SULPHONAMIDE DERIVATIVES OF ALICYCLIC AMINES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES

Description

FIELD OF THE INVENTION

The present invention relates to novel sulphonamide derivatives of alicyclic amines having affinity to dopaminergic, serotoninergic, adrenergic receptors and to serotonin transporter receptors, pharmaceutical compositions containing the same and to the use thereof. The compounds may be useful for the treatment of diseases of the central nervous system (CNS), such as schizophrenia, bipolar affective disorder, depression, anxiety disorders, sleep disorders or Alzheimer disease.

STATE OF ART

CNS disorders are considered a global medical problem. A number of people suffering from those diseases constantly grows, particularly in highly developed countries and intensively developing ones.

Among all psychiatric diseases, schizophrenia, depression, bipolar affective disorder, anxiety, sleep disorders and addictions are the major ones. The main neurologic disorders are Alzheimer's disease, Parkinson's disease, epilepsy and different pain disorders.

Antipsychotic drugs, which are main treatment of schizophrenia, are divided into two main classes on the basis of their liability to induce neurological side effects after long-term treatment. Typical antipsychotic drugs, such as chlorpromazine and haloperidol, induce after repeated administration various extrapyramidal side effects (EPS) including Parkinson-like symptoms and tardive dyskinesia. Repeated treatment with so called atypical antipsychotic drugs, such as clozapine, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole, is associated with a lower incidence of neurological side effects. Typical antipsychotics reduce positive symptoms but do not reduce negative symptoms and cognitive dysfunctions. Plasma prolactin levels are increased in humans, and there is a gain in body weight potentially leading to the development of metabolic syndrome. Atypical antipsychotic drugs effectively reduce positive symptoms and also to some extent negative symptoms and cognitive disturbances, while producing less serious EPS. Atypical antipsychotic drugs differ in their propensity to elevate plasma prolactin levels in humans. Typical antipsychotic drugs block dopamine D2 receptors in the mesolimbic and nigrostriatal system. This mechanism is responsible for the antipsychotic effect (reduction of positive symptoms) as well as induction of EPS. Clinical support for the dopamine hypothesis of antipsychotic drug action was provided by PET findings of high dopamine D2 receptor occupancy in the striatum of patients responding to different antipsychotic drug treatments. Patients with a good response show dopamine D2 receptor occupancy of more than 65% (Nord M, Farde L., CNS Neuroscience & Therapeutics. 2010; 17:97.). The occurrence of EPS seems to be related to a higher occupancy of dopamine D2 receptors (above 80%). Atypical antipsychotics, also called second generation antipsychotic drugs, have clinical approvals for the treatment of psychosis and mania. Each drug has a unique pharmacodynamic and pharmacokinetic profile. Some of atypical antipsychotic drugs have additional antidepressant, anxiolytic or hypnotic profile (Schwartz T. L., Stahl S. M., CNS Neurosci. Ther.; 17(2), 110-7, 2011). Atypical antipsychotic drugs have in common a potent serotonin 5-HT2A receptor antagonism in relation to a weaker dopamine D2 receptor antagonism. This pharmacodynamic property is the basis of “atypicality” (Meltzer H. Y., Neuropsychopharmacology; 1, 193-6, 1989). Antagonism of 5-HT2A receptors likely allows more dopamine activity and neurotransmission to occur in the nigrostriatal system to avoid EPS. The same mechanism may allow small improvement in negative symptoms, and 5-HT2 antagonism in the tuberoinfundibular pathway may help to avoid hyperprolactinemia (Schwartz T. L., Stahl S. M., CNS Neurosci. Ther.; 17(2), 110-7, 2011).

Dopaminergic D2 receptors are the primary biological target of antipsychotic therapy. It is a recognized fact that blockade of these receptors in the mesolimbic system is responsible for the antipsychotic activity of neuroleptics, in particular for preventing positive symptoms. All antipsychotic drugs currently used exhibit at least moderate affinity for dopamine D2 receptors. However, blockade of these receptors in the nigrostriatal system if not compensated by a partial agonism to these receptors or by affecting other receptors (5-HT2A, 5-HT1A, alfa2c), may be a cause of extrapyramidal disorders, such as drug-induced parkinsonism, and within tuberoinfundibular pathway—of hyperprolactinaemia (Miyamoto S. et al., Mol. Psychiatry; 10(1), 79-104, 2005).

Dopaminergic D3 receptors are localized in limbic cortex and thus a preferential blockade of these receptors offers locally selective antidopaminergic activity. This results in increased effectiveness in reducing positive symptoms of schizophrenia sparing the blockade of extrapyramidal system and therefore reduces the risk of the main side effect such as pseudoparkinson's syndrome. Moreover, several preclinical data suggests that D3 dopamine receptor antagonism is more efficient in reducing the negative symptoms of schizophrenia and improves working memory. (Gray, J. A., Roth B. L.; Schizophr. Bull.; 33(5, 1100-19, 2007).

Serotoninergic neurons interact with dopaminergic neurons. Antagonistic activity of antipsychotics against serotoninergic receptors 5-HT2A type can stimulate the release of dopamine in the extrapyramidal, tuberoinfundibular systems and prefrontal cortex but not in the limbic system, what can result in alleviation of undesirable extrapyramidal symptoms and hyperprolactinaemia induced by D2 receptor blockade and in increased effectiveness of the drug against some of negative symptoms of schizophrenia, without increasing the positive symptoms. It is considered that high affinity for 5-HT2A receptors, higher than for D2 receptors, is one of the reasons of atypicality of the second-generation antipsychotics. Similar effects to those caused by the blockade of 5-HT2A receptors, are achieved by stimulation of serotonin receptor type 5-HT1A (aripiprazole, ziprasidone). It is assumed that stimulation of 5-HT1A receptors takes part in the antipsychotic effect in combination with D2 receptor blockade, especially in the safety profile of drug as well as is beneficial in fighting mood and cognitive symptoms of schizophrenia (Kim D. et al., Neurotheropeutics, 6(1), 78-85, 2009).

Serotoninergic receptors type 5-HT6 are almost exclusively localized in the central nervous system (CNS). Both the localization of the 5-HT6 receptors in limbic and cortical brain areas and relatively potent affinity and antagonistic activity of several antipsychotics (clozapine, olanzapine, sertindole) and antidepressants (mianserin, amitryptiline) at 5-HT6 receptors are suggestive of a potential role in pathophysiology and treatment of CNS disorders. Recent data in the literature indicate that blockade of 5-HT6 receptors may be implicated in a pro-cognitive effect due to the increase in cholinergic transmission, in antidepressant activity due to the increase in noradrenergic and dopaminergic one, as well as in an anxiolytic effect, It is evident that 5-HT6 receptor has emerged as a very interesting molecular target and antagonists of this receptor may serve as potential drugs in treatment of disorders characterized by cognitive impairments, such as Alzheimer's disease, schizophrenia, depression, anxiety (Liu K., Robichaud A., Drug Development Research 70,145-168, 2009; Wesotowska, A; Nikiforuk, A, Neuropharmacology 52(5), 1274-83, 2007). Moreover, 5-HT6 receptor antagonists have been demonstrated to be active in reduction of food intake and body weight by clinically approved mechanism that is consistent with the enhancement of satiety. Hence, several compounds with 5-HT6 receptor antagonistic activity are currently being clinically evaluated for the treatment of obesity (Heal D. et al., Pharmacology therapeutics, 117(2), 207-231, 2008).

Intensive research conducted since 1993 indicates that serotoninergic 5-HT7 receptors may play some role in the control of circadian rhythms, sleep, thermoregulation, cognitive processes, pain and migraine, as well as in neuronal excitability. Potent affinity and antagonistic activity of several antipsychotic and antidepressant drugs at 5-HT7 receptors suggest a potential role of these receptors in pathophysiology of many neuropsychiatric disorders. Taking into account the behavioral data presented in the literature, it has been established that selective 5-HT7 receptor antagonists produce antidepressant and anxiolytic activity in rats and mice (Wesotowska A. et al., Neuropharmacology 51, 578-586, 2006). Using mouse models of antipsychotic activity, Galici et al. showed that a selective 5-HT7 receptor antagonist SB-269970 may also evoke antipsychotic-like effects (Galici R. et al., Behav. Pharmacol.; 19(2), 153-9, 2008).

Serotoninergic 5-HT2C and histaminergic H1 receptors localized in hypothalamus play important role in food intake regulation. Blockade of both types of these receptors produced by antipsychotic drugs is most closely correlated with increased risk of weight gain and diabetes. On the other hand, blockade of 5-HT2C receptors, mostly localized in cortical areas and in the hippocampus, striatum, septal nuclei, thalamic and midbrain nuclei, may produce beneficial antidepressant and pro-cognitive effects. In the substantia nigra, 5-HT2C receptors are co-localised with GABA, indicating that they yield indirect control of dopaminergic transmission. Consequently, the blockade of 5-HT2C receptors, together with the 5-HT2A receptor one, would potentiate the D2 receptor-mediated tonic inhibitory control of dopaminergic projection, with protective effect against extrapyramidal symptoms (Kim D. et al., Neurotherapeutics, 6(1), 78-85, 2009). Histaminergic H1 receptor blockade produced by antipsychotic drugs may be implicated in sedative effect that is clinically profitable in controlling arousal that accompanies the acute phase of psychosis. It seems that simultaneous reduction in affinity of new molecule for both types of these receptors may be an element that protects against excessive body weight. However, the total elimination of affinity for these receptors may not be necessary because of certain benefits of blockade of 5-HT2C and H1 receptors.

Blockade of alpha2 adrenergic receptors potentiates antidepressants-induced increase of extracellular monoamines. This may suggest that substances inhibiting monoamine transporters and simultaneously blocking alpha2 adrenergic receptors may be potent and fast acting new antidepressants. Moreover, alpha2 antagonists potentiate acetylcholine secretion in the frontal cortex and may improve cognitive functions, what may provide additional advantages both in antidepressant therapy and antipsychotic therapy (especially improvement in negative symptoms). Blockade of alpha2 adrenergic receptors may also counteract sexual dysfunctions caused by serotonin reuptake inhibitors (Millan M., Neurotherapeutics, 6(1), 53-77, 2009). Alpha2 antagonists may also be beneficial in reducing extrapyramidal symptoms caused by blockade of D2 receptors in the striatum. Similarly, blockade of alpha1 adrenergic receptors, despite potential peripheral adverse effects involving hypotension, may cause some central nervous system benefits involving decrease in the risk of extrapyramidal side effects caused be antipsychotics. This may be associated with interaction between noradrenergic and serotoninergic neurons (Horacek J. et al., CNS Drugs, 20(5), 389-409, 2006).

Sigma receptors are a separate group of CNS receptors; however their physiological role is still unknown. It has been shown that some psychotomimetic substances like phencyclidine, metamphetamine, heroin or dextrometorphan are potent sigma receptor agonists. On the other hand, a classic antipsychotic drug haloperidol is a strong antagonist of sigma receptors, what may be important for its antipsychotic potential. It has been established that selective sigma receptor agonists may produce antidepressant effect (Cobos E. et al., Curr. Neuropharmacol., 6(4), 344-66, 2008). The above findings provide evidence that sigma receptors affinity may contribute to the overall beneficial pharmacological profile of a new psychotropic drug.

Because of important role of cholinergic system in the cognitive processes, current research is focused on substances which can directly or indirectly potentiate the activity of cholinergic system. This includes substances which are agonists of selected subtypes of nicotinic or muscarinic receptors and antagonists of 5-HT6 receptors. On the other hand, potential procognitive effects evoked by interaction with the above receptors may be masked by cholinolytic activity. Thus, in the scope of interest are substances free of antagonistic properties against cholinergic receptors. Moreover, this strategy allows to eliminate many undesired peripheral autonomic effects like constipations, dry mouth or tachycardia (Miyamoto S. et al., Mol. Psychiatry; 10(1), 79-104, 2005). In addition, it has been found that M3 muscarinic receptors are engaged in the control of insulin secretion, and their activation stimulates pancreas to secrete insulin. Hence, it can be expected that M3 receptors blockade may be unfavorable in terms of the risk of development of type II diabetes in patients treated with second generation antipsychotics (ex. olanzapine, clozapine, quetiapine). Recent research is focused on substances free of this undesired effect (Silvestre J. S., Prous J., Methods Find. Exp. Clin. Pharmacol.; 27(5), 289-304, 2005).

Another serious side effects caused by antipsychotic drugs, e.g. sertindole, ziprasidone, are cardiac arrhythmias associated with delayed repolarization of cardiomyocytes. This condition appears on electrocardiograms (ECG) as prolonged corrected QT interval (QTc), what is most often evoked by substances which block hERG potassium channels. To prevent introduction to the developmental pipelines drugs with proarrhythmic potential, at a very early stage of research new substances are screened in vitro for their potency to block hERG potassium channels, using electrophysiological methods (Recanatini M. et al., Med. Res. Rev., 25(2), 133-66, 2005).

Although introduction of new psychotropic drugs (among others neuroleptics, antidepressants, benzodiazepines, acetylocholinesterase inhibitors) since 50-thies of the XX century was an unquestioned breakthrough, therapy of neuropsychiatric disorders is still far from satisfactory both because of limited efficacy and wide spectrum of side effects evoked by available drugs. These disadvantages are a challenge for modern pharmacotherapy and there is a continuous effort to search for new, more effective psychotropic drugs.

Some sulphonamide derivatives of alicyclic amines are known in the art.

US2001/0034352 discloses sulphonamide derivatives of piperidine, useful for the treatment of diseases related to endothelial dysfunction.

In WO98/29411 some sulphonamide derivatives are disclosed, having affinity for 5-HT1A and D2, d3 and D4 receptors and useful for the treatment of CNS diseases.

Certain sulphonamide derivatives of alicyclic amines having hypotensive activity are known from U.S. Pat. No. 4,034,098.

EP976732A discloses compounds revealing serotonin antagonism and useful for treatment, ameliorating or preventing spastic paralysis or as central muscle relaxants for ameliorating myotonia.

In WO02/22579 sulphonamide heterocycles having antipsychotic activity are disclosed. These compounds are useful for treatment of diseases caused by abnormal activity of one or more GPCR-s or ligand-gated ion-channels, i.a. for the treatment of psychiatric disorders.

WO2007/110449, WO2007/118853 and WO 2009/040659 disclose benzenesulphonamide derivatives as calcium channel blockers, especially useful for the treatment of pain.

Further, in WO2006/105127 sulphonamide derivatives active as hydroxysteride dehydrogenase inhibitors.

EP1190710A relates to compounds, i.a. piperidine sulphonamides, useful for the treatment of diabetes.

WO03/087086 discloses a broad group of substituted indole derivatives for the prophylaxis and/or therapy of diseases in which 5HT plays a role, i.a. depression.

U.S. Pat. No. 5,739,135, U.S. Pat. Nos. 5,827,875 and 5,885,983 relate to compounds potentially useful as inhibitors of microsomal triglyceride transfer protein.

WO01/07436 discloses substituted oxoazaheterocyclyl compounds, which inhibit both factor Xa and Factor IIa, thus being useful in the treatment and prophylaxis of diseases relating to blood coagulation.

In WO2004/002490 piperidine derivatives for the treatment of bacterial infections in mammals were disclosed.

AIM OF THE INVENTION

The aim of the present invention is to provide novel compounds potentially useful for the treatment of diseases of the central nervous system. A further aim of the invention is to provide novel compounds useful for the treatment of diseases of central nervous system having higher effectiveness compared to currently used medicaments. Yet further aim of the present invention is to provide novel compounds useful for the treatment of diseases of the central nervous system, which could allow to eliminate or minimize adverse effects associated with currently used therapies.

DISCLOSURE OF THE INVENTION

The present invention relates to novel sulphonamide derivatives of alicyclic amines having the structure represented by the general formula (I)

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wherein

A represents naphthyl or 9- or 10-membered bicyclic group, linked to —(O)_p—(CH₂)_n— through one of its aromatic carbon atoms, consisting of benzene ring fused with:

- 5-membered heteroaromatic ring having 1 heteroatom selected from N and S or 2 heteroatoms independently selected from N, O, and S, wherein such a bicyclic group may be unsubstituted or substituted with halogen atom; or
- 5- or 6-membered heterocyclic non-aromatic ring having 1 or 2 heteroatoms independently selected from N and O, wherein heterocyclic ring may be unsubstituted or substituted with ═O or one or more C₁-C₃-alkyls;
  
  D represents a moiety selected from the group consisting of:
- phenyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C₁-C₄-alkyl, C₁-C₃-alkyloxy, halogeno-C₁-C₃-alkyl, halogen atom, halogeno-C₁-C₃-alkyloxy-, —CN, —OH, and phenyl;
- naphthyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C₁-C₄-alkyl, C₁-C₃-alkyloxy and halogen atom;
- 5-membered aromatic heterocyclic group having 1 or 2 heteroatoms independently selected from N, O, and S, unsubstituted or substituted with one or more substituents independently selected from the group consisting of C₁-C₄-alkyl, halogen atom, and 5-membered heteroaromatic ring having 1 or 2 heteroatoms independently selected from N and O, linked to sulphonamide group through one of its aromatic carbon atoms; and
- bicyclic group consisting of a ring selected from benzene and pyridine, fused with 5-membered aromatic or non-aromatic heterocyclic ring, having 1 or 2 heteroatoms independently selected from N, O, and S, unsubstituted or substituted with one or more substitutents independently selected from the group consisting of C₁-C₄-alkyl, halogen atom, and ═O, linked to sulphonamide moiety through one of its aromatic carbon atoms;
  
  r represents 0 or 1;
  
  x and z represent independently 1 or 2;
  
  n represents 3 and p represents 0, or n represents 2 and p represents 1;
  
  and enantiomers, pharmaceutically acceptable salts and solvates thereof.

For one particular group of compounds of the present invention D represents a moiety selected from the group consisting of:

- phenyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C₁-C₄-alkyl, C₁-C₃-alkyloxy, halogeno-C₁-C₃-alkyl, halogen atom, —CN, —OH, and phenyl;
- naphthyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C₁-C₄-alkyl and halogen atom;
- 5-membered aromatic heterocyclic group having 1 or 2 heteroatoms independently selected from N, O, and S, unsubstituted or substituted with one or more substituents independently selected from the group consisting of C₁-C₄-alkyl, halogen atom, and 5-membered heteroaromatic ring having 1 or 2 heteroatoms independently selected from N and O; linked to sulphonamide group through one of its aromatic carbon atoms; and
- bicyclic group consisting of a ring selected from benzene and pyridine, fused with 5-membered aromatic or non-aromatic heterocyclic ring, having 1 or 2 heteroatoms independently selected from N, O, S, unsubstituted or substituted with one or more substitutents independently selected from the group consisting of C₁-C₄-alkyl, halogen atom, and ═O, linked to sulphonamide moiety through one of its aromatic carbon atoms.

In one of embodiments of the present invention, A is linked to oxygen atom of —(O)_p—(CH₂)_n— moiety when p is 1, or to carbon atom of —(CH₂)_n— moiety when p is 0, through carbon atom of benzene ring. Preferably, when p is 1, then A is linked to oxygen atom of —(O)_p—(CH₂)_n— moiety through carbon atom of benzene ring.

In an alternative embodiment of the invention A is linked to oxygen atom of —(O)_p—(CH₂)_n— moiety when p is 1, or to carbon atom of —(O)_p—(CH₂)_n— moiety when p is 0, through carbon atom of heterocyclic ring. Preferably, when p is 0, then A is linked to carbon atom of —(O)_p—(CH₂)_n— moiety through carbon atom of heterocyclic ring.

Preferably, for compounds of formula (I) as described above, if A is linked to —(O)_p—(CH₂)_n— moiety through carbon atom of benzene ring, then n is 2 and p is 1, and if A is linked to —(O)_p—(CH₂)_n— moiety through carbon atom of 5-membered heteroaromatic ring, then n is 2 and p is 1, or n is 3 and p is 0.

One of variants of the compounds of the present invention are compounds of formula (I) wherein A represents naphthyl. Naphthyl may be linked to oxygen atom of —(O)_p—(CH₂)_n— moiety when p is 1, or to carbon atom of —(CH₂)_n— moiety when p is 0, through position 1 (alpha) or 2 (beta) of naphthyl ring. Preferred in the above variant are compounds (I) of the invention where A is naphthyl and is linked to oxygen atom of —(O)_p—(CH₂)_n— moiety (p=1).

Another group of compounds of the invention are compounds of formula (I), wherein A represents 9-membered bicyclic group consisting of benzene ring fused with 5-membered monoheteroaromatic ring having 1 heteroatom selected from N and S, preferably having N as heteroatom. In this case A may be linked to oxygen atom, of —(O)_p—(CH₂)_n— moiety when p is 1, or to carbon atom of —(O)_p—(CH₂)_n— moiety when p is 0, through carbon atom of benzene ring or through carbon atom of 5-membered heteroaromatic ring. Advantageously, in this case A is linked to oxygen atom of —(O)_p—(CH₂)_n— moiety when p is 1, through carbon atom of benzene ring, or to carbon atom of —(O)_p—(CH₂)_n— moiety when p is 0, through carbon atom of 5-membered heteroaromatic ring. Preferably A in this group represents 1H-indol-4-yl, 1H-indol-6-yl, or 1H-indol-3-yl, which may be optionally substituted with halogen atom. More preferably, A in this group represents 1H-indol-4-yl or 1H-indol-6-yl linked to oxygen atom of —(O)_p—(CH₂)_n— moiety (p=1), or 1H-indol-3-yl substituted with halogen atom and linked to carbon atom of —(CH₂)_n— moiety (p=0).

Further group of compounds of the present invention are the compounds of formula (I), wherein A represents 9-membered bicyclic group consisting of benzene ring fused with 5-membered heteroaromatic ring having 2 heteroatoms independently selected from N, O, and S. A may be linked to oxygen atom of —(O)_p—(CH₂)_n— moiety when p is 1, or to carbon atom of —(CH₂)_n— moiety when p is 0, through carbon atom of benzene ring or through carbon atom of 5-membered heteroaromatic ring, preferably through carbon atom of 5-membered heteroaromatic ring. Preferred A in this group of compounds is selected from 1,2-benzoxazol-3-yl and 1,2-benzothiazol-3-yl, which may be optionally substituted with halogen atom.

Another group of compounds of the present invention are the compounds of formula (I), wherein A represents 10-membered bicyclic group consisting of benzene ring fused with 6-membered heterocyclic ring having 1 or 2 heteroatoms independently selected from N and O. In this variant A may only be linked to oxygen atom of —(O)_p—(CH₂)_n— moiety when p is 1, or to carbon atom of —(CH₂)_n— moiety when p is 0, through carbon atom of benzene ring. Preferably in this variant A represents 1,4-benzodioxan-5-yl.

Yet another group of compounds of the present invention are the compounds of formula (I), wherein A represents 9-membered bicyclic group consisting of benzene ring fused with 5-membered heterocyclic non-aromatic having 1 or 2 heteroatoms independently selected from N and O, and wherein heterocyclic ring is substituted with ═O or with one or more C₁-C₃-alkyl. Preferably in this group of compounds A is selected from 1,3-dihydro-2H-indol-2-on-4-yl, 1,3-benzoxazol-2(3H)-on-7-yl, 1,3-benzoxazol-2(3H)-on-4-yl and 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl.

Further group of compounds of the present invention are the compounds of formula (I), wherein D represents phenyl. Phenyl may be unsubstituted or substituted, as defined for substituent D above.

Yet another group of compounds of the invention are compounds of formula (I), wherein D represents naphthyl. Naphthyl may be linked to sulphur atom of sulphonamide moiety in position 1 (alpha) or 2 (beta) of naphthyl ring. Naphthyl may be unsubstituted or substituted, as defined for substituent D above, for example with halogen atom or C₁-C₃-alkyloxy. Preferably, naphthyl is unsubstituted.

Further group of compounds of the invention are compounds of formula (I), wherein D represents bicyclic group consisting of a ring selected from benzene and pyridine, fused with 5-membered aromatic or non-aromatic heterocyclic ring, having 1 or 2 heteroatoms independently selected from N, O, and S, unsubstituted or substituted with one or more substituents independently selected from the group consisting of C₁-C₄-alkyl, halogen atom, and ═O. Preferably, in this variant D is selected from the group consisting of 2,3-dihydrobenzofuran-6-yl, benzotiophen-2-yl, benzotiophen-3-yl, imidazo[1,2-a]pyridyn-3-yl, 1,3-benzothiazol-4-yl, and 1,3-benzothiazol-5-yl, which may be optionally substituted with halogen atom and/or C₁-C₃-alkyl.

Further variant of the compounds of formula (I) according to the invention are compounds wherein n is 3 and p is 0.

Another variant of the compounds of formula (I) according to the invention are compounds wherein n is 2 and p is 0.

Yet another group of the compounds of formula (I) according to the invention are compounds, wherein x and z are both 2. These group are therefore piperidine derivatives.

Further group of the compounds of formula (I) according to the invention are compounds wherein x is 2 and z is 1. These group are therefore pyrrolidine derivatives.

Yet further group of the compounds of formula (I) according to the invention are compounds wherein x and z are both 1. These group are therefore azetidine derivatives.

Another variant of the compounds of formula (I) of the present invention are compounds wherein r is 0.

Further variant of the compounds of formula (I) of the present invention are compounds wherein r is 1.

The following specific compounds of formula (I) of the invention can be mentioned:

1. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide,
2. 3-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide,
3. 4-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide,
4. 3-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide,
5. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-3-methylbenzene-sulphonamide,
6. N-[1 [3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,
7. 3-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
8. 4-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
9. 3-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
10. 4-bromo-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
11. 4-chloro-3-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,
12. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methylbenzene-sulphonamide,
13. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-propylbenzene-sulphonamide,
14. 4-tert-butyl-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzenesulphonamide,
15. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-(trifluoro-methyl)-benzenesulphonamide,
16. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-(trifluoro-methyl)-benzenesulphonamide,
17. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methoxy-benzenesulphonamide,
18. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-hydroxy-benzenesulphonamide,
19. 3-cyano-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
20. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,
21. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
22. 5-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide,
23. 6-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
24. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,3-dihydrobenzo-furano-6-sulphonamide,
25. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,
26. N-[1 [3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide,
27. 6-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-thiophene-2-sulphonamide,
28. 5-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,
29. 5-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,
30. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]imidazo[1,2-a]-pyridine-3-sulphonamide,
31. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1,3-benzothiazole-4-sulphonamide,
32. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]benzenesulphonamide,
33. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]-3-methylbenzene-sulphonamide,
34. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]naphthalene-1-sulphonamide,
35. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]naphthalene-2-sulphonamide,
36. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]-3-methy-benzenesulphonamide,
37. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]-naphthalene-1-sulphonamide,
38. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]-naphthalene-2-sulphonamide,
39. N-[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
40. N-[1 [2-(1,2-benzothiazol-3-yloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide,
41. N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]-3-hydroxy-benzene-sulphonamide,
42. N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,
43. N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzene-sulphonamide,
44. N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,
45. N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide,
46. 4-fluoro-N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide,
47. 3-chloro-N-[1-[2-(1 N-indol-4-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide,
48. N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]-3-methyl-benzenesulphonamide,
49. N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]naphthalene-1-sulphonamide,
50. N-[1-[2-(l N-indol-4-yloxy)ethyl]azetidin-3-yl]naphthalene-2-sulphonamide,
51. N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide,
52. N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]-3-methylbenzenesulphonamide,
53. N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,
54. N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
55. N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzenesulphonamide,
56. N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]-3-methylbenzenesulphonamide,
57. 4-tert-butyl-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzene-sulphonamide,
58. N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]-4-(trifluoromethyl)benzene-sulphonamide,
59. 4-cyano-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzenesulphonamide,
60. N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]naphthalene-1-sulphonamide,
61. N-[1-[2-(1H-indo-4-yloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide,
62. 5-chloro-N-[1-[2-(1H-indo-4-yloxy)ethyl]-4-piperidine]-3-methylbenzo-thiophene-2-sulphonamide,
63. N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]benzenesulphonamide,
64. N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]-3-methyl-benzene-sulphonamide,
65. 3-hydroxy-N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]benzene-sulphonamide,
66. N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]naphthalene-1-sulphonamide,
67. N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]naphthalene-2-sulphonamide,
68, N-[1-[2-(1H-indol-6-yloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide,
69. N-[1-[2-(1H-indol-6-yloxy)ethyl]pyrrolidin-3-yl]-3-methylbenzenesulphonamide,
70. N-[[1-[2-(1H-indol-6-yloxy)ethyl]-4-piperidine]methyl]benzenesulphonamide,
71. N-[[1-[2-(1H-indo-6-yloxy)ethyl]-4-piperidine]methyl]naphthalene-1-sulphonamide,
72. N-[[1-[2-(1H-indol-6-yloxy)ethyl]-4-piperidine]methyl]naphthalene-2-sulphonamide,
73. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,
74. 3-fluoro-N-[1-[3-(5-fluoro-1H-indo-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
75. 4-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
76. 3-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
77. 4-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
78. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzene-sulphonamide,
79. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,
80. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
81. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,
82. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-fluoro-benzene-sulphonamide,
83. N-[1-[3-(5-chloro-1-indol-3-yl)propyl]pyrrolidin-3-yl]-4-fluoro-benzene-sulphonamide,
84. 3-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
85. 4-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,
86. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzene-sulphonamide,
87. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
88. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]benzene-sulphonamide,
89. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-3-fluoro-benzenesulphonamide,
90. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-4-fluoro-benzenesulphonamide,
91. 3-chloro-N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-benzene-sulphonamide,
92. 4-chloro-N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-benzenesulphonamide,
93. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-3-methyl-benzenesulphonamide,
94. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]naphthalene-1-sulphonamide,
95. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]naphthalene-2-sulphonamide,
96. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]benzene-sulphonamide,
97. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-3-methyl-benzene-sulphonamide,
98. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-naphthalene-1-sulphonamide
99. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide,
100. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]naphthalene-1-sulphonamide,
101. N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-benzenesulphonamide,
102. N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-3-methylbenzenesulphonamide,
103. N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-3-hydroxybenzenesulphonamide,
104. N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-naphthalene-1-sulphonamide,
105. N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-naphthalene-2-sulphonamide,
106. N-[[1-[2-(2-oxoindolin-4-yl)oxyethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,
107. N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]-3-hydroxy-benzenesulphonamide,
108. N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide,
109. N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]-4-piperidine]-3-hydroxy-benzene-sulphonamide,
110. N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]-4-piperidine]naphthalene-2-sulphonamide,
111. N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]azetidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide,
112. N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,
113. N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide,
114. N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,
115. 3-hydroxy-N-[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide,
116. N-[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
117. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]benzene-sulphonamide,
118. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]-3-methyl-benzenesulphonamide,
119. 3-hydroxy-N-[1-[2-(1-naphthyloxy)ethyl]-4-piperidine]benzenesulphonamide,
120. N-[1-[2-(1-naphthyloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide,
121. 3-hydroxy-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzene-sulphonamide,
122. N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,
123. 3-hydroxy-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzene-sulphonamide,
124. N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,
125. N-[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]-3-hydroxybenzene-sulphonamide,
126. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide,
127. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzo-thiophene-2-sulphonamide,
128. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide,
129. 6-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]-naphthalene-2-sulphonamide,
130. 5-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide,
131. 5-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]-3-methyl-benzothiophene-2-sulphonamide,
132. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzothiazole-5-sulphonamide,
133. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-naphthalene-1-sulphonamide,
134. N-[[1-[3-(6-fluoro 1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,
135. N-[[1. [3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-phenyl-benzenesulphonamide,
136. 4-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]benzenesulphonamide,
137. 3-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]benzenesulphonamide,
138. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-methyl-benzenesulphonamide,
139. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzene-sulphonamide,
140. N-[[1. [3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide,
141. 4-tert-butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,
142. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methyl-benzenesulphonamide,
143. N-[[1-[3-(6-fluoro 1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methoxy-benzenesulphonamide,
144. 3-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzenesulphonamide,
145. 4-cyano-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzenesulphonamide,
146. 3,4-dichloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]benzenesulphonamide,
147. 4-fluoro-N-[[1. [3-(6-fluoro 1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzenesulphonamide,
148. 4-bromo-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzenesulphonamide,
149. N-[[1-[3-(6-fluoro 1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide, N-[[1-[3-(6-fluoro 1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,
151. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzofuran-2-sulphonamide,
152. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,
153. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzo-thiophene-2-sulphonamide,
154. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-thiophene-3-sulphonamide,
155. 5-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-thiophene-2-sulphonamide,
156. 3-chloro-4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]benzenesulphonamide,
157. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-propyl-benzenesulphonamide,
158. 3,4-difluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]benzenesulphonamide,
159. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-(trifluoro-methoxy)benzenesulphonamide,
160. N-[[1-[3-(5-fluoro-1H-indol-3-yl)propyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,
161. N-[[1-[3-(5-chloro-1 I-indol-3-yl)propyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,
162. N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,
163. N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide,
164. 6-chloro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]-benzothiophene-2-sulphonamide,
165. 6-chloro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,
166. 5-fluoro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzo-thiophene-2-sulphonamide,
167. 5-chloro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzo-thiophene-2-sulphonamide,
168. N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-1-sulphonamide,
169. 1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]indole-5-sulphonamide,
170. 1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]indol-4-sulphonamide,
171. N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-3-sulphonamide,
172. 3-chloro-4-fluoro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzene-sulphonamide,
173. 3,4-difluoro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]-benzene-sulphonamide,
174. 6-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]-methyl]naphthalene-2-sulphonamide,
175. 5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]-methyl]-3-methyl-benzothiophene-2-sulphonamide,
176. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-1-sulphonamide,
177. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,
178. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-phenyl-benzenesulphonamide,
179. 4-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,
180. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide,
181. 4-tert-butyl-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,
182. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-fluoro-benzenesulphonamide
183. 3,4-dichloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,
184. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-thiophene-2-sulphonamide,
185. 4-bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,
186. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-benzofuran-2-sulphonamide,
187. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,
188. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,
189. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide,
190. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-benzothiophene-3-sulphonamide,
191. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-thiophene-3-sulphonamide,
192. 5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]thiophene-2-sulphonamide,
193. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-iodo-benzenesulphonamide,
194. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1,3-benzo-dioxole-5-sulphonamide,
195. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-phenyl-benzenesulphonamide,
196. N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-thiophene-2-sulphonamide,
197. N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-thiophene-2-sulphonamide,
198. 6-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzothiophene-2-sulphonamide,
199. 6-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzothiophene-2-sulphonamide,
200. 6-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide,
201. 6-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide,
202. 5-fluoro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,
203. 5-fluoro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,
204. 5-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,
205. 5-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,
206. N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
207. N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide,
208. 4-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzenesulphonamide,
209. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-methyl-benzene-sulphonamide,
210. 4-cyano-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzene-sulphonamide
211. 3,4-dichloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzenesulphonamide,
212. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide,
213. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-methoxy-benzenesulphonamide,
214. N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-furan-2-sulphonamide,
215. N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-furan-2-sulphonamide,
216. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzofuran-2-sulphonamide,
217. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-imidazole-4-sulphonamide,
218. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide,
219. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide,
220. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2-oxo-indoline-5-sulphonamide,
221. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide,
222. N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide,
223. N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide,
224. N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzo-thiophene-3-sulphonamide
225. N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzo-thiophene-3-sulphonamide,
226. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methyl-benzo-thiophene-2-sulphonamide,
227. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide,
228. N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methyl-benzothiophene-2-sulphonamide,
229. N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methyl-benzothiophene-2-sulphonamide,
230. N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide,
231. N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide,
232. 7-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
233. 7-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
234. 6-fluoro-N-[1-[3-(6-<fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-thiophene-2-sulphonamide,
235. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide,
236. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide,
237. 6-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,
238. 5-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide,
239. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl]propyl]pyrrolidin-3-yl)methyl]-naphthalene-1-sulphonamide,
240. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,
241. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-phenyl-benzenesulphonamide,
242. 4-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide,
243. 3-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide,
244. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-methyl-benzenesulphonamide,
245. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide,
246. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide,
247. N-[[1-[3-(6-fluoro 1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulphonamide,
248. 4-tert-butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
249. 3-tert-butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
250. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-methoxy-benzenesulphonamide,
251. 4-cyano-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
252. 4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide,
253. 3,4-dichloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
254. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide,
255. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-methoxy-benzenesulphonamide,
256. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2,3-dihydrobenzofuran-5-sulphonamide,
257. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzofuran-2-sulphonamide,
258. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,
259. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,
260. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2-oxo-indoine-5-sulphonamide,
261. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzo-thiophene-3-sulphonamide,
262. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2,5-dimethylthiophene-3-sulphonamide,
263. 3-chloro-4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,
264. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-propyl-benzenesulphonamide,
265. 3,4-difluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
266. N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide,
267. N-[[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,
268. N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide,
269. 6-chloro-N-[[1-[2-(1-naphthyloxy)ethylpyrrolidin-3-yl]methyl]-benzothiophene-2-sulphonamide,
270. 6-chloro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,
271. 5-fluoro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzothiophene-2-sulphonamide,
272. 5-chloro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzothiophene-2-sulphonamide,
273. N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-1-sulphonamide,
274. 1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]indole-5-sulphonamide,
275. 1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]indole-4-sulphonamide,
276. N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-3-sulphonamide,
277. 3-chloro-4-fluoro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide,
278. 3,4-difluoro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzene-sulphonamide,
279. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide,
280. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-benzothiophene-2-sulphonamide,
281. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide,
282. 6-chloro-N-[[1. [2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]naphthalene-2-sulphonamide,
283. 5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-3-methyl-benzothiophene-2-sulphonamide,
284. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-thiazole-2-sulphonamide,
285. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-5-sulphonamide,
286. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-naphthalene-1-sulphonamide,
287. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,
288. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-phenyl-benzenesulphonamide,
289. 4-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
290. 3-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
291. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-methyl-benzenesulphonamide,
292. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide,
293. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide,
294. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulphonamide,
295. 4-tert-butyl-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,
296. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-methylbenzenesulphonamide,
297. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-methoxybenzenesulphonamide,
298. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-fluoro-benzenesulphonamide,
299. 4-cyano-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
300. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-fluoro-benzenesulphonamide,
301. 3,4-dichloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,
302. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-thiophene-2-sulphonamide,
303. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-hydroxybenzenesulphonamide,
304. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-methoxybenzenesulphonamide,
305. 4-bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,
306. N-[[1-[2-(2,3-dihydro 1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2,3-dihydrobenzofuran-5-sulphonamide,
307. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-benzofuran-2-sulphonamide,
308. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,
309. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,
310. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide,
311. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-benzothiophene-3-sulphonamide,
312. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2,5-dimethyl-thiophene-3-sulphonamide,
313. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-thiophene-3-sulphonamide,
314. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-5-isoxazol-5-yl-thiophene-2-sulphonamide,
315. 3-cyano-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]benzenesulphonamide,
316. 5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]thiophene-2-sulphonamide,
317. 3-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-4-fluorobenzenesulphonamide,
318. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-propylbenzenesulphonamide,
319. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3,4-difluoro-benzenesulphonamide,
320. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide,
321. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-iodobenzenesulphoniamide,
322. 3-bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,
323. N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-5-methyl-isoxazole-4-sulphonamide,
324. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]benzothiophene-2-sulphonamide
325. 6-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-naphthalene-2-sulphonamide,
326. 5-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-3-methyl-benzothiophene-2-sulphonamide,
327. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-4-phenylbenzene-sulphonamide,
328. 4-tert-butyl-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-benzenesulphonamide,
329. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-1-methyl-indole-4-sulphonamide,
330. N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]benzothiophene-3-sulphonamide,
331. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,
332. 6-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,
333. 6-chloro-N-[1-[3-(5-chloro-1 N-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
334. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-5-fluoro-3-methyl-benzothiophene-2-sulphonamide,
335. 5-chloro-N-[1-[3-(5-chloro-1 N-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methy-benzothiophene-2-sulphonamide,
336. 3,4-dichloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,
337. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide,
338. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide,
339. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide,
340. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide,
341. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,
342. 3-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-4-fluoro-benzenesulphonamide,
343. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3,4-difluoro-benzenesulphonamide,
344. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,
345. 6-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,
346. 6-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,
347. 5-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methy-benzothiophene-2-sulphonamide,
348. 5-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,
349. 3,4-dichloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,
350. N-[1-[3-(5-fluoro-1-indol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide,
351. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide,
352. N-[1-[3-(5-fluoro-1 N-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide,
353. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide,
354. 3-chloro-4-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,
355. 3,4-difluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,

and enantiomers, pharmaceutically acceptable salts and solvates thereof.

Sulphonamide derivatives of alicyclic amines of the above formula (I) exhibit affinity for receptors which are recognized therapeutical targets in the treatment of CNS disorders, such as dopaminergic, in particular D2 and D3, serotoninergic, in particular 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, adrenergic, in particular α1 and α2C, and to serotonin transporter receptors. They have low affinity for biological targets associated with adverse effects, such as muscarinic receptors M3, histaminergic receptors H1 or serotoninergic receptors 5-HT2C. Due to such a broad pharmacological profile, the compounds of the invention may be useful in medicine as medicaments, for the treatment and/or prevention of the central nervous system disorders such as schizophrenia, schizoaffective disorders, schizophreniform disorders, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, depression, affective bipolar disorder, mania and depression episodes, anxiety disorders of various etiology, conciousness disorders including coma, delirium of alcoholic or other etiology, aggression, psychomotor agitation and other conduct disorders, sleep disorders of various etiology, withdrawal syndromes of various etiology, addiction, pain syndromes of various etiology, intoxication with psychoactive substances, cerebral circulatory disorders of various etiology, psychosomatic disorders of various etiology, conversion disorders, dissociative disorders, urination disorders, autism and other developmental disorders, including nocturia, stuttering, tics, cognitive disorders of various types, such as Alzheimer's disease, psychopatological symptoms and neurological disorders in the course of other diseases of the central and peripheral nervous systems.

Thus, the subject of the present invention are the compounds of formula (I) as defined above, for use as a medicament.

In the treatment of central nervous system disorders compounds of formula (I) may be administered in the form of a pharmaceutical composition or preparation containing it.

Thus, the subject of the present invention is also the pharmaceutical composition containing the compound or compounds of formula (I) as defined above as an active substance, in combination with pharmaceutically acceptable carrier(s) and/or excipient(s).

The subject of the invention are also sulphonamide derivatives of the above formula (I) for use in the treatment of disorders of central nervous system.

The invention relates also to a method for the treatment of disorders of the central nervous system in mammals, including humans, comprising administration of a therapeutically effective amount of the compound of above formula (I) or the pharmaceutical composition containing the compound of formula (I) as defined above as an active substance.

Terms used in the description of the present invention have the following meanings.

Unless otherwise indicated, the term “C₁-C₄-alkyl” relates to a saturated, straight or branched hydrocarbon group, having indicated number of carbon atoms. Specific examples of groups encompassed by this term are methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and sec-butyl.

The term “C₁-C₃-alkyloxy” relates to —O—C₁-C₃-alkyl group, wherein C₁-C₃-alkyl relates to a saturated, straight or branched hydrocarbon group, having indicated number of carbon atoms. Specific examples of groups encompassed by this term are methoxy, ethoxy, n-propoxy, isopropoxy.

The term “halogen atom” relates to a substituent selected from F, Cl, Br and I.

The term “halogeno-C₁-C₃-alkyl” relates to a saturated, straight or branched hydrocarbon group, having indicated number of carbon atoms and in which one carbon atom may be substituted with from 1-3 halogen atoms, depending on the number of carbon atoms bonded to it. Halogen atom has the meaning as defined above. Particularly preferred example of a group encompassed by this term is trifluoromethyl group —CF₃.

The term “halogeno-C₁-C₃-alkyloxy” relates to —O—C₁-C₃-halogenoalkyl group, wherein C₁-C₃-halogenoalkyl relates to a saturated, straight or branched hydrocarbon group, having indicated number of carbon atoms and in which one carbon atom may be substituted with from 1-3 halogen atoms, depending on the number of carbon atoms bonded to it. Halogen atom has the meaning as defined above. Particularly preferred example of a group encompassed by this term is trifluoromethoxy group —O—CF₃.

The compounds of formula (I) according to the invention can be prepared in a process presented in the following scheme:

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In the first step, an appropriate diamine having Boc-protected (tert-butyl carboxylate) primary amino group (IVa) is subjected to nucleophillic substitution reaction with an appropriate halogen derivative (IVb) in a solvent, for example in acetonitrite, in the presence of a base, for example triethylamine and/or potassium carbonate, at elevated temperature, for example at the boiling point of the solvent, to afford a derivative of formula (III). Product of the substitution reaction, amine Boc-(IIA), is deprotected using 4M solution of hydrogen chloride in dioxane or using a solution of trifluoroacetic acid in methylene chloride. The resulting amine (IIa) is reacted with sulfonyl chloride (IIb) in a solvent, for example N,N-dimethylformamide or methylene chloride, in the presence of a base, for example diisopropylethylamine, pyridine, or cesium carbonate, and 4-dimethylaminopyridine (DMAP) to give sulphonamide derivative of alicyclic amine (I) according to the invention.

Starting materials of formulas (IVa), (IVb) and (IIb) are either well known or commercially available, or can be prepared from commercially available starting materials by adapting and applying known methods.

Preparation of exemplary starting compounds of formula (IIa) is described in detail in the experimental part.

Since the compounds of formula (I) have alkaline character (contain at least one tertiary amine group), they can form acid addition salts.

Salts with acids can be pharmaceutically acceptable, especially when they are intended to be an active ingredient in a pharmaceutical composition. The present invention relates also to salts of the compounds of formula (I) with acids other than pharmaceutically acceptable ones, which may be useful for example as intermediates suitable for purification of the compounds of the invention. In practice, it is often desirable to isolate first the compound from a reaction mixture in the form of a salt which is not pharmaceutically acceptable to purify the compound, and then convert the salt into free base by treatment with alkaline agent and to isolate, and optionally convert into the salt again.

Acid addition salts can be formed with inorganic (mineral) or organic acids. In particular, hydrochloric, hydrobromic, hydroiodic, phosphoric, sulphuric, nitric, carbonic, succinic, maleic, formic, acetic, propionic, fumaric, citric, tartaric, lactic, benzoic, salicylic, glutamic, aspargic, p-toluenesulphonic, benzenesulphonic, methanesulphonic, ethanesulphonic, naphthalenesulphonic such as 2-naphthalene-sulphonic, pamoic, xinafoic or hexanoic acids can be mentioned as examples of acids.

Acid addition salt can be prepared in a simple manner by reaction of the compound of formula (I) with suitable inorganic or organic acid, optionally in suitable solvent, such as organic solvent, to form a salt that is usually isolated, for example by crystallization and filtration. For example, compounds in the form of a free base can be converted into corresponding hydrochloride salts by reaction of a compound in a solution, for example in methanol, with stoichiometric amount of hydrochloric acid or with solution of hydrochloric acid in methanol, ethanol or diethyl ether, followed by evaporation of solvent(s).

The term “disorders of the central nervous system” should be understood as including disorders selected from schizophrenia, schizoaffective disorders, schizophreniform disorders, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, affective disorder, bipolar disorder, mania, depression, anxiety disorders of various etiology, stress reactions, conciousness disorders, coma, delirium of alcoholic and other etiology, aggression, psychomotor agitation and other conduct disorders, sleep disorders of various etiology, withdrawal syndromes of various etiology, addiction, pain syndromes of various etiology, intoxication with psychoactive substances, cerebral circulatory disorders of various etiology, psychosomatic disorders of various etiology, conversion disorders, dissociative disorders, urination disorders, autism and other developmental disorders, including nocturia, stuttering, and tics, cognitive disorders of various types, like Alzheimer's disease, psychopathological symptoms and neurological disorders in the course of other diseases of the central and peripheral nervous systems.

In the treatment of the disorders mentioned above, compounds of formula (I) of the present invention can be administered as a chemical compound, but usually will be applied in the form of a pharmaceutical compositions containing the compound of the present invention or its pharmaceutically acceptable salt as defined above as an active ingredient in combination with pharmaceutically acceptable carrier(s) and/or excipient(s).

In the treatment of the above mentioned disorders the pharmaceutical compositions of the invention can be delivered by any route of administration, preferably oral or parenteral, and will have the form of a preparation for use in medicine, depending on the intended route of administration.

Compositions for oral administration may have the form of solid or liquid preparations. Solid preparations may be in the form, for example, tablets or capsules prepared in conventional manner using pharmaceutically acceptable inactive ingredients, such as binding agents (e.g. pregelatinized maize starch, polyvinylpyrrolidone or hydroxypropylmethylcellulose); fillers (e.g. lactose, sucrose, carboxymethylcellulose, microcrystalline cellulose or calcium hydrogen phosphate) lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g. crospovidone, maize starch or sodium starch glycolate); wetting agents (e.g. sodium lauryl sulfate). The tablets may be coated using methods well known in the art with conventional coatings, delaying/controlling release coatings or enteric coatings. Liquid preparations for oral administration may have the form of e.g. solutions, syrups or suspensions, or may be prepared from a dry product suitable for reconstitution with water or other suitable carrier ex tempore. Such liquid preparations may be prepared by conventional methods with pharmaceutically acceptable inactive ingredients, such as suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats), emulsifying agents (e.g. lecithin or acacia gum), non-aqueous matrix components (e.g. almond oil, oils esters, ethyl alcohol or fractionated vegetable oils) and preservatives (e.g. methyl or propyl p-hydroxybenzoates or sorbic acid). The preparations may also contain suitable buffering systems, flavouring and aroma agents, colourants and sweeteners.

Preparations for oral administration can be formulated according to methods well known to those skilled in the art to afford a controlled release of the active compound.

The parenteral route of administration comprises administration by intramuscular and intravenous injections and intravenous continuous infusions. Compositions for parenteral administration may be in the form of a dosage unit, e.g. in ampoules or in multidose containers with the addition of a preservative. The compositions may be in the form of suspensions, solutions or emulsions in oily or aqueous media, and may contain pharmaceutically acceptable excipients, such as suspending agents, stabilizing and/or dispersing agents. Alternatively, the active ingredient may be in the form of a powder for reconstitution ex tempore in a suitable carrier, e.g. sterile pyrogen-free water.

Method of treatment using compounds of this invention will be based on administration of a therapeutically effective amount of the compound of the invention, preferably in the form of a pharmaceutical composition, to a subject in need of such a treatment.

The proposed dose of the compounds of the invention will be comprised in the range from 1 to about 1000 mg per day, in a single dose or in divided doses. It will be apparent to those skilled in the art that selection of a dose required to achieve the desired biological effect will depend on several factors, such as the type of specific compound, the indication, route of administration, age and condition of a patient and the exact dose will be finally determined at the discretion of attending physician.

EXAMPLE 1
Preparation of Starting Compounds of Formula IIa

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1a) Procedure for Halogen Derivative (IVb) Wherein X is Br and p=1

The amine (IVa) (1 mmol), bromoderivative (IVb) (1 mmol) and potassium carbonate (1.5 mmol) were stirred in acetonitrile (50 ml) under reflux overnight. Then the inorganic precipitate was filtered off, the filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel using methylene chloride methanol 100:0 to 95:5 v/v as eluent.

Then the resulting protected amine Boc-(IIa) was subjected to deprotection according to one of the following procedures.

1a-1) Procedure for Deprotection of Amines Boc-(IIa) where r=0

To amine Boc-(IIIa) (0.5 mmol) 20 ml of methylene chloride and 5 ml of trifluoroacetic acid were added and the mixture was stirred at room temperature for 1 hour. Then the solvent was evaporated under reduced pressure and the product amine (IIa) as trifluoroacetic acid salt was used in the next step without purification.

1a-2) Procedure for Deprotection of Amines Boc-(IIa) where r=1

To amine Boc-(IIa) (0.5 mmol) 20 ml of methylene chloride and 5 ml of trifluoroacetic acid were added and the mixture was stirred at room temperature for 1 hour. Then the solvent was evaporated under reduced pressure and to the residue saturated aqueous sodium bicarbonate solution was added and then the mixture was extracted with ethyl acetate. After drying the organic phase over anhydrous magnesium sulfate, the residue after evaporation was purified by column chromatography on silica gel using methylene chloride/methanol 100:0-90:10 v/v as eluent to afford amine (IIa).

1b) Procedure for Halogen Derivatives (IVb) where X Represents Cl

A mixture of halogen derivative (IVb) (2.43 mmol), amine (IVa) (2.68 mmol), potassium carbonate (5.36 mmol), triethylamine (5.36 mmol) in acetonitrile (15 mL) was stirred at 70° C. for 16 hours. Then the inorganic precipitate was filtered off, the filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel using methylene chloride/methanol 95:5 v/v as eluent. Then the resulting protected amine Boc-(IIa) was deprotected according to the following procedure.

Amine Boc-(IIa) (1.73 mmol) and 4M solution of hydrogen chloride in dioxane (10 ml) were stirred at room temperature for 45 min. Then dioxane was removed under reduced pressure and the residue was dried under vacuum for 1 hour to afford amine (IIa) as hydrochloride. The product was used directly in the next step without further purification.

Yields of amines (IIa) were in the range of 70-90%, and HPLC purities in the range of 90-95%.

Structure of prepared compounds was confirmed by MS analysis.

Starting Amines (IVa):

tert-butyl azetidin-3-ylcarbamate (IVa-1),

tert-butyl pyrrolidin-3-ylcarbamate (IVa-2),

tert-butyl piperidin-4-ylcarbamate (IVa-3),

tert-butyl (azetidin-3-ylmethyl)carbamate (IVa-4),

tert-butyl (pyrrolidin-3-ylmethyl)carbamate (IVa-5),

tert-butyl (piperidin-4-ylmethyl)carbamate (IVa-6),

tert-butyl (3R)-pyrrolidin-3-ylcarbamate (IVa-7),

tert-butyl (3S)-pyrrolidin-3-ylcarbamate (IVa-8).

Starting Halogen Derivatives (IVb):

3-(3-chloropropyl)-6-fluoro-1,2-benzoxazol (IVb-1),

3-(2-bromoethoxy)-1,2-benzothiazol (IVb-2),

4-(2-bromoethoxy)-1H-indole (IVb-3),

6-(2-bromoethoxy)-1H-indole (IVb-4),

3-(3-chloropropyl)-5-fluoro-1H-indole (IVb-5),

3-(3-chloropropyl)-5-chloro-1H-indole (IVb-6),

5-(2-bromoethoxy)-2,3-dihydro-1,4-benzodioxane (IVb-7),

4-(2-bromoethoxy)-1,3-dihydro-2H-indol-2-one (IVb-8),

7-(2-bromoethoxy)-2,2-dimethyl-2,3-dihydro-1-benzofuran (IVb-9),

1-(2-bromoethoxy)naphthalene (IVb-10).

Starting from appropriate amines (IVa) and halogen derivatives (IVb), the following amines (IIa) were prepared:

1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidine-3-amine (IIa-1), hydrochloride; MS: 250 [M+H⁺],
1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidine-3-amine (IIa-2), hydrochloride; MS: 264 [M+H⁺],
1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]piperidine-4-amine (IIa-3), hydrochloride; MS: 278 [M+H⁺],
1-{1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]piperidin-4-yl}methaneamine (IIa-4), hydrochloride; MS: 292 [M+H⁺],
N-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidine-3-amine (IIa-5), trifluoroacetate; MS: 264 [M+H⁺],
1-[2-(1,2-benzothiazol-3-yloxy)ethyl]piperidine-4-amine (IIa-6), trifluoroacetate; MS: 278 [M+H⁺],
1-{1-[2-(1,2-benzothiazol-3-yloxy)ethyl]azetidin-3-yl}methaneamine (IIIa-7), MS: 264 [M+H⁺],
1-{1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl}methaneamine (IIa-8), MS: 278 [M+H⁺],
1-[2-(1H-indol-4-yloxy)ethyl]azetidine-3-amine (IIa-9), trifluoroacetate; MS: 232 [M+H⁺],
1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidine-3-amine (IIa-10), trifluoroacetate; MS: 246 [M+H⁺],
1-[2-(1H-indol-4-yloxy)ethyl]piperidine-4-amine (IIa-11), trifluoroacetate; MS: 260 [M+H⁺],
1-{1-[2-(1H-indol-4-yloxy)ethyl]piperidin-4-yl}methaneamine (IIa-12), MS: 274 [M+H⁺],
1-[2-(1H-indol-6-yloxy)ethyl]pyrrolidine-3-amine (IIa-13), MS: 246 [M+H⁺],
1-{1-[2-1H-indol-6-yloxy)ethyl]piperidin-4-yl}methaneamine (IIa-14), trifluoroacetate; MS: 274 [M+H⁺],
1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidine-3-amine (IIa-15), hydrochloride; MS: 262 [M+H⁺],
1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidine-3-amine (IIa-16), hydrochloride; MS: 278 [M+H⁺],
1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]azetidine-3-amine (IIa-17), trifluoroacetate; MS: 251 [M+H⁺],
1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]pyrrolidine-3-amine (IIa-18), trifluoroacetate; MS: 265 [M+H⁺],
1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]piperidine-4-amine (IIa-19), trifluoroacetate; MS: 279 [M+H⁺],
4-{2-[3-(aminomethyl)pyrrolidin-1-ylo]etoksy}-1,3-dihydro-2H-indol-2-on (IIa-21), MS: 276 [M+H⁺],
1-{2-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]ethyl}pyrrolidine-3-amine (IIa-22), trifluoroacetate; MS: 277 [M+H⁺],
1-{2-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]ethyl}piperidine-4-amine (IIa-23), trifluoroacetate; MS: 291 [M+H⁺],
1-(1-{2-[(2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl)oxy]ethyl}azetidin-3-yl)methaneamine (IIa-24), MS: 277 [M+H⁺],
1-(1-{2-[2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yloxy]ethyl}pyrrolidin-3-yl)methaneamine (IIa-25), MS: 291 [M±H],
1-[2-(naphthalen-1-yloxy)ethyl]pyrrolidine-3-amine (IIa-26), trifluoroacetate; MS: 257 [M+H⁺],
1-[2-(naphthalen-1-yloxy)ethyl]piperidine-4-amine (IIa-27), trifluoroacetate; MS: 271 [M+H⁺],
1-{1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]piperidin-4-yl}methaneamine (IIa-20), MS: 293 [M+H⁺],
1-{1-[2-(naphthalen-1-yloxy)ethyl]azetidin-3-yl}methaneamine (IIa-28), MS: 257 [M+H⁺],
1-{1-[2-(naphthalen-1-yloxy)ethyl]pyrrolidin-3-yl}methaneamine (IIa-29), MS: 271 [M+H⁺],
1-{1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl}methaneamine (IIa-30), hydrochloride; MS: 264 [M+H⁺],
1-{1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl}methaneamine (IIa-31), hydrochloride; MS: 278 [M+H⁺],
(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidine-3-amine (IIa-32), hydrochloride; MS: 264 [M+H⁺],
(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidine-3-amine (IIa-33), hydrochloride; MS: 264 [M+H⁺],
1-{1-[3-(5-fluoro-1H-indol-3-yl)propyl]azetidin-3-yl}methaneamine (IIa-34), hydrochloride; MS: 262 [M+H⁺],
1-{1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl}methaneamine (IIa-35), hydrochloride; MS: 276 [M+H⁺],
1-{1-[3-(5-chloro-1H-indol-3-yl)propyl]azetidin-3-yl}methaneamine (IIa-36), hydrochloride; MS: 278 [M+H⁺],
1-{1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]azetidin-3-yl}methaneamine (IIa-37), MS: 275 [M+H⁺],
1-{1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]pyrrolidin-3-yl}methaneamine (IIa-38), MS: 289 [M+H⁺].

EXAMPLE 2
Preparation of Compounds (I) According to the Invention

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Depending on the type and form of the starting amine (IIa), the compounds (I) according to the invention were prepared using one of the three following procedures.

2a) Procedure for Starting Amines (IIa) as Hydrochlorides

To a solution of amine (IIa) hydrochloride (0.6 mmol) in methylene chloride cesium carbonate (1.2 mmol), the appropriate sulphonyl chloride (IIb) and DMAP (0.12 mmol) were added. The mixture was stirred overnight at room temperature, then inorganic solid was filtered off and from the filtrate solvent was evaporated under reduced pressure. Residue was purified by column chromatography on silica gel with a solvent system methylene chloride/methanol 95:5 v/v as eluent, to afford compound (I).

2b) Procedure for Starting Amines (IIa) as Trifluoroacetates

To amine (IIa) trifluoroacetate (0.5 mmol) 10 ml of dry N,N-dimethylformamide (10 ml), DIPEA (1 ml) and sulphonyl chloride (IIb) (0.6 mmol) in one portion were added. The mixture was stirred overnight at room temperature. Then saturated aqueous sodium bicarbonate solution was added to the mixture and the whole was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulphate, and subsequently the solvent was evaporated under reduced pressure. Residue was purified by column chromatography on silica gel using a solvent system methylene chloride/methanol 100:0-90:10 v/v as eluent to obtain compound (I).

2c) the Procedure for Starting Amines (IIa) as Free Bases

To amine (IIa) (0.4 mmol) dry methylene chloride (10 ml), pyridine (1 ml) and sulphonyl chloride (IIb) (0.4 mmol) in one portion were added. The mixture was stirred overnight at room temperature. Then, after addition of small amount of toluene, pyridine was evaporated under reduced pressure, and the residue was extracted using solvent system system water/ethyl acetate. The organic layer was dried over anhydrous magnesium sulphate and after evaporation of the solvent, the residue was purified by column chromatography on silica get using a solvent system methylene chloride/methanol 100:0-90:10 v/v as eluent to obtain compound (I).

Structures of compounds (I) according to the invention were confirmed by MS and/or ¹H NMR.

Yields of compounds (I) were in the range of 65-90%, and HPLC purities thereof in the range of 90-100%.

According to the above procedures, the following compounds (I) of the invention were prepared.

As starting materials commercially available sulphonyl chlorides (IIb) were used:

benzenesulphonyl chloride (IIb-1),
3-fluorobenzenesulphonyl chloride (IIb-2),
4-fluorobenzenesulphonyl chloride (IIb-3),
3-chlorobenzenesulphonyl chloride (IIIb-4),
4-chlorobenzenesulphonyl chloride (IIb-5),
4-bromobenzenesulphonyl chloride (IIb-6),
3-chloro-4-fluoro-benzenesulphonyl chloride (IIb-7),
3-methylbenzenesulphonyl chloride (IIb-8),
4-propylbenzenesulphonyl chloride (IIb-9),
4-tert-butylbenzenesulphonyl chloride (IIb-10),
3-(trifluoromethyl)benzenesulphonyl chloride (IIb-11),
4(trifluoromethyl)benzenesulphonyl chloride (IIb-12),
3-methoxybenzenesulphonyl chloride (IIb-13),
3-hydroxybenzenesulphonyl chloride (IIb-14),
3-cyanobenzenesulphonyl chloride (IIb-15),
4-cyanobenzenesulphonyl chloride (IIb-16),
naphthalene-1-sulphonyl chloride (IIb-17),
naphthalene-2-sulphonyl chloride (IIb-18),
6-chloronaphthalene-2-sulphonyl chloride (IIb-19),
5-chlorothiophene-2-sulphonyl chloride (IIb-20),
2,3-dihydrobenzofuran-6-sulphonyl chloride (IIb-21),
benzothiophene-2-sulphonyl chloride (IIb-22),
benzothiophene-3-sulphonyl chloride (IIb-23),
6-chlorobenzothiophene-2-sulphonyl chloride (IIb-24),
5-fluoro-3-methyl-benzothiophene-2-sulphonyl chloride (IIb-25),
5-chloro-3-methyl-benzothiophene-2-sulphonyl chloride (IIb-26),
imidazo[1,2-a]pyridine-3-sulphonyl chloride (IIb-27),
1,3-benzothiazole-4-sulphonyl chloride (IIb-28),
3-bromobenzenesulphonyl chloride (IIb-29),
4-iodobenzenesulphonyl chloride (IIb-30),
3,4-difluorobenzenesulphonyl chloride (IIb-31),
3,4-dichlorobenzenesulphonyl chloride (IIb-32),
4-methylbenzenesulphonyl chloride (IIb-33),
4-methoxybenzenesulphonyl chloride (IIb-34),
4-(trifluoromethoxy)benzenesulphonyl chloride (IIb-35),
biphenyl-4-sulphonyl chloride (IIb-36),
6-chloronaphthalene-2-sulphonyl chloride (IIb-37),
7-chloronaphthalene-2-sulphonyl chloride (IIb-38),
6-methoxynaphthalene-2-sulphonyl chloride (IIb-39),
thiophene-2-sulphonyl chloride (IIb-40),
thiophene-3-sulphonyl chloride (IIb-41),
2,5-dimethylthiophene-3-sulphonyl chloride (IIb-42),
5-isoxazol-5-ylthiophene-2-sulphonyl chloride (IIb-43),
1-methyl-1H-imidazole-4-sulphonyl chloride (IIb-44),
5-methylisoxazole-4-sulphonyl chloride (IIb-45),
1,3-thiazole-2-sulphonyl chloride (IIb-46),
2-oxo-2,3-dihydro-1H-indole-5-sulphonyl chloride (IIb-47),
1,3-benzodioxole-5-sulphonyl chloride (IIb-48),
1-methyl-1H-indole-4-sulphonyl chloride (IIb-50),
1-methyl-1H-indole-5-sulphonyl chloride (IIb-51),
1-benzofuran-2-sulphonyl chloride (IIb-52),
6-fluoro-1-benzothiophene-2-sulphonyl chloride (IIb-53),
5-methyl-1-benzothiophene-2-sulphonyl chloride (IIb-54),
1,3-benzothiazole-5-sulphonyl chloride (IIb-55),

and the appropriate amines (IIa), as described above.

According to the above procedures the following compounds (I) of the invention were prepared.

Compound 1. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-1) and sulphonyl chloride (IIb-1). MS: 390 [M+H⁺]

Compound 2. 3-Fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-1) and sulphonyl chloride (IIb-2). MS: 408 [M+H⁺]

Compound 3. 4-Fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-1) and sulphonyl chloride (IIb-3). MS: 408 [M+H⁺]

Compound 4. 3-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-1) and sulphonyl chloride (IIIb-4). MS: 424 [M+H⁺]

Compound 5. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-3-methyl-benzene-sulphonamide

The title compound was prepared starting from amine (IIa-1) and sulphonyl chloride (IIb-8). MS: 404 [M+H⁺]

Compound 6. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIIa-2) and sulphonyl chloride (IIb-1).

¹H-NMR (300 MHz, CDCl₃): 7.96-7.88 (m, 2H), 7.60-7.43 (m, 4H), 7.21-7.18 (m, 1H), 7.08-7.01 (m, 1H), 3.88-3.82 (m, 1H), 3.01-2.96 (m, 2H), 2.82-2.77 (m, 1H), 2.50-2.38 (m, 3H), 2.20-1.87 (m, 4H), 1.62-1.52 (m, 2H); MS: 444 [M+H⁺].

Compound 7. 3-Fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-2).

¹H-NMR (300 MHz, CDCl₃): 7.78-7.461 (m, 4H), 7.18-7.11 (m, 2H), 7.08-7.00 (m, 1H), 3.98-3.82 (m, 1H), 3.02-2.95 (m, 2H), 2.80-2.78 (m, 1H), 2.44-2.37 (m, 3H), 2.21-1.95 (m, 4H), 1.60-1.52 (m, 2H); MS: 422 [M+H⁺].

Compound 8. 4-Fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-3).

¹H-NMR (300 MHz, CDCl₃): 7.98-7.82 (m, 2H), 7.61-7.58 (m, 1H), 7.20-7.16 (m, 3H), 7.08-7.00 (m, 1H), 3.82-3.78 (m, 1H), 3.00-2.83 (m, 2H), 2.80-2.72 (m, 1H), 2.45-2.28 (m, 3H), 2.20-1.96 (m, 4H), 1.52-1.40 (m, 2H); MS: 422 [M+H⁺].

Compound 9. 3-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-4).

¹H-NMR (300 MHz, CDCl₃): 7.82-7.78 (m, 1H), 7.75-7.70 (d, 1H, J=7.9 Hz), 7.60-7.52 (m, 3H), 7.21-7.19 (m, 1H), 7.06-7.01 (m, 1H), 3.85-3.80 (m, 1H), 3.00-2.96 (m, 2H), 2.80-2.76 (m, 1H), 2.52-2.38 (m, 3H), 2.20-1.85 (m, 4H), 1.58-1.43 (m, 2H); MS: 438[M+H⁺].

Compound 10. 4-Bromo-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-6).

¹H-NMR (300 MHz, CDCl₃): 7.78-7.72 (m, 2H), 7.62-7.58 (m, 3H), 7.21-7.18 (m, 1H), 7.08-7.01 (m, 1H), 3.83-3.80 (m, 1H), 3.00-2.95 (m, 2H), 2.80-2.75 (m, 1H), 2.52-2.43 (m, 2H), 2.30-2.28 (m, 1H), 2.20-1.83 (m, 4H), 1.58-1.50 (m, 2H); MS: 483 [M+H⁺].

Compound 11. 4-Chloro-3-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-pyrrolidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-7).

¹H-NMR (300 MHz, CDCl₃): 7.97-7.93 (m, 1H), 7.80-7.65 (m, 1H), 7.60-7.55 (m, 1H), 7.22-7.20 (m, 2H), 7.08-7.01 (m, 1H), 3.80-3.71 (m, 1H), 2.97-2.83 (m, 2H), 2.80-2.72 (m, 1H), 2.45-2.28 (m, 3H), 2.21-1.97 (m, 4H), 1.60-1.53 (m, 2H); MS: 456 [M+H⁺].

Compound 12. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-8).

¹H-NMR (300 MHz, CDCl₃): 7.61-7.57 (m, 3H), 7.43-7.38 (m, 2H), 7.21-7.18 (m, 1H), 7.08-7.01 (m, 1H), 3.80-3.76 (m, 1H), 2.96-2.82 (m, 2H), 2.81 (s, 3H), 2.79-2.74 (m, 1H), 2.42-2.28 (m, 3H), 2.20-1.96 (m, 4H), 1.59-1.50 (m, 2H); MS: 418 [M+H⁺].

Compound 13. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-propyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-9).

¹H-NMR (300 MHz, CDCl₃): 7.80 (d, 2H, J=7.9 Hz), 7.62-7.58 (m, 1H), 7.36 (d, 2H, J=7.9 Hz), 7.21-7.18 (m, 1H), 7.08-7.01 (m, 1H), 3.12-3.02 (m, 4H), 2.98-2.90 (m, 1H), 2.67-2.60 (m, 4H), 2.27-2.20 (m, H), 1.75-1.60 (m, 5H), 0.95 (t, 2H, J=3.4 Hz); MS: 446[M+H⁺].

Compound 14. 4-tert-Butyl-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-10).

¹H-NMR (300 MHz, CDCl₃): 7.78-7.63 (m, 2H), 7.62-7.45 (m, 3H), 7.20-7.18 (m, 1H), 7.06-7.02 (m, 1H), 3.82-3.78 (m, 1H), 2.98-2.92 (m, 2H), 2.80-2.75 (m, 1H), 2.55-2.42 (m, 3H), 1.98-1.92 (m, 4H), 1.58-1.48 (m, 2H), 1.32 (s, 9H); 4260[M+H⁺].

Compound 15. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-11).

¹H-NMR (300 MHz, CDCl₃): 8.18-8.02 (m, 2H), 7.82 (d, 1H, J=7.9 Hz), 7.65-7.54 (m, 2H), 7.20 (t, 1H, J=7.4 Hz), 7.02 (t, 1H, J=7.9 Hz), 3.84-3.80 (m, 1H), 2.98-2.90 (m, 2H), 2.80-2.75 (m, 1H), 2.52-2.38 (m, 3H), 2.20-1.85 (m, 4H), 1.60-1.65 (m, 2H); MS: 472[M+H⁺].

Compound 16. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-12).

¹H-NMR (300 MHz, CDCl₃): 7.98 (d, 2H, J=7.9 Hz), 7.78 (d, 2H, J=7.9 Hz), 7.60-7.57 (m, 1H), 7.21-7.19 (m, 1H), 7.07-7.01 (m, 1H), 3.95-3.92 (m, 1H), 2.98-2.92 (m, 2H), 2.90-2.87 (m, 1H), 2.55-2.38 (m, 3H), 2.20-1.85 (m, 4H), 1.60-1.52 (m, 2H); MS: 472 [M+H⁺].

Compound 17. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methoxybenzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-13).

¹H-NMR (300 MHz, CDCl₃): 7.61-7.57 (m, 1H), 7.53-7.40 (m, 3H), 7.21-7.18 (m, 1H), 7.08-7.00 (m, 1H), 3.81 (s, 3H), 3.83-3.78 (m, 1H), 2.98-2.82 (m, 2H), 2.80-2.74 (m, 1H), 2.43-2.28 (m, 3H), 2.20-1.96 (m, 4H), 1.58-1.50 (m, 2H); MS: 435 [M+H⁺].

Compound 18. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-hydroxybenzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-14).

¹H-NMR (300 MHz, CDCl₃): 7.58-7.50 (m, 1H), 7.38-7.20 (m, 4H), 7.04-6.97 (m, 2H), 5.31 (s, 1H), 3.82-3.78 (m, 1H), 2.97-2.82 (m, 2H), 2.81-2.74 (m, 1H), 2.42-2.28 (m, 3H), 2.21-1.96 (m, 4H), 1.61-1.56 (m, 2H); MS: 420 [M+H⁺].

Compound 19. 3-Cyano-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-15).

¹H-NMR (300 MHz, CDCl₃): 8.20-8.17 (m, 1H), 8.14-7.98 (m, 1H), 7.87-7.82 (m, 1H), 7.68-7.56 (m, 2H), 7.26-7.22 (m, 1H), 7.10-7.02 (m, 1H), 3.90-3.80 (s, 1H), 3.02-2.94 (m, 2H), 2.84-2.78 (m, 1H), 2.54-2.42 (m, 2H), 2.40-2.32 (m, 1H), 2.20-1.90 (m, 4H), 1.60-1.56 (m, 2H), MS: 429 [M+H⁺].

Compound 20. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-17). MS: 454 [M+H⁺].

Compound 21. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-18). MS: 454 [M+H⁺].

Compound 22. 5-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-20).

¹H-NMR (300 MHz, CDCl₃): 7.65-7.58 (m, 1H), 7.41 (d, 1H, J=2.9 Hz), 7.22-7.20 (m, 1H), 7.08-7.01 (m, 1H), 6.91 (d, 1H, J=2.9 Hz), 3.91-3.86 (m, 1H), 2.92-2.84 (m, 2H), 2.78-2.64 (m, 1H), 2.42-2.22 (m, 3H), 2.15-1.95 (m, 2H), 1.80-1.75 (m, 2H), 1.62-1.56 (m, 2H); MS: 444[M+H⁺].

Compound 23. 6-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-19).

¹H-NMR (300 MHz, CDCl₃): 8.40 (s, 1H), 7.90-7.84 (m, 4H), 7.58-7.52 (m, 2H), 7.22-7.19 (m, 1/h), 6.98-6.90 (m, 1H), 3.89-3.82 (m, 1H), 2.98-2.92 (t, 2H, J=7.4 Hz), 2.78-2.70 (m, 1H), 2.50-2.40 (m, 2H), 2.38-2.32 (m, 1H), 2.18-1.84 (m, 4H), 1.58-1.48 (m, 2H); MS: 488 [M+H⁺].

Compound 24. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,3-dihydrobenzofuran-6-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-21).

¹H-NMR (300 MHz, CDCl₃): 7.60-7.52 (m, 3H), 7.21-7.18 (m, 1H), 7.08-7.00 (m, 1H), 6.75 (d, 1H, J=8.4 Hz), 4.70-4.60 (t, 2H, J=8.9 Hz), 3.80-3.74 (m, 1H), 3.28-3.18 (t, 2H, J=8.9 Hz), 2.98-2.92 (t, 2H, J=7.4 Hz), 2.74-2.64 (m, 1H), 2.50-2.38 (m, 3H), 2.26-2.16 (m, 1H), 2.10-1.87 (m, 3H), 1.60-1.48 (m, 2H), MS: 446 [M+H⁺].

Compound 25. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-2) and sulphonyl chloride (IIb-22).

¹H-NMR (300 MHz, CDCl₃): 7.88-7.80 (m, 3H), 7.60-7.54 (m, 1H), 7.50-7.40 (m, 2H), 7.22-7.20 (m, 1H), 7.08-7.00 (m, 1H), 3.90-3.82 (m, 1H), 2.93-2.82 (m, 2H), 2.77-2.63 (m, 1H), 2.43-2.22 (m, 3H), 2.19-1.95 (m, 2H), 1.81-1.77 (m, 2H), 1.55-1.43 (m, 2H); MS: 460[M+H⁺].

Compound 26. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-23).

¹H-NMR (300 MHz, CDCl₃): 8.21 (s, 1H), 8.20-8.17 (d, 1H, J=7.4 Hz), 7.84-7.80 (d, 1H, J=7.4 Hz), 7.58-7.50 (m, 1H), 7.48-7.45 (m, 2H), 7.24-7.20 (m, 1H), 7.08-7.02 (m, 1H), 3.90-3.80 (m, 1H), 2.90-2.80 (m, 2H), 2.78-2.64 (m, 1H), 2.43-2.24 (m, 3H), 2.18-1.97 (m, 2H), 1.80-1.75 (m, 2H), 1.57-1.45 (m, 2H); MS: 460[M+H⁺].

Compound 27. 6-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-24).

¹H-NMR (300 MHz, CDCl₃): 7.84-7.78 (m, 3H), 7.60-7.56 (m, 1H), 7.39 (d, 1H, J=7.6 Hz), 7.20 (d, 1H, J=7.6 Hz), 7.06-7.00 (m, 1H), 3.98-3.82 (m, 1H), 3.00-2.94 (m, 2H), 2.82-2.76 (m, 1H), 2.44-2.35 (m, 3H), 2.20-1.90 (m, 4H), 1.62-1.54 (m, 2H); MS: 494 [M+H⁺].

Compound 28. 5-Fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-25).

¹H-NMR (300 MHz, CDCl₃): 7.78-7.70 (m, 1H), 7.60-7.54 (m, 1H), 7.44-7.41 (m, 1H), 7.24-7.19 (m, 2H), 7.08-7.02 (m, 1H), 4.04-3.98 (m, 1H), 3.01-2.97 (m, 2H), 2.94-2.87 (m, 1H), 2.63 (s, 3H), 2.42-2.35 (m, 3H), 2.21-1.91 (m, 4H), 1.61-1.56 (m, 2H); MS: 492 [M+H⁺].

Compound 29. 5-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-26).

¹H-NMR (300 MHz, CDCl₃): 7.80-7.76 (m, 2H), 7.61-7.56 (m, 1H), 7.43-7.40 (m, 1H), 7.20-7.18 (m, 1H), 6.98-6.90 (m, 1H), 3.98-3.92 (m, 1H), 2.98-2.92 (t, 2H, J=7.4 Hz), 2.80-2.74 (m, 2H), 2.62 (s, 3H), 2.58-2.40 (m, 2H), 2.18-1.98 (m, 4H), 1.78-1.72 (m, 2H); MS: 510 [M+H⁺].

Compound 30. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]imidazo-[1,2-a]pyridine-3-sulphonamide

The title compound was prepared starting from amine (IIIa-2) and sulphonyl chloride (IIb-27).

¹H-NMR (300 MHz, CDCl₃): 8.60 (m, 1H), 8.18 (s, 1H), 7.68-7.65 (m, 1H), 7.61-7.42 (m, 4H), 7.08-7.01 (m, 1H), 3.85-3.81 (m, 1H), 3.02-2.96 (m, 2H), 2.79-2.76 (m, 1H), 2.52-2.38 (m, 3H), 2.21-1.87 (m, 4H), 1.62-1.52 (m, 2H); MS: 444[M+H⁺].

Compound 31. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1,3-benzothiazole-4-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-28).

¹H-NMR (300 MHz, CDCl₃): 9.20 (s, 1H), 8.20-8.15 (m, 2H), 7.60-7.55 (m, 2H), 7.20-7.18 (m, 1H), 7.08-7.01 (m, 1H), 3.87-3.80 (m, 1H), 3.00-2.96 (m, 2H), 2.82-2.77 (m, 1H), 2.50-2.38 (m, 3H), 2.20-1.87 (m, 4H), 1.62-1.52 (m, 2H); MS: 444[M+H⁺].

Compound 32. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]benzene-sulphonamide

The title compound was prepared starting from amine (IIIa-3) and sulphonyl chloride (IIb-1). MS: 418 [M+H⁺].

Compound 33. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIIa-3) and sulphonyl chloride (IIb-8). MS: 432 [M+H⁺].

Compound 34. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]-naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIIa-3) and sulphonyl chloride (IIb-17). MS: 468 [M+H⁺].

Compound 35. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-18). MS: 468 [M+H⁺].

Compound 36. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]-3-methylbenzenesulphonamide

The title compound was prepared starting from amine (IIa-4) and sulphonyl chloride (IIb-8). MS: 446 [M+H⁺].

Compound 37. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]-naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-4) and sulphonyl chloride (IIb-17). MS: 482 [M+H⁺].

Compound 38. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-4) and sulphonyl chloride (IIb-18). MS: 482 [M+H⁺].

Compound 39. N-[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-5) and sulphonyl chloride (IIb-18). MS: 454 [M+H⁺].

Compound 40. N-[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-6) and sulphonyl chloride (IIb-18). MS: 468 [M+H⁺].

Compound 41. N-[[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]-3-hydroxybenzenesulphonamide

The title compound was prepared starting from amine (IIa-7) and sulphonyl chloride (IIb-14). MS: 420 [M+H⁺].

Compound 42
N-[[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-7) and sulphonyl chloride (IIb-18). MS: 454 [M+H⁺].

Compound 43. N-[[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-8) and sulphonyl chloride (IIb-14). MS: 434 [M+H⁺].

Compound 44. N-[[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-8) and sulphonyl chloride (IIb-18). MS: 468 [M+H⁺].

Compound 45
N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-9) and sulphonyl chloride (IIb-1). MS: 372 [M+H⁺]

Compound 46. 4-Fluoro-N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-9) and sulphonyl chloride (IIb-3). MS: 390 [M+H⁺]

Compound 47. 3-Chloro-N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-9) and sulphonyl chloride (IIb-4). MS: 406 [M+H⁺]

Compound 48. N-[1-[2-(1H-Indol-4-yloxy)ethyl]azetidin-3-yl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-9) and sulphonyl chloride (IIb-8). MS: 386 [M+H⁺]

Compound 49. N-[1-[2-(1H-Indol-4-yloxy)ethyl]azetidin-3-yl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIIa-9) and sulphonyl chloride (IIb-17). MS: 422 [M+H⁺]

Compound 50. N-[1-[2-(1H-Indol-4-yloxy)ethyl]azetidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-9) and sulphonyl chloride (IIb-18). MS: 422 [M+H⁺]

Compound 51. N-[1-[2-(1H-Indol-4-yloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-10) and sulphonyl chloride (IIb-1). MS: 386 [M+H⁺]

Compound 52. N-[1-[2-(1H-Indol-4-yloxy)ethyl]pyrrolidin-3-yl]-3-methylbenzene-sulphonamide

The title compound was prepared starting from amine (IIa-10) and sulphonyl chloride (IIb-8). MS: 400 [M+H⁺]

Compound 53. N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-10) and sulphonyl chloride (IIb-17). MS: 436 [M+H⁺]

Compound 54. N-[1-[2-(1H-Indol-4-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-10) and sulphonyl chloride (IIb-18). MS: 436 [M+H⁺]

Compound 55. N-[1-[2-(1H-Indol-4-yloxy)ethyl]-4-piperidine]benzenesulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-1). MS: 400 [M+H⁺]

Compound 56. N-[1-[2-(1H-Indol-4-yloxy)ethyl]-4-piperidine]-3-methylbenzene-sulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-8). MS: 414 [M+H⁺]

Compound 57. 4-tert-Butylo-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-10). MS: 456 [M+H⁺]

Compound 58. N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]-4-(trifluoromethyl)-benzene-sulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-12). MS: 468 [M+H⁺]

Compound 59. 4-Cyano-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-16). MS: 425 [M+H⁺]

Compound 60. N-[1-[2-(1H-Indol-4-yloxy)ethyl]-4-piperidine]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-17). MS: 450 [M+H⁺]

Compound 61. N-[1-[2-(1H-Indol-4-yloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-18). MS: 450 [M+H⁺]

Compound 62. 5-Chloro-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-11) and sulphonyl chloride (IIb-26). MS: 504 [M+H⁺]

Compound 63. N-[[1-[2-(1H-Indol-4-yloxy)ethyl]-4-piperidine]methyl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-12) and sulphonyl chloride (IIb-1). MS: 414 [M+H⁺]

Compound 64. N-[[1-[2-(1H-Indol-4-yloxy)ethyl]-4-piperidine]methyl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-12) and sulphonyl chloride (IIb-8). MS: 428 [M+H⁺]

Compound 65. 3-Hydroxy-N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-12) and sulphonyl chloride (IIb-14). MS: 430 [M+H⁺]

Compound 66. N-[[1-[2-(1H-Indo-4-yloxy)ethyl]-4-piperidine]methyl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-12) and sulphonyl chloride (IIIb-17). MS: 464 [M+H⁺]

Compound 67. N-[[1-[2-(1H-Indol-4-yloxy)ethyl]-4-piperidine]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-12) and sulphonyl chloride (IIb-18). MS: 464 [M+H⁺]

Compound 68. N-[1-[2-(1H-Indol-6-yloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-13) and sulphonyl chloride (IIb-1). MS: 386 [M+H⁺]

Compound 69. N-[1-[2-(1H-Indol-6-yloxy)ethyl]pyrrolidin-3-yl]-3-methylbenzene-sulphonamide

The title compound was prepared starting from amine (IIa-13) and sulphonyl chloride (IIb-8). MS: 400 [M+H⁺]

Compound 70. N-[[1-[2-(1H-Indol-6-yloxy)ethyl]-4-piperidine]methyl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-14) and sulphonyl chloride (IIb-1). MS: 414 [M+H⁺]

Compound 71. N-[[1-[2-(1H-Indol-6-yloxy)ethyl]-4-piperidine]methyl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-14) and sulphonyl chloride (IIb-17). MS: 464 [M+H⁺]

Compound 72. N-[[1-[2-(1H-Indol-6-yloxy)ethyl]-4-piperidine]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-14) and sulphonyl chloride (IIb-18). MS: 464 [M+H⁺]

Compound 73. N-[1-[3-(5-Fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-1). MS: 402 [M+H⁺]

Compound 74. 3-Fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-2). MS: 420 [M+H⁺]

Compound 75. 4-Fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-3). MS: 420 [M+H⁺]

Compound 76. 3-Chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-4). MS: 436 [M+H⁺]

Compound 77. 4-Chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-5). MS: 436 [M+H⁺]

Compound 78. N-[1-[3-(5-Fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-8). MS: 416 [M+H⁺]

Compound 79. N-[1-[3-(5-Fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-17). MS: 452 [M+H⁺]

Compound 80. N-[1-[3-(5-Fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-18). MS: 452 [M+H⁺]

Compound 81. N-[1-[3-(5-Chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-1). MS: 418 [M+H⁺]

Compound 82. N-[1-[3-(5-Chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-fluoro-benzene-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-2). MS: 436 [M+H⁺]

Compound 83. N-[1-[3-(5-Chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-4-fluoro-benzenesulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-3). MS: 436 [M+H⁺]

Compound 84. 3-Chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-4). MS: 452 [M+H⁺]

Compound 85. 4-Chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-benzene-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIIb-5). MS: 452 [M+H⁺]

Compound 86
N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-8). MS: 432 [M+H⁺]

Compound 87. N-[1-[3-(5-Chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-18). MS: 468 [M+H⁺]

Compound 88. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-17) and sulphonyl chloride (IIb-1). MS: 391 [M+H⁺]

Compound 89. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-3-fluoro-benzenesulphonamide

The title compound was prepared starting from amine (IIa-17) and sulphonyl chloride (IIb-2). MS: 409 [M+H⁺]

Compound 90. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-4-fluoro-benzenesulphonamide

The title compound was prepared starting from amine (IIa-17) and sulphonyl chloride (IIb-3). MS: 409 [M+H⁺]

Compound 91. 3-Chloro-N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-17) and sulphonyl chloride (IIb-4). MS: 425 [M+H⁺]

Compound 92. 4-Chloro-N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-17) and sulphonyl chloride (IIb-5). MS: 425 [M+H⁺]

Compound 93. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-17) and sulphonyl chloride (IIb-8). MS: 405 [M+H⁺]

Compound 94. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-17) and sulphonyl chloride (IIb-17). MS: 441 [M+H⁺]

Compound 95. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-17) and sulphonyl chloride (IIb-18). MS: 441 [M+H⁺]

Compound 96. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-benzenesulphonamide

The title compound was prepared starting from amine (IIIa-18) and sulphonyl chloride (IIb-1). MS: 405 [M+H⁺]

Compound 97. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-3-methylbenzenesulphonamide

The title compound was prepared starting from amine (IIa-18) and sulphonyl chloride (IIb-8). MS: 419 [M+H⁺]

Compound 98. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-18) and sulphonyl chloride (IIb-17). MS: 457 [M+H⁺]

Compound 99. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-18) and sulphonyl chloride (IIb-18). MS: 457 [M+H⁺]

Compound 100. N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]-naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-19) and sulphonyl chloride (IIb-17). MS: 469 [M+H⁺]

Compound 101. N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]-methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-20) and sulphonyl chloride (IIb-1). MS: 433 [M+H⁺]

Compound 102. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]-methyl]-3-methy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-20) and sulphonyl chloride (IIb-8). MS: 447 [M+H⁺]

Compound 103. N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]-methyl]-3-hydroxybenzenesulphonamide

The title compound was prepared starting from amine (IIIa-20) and sulphonyl chloride (IIb-14). MS: 449 [M+H⁺]

Compound 104. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]-methyl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-20) and sulphonyl chloride (IIb-17). MS: 483 [M+H⁺]

Zwiazek 105. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]-methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-20) and sulphonyl chloride (IIb-18). MS: 483 [M+H⁺]

Compound 106. N-[[1-[2-(2-Oxoindolin-4-yl)oxyethyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-21) and sulphonyl chloride (IIb-18). MS: 452 [M+H⁺]

Compound 107. N-[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]-3-hydroxybenzenesulphonamide

The title compound was prepared starting from amine (IIa-22) and sulphonyl chloride (IIb-14). MS: 433 [M+H⁺]

Compound 108. N-[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-22) and sulphonyl chloride (IIb-18). MS: 467 [M+H⁺]

Compound 109. N-[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]-4-piperidine]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-23) and sulphonyl chloride (IIb-14). MS: 447 [M+H⁺]

Compound 110. N-[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]-4-piperidine]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-23) and sulphonyl chloride (IIb-18). MS: 481 [M+H⁺]

Compound 111. N-[[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]azetidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-24) and sulphonyl chloride (IIb-14). MS: 481 [M+H⁺]

Compound 112. N-[[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-24) and sulphonyl chloride (IIIb-18). MS: 467 [M+H+]

Compound 113. N-[[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-25) and sulphonyl chloride (IIb-14). MS: 447 [M+H⁺]

Compound 114. N-[[1-[2-[(2,2-Dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-25) and sulphonyl chloride (IIb-18). MS: 481 [M+H⁺]

Compound 115
3-Hydroksy-N-[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-26) and sulphonyl chloride (IIb-14). MS: 413 [M+H⁺]

Compound 116. N-[1-[2-(1-Naphthyloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-26) and sulphonyl chloride (IIb-18). MS: 447 [M+H⁺]

Compound 117. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-19) and sulphonyl chloride (IIb-1). MS: 418 [M+H⁺]

Compound 118. N-[1-[2-(2,3-Dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIIa-19) and sulphonyl chloride (IIb-8). MS: 433 [M+H⁺]

Compound 119. 3-Hydroxy-N-[1-[2-(1-naphthyloxy)ethyl]-4-piperidine]benzene-sulphonamide

The title compound was prepared starting from amine (IIa-27) and sulphonyl chloride (IIb-14). MS: 427 [M+H⁺]

Compound 120. N-[1-[2-(1-Naphthyloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-27) and sulphonyl chloride (IIb-18). MS: 461 [M+H⁺]

Compound 121. 3-Hydroxy-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]-benzenesulphonamide

The title compound was prepared starting from amine (IIIa-28) and sulphonyl chloride (IIb-14). MS: 413 [M+H⁺]

Compound 122. N-[[1-[2-(1-Naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-18). MS: 447 [M+H⁺]

Compound 123. 3-Hydroxy-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-14). MS: 427 [M+H⁺]

Compound 124. N-[[1-[2-(1-Naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-18). MS: 461 [M+H⁺]

Compound 125. N-[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-5) and sulphonyl chloride (IIIb-14). MS: 450 [M+H⁺]

Compound 126. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIIb-48). MS: 420 [M+H⁺]

Compound 127. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzo-thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-22). MS: 460 [M+H⁺]

Compound 128. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-28). MS: 461 [M+H⁺]

Compound 129. 6-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-37). MS: 488 [M+H⁺]

Compound 130. 5-Fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-30) and sulphonyl chloride (IIb-25). MS: 492 [M+H⁺]

Compound 131. 5-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-26). MS: 508 [M+H⁺]

Compound 132. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzothiazole-5-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-55). MS: 461 [M+H⁺]

Compound 133. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-17). MS: 454 [M+H⁺]

Compound 134. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-18). MS: 454 [M+H⁺]

Compound 135. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-phenyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-36). MS: 480 [M+H⁺]

Compound 136. 4-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-5). MS: 438 [M+H+]

Compound 137. 3-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-4). MS: 438 [M+H⁺]

Compound 138. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-33). MS: 418 [M+H⁺]

Compound 139. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-1). MS: 404 [M+H⁺]

Compound 140. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-12). MS: 472 [M+H⁺]

Compound 141. 4-tert-Butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-10). MS: 460 [M+H⁺]

Compound 142. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-8). MS: 418 [M+H⁺]

Compound 143. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methoxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-13). MS: 434 [M+H⁺]

Compound 144. 3-Fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-2). MS: 422 [M+H⁺]

Compound 145. 4-Cyano-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-30) and sulphonyl chloride (IIb-16). MS: 429 [M+H⁺]

Compound 146. 3,4-Dichloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-3). MS: 422 [M+H⁺]

Compound 147. 4-Fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-30) and sulphonyl chloride (IIb-32). MS: 472 [M+H⁺]

Compound 148. 4-Bromo-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-6). MS: 482 [M+H⁺]

Compound 149. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-14). MS: 420 [M+H⁺]

Compound 150. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-51). MS: 457 [M+H⁺]

Compound 151. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzofuran-2-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-52). MS: 444 [M+H⁺]

Compound 152. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-50). MS: 456 [M+H⁺]

Compound 153. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-23). MS: 460 [M+H⁺]

Compound 154. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-thiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-41). MS: 410 [M+H⁺]

Compound 155. 5-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-20). MS: 444 [M+H⁺]

Compound 156. 3-Chloro-4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-7). MS: 456 [M+H⁺]

Compound 157. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-propyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-9). MS: 446 [M+H⁺]

Compound 158. 3,4-Difluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIb-31). MS: 440 [M+H⁺]

Compound 159. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide

The title compound was prepared starting from amine (IIa-30) and sulphonyl chloride (IIIb-35). MS: 488 [M+H⁺]

Compound 160. N-[[1-[3-(5-Fluoro-1H-indol-3-yl)propyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-34) and sulphonyl chloride (IIb-18). MS: 452 [M+H⁺]

Compound 161. N-[[1-[3-(5-Chloro-1H-indol-3-yl)propyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-36) and sulphonyl chloride (IIb-18). MS: 468 [M+H⁺]

Compound 162. N-[[1-[2-(1,2-Benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-7) and sulphonyl chloride (IIb-18). MS: 454 [M+H⁺]

Compound 163. N-[[1-[2-(1-Naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-22). MS: 453 [M+H⁺]

Compound 164. 6-Chloro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-24). MS: 487 [M+H⁺]

Compound 165. 6-Chloro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-37). MS: 481 [M+H⁺]

Compound 166. 5-Fluoro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-25). MS: 485 [M+H⁺]

Compound 167. 5-Chloro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-26). MS: 501 [M+H⁺]

Compound 168. N-[[1-[2-(1-Naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-17). MS: 447 [M+H⁺]

Compound 169. 1-Methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-51). MS: 450 [M+H⁺]

Compound 170. 1-Methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-50). MS: 450 [M+H⁺]

Compound 171. N-[[1-[2-(1-Naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-23). MS: 453 [M+H⁺]

Compound 172. 3-Chloro-4-fluoro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-7). MS: 449 [M+H⁺]

Compound 173. 3,4-Difluoro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]-benzenesulphonamide

The title compound was prepared starting from amine (IIa-28) and sulphonyl chloride (IIb-31). MS: 433 [M+H⁺]

Compound 174. 6-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-37) and sulphonyl chloride (IIb-37). MS: 489 [M+H⁺]

Compound 175. 5-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-37) and sulphonyl chloride (IIb-26). MS: 509 [M+H⁺]

Compound 176. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-17). MS: 455 [M+H⁺]

Compound 177. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-37) and sulphonyl chloride (IIb-18). MS: 455 [M+H⁺]

Compound 178. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-phenyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-36). MS: 481 [M+H⁺]

Compound 179. 4-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-5). MS: 439 [M+H⁺]

Compound 180. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIIa-37) and sulphonyl chloride (IIb-12). MS: 473 [M+H⁺]

Compound 181. 4-tert-Butyl-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-10). MS: 461 [M+H⁺]

Compound 182. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-fluoro-benzenesulphonamide

The title compound was prepared starting from amine (IIIa-37) and sulphonyl chloride (IIb-3). MS: 423 [M+H⁺]

Compound 183. 3,4-Dichloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-32). MS: 473 [M+H⁺]

Compound 184. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-40). MS: 411 [M+H⁺]

Compound 185. 4-Bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-6). MS: 483 [M+H⁺]

Compound 186. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-benzofuran-2-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-52). MS: 445 [M+H⁺]

Compound 187. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-51). MS: 458 [M+H⁺]

Compound 188. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-50). MS: 458 [M+H⁺]

Compound 189. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide

The title compound was prepared starting from amine (IIIa-37) and sulphonyl chloride (IIb-47). MS: 460 [M+H⁺]

Compound 190. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-23). MS: 461 [M+H⁺]

Compound 191. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-thiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-41). MS: 411 [M+H⁺]

Compound 192. 5-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-20). MS: 445 [M+H⁺]

Compound 193. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-iodo-benzenesulphonamide

The title compound was prepared starting from amine (IIa-37) and sulphonyl chloride (IIb-30). MS: 531 [M+H⁺]

Compound 194. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1,3-benzo-dioxole-5-sulphonamide

The title compound was prepared starting from amine (IIIa-3) and sulphonyl chloride (IIb-48).

¹H-NMR (300 MHz, CDCl₃): δ 7.60-7.56 (m, 1H), 7.40 (dd, 1H, J=1.8 and 8.2 Hz) 7.26-7.20 (m, 1H), 7.20 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.7 Hz), 6.82 (d, 1H, J=8.2 Hz), 6.03 (s, 2H), 3.78 (s, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.79-2.69 (m, 1H), 2.50-2.40 (m, 3H), 2.26-2.18 (m, 1H), 2.10-2.00 (m, 1H), 1.98-1.80 (m, 2H), 1.60-1.49 (m, 2H); MS: 448 [M+H⁺].

Compound 195. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-phenyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-36). MS: 480 [M+H⁺]

Compound 196. N-[(3R)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-22).

¹H-NMR (300 MHz, CDCl₃): δ 7.87-7.80 (m, 3H), 7.58-7.54 (m, 1H), 7.48-7.42 (m, 2H), 7.24-7.19 (m, 1H), 7.04 (dt, 1H, J=2.3 and 8.9 Hz), 4.00-3.92 (m, 1H), 2.96 (t, 2H, J=7.4 Hz), 2.84-2.76 (m, 1H), 2.60-2.38 (m, 3H), 2.20-2.08 (m, 2H), 2.00-1.88 (m, 2H), 1.64-1.54 (m, 2H); MS: 460 [M+H⁺].

Compound 197. N-[(3S)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-22).

¹H-NMR (300 MHz, CDCl₃): δ 7.87-7.80 (m, 3H), 7.58-7.54 (m, 1H), 7.47-7.42 (m, 2H), 7.23-7.18 (m, 1H), 7.04 (dt, 1H, J=1.8 and 8.4 Hz), 4.00-3.92 (m, 1H), 2.95 (t, 2H, J=7.4 Hz), 2.82-2.78 (m, 1H), 2.60-2.54 (m, 1H), 2.50-2.38 (m, 2H), 2.20-2.06 (m, 2H), 2.00-1.88 (m, 2H), 1.64-1.54 (m, 2H); MS: 460 [M+H⁺].

Compound 198. 6-Chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-32) and sulphonyl chloride (IIb-24).

¹H-NMR (300 MHz, CDCl₃): δ 7.82-7.74 (m, 3H), 7.58-7.54 (m, 1H), 7.39 (dd, 1H, J=1.7 and 8.7 Hz), 7.21 (dd, 1H, J=1.5 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 4.00-3.92 (m, 1H), 2.95 (t, 2H, J=8.4 Hz), 2.84-2.78 (m, 1H), 2.58 (dd, 1H, J=2.8 and 9.7 Hz), 2.50-2.38 (m, 2H), 2.20-2.10 (m, 2H), 2.0-1.90 (m, 2H), 1.68-1.58 (m, 2H); MS: 494 [M+H⁺].

Compound 199. 6-Chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-24).

¹H-NMR (300 MHz, CDCl₃): δ 7.82-7.74 (m, 3H), 7.59-7.54 (m, 1H), 7.40 (dd, 1H, J=1.7 and 8.7 Hz), 7.22 (dd, 1H, J=1.5 and 8.4 Hz), 7.05 (dt, 1H, J=2.0 and 8.9 Hz), 4.00-3.92 (m, 1H), 2.95 (t, 2H, J=8.4 Hz), 2.84-2.78 (m, 1H), 2.59 (dd, 1H, J=2.8 and 9.7 Hz), 2.50-2.38 (m, 2H), 2.20-2.10 (m, 2H), 2.0-1.90 (m, 2H), 1.68-1.58 (m, 2H); MS: 494 [M+H⁺].

Compound 200. 6-Chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-37).

¹H-NMR (300 MHz, CDCl₃): δ 8.40 (s, 1H), 7.89-7.84 (m, 4H), 7.56-7.50 (m, 2H), 7.21 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=1.0 and 8.9 Hz), 3.90-3.82 (m, 1H), 2.94 (t, 2H, J=7.4 Hz), 2.78-2.70 (m, 1H), 2.50-2.40 (m, 3H), 2.38-2.30 (m, 1H), 2.18-1.86 (m, 3H), 1.58-1.48 (m, 2H); MS: 488 [M+H⁺].

Compound 201. 6-Chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-37).

¹H-NMR (300 MHz, CDCl₃): δ 8.40 (s, 1H), 7.88-7.84 (m, 4H), 7.58-7.52 (m, 2H), 7.21 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 3.90-3.82 (m, 1H), 2.95 (t, 2H, J=7.4 Hz), 2.81-2.73 (m, 1H), 2.52-2.40 (m, 2H), 2.38-2.30 (m, 1H), 2.18-1.86 (m, 4H), 1.58-1.48 (m, 2H); MS: 488 [M+H⁺].

Compound 202. 5-Fluoro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-25).

¹H-NMR (300 MHz, CDCl₃): δ 7.78-7.74 (m, 1H), 7.60-7.54 (m, 1H), 7.45 (dd, 1H, J=2.0 and 9.2 Hz), 7.25-7.21 (m, 2H), 7.06 (dt, 1H, J=2.0 and 8.9 Hz), 3.90-3.82 (m, 1H), 2.98 (t, 2H, J=8.4 Hz), 2.86-2.78 (m, 1H), 2.63 (s, 3H), 2.58 (dd, 1H, J=2.8 and 9.7 Hz), 2.47 (t, 2H, J=6.9 Hz), 2.38 (dd, 1H, J=5.8 and 9.7 Hz), 2.18-2.10 (m, 2H), 2.00-1.90 (m, 2H), 1.64-1.58 (m, 1H); MS: 492 [M+H⁺].

Compound 203. 5-Fluoro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-25).

¹H-NMR (300 MHz, CDCl₃): δ 7.77-7.72 (m, 1H), 7.60-7.54 (m, 1H), 7.44 (dd, 1H, J=2.0 and 9.2 Hz), 7.26-7.21 (m, 2H), 7.06 (dt, 1H, J=2.0 and 8.9 Hz), 3.90-3.82 (m, 1H), 2.98 (t, 2H, J=8.4 Hz), 2.86-2.78 (m, 1H), 2.63 (s, 3H), 2.58 (dd, 1H, J=2.8 and 9.7 Hz), 2.47 (t, 2H, J=6.9 Hz), 2.38 (dd, 1H, J=5.8 and 9.7 Hz), 2.18-2.10 (m, 2H), 2.00-1.90 (m, 2H), 1.64-1.58 (m, 1H); MS: 492 [M+H⁺].

Compound 204. 5-Chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-26).

¹H-NMR (300 MHz, CDCl₃): δ 7.77-7.70 (m, 2H), 7.59-7.52 (m, 1H), 7.43 (dd, 1H, J=2.0 and 8.7 Hz), 7.21 (dd, 1H, J=1.7 and 8.4 Hz), 7.05 (dt, 1H, J=2.0 and 8.9 Hz), 4.00-3.93 (m, 1H), 2.98 (t, 2H, J=8.4 Hz), 2.83-2.78 (m, 1H), 2.62 (s, 3H), 2.60-2.42 (m, 1H), 2.50-2.42 (m, 2H), 2.40-2.36 (m, 1H), 2.20-2.14 (m, 2H), 2.00-1.90 (m, 2H), 1.68-1.58 (m, 1H); MS: 508 [M+H⁺].

Compound 205. 5-Chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-26).

¹H-NMR (300 MHz, CDCl₃): δ 7.78-7.70 (m, 2H), 7.59-7.52 (m, 1H), 7.43 (dd, 1H, J=2.0 and 8.7 Hz), 7.21 (dd, 1H, J=1.7 and 8.4 Hz), 7.05 (dt, 1H, J=2.0 and 8.9 Hz), 4.01-3.93 (m, 1H), 2.97 (t, 2H, J=8.4 Hz), 2.83-2.78 (m, 1H), 2.62 (s, 3H), 2.60-2.42 (m, 1H), 2.51-2.42 (m, 2H), 2.40-2.36 (m, 1H), 2.20-2.14 (m, 2H), 2.00-1.90 (m, 2H), 1.68-1.58 (m, 1H); MS: 508 [M+H⁺].

Compound 206. N-[(3R)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-18).

¹H-NMR (300 MHz, CDCl₃): δ 8.43 (d, 1H, J=1.8 Hz), 7.98-7.80 (m, 4H), 7.68-7.52 (m, 3H), 7.21 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.3 and 8.9 Hz), 3.83 (m, 1H), 2.84 (t, 2H, J=7.4 Hz), 2.78-2.68 (m, 1H), 2.50-2.32 (m, 3H), 2.18-1.85 (m, 4H), 1.58-1.47 (m, 2H); MS: 454 [M+H⁺].

Compound 207. N-[(3S)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-18).

¹H-NMR (300 MHz, CDCl₃): δ 8.43 (d, 1H, J=1.8 Hz), 7.90-7.80 (m, 4H), 7.68-7.52 (m, 3H), 7.21 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.3 and 8.4 Hz), 3.88-3.83 (m, 1H), 2.94 (t, 2H, J=7.4 Hz), 2.78-2.68 (m, 1H), 2.40-2.31 (m, 3H), 2.18-1.84 (m, 4H), 1.58-1.48 (m, 2H); MS: 454 [M+H⁺].

Compound 208. 4-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-5). MS: 438 [M+H⁺]

Compound 209. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-33). MS: 418 [M+H⁺]

Compound 210. 4-Cyano-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-16).

¹H-NMR (300 MHz, CDCl₃): δ 8.01-7.96 (m, 2H), 7.82-7.78 (m, 2H), 7.60-7.54 (m, 1H), 7.24 (dd, 1H, J=2.0 and 8.4 Hz), 7.06 (dt, 1H, J=2.3 and 8.9 Hz), 3.80 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.84-2.78 (m, 1H), 2.52-2.44 (m, 3H), 2.40-2.34 (m, 1H), 2.18-2.02 (m, 2H), 2.00-1.98 (m, 2H), 1.58-1.48 (m, 1H); MS: 429 [M+H⁺].

Compound 211. 3,4-Dichloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-32). MS: 429 [M+H⁺]

Compound 212. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-40). MS: 410 [M+H⁺]

Compound 213. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-methoxybenzenesulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-34). MS: 434 [M+H⁺]

Compound 214. N-[(3R)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-furan-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-52).

¹H-NMR (300 MHz, CDCl₃): δ 7.67-7.63 (m, 1H), 7.58-7.53 (m, 1H), 7.51-7.48 (m, 1H), 7.45-7.38 (m, 1H), 7.37-7.28 (m, 1H), 7.34-7.28 (m, 1H), 7.20 (dd, 1H, J=1.7 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 4.04-3.96 (m, 1H), 2.96 (t, 2H, J=8.4 Hz), 2.84-2.78 (m, 1H), 2.60-2.40 (m, 3H), 2.20-2.08 (m, 2H), 2.00-1.90 (m, 2H), 1.64-1.58 (m, 2H); MS: 444 [M+H⁺].

Compound 215. N-[(3S)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-furan-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-52).

¹H-NMR (300 MHz, CDCl₃): δ 7.67-7.63 (m, 1H), 7.58-7.53 (m, 1H), 7.51-7.48 (m, 1H), 7.45-7.38 (m, 1H), 7.37-7.28 (m, 1H), 7.34-7.28 (m, 1H), 7.20 (dd, 1H, J=1.7 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 4.04-3.96 (m, 1H), 2.96 (t, 2H, J=8.4 Hz), 2.84-2.78 (m, 1H), 2.61-2.40 (m, 3H), 2.20-2.08 (m, 2H), 2.00-1.90 (m, 2H), 1.64-1.58 (m, 2H); MS: 444 [M+H⁺].

Compound 216. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzofuran-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-52).

¹H-NMR (300 MHz, CDCl₃): δ 7.68-7.64 (m, 1H), 7.58-7.56 (m, 1H), 7.52-7.48 (m, 1H), 7.46-7.40 (m, 1H), 7.38-7.29 (m, 2H), 7.24-7.20 (m, 1H), 7.05 (dt, 1H, J=2.3 and 8.9 Hz), 4.00 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.84-2.78 (m, 1H), 2.60-2.38 (m, 4H), 2.20-2.08 (m, 2H), 2.00-1.90 (m, 2H), 1.64-1.58 (m, 1H); MS: 444 [M+H⁺].

Compound 217. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-imidazole-4-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-44).

¹H-NMR (300 MHz, CDCl₃): δ 7.70 (dd, 1H, J=1 and 7.70 Hz), 7.54-7.50 (m, 1H), 7.15 (d, 1H, J=3.0 Hz), 7.06 (dd, 1H, J=2.0 and 8.7 Hz), 6.87 (dd, 1H, J=0.7 and 3.0 Hz), 3.80 (s, 3H), 3.78 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.72-2.62 (m, 1H), 2.46-2.30 (m, 3H), 2.12-2.02 (m, 2H), 1.98-1.78 (m, 3H), 1.48-1.38 (m, 1H); MS: 458 [M+H⁺].

Compound 218. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-51).

¹H-NMR (300 MHz, CDCl₃): δ 8.18 (d, 1H, J=1.3 Hz), 7.66 (dd, 1H, J=1.8 and 8.7 Hz), 7.59-7.54 (m, 1H), 7.38-7.34 (m, 1H), 7.23-7.14 (m, 2H), 7.04 (dt, 1H, J=2.0 and 8.7 Hz), 6.56 (dt, 1H, J=0.7 and 3.0 Hz), 3.80 (m, 4H), 2.94 (t, 2H, J=7.4 Hz), 2.78-2.64 (m, 1H), 2.50-2.34 (m, 4H), 2.22-2.18 (m, 1H), 2.08-1.88 (m, 3H), 1.58-1.48 (m, 1H); MS: 458 [M+H⁺].

Compound 219. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIIa-2) and sulphonyl chloride (IIb-50). MS: 457 [M+H⁺]

Compound 220. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2-oxo-indoline-5-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-47).

¹H-NMR (300 MHz, DMSO): δ 10.78 (s, 1H), 7.98-7.80 (m, 1H), 7.64-7.58 (m, 3H), 7.24-7.18 (m, 1H), 6.96-6.90 (dt, 1H, J=2.3 and 8.9 Hz), 3.60 (s, 2H), 3.56 (s, 1H), 2.94 (t, 2H, J=7.4 Hz), 2.56 (m, 1H), 2.46-2.30 (m, 4H), 2.24-2.18 (m, 1H), 1.88-1.74 (m, 2H), 1.47-1.38 (m, 2H); MS: 459 [M+H⁺].

Compound 221. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-42).

¹H-NMR (300 MHz, CDCl₃): δ 7.62-7.58 (m, 1H), 7.28-7.21 (m, 1H), 7.06 (dt, 1H, J=2.3 and 8.9 Hz), 6.87 (d, 1H, J=1.0 Hz), 3.81-3.78 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.80-2.72 (m, 1H), 2.59 (s, 3H), 2.54-2.46 (m, 3H), 2.38 (s, 3H), 2.21-2.06 (m, 2H), 2.02-1.90 (m, 2H), 1.62-1.58 (m, 2H); MS: 438 [M+H⁺].

Compound 222. N-[(3R)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-42).

¹H-NMR (300 MHz, CDCl₃): δ 7.62-7.58 (m, 1H), 7.23-7.19 (m, 1H), 7.05 (dt, 1H, J=2.3 and 8.9 Hz), 6.87-6.85 (m, 1H), 3.81-3.78 (m, 1H), 2.98 (t, 2H, J=8.4 Hz), 2.80-2.72 (m, 1H), 2.58 (s, 3H), 2.54-2.40 (m, 2H), 2.35 (s, 3H), 2.28-2.08 (m, 1H), 2.14-2.04 (m, 2H), 2.02-1.90 (m, 2H), 1.64-1.56 (m, 2H); MS: 438 [M+H⁺].

Compound 223. N-[(3S)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide

The title compound was prepared starting from amine (IIIa-33) and sulphonyl chloride (IIb-42).

¹H-NMR (300 MHz, CDCl₃): δ 7.62-7.58 (m, 1H), 7.23-7.19 (m, 1H), 7.05 (dt, 1H, J=2.3 and 8.9 Hz), 6.87-6.85 (m, 1H), 3.81-3.78 (m, 1H), 2.98 (t, 2H, J=8.4 Hz), 2.80-2.72 (m, 1H), 2.58 (s, 3H), 2.54-2.40 (m, 2H), 2.35 (s, 3H), 2.28-2.08 (m, 1H), 2.13-2.04 (m, 2H), 2.00-1.98 (m, 2H), 1.64-1.56 (m, 2H); MS: 438 [M+H⁺].

Compound 224. N-[(3R)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-23).

¹H-NMR (300 MHz, CDCl₃): δ 8.23 (s, 1H), 8.18-8.16 (m, 1H), 7.87-7.83 (m, 1H), 7.58-7.52 (m, 1H), 7.48-7.36 (m, 2H), 7.22 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.3 and 8.9 Hz), 3.90-3.80 (m, 1H), 2.80 (t, 2H, J=8.4 Hz), 2.72-2.64 (m, 1H), 2.48-2.24 (m, 3H), 2.18-1.94 (m, 2H), 1.88-1.78 (m, 2H), 1.54-1.40 (m, 2H); MS: 460 [M+H⁺].

Compound 225. N-[(3S)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-23).

¹H-NMR (300 MHz, CDCl₃): δ 8.23 (s, 1H), 8.18-8.16 (m, 1H), 7.88-7.84 (m, 1H), 7.58-7.52 (m, 1H), 7.50-7.36 (m, 2H), 7.22 (dd, 1H, J=1.8 and 8.4 Hz), 7.06 (dt, 1H, J=2.3 and 8.9 Hz), 3.90-3.80 (m, 1H), 2.80 (t, 2H, J=8.4 Hz), 2.72-2.64 (m, 1H), 2.5-2.24 (m, 3H), 2.18-1.94 (m, 2H), 1.88-1.78 (m, 2H), 1.54-1.40 (m, 2H); MS: 460 [M+H⁺].

Compound 226. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methylbenzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-54).

¹H-NMR (300 MHz, CDCl₃): δ 7.77 (d, 1H, J=0.7 Hz), 7.69 (d, 1H, J=8.4 Hz), 7.64-7.62 (m, 1H), 7.59-7.54 (m, 1H), 7.32-7.28 (m, 1H), 7.21 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 4.00-3.92 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.84-2.76 (m, 1H), 2.60-2.38 (m, 3H), 2.45 (s, 3H), 2.20-2.10 (m, 2H), 1.98-1.78 (m, 2H), 1.66-1.58 (m, 2H); MS: 474 [M+H⁺].

Compound 227. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-39).

¹H-NMR (300 MHz, CDCl₃): δ 8.32 (s, 1H), 7.84-7.78 (m, 2H), 7.58-7.52 (m, 1H), 7.24-7.14 (m, 4H), 7.03 (dt, 1H, J=2.0 and 8.9 Hz), 3.95 (s, 3H), 3.90-3.80 (m, 1H), 2.96 (t, 2H, J=8.4 Hz), 2.75-2.68 (m, 1H), 2.49-2.32 (m, 3H), 2.20-1.84 (m, 4H), 1.60-1.48 (m, 2H); MS: 484 [M+H⁺].

Compound 228. N-[(3R)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-54).

¹H-NMR (300 MHz, CDCl₃): δ 7.78 (d, 1H, J=0.7 Hz), 7.70 (d, 1H, J=8.4 Hz), 7.65-7.63 (m, 1H), 7.59-7.54 (m, 1H), 7.32-7.28 (m, 1H), 7.21 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 3.90-3.82 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.82-2.75 (m, 1H), 2.48-2.38 (m, 3H), 2.45 (s, 3H), 2.18-2.10 (m, 2H), 1.98-1.78 (m, 2H), 1.64-1.58 (m, 2H); MS: 474 [M+H⁺].

Compound 229. N-[(3S)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methylbenzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-54).

¹H-NMR (300 MHz, CDCl₃): δ 7.68 (d, 1H, J=0.7 Hz), 7.69 (d, 1H, J=8.4 Hz), 7.64-7.62 (m, 1H), 7.58-7.54 (m, 1H), 7.31-7.28 (m, 1H), 7.21 (dd, 1H, J=1.8 and 8.4 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 3.90-3.82 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.82-2.74 (m, 1H), 2.50-2.38 (m, 3H), 2.45 (s, 3H), 2.18-2.10 (m, 2H), 1.98-1.78 (m, 2H), 1.64-1.58 (m, 2H); MS: 474 [M+H⁺].

Compound 230. N-[(3R)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-39).

¹H-NMR (300 MHz, CDCl₃): δ 8.33 (s, 1H), 7.82-7.78 (m, 2H), 7.56-7.50 (m, 1H), 7.22-7.12 (m, 4H), 7.02 (dt, 1H, J=2.0 and 8.9 Hz), 3.95 (s, 3H), 3.90-3.80 (m, 1H), 2.96 (t, 2H, J=8.4 Hz), 2.74-2.68 (m, 1H), 2.49-2.32 (m, 3H), 2.20-2.10 (m, 1H), 2.08-1.98 (m, 1H), 1.94-1.84 (m, 2H), 1.60-1.48 (m, 2H); MS: 484 [M+H⁺].

Compound 231. N-[(3S)-1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-39).

¹H-NMR (300 MHz, CDCl₃): δ 8.33 (s, 1H), 7.82-7.78 (m, 2H), 7.57-7.51 (m, 1H), 7.23-7.13 (m, 4H), 7.02 (dt, 1H, J=2.0 and 8.9 Hz), 3.95 (s, 3H), 3.90-3.80 (m, 1H), 2.95 (t, 2H, J=8.4 Hz), 2.74-2.68 (m, 1H), 2.49-2.32 (m, 3H), 2.20-2.10 (m, 1H), 2.08-1.98 (m, 1H), 1.94-1.84 (m, 2H), 1.60-1.48 (m, 2H); MS: 484 [M+H⁺].

Compound 232. 7-Chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-32) and sulphonyl chloride (IIb-38).

¹H-NMR (300 MHz, CDCl₃): δ 8.40 (s, 1H), 7.89-7.83 (m, 4H), 7.58-7.50 (m, 2H), 7.21 (dd, 1H, J=1.8 and 8.2 Hz), 7.03 (dt, 1H, J=2.0 and 8.9 Hz), 3.92-3.82 (m, 1H), 2.98 (t, 2H, J=8.4 Hz), 2.78-2.70 (m, 1H), 2.50-2.32 (m, 3H), 2.20-1.84 (m, 4H), 1.60-1.58 (m, 2H); MS: 488 [M+H⁺].

Compound 233. 7-Chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-33) and sulphonyl chloride (IIb-38).

¹H-NMR (300 MHz, CDCl₃): δ 8.40 (s, 1H), 7.89-7.84 (m, 4H), 7.58-7.50 (m, 2H), 7.21 (dd, 1H, J=1.8 and 8.2 Hz), 7.04 (dt, 1H, J=2.0 and 8.9 Hz), 3.91-3.82 (m, 1H), 2.98 (t, 2H, J=8.4 Hz), 2.80-2.70 (m, 1H), 2.52-2.32 (m, 3H), 2.20-1.84 (m, 4H), 1.60-1.58 (m, 2H); MS: 488 [M+H⁺].

Compound 234. 6-Fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-2) and sulphonyl chloride (IIb-53).

¹H-NMR (300 MHz, CDCl₃): δ 7.84-7.79 (m, 2H), 7.60-7.54 (m, 1H), 7.50 (dd, 1H, J=2.3 and 8.4 Hz), 7.24-7.16 (m, 2H), 7.05 (dt, 1H, J=2.0 and 8.7 Hz), 3.98 (m, 1H), 2.98 (t, 2H, J=7.4 Hz), 2.86-2.80 (m, 1H), 2.62-2.58 (m, 2H), 2.52-2.46 (m, 1H), 2.44-2.38 (m, 1H), 2.20-2.10 (m, 2H), 2.00-1.90 (m, 2H), 1.68-1.58 (m, 1H); MS: 478 [M+H⁺].

Compound 235. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-48). MS: 462 [M+H⁺]

Compound 236. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-28). MS: 475 [M+H⁺]

Compound 237. 6-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-31) and sulphonyl chloride (IIb-37). MS: 502 [M+H⁺]

Compound 238. 5-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-26). MS: 522 [M+H⁺]

Compound 239. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-17). MS: 468 [M+H⁺]

Compound 240. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-18). MS: 468 [M+H⁺]

Compound 241. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-phenyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-36). MS: 494 [M+H⁺]

Compound 242. 4-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-5). MS: 452 [M+H⁺]

Compound 243. 3-Chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-31) and sulphonyl chloride (IIb-4). MS: 452 [M+H⁺]

Compound 244. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-33). MS: 432 [M+H⁺]

Compound 245. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-1). MS: 418 [M+H⁺]

Compound 246. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-12). MS: 486 [M+H⁺]

Compound 247. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-11). MS: 486 [M+H⁺]

Compound 248. 4-tert-Butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-10). MS: 474 [M+H⁺]

Compound 249. 3-tert-Butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-8). MS: 432 [M+H⁺]

Compound 250. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-methoxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-13). MS: 448 [M+H⁺]

Compound 251. 4-Cyano-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-16). MS: 443 [M+H⁺]

Compound 252. 4-Fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-3). MS: 436 [M+H⁺]

Compound 253. 3,4-Dichloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-32). MS: 486 [M+H⁺]

Compound 254. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-14). MS: 434 [M+H⁺]

Compound 255. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-methoxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-34). MS: 448 [M+H⁺]

Compound 256. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2,3-dihydrobenzofuran-5-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-21). MS: 460 [M+H⁺]

Compound 257. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzofuran-2-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-52). MS: 458 [M+H⁺]

Compound 258. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-51). MS: 473 [M+H⁺]

Compound 259. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-50). MS: 471 [M+H⁺]

Compound 260. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-47). MS: 473 [M+H⁺]

Compound 261. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-23). MS: 474 [M+H⁺]

Compound 262. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2,5-dimethyl-thiophene-3-sulphonamide

The title compound was prepared starting from amine (IIIa-31) and sulphonyl chloride (IIb-42). MS: 452 [M+H⁺]

Compound 263. 3-Chloro-4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-31) and sulphonyl chloride (IIb-7). MS: 470 [M+H⁺]

Compound 264. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-propyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-9). MS: 460 [M+H⁺]

Compound 265. 3,4-Difluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-31). MS: 454 [M+H⁺]

Compound 266. N-[[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide

The title compound was prepared starting from amine (IIa-31) and sulphonyl chloride (IIb-35). MS: 502 [M+H⁺]

Compound 267. N-[[1-[3-(5-Fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-35) and sulphonyl chloride (IIb-18). MS: 466 [M+H⁺]

Compound 268. N-[[1-[2-(1-Naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-22). MS: 467 [M+H⁺]

Compound 269. 6-Chloro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-29) and sulphonyl chloride (IIb-24). MS: 501 [M+H⁺]

Compound 270. 6-Chloro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-37). MS: 495 [M+H⁺]

Compound 271. 5-Fluoro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-25). MS: 499 [M+H⁺]

Compound 272. 5-Chloro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-26). MS: 515 [M+H⁺]

Compound 273. N-[[1-[2-(1-Naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-17). MS: 461 [M+H⁺]

Compound 274. 1-Methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-51). MS: 464 [M+H⁺]

Compound 275. 1-Methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-50). MS: 464 [M+H⁺]

Compound 276. N-[[1-[2-(1-Naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-23). MS: 467 [M+H⁺]

Compound 277. 3-Chloro-4-fluoro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-29) and sulphonyl chloride (IIb-7). MS: 463 [M+H⁺]

Compound 278. 3,4-Difluoro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-29) and sulphonyl chloride (IIb-31). MS: 447 [M+H⁺]

Compound 279. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-48). MS: 463 [M+H⁺]

Compound 280. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-22). MS: 475 [M+H⁺]

Compound 281. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-28), MS: 476 [M+H⁺]

Compound 282. 6-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-37). MS: 503 [M+H⁺]

Compound 283. 5-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-26). MS: 523 [M+H⁺]

Compound 284. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]thiazole-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-46). MS: 426 [M+H⁺]

Compound 285. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-5-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-55). MS: 476 [M+H⁺]

Compound 286. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-17). MS: 469 [M+H⁺]

Compound 287. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-18). MS: 469 [M+W]

Compound 288. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-4-phenyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-36). MS: 495 [M+H⁺]

Compound 289. 4-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-5). MS: 453 [M+H⁺]

Compound 290. 3-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-4). MS: 453 [M+H⁺]

Compound 291. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-33). MS: 433 [M+H⁺]

Compound 292. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-1). MS: 419 [M+H⁺]

Compound 293. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-12). MS: 487 [M+H⁺]

Compound 294. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-3-(trifluoromethyl)benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-11). MS: 487 [M+H⁺]

Compound 295. 4-tert-Butyl-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]-pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-10). MS: 475 [M+H⁺]

Compound 296. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-methyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-8). MS: 433 [M+H⁺]

Compound 297. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-3-methoxybenzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-13). MS: 449 [M+H⁺]

Compound 298. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-3-fluoro-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-2). MS: 437 [M+H⁺]

Compound 299. 4-Cyano-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-16). MS: 444 [M+H⁺]

Compound 300. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-4-fluoro-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-3). MS: 437 [M+H⁺]

Compound 301. 3,4-Dichloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]-pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-32). MS: 487 [M+H⁺]

Compound 302. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-40). MS: 425 [M+H⁺]

Compound 303. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-3-hydroxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-14). MS: 435 [M+H⁺]

Compound 304. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-4-methoxy-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIIb-34). MS: 449 [M+H⁺]

Compound 305. 4-Bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-6). MS: 497 [M+H⁺]

Compound 306. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-2,3-dihydrobenzofuran-5-sulphonamide

The title compound was prepared starting from amine (IIIa-38) and sulphonyl chloride (IIb-21). MS: 461 [M+H⁺]

Compound 307. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzofuran-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-52). MS: 459 [M+H⁺]

Compound 308. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-51). MS: 472 [M+H⁺]

Compound 309. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-50). MS: 472 [M+H⁺]

Compound 310. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-47). MS: 474 [M+H⁺]

Compound 311. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-23). MS: 475 [M+H⁺]

Compound 312. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2,5-dimethylthiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-42). MS: 453 [M+H⁺]

Compound 313. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]thiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-41). MS: 425 [M+H⁺]

Compound 314. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-5-isoxazol-5-yl-thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-43). MS: 492 [M+H⁺]

Compound 315. 3-Cyano-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-15). MS: 444 [M+H⁺]

Compound 316. 5-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-20). MS: 459 [M+H⁺]

Compound 317. 3-Chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-fluorobenzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-7). MS: 471 [M+H⁺]

Compound 318. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-propyl-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-9). MS: 461 [M+H⁺]

Compound 319. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3,4-difluorobenzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-31). MS: 455 [M+H⁺]

Compound 320. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-35). MS: 503 [M+H⁺]

Compound 321. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-iodo-benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-30). MS: 545 [M+H⁺]

Compound 322. 3-Bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-29). MS: 497 [M+H⁺]

Compound 323. N-[[1-[2-(2,3-Dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-5-methyl-isoxazole-4-sulphonamide

The title compound was prepared starting from amine (IIa-38) and sulphonyl chloride (IIb-45). MS: 424 [M+H⁺]

Compound 324. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-22). MS: 474 [M+H⁺]

Compound 325. 6-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-37). MS: 502 [M+H⁺]

Compound 326. 5-Chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-3-methyl-benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-26). MS: 522 [M+H⁺]

Compound 327. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-4-phenylbenzenesulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-36). MS: 494 [M+H⁺]

Compound 328. 4-tert-Butyl-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-10). MS: 474 [M+H⁺]

Compound 329. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-50). MS: 471 [M+H⁺]

Compound 330. N-[1-[3-(6-Fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-3) and sulphonyl chloride (IIb-23). MS: 474 [M+H⁺]

Compound 331. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-22). MS: 474 [M+H⁺]

Compound 332. 6-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-24). MS: 508 [M+H⁺]

Compound 333. 6-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-37). MS: 502 [M+H⁺]

Compound 334. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-5-fluoro-3-methylbenzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-25). MS: 506 [M+H⁺]

Compound 335. 5-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methylbenzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-26). MS: 522 [M+H⁺]

Compound 336. 3,4-dichloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIIa-16) and sulphonyl chloride (IIb-32). MS: 486 [M+H⁺]

Compound 337. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-40). MS: 424 [M+H⁺]

Compound 338. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-51). MS: 471 [M+H⁺]

Compound 339. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-50). MS: 471 [M+H⁺]

Compound 340. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-23). MS: 474 [M+H⁺]

Compound 341. N-[1-[3-(5-chloro-H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-17). MS: 468 [M+H⁺]

Compound 342. 3-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-4-fluorobenzenesulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-7). MS: 470 [M+H⁺]

Compound 343. N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3,4-difluorobenzenesulphonamide

The title compound was prepared starting from amine (IIa-16) and sulphonyl chloride (IIb-31). MS: 454 [M+H⁺]

Compound 344. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-22). MS: 458 [M+H⁺]

Compound 345. 6-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-24). MS: 492 [M+H⁺]

Compound 346. 6-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-37). MS: 486 [M+H⁺]

Compound 347. 5-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methylbenzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-25). MS: 490 [M+H⁺]

Compound 348. 5-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methylbenzothiophene-2-sulphonamide

The title compound was prepared starting from amine (IIIa-15) and sulphonyl chloride (IIb-26). MS: 506 [M+H⁺]

Compound 349. 3,4-dichloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-32). MS: 470 [M+H⁺]

Compound 350. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-40). MS: 408 [M+H⁺]

Compound 351. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-51). MS: 455 [M+H⁺]

Compound 352. N-[1-[3-(5-fluoro-1H-indo-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-50). MS: 455 [M+H⁺]

Compound 353. N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-23). MS: 457 [M+H⁺]

Compound 354. 3-chloro-4-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-7). MS: 454 [M+H⁺]

Compound 355. 3,4-difluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide

The title compound was prepared starting from amine (IIa-15) and sulphonyl chloride (IIb-31). MS: 438 [M+H⁺]

EXAMPLE 3
In Vitro Pharmacology: Binding Assays

The affinity of compounds of the present invention for dopaminergic, serotoninergic, adrenergic, muscarinic M3, histaminergic H1, and sigma receptors and to serotonin transporter SERT was tested using the methods as described below, by measurement their binding to these receptors using radioreceptors methods. Moreover, the ability of the compounds of the invention to block potassium channel hERG was tested.

The specific ligand binding to the receptors is defined as the difference between the total binding and the non-specific binding determined in the presence of the excess of unlabelled ligand.

The compounds were tested for their affinity to receptors at a concentration of 1×10⁻⁶M, and for ability to block potassium channel hERG at a concentration of 1×10⁻⁵M.

The results are expressed as a percent of control specific binding ((measured specific binding/control specific binding)×100) and as a percent inhibition of control specific binding (100−((measured specific binding/control specific binding)×100)) obtained in the presence of the test compounds. The specific ligand binding to the receptors is defined as the difference between the total binding and the nonspecific binding determined in the presence of an excess of unlabelled ligand. Scintillation counting was the method of detection of ligand binding. The IC50 values (concentration causing a half-maximal inhibition of control specific binding) were determined by non-linear regression analysis of the competition curves generated with mean replicate values using Hill equation curve fitting (Y=D+[(A−D)/(1+(C/C50)nH)], where Y=specific binding, D=minimum specific binding, A=maximum specific binding, C=compound concentration, C50=IC50, and nH=slope factor). This analysis was performed using a software developed at Cerep (Hill software) and validated by comparison with data generated by the commercial software SigmaPlot® 4.0 for Windows® (© 1997 by SPSS Inc.). The inhibition constants (Ki) were calculated using the Cheng Prusoff equation (Ki=IC50/(1+(L/KD)), where L=concentration of radioligand in the assay, and KD=affinity of the radioligand for the receptor). A scatchard plot was used to determine the Kd.

Conditions and methodology of in vitro tests are given by reference to the literature.

Affinity for Dopaminergic Receptors D2, D3 and D4

Experimental conditions for tests are given in Table 1, the results of tests for representative compounds are given in Tables 2a and 2b (receptors D2 and D3) and in Table 3 (receptors D4).

TABLE 1

Experimental conditions for testing the affinity for dopaminergic receptors

D2
D3
D4

Biological
human recombinant
human recombinant
human recombinant

material
(Invitrogen, GeneBLAzer ®
receptors (Membrane
(CHO cells)

D2-Gqo5 CHO-K1 DA)
Target Systems ™ human

dopamine D3 Receptor,

PerkinElmer)

Radioligand
[3H]methylspiperone
[3H]methylspiperone
[³H]methylspiperone

Concentration
about 0.5 nM
0.3 nM
0.3 nM

Kd
0.4 nM
0.1 nM
0.19 nM

Non-specific
haloperidol (1 μM)
(+)-butaclamol (1 μM)
(+)-butaclamol (10 μM)

binding

Incubation
60 min, 30° C.
60 min, 24° C.
60 min, 22° C.

Methodology
Bryan L. Roth. Assay
Missale et al. (1998),
Van Tol, H. H. M et

Protocol Book. University of
Physiol. Rev., 78: 189-
al. (1992) Nature,

North Carolina At Chapel
225
358: 149-152

Hill. National Institute of

Mental Health.

Psychoactive Drug

Screening Program.

Available on-line at

31.08.2008:

http://pdsp.med.unc.edu/

UNC-

CH%20Protocol%20Book.pdf

TABLE 2a

Results of binding assays for receptors D2 and D3

for representative compounds of the invention

Compound No.
D2 [%]
D3 [%]

6
70
8

8
72
18

9
88
30

10
99
49

11
89
49

14
100
90

15
75
14

17
80
20

18
73
31

20
95
69

21
100
96

22
85
23

23
100
95

24
94
52

25
98
97

26
98
81

28
97
96

29
97
85

30
62
−2

31
87
27

32
63
57

33
54
58

34
76
58

35
77
56

36
57
38

37
83
66

38
77
64

39
86
95

40
49
39

43
55
29

44
76
52

45
53
87

46
93
104

47
83
97

48
84
104

49
99
106

50
96
104

51
54
103

52
77
106

53
74
99

54
83
105

55
44
93

56
34
98

60
41
102

61
39
83

67
57
94

71
27
−1

75
91
86

77
93
93

78
89
98

79
95
97

80
96
100

81
60
86

82
90
94

83
44
76

84
89
99

85
45
75

86
93
97

87
63
86

88
−5
−2

89
24
23

90
5
−7

91
15
−8

92
49
60

93
78
75

94
102
105

95
5
1

96
46
56

97
29
40

98
62
67

99
38
78

100
41
74

107
89
97

108
93
95

109
92
86

110
74
73

111
97
87

113
47
55

114
49
62

115
74
97

116
91
98

117
24
29

118
32
20

119
79
93

120
−33
30

122
99
100

123
38
86

124
94
94

127
95
79

130
97
94

131
97
94

132
82
60

133
93
74

134
96
80

135
92
94

136
62
57

137
76
50

141
74
58

142
58
45

143
80
46

147
88
74

149
91
39

150
53
60

153
82
61

155
61
68

157
81
72

160
86
87

161
84
75

162
61
100

163
73
99

164
78
98

165
66
100

166
82
101

167
60
97

168
64
94

169
84
100

170
79
98

171
72
99

172
76
100

173
59
99

174
25
22

175
68
78

176
21
8

177
13
42

178
8
25

179
6
40

180
23
46

181
73
77

182
33
45

183
92
79

184
24
39

185
25
0

186
77
78

187
56
48

188
52
51

189
71
61

190
51
62

191
7
25

192
42
70

193
81
55

194
19
48

195
93
82

196
100
94

197
101
83

198
99
97

199
96
88

200
100
94

201
99
84

202
101
96

203
101
95

204
98
96

205
99
99

206
101
95

207
101
85

208
90
49

209
64
34

210
64
27

211
93
63

213
81
57

214
97
89

215
97
85

216
98
85

217
96
84

218
99
95

219
96
81

221
97
92

222
97
74

223
89
57

224
98
87

225
97
84

226
99
95

227
97
96

228
100
97

229
101
93

230
99
99

231
95
91

234
99
94

235
31
41

237
97
89

238
98
95

239
96
76

240
95
75

241
81
87

242
55
71

243
14
47

245
−4
40

249
4
36

250
18
55

252
36
43

253
87
55

254
75
34

256
37
25

257
92
62

258
92
43

259
84
61

261
88
65

262
26
44

263
59
71

268
54
93

269
38
89

270
32
91

271
45
93

272
40
88

273
58
90

274
62
81

275
66
94

276
41
91

277
34
90

278
31
94

285
24
18

289
−19
41

291
29
33

293
66
60

298
52
35

300
35
30

301
−22
34

302
34
37

303
79
52

305
57
48

306
51
26

308
57
43

312
36
36

316
−2
36

317
53
49

324
77
41

325
91
59

326
86
61

327
79
56

328
64
40

329
84
68

330
77
64

TABLE 2b

Inhibition constants K_ifor D2 receptors for

representative compounds of the invention

Compound No.
D2 [nM]

127
22.0

130
10.0

131
19.0

196
0.8

197
5.8

198
1.8

199
4.4

200
0.1

201
15.0

202
1.2

203
0.9

204
0.4

205
1.6

206
0.3

207
3.8

214
2.8

215
3.0

224
8.7

225
9.2

228
0.7

229
2.4

230
1.1

231
6.4

238
3.9

TABLE 3

Results of binding assay for receptors D4.4

for representative compounds of the invention

Compound No.
D4.4 [%]

11
92

20
100

21
83

23
55

25
84

26
101

28
75

29
16

34
37

39
73

46
72

47
80

48
80

49
82

50
94

55
31

75
76

77
78

78
79

79
92

80
91

82
94

84
94

86
88

89
22

92
35

93
39

94
90

107
83

108
85

109
69

110
42

111
61

115
55

116
64

122
63

124
54

127
55

130
67

131
50

132
39

133
88

134
77

135
60

143
80

181
64

183
80

186
55

196
78

197
81

198
48

199
69

200
49

201
50

202
76

203
78

204
71

205
73

206
87

207
85

214
61

215
88

216
87

217
72

218
86

221
93

222
98

223
92

224
101

225
91

226
69

227
88

228
68

229
86

230
88

231
89

234
70

237
48

238
48

239
78

240
57

241
33

293
35

298
48

300
52

303
39

305
52

306
33

308
26

312
52

317
59

Affinity for Serotoninergic Receptors 5-HT1A, 5-HT2A, 5-HT6, 5-HT7 and 5-HT2C

Experimental conditions for tests are given in Table 4, and results of tests for representative compounds of the invention are given in Table 5a and 5b (receptors 5-HT1A, 5-HT2A, 5-HT6 and 5-HT7) and in Table 6 (receptors 5-HT2C).

TABLE 4

Experimental conditions for testing the affinity for serotoninergic receptors

5-HT1A
5-HT2A
5-HT2C
5-HT6
5-HT7

Biological
rat
human
human recombinant
human
human

material
hippocampus
recombinant
(HEK-293 cells)
recombinant
recombinant

(Membrane

(Membrane
(Membrane

Target Systems ™

Target Systems ™
Target

Human Serotonin

human
Systems ™

5-HT2A Receptor,

Serotonin 5-HT6
human

PerkinElmer)

Receptor,
Serotonin 5-

PerkinElmer)
HT7 Receptor,

PerkinElmer)

Radioligand
[3H]8-OH-DPAT
[3H]ketanserin
[³H]mesulergine
[3H]LSD
[3H]LSD

Concentration
0.8-1.0 nM
1 nM
1 nM
2.5 nM
3 nM

Kd
1.0 nM
0.95 nM
0.5 nM
1.9 nM
2.6 nM

Non-specific
serotonin
mianserin
RS 102221
methiothepin
methiothepin

binding
(1 μM)
(1 μM)
(10 μM)
(1 μM)
(1 μM)

Incubation
20 min, 37° C.
60 min, 30° C.
120 min, 37° C.
60 min, 30° C.
120 min, 30° C.

5-HT1A: Borsini et al. (1995), Naunyn. Sch. Arch. Pharmacol. 352: 276-282

5-HT2A: Bryan L. Roth. Assay Protocol Book. University of North Carolina At Chapel Hill. National Institute of Mental Health. Psychoactive Drug Screening Program. Available on-line at 31 Aug. 2008: http://pdsp.med.unc.edu/UNC-CH%20Protocol%20Book.pdf

5-HT2C: Stam et al. (1994), Eur. J. Pharmacol., 269: 339-348

5-HT6: Bryan L. Roth. Assay Protocol Book. University of North Carolina At Chapel Hill. National Institute of Mental Health. Psychoactive Drug Screening Program. Available on-line at 31 Aug. 2008: http://pdsp.med.unc.edu/UNC-CH %20Protocol%20Book.pdf

5-HT7: Bryan L. Roth. Assay Protocol Book. University of North Carolina At Chapel Hill. National Institute of Mental Health. Psychoactive Drug Screening Program. Available on-line at 31 Aug. 2008: http://pdsp.med.unc.edu/UNC-CH %20Protocol%20Book.pdf

TABLE 5a

Results of binding assays for serotoninergic receptors

for representative compounds of the invention

Compound
5-HT1A
5-HT2A
5-HT6
5-HT7

No.
[%]
[%]
[%]
[%]

6
14
77
44
83

8
5
97
64
85

9
12
95
75
90

10
20
96
85
86

11
60
100
94
97

14
24
80
82
76

15
18
57
83
48

17
23
94
76
80

18
18
85
59
94

20
67
100
97
98

21
66
100
95
100

22
0
95
72
85

23
24
99
97
95

24
19
95
78
82

25
74
102
95
98

26
79
102
98
97

28
61
101
96
94

29
70
95
92
52

30
5
95
77
82

31
58
84
76
89

32
37
83
63
92

33
22
97
91
100

34
32
98
40
100

35
28
91
97
98

36
18
59
75
88

37
29
56
97
94

38
25
82
104
94

39
99
99
92
90

40
68
102
72
85

43
83
81
87
71

44
62
78
81
68

45
88
75
0
93

46
101
34
9
100

47
98
80
45
100

48
100
88
17
98

49
100
82
34
100

50
101
97
43
99

51
91
67
10
101

52
90
89
41
90

53
90
85
54
102

54
90
88
87
102

55
96
94
3
96

56
75
84
36
106

60
85
76
69
96

61
77
92
71
95

67
76
80
87
79

71
28
26
80
31

75
100
90
94
90

77
99
100
95
89

78
99
95
94
89

79
99
99
86
96

80
98
100
96
93

81
109
75
75
84

82
99
91
93
96

83
104
82
84
86

84
99
78
96
98

85
102
64
82
89

86
101
97
98
98

87
105
78
91
71

88
96
34
13
84

89
98
74
19
96

90
82
49
−16
92

91
88
47
−20
91

92
100
60
23
99

93
98
72
29
99

94
98
99
65
100

95
94
0
9
94

96
92
93
5
98

97
84
89
43
105

98
92
87
32
100

99
96
97
64
90

100
94
97
28
103

107
100
97
39
84

108
98
98
59
98

109
96
95
67
99

110
95
91
−60
99

111
99
92
41
100

113
81
65
52
85

114
98
90
56
97

115
100
99
88
98

116
99
96
95
−49

117
76
86
34
93

118
85
83
51
99

119
89
69
57
85

120
8
68
24
89

122
99
83
99
100

123
99
64
72
88

124
99
87
99
99

127
71
99
96
96

130
85
100
98
98

131
87
99
97
95

132
57
97
69
94

133
52
95
92
97

134
73
99
94
95

135
77
99
92
97

136
35
82
72
80

137
14
62
14
82

141
9
85
92
80

142
29
77
37
87

143
44
94
78
87

147
60
95
86
89

149
82
96
71
113

150
−9
85
65
84

153
55
96
80
86

155
42
89
62
82

157
61
95
80
93

160
76
97
83
75

161
86
88
87
83

162
85
−17
−56
91

163
88
99
87
88

164
83
102
94
92

165
87
99
97
105

166
78
100
98
97

167
75
95
94
90

168
79
96
93
92

169
84
69
100
93

170
90
72
93
104

171
92
101
96
94

172
85
71
96
92

173
83
73
91
105

174
91
44
64
90

175
75
105
95
92

176
98
35
14
87

177
97
66
44
88

178
96
73
21
89

179
92
57
−15
90

180
93
68
31
94

181
98
89
30
92

182
63
61
31
95

183
98
94
81
102

184
71
76
20
89

185
88
39
23
90

186
98
87
32
97

187
78
93
44
98

188
101
89
14
91

189
112
74
46
90

190
100
68
34
97

191
98
42
5
93

192
79
86
30
97

193
84
88
9
92

194
63
29
53
82

195
47
101
86
86

196
54
100
99
101

197
56
99
97
101

198
45
100
97
93

199
38
99
91
94

200
50
99
99
93

201
32
98
94
95

202
65
99
100
98

203
60
99
100
99

204
71
98
97
87

205
63
99
94
98

206
68
100
101
100

207
58
100
101
99

208
9
100
87
96

209
11
86
62
90

210
8
80
68
80

211
32
100
92
107

213
63
100
78
93

214
34
99
97
98

215
52
99
93
98

216
35
101
97
99

217
54
101
98
97

218
91
100
95
98

219
85
99
94
96

221
67
101
92
95

222
72
99
94
102

223
49
99
94
100

224
76
99
99
103

225
62
99
99
100

226
43
101
92
91

227
62
101
94
91

228
27
99
100
92

229
46
100
98
99

230
77
99
96
87

231
34
100
86
88

234
45
100
98
97

235
14
91
62
81

237
45
97
87
96

238
71
99
96
94

239
56
98
97
92

240
30
99
93
90

241
39
97
68
100

242
11
99
60
83

243
21
90
75
89

245
35
73
57
81

249
23
79
58
87

250
30
87
74
91

252
44
89
75
90

253
34
99
101
97

254
49
98
78
102

256
29
87
74
92

257
87
100
94
88

258
64
98
89
78

259
42
100
92
91

261
78
101
97
104

262
25
85
69
92

263
19
97
85
92

268
77
82
84
88

269
60
91
82
98

270
47
86
86
94

271
82
97
76
104

272
63
82
67
88

273
85
95
90
77

274
77
89
97
86

275
86
91
84
111

276
81
92
84
82

277
85
85
93
108

278
84
91
85
102

285
62
77
34
86

289
99
61
−1
81

291
94
63
19
80

293
100
86
47
90

298
97
88
40
93

300
99
72
38
90

301
96
81
61
98

302
89
52
35
105

303
96
96
48
98

305
101
93
52
96

306
99
81
45
94

308
98
91
44
83

312
98
87
19
86

316
74
82
36
87

317
100
72
76
95

324
49
99
78
101

325
80
92
72
89

326
−1
97
83
91

327
20
94
68
86

328
49
96
94
90

329
49
94
62
97

330
82
102
79
101

TABLE 5b

Inhibition constants K_ifor 5-HT2A and 5-HT6 serotoninergic

receptors for representative compounds of the invention

Compound No.
5-HT2A [nM]
5-HT6 [nM]

75

34.0

77

39.0

78

42.0

80

15.0

82

37.0

84

18.0

86

13.0

116

71.0

122

13.0

127
4.2
18.0

130
4.2
9.7

131
5.5
9.0

196
0.4
6.4

197
0.7
16.0

198
0.7
8.6

199
0.7
99.0

200
2.3
10.0

201
7.0
79.0

202
1.4
7.1

203
0.7
12.0

204
0.8
6.9

205
1.6
41.0

206
0.7
6.1

207
0.5
7.7

214
2.1
7.5

215
1.2
21.0

224
1.6
4.0

225
0.9
1.6

228
1.0
14.0

229
0.6
43.0

230
0.4
15.0

231
1.9
79.0

238
3.0
17.0

TABLE 6

Results of binding assays for serotoninergic 5-HT2C receptors

for representative compounds of the invention

Compound No.
5-HT2C [%]

11
27

20
33

21
71

23
67

25
83

26
51

28
72

29
28

34
94

39
74

46
21

47
33

48
32

49
59

50
54

55
30

75
83

77
77

78
78

80
86

82
82

84
88

89
53

92
52

93
50

94
91

107
86

110
85

111
87

122
98

124
80

127
84

130
89

131
88

132
43

133
47

134
87

135
86

143
68

181
93

183
98

186
79

196
86

197
84

198
86

199
83

200
77

201
72

202
88

203
90

204
87

205
86

206
84

214
65

215
74

216
62

217
67

218
82

221
81

222
65

223
65

224
71

225
72

226
89

227
82

228
91

230
91

231
75

234
86

237
79

239
49

240
81

241
66

293
50

298
37

300
34

303
47

305
59

306
36

308
61

312
55

317
45

Affinity for Adrenergic α1 and α2C Receptors

Experimental conditions for tests are given in Table 7, and results of tests for representative compounds are given in Tables 8 (α1 receptors) and in Tables 9 (α2C receptors).

TABLE 7

Experimental conditions for testing the affinity for adrenergic receptors

α1
α2C

Biological
rat cerebral cortex
human recombinant (CHO

material

cells)

Radioligand
[3H]prazosina
[³H]RX 821002

Concentration
0.2 nM
2 nM

Kd
0.2 nM
0.95 nM

Non-specific
Risperidon (1 μM)
(−)epinephrine

binding

(100 μM)

Incubation
30 min, 30° C.
60 min, 22° C.

Methodology
Leopoldo M et al. (2002),
Devedjian et al. (1994), Eur.

J Med Chem., (26): 5727-35

J.
Pharmacol., 252: 43-49

TABLE 8

Results of test of affinity for α1 adrenergic receptors

for representative compounds of the invention

Compound No.
α1 [%]

6
98

8
95

9
83

10
89

11
70

14
87

15
89

17
98

18
98

20
86

21
95

22
91

23
64

24
101

25
85

26
87

28
70

29
18

30
84

31
100

34
91

35
99

36
103

37
96

38
98

39
29

40
12

43
68

44
46

45
72

46
85

47
71

48
87

49
89

50
88

51
77

52
81

53
88

54
90

55
51

56
74

60
87

61
79

67
91

71
36

75
45

77
29

78
39

79
37

80
50

81
36

82
43

83
23

84
51

85
9

86
50

87
18

88
−23

89
45

90
−25

91
−15

92
47

93
52

94
87

95
−21

96
60

97
64

98
78

99
70

100
87

107
28

108
40

109
44

110
45

111
68

113
55

114
27

115
24

116
23

117
53

118
72

119
78

120
−9

122
53

123
43

124
33

127
93

130
86

131
70

132
86

133
90

134
61

135
88

143
97

150
98

160
49

161
46

162
83

163
27

164
13

165
15

166
23

167
3

168
31

169
74

170
63

171
50

172
40

173
56

174
15

175
50

176
51

177
55

178
20

179
61

180
39

181
50

182
78

183
85

184
88

185
34

186
80

187
88

188
91

189
71

190
86

191
54

192
88

193
71

194
96

195
79

196
95

197
93

198
76

199
66

200
85

201
82

202
98

203
91

204
76

205
71

206
93

207
95

210
94

211
90

214
91

215
89

216
84

217
40

218
96

221
85

222
92

223
86

224
89

225
93

226
73

227
85

228
88

229
89

230
83

231
79

234
92

237
88

238
82

239
91

240
86

241
62

253
94

268
9

269
−1

270
−5

271
−1

272
−7

273
25

274
41

275
53

276
16

277
21

278
37

285
69

289
46

291
66

293
77

298
77

300
83

301
46

302
63

303
89

305
84

306
90

308
69

312
65

316
66

317
84

325
76

326
70

327
81

TABLE 9

Results of test of affinity for α2C

adrenergic receptors for representative

compounds of the invention

Compound

No.
α2C [%]

11
71

20
78

21
78

23
89

25
90

26
76

28
93

29
84

34
94

39
92

46
101

47
80

48
105

49
110

50
108

55
99

75
76

77
78

78
85

79
96

80
88

82
101

84
105

86
106

89
69

92
76

93
84

94
106

107
77

108
83

109
98

110
98

111
90

115
90

116
93

122
101

124
95

127
93

130
88

131
92

132
73

133
91

134
87

135
95

143
78

181
96

183
99

186
96

196
89

197
90

198
80

199
82

200
96

201
89

202
95

203
93

204
89

205
86

206
93

207
90

214
74

215
66

216
80

217
96

218
94

221
88

222
77

223
60

224
79

225
80

226
86

227
90

228
95

229
98

230
92

231
89

234
90

237
82

238
94

239
89

240
84

241
87

293
95

298
94

300
92

303
100

305
96

306
98

308
96

312
94

317
95

Affinity for Muscarinic M3 Receptors

Experimental conditions for tests are given in Table 10, and results of tests for representative compounds are given in Table 11.

TABLE 10

Experimental conditions for testing the affinity for M3 muscarinic receptors

M3

Biological material
human recombinant, (CHO cells)

Radioligand
[³H]4-DAMP

Concentration
0.2 nM

Kd
0.5 nM

Non-specific binding
atropine (1 μM)

Incubation
60 min, 22° C.

Methodology
Peralta et al. (1987), Embo.J., 6: 3923-3929.

TABLE 11

Results of test of affinity for M3

muscarinic receptors for representative

compounds of the invention

Compound

No.
M3 [%]

11
3

20
−7

21
−11

23
10

25
23

26
11

28
13

29
30

34
12

39
19

46
−13

47
-8

48
1

49
11

50
2

55
−1

75
17

77
17

78
5

79
−3

80
2

82
9

84
3

86
1

89
−6

92
4

93
1

94
1

107
8

108
−4

109
3

110
−7

111
14

115
13

116
9

122
30

124
49

127
1

130
15

131
17

132
10

133
17

134
34

135
19

143
−4

181
0

183
13

186
−9

196
11

197
26

198
37

199
38

200
3

201
9

202
9

203
12

204
17

205
3

206
9

207
12

214
11

215
39

216
28

217
6

218
0

221
12

222
18

223
25

224
25

225
23

226
8

227
13

228
12

229
15

230
15

231
22

234
17

237
16

238
26

239
23

240
21

241
19

293
10

298
22

300
−2

303
9

305
11

306
12

308
13

312
10

317
8

Affinity for Serotonin Transporter (SERT)

Experimental conditions for tests are given in Table 12, and results of tests for representative compounds are given in Tables 13a and 13b.

TABLE 12

Experimental conditions for testing the affinity for

serotonin transporter (SERT)

SERT

Biological material
human recombinant SERT receptor (CHO cells)

Radioligand
[³H]imipramine

Concentration
2 nM

Kd
1.7 nM

Non-specific binding
imipramine (10 μM)

Incubation
60 min, 22° C.

Methodology
Tatsumi et al. (1999), Eur.J.Pharmacol.,

368: 277-283.

TABLE 13a

Results of serotonin transporter (SERT) receptor affinity

tests for representative compounds of the invention

Compound No.
SERT [%]

6
18

8
−13

9
2

10
−2

11
−6

14
−3

15
−7

17
52

18
37

20
6

21
59

22
5

23
53

24
−10

25
42

26
66

28
54

29
44

30
36

31
36

32
5

33
−4

34
43

35
29

36
0

37
30

38
17

39
29

40
−5

43
−7

44
25

45
−4

46
7

47
6

48
−3

49
41

50
20

51
6

52
38

53
56

54
46

55
6

56
15

60
21

61
43

67
38

71
49

75
103

77
104

78
101

79
105

80
104

81
78

82
100

83
78

84
104

85
70

86
105

87
64

88
−13

89
3

90
18

91
−4

92
10

93
23

94
62

95
−4

96
11

97
−1

98
16

99
36

100
57

107
−4

108
36

109
−10

110
39

111
15

113
18

114
5

115
83

116
95

117
33

118
41

119
10

120
21

122
98

123
83

124
100

127
49

130
64

131
55

132
20

133
42

134
47

136
9

135
68

137
−5

141
−10

142
−4

143
6

147
24

149
22

150
12

153
21

155
−12

157
25

160
100

161
66

162
−9

163
45

164
34

165
111

166
32

167
31

168
25

169
75

170
93

171
44

172
46

173
50

174
20

175
19

176
−2

177
25

178
−6

179
−8

180
14

181
26

182
−7

183
48

184
1

185
23

186
39

187
69

188
44

189
41

190
31

191
32

192
38

193
41

194
1

195
7

196
42

197
58

198
44

199
39

200
74

201
59

202
58

203
73

204
70

205
45

207
58

206
62

208
−2

209
6

210
35

211
4

213
12

214
15

215
35

216
53

217
90

218
95

219
52

221
67

222
2

223
17

224
64

225
77

226
54

227
69

228
61

229
50

230
75

231
63

234
65

235
11

237
61

238
64

239
36

240
43

241
71

242
37

243
7

245
18

249
28

250
23

252
−2

253
12

254
10

256
40

257
20

258
25

259
−5

261
3

262
26

263
11

268
85

269
53

270
15

271
40

272
20

273
64

274
109

275
93

276
84

277
68

278
91

285
60

291
66

289
53

293
82

298
72

300
64

301
38

302
37

303
73

305
94

306
90

308
95

312
87

316
8

317
63

324
18

325
21

326
10

327
33

328
25

329
43

330
22

TABLE 13b

Inhibition constants K_ifor SERT for

representative compounds of the invention

Compound No.
SERT [nM]

75
1.5

77
0.5

78
1.0

79
0.7

80
0.5

82
1.3

84
2.6

86
1.1

116
31.0

122
17.0

Affinity for H1Histaminergic and σ Receptors

Experimental conditions for tests are given in Table 14, and results of tests for representative compounds are presented in Table 15.

TABLE 14

Experimental conditions tor testing the affinity for H1

histaminergic and σ receptors

σ
H1

Biological
rat cerebral cortex
human recombinant

material

(HEK-293 cells)

Radioligand
[³H]DTG
[³H]pyrilamine

Concentration
8 nM
1 nM

Kd
29 nM
1.7 nM

Non-specific
haloperidol (10 μM)
pyrilamine (1 μM)

binding

Incubation
120 min, 22° C.
60 min, 22° C.

Methodology
Shirayama et al. (1993).
Smit et al. (1996), .

Eur.
J.
Pharmacol.,

Brit.
J
Pharmacol.,

237: 117-126
117: 1071-1080.

TABLE 15

Results of σ and H1 receptors affinity tests for

representative compounds of the invention

Compound No.
σ [%]
H1 [%]

11
74
37

20
83
36

21
60
57

23
61
60

25
70
75

26
80
44

28
70
63

29
60
59

34
50
56

39
54

46
15
6

47
44
−3

48
18
21

49
50

50
59
34

55
37
0

75
75
57

77
48
54

78
70
65

79
67
72

80
81

82
63
61

84
59
79

86
65
70

89
24
3

92
15
6

93
35
34

94
71

107
47
30

108
45
23

109
39
65

110
56
52

111
81
38

115
69
72

116
56

122
81

124
82

127

54

130
94
51

131
92
51

132
80
33

133
93
58

134
88
45

135
94
79

143

36

181
75
27

183
94
42

186
84
17

196

84

197

76

198
86
81

199
80
58

200

201

64

203

67

204
90

205
92
50

207

65

214
84
52

215
81
50

216
88
61

217
86
46

218

77

221
83
66

222
95
79

223
89
52

224
91
60

225
96
57

226
82
73

227
59
69

229

75

230
90
71

231
87
54

234

75

237
88
66

238
95
65

239
97

240
92
55

241
88
69

293

38

298

40

300

28

303

68

305

54

306

57

308
91
37

312
92
35

317

47

Ability to Block hERG Potassium Channel

Ability to block hERG potassium channels was determined using the electrophysiological method and cloned hERG potassium channels (KCNH2 gene, expressed in CHO cells) as biological material. The effects were evaluated using IonWorks™ Quattro system (MDS-AT).

hERG current was elicited using a pulse pattern with fixed amplitudes (conditioning pre-pulse: −80 mV for 25 ms; test pulse: +40 mV for 80 ms) from a holding potential of 0 mV. hERG current was measured as a difference between the peak current at 1 ms after the test step to +40 mV and the steady-state current at the end of the step to +40 mV.

Data Analysis

Data acquisition and analyses was performed using the IonWorks Quattro™ system operation software (version 2.0.2; Molecular Devices Corporation, Union City, Calif.). Data were corrected for leak current.

The hERG block was calculated as:

% Block=(1−ITA/IControl)×100%,

where IControl and ITA were the currents elicited by the test pulse in control and in the presence of a test article, respectively.

Concentration-response data for the blocks were fit to an equation of the following form:

% Block=% VC+{(% PC−% VC)−(% PC−% VC)/[1+([Test]/IC50)N]},

where [Test] is the concentration of test article, IC50 was the concentration of the test article producing half-maximal inhibition, N was the Hill coefficient, % VC was the percentage of the current run-down (the mean current inhibition at the vehicle control), % PC was the mean inhibition of the current with the positive control (1 μM E-4031) and % Block was the percentage of ion channel current inhibited at each concentration of a test article. Nonlinear least squares fits were solved with the XLfit add-in for Excel 2003 (Microsoft, Redmond, Wash.).

Results of tests for representative compounds are presented in Table 16.

TABLE 16

Results of hERG potassium channels affinity tests

for representative compounds of the invention

Compound No.
hERG [%]

21
3.3

25
2.9

26
6.1

34
−1.1

94
4.8

Results of in vitro tests as presented above show that compounds of the invention display high affinity for D2, D3, 5-HT1A, 5-HT2A, 5-HT6, 5-HT7, as well as for adrenergic receptors and for serotonin transporter. This confirms their potential usefulness in the treatment of diseases connected with disturbances in dopaminergic, serotoninergic and noradrenergic transmission, e.g. psychoses, depression as well as anxiety disorders etc. It should be stressed that some of the compounds possess simultaneously high affinity for 5-HT6 and 5-HT7 as well as for D2, and 5-HT2A receptors, what particularly distinguishes them from drugs currently used in therapy. Such a pharmacological profile suggests possible efficacy in the treatment of psychoses as well as antidepressant and procognitive activity. At the same time compounds of the invention possess weak affinity for hERG potassium channel and M3 muscarinic receptor, and in straight majority low affinity for H1 and 5-HT2C receptors. This may potentially contribute to lack of side effects such as excessive appetite or metabolic disorders, which may be caused by drugs currently used in therapy of the above-mentioned diseases.

EXAMPLE 4
In Vitro Pharmacology: Cellular Functional Assays

Conditions and methodology (by reference to the literature) of cellular functional assays are given in Table 17 and the tests results for representative compounds of the invention are presented in Tables 18, 19, 20, 21, 22 and 23.

The results are expressed as a percent of control specific agonist response ((measured specific response/control specific agonist response)×100) obtained in the presence of the test compounds.

The EC50 values (concentration producing a half-maximal specific response) and IC50 values (concentration causing a half-maximal inhibition of the control specific agonist response) were determined by non-linear regression analysis of the concentration-response curves generated with mean replicate values using Hill equation curve fitting (Y=D+[(A−D)/(1+(C/C50)nH)], where Y=specific response, D=minimum specific response, A=maximum specific response, C=compound concentration, and C50=EC50 or IC50, and nH=slope factor). This analysis was performed using a software developed at Cerep (Hill software) and validated by comparison with data generated by the commercial software SigmaPlot® 4.0 for Windows® (© 1997 by SPSS Inc.).

For the antagonists, the apparent dissociation constants (Kb) were calculated using the modified Cheng Prusoff equation (Kb=IC50/(1+(A/EC50A)), where A=concentration of reference agonist in the assay, and EC50A=EC50 value of the reference agonist).

Reaction

Assay
Origin
Stimulus
Incubation
product
method of detection
Literature

D2S (h)
human recombinant,
none (3 μM dopamine
28° C.
impedance
cellular dielectric
Payne et al. (2002), J.

(agonism)
(HEK-293 cells)
for control)

spectroscopy
Neurochem., 82: 1106-1117

D2S (h)
human recombinant,
dopamine (30 nM)
28° C.
impedance
cellular dielectric
Payne et al. (2002), J.

(antagonism)
(HEK-293 cells)

spectroscopy
Neurochem., 82: 1106-1117

D3 (h)
human recombinant,
none (0.3 μM
10 min.
cAMP
HTRF (Homogenous
Missale et al. (1998), Physiol. Rev.,

(agonism)
(CHO cells)
dopamine for control)
37° C.

Time Resolved
78: 189-225

Fluorescence)

D3 (h)
human recombinant,
dopamina (10 nM)
10 min.
cAMP
HTRF
Missale et al. (1998), Physiol. Rev.,

(antagonism)
(CHO cells)

37° C.

78: 189-225

D4.4 (h)
human recombinant
none (300 nM
10 min
cAMP
HTRF
Missale et al. (1998), Physiol. Rev.,

(agonism)
(CHO cells)
dopamine for control)
37° C.

78: 189-225

D4.4 (h)
human recombinant
dopamine
10 min
cAMP
HTRF
Missale et al. (1998), Physiol. Rev.,

(antagonistm)
(CHO cells)
(100 nM)
37° C.

78: 189-225

5-HT1A (h)
human recombinant,
none (100 nM 8-
30 min.
cAMP
HTRF
Newman-tancredi et al. (2001),

(agonism)
(CHO cells)
OHDPAT for control)
22° C.

Brit. J. Pharmacol., 132: 518-524

5-HT1A (h)
human recombinant,
8-OH-DPAT (10 nM)
30 min.
cAMP
HTRF
Newman-tancredi et al. (2001),

(antagonism)
(CHO cells)

22° C.

Brit. J. Pharmacol., 132: 518-524

5-HT2A (h)
human recombinant,
none (10 μM serotonin
30 min.
IP1
HTRF
Porter et al. (1999), Brit. J.

(agonism)
(HEK-293 cells)
for control)
37° C.

Pharmacol., 128: 13-20

5-HT2A (h)
human recombinant,
serotonin (100 nM)
30 min.
IP1
HTRF
Porter et al. (1999), Brit. J.

(antagonism)
(HEK-293 cells)

37° C.

Pharmacol., 128: 13-20

5-HT6 (h)
human recombinant,
none (10 μM serotonin
45 min.
cAMP
HTRF
Kohen et al. (1996), J.

(agonism)
(CHO cells)
for control)
37° C.

Neurochem., 66: 47-56

5-HT6 (h)
human recombinant,
serotonin (100 nM)
45 min.
cAMP
HTRF
Kohen et al. (1996), J.

(antagonism)
(CHO cells)

37° C.

Neurochem., 66: 47-56

5-HT7 (h)
human recombinant,
none (10 μM serotonin
45 min.
cAMP
HTRF
Adham et al. (1998), J. Pharmacol.

(agonism)
(CHO cells)
for control)
37° C.

Exp. Ther., 287: 508-514

5-HT7 (h)
human recombinant,
serotonin (300 nM)
45 min.
cAMP
HTRF
Adham et al. (1998), J. Pharmacol.

(antagonism)
(CHO cells)

37° C.

Exp. Ther., 287: 508-514

5-HT2C (h)
human recombinant
none (1 μM serotonin
30 min
IP1
HTRF
Porter et al. (1999), Brit. J.

(agonism)
(HEK-293 cells)
for control)
37° C.

Pharmacol., 128: 13-20

5-HT2C (h)
human recombinant
Serotonin (10 nM)
30 min
IP1
HTRF
Porter et al. (1999), Brit. J.

(antagonism)
(HEK-293 cells)

37° C.

Pharmacol., 128: 13-20

TABLE 18

Results of cellular functional assays for D2 and D3 dopaminergic

receptors for representative compounds of the invention

Compound
D2 ag
D2 antag
D3 ag
D3 antag

No.
[%]
[%]
[%]
[%]

20
4
32

21
6
98
−8
83

23
1
87
−10
68

25
3
89
0
82

26
3
68

28
1
87
−8
74

39

66
16

49
57
97
75
12

50
56
92
85
0

55

82
−33

78

89
−10

80
33
78
91
−5

94
45
99
51
38

111
36
89

122
33
62
38
56

124
33
44
11
43

130
6
34
5
61

131
5
20
−13
55

134
6
47

183
8
53

196
0
95
−16
77

197
1
82

198
4
83
−17
97

199
4
46

200
0
96
−1
93

202
0
95
−5
81

203
0
80
11
65

204
1
86
−8
109

205
3
61
7
95

206
1
96
3
77

214
3
89

117

215
6
91

216
0
86

217
10
79

221
14
97
−3
100

222
6
65

223

224
5
57

225
7
52

226
0
87
−26
107

227
11
99
−6
105

228
−1
94
−15
98

230
3
94
0
89

231
13
49
−6
54

234
2
91
−14
89

239
2
56

240
3
64

TABLE 19

Results of cellular functional assays for D4

dopaminergic receptors for

representative compounds of the invention

Compound
D4 ag
D4 antag

No.
[%]
[%]

20
17
79

26
−4
88

50
62
32

80
6
80

94
60
9

221
10
73

222
6
58

223
4
22

224
−7
84

225
−3
35

TABLE 20

Results of cellular functional assays for 5-HT1A, 5-HT2A, 5-HT6 and 5-HT7

serotoninergic receptors for representative compounds of the invention

Compound
5-HT1A
5-HT1A
5-HT2A
5-HT2A
5-HT6
5-HT6
5-HT7
5-HT7

No.
ag [%]
antag [%]
ag [%]
antag [%]
ag [%]
antag [%]
ag [%]
antag [%]

20

0
88
1
68
−2
82

21

2
85
1
55
−1
87

23

−2
81
−1
52
−2
36

25

−2
99
0
91
−2
99

26

−1
96
0
101
−3
95

28

−2
84
−1
91
−3
68

34

−1
59

−1
99

39
34
70
3
65
−1
6
1
40

49
39
97

26
70

50
48
92
−2
63

21
78

55
72
18
−1

5
48

78
54
76
51
−1
54
19

80
42
66
34
23
9
54
3
38

92
47
89

18
69

93
37
76

13
76

94
41
90
7
48

19
68

111
48
89
5
58

24
55

122
35
83

0
78
21
39

124
16
77

7
72
10
1

130

0
84
4
65
0
59

131

−2
69
3
53
1
45

134

−3
92
4
62
1
64

181
66
100

0
33

183
71
103
1
72

2
82

196

0
98
−2
75
0
97

197

1
96
−1
59
0
94

198

−3
98
−1
37
1
19

199

−2
96
−3
−1
1
42

200

0
56
−2
53
−1
40

202

0
90
1
67
−3
73

203

−1
90
−2
62
0
77

204

−1
94
−1
49

205

−3
87
1
20
−1
38

206

−1
96
−2
69
−1
97

214

−2
98
−4
76
−1
96

215

−2
100
−2
50
0
90

216

−2
100
−5
80
−5
90

217

−2
101
−6
85
5
74

221

−2
100
−4
79
2
80

222

−1
96
−1
70
−1
95

223

0
96
−1
66
0
85

224

−2
97
−1
87
−1
98

225

−1
98
1
89
0
84

226

−1
96
−5
48
−2
10

227

−2
103
−4
66
−2
30

228

1
82
−2
50
0
27

230

−2
101
−1
51

231

0
94

_—

234

1
98
−1
51
0
70

239

−2
73
2
82
1
63

240

−1
89
4
61
0
63

TABLE 21

Results of cellular functional assays for

5-HT2C serotoninergic receptors for

representative compounds of the invention

Compound
5-HT2C ag
5-HT2C antag

No.
[%]
[%]

94
92
−57

122
78
−10

181
46
6

183
50
12

203
1
33

228
0
30

230
−2
5

TABLE 22

Cellular functional profile for the representative

compounds of the invention

D2
D3
5-HT2A
5-HT6
5-HT7

antag
antag
antag
antag
antag

Compound
Kb
Kb
Kb
Kb
Kb

No.
[nM]
[nM]
[nM]
[nM]
[nM]

21
1.6
7.3
8.3

1.7

25
2.3
8.0
4.7
10.0
1.4

34

0.077

196
10.0
71.0
8.3
38.0
0.57

5-HT reuptake was tested according to Perovic, S. and Muller, W.E.G. (1995) Arzneim-Forsch. Drug Res., 45: 1145-1148 by measuring [³H]5-HT incorporation into rat brain synaptosomes. Assay conditions are as follows:

Tracer: [³H]5-HT (0.2 μCi/ml)

Incubation: 15 min/37° C.

Detection method: Scintillation counting

Reference: imipramine (IC₅₀:30 nM)

TABLE 23

Compound
SERT

No.
IC50 [nM]

80
2.1

84
64.0

86
17.0

Compounds of invention displayed significant antagonistic properties at 5-HT6 and/or 5-HT7 receptors which was either isolated or combined with some other beneficial properties like blockade of dopaminergic D2 and serotonin 5-HT2A receptors and/or 5-HT1A receptor partial agonism. Some of the compounds of invention possessed also ability to inhibit serotonin uptake. Selected compounds of invention, possessing significant affinity for 5-HT2C receptor were found to either be weak antagonists or display agonistic profile. Those properties, taken together with their low affinity for muscarinic receptors or hERG channels, indicate potential usefulness of the compounds of invention in the treatment of numerous CNS disorders, especially psychotic states, as well as mood disorders and cognitive deficits.

EXAMPLE 5
Behavioral Tests in Mice
Antipsychotic Activity in Mice

Potential antipsychotic activity was tested for the representative compounds in mouse model of psychosis, involving the induction of locomotor hyperactivity by administering psychotomimetic substance—dizocilpine. The ability of a test compound to remove this effect is a measure of potential antipsychotic activity.

Animals

Male CD-1 mice were group-housed for 2-3 day period in polycarbonate Makrolon type 3 cages (dimensions 26.5×15×42 cm) in an environmentally controlled, experimental room (ambient temperature 22-20° C.; relative humidity 50-60%; 12:12 light:dark cycle, lights on at 8:00), in groups of 15. Standard laboratory food (Ssniff M-Z) and filtered water were freely available. On the day before experiments the equipment produced “white noise” was turned on for 30 minutes and mice were weighted exact to 1 g. Animals were assigned randomly to treatment groups. All the experiments were performed by two observers unaware of the treatment applied between 9:00 and 14:00 on separate groups of animals. Mice were used only once and were killed immediately after the experiment.

Dizocilpine-Induced Locomotor Hyperactivity

The locomotor activity was recorded with an Opto M3 multi-channel activity monitor (MuttiDevice Software v.1.3, Columbus Instruments). The mice were individually placed in plastic cages (22×12×13 cm) for 30 minutes habituation period, and then the crossings of each channel (ambulation) were counted during 1 h with data recording every 5 minutes. The cages were cleaned up with 70% ethanol after examining each mouse. Drugs were administered to 10 mice per treatment group. Test compounds were given 30 minutes before the experiment. Dizocilpine was administered 30 minutes before the test.

Test Compounds

Test compounds were prepared as a suspension in 1% aqueous solution of Tween 80, and dizocilpine was dissolved in distilled water immediately before administration. An injection volume of 10 ml/kg was used and all compounds were administered intraperitoneally (i.p.).

TABLE 24

Results of behavioural test in mice for the representative

compounds of the invention—reversal of dizocilpine

(MK-801)-induced hyperlocomotion in mice

Compound No.
MED* [mg/kg]

21
10

25
5

196
2.5

*minimum effective dose

Dizocilpine (MK-801) is widely recognized as a useful pharmacological tool for modeling of psychotic states in animals by causing glutamatergic dysregulation, similar to that occurring in humans. Ability of the compounds of invention to reverse the dizocilpine-induced hyperlocomotion proves their antipsychotic-like activity in animals and additionally confirms their therapeutic potential in treatment of psychotic states in humans.

Claims

1. Compound of the general formula (I)
2. The compound according to claim 1, wherein D represents the moiety selected from the group consisting of: phenyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C1-C4-alkyl, C1-C3-alkyloxy, halogeno-C1-C3-alkyl, halogen atom, —CN, —OH, and phenyl;naphthyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C1-C4-alkyl and halogen atom;5-membered aromatic heterocyclic group having 1 or 2 heteroatoms independently selected from N, O, S, unsubstituted or substituted with one or more substituents independently selected from the group consisting of C1-C4-alkyl, halogen atom, 5-membered heteroaromatic ring having 1 or 2 heteroatoms independently selected from N, O; linked to sulphonamide group through one of its aromatic carbon atoms; andbicyclic group consisting of a ring selected from benzene and pyridine, fused with 5-membered aromatic or non-aromatic heterocyclic ring, having 1 or 2 heteroatoms independently selected from N, O, and S, unsubstituted or substituted with one or more substitutents independently selected from the group consisting of C1-C4-alkyl, halogen atom, and ═O, linked to sulphonamide moiety through one of its aromatic carbon atoms.
3. The compound according to claim 2, wherein A represents naphthyl.
4. The compound according to claim 1, wherein A represents 9-membered bicyclic group consisting of benzene ring fused with 5-membered monoheteroaromatic ring having atom N.
5. The compound according to claim 1, wherein A represents 9-membered bicyclic group consisting of benzene ring fused with 5-membered heteroaromatic ring having 2 heteroatoms independently selected from N, O, and S.
6. The compound according to claim 1, wherein A represents 10-membered bicyclic group consisting of benzene ring fused with 6-membered heterocyclic ring having 1 or 2 heteroatoms independently selected from N and O.
7. The compound according to claim 1, wherein A represents 9-membered bicyclic group, consisting of benzene ring fused with non-aromatic 5-membered heterocyclic ring having 1 or 2 heteroatoms independently selected from N and O, wherein heterocyclic ring is substituted with ═O or one or more C1-C3-alkyls.
8. The compound according to claim 1, wherein D represents phenyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C1-C4-alkyl, C1-C3-alkyloxy, halogeno-C1-C3-alkyl, halogen atom, halogeno-C1-C3-alkyloxy-, —CN, —OH, and phenyl.
9. The compound according to claim 1, wherein D represents naphthyl unsubstituted or substituted with one or more substituents independently selected from the group consisting of C1-C4-alkyl, C1-C3-alkyloxy and halogen atom.
10. The compound according to claim 1, wherein D represents bicyclic group consisting of benzene ring fused with 5-membered aromatic or non-aromatic heterocyclic ring, having 1 or 2 heteroatoms independently selected from N, O, and S, unsubstituted or substituted with one or more substitutents independently selected from the group consisting of C1-C4-alkyl, halogen atom, and ═O.
11. The compound according to claim 1 wherein n is 3 and p is 0.
12. The compound according to claim 1 wherein n is 2 and p is 1.
13. The compound according to claim 1 wherein x and z are both 2.
14. The compound according to claim 1 wherein x is 2 and z is 1.
15. The compound according to claim 1 wherein x and z are both 1.
16. The compound according to claim 1 wherein r is 0.
17. The compound according to claim 1 wherein r is 1.
18. The compound according to claim 1 selected from the group consisting of the following: N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzenesulphonamide,3-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide,4-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide,3-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]benzene-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-3-methylbenzene-sulphonamide,N-[1-(3-(6-fluoro-1,2-benzoxazol-3-yl)propyl)pyrrolidin-3-yl]benzenesulphonamide,3-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,4-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,3-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,4-bromo-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,4-chloro-3-fluoro-N-[1-[(3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methylbenzene-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-propylbenzene-sulphonamide,4-tert-butyl-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl)benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-(trifluoromethyl)-benzenesulphonamide,N-[1-(3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-(trifluoromethyl)-benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methoxybenzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-hydroxy-benzenesulphonamide,3-cyano-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzene-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,5-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide,6-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,3-dihydrobenzofurano-6-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide,6-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,5-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,5-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]imidazo[1,2-a]pyridine-3-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1,3-benzothiazole-4-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]-3-methylbenzene-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]naphthalene-1-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]naphthalene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]-3-methyl-benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]naphthalene-1-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidine]methyl]naphthalene-2-sulphonamide,N-[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide,N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]-3-hydroxy-benzene-sulphonamide,N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzene-sulphonamide,N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide,4-fluoro-N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide,3-chloro-N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]-3-methyl-benzenesulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]naphthalene-1-sulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]azetidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]-3-methylbenzenesulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzenesulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]-3-methylbenzenesulphonamide,4-tert-butyl-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzenesulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]-4-(trifluoromethyl)benzenesulphonamide,4-cyano-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]benzenesulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]naphthalene-1-sulphonamide,N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide,5-chloro-N-[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]-3-methylbenzothiophene-2-sulphonamide,N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]benzenesulphonamide,N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]-3-methylbenzenesulphonamide,3-hydroxy-N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]benzenesulphonamide,N-[[1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]naphthalene-1-sulphonamide,N-[[(1-[2-(1H-indol-4-yloxy)ethyl]-4-piperidine]methyl]naphthalene-2-sulphonamide,N-[1-[2-(1H-indol-6-yloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[2-(1H-indol-6-yloxy)ethyl]pyrrolidin-3-yl]-3-methylbenzenesulphonamide,N-[[(1-[2-(1H-indol-6-yloxy)ethyl]-4-piperidine]methyl]benzenesulphonamide,N-[[1-[2-(1H-indol-6-yloxy)ethyl]-4-piperidine]methyl]naphthalene-1-sulphonamide,N-[[1-[2-(1H-indol-6-yloxy)ethyl]-4-piperidine]methyl]naphthalene-2-sulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,3-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,4-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,3-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,4-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzenesulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-fluoro-benzenesulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-4-fluoro-benzenesulphonamide,3-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,4-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzenesulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]benzene-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-3-fluoro-benzenesulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-4-fluoro-benzenesulphonamide,3-chloro-N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]benzene-sulphonamide,4-chloro-N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]benzenesulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]-3-methyl-benzenesulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]naphthalene-1-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]azetidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]benzene-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]-3-methyl-benzene-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-1-sulphonamideN-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]naphthalene-1-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-3-methylbenzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-3-hydroxybenzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-naphthalene-1-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxan-5-yloxy)ethyl]-4-piperidine]methyl]-naphthalene-2-sulphonamide,N-[[1-[2-(2-oxoindolin-4-yl)oxyethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]-3-hydroxy-benzenesulphonamide,N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]-4-piperidine]-3-hydroxy-benzene-sulphonamide,N-[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]-4-piperidine]naphthalene-2-sulphonamide,N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]azetidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide,N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide,N-[[1-[2-[(2,2-dimethyl-3H-benzofuran-7-yl)oxy]ethyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,3-hydroxy-N-[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]benzene-sulphonamide,N-[1-[2-(2,3-dihydro-1,4-benzodioxan-8-yloxy)ethyl]-4-piperidine]-3-methyl-benzenesulphonamide,3-hydroxy-N-[1-[2-(1-naphthyloxy)ethyl]-4-piperidine]benzenesulphonamide,N-[1-[2-(1-naphthyloxy)ethyl]-4-piperidine]naphthalene-2-sulphonamide,3-hydroxy-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,3-hydroxy-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,N-[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]pyrrolidin-3-yl]-3-hydroxybenzene-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzo-thiophene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide,6-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]-naphthalene-2-sulphonamide,5-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide,5-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]-methyl]-3-methyl-benzothiophene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1,3-benzothiazole-5-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-naphthalene-1-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-phenyl-benzenesulphonamide,4-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,3-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-methyl-benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide,4-tert-butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methyl-benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-methoxy-benzenesulphonamide,3-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,4-cyano-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,3,4-dichloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,4-bromo-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzofuran-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]thiophene-3-sulphonamide,5-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]thiophene-2-sulphonamide,3-chloro-4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-propyl-benzenesulphonamide,3,4-difluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]azetidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide,N-[[1-[3-(5-fluoro-1H-indol-3-yl)propyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,N-[[1-[3-(5-chloro-1H-indol-3-yl)propyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,N-[[1-[2-(1,2-benzothiazol-3-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide,6-chloro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]-benzothiophene-2-sulphonamide,6-chloro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,5-fluoro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide,5-chloro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-2-sulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]naphthalene-1-sulphonamide,1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]indole-5-sulphonamide,1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]indole-4-sulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-3-sulphonamide,3-chloro-4-fluoro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,3,4-difluoro-N-[[1-[2-(1-naphthyloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,6-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]naphthalene-2-sulphonamide,5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-3-methylbenzothiophene-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-1-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-naphthalene-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-phenyl-benzenesulphonamide,4-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide,4-tert-butyl-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-fluoro-benzenesulphonamide3,4-dichloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-thiophene-2-sulphonamide,4-bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzofuran-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]benzothiophene-3-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-thiophene-3-sulphonamide,5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]thiophene-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]azetidin-3-yl]methyl]-4-iodo-benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1,3-benzo-dioxole-5-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-phenylbenzenesulphonamide,N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,N-[(3S)-1-[3-CE-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,6-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,6-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,6-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,6-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,5-fluoro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,5-fluoro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,5-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,5-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-naphthalene-2-sulphonamide,4-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-methylbenzenesulphonamide,4-cyano-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide3,4-dichloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-4-methoxybenzenesulphonamide,N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-furan-2-sulphonamide,N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzo-furan-2-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzofuran-2-sulphonamide, N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-imidazole-4-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2-oxo-indoline-5-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide,N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide,N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-2,5-dimethyl-thiophene-3-sulphonamide,N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzothiophene-3-sulphonamideN-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-benzothiophene-3-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methylbenzothiophene-2-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide,N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methylbenzothiophene-2-sulphonamide,N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-5-methylbenzothiophene-2-sulphonamide,N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide,N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]-6-methoxy-naphthalene-2-sulphonamide,7-chloro-N-[(3R)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,7-chloro-N-[(3S)-1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,6-fluoro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide,6-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,5-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-methylbenzothiophene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]naphthalene-1-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-phenyl-benzenesulphonamide,4-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,3-chloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-methyl-benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethyl)benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulphonamide,4-tert-butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,3-tert-butyl-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-methoxy-benzenesulphonamide,4-cyano-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,3,4-dichloro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-3-hydroxy-benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-methoxy-benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2,3-dihydrobenzofuran-5-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-benzofuran-2-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzothiophene-3-sulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-2,5-dimethyl-thiophene-3-sulphonamide,3-chloro-4-fluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-propyl-benzenesulphonamide,3,4-difluoro-N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide,N-[[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]methyl]-naphthalene-2-sulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide,6-chloro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzothiophene-2-sulphonamide,6-chloro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,5-fluoro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide,5-chloro-3-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-1-sulphonamide,1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]indole-5-sulphonamide,1-methyl-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]indole-4-sulphonamide,N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-3-sulphonamide,3-chloro-4-fluoro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl-benzene-sulphonamide,3,4-difluoro-N-[[1-[2-(1-naphthyloxy)ethyl]pyrrolidin-3-yl]methyl]-benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzodioxole-5-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-4-sulphonamide,6-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-methyl-benzothiophene-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]thiazole-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1,3-benzothiazole-5-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-1-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]naphthalene-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-4-phenyl-benzenesulphonamide,4-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,3-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-methyl-benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-(trifluoro-methyl)benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-(trifluoromethyl)benzenesulphonamide,4-tert-butyl-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-methyl-benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-3-methoxybenzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]-methyl]-3-fluoro-benzenesulphonamide,4-cyano-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-fluoro-benzenesulphonamide,3,4-dichloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]thiophene-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3-hydroxybenzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-methoxybenzenesulphonamide,4-bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2,3-dihydrobenzofuran-5-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzofuran-2-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-5-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-1-methyl-indole-4-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2-oxo-indoline-5-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzothiophene-3-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-2,5-dimethyl-thiophene-3-sulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]thiophene-3-sulphonamide,N-[[(1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-5-isoxazol-5-yl-thiophene-2-sulphonamide,3-cyano-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,5-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]thiophene-2-sulphonamide,3-chloro-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-fluoro-benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-propyl-benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-3,4-difluoro-benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-(trifluoromethoxy)benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-4-iodo-benzenesulphonamide,3-bromo-N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]benzenesulphonamide,N-[[1-[2-(2,3-dihydro-1,4-benzodioxin-5-yloxy)ethyl]pyrrolidin-3-yl]methyl]-5-methyl-isoxazole-4-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]benzothiophene-2-sulphonamide6-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]naphthalene-2-sulphonamide,5-chloro-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-3-methyl-benzothiophene-2-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-4-phenyl-benzenesulphonamide,4-tert-butyl-N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-benzenesulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]-1-methyl-indole-4-sulphonamide,N-[1-[3-(6-fluoro-1,2-benzoxazol-3-yl)propyl]-4-piperidyl]benzothiophene-3-sulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,6-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,6-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-5-fluoro-3-methyl-benzothiophene-2-sulphonamide,5-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,3,4-dichloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]thiophene-2-sulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-1-sulphonamide,3-chloro-N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-4-fluorobenzenesulphonamide,N-[1-[3-(5-chloro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3,4-difluorobenzenesulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,6-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-2-sulphonamide,6-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]naphthalene-2-sulphonamide,5-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methyl-benzothiophene-2-sulphonamide,5-chloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-3-methylbenzothiophene-2-sulphonamide,3,4-dichloro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,N-[1-(3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl)thiophene-2-sulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-5-sulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]-1-methyl-indole-4-sulphonamide,N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzothiophene-3-sulphonamide,3-chloro-4-fluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,3,4-difluoro-N-[1-[3-(5-fluoro-1H-indol-3-yl)propyl]pyrrolidin-3-yl]benzenesulphonamide,and pharmaceutically acceptable salts and solvates thereof.
19. (canceled)
20. A pharmaceutical composition comprising a compound of formula (I) as defined in claim 1 as an active ingredient in combination with pharmaceutically acceptable carrier(s) and/or excipient(s).
21-22. (canceled)
23. A method of treatment and/or prevention of disorders of the central nervous system related to serotoninergic and dopaminergic transmission in mammals, comprising administration of the pharmaceutically effective amount of a compound of formula (I) as defined in claim 1 wherein the disorder of the central nervous system is selected from the group consisting of schizophrenia; schizoaffective disorders; schizophreniform disorders; delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances; affective disorder; bipolar disorder; mania; depression; anxiety disorders of various etiology; stress reactions; consciousness disorders; coma; delirium of alcoholic or other etiology; aggression; psychomotor agitation and other conduct disorders; sleep disorders of various etiology; withdrawal syndromes of various etiology; addiction; pain syndromes of various etioloqy; intoxication with psychoactive substances; cerebral circulatory disorders of various etiology psychosomatic disorders of various etiology; conversion disorders; dissociative disorders; urination disorders; autism and other developmental disorders, including nocturia, stuttering, tics; cognitive disorders of various types, including Alzheimer's disease; and psychopathological symptoms and neurological disorders in the course of other diseases of the central and peripheral nervous systems.

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Number	Date	Country	Kind
P-395470	Jun 2011	PL	national

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PCT/IB2012/053318	6/29/2012	WO	00	12/18/2013

SULPHONAMIDE DERIVATIVES OF ALICYCLIC AMINES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES

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