, 0.1 equiv.) were added. Stirring was continued for 30 minutes, and then distilled water (approximately 20 ml) was slowly added. The precipitated product was filtered under vacuum and dried. The crude product was usually sufficiently pure and did not require purification before the next step. The following procedure was used for products that did not precipitate: methanol was evaporated on a rotary evaporator. The resulting suspension was extracted with ethyl acetate (3 x 20 ml). The combined extracts were washed with brine, dried over MgSCh and purified by flash chromatography (SiCh, ethyl acetate : methanol 0 - 5%)

[0145] Step 2. Hydrolysis of 3-[l-(2-phenoxyethyl)-lH-imidazol-5-yl]-lH-indole-5- carbonitrile derivatives (A) to 3-[l-(2-phenoxyethyl)-lH-imidazol-5-yl]-lH-indole-5- carboxamide derivatives according to the invention (B)

[0146] An appropriate 3-[ l -(2-phcnoxycthyl)- l / 7-imidazol-5-yl]- l / 7-indole-5-carbonitrilc derivative (3.18 mmol) was weighed into a round -bottomed flask, to which a mixture of methanol (7.5 ml) and dioxane (10 ml) was then added. To the mixture was added 30% hydrogen peroxide solution (10 ml, 30 equiv.) followed by sodium hydroxide solution (2.41 g, 18.85 equiv. in 5 ml H2O). The mixture was vigorously stirred overnight. The precipitated product (if present) was filtered off, washed with a mixture of water and methanol (1: 1). The filtrate was neutralized with hydrochloric acid solution to pH = 8, evaporated to dryness, and the product was washed from the bed consisting mainly of sodium chloride with hot methanol (4 x 20 ml). Extractions were assisted by the use of an ultrasonic bath. Methanol used for leaching was filtered through a fluted filter, and then evaporated. The combined crude product usually contained some unreacted nitrile and was purified by flash chromatography (SiC , ethyl acetate : methanol 0 - 10%).

[0147] Any derivative of Formula (I) according to the invention can be synthesized using the abovedescribed general procedure. The selection of a specific starting compound - a 2- phenoxyethyl- 1 -amine derivative - depends on the type of synthesized derivative according to the invention and it is within the skills of a person skilled in the art. Similarly, the selection of appropriate reaction conditions (type of solvent, temperature, reaction time, etc.) is within the skills of a person skilled in the art. Substrates for manufacturing the derivatives according to the invention can be synthesized using procedures known in this art or they are commercially available. The derivatives of Formula (I) according to the invention - the products of the above-discussed general reaction - can be isolated and purified, if necessary, using conventional techniques, including, e.g. filtration, distillation, crystallization and chromatography. Moreover, the obtained products can be characterized by conventional methods, e.g. those described below. Analysis of the derivatives according to the invention

[0148] The products of the above-discussed general reaction, i.e. the derivatives of Formula (I) according to the invention were characterized by conventional analyses, as described in detail below.

[0149] UPLC / MS analyses were performed on Waters TQD spectrometer connected to UPLC Acquity H-Class with PDA eLambda detector. Waters Aquity UPLC BEH C18 1.7 pm 2.1 x 50 mm chromatographic column was used, at the flow rate of 0.300 ml / min, maintained at 40°C. The injection volume of 1.0 pl was used (samples were dissolved in LC-MS grade acetonitrile or water). All mass spectra were recorded under electrospray ionization in positive mode (ESI+), m / z in the range of 100 - 600, and chromatograms were recorded with UV detection in the range of 190 - 300 nm. The gradient conditions used were: 80% phase A (water + 0.1% formic acid) and 20% phase B (acetonitrile + 0.1% formic acid) to 100% phase B (acetonitrile + 0.1% formic acid) for 3 min, 100% phase B for 0.5 min and back to 80% - 20%. The total time of analysis was 6 minutes.

[0150] ’ H NMR spectra were recorded on BRUKER AVANCE III HD 500 MHz spectrometer, JOEL JNMR-ECZS 400 MHz spectrometer, Bruker DRX 500 NMR spectrometer, and JOEL JNMR-ECZR 600 MHz spectrometer, with the magnetic resonance spectrum for1H nuclei observed at 400 MHz, 500 MHz, and 600 MHz, respectively.

[0151] 13C NMR spectra were recorded at 100 MHz and 126 MHz for13C, respectively. Due to the poor solubility of some of the final compounds, the usual characterization using13C NMR was omitted. Chemical shifts for1H and13C NMR spectra are reported on the 5 scale (ppm) using tetramethylsilane as the internal standard or according to the residual undeuterated solvent signal (2.50 ppm for DMSO-d6 and 7.26 ppm for CDCh). Abbreviations for spin- coupled ’ H signals are: s (singlet), d (doublet), t (triplet), m (multiplet), dd (doublet of doublets), dt (doublet of triplets), and q (quartet). Coupling constants (J) are expressed in hertz. The abbreviation tR denotes retention time.

[0152] The synthesis of the exemplary derivatives of Formula (I) according to the invention and their characterization are presented below.

[0153] Example 1

[0154] 3-[l-(2-Phenoxyethyl)-l / Z-imidazol-5-yl]-l / Z-indole-5-carbonitrile (Al) was obtained from 2-phenoxyethyl-l -amine according to step 1 of the general procedure. Yield: 76%. LC-MS: (m / z) = 328.43 [M+]; tR= 1.95 min.

[0155] 3-[ l -(2-Phcnoxycthyl)- l / 7-imidazol-5-yl]- l / 7-indole-5-carboxamidc (Bl) was obtained from 3-[l-(2-phenoxyethyl)-l / / -imidazol-5-yl]-l / / -indole-5-carbonitrile (Al) according to step 2 of the general procedure. Yield: 95%.

[0156] ’ H NMR (400 MHz): 5 = 11.68 (d, J = 1.3 Hz, 1H); 8.13 (d, J = 1.3 Hz, 1H); 7.96 (s, 1H); 7.85 (d, 7 = 1.1 Hz, 1H); 7.75 (dd, 1H); 7.66 (d, J = 2.3 Hz, 1H); 7.47 (dd, J = 8.6, 0.4 Hz, 1H); 7.21 - 7.15 (m, 2H); 7.12 (d, J = 7.3, 1.1 Hz, 1H); 7.09 (s, 1H); 6.89 - 6.83 (m, 1H); 6.81 - 6.74 (m, 2H); 4.34 (t, J = 5.4 Hz, 2H); 4.11 (t, J = 5.4 Hz, 2H).

[0157] 13C NMR (101 MHz): 5 = 169.44; 158.40; 138.79; 138.21; 130.01; 128.18; 126.64; 126.62; 126.41; 126.18; 122.32; 121.44; 119.62; 114.94; 111.84; 105.29; 67.22; 44.43.

[0158] LC-MS: (m / z) = 346.84 [M+]; tR= 1.13 min.

[0159] Example 2

[0160] 3-{ l-[2-(4-Methoxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A2) was obtained from 2-(4-methoxyphenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 85%.

[0161] LC-MS: (m / z) = 358.69 [M+]; tR= 2.20 min.

[0162] 3-{ l-[2-(4-Methoxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B2) was obtained from 3-{ l-[2-(4-methoxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A2) according to step 2 of the general procedure. Yield 85%.

[0163] ’ H NMR (500 MHz, DMSO-76, TMS, PPM-6, TMS, ppm): 5 = 11.66 (d, J = 1.9 Hz, 1H); 8.12 - 8.11 (m, 1H); 7.94 (s, 1H); 7.85 (d, J = 1.1 Hz, 1H); 7.74 (dd, J = 8.6, 1.7 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.47 (dd, J = 8.5, 0.6 Hz, 1H); 7.11 (d, J = 1.1 Hz, 1H); 7.09 (s, 1H); 6.80 - 6.73 (m, 4H); 4.33 (t, J = 5.4 Hz, 2H); 4.07 (t, J = 5.4 Hz, 2H); 3.66 (s, 3H).

[0164] 13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.82; 153.57; 151.88; 138.24; 137.63; 127.62; 126.08; 126.04; 125.81; 125.58; 121.74; 119.06; 115.40; 114.56; 111.26; 104.74; 67.29; 55.32; 43.96.

[0165] LC-MS: (m / z) = 376.83 [M+]; tR= 1.69 min. Example 3

[0166] 3-{ l-[2-(4-Methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A3) was obtained from 2-(4-methylphenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 58%.

[0167] LC-MS: (m / z) = 342.43 [M+]; fa = 2.07 min.

[0168] 3-{ l-[2-(4-Methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B3) was obtained from 3-{ l-[2-(4-methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A3) according to step 2 of the general procedure. Yield 52%.

[0169] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.69 (d, J = 2.0 Hz, 1H); 8.14 - 8.12 (m, 1H); 7.97 (s, 1H); 7.87 (d, 7 = 1.1 Hz, 1H); 7.76 (dd, 1H); 7.68 (d, J = 2.5 Hz, 1H); 7.50 - 7.48 (m, 1H); 7.13 (d, J = 1.1 Hz, 1H); 7.12 (s, 1H); 7.01 (dt, 2H); 6.70 (dt, 2H); 4.35 (t, J =

[0170] 5.4 Hz, 2H); 4.10 (t, J = 5.4 Hz, 2H); 2.19 (s, 3H).

[0171] 13C NMR (126 MHz, DMSO-76, TMS, PPM-6, TMS, ppm): 5 = 168.87; 155.78; 138.24; 137.65; 129.81; 129.58; 127.61; 126.09; 126.06; 125.83; 125.62; 121.76; 119.08; 114.27; 111.28; 104.74; 66.77; 43.92; 20.05.

[0172] LC-MS: (m / z) = 361.09 [M+]; fa = 1.56 min.

[0173] Example 4

[0174] 3-(l-{2-[4-(Trifluoromethyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile (A4) was obtained from 2- [4-(trifluoromethyl)phenoxy] ethyl- 1 -amine according to step 1 of the general procedure. Yield: 85%.

[0175] LC-MS: (m / z) = 396.69 [M+]; fa = 2.35 min.

[0176] 3-(l-{2-[4-(Trifluoromethyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carboxamide (B4) was obtained from 3-(l-{2-[4-(trifluoromethyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z- indole-5-carbonitrile (A4) according to step 2 of the general procedure. Yield 40%.

[0177] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.68 (d, J = 1.9 Hz, 1H); 8.13 (d, J = 1.6 Hz, 1H); 7.96 (s, 1H); 7.89 (d, J = 1.0 Hz, 1H); 7.75 (dd, J = 8.6, 1.7 Hz, 1H); 7.68 (d, J =

[0178] 2.5 Hz, 1H); 7.57 (d, J = 8.5 Hz, 2H); 7.48 (dd, J = 8.6, 0.5 Hz, 1H); 7.12 (d, J = 1.1 Hz, 2H); 7.00 (d, J = 8.5 Hz, 2H); 4.40 (t, J = 5.3 Hz, 2H); 4.24 (t, J = 5.3 Hz, 1H).13C NMR (126 MHz, DMSO-t / 6, TMS, ppm): 5 = 168.84; 160.71; 138.27; 137.65; 127.70; 126.90; 126.87; 126.84; 126.10; 126.07; 125.89; 125.62; 125.56; 123.40; 121.75; 121.56; 121.30; 119.06; 114.94; 111.28; 104.67; 67.17; 43.68.

[0179] LC-MS: (m / z) = 414.89 [M+]; fa = 2.06 min.

[0180] Example 5

[0181] 3-{ l-[2-(4-Fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A5) was obtained from 2-(4-fluorophenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 73%.

[0182] LC-MS: (m / z) = 346.56 [M+]; fa = 1.97 min.

[0183] 3-{ l-[2-(4-Fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B5) was obtained from 3-{ l-[2-(4-fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A5) according to step 2 of the general procedure. Yield 40%.

[0184] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.69 (d, J = 1.4 Hz, 1H); 8.12 (s, 1H);

[0185] 7.96 (s, 1H); 7.87 (s, 1H); 7.75 (dd, J = 8.6, 1.6 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.48 (d, J = 8.5 Hz, 1H); 7.12 (s, 2H); 7.08 - 6.99 (m, 2H); 6.86 - 6.79 (m, 2H); 4.35 (t, J = 5.3 Hz, 2H); 4.13 (t, 7 = 5.3 Hz, 2H).

[0186] 13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.85; 157.57; 155.69; 154.23; 154.21; 138.26; 137.65; 127.64; 126.09; 126.06; 125.85; 125.61; 121.75; 119.06; 115.89; 115.78; 115.71; 111.28; 104.71; 67.36; 43.86.

[0187] LC-MS: (m / z) = 364.89 [M+]; fa = 1.59 min.

[0188] Example 6

[0189] 3-{ l-[2-(4-Chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A6) was obtained from 2-(4-chlorophenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 89%.

[0190] LC-MS: (m / z) = 362.69 [M+]; fa = 2.31 min.

[0191] 3-{ l-[2-(4-Chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B6) was obtained from 3-{ l-[2-(4-chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A6) according to step 2 of the general procedure. Yield 18%.

[0192] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.69 (d, J = 1.5 Hz, 1H); 8.13 (s, 1H);

[0193] 7.97 (s, 1H); 7.87 (d, J = 0.6 Hz, 1H); 7.76 (dd, J = 8.6, 1.6 Hz, 1H); 7.67 (d, J = 2.5 Hz, 1H); 7.49 (d, J = 8.5 Hz, 1H); 7.25 (dt, 2H); 7.12 (d, J = 0.7 Hz, 2H); 6.87 - 6.79 (m, 2H);

[0194] 4.36 (t, J = 5.3 Hz, 2H); 4.15 (t, J = 5.3 Hz, 2H).

[0195] 13C NMR (126 MHz, DMSO-<76, TMS, ppm): 5 = 168.88; 156.74; 138.27; 137.66; 129.21; 127.66; 126.10; 126.08; 125.89; 125.62; 124.60; 121.77; 119.08; 116.21; 111.30; 104.70; 67.14; 43.78.

[0196] LC-MS: (m / z) = 380.83 [M+]; tR= 1.85 min.

[0197] Example 7

[0198] 3-{ l-[2-(4-Bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A7) was obtained from 2-(4-bromophenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 77%.

[0199] LC-MS: (m / z) = 408.69 [M+]; tR= 2.20 min.

[0200] 3-{ l-[2-(4-Bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B7) was obtained from 3-{ l-[2-(4-bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A7) according to step 2 of the general procedure. Yield 29%.

[0201] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.68 (d, J = 1.9 Hz, 1H); 8.14 - 8.10 (m, 1H); 7.96 (s, 1H); 7.87 (d, J = 0.9 Hz, 1H); 7.75 (dd, J = 8.6, 1.7 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.48 (dd, J = 8.5, 0.5 Hz, 1H); 7.39 - 7.35 (m, 2H); 7.12 (d, J = 1.0 Hz, 2H); 6.79 (dt, 2H); 4.36 (t, J = 5.3 Hz, 2H); 4.14 (t, J = 5.4 Hz, 2H).

[0202] 13C NMR (126 MHz, DMSO-<76, TMS, ppm): 5 = 168.84; 157.18; 138.25; 137.64; 132.09; 127.66; 126.09; 126.06; 125.86; 125.60; 121.75; 119.06; 116.73; 112.31; 111.28; 104.68; 67.07; 43.74.

[0203] LC-MS: (m / z) = 424.69 [M+]; tR= 1.85 min.

[0204] Example 8

[0205] 3-{ l-[2-(4-Iodophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A8) was obtained from 2-(4-iodophenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 69%.

[0206] LC-MS: (m / z) = 455.07 [M+]; tR= 2.87 min.

[0207] 3-{ l-[2-(4-Iodophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B8) was obtained from 3-{ l-[2-(4-Iodophenoxy)ethyl]-l / Z-imidazol-5-yl}-lH-indole-5-carbonitrile (A8) according to step 2 of the general procedure. Yield 56%. ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.67 (d, J = 1.4 Hz, 1H); 8.11 (s, 1H); 7.95 (s, 1H); 7.86 (d, J = 0.7 Hz, 1H); 7.74 (dd, J = 8.6, 1.6 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.52 (dt, 2H); 7.48 (d, J = 8.6 Hz, 1H); 7.11 (d, J = 0.8 Hz, 2H); 6.69 - 6.64 (m, 2H); 4.35 (t, J = 5.3 Hz, 2H); 4.13 (t, J = 5.3 Hz, 2H).

[0208] 13C NMR (126 MHz, DMSO-<76, TMS, ppm): 5 = 168.82; 157.79; 138.23; 137.93; 137.63; 127.64; 126.08; 126.05; 125.86; 125.59; 121.74; 119.05; 117.22; 111.27; 104.67; 83.59; 66.92; 43.73.

[0209] LC-MS: (m / z) = 472.53 [M+]; fa = 2.52 min.

[0210] Example 9

[0211] 3-(l-{2-[4-(Trifhioromethoxy)phenoxy]ethyl}-lH-imidazol-5-yl)-l / Z-indole-5-carbonitrile (A9) was obtained from 2-[4-(trifluoromethoxy)phenoxy]ethyl-l -amine according to step 1 of the general procedure. Yield: 45%.

[0212] LRMS (ESI+): (m / z) calculated for C21H16F3N4O2 [M+H]: 413.12; measured: 413.1.

[0213] 3-(l-{2-[4-(Trifluoromethoxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5- carboxamide (B9) was obtained from 3-(l-{2-[4-(trifluoromethoxy)phenoxy]ethyl }-lH- imidazol-5-yl)- l / 7-indole-5-carbonitrilc (A9) according to step 2 of the general procedure. Yield 25%.

[0214] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.69 (d, J = 1.6 Hz, 1H); 8.13 (d, J = 1.1 Hz, 1H); 7.97 (s, 1H); 7.88 (d, J = 0.7 Hz, 1H); 7.75 (dd, J = 8.6, 1.6 Hz, 1H); 7.67 (d, J = 2.5 Hz, 1H); 7.48 (d, J = 8.5 Hz, 1H); 7.22 (d, J = 8.7 Hz, 2H); 7.12 (d, J = 0.8 Hz, 2H); 6.91 (dt, 2H); 4.37 (t, J = 5.3 Hz, 2H); 4.18 (t, J = 5.3 Hz, 2H).

[0215] 13C NMR (126 MHz, DMSO-<76, TMS, ppm): 5 = 168.86; 156.76; 141.97; 141.96; 138.27; 137.67; 127.66; 126.11; 126.07; 125.90; 125.63; 122.48; 121.76; 121.17; 119.14; 119.07; 115.69; 111.29; 104.70; 67.30; 43.79.

[0216] LC-MS: (m / z) = 431.07 [M+]; fa = 2.14 min.

[0217] Example 10

[0218] 3-(l-{2-[4-(Benzyloxy)phenoxy]ethyl}-lH-imidazol-5-yl)-lH-indole-5-carbonitrile (A10) was obtained from 2- [4-(benzyloxy)phenoxy] ethyl- 1 -amine according to step 1 of the general procedure. Yield: 57%.

[0219] LC-MS: (m / z) = 435.27 [M+]; fa = 3.01 min. 3-(l-{2-[4-(Benzyloxy)phenoxy]ethyl}-l / 7-imidazol-5-yl)-lH-indole-5-carboxamide

[0220] (BIO) was obtained from 3-(l-{2-[4-(benzyloxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z- indole-5-carbonitrile (A10) according to step 2 of the general procedure. Yield 62%.

[0221] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.66 (d, J = 2.1 Hz, 1H); 8.13 - 8.11 (m, 1H); 7.95 (s, 1H); 7.86 (d, J = 0.8 Hz, 1H); 7.74 (dd, J = 8.6, 1.7 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.48 (dd, J = 8.5, 0.6 Hz, 1H); 7.42 - 7.39 (m, 2H); 7.39 - 7.34 (m, 2H); 7.33 - 7.28 (m, 1H); 7.12 (d, J = 0.9 Hz, 1H); 7.10 (s, 1H); 6.86 (dt, 2H); 6.74 (dt, 2H); 5.00 (s, 2H); 4.33 (t, J = 5.4 Hz, 2H); 4.08 (t, J = 5.4 Hz, 2H).

[0222] 13C NMR (126 MHz, DMSO-<76, TMS, ppm): 5 = 168.85; 152.62; 152.05; 138.24; 137.64; 137.29; 128.38; 127.73; 127.62; 126.08; 126.04; 125.83; 125.60; 121.75; 119.06; 115.65; 115.38; 111.28; 104.73; 69.60; 67.25; 43.97.

[0223] LC-MS: (m / z) = 453.00 [M+]; fa = 2.12 min.

[0224] Example 11

[0225] 3-{ l-[2-(4-Hydroxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (Bll) was obtained in the following manner. B10 (120 mg, 0.265 mmol) was dissolved in 60 ml of methanol. Then the resulting solution was subjected hydrogenolysis using H-Cube® Pro ThalesNano flow reactor under the following conditions:

[0226] - cartridge: 70 x 4 mm 10% Pd / C;

[0227] - temperature: 60°C;

[0228] - flow: 2 ml / min;

[0229] - pressure: 1 bar.

[0230] The resulting reaction mixture was suspended on ~4 g of silica gel by evaporating the solvent. The product was then purified chromatographically (0 to 10% MeOH in DCM). The product was obtained as a crystallizing oil. The solvent was evaporated to give the product in 33% yield.

[0231] ’ H NMR (600 MHz, DMSO-t / 6, ppm): 5 = 11.65 (d, J = 1.4 Hz, 1H); 8.92 (br s, 1H); 8.12 - 8.10 (m, 1H); 7.94 (br s, 1H); 7.84 (d, J = 0.7 Hz, 1H); 7.74 (dd, J = 8.6, 1.6 Hz, 1H); 7.65 (d, J = 2.5 Hz, 1H); 7.47 (dd, J = 8.5, 0.4 Hz, 1H); 7.11 (d, J = 0.9 Hz, 1H); 7.08 (br s, 1H); 6.63 (d, J = 9.2 Hz, 2H); 6.60 (d, J = 9.2 Hz, 2H); 4.3 (t, J = 5.4 Hz, 2H); 4.03 (t, J = 5.4 Hz, 2H). HRMS (ESI+): (m / z) calculated for C20H19N4O3 [M+H]: 363.1452, measured 362.1455.

[0232] Example 12

[0233] 3-(l-{2-[4-(2-Methoxyethyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile (A12) was obtained from 2-[4-(2-methoxyethyl)phenoxy]ethyl-l -amine according to step 1 of the general procedure. Yield: 67%.

[0234] LC-MS: (m / z) = 388.22 [M+H]; fa = 2.05 min.

[0235] 3-(l-{2-[4-(2-Methoxyethyl)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carboxamide (B12) was obtained from 3-(l-{2-[4-(2-methoxyethyl)phenoxy]ethyl]-l / Z-imidazol-5-yl)- l / Z-indole-5-carbonitrile (A12) according to step 2 of the general procedure. Yield 57%.

[0236] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.69 (d, J = 2.0 Hz, 1H); 8.14 - 8.12 (m, 1H); 7.97 (s, 1H); 7.87 (d, J = 1.0 Hz, 1H); 7.76 (dd, 1H); 7.68 (d, J = 2.5 Hz, 1H); 7.49 (dd, 7 = 8.5, 0.6 Hz, 1H); 7.13 (d, J = 1.0 Hz, 1H); 7.11 (s, 1H); 7.06 (dt, 2H); 6.72 (dt, 2H); 4.35 (t, J = 5.4 Hz, 2H); 4.11 (t, J = 5.4 Hz, 2H); 3.44 (t, J = 6.9 Hz, 2H); 2.69 (t, J = 6.9 Hz, 2H); 1.91 (s, 3H).

[0237] 13C NMR (126 MHz, DMSO-6, TMS, ppm): 5 = 168.89; 156.27; 138.22; 137.66; 131.42; 129.75; 127.54; 125.86; 125.64; 121.76; 119.07; 114.23; 111.30; 104.71; 72.99; 66.77; 63.10; 62.81; 57.77; 43.94; 34.44.

[0238] LC-MS: (m / z) = 404.88 [M+]; fa = 1.20 - 1.76 min.

[0239] Example 13

[0240] 3-{ l-[2-(4-terZ-Butylphenoxy)ethyl)-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile (A13) was obtained from 2-(4-terZ-butylphenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 46%.

[0241] ’ H NMR (600 MHz, DMSO-76, TMS, ppm): 5 = 12.01 (s, 1H); 7.99 - 7.95 (m, 1H); 7.87 (d, J = 1.0 Hz, 1H); 7.82 (d, J = 1.2 Hz, 1H); 7.64 (dd, J = 8.5, 0.7 Hz, 1H); 7.52 (dd, J = 8.4, 1.6 Hz, 1H); 7.24 - 7.19 (m, 2H); 7.10 (d, J = 1.1 Hz, 1H); 6.72 - 6.67 (m, 2H); 4.34 (t, J = 5.3 Hz, 2H); 4.11 (t, 7 = 5.4 Hz, 2H); 1.22 (s, 9H).

[0242] 3-{ l-[2-(4-terZ-Butylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B13) was obtained from 3-{ l-[2-(4-terZ-butylphenoxy)ethyl)-l / Z-imidazol-5-yl)-l / 7-indole-5- carbonitrile (A13) according to step 2 of the general procedure. Yield 30%. ’ H NMR (400 MHz, DMSO-76, ppm): 5 = 11.68 (d, J = 1.5 Hz, 1H); 8.14 (d, J = 1.3 Hz, 1H); 7.96 (br s, 1H); 7.87 (d, J = 1.0 Hz, 1H); 7.76 (dd, 7 = 8.6, 1.6 Hz, 1H); 7.68 (d, 7= 2.4 Hz, 1H); 7.51 - 7.47 (m, 1H); 7.23 - 7.19 (m, 2H); 7.13 (d, 7 = 1.0 Hz, 1H); 7.11 (br s, 1H); 6.74 - 6.71 (m, 2H); 4.35 (t, 7 = 5.4 Hz, 2H); 4.11 (t, 7 = 5.4 Hz, 2H); 1.21 (s, 9H).

[0243] 13C NMR (100 MHz, DMSO-76, ppm): 5 = 168.86; 155.64; 143.11; 138.24; 137.66; 127.65; 126.10; 126.06; 126.06; 125.83; 125.60; 121.76; 119.08; 113.93; 111.28; 104.76; 66.76; 43.94; 33.74; 31.30.

[0244] HRMS (ESI+): (m / z) calculated for C24H27N4O2 [M+H]: 403.2129; measured: 403.2123.

[0245] Example 14

[0246] 3 -( 1 - { 2-[4-(Methanesulfonyl)phenoxy]ethyl } - l / Z-imidazol-5-yl)- l / Z-indole-5-carbonitrile (A14) was obtained from (4-methanesulfonylphenoxy)ethylamine according to step 1 of the general procedure. Yield: 60%.

[0247] ’ H NMR (400 MHz, DMSO-76, TMS, ppm): 5 = 12.01 (s, 1H); 7.96 (d, 7 = 1.2 Hz, 1H); 7.89 (d, 7 = 1.1 Hz, 1H); 7.81 (d, 7 = 2.4 Hz, 1H); 7.78 - 7.74 (m, 2H); 7.63 (dd, 7 = 8.5, 0.7 Hz, 1H); 7.52 (dd, 7 = 8.5, 1.6 Hz, 1H); 7.11 (d, 7 = 1.1 1H); 7.02 - 6.99 (m, 1H); 4.40 (t, 7 = 5.2 Hz, 2H); 4.27 (t, 7 = 5.2 Hz, 2H); 3.13 (s, 3H).

[0248] 3-(l-{2-[4-(Methanesulfonyl)phenoxy]ethyl}-lH-imidazol-5-yl)-l / Z-indole-5-carboxamide (B14) was obtained from 3-(l-{2-[4-(methanesulfonyl)phenoxy]ethyl]-l / Z-imidazol-5-yl)- l / Z-indole-5-carbonitrile (A14) according to step 2 of the general procedure. Yield: 14%.

[0249] 1H NMR (600 MHz, DMSO-76, ppm): 5 = 12.01 (s, 1H); 7.96 (d, 7 = 0.9 Hz, 1H); 7.89 (d, 7 = 1 Hz, 1H); 7.81 (d, 7 = 2.0 Hz, 1H); 7.77 - 7.75 (m, 1H); 7.63 (dd, 7 = 8.5, 0.6 Hz, 1H); 7.52 (dd, 7 = 8.45, 1.6, 1H); 7.11 (d, 7 = 1.0 Hz, 1H); 7.02 - 6.99 (m, 1H); 4.40 (t, 7 = 5.2 Hz, 2H); 4.27 (t, 7 = 5.2 Hz, 2H); 3.13 (s, 3H).

[0250] HRMS (ESI+): (m / z) calculated for C21H21N4O4S [M+H]: 425.1278; measured: 425.1272.

[0251] Example 15

[0252] 3- [ 1 -(2- { 4- [(Trifluoromethyl) sulfanyl] phenoxy } ethyl)- 1 H-i m idazo 1 -5 -y 1 ] - 1 H- i ndo le-5 - carbonitrile (A15) was obtained from {4-[(trifluoromethyl)sulfanyl]phenoxy]ethyl-l-amine according to step 1 of the general procedure without purification.

[0253] LRMS (ESI+): (m / z) calculated for C21H16F3N4OS [M+H]: 429.1; measured: 429.2; (m / z) calculated for C21H14F3N4OS [M-H]: 427.1; measured: 427.1. 3- [ 1 -(2- { 4- [(Trifluoromethyl) sulfanyl] phenoxy } ethyl)- 1 H-i m idazo 1 -5 -y 1 ] - 1 H- i ndo le-5 - carboxamide (B15) was obtained from 3-[l-(2-{4- [(trifluoromethyl)sulfanyl]phenoxy}ethyl)-lH-imidazol-5-yl)-l / Z-indole-5-carbonitrile (A15) according to step 2 of the general procedure. Yield: 8%.

[0254] ’ H NMR (600 MHz, DMSO): 5 = 11.67 (s, 1H); 8.11 (d, J = 1.5 Hz, 1H); 7.94 (br s, 1H); 7.88 (d, J = 1.0 Hz, 1H); 7.74 (dd, J = 8.5, 1.6 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.59 - 7.54 (m, 2H); 7.47 (dd, J = 8.5, 0.5 Hz, 1H); 7.10 (d, J = 1.0 Hz, 1H); 7.09 (br s, 1H) 7.00 - 6.91 (m, 2H); 4.38 (t, J = 5.3 Hz, 2H); 4.22 (t, J = 5.4 Hz, 2H).

[0255] HRMS (ESI+): (m / z) calculated for C21H18F3N4O2S [M+H]: 447.1097; measured: 447.1098.

[0256] Example 16

[0257] 3-{ l-[2-(4-Cyanophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A16) was obtained from 4-(2-aminoethoxy)benzonitrile according to step 1 of the general procedure without purification.

[0258] LRMS (ESI+): (m / z) calculated for C2IHI6N5O [M+H]: 354.1; measured: 354.2; (m / z) calculated for C21H14N5O [M-H]: 352.1; measured: 352.2.

[0259] 3-{ l-[2-(4-Carbamoylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B16) was obtained from 3-{ l-[2-(4-cyanophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A16) according to step 2 of the general procedure. Yield: 3%.

[0260] ’ H NMR (400 MHz, DMSO-t / 6, ppm): 5 = 11.72 (s, 1H); 8.11 (d, J = 1.0 Hz, 1H); 7.94 (br s, 1H); 7.87 (d, J = 1.0 Hz, 1H); 7.82 - 7.76 (m, 3H); 7.74 (dd, J = 8.6, 1.6 Hz, 1H); 7.67 (s, 1H); 7.48 (d, 7 = 8.6 Hz, 1H); 7.15 (br s, 1H); 7.11 (d, J = 1.0 Hz, 1H); 7.08 (br s, 1H); 6.88

[0261] - 6.85 (m, 2H); 4.38 (t, J = 5.3 Hz, 2H); 4.21 (t, J = 5.3 Hz, 2H).

[0262] HRMS (ESI+): (m / z) calculated for C21H20N5O3 [M+H]: 390.1561; measured: 390.1548.

[0263] Example 17

[0264] 3-{ l-[2-(3-Methoxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A17) was obtained from 2-(3-methoxyphenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 55%.

[0265] LC-MS: (m / z) = 358.83 [M+]; fa = 2.25 min. 3-{ l-[2-(3-Methoxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B17) was obtained from 3-{ l-[2-(3-methoxyphenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5- carbonitrile (A17) according to step 2 of the general procedure. Yield 41%.

[0266] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.67 (s, 1H); 8.13 (s, 1H); 7.96 (s, 1H); 7.87 (d, J = 0.7 Hz, 1H); 7.75 (dd, J = 8.6, 1.6 Hz, 1H); 7.67 (d, J = 2.5 Hz, 1H); 7.48 (d, J = 8.6 Hz, 1H); 7.15 - 7.07 (m, J = 11.4, 4.6 Hz, 3H); 6.48 (dd, 1H); 6.40 (dd, 7 = 8.1, 1.7 Hz, 1H); 6.38 (t, J = 2.3 Hz, 1H); 4.36 (t, J = 5.3 Hz, 2H); 4.14 (t, J = 5.3 Hz, 2H); 3.68 (s, 3H).

[0267] 13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.85; 160.46; 159.13; 138.24; 137.65; 129.96; 127.60; 126.08; 126.05; 125.82; 125.65; 121.75; 119.06; 111.28; 106.83; 106.46; 104.75; 100.63; 66.84; 55.06; 43.88.

[0268] LC-MS: (m / z) = 377.09 [M+]; fa = 1.74 min.

[0269] Example 18

[0270] 3-{ l-[2-(3-Methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A18) was obtained from 2-(3-methylphenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 66%.

[0271] LC-MS: (m / z) = 342.50 [M+]; fa = 2.07 min.

[0272] 3-{ l-[2-(3-Methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B18) was obtained from 3-{ l-[2-(3-methylphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A18) according to step 2 of the general procedure. Yield 26%.

[0273] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.68 (d, J = 1.9 Hz, 1H); 8.14 - 8.12 (m, 1H); 7.96 (s, 1H); 7.87 (d, J = 1.0 Hz, 1H); 7.75 (dd, J = 8.6, 1.7 Hz, 1H); 7.68 (d, J = 2.5 Hz, 1H); 7.48 (dd, J = 8.5, 4.4, 0.6 Hz, 1H); 7.12 (d, J = 1.0 Hz, 1H); 7.11 - 7.05 (m, J = 9.8, 7.3, 3.3 Hz, 2H); 6.74 - 6.68 (m, 1H); 6.62 - 6.57 (m, 2H); 4.36 (t, J = 5.4 Hz, 2H); 4.12 (t, J = 5.4 Hz, 2H); 2.21 (s, 3H).

[0274] 13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.84; 157.87; 139.02; 138.22; 137.64; 129.19; 127.60; 126.07; 125.81; 125.63; 121.74; 121.64; 119.08; 115.11; 111.33; 111.27; 104.75; 66.65; 43.90; 25.50; 21.01.

[0275] LC-MS: (m / z) = 360.83 [M+]; fa = 1.65 min. Example 19

[0276] 3-{ l-[2-(3-Fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A19) was obtained from 2-(3-fluorophenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 67%.

[0277] LC-MS: (m / z) = 347.30 [M+]; tR= 2.00 min.

[0278] 3-{ l-[2-(3-Fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B19) was obtained from 3-{ l-[2-(3-fluorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A19) according to step 2 of the general procedure. Yield 56%.

[0279] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.67 (d, J = 1.7 Hz, 1H); 8.12 (d, J = 1.5 Hz, 1H); 7.95 (s, 1H); 7.87 (d, J = 0.9 Hz, 1H); 7.75 (dd, J = 8.6, 1.6 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.47 (dd, 1H); 7.24 (dd, J = 15.4, 8.2 Hz, 1H); 7.11 (d, J = 0.9 Hz, 1H); 7.10 (s, 1H); 6.77 - 6.69 (m, 2H); 6.67 (ddd, J = 8.4, 2.3, 0.7 Hz, 1H); 4.36 (t, J = 5.3 Hz, 2H); 4.18 (t, 7 = 5.3 Hz, 2H).

[0280] 13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.82; 163.86; 161.93; 159.39; 159.30; 138.23; 137.64; 130.71; 130.63; 127.63; 126.07; 126.05; 125.86; 125.62; 121.74; 119.04; 111.27; 110.78; 110.76; 107.62; 107.45; 104.68; 102.15; 101.95; 67.21; 43.72.

[0281] LC-MS: (m / z) = 364.69 [M+]; tR= 0.97 min.

[0282] Example 20

[0283] 3-{ l-[2-(3-Chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A20) was obtained from 2-(3-chlorophenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 96%.

[0284] LC-MS: (m / z) = 363.29 [M+]; tR= 2.11 min.

[0285] 3-{ l-[2-(3-Chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B20) was obtained from 3-{ l-[2-(3-chlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A20) according to step 2 of the general procedure. Yield 42%.

[0286] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.67 (d, J = 1.7 Hz, 1H); 8.14 - 8.11 (m, 1H); 7.95 (s, 1H); 7.87 (d, J = 0.7 Hz, 1H); 7.75 (dd, J = 8.6, 1.6 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.50 - 7.46 (m, 1H); 7.23 (t, 1H); 7.12 (d, 7 = 0.8 Hz, lH); 7.10 (s, 1H); 6.96 (ddd, 7 = 8.0, 1.9, 0.8 Hz, 1H); 6.92 (t, 7 = 2.2 Hz, 1H); 6.81 - 6.77 (m, 1H); 4.36 (t, 7 = 5.2 Hz, 2H); 4.19 (t, 7 = 5.3 Hz, 2H).13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.83; 158.83; 138.24; 137.64; 133.72; 130.82; 127.60; 126.08; 126.05; 125.84; 125.63; 121.75; 120.88; 119.05; 114.56; 113.49; 111.27; 104.68; 62.02; 43.74.

[0287] LC-MS: (m / z) = 381.03 [M+]; tR= 1.70 min.

[0288] Example 21

[0289] 3-{ l-[2-(3-Bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A21) was obtained from 2-(3-bromophenoxy)ethyl-l -amine according to step 1 of the general procedure without purification.

[0290] LRMS (ESI+): (m / z) calculated for C2oHi6BrN40 [M+H]: 406.0; measured: 406.0; (m / z) calculated for C2oHi4BrN40 [M-H]: 404.0; measured: 404.0.

[0291] 3-{ l-[2-(3-Bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B21) was obtained from 3-{ l-[2-(3-bromophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A21) according to step 2 of the general procedure. Yield 3%.

[0292] ’ H NMR (600 MHz, DMSO-76, ppm): 5 = 11.60 (s, 1H); 8.11 (narr m, 1H); 7.93 (br s, 1H); 7.91 (br s, 1H); 7.74 (dd, J = 8.5, 1.6 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.47 (dd, J = 8.5, 0.5 Hz, 1H) 7.18 (t, 7= 8.1 Hz, lH) 7.13 (br s, 1H); 7.10 (ddd, J = 7.9, 1.8, 0.9 Hz, 1H); 7.08 (br s, 1H); 7.05 (narr m, 1H); 6.84 (ddd, J = 8.4, 2.5, 0.9 Hz, 1H); 4.36 (t, J = 5.2 Hz, 2H); 4.19 (t, 7 = 5.2 Hz, 2H).

[0293] HRMS (ESI+): (m / z) calculated for C2oHi8BrN402 [M+H]: 425.0608; measured: 425.0593.

[0294] Example 22

[0295] 3-(l-{2-[3-(Trifluoromethoxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile (A22) was obtained from 2-[3-(trifluoromethoxy)phenoxy]ethyl-l-amine according to step 1 of the general procedure. Yield: 80%.

[0296] LC-MS: (m / z) = 412.55 [M+]; fa = 2.31 min.

[0297] 3-(l-{2-[3-(Trifluoromethoxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5- carboxamide (B22) was obtained from 3-(l-{2-[3-(trifluoromethoxy)phenoxy]ethyl}-l / Z- imidazol-5-yl)- l / 7-indole-5-carbonitrilc (A22) according to step 2 of the general procedure. Yield 30%.

[0298] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.67 (d, 7 = 2.0 Hz, 1H); 8.13 - 8.12 (m, 1H); 7.95 (s, 1H); 7.89 (d, 7 = 1.0 Hz, 1H); 7.75 (dd, 7 = 8.6, 1.7 Hz, 1H); 7.66 (d, 7 = 2.5 Hz, 1H); 7.48 (dd, J = 8.5, 0.6 Hz, 1H); 7.34 (t, J = 8.3 Hz, 1H); 7.12 (d, 7 = 1.1 Hz, 1H); 7.10 (s, 1H); 6.92 - 6.88 (m, 1H); 6.88 - 6.85 (m, 1H); 6.83 (dd, J = 6.8, 1.5 Hz, 1H); 4.38 (t, J = 5.2 Hz, 2H); 4.21 (t, J = 5.3 Hz, 2H).

[0299] 13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.83; 159.09; 149.16; 138.27; 137.65; 130.85; 127.60; 126.09; 126.05; 125.84; 125.65; 121.75; 121.03; 119.05; 113.61; 113.06; 111.27; 107.74; 104.68; 67.37; 43.72.

[0300] LC-MS: (m / z) = 431.21 [M+]; fa = 1.97 min.

[0301] Example 23

[0302] 3-(l-{2-[3-(Benzyloxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carbonitrile (A23) was obtained from 2-[3-(benzyloxy)phenoxy]ethyl-l-amine according to step 1 of the general procedure. Yield: 82%.

[0303] LC-MS: (m / z) = 435.34 [M+]; fa = 2.47 min.

[0304] 3-(l-{2-[3-(Benzyloxy)phenoxy]ethyl}-lH-imidazol-5-yl)-lH-indole-5-carboxamide

[0305] (B23) was obtained from 3-(l-{2-[3-(benzyloxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z- indole-5-carbonitrile (A23) according to step 2 of the general procedure. Yield 33%.

[0306] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.67 (d, J = 2.1 Hz, 1H); 8.14 - 8.12 (m, 1H); 7.96 (s, 1H); 7.87 (d, J = 1.0 Hz, 1H); 7.75 (dd, J = 8.6, 1.7 Hz, 1H); 7.66 (d, J = 2.5 Hz, 1H); 7.48 (dd, J = 8.6, 0.5 Hz, 1H); 7.43 - 7.34 (m, 4H); 7.31 (tt, 1H); 7.15 - 7.07 (m, 3H); 6.57 (ddd, 1H); 6.49 (t, J = 2.3 Hz, 1H); 6.41 (ddd, J = 8.3, 2.4, 0.7 Hz, 1H); 5.02 (s, 2H); 4.36 (t, J = 5.3 Hz, 2H); 4.14 (t, J = 5.3 Hz, 2H).

[0307] 13C NMR (126 MHz, DMSO-<76, TMS, ppm): 5 = 168.83; 159.52; 159.10; 138.22; 137.64; 137.00; 129.98; 128.40; 127.80; 127.68; 127.57; 126.08; 126.03; 125.80; 125.64; 121.75; 119.05; 111.27; 107.59; 106.76; 104.73; 101.53; 69.17; 66.84; 43.87.

[0308] LC-MS: (m / z) = 453.27 [M+]; fa = 2.17 min.

[0309] Example 24

[0310] 3-{ l-[2-(3-Hydroxyphenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B24) was obtained as follows. 10 ml of methanol was added to 3-(l-{2-[3- (benzyloxy)phenoxy]ethyl}-l / Z-imidazol-5-yl)-l / Z-indole-5-carboxamide (B23) (110 mg, 0.243 mmol). The whole was washed with argon, and then 20 mg of 10% Pd / C catalyst was added. Argon was removed by vacuum, and then hydrogen was injected. The reaction was left under reducing conditions for 2 hours. The reaction mixture was again washed with argon, and then passed through celite, separating the catalyst. The crude product was purified by chromatography (0 - 10% MeOH in CHCh). The product was obtained as a crystallizing yellowish oil (60 mg, 34% yield).

[0311] ’ H NMR (600 MHz, DMSO-76, ppm): 5 = 11.67 (s, 1H); 9.40 (br s, 1H); 8.13 (d, J = 1.3Hz, 1H); 7.95 (br s, 1H); 7.85 (d, 7= 0.9 Hz, 1H); 7.75 (dd, J= 8.5, 1.6 Hz, 1H); 7.67 (d, 7= 2.3 Hz, 1H); 7.48 (dd, 7 = 8.5, 0.5 Hz, 1H) 7.12 (s, 1H); 7.09 (br s, 1H); 7.00 - 6.98 (m, 1H); 6.34 (ddd, 7 = 8.1, 2.0, 1.0 Hz, 1H); 6.26 - 6.24 (m, 2H); 4.34 (t, 7 = 5.3 Hz, 2H); 4.09 (t, 7 = 5.3 Hz, 2H).

[0312] 13C NMR (151 MHz, DMSO-76,ppm): 5 = 168.85; 159.08; 158.53; 138.19; 137.63; 129.87; 127.54; 126.09; 125.99; 125.75; 125.60; 121.75; 119.03; 111.26; 108.27; 104.95; 104.73; 101.83; 66.60; 43.89.

[0313] HRMS (ESI+): (m / z) calculated for C20H19N4O3 [M+H]: 363.1452; measured: 363.1454.

[0314] Example 25

[0315] 3 - { 1 -[2-(4-Chl oro-3 -fluorophenoxy)ethyl] - 1 7-i m i dazol -5 -yl } - 1 / / -indole-5 -carbonitrile (A25) was obtained from 2-(4-chloro-3-fluorophenoxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 44%.

[0316] LC-MS: (m / z) = 380.82 [M+]; tR= 2.30 min.

[0317] 3 - { 1 -[2-(4-Chl oro-3 -fluorophenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide (B25) was obtained from 3-{ l-[2-(4-chloro-3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / - indole-5-carbonitrile (A25) according to step 2 of the general procedure. Yield 53%.

[0318] ’ H NMR (500 MHz, DMSO-76, TMS, ppm): 5 = 11.71 (s, 1H); 8.11 (s, 1H); 7.96 (s, 1H); 7.87 (s, 1H); 7.75 (dd, 7 = 8.5, 1.4 Hz, 1H); 7.65 (d, 7 = 2.4 Hz, 1H); 7.48 (d, 7 = 8.5 Hz, 1H); 7.38 (t, 7 = 8.9 Hz, 1H); 7.11 (s, 2H); 6.95 (dd, 7 = 11.4, 2.8 Hz, 1H); 6.70 (dd, 7 = 8.9, 1.9 Hz, 1H); 4.36 (t, 7 = 5.1 Hz, 2H); 4.19 (t, 7 = 5.2 Hz, 2H).

[0319] 13C NMR (126 MHz, DMSO-76, TMS, ppm): 5 = 168.85; 158.52; 158.05; 157.97; 156.57; 138.25; 137.66; 130.63; 127.64; 126.07; 125.89; 125.65; 121.73; 119.06; 112.13; 112.11; 111.28; 110.97; 110.83; 104.63; 103.80; 103.60; 72.36; 69.81; 67.63; 62.82; 60.22; 43.63.

[0320] LC-MS: (m / z) = 399.22 [M+]; tR= 1.75min. Example 26

[0321] 3-{ l-[2-(2 / Z-l,3-Benzodioxol-5-yloxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A26) was obtained from 2-(2 / Z-l,3-benzodioxol-5-yloxy)ethyl-l -amine according to step 1 of the general procedure. Yield: 33%.

[0322] LC-MS: (m / z) = 373.09 [M+]; tR= 2.08 min.

[0323] 3-{ l-[2-(2 / Z-l,3-Benzodioxol-5-yloxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B26) was obtained from 3-{ l-[2-(2 / Z-l,3-benzodioxol-5-yloxy)ethyl]-l / Z-imidazol-5-yl}- l / Z-indole-5-carbonitrile (A26) according to step 2 of the general procedure. Yield 41%.

[0324] ’ H NMR (500 MHz, DMSO-t / 6, TMS, ppm): 5 = 11.68 (s, 1H); 8.12 (s, 1H); 7.96 (s, 1H); 7.86 (s, 1H); 7.75 (dd, J = 8.5, 1.5 Hz, 1H); 7.65 (d, J = 2.3 Hz, 1H); 7.48 (d, J = 8.5 Hz, 1H); 7.12 (s, 1H); 7.11 (s, 1H); 6.72 (d, J = 8.5 Hz, 1H); 6.52 (d, 7 = 2.5 Hz, 1H); 6.25 (dd, 1H); 5.93 (s, 2H); 4.32 (t, J = 5.3 Hz, 2H); 4.07 (t, J = 5.3 Hz, 2H).

[0325] 13C NMR (126 MHz, DMSO-6, TMS, ppm): 5 = 168.86; 153.29; 147.90; 141.37; 138.24; 137.65; 127.59; 126.08; 126.04; 125.83; 125.62; 121.75; 119.06; 111.29; 107.96; 105.74; 104.73; 101.03; 97.85; 72.37; 69.81; 67.63; 63.11; 60.23; 43.90.

[0326] LC-MS: (m / z) = 391.16 [M+]; tR= 1.07 min.

[0327] Example 27

[0328] 3-{ l-[2-(3,4-Dichlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carbonitrile (A27) was obtained from 2-(3,4-dichlorophenoxy)ethyl-l -amine according to step 1 of the general procedure without purification.

[0329] LRMS (ESI+): (m / z) calculated for C20H15CI2N4O [M+H]: 397.1; measured: 397.1; (m / z) calculated for C20H13CI2N4O [M-H]: 395.1; measured: 395.1.

[0330] 3-{ l-[2-(3,4-Dichlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5-carboxamide (B27) was obtained from 3-{ l-[2-(3,4-dichlorophenoxy)ethyl]-l / Z-imidazol-5-yl}-l / Z-indole-5- carbonitrile (A27) according to step 2 of the general procedure. Yield 25%.

[0331] ’ H NMR (400 MHz, DMSO-76, TMS, ppm): 5 = 11.68 (s, 1H); 8.12 (narr m, 1H); 7.94 (s, 1H); 7.86 (d, J = 1 Hz, 1H); 7.75 (dd, J = 8.6, 1.6 Hz, 1H); 7.69 (d, J = 2.5 Hz, 1H); 7.47 (dd, J = 8.5, 0.5 Hz, 1H); 7.18 (ddd, J = 11.9, 8.1, 1.5 Hz, 1H); 7.13 (d, J = 1.0Hz, 1H); 7.08 (br s, 1H); 7.07 - 6.98 (m, 2H); 4.39 (t, J = 5.3 Hz, 2H); 4.24 (t, J = 5.3 Hz, 2H).

[0332] HRMS (ESI+): (m / z) calculated for C20H17CI2N4O2 [M+H]: 415.0723; measured: 415.0723. As mentioned above, the derivatives of Formula (I) according to the invention can form salts by reaction with organic and inorganic acids. The reaction proceeds according to the following scheme, wherein the R1and R2substituents are as defined in the present specification, and HA is an organic or inorganic acid.

[0333] II. General procedure of obtaining salts (C) of derivatives of Formula (I)

[0334] 1) General procedure of obtaining salts of organic acids.

[0335] 3-[l-(2-Phenoxyethyl)-l / Z-imidazol-5-yl]-l / Z-indole-5-carboxamide or its derivative (1.44 mmol) was weighed to a round-bottomed flask, to which 3: 1 mixture of ethanol and water (5 ml) was then added. The mixture was heated to 50°C and stirred at this temperature until the substrate was completely dissolved. Then, an appropriate organic acid (2.16 mmol) was added, and the heating was turned off, allowing the mixture to cool down to room temperature. After stirring the mixture at room temperature overnight, the solvent was evaporated on a rotary evaporator, and 10 ml of acetone was added. The resulting suspension was placed in an ultrasonic bath for 15 minutes. After this time, the precipitate formed was fdtered using G4 Schott funnel and washed with 2 x 5 ml of cold acetone. The precipitate was dried under a high vacuum.

[0336] Below are presented examples of the synthesis of specific salts of organic acids.

[0337] Fumarate (Cl)

[0338] 5-(5-Carbamoyl-l / Z-indol-3-yl)-l-(2-phenoxyethyl)-l / Z-imidazol-3-ium (2£)-3- carboxypropenoate (Cl) was obtained according to the above presented general procedure of obtaining organic salts using fumaric acid and 3-[ l -(2-phcnoxycthyl)- l / 7-imidazol-5-yl]- l / Z-indole-5-carboxamide (Bl). Yield 14%. ’ H NMR (600 MHz, DMSO-76, TMS, ppm): 5 = 16.97 (br s, 1H); 12.13 (d, J = 2.3 Hz, 1H); 9.42 (d, J = 1.6 Hz, 1H); 8.13 (narr m, 1H); 7.98 (d, J = 1.6 Hz, 1H); 7.94 (m, 2H); 7.80 (d, J = 8.6, 1.6 Hz, 1H); 7.56 (dd, J = 8.6, 0.5 Hz, 1H); 7.26 - 7.22 (m, 1H); 6.93 (tt, J = 7.5, 1.0 Hz, 1H); 6.88 - 6.85 (m, 2H); 5.35 (dd, J = 9.9, 4.4 Hz, 1H); 4.60 (narr m, 2H); 4.26 (narr m, 2H); 3.48 (dd, J = 16.1, 9.9 Hz, 1H); 2.81 (dd, J = 16.1, 4.5, 1H).

[0339] 13C NMR (151 MHz, DMSO-76,ppm): 5 = 170.99; 168.72; 168.61; 157.60; 137.61; 137.07; 129.44; 128.36; 127.38; 126.87; 125.39; 122.26; 121.23; 120.16; 118.48; 114.67; 111.76; 100.28; 65.26; 59.21; 46.47; 39.18.

[0340] Citrate (C2)

[0341] 5-(5-Carbamoyl- l / 7-indol-3-yl)- l -(2-phenoxycthyl)- l / 7-imidazol-3-ium 3-carboxy-2- (carboxymethyl)-2-hydroxypropionate (C2) was obtained according to the above presented general procedure of obtaining organic salts using citric acid and 3-[l-(2-phenoxyethyl)-lH- imidazol-5-yl]-l / Z-indole-5-carboxamide (Bl). Yield 48%.

[0342] ’ H NMR (600 MHz, DMSO-76, TMS, ppm): 5 = 11.75 (s, 1H); 8.16 (s, 1H); 8.14 (s, 1H); 7.97 (s, 1H); 7.77 (dd, J = 8.6, 1.4 Hz, 1H); 7.73 (d, J = 2.4 Hz, 1H); 7.51 (d, J = 8.5 Hz, 1H); 7.28 (s, 1H); 7.22 (m, 2H); 7.13 (s, 1H); 6.90 (t, J = 7.3 Hz, 1H); 6.82 (d, J = 7.9, 2H); 4.41 (t, 7 = 5.2 Hz, 1H); 4.17 (t, 7 = 5.2 Hz, 2H); 2.74 (d, 7 = 15.3 Hz, 2H); 2.64 (d, 7 = 15.3 Hz, 2H).

[0343] 13C NMR (151 MHz, DMSO-76,ppm): 5 = 206.51; 175.16; 171.35; 168.86; 157.83; 137.87; 137.68; 129.50; 126.37; 126.24; 126.15; 126.04; 125.79; 121.87; 120.99; 118.99; 114.45; 111.40; 103.92; 72.23; 66.47; 44.35; 43.11; 30.68.

[0344] Succinate (C3)

[0345] 5 -(5 -Carbamoyl- 1 TZ-indol-3 -yl)- 1 -(2 -phenoxyethyl)- 1 TZ-imidazol-3 -ium 3 - carboxypropionate (C3) was obtained according to the above presented general procedure of obtaining organic salts using succinic acid and 3-[l-(2-phenoxyethyl)-lH-imidazol-5-yl]- l / Z-indole-5-carboxamide (Bl). Yield 48%

[0346] ’ H NMR (600 MHz, DMSO-76, TMS, ppm): 5 = 12.29 (br s, 2H); 11.69 (s, 1H); 8.14 (s, 1H); 7.97 (s, 1H); 7.93 (s, 1H); 7.76 (dd, 7 = 8.6, 1.5 Hz, 1H); 7.69 (d, 7 = 2.4 Hz, 1H); 7.49 (d, 7 = 8.5 Hz, 1H); 7.22 (m, 2H); 7.16 (s, 1H); 6.90 (t, 7 = 7.3 Hz, 1H); 6.81 (d, 7 = 7.9, 2H); 4.38 (t, 7 = 5.3 Hz, 1H); 4.15 (t, 7 = 5.3 Hz, 2H); 2.43 (s, 6H).13C NMR (151 MHz, DMSO-t / 6,ppm): 5 = 173.67; 168.91; 157.88; 138.20; 137.69; 129.50; 127.30; 126.14; 126.09; 125.99; 125.75; 121.81; 120.94; 119.07; 114.44; 111.33; 104.60; 66.66; 43.99; 28.89.

[0347] 2) General procedure of obtaining salts of inorganic acids.

[0348] 3-[l-(2-Phenoxyethyl)-l / Z-imidazol-5-yl]-l / Z-indole-5-carboxamide or its derivative was weighted to an Erlenmeyer flask, to which ethanol (6.5 vol.) was then added. The mixture was heated to 50°C and placed in an ultrasonic bath until the compound was completely dissolved. A solution of an appropriate acid (1 equiv.) in ethanol (2 vol.) was then added, which caused the immediate precipitation of a salt. Stirring was continued for 1 h, and then the mixture was filtered under vacuum. The precipitate was washed with ethanol (5 x 2 vol.), diethyl ether (2 x 2 vol.) and dried in a vacuum dryer.

[0349] Examples of the synthesis of specific salts of inorganic acids are presented below.

[0350] Phosphate (C4)

[0351] 5-(5-Carbamoyl-l / Z-indol-3-yl)-l-(2-phenoxyethyl)-l / Z-imidazol-3-ium dihydrogen phosphate(V) (C4) was obtained according to the above presented general procedure of obtaining inorganic salts using phosphoric acid(V) and 4.636 g (mmol) 3-[l-(2- phenoxyethyl)-l / Z-imidazol-5-yl]-l / Z-indole-5-carboxamide (Bl). Yield 75%

[0352] ’ H NMR (600 MHz, DMSO-t / 6): 8 = 11.72 (d, J = 1.9 Hz, 1H); 8.14 - 8.10 (m, 1H); 8.27 - 8.01 (m, 1H); 8.20 - 8.01 (m, 1H); 8.01 (t, J = 28.5 Hz, 1H); 7.88 - 7.75 (m, 1H); 7.75 - 7.65 (m.l H); 7.65 - 7.42 (m, 1H); 1H, 7.38 - 7.05 (m, 3H); 7.05 - 6.76 (m, 3H); 4.39 (t, J = 5.4 Hz, 2H); 4.16 (t, J = 5.4 Hz, 2H).

[0353] 31P NMR (600 MHz, DMSO-t / 6): 6 = 0.06 (s).

[0354] Elementary analysis

[0355] For Formula C20H21N4O6P

[0356] Calculated (%) C 54.06, H 4.76, N 12.61

[0357] Measured (%) C 49.54, H 4.68, N 11.47

[0358] Sulfate (C5)

[0359] 5-(5-Carbamoyl-l / Z-indol-3-yl)-l-(2-phenoxyethyl)-l / Z-imidazol-3-ium sulfate(VI) (C5) was obtained according to the above presented general procedure of obtaining inorganic salts using sulfuric acid (VI) and 0.15 g (0.433 mmol) 3-[l-(2-phenoxyethyl)-lH-imidazol-5-yl]- l / Z-indole-5-carboxamide (Bl). Yield 63%.

[0360] 1H NMR (600 MHz, DMSO-76): 8 = 14.65 (s, br, 1H); 12.03 (d, J = 2.3 Hz, 1H); 9.39 (d, J = 1.5 Hz, 1H); 8.21 - 8.05 (m, 1H); 7.93 (d, J = 1.7 Hz, 3H); 7.80 (dd, J = 8.6, 1.6 Hz, 2H); 7.73 - 7.31 (m, 4H); 7.32 - 7.04 (m, 3H); 6.97 - 6.89 (m, 1H); 6.87 - 6.79 (m, 2H); 4.61 (t, J = 5.0 Hz, 2H); 4.27 (t, J = 5.0 Hz, 2H).

[0361] Elementary analysis

[0362] For Formula C20H20N4O6S

[0363] Calculated (%) C 54.05, H 4.54, N 12.61

[0364] Measured (%) C 55.92, H 4.93, N 12.89

[0365] Chloride (C6)

[0366] 5-(5-Carbamoyl-l / Z-indol-3-yl)-l-(2-phenoxyethyl)-l / Z-imidazol-3-ium chloride (C6) was obtained according to the modified general procedure of obtaining inorganic salts, using 126 mg (0.363 mmol) 3-[l-(2-phenoxyethyl)-l / Z-imidazol-5-yl]-l / Z-indole-5-carboxamide (Bl). The modification consisted in using 1.1 equiv. hydrochloric acid, i.e. 35 pl 36% solution. Yield 52%.

[0367] 1H NMR (600 MHz, DMSO-76): 6 = 15.26 (s, br, 1H); 12.23 (d, J = 2.4 Hz, 1H); 9.45 (d, J = 1.5 Hz, 1H); 8.19 - 8.10 (m, 1H); 8.07 - 7.89 (m); 7.85 - 7.76 (m, 4H); 7.56 (dd, J = 8.6, 0.5 Hz, 1H); 7.29 - 7.11 (m, 4H); 6.92 (tt, 7 = 7.6, 1.0 Hz, 1H); 6.87 - 6.76 (m, 3H); 4.61 (t, 7 = 5.0 Hz, 2H); 4.28 (t, 7 = 5.1 Hz, 2H).

[0368] III. Biological studies

[0369] 1. In-vitro studies of affinity for 5-HT? serotonin receptor and agonist activity towards this receptor a) Cell culture and preparation of membranes for isotopic assays.

[0370] HEK293 cells stably expressing the human serotonin 5-HTIA and 5-HT? receptors (obtained with the use of Eipofectamine 2000) were grown in supplemented Dulbecco’s Modified Eagle’s Medium (DMEM) with the addition of 10% dialyzed foetal bovine serum (FBS) and 500 pg / ml geneticin antibiotic (G418) at 37°C in a humidified atmosphere with 5% CO2. To prepare membranes for in vitro affinity study by isotope-labelled ligand displacement method, the cells were seeded in 150 cm2flasks and were grown until 90% confluence was obtained. Then, the cells were washed twice with PBS buffer pre-warmed to 37° C and were centrifuged (200 x g) for 5 min in the same buffer with the addition of 0.1 mM ethylenediaminetetraacetic acid (EDTA) and 1 mM dithio threitol (DTT). After centrifugation, membrane pellets were frozen and stored at -80°C until further studies. b) Affinity study by isotope-labelled ligand displacement method

[0371] Frozen pellets of the HEK293 cells stably expressing 5-HTIA or 5-HT7receptor were homogenized (Ultra Turrax tissue homogenizer) in 10 ml volume of a buffer for a competitive experiment and then were centrifuged twice for 20 min at 4°C (35 000 x g). The centrifuged material was suspended in supplemented buffer Tris-HCl. The compositions of buffers for the analysis were as follows: for 5-HTIAR: 50 mM Tris HC1, 0.1 mM EDTA, 4 mM MgCh, 10 pM pargyline and 0.1% ascorbic acid; for 5-HT7bR: 50 mM Tris HC1, 4 mM MgCh, 10 pM pargyline and 0.1% ascorbic acid. Samples having the total volume of 200 pl were incubated until equilibrium was obtained (incubation for 60 min at 37°C). After that time, the samples were filtered several times and washed with cold (4°C) Tris-HCl buffer onto UniFilter plates by means of Unifilter Harvester (PerkinElmer). The radioactivity of the pellet remaining on the filters was measured with Microbeta plate reader (PerkinElmer, USA). The following were used as specific radioligands: for 5-HTIAR: 2.5 nM [3H]-8-OH- DPAT (135.2 Ci / mmol, PerkinElmer, USA), for 5-HT7R: 0.8 nM [3H]-5-CT (39.2 Ci / mmol). Nonspecific binding was determined using 10 pM serotonin solution. Each experiment was repeated three times and 7 concentrations of the tested compound (10-10- 10"4M) were used. The inhibition constant (Ki) was calculated using the Cheng-Prusoff equation. The results were presented as averages from at least two separate experiments. c) Study of the agonist activity of compounds towards 5-HT? receptor

[0372] The agonist activity of compounds was tested in HEK293 cells stably expressing 5-HT7receptor as their ability to increase the production of cyclic adenosine-3',5'-monophosphate (cAMP). Each compound was tested at 7 concentrations in the range of 10-11- 10-5M. The cells stably expressing the human 5-HT7serotonin receptor (prepared with the use of Lipofectamine 2000) for the activity study were grown in supplemented DMEM with the addition of 10% dialyzed foetal bovine serum (FBS) and 500 pg / ml geneticin antibiotic (G418) at 37°C in a humidified atmosphere with 5% CO2. For the activity studies, the cells were seeded in 25 cm2flasks and were grown until 90% confluence was obtained. Then, the cells were washed twice with PBS buffer pre-warmed to 37°C and centrifuged (160xg) for 5 min. The supernatant was separated, and the pellet was re-suspended in a stimulation buffer (1 x HBSS, 5 mM HEPES, 0.5 mM IBMX and 0.1% BSA). The total cAMP concentration was measured using LANCE Ultra cAMP detection kit (PerkinElmer) according to the manufacturer’s directions. To determine the cAMP concentration, the cells (5 pl) were incubated with a solution of the tested compound (5 pl) for 30 min at room temperature in 384-well plates (white opaque microtiter plate). After incubation, 10 pl of a reagent (5 pl of Eu-cAMP and 5 pl of ULight-anti-cAMP) was added to stop the reaction and induce cell lysis. The assay plate was incubated for 1 hour at room temperature, and time-resolved fluorescence resonance energy transfer (TR-FRET) was detected by Infinite Ml 000 Pro apparatus (Tecan, Mannedorf, Switzerland) using the settings described in the LANCE Ultra cAMP detection kit manual.

[0373] Table 1 below shows the results of the above-described studies for the exemplary derivatives according to the invention.

[0374] Table 1: Results of the studies of affinity for 5-HT? serotonin receptor and agonist activity towards this receptor

[0375] 2. In vivo behavioral test using a peripheral neuropathy model

[0376] The tests were performed using male / female Swiss and male Wistar rats and mice purchased from Charles River (Sulzfeld, Germany). In the peripheral neuropathy model (CCI model), the loose ligation of the sciatic nerve is performed under isoflurane anesthesia (2% isoflurane in a mixture with 100% oxygen administered by inhalation). After gently separating the lateral head of the quadriceps muscle from the biceps muscle of the thigh, the sciatic nerve is exposed, and three (in a mouse) / four (in a rat) loose ligations are performed using a sterile surgical thread. The procedure ends with suturing of the skin. Day “0” is considered as the day of sciatic nerve damage. Seven days after inducing neuropathic pain in the CCI model, behavioral tests were performed to determine hypersensitivity to a mechanical stimulus (the von Frey test) and a thermal stimulus (the Cold Plate Test) at several time points (0.5 h, 1.5 h, 3 h and 24 h) after the administration of the tested compounds. A response to a tactile stimulus was measured using Dynamic Plantar Aesthesiometer (Ugo Basile). The measured parameter was a filament’s automatically increasing pressure force on the sole of the right paw - it is not a pain stimulus because such stimulation does not cause a response in healthy animals, hence, no measurement was performed on the left paw without the sciatic nerve ligated. A response to a thermal stimulus - low temperature - was measured using Cold Plate Analgesia Meter (Columbus Instruments). Animals were placed individually in a cage with regulated floor temperature, set at 2°C (for mice) and 5°C (for rats). The measured parameter was a response time from the moment of placing the rodent in the cage. The response was considered to be a characteristic lifting of the paw from the floor, and the maximum test time was 30 seconds.

[0377] The behavioural tests in mice have shown that compound Bl according to the invention (Example 1), when administered once intraperitoneally in the dose of 20 mg / kg in male mice in the model of neuropathic pain induced by sciatic nerve ligation, shows very good analgesic effects, which are comparable with the effect of the reference compound - the compound described in Example 26 in US 10844046 B2. However, the reference compound was administered in very high dose of 60 mg / kg. It has been further shown that, in the von Fey test, the compound according to the invention is more effective than the reference compound, even if it is administered in a smaller dose (20 mg / kg of the compound according to the invention as compared to 60 mg / kg of the reference compound). The results of the tests are presented in Figure 1.

[0378] Furthermore, after both the intraperitoneal and oral administration of the reference compound (Example 26 in US 10844046 B2) and compound Bl according to the invention (Example 1) no disorders of locomotor functions were observed; these compounds did not affect the body temperature of the mice, either. Moreover, compound B 1 according to the invention (Example 1) did not cause diarrhoea in contrast to the reference compound. The summary of the obtained results is presented in Table 2.

[0379] Table 2: Comparison of analgesic properties and side effects for the compound from Example 26 (US 10844046 B2) and compound Bl from Example 1 according to the invention in the model of neuropathic pain induced by sciatic nerve ligation.

[0380] 3. In vivo pharmacokinetics tests

[0381] The tested compounds were administered to CD-I mice (male) intragastrically using a gavage tube in the dose of 10 mg / kg of body weight or intravenously into the tail vein in the dose of 2.5 mg / kg of body weight. Blood samples were collected, respectively, 5 min., 15 min., 30 min., 60 min., 120 min., 240 min. and 480 min. after the intragastric administration of the compound and 5 min., 15 min., 30 min., 60 min., 120 min., 240 min. and 480 min. after the intravenous administration of the compound. The samples were collected into test tubes to which 20 pl of heparin had previously been added. After centrifugation, the plasma was frozen at -80°C. Concentrations were measured by LC-MS / MS method (LC- ESI / MS / MS system, ACQUITYUPLC I-Class / Xevo TQD IVD series (Waters Corporation, USA), Acquity UPLC BEH Cl 8 chromatographic column (1.7 pm, 2.1 x 50 mm, Waters, USA); mobile phase: 1% formic acid in water (Phase A) - 1% formic acid in acetonitrile (Phase B); isocratic conditions: 95% A : 5% B for 6 min, internal standard (IS) - 2-(4-methyl- l-piperazinyl)-4-phenylquinazoline). The analysis was performed under positive ionisation, in the mode of tracking selected fragmentation reactions. The analysis of pharmacokinetic parameters was performed using model-free analysis (WinNonlin Professional v. 3.3). Bioavailability was calculated from the analysis of the area under the curve of plasma concentrations.

[0382] The obtained results indicate that compound Bl according to the invention (Example 1) has the bioavailability after oral administration more than twice as high as the reference compound described in Example 26 in US 10844046 B2.

Claims

Claims1. An imidazole-indole derivative of Formula (I):Formula (I) wherein:- R1and R2represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-Ci-C3 alkylsulfanyl group, or- R1and R2together form a C1-C3 alkylenedioxy group, or its pharmaceutically acceptable salt.

2. The imidazole-indole derivative according to claim 1, wherein the substituted C1-C3 alkoxy group is selected from the group consisting of a halo-Ci-C3 alkoxy group and a phenyl-Ci-C3 alkoxy group, wherein the halo-Ci-C3 alkoxy group comprises at least one halogen atom selected from the group consisting of a bromine atom, a fluorine atom, a chlorine atom and an iodine atom.

3. The imidazole-indole derivative according to claim 2, wherein all hydrogen atoms in the halo-Ci-C3 alkoxy group have been substituted with halogen atoms.

4. The imidazole-indole derivative according to any one of claims 1 to 3, wherein the substituted C1-C4 alkyl group is selected from the group consisting of a halo-Ci-C4 alkyl group and a C1-C3 alkoxy-Ci-C4 alkyl group, wherein the halo-Ci-C4 alkyl group comprises at least one halogen atom selected from the group consisting of a bromine atom, a fluorine atom, a chlorine atom and an iodine atom.

5. The imidazole-indole derivative according to claim 4, wherein all hydrogen atoms in the halo-Ci-C4 alkyl group have been substituted with halogen atoms.

6. The imidazole-indole derivative according to any one of claims 1 to 5, wherein the halo- C1-C3 alkylsulfanyl group comprises at least one halogen atom selected from the group consisting of a bromine atom, a fluorine atom, a chlorine atom and an iodine atom.

7. The imidazole-indole derivative according to claim 6, wherein all hydrogen atoms in the halo-Ci-Cs alkylsulfanyl group have been substituted with halogen atoms.

8. The imidazole-indole derivative according to any one of claims 1 to 7, wherein R1and R2represent, independently of each other, a hydrogen atom, a chlorine atom, a bromine atom, an iodine atom, a fluorine atom, a hydroxy group, a methoxy group, a trifluoromethoxy group, a benzyloxy group, a methyl group, a tert-butyl group, a trifluoromethyl group, a methoxyethyl group, a methylsulfonyl group, an amide group or a trifluoromethylsulfanyl group, or whereinR1and R2together form a methylenedioxy group.

9. The imidazole-indole derivative according to claim 8, wherein R1and R2represent, independently of each other, a hydrogen atom, a methoxy group, a chlorine atom, a bromine atom or an iodine atom.

10. The imidazole-indole derivative according to any one of claims 1 to 9, wherein R1and / or R2are in the para and / or meta position relative to the oxygen atom of the phenoxy group.

11. The imidazole-indole derivative according to claim 10, wherein R1or R2is in the para position relative to the oxygen atom of the phenoxy group.

13. The imidazole-indole derivative according to any one of claims 1 to 11, wherein the derivative is selected from the group consisting of the following compounds:- 3-[l-(2-phenoxyethyl)-l / / -imidazol-5-yl]-l / / -indole-5-carboxamide,- 3 - { 1 - [2-(4-methoxyphenoxy)ethyl] - 1 7-i m i dazol -5 -yl } - 1 / / -indole-5 -carboxamide,- 3 - { 1 - [2-(4-methylphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide.- 3-(l-{2-[4-(trifluoromethyl)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5- carboxamide,- 3-{ l-[2-(4-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,- 3 - { 1 - [2-(4-chlorophenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,- 3-{ l-[2-(4-bromophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,- 3-{ l-[2-(4-iodophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,- 3 -( 1 - { 2- [4-(trifluoromethoxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 - carboxamide,- 3 -( 1 - { 2- [4-(benzyloxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 -carboxamide,- 3 - { 1 - [2-(4-hydroxyphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,- 3-(l-{2-[4-(2-methoxyethyl)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5- carboxamide,- 3 - { 1 - [2-(4-terZ-butylphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,- 3-(l-{2-[4-(methanesulfonyl)phenoxy]ethyl]-l / / -imidazol-5-yl)-l / / -indole-5- carboxamide,- 3 - [ 1 -(2- { 4- [(trifluoromethyl) sulfanyl] phenoxy } ethyl)- 1 H- imidazol-5 -yl] - l / Z-indole-5- carboxamide,- 3-{l-[2-(4-carbamoylphenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,- 3 - { 1 - [2-(3 -methoxyphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,- 3 - { 1 - [2-(3 -methylphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,- 3-{l-[2-(3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,- 3 - { 1 - [2-(3 -chlorophenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,- 3-{l-[2-(3-bromophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide,- 3 -( 1 - { 2- [3 -(trifluoromethoxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 - carboxamide,- 3 -( 1 - { 2- [3 -(benzyloxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 -carboxamide,- 3 - { 1 - [2-(3 -hydroxyphenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carboxamide,- 3-{l-[2-(4-chloro-3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5- carboxamide,- 3-{l-[2-(2 / / -l,3-benzodioxol-5-yloxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5- carboxamide,- 3-{l-[2-(3,4-dichlorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carboxamide, and their pharmaceutically acceptable salts.

13. The imidazole-indole derivative according to any one of claims 1 to 12, wherein the pharmaceutically acceptable salt is a salt of an organic or inorganic acid.

14. The imidazole-indole derivative according to claim 13, wherein the organic or inorganic acid is selected from the group consisting of fumaric acid, citric acid, succinic acid, phosphoric acid, sulfuric acid and hydrochloric acid.

15. A pharmaceutical composition comprising a therapeutically and / or prophylactically effective amount of an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as defined in any one of claims 1 to 14 as an active substance and at least one pharmaceutically acceptable excipient.

16. The pharmaceutical composition according to claim 15 designed to be administered orally, parenterally, by inhalation, transdermally or transmucosally.

17. An imidazole-indole derivative of Formula (I) as defined in any one of claims 1 to 14 or a pharmaceutical composition as defined in any one of claims 15 to 16, for use as a 5-HT? serotonin receptor agonist.

18. An imidazole-indole derivative of Formula (I) as defined in any one of claims 1 to 14 or a pharmaceutical composition as defined in any one of claims 15 to 16, for use as a medicine.

19. An imidazole-indole derivative of Formula (I) as defined in any one of claims 1 to 14 or a pharmaceutical composition as defined in any one of claims 15 to 16, for use in the treatment and / or prevention of a disease or disorder in which 5-HT? serotonin receptor is involved.

20. The imidazole-indole derivative of Formula (I) or the pharmaceutical composition for use according to claim 19, in the treatment and / or prevention of acute or chronic pain.

21. The imidazole-indole derivative of Formula (I) or the pharmaceutical composition for use according to claim 20, in the treatment and / or prevention of pain selected from the group comprising fibromyalgia, migraine, neuropathic pain, cancer pain, burning mouth syndrome, tension-type pain, vulvodynia, pain in irritable bowel syndrome, pain in the course of functional disorders of the gastrointestinal tract, pain in the course of Oddi’s sphincter dysfunction, back pain, psychogenic purpura, postoperative pain, post-traumatic pain, rheumatic pain, inflammatory pain, pain in the course of osteoarthritis, musculoskeletal pain in the course of neurological diseases, trigeminal neuralgia and pain of unknown origin.

22. A method for the treatment or prevention of a disease or disorder in which 5-HT? serotonin receptor is involved in a subject, the method comprising administering to the subject in need thereof an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as defined in any one of claims 1 to 14 or a pharmaceutical composition as defined in any one of claims 15 to 16, in an amount effective for the treatment or prevention of the disease or disorder in which 5-HT? serotonin receptor is involved.

23. The method for the treatment or prevention according to claim 22, wherein the disease or disorder in which 5-HT? serotonin receptor is involved is acute or chronic pain.

24. The method for the treatment or prevention according to claim 23, wherein the pain is selected from the group comprising fibromyalgia, migraine, neuropathic pain, cancer pain, burning mouth syndrome, tension-type pain, vulvodynia, pain in irritable bowel syndrome, pain in the course of functional disorders of the gastrointestinal tract, pain in the course of Oddi’s sphincter dysfunction, back pain, psychogenic purpura, postoperative pain, post- traumatic pain, rheumatic pain, inflammatory pain, pain in the course of osteoarthritis, musculoskeletal pain in the course of neurological diseases, trigeminal neuralgia and pain of unknown origin.

25. An intermediate product of Formula (II):Formula (II) wherein:- R1and R2represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-Ci-C3 alkylsulfanyl group, or- R1and R2together form a C1-C3 alkylenedioxy group.

26. The intermediate product of Formula (II) according to claim 25, wherein the intermediate product is selected from the group consisting of the following compounds:- 3 - [ 1 -(2-phenoxyethyl)- 1 / 7-i m i dazol - 5 -yl ] - 1 / 7-i n dol e- 5 -carbonitrile ;- 3-{ l-[2-(4-methoxyphenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(4-methylphenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-(l-{2-[4-(trifluoromethyl)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5-carbonitrile;- 3-[ l -[2-(4-fluorophcnoxy)cthyl]- l / 7-imidazol-5-yl J- l / 7-indole-5-carbonitrilc;- 3-{ l-[2-(4-chlorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(4-bromophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(4-iodophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;3 -( 1 - { 2- [4-(trifluoromethoxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 - carbonitrile;- 3 -( 1 - { 2- [4-(benzyloxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 -carbonitrile;- 3-(l-{2-[4-(2-methoxyethyl)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5-carbonitrile;- 3-{ l-[2-(4-tert-butylphenoxy)ethyl)-l / / -imidazol-5-yl)-l / / -indole-5-carbonitrile;3-(l-{2-[4-(methanesulfonyl)phenoxy]ethyl}-l / / -imidazol-5-yl)-l / / -indole-5- carbonitrile;3-[ 1 -(2- { 4- [(trifluoromethyl) sulfanyl] phenoxy } ethyl)- 1 / Z- imidazol-5 -yl] - 1 / / - indole-5 - carbonitrile;- 3-{ l-[2-(4-cyanophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(3-methoxyphenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(3-methylphenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(3-chlorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;- 3-{ l-[2-(3-bromophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;3 -( 1 - { 2- [3 -(trifluoromethoxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 - carbonitrile;- 3 -( 1 - { 2- [3 -(benzyloxy)phenoxy] ethyl } - 1 / / -imidazol-5 -yl)- 1 / / -indole-5 -carbonitrile;- 3-{ l-[2-(4-chloro-3-fluorophenoxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5-carbonitrile;3-{ l-[2-(2 / / -l,3-benzodioxol-5-yloxy)ethyl]-l / / -imidazol-5-yl}-l / / -indole-5- carbonitrile; and- 3 - { 1 - [2-(3 ,4-dichlorophenoxy)ethyl] - 1 / / -imidazol-5 -yl } - 1 / / -indole-5 -carbonitrile.

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