Heterocyclic compounds as positive modulators of metabotropic glutamate receptor 2 (mglu2 receptor)

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae

,

where X is O, NH or N-Rx, and Rx, Ra, Rb, R10a, R11a, R2, R3, R4 are selected from hydrogen, different aliphatic, alicyclic, aromatic, heteroaromatic and functional groups which can be optionally substituted, wherein R4 together with R2 can form a C1-C5alkylene or C3-C5alkenylene fragment. Said compounds are positive modulators of metabotropic glutamate receptor 2 and can be used in medicine.

EFFECT: novel biologically active compounds are efficient when treating a range of diseases of the nervous system which are mediated by the dysfunction of the glutamate receptor.

23 cl, 590 ex, 1 tbl

 

The present invention relates to heterocyclic compounds which are positive modulators of metabotropic glutamate receptor. The present invention also relates to the use of such compounds, to pharmaceutical compositions and to a method for the treatment of painful disorders selected from neurological and psychiatric disorders associated with glutamate dysfunction.

Glutamate, the main excitatory neurotransmitter in the brain, causing his actions by activating ligand-opening of cation channels, called ionotropic glutamate receptors (iGluR)and metabotropic glutamate receptors (mGlu receptors). The latter belong to the family 3 G-protein linked receptor (GPCR) (Conn and Pin, Annu. Rev. Pharmacol. Toxicol. 37, 205-37, 1997) and are connected via heterotrimeric G-proteins with intracellular effector systems. These receptor types are multiple modulatory actions within the Central nervous system (CNS). To date, eight mGlu receptor subtypes cloned from the brain of mammals. Depending on their G-protein binding profile, pharmacology and identity sequence such receptors are classified into three groups (Conn and Pin, Annu. Rev. Pharmacol. Toxicol. 37, 205-37, 1997). The mGlu receptors group I, mainly due yaytsa through Gq with increasing hydrolysis of phosphoinositide and cellular CA 2+system through the phospholipase C (PLC) and include receptor mGlu1 and mGlu5 receptor. Receptors mGlu group II, which include mGlu2 and mGlu3, inhibit adenylylcyclase (AU) is exactly the same as the mGlu receptors of group III, which include mGlu4, mGlu6, mGlu7 and mGlu8. Thus, in groups II and III are sensitive to pertussis toxin G-protein Gi is involved in signal transduction. However, receptors mGlu group II and group III are identical sequence and pharmacological profile.

8 mGlu receptor subtypes there are different ways to splanirovanie. Inside of mGlu receptors group I variety of splicing the most significant. Mglu1 exists in 6 different splicing forms. All mGlu1a receptors, 1b/b, 1c, 1d and 1f differ in their C-terminal intracellular domain (Prezaeu et al., Mol. Pharmacol. 49, 422-429, 1996; Soloviev et al., Biochimica et Biophysica Acta 1446, 161-166, 1999) and mGlu1e truncated at the N-terminal part, lacking the largest part of the protein-binding region (Pin and Duvoisin, Neuropharmacol. 34, 1-26, 1995). While demonstrated two splicing variants of mGlu5 receptors (group 1) and mGlu4, mGlu7 and mGlu8 group II. mGlu6, which is solely to ON-bipolar cells of the retina (Nakanishi et al., Brain Res. Rev. 26, 230-235, 1998), has only one isoform. The same is true for receptor mGlu2 and mGlu3 (Fagni et al., TINS 23 (2), 80-88, 2000).

Synaptic localization of mGlu receptors group I and receptors mGlu II/III varies. While the receptors group I predominantly localized postsynaptic, receptors of group III mGlu demonstrate rather presynaptic localization (Shigemoto et al., J. Neurosci. 17, 7503-7522, 1997; Cartmell & Schoepp, J. Neurochem. 75(3), 889-907, 2000). It turns out that the group II receptors localized pre - and postsynaptic, depending on the area of the brain and the type of synapse. Demonstrated presinapticheskie localization mGlu2. In this case, the receptor can be activated only during high-frequency stimulation, then preventing further release of transmitter, thus reducing pathologically high levels of glutamate in the synaptic cleft. Autoreceptor function (medial perforating path, mossy fiber-SA, spinal synapse, corticostriatal the synapse) and heteroreceptors functions demonstrated for receptors mGlu group II at synapses in different parts of the brain. Pre - and presinapticheskie localization mGlu receptors, combined with their auto - and heteroreceptors function, and their interaction with inhibitory intracellular cascades signal indicates an important role of this receptor type for the regulation of excitatory neurotransmission.

The first compounds that recognize 3 different groups of mGlu receptors, represented agonists with low affin the stew: 3,5-dihydroxyphenylglycol (3,4-DHPG), which selectively stimulates mGlu receptors of group 1; (2R,4R)-4-aminopyrrolidine acid (2R,4R-APDC), activating mGlu receptors of group II (Monn et al., J. Med. Chem. 39(15), 2990-3000, 1996) and L-amino-4-phosphonobutyric (L-AP4, Trombley and Westbrook, J.Neurosci. 12(6), 2043-50, 1992) for the activation of mGlu receptors of group III. All such compounds represent valuable tools to study the various functions of mGlu receptors in vitro studies, but it is shown that none of these compounds does not have strong effects on the Central nervous system after systemic injection. It turns out that other previously known compounds that are mainly used for in vitro studies, activate ionotropic glutamate receptors to the same extent. As widely used agonist mGlu receptor group II (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxylate)glycine also activates NMDA receptors.

Toward action research in vivo and therapeutic uses of agonists of group II major achievement resulting from the opening of LY354740 and LY379268 (formulas are given, for example, D.A. Barda et al., Bioorganic and Medicinal Chemistry Letters, 14, 3099-3102, 2004). Two such compounds are highly specific agonists of the receptor group II, only with a very low affinity for other mGlu receptors or ionotropic glutamate receptors. They had an EC50from 10 to 20 nm (LY354740), and is 3 to 5 nm (LY379268) for mGlu2 and 3, respectively. Despite the fact that the differentiation between the two group II receptors impossible, specificity >1:30000 to receptors group I and from 1:100 (mGlu6) to >1:30000 (mGlu7) to the receptors of group III is the highest discriminatory potential for these receptor types (Cartmell and Schoepp, J.Neurochem. 75(3), 889-907, 2000; Brauner-Osborne et al., J. Med. Chem. 43(14), 2609-2645, 2000). Both connections are designed as conformationally restricted analogues of glutamate (Monn et al., J. Med. Chem. 40(4), 528-37, 1997; J. Med. Chem. 42(6), 1027-40, 1999) and representative competitive antagonists at the glutamate binding site. Moreover, these two compounds are systemically active.

Derivatives of such compounds, MGS 0008 and MGS 0028 (Nakazato et al., J. Med. Chem. 43(25), 4893-909, 2000), have a higher oral absorption. They also demonstrate increased antagonistic effect on PCP-induced stereotyped head movements (head-weaving) and hyperactivity in rats. Also recently identified a highly selective antagonist of mGlu receptor group II (Kingston et al., Neuropharmacology 37(1), 1-12, 1998; Johnson et al., Neuropharmacology 38(10), 1519-29, 1999). We detected no appreciable specific binding of radioligand[3H]-LY431495 (formula given in the publication D.A.Barda et al., 2004) in the membranes of cells expressing human mGlu1a receptors, mGlu5a, mGlu4a, mGlu6 or mGlu7a. Many of the effects induced by agonists of group II receptors, can be subjected to what I term reversal with such connection. Therefore, LY341495 is also a highly selective tool connection.

Positive modulators activate mGlu2 receptor depending on the presence of glutamate (potentiator). Thus, the connection sencibilisiruet receptor for interaction already at lower concentrations of ligand. Positive modulators can also directly activate mGlu2 receptor. MGlu receptors are composed of a large extracellular N-terminal domain which binds to a natural ligand, glutamate, which is homologous periplasmatic the amino acid binding proteins from bacteria. This domain is associated with a 7-transmembrane domain. Such a canonical domain, common to all G-protein-linked receptors, contains the canonical ligand-binding site for GPCR (compare with rhodopsin in retinal). In mGluR this site is free and may play a modulatory role as a site for positive and negative allosteric compounds.

The exact aminokisloty sites responsible for ligand binding model potentiator (LY487379, see Johnson et al., J. Med. Chem. 46(15), 3189-92, 2003), derived from the amino acid comparison between mGlu2 receptor and mGluR3 in this area. Because potentiator is specific for mGlu2 receptor, the binding should not take place at mGluR3 and responsible Amin the acid must be exactly amino acids, which differ from the two receptors. Recently, the binding site model potentiator (LY487379) mapped by the directed site-mutagenesis. It turned out that the binding site is located within the transmembrane domain mGlu2 receptor (Schaffhauser et al., Mol. Pharmacol. 64(4), 798-810, 2003). In particular, amino acids 688, 689 and 735 are characteristic for the binding.

MGlu receptor expressed both in single and overlapping cycles responsible for neuropsychiatric and neurological disorders. The cycle includes the expression in the neocortex, thalamus, striatum, amygdala and hippocampus. Within such cycles mGlu2 receptor expressed mainly presynaptic. As a result of such patterns of expression, demonstrated that the release of excitatory transmitter is regulated by agonists of group II in different parts of the brain. Demonstrated that agonists of group II normalize PCP-induced glutamate release in the prefrontal cortex (PFC) and that dopamine is regulated by agonists of group II-specific plot method. As, for example, one function of agonists of group II increases dopamine and metabolites in the PFC. Serotonin and metabolites are also regulated in the PFC. In addition, it demonstrated the functional antagonism of 5-NTA receptors in this area goal the main brain.

These data show that the method mGlu2 receptor can normalize the number of fixed transmitters in schizophrenia. The concept of agonist/potentiator mGlu2 receptor is likely to result in the ability to normalize

positive symptoms due to regulation of glutamate,

negative symptoms due to the regulation of dopamine and serotonin and

cognitive symptoms due to regulation of acetylcholine in the PFC.

In addition to schizophrenia interest symptom can be the abuse of the medicinal product, as agonists of group II block the expression of locomotor sensitization by amphetamine, among a large number of other described actions. The use of such compounds is not limited to painful conditions described above.

The concept of potentiator mGlu receptor is relatively new (Barda et al., 2004), but it is necessary to evaluate the significance of the mGlu2 receptor in relation to mGlu3. It is known, as described above, agonists of group II to cross-react engagement with both receptor types. Over the last year messages directly demonstrate the importance of mGlu2 receptors in models of psychosis in rodents when describing the functions of potentiation mGlu receptor models PCP-induced hyperlocomotion induced by amphetamine of hyperlocomotion, and is changing the direction of amphetamine-induced degradation of PPI in mice (Galici et al., JPET 315(3), 1181-1187, 2005).

In addition to these data, indicating the importance of potentiation mGlu2 receptor in schizophrenia, new messages, in addition, demonstrate the effectiveness of potentiation mGlu2 receptor in anxiety, as it is shown, that potentiator are effective in potentsiiruya fear frightened rats and induced stress hyperthermia in mice (Johnson et al., Psychopharmacol, 179(1), 271-83, 2005).

The net method is the activation of NMDA ("glutamate hypothesis of schizophrenia") can lead to possible side effects. In particular, excitotoxicity is a relevant side effect that should be considered within the potential screening cascade such design work. This possibility of side effects may limit the usefulness of such methods.

As described above, the positive modulatory method of the mGlu2 receptor does not rely entirely on glutamatergic hypothesis, but probably involved in the normalization of the release of a number of excitatory neurotransmitters. Therefore, there is still no proof of possibility excitotoxicity agonists of group II or positive modulators of mGlu2 receptor. Agonists of group II show even the opposite effect. They are neuroprotective in MRTR model of Parkinson's disease, they restore the Indus the grids Mg +2reduced epileptiform discharge into the drugs sections, and they possess anticonvulsant activity in models of acute attack.

As a possible side effect was described negative effects of agonists of group II on cognitive ability (Higgins et al., Neuropharmacol 46, 907-917, 2004). However, to date, in the literature this result is controversial. While one group finds the reversibility of insufficient cognitive abilities induced by PCP (Moghaddam and Adams, Science 281(5381), 1349-52, 1998), the second group detects a decrease in the functioning of the DNMTP in the case of mGlu2 receptor agonist LY354740, which is not present in the mGlu2 receptor knocked out mouse (Higgins et al., Neuropharmacol. 46, 907-917, 2004). This result is opposite to the data Modhaddam and Adams, and may also contradict the normalization of Ach release in the PFC in this connection (see above).

In WO 2001/56990 described N-substituted N-(phenyl)aminomethylpyridine compounds that are potentiator glutamate receptors.

In WO 2006/014918 described heterocyclic compounds with 4-allfamily fragment. Connections are potentiator metabotropic glutamate receptors, including mGlu2 receptor, and is therefore useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dish what nccia, and diseases that involve metabotropic glutamate receptors.

In WO 2006/015158 and WO 2006/047237 described heterocyclic compounds having inderoy fragment, and the connections represent potentiator metabotropic glutamate receptors, including the mGlu2 receptor.

In WO 2006/0030032 described pyridinone compounds that are potentiator metabotropic glutamate receptors, including the mGlu2 receptor.

In WO 2006/049969 described N-(phenyl)aminoalkylsilane pyrimidine compounds that are potentiator metabotropic glutamate receptors, including the mGlu2 receptor.

In WO 2006/057860, WO 2006/057869 and WO 2006/057870 described in connection with 4-acyl-3-hydroxyproline fragment. I believe that these connections are potentiator metabotropic glutamate receptors, including the mGlu2 receptor.

In WO 2006/091496 described compounds having benzazolyl fragment and the connections proposed as potentiators metabotropic glutamate receptors, including the mGlu2 receptor.

In WO 2006/020879, WO 2007/021308 and WO 2007/021309 described isoindoline compounds that are proposed as potentiators metabotropic glutamate receptors, including the mGlu2 receptor.

Although the compounds of the prior art have a high affinity against mGlu2 is eceptor, their receptor binding profile and/or their pharmacological profile is not always satisfactory. In particular, these compounds often have insufficient selectivity for mGlu2 receptor compared to mGlu3 or mGlu receptors of group III, or represent glutamate agonists. In addition, the metabolic stability or the metabolic behavior and/or bioavailability are unsatisfactory.

The present invention is the provision of additional compounds that are positive modulators of metabotropic glutamate receptors, in particular, mGlu2 receptor and are thus useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases that involve metabotropic glutamate receptors. Connections must be positive modulators of mGlu2 receptor lacking or having reduced agonistic activity in order to reduce or avoid side effects associated with agonistic activity. These compounds preferably should also have a favorable metabolic behavior, such as reduced inhibition of mitochondrial respiration, and reduced interaction with isoenzymes qi is Krom P450. Connections must also have appropriate bioavailability.

These and additional objectives are compounds of General formula I as described herein, as well as their tautomers and pharmaceutically acceptable salts.

Thus, the present invention provides compounds of formula I

where

X represents O, S, S(O), S(O)2, NH, NHC(O)NRxor a chemical bond;

Rxrepresents a C1-6alkyl, which is unsubstituted or is a radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals Rxa,

C1-C6halogenated,3-C8cycloalkyl,1-C6alkoxy, C1-C6halogenoalkane,

phenyl, 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where heteroaryl and phenyl are unsubstituted or have 1, 2, 3, 4 or 5 identical or different radicals Rxb,

C(=O)-Rx1C(=O)-ORx2C(=O)NRx3Rx4, S(O)2Rx5or S(O)2NRx3Rx4where

Rx1selected from hydrogen, C1-C8of alkyl, which is unsubstituted or carries one radical selected the from HE, With1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals Rxa,

C1-C6halogenoalkane,3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl and 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where phenyl and heteroaryl are unsubstituted or may have a condensed benzene ring and/or may have 1, 2, 3, 4 or 5 identical or different radicals Rxb;

Rxaselected from the group consisting of halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

Rxbselected from the group consisting of halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

Rx2selected from C1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, where the very phenyl ring which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals Rxa,

C1-C8halogenoalkane and C3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

Rx3selected from hydrogen, C1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals Rxa,

With1-C6halogenoalkane,1-C8alkoxy and C1-C8halogenoalkane,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

Rx4selected from hydrogen and C1-C8the alkyl or

Rx3and Rx4together with the nitrogen atom to which they are linked, form a heterocyclic radical selected from pyrrolidinyl, piperidinyl, piperazinil, N-alkylpiperazine, N-phenylpiperazine and morpholinyl; and

Rx5has one of the meanings given for Rx1;

Y represents O, S, S(O), S(O)2, NH, NRx, O-phenylene, S-phenylene, NH-phenylene or a chemical bond, where the heteroatom is-phenylene, S-phenylene and NH-phenylene attached to Het and where phenylenebis fragment is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4halogenoalkane;

provided that at least one of X and Y is different from a chemical bond;

But a1-C5alkylene, which may have 1, 2, 3 or 4 radicals selected from halogen, HE1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

Ar represents phenyl, or represents 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N;

R1represents a C1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and C3-C8cycloalkyl,

With1-C8alkoxy, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and C3-C8cycloalkyl,

With1-C8halogenated,1-C8halogenoalkane,

With3-C8cycloalkyl,3-C8cycloalkane, where the last two shows of the radical are unsubstituted or have 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and 1-C4alkoxy;

C(=O)-R4C(=O)-OR5, NR6R7C(=O)NR6R7, SO2NR6R7, NR8C(=O)R9, SO2R9, NR8SO2R9,

phenyl, O-phenyl, CH2-phenyl, CH(CH3)phenyl, CH(OH)phenyl, S-phenyl and O-CH2-phenyl, where the phenyl ring in the last seven following radicals may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane,

or the radical Het', O-Het', CH2-Het', CH(CH3)-Het', CH(OH)-Het', S-Het', OCH2-Het, where Het' is a 5 - or 6-membered saturated, unsaturated or aromatic heterocycle having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where the heterocycle may be unsubstituted or may have 1, 2, 3, or 4 substituent selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R2represents hydrogen, CN, OH, halogen, C1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C3-C6cycloalkyl and C1-C4alkoxy,

the 3-C6cycloalkyl,1-C8halogenated,1-C8alkoxy and C1-C8halogenoalkane, or

R1and R2if they are linked to adjacent carbon atoms may together form a 5 - or 6-membered heterocyclic ring condensed with the benzene ring and having 1, 2 or 3 nitrogen atom in the ring or 1 oxygen atom and optionally a further heteroatom selected from O, S and N, in the ring, and where the condensed heterocyclic ring may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, HE, CN, NH2With1-C4of alkyl, C3-C6cycloalkyl,1-C4alkoxy, C1-C4the alkylamine, di(C1-C4alkyl)amino, C1-C4halogenoalkane,1-C4halogenoalkane,1-C4alkylsulfonyl,1-C4halogenallylacetic and phenylsulfonyl, where the phenyl ring may be unsubstituted or may have 1, 2, 3, or 4 substituent selected from halogen, CN, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R3represents hydrogen, halogen, C1-C4alkyl, which is unsubstituted or carries one radical selected from HE, and1-C4alkoxy,

1-C4halogenated,1-C4alkoxy and C1-C4halogenoalkane,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

R4selected from hydrogen,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4a,

With1-C8halogenoalkane,

With2-C8alkenyl,

With2-C8the quinil,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy, and

phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4b,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where heteroaryl is unsubstituted or has 1, 2, 3 or 4 identical or different radicals R4bor

R4together with R2form1-C5alkalinity or2-C5alkenylamine fragment, where one CH2-h is the terrain may be replaced by oxygen, sulfur or N-R4c-part of, and where C1-C5alkylene and C2-C5albaniles can be unsubstituted or have 1, 2, 3 or 4 radicals selected from halogen, CN, OH, NH2With1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkylamino, di(C1-C4alkyl)amino, C1-C4alkoxy and C1-C4halogenoalkane;

R4aselected from the group consisting of halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R4bselected from the group consisting of halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R4cselected from the group consisting of hydrogen, CN, OH,

C1-C8of alkyl, in particular With1-C4of alkyl, which is unsubstituted or is a radical selected from C1-C4alkoxy, C1-C4alkylthio,1-C4halogenoalkane,1-C4allogenicity,3-C6cycloalkyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from halogen and C1-C4of alkyl, and

phenyl is or benzyl, where the very phenyl ring in the last two radicals is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane,

With3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R5selected from C1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R5a,

With1-C8halogenoalkane and

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

R5ahas one of the meanings given for R4a;

R6selected from hydrogen,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different is dikalov R 6aand

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

R6ahas one of the meanings given for R4a;

R7selected from hydrogen and C1-C8the alkyl, or

R6and R7together with the nitrogen atom to which they are linked, form a heterocyclic radical selected from pyrrolidinyl, piperidinyl, piperazinil, N-alkylpiperazine, N-phenylpiperazine and morpholinyl;

R8selected from hydrogen,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R6aand

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

R6ahas one of the meanings given for R4a;

R9has one of the meanings given for R4;

Het represents a 5 - or 6-membered saturated, unsaturated or aromatic heterocycle having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where Het is tamaseni or may have first Deputy R 10and optionally 1 or 2 additional substituent R11, R12and where Het may also be condensed benzene, pyridine, pyrimidine or pyridazine ring;

R10selected from halogen, cyano,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4a,

With1-C8alkoxy, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4a,

With1-C8halogenoalkane,

With1-C8halogenoalkane,

With2-C8alkenyl,

With2-C8the quinil,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With3-C8cycloalkane, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

C(=O)-R13C(=O)-OR14, NR15R16C(=O)NR15R16, SO2R17 ,

phenyl, O-phenyl, CH2-phenyl, CH(CH3)phenyl, CH(OH)phenyl, S-phenyl and O-CH2-phenyl, where the phenyl ring in the last seven following radicals may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R11represents CN, OH, halogen, C1-C8alkyl, which is unsubstituted or carries one radical selected from HE, and1-C4alkoxy,

With1-C8halogenated,1-C8alkoxy, C1-C8halogenoalkane or phenyl which may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R12represents CN, OH, halo is Yong, With1-C8alkyl, which is unsubstituted or carries one radical selected from HE, and1-C4alkoxy,

With1-C8halogenated,1-C8alkoxy and C1-C8halogenoalkane or

R11and R12together with the carbon atom to which they are bound, form a carbonyl group;

R13selected from hydrogen,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R13a,

With1-C8halogenoalkane,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl and 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where phenyl and heteroaryl are unsubstituted or have 1, 2, 3, 4 or 5 identical or different radicals R13b;

R13aselected from the group consisting of halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R13bselected from the group consisting of ha is ogena, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

R14selected from C1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R13a,

With1-C8halogenoalkane and

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

R15selected from hydrogen,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R13aand

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;

R16selected from hydrogen and C1-C8the alkyl, or

R15and R16together with the nitrogen atom to which they are linked, form a heterocyclic radical selected from pyrrolidinyl, piperidinyl,piperazinil, N-alkylpiperazine, N-phenylpiperazine and morpholinyl;

R17selected from C1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R17a,

With1-C8halogenoalkane,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen and C1-C4alkoxy,

phenyl or 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where phenyl and heteroaryl are unsubstituted or have 1, 2, 3, 4 or 5 identical or different radicals R17bwhere R17ais the same as defined for R13aand R17bis the same as defined for R13b;

provided that Het is a radical selected from Furie, pyrrolyl, teinila, pyrazolyl, thiazolyl, benzothiazolyl, oxazolyl, isoxazolyl, isothiazoline, pyrazinyl, pyridazinyl, triazolyl, thiadiazolyl, imidazolyl, oxazolyl, thiazolyl, tetrahydroaminoacridine, tetrahydropyrimidine, isoindolyl, pyridinyl, phthalazine, naphthyridine, khinoksalinona, chinadoll, oxazolopyridine, triazolopyridine, imidate is Yasinya, oxazolopyridine, triazolopyridine, cinnoline, pteridine, furazane, benzotriazolyl, pyrazolopyrimidine and naphthyridine, if X represents O, NHC(O), S(O)2or a link where the above heterocyclic radicals may be the first Deputy R10and optionally 1 or 2 additional substituent R11, R12,

further, when the condition that is satisfied at least one of the conditions (1) or (2)when Het is a 6-membered heterocycle or 6-membered heterocycle condensed with a benzene, pyridine, pyrimidine or pyridazinone ring, 6-membered heterocycle and 6-membered heterocycle condensed with a benzene, pyridine, pyrimidine or pyridazinone ring may have a first Deputy R10and optionally 1 or 2 additional substituent R11, R12;

(1) R1represents a radical selected from the

group consisting of C(=O)-R4C(=O)-OR5, NR6R7C(=O)NR6R7, SO2NR6R7, NR8C(=O)R9, SO2R9and NR8SO2R9,

or from the group consisting of Het', O-Het', CH2-Het', CH(CH3)-Het', CH(OH)-Het', S-Het', OCH2-Het, where Het' is a 5 - or 6-membered saturated, unsaturated or aromatic heterocycle having 1, 2 or 3, g is teratoma in the ring, moreover, the heteroatoms selected from O, S and N, where the heterocycle may be unsubstituted or may have 1, 2, 3, or 4 substituent selected from halogen, CN, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

(2) Het has a first substituent R10and optionally has 1 or 2 additional substituent R11, R12and R10selected from C2-C8alkenyl,2-C8the quinil,3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

C(=O)-R13C(=O)-OR14, NR15R16C(=O)NR15R16, SO2R17and

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;

and their pharmaceutically acceptable salts and tautomers.

Compounds of the present invention are positive modulators of metabotropic glutamate (mGlu) receptor function, in particular, they represent the floor of the positive modulators of mGlu2 receptors. That is, it turns out that the compounds of the present invention do not bind the glutamate-recognition site on the mGlu receptor, but in the presence of glutamate or glutamate agonist compounds of the present invention increase mGlu receptor response. Assume that the data are positive modulators exert their effects at mGlu receptors, due to its ability to increase the response of these receptors to glutamate or glutamate agonists, increasing function of receptors. It was found, as was to be expected that the compounds of the present invention increase the efficiency of glutamate and glutamate agonists mGlu2 receptor. Therefore, assume that the compounds of the present invention are useful in the treatment of various neurological and psychiatric disorders associated with glutamate dysfunction, which, as described herein, is subjected to treatment, and other diseases), which can be treated by the positive modulators, as it is clear to experts in this field.

The present invention also relates to pharmaceutical compositions containing at least one compound of formula I, its tautomer and/or its pharmaceutically acceptable salt, optionally together with at least one physiologically acceptable carrier or auxiliary substances is om.

The present invention also relates to a method for treatment of painful disorders selected from neurological and psychiatric disorders associated with glutamate dysfunction, which includes the introduction of an effective amount of at least one of the compounds of formula I, its tautomer and/or its pharmaceutically acceptable salt to the needy in this subject.

The present invention also relates to a method for potentiation of the activity of a metabotropic glutamate receptor in a mammal, which comprises introducing an effective amount of at least one of the compounds of formula I, its tautomer and/or its pharmaceutically acceptable salt.

The compounds of formula I, their tautomers and their pharmaceutically acceptable salt, in particular, useful to obtain

medicines for treating, suppressing, reducing the intensity or reduce the risk of anxiety in a mammal;

medicines to obtain the drug for treating, suppressing, reducing the intensity or reduce the risk of depression in a mammal; medicines for treating, suppressing, reducing the intensity or reduce the risk of migraine in a mammal;

medicines for treating, suppressing, reducing the intensity or reduce the risk of schizophrenia in a mammal;/p>

medicines for treating, suppressing, reducing the intensity or reduce the risk of epilepsy in a mammal;

medicines for treating or reducing the intensity of symptoms associated with disorders in a mammal, related to the substance.

The present invention also applies to

the method of treating, suppressing, reducing the intensity or reduce the risk of anxiety in a mammal;

the method of treating, suppressing, reducing the intensity or reduce the risk of depression in a mammal;

the method of treating, suppressing, reducing the intensity or reduce the risk of schizophrenia in a mammal;

the method of treating, suppressing, reducing the intensity or reducing the risk of epilepsy in a mammal;

the method of treating, suppressing, reducing the intensity or reduce the risk of migraine in a mammal;

the method of treating or reducing the intensity of symptoms associated with disorders in a mammal, related to the substances;

which include the introduction of an effective amount of at least one of the compounds of formula I, its tautomer and/or its pharmaceutically acceptable salt to the needy in the mammal.

Compounds of the present invention may contain one or more asymmetric centers Kogut, thus, to be in the form of racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. There may be additional asymmetric centers depending on the nature of the various substituents in the molecule. Each such asymmetric center will independently produce two optical isomers, and imply that all of the possible optical isomers and diastereomers in mixtures and as pure or partially purified compounds are included in the scope of the present invention. The present invention is meant to include all such isomeric forms of these compounds. The independent syntheses of such diastereoisomers or their chromatographic separation can be accomplished, as is well known in this area, appropriate modification described in this method description. Their absolute stereochemistry can be determined by x-ray crystallography of crystalline products or crystalline intermediates which functionalitywith, if necessary, a reagent containing an asymmetric center is known absolute configuration.

If you want, racemic mixtures of compounds can be divided in such a way as to highlight the individual enantiomers. The separation can be performed by methods well known in this field, such as the transformation of enantiomeric mixtures of compounds I in diastereomer mixture, for example, interaction with the chiral auxiliary substance, such as chiral acid or base, followed by separation of the individual diastereomers by standard methods, such as fractional crystallization or chromatography. The enantiomeric mixture of compounds is also possible to directly separate chromatographic methods using chiral stationary phases, such methods are well known in this field. Alternatively, any enantiomer of a compound can be obtained stereoselective synthesis using optically pure starting compounds or reagents of known configuration of ways, well known in this field.

The term "pharmaceutically acceptable salt" refers to a cationic or anionic salts of the compounds, where the counterion derived from pharmaceutically acceptable non-toxic bases or acids including inorganic or organic bases and inorganic or organic acids.

When the compound of formula I is an acid, salts can be obtained from pharmaceutically acceptable non-toxic bases, including inorganic and organic bases. Salts derived from inorganic bases include salts, where the counterion is an ion of aluminum, ammonium, calcium, copper, ferric, ferrous is elesa, lithium, magnesium, trivalent manganese, divalent manganese, potassium, sodium, zinc and the like. Especially preferably represents ammonium, calcium, magnesium, potassium and sodium. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary and tertiary amines, substituted amines, including substituted amines of natural origin, cyclic amines and basic ion-exchange resin, such as arginine, betaine, caffeine, choline, dibenziletilendiaminom, diethylamin, 2-Diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, Ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, geranamine, Isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, Tripropylamine, tromethamine and the like.

When the compound of the present invention has a main character, salts can be obtained from pharmaceutically acceptable non-toxic acids, including inorganic and organic acids. Such acids include acetic, benzosulfimide, benzoic, camphorsulfonic, lemon, econsultancy, fumaric, gluconic, glutamic, Hydrobromic, hydrochloric, isetionate, lactic, maleic, malic, mandelbug methansulfonate, mucus, nitrogen, pambou, Pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluensulfonate acid and the like. Particularly preferred are citric, Hydrobromic, hydrochloric, maleic, phosphoric, sulfuric, fumaric, and tartaric acid. It is clear that used in this description, references to the compounds of formula I also mean the inclusion of pharmaceutically acceptable salts.

The compounds of formula I and their salts in solid form can exist in more than one crystal structure (polymorphism) and may also be in the form of a hydrate or other solvate. The present invention includes any polymorph of compound I or its salt or any hydrate or other MES.

Organic fragments, contained in the above notation symbols, are - like the term halogen - aggregate terms for individual listings of the individual group members. The prefix Cn-Cmindicates in each case the possible number of carbon atoms in the group.

The term "halogen" means, in each case fluorine, bromine, chlorine or iodine, in particular fluorine, chlorine or bromine.

Used in this description, the term "alkyl" and the alkyl fragments alkoxyalkyl, alkylamino, dialkylamino and alkylsulfonyl means in each case alkyl group with unbranched or R is Svetlanas chain having usually from 1 to 8 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms. Examples of alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylbutane, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-heptyl, 1-etylhexyl, 2-etylhexyl, 3-etylhexyl, 4-etylhexyl, 5-methylhexan, 1-ethylphenyl, 2-ethylphenyl, 3-ethylphenyl, 1-propylpentyl, n-octyl, 1-metrotel, 2-methylheptan, 1-ethylhexyl, 2-ethylhexyl, 1,2-diethylhexyl, 1-propylpentyl and 2-propylpentyl.

Used in this description, the term "halogenated" and halogenating fragments halogenallylacetic means in each case the alkyl group with an unbranched or branched chain, having usually from 1 to 8 carbon atoms, frequently from 1 to 6 carbon atoms, where the hydrogen atoms of this group are partially or completely replaced by halogen atoms. Preferred halogenoalkane fragments selected from C1-C4halogenoalkane, more p is edocfile from C 1-C2halogenoalkane, in particular, from1-C2foralkyl, such as vermeil, deformity, trifluoromethyl, 1-foretel, 2-foretel, 2,2-dottorati, 2,2,2-triptorelin, pentafluoroethyl or1-C4foralkyl, such as vermeil, deformity, trifluoromethyl, 1-foretel, 2-foretel, 2,2-dottorati, 2,2,2-triptorelin, pentafluoroethyl, 2-fluoro-1-methylethyl, 2,2-debtor-1-methylethyl, 2,2,2-Cryptor-1-methylethyl, 2,2,2-Cryptor-1-trifloromethyl, 3,3,3-cryptochromes, 4,4,4-triptorelin and the like.

Used in this description, the term "alkylene" means a saturated divalent landiolol group with unbranched or branched chain, having usually from 1 to 5 carbon atoms, examples including methylene, 1,1-ethylene (1,1-ethandiyl), 1,2-ethylene (1,2-ethandiyl), 1,1-propanediyl, 1,2-propanediyl, 2,2-propanediyl, 1,3-PROPANEDIOL, 1,1-butandiol, 1,2-butandiol, 1,3-butandiol, 1,4-butandiol, 2,3-butandiol, 2,2-butandiol. Used in this description, the term "C1-C5alkylene" means, preferably, the divalent landiolol group with a non-branched chain, having from 1 to 5 carbon atoms, examples including methylene, 1,2-ethylene, 1,3-propandiol, 1,4-butandiol or 1.5-pentandiol.

Used in this description, the term "albaniles" means landiolol group with unbranched or branched chain, having usually is 2 to 5 carbon atoms and containing unsaturated ethylene double bond, examples include 1,2-ethandiyl, 1,3-propandiol, 1-butene-1,4-diyl, 2-butene-1,4-diyl, 1-penten-1,5-diyl, 2-penten-1,5-diyl etc.

Used in this description, the term "alkoxy" means in each case the alkyl group with an unbranched or branched chain, which is linked via an oxygen atom and is usually from 1 to 8 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms. Examples of alkoxygroup are methoxy, ethoxy, n-propoxy, ISOProx, n-butoxy, 2-butoxy, isobutoxy, tert-butoxy, pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3 methylbutoxy, 2,2-dimethylpropylene, 1 ethylpropoxy, hexyloxy, 1,1-dimethylpropyl, 1,2-dimethylpropylene, 1 methylpentylamino, 2-methylpentylamino, 3 methylpentane, 4-methylpentane, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,2-dimethylbutylamino, 2,3-dimethylbutylamino, 3,3-dimethylbutylamino, 1-ethylbutyrate, 2-ethylbutylamine, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyloxy, 1-ethyl-2-methylpropyloxy, n-heptyloxy, 1 methylhexanoic, 2-methylhexane, 3 methylhexane, 4-methylhexane, 5-methylhexane, 1 ethylpentane, 2-ethylpentane, 3 ethylpentane, 1 propylpentanoic, n-octyloxy, 1 methylacrylate, 2-methylheptane, 1 ethylhexyloxy, 2-ethylhexyloxy, 1,2-dimethylhexylamine, 1 propylpentanoic is 2-propylpentanoic.

Used in this description, the term "halogenoalkane" means in each case alkoxygroup with unbranched or branched chain, having from 1 to 8 carbon atoms, frequently from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, where the hydrogen atoms of this group are partially or completely replaced by halogen atoms, especially fluorine atoms. The preferred halogenoalkane fragments include1-C4halogenoalkane, in particular With1-C2feralcode, such as formatosi, deformedarse, triptoreline, 1 floratone, 2-floratone, 2,2-diflorasone, 2,2,2-triptoreline, 2-chloro-2-floratone, 2-chloro-2,2-diflorasone, 2,2-dichloro-2-floratone, 2,2,2-trichloroethane, pentaborate and the like.

Used in this description, the term "cycloalkyl" and cycloalkyl fragments With3-C6cycloalkylation means in each case mono - or bicyclic cycloaliphatic radical having usually from 3 to 8 C-atoms or 3 to 6 C-atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2,1,1]hexyl, bicyclo[3,1,1]heptyl, bicyclo[2,2,1]heptyl and bicyclo[2,2,2]octyl.

As used in this description, the term "alkenyl" means, in each case singly unsaturated hydrocarbon radical having 2, 3, 4, 5, 6, 7 or 8 C-atoms, for example inil, allyl (2-propen-1-yl), 1-propen-1-yl, 2-propen-2-yl, methallyl (2-methylprop-2-EN-1-yl), 2-butene-1-yl, 3-butene-1-yl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-EN-1-yl, 2-aterproof-2-EN-1-yl and the like.

Used in this description, the term "quinil" means, in each case singly unsaturated hydrocarbon radical having usually 2, 3, 4, 5, 6, 7 or 8 C-atoms, such as ethinyl, propargyl (2-propyne-1-yl), 1-propyne-1-yl, 1-methylprop-2-in-1-yl), 2-butyn-1-yl, 3-buten-1-yl, 1-pentyn-1-yl, 3-pentyn-1-yl, 4-pentyn-1-yl, 1-methylbut-2-in-1-yl, 1-aterproof-2-in-1-yl and the like.

The term "5 - or 6-membered heterocyclic radicals, including the ring 2 or 3 heteroatoms selected from N, O or S" includes saturated, unsaturated and aromatic radicals (=heteroaryl)(=hetaryl).

Used in this description, the term "heteroaryl" means in each case heterocyclic radical selected from the group consisting of monocyclic 5 - or 6-membered heteroaromatic radicals, including the ring 1, 2 or 3 heteroatoms selected from N, O and S. Examples of 5 - or 6-membered heteroaromatic radicals include pyridyl, i.e. the 2-, 3 - or 4-pyridyl, pyrimidyl, i.e. the 2-, 4 - or 5-pyrimidinyl, pyrazinyl, pyridazinyl, i.e. the 3 - or 4-pyridazinyl, thienyl, ie 2- or 3-thienyl, furyl, i.e. the 2 - or 3-furyl, pyrrolyl, i.e. the 2 - or 3-pyrrolyl, oxazolyl, i.e. the 2-, 3 - or 5-oxazolyl, isaxis is poured, ie, 3-, 4 - or 5-isoxazolyl, thiazolyl, ie 2, 3 or 5 thiazolyl, isothiazolin, i.e. the 3-, 4 - or 5-isothiazole, pyrazolyl, i.e. the 1-, 3-, 4 - or 5-pyrazolyl, i.e. the 1-, 2-, 4 - or 5-imidazolyl, oxadiazolyl, for example 2 - or 5-[1,3,5]oxadiazolyl, 4 - or 5-(1,2,3-oxadiazol)yl, 3 - or 5-(1,2,4-oxadiazol)yl, 2 - or 5-[1,3,4]oxadiazolyl, 4 - or 5-(1,2,3-oxadiazol)yl, 3 - or 5-(1,2,4-oxadiazol)yl, 2 - or 5-(1,3,4-thiadiazole)Il, thiadiazolyl, for example 2 - or 5-(1,3,4-thiadiazole)yl, 4 - or 5-(1,2,3-thiadiazole)yl, 3 - or 5-(1,2,4-thiadiazole)Il, triazolyl, for example, 1H-, 2H or 3H-1,2,3-triazole-4-yl, 2H-triazole-3-yl, 1H-, 2H or 4H-1,2,4-triazolyl and tetrazolyl, i.e. 1H - or 2H-tetrazolyl.

Examples of 5 - or 6-membered heteroaromatic ring fused with the phenyl ring or 5 - or 6-membered heteroaromatic radical, include benzofuranyl, benzothiazol, indolyl, indazoles, benzimidazoles, benzoxadiazole, benzoxadiazole, benzothiadiazole, benzoxazines, chinoline, ethenolysis, purinol, 1,8-naphthyridin, pteridyl, pyrido[3,2-d]pyrimidyl or predominatly and the like. Such condensed heteroaryl radicals can be linked to the rest of the molecule through any atom of the ring is 5 - or 6-membered heteroaromatic ring or via a carbon atom condensed phenyl part.

Saturated or unsaturated 5 - or 6-membered heterocyclic rings include saturated is whether unsaturated, non-aromatic heterocyclic ring. Examples include di - and tetrahydrofuranyl, pyrrolyl, pyrrolidinyl, oxopyrrolidin, pyrazolines, pyrazolidine, imidazoline, imidazolidine, oxazoline, oxazolidine, oxoacridine, isoxazolyl, isoxazolidine, piperidine, piperazinil, morpholinyl, thiomorpholine, Osotimehin, diocletianopolis and the like.

The term chemical bond used in the designation of X and Y should be understood as a covalent bond (single bond).

The preferred implementation of the present invention relates to compounds of formula I where Ar is a phenyl ring, and their pharmaceutically acceptable salts and tautomers. In other embodiments of the invention Ar is a 5 - or 6-membered aromatic heterocycle, as defined above.

The preferred implementation of the present invention relates to compounds of formula I, where X represents O, S, S(O)2, NH or NRxin particular O, NH or NRxand their pharmaceutically acceptable salts and tautomers.

Among such compounds, where X represents NRxthe radical Rxpreferably selected from the group consisting of C1-C6of alkyl, C1-C4halogenoalkane,1-C4alkoxy-C1-C4the alkyl, the 3-C6cycloalkyl,3-C6cycloalkenyl, benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, and radical SO2-Rx5where Rx5is the same as defined above. Rx5preferably selected from C1-C4of alkyl, C1-C4-foralkyl, in particular CH2CF3A 5 - or 6-membered heteroaryl, which may contain a condensed benzene ring, in particular pyridyl, pyrimidinyl and chinoline, and phenyl, which is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. Among the preferred compounds of the compounds of formula I where the radical Rxand radical SO2-Rx5where Rx5such as defined above. Also preferred are the compounds of formula I where the radical Rxrepresents a C1-C6alkyl, C1-C4halogenated,1-C4alkoxy-C1-C4alkyl, C3-C6cycloalkyl,3-C6the CEC is valkilmer or benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

In the preferred embodiment, where X represents NHC(O), nitrogen atom may be attached either to a or to Ar.

Preferably, Y is selected from O, S, S(O)2, NH or chemical bonding. The preferred implementation of the present invention relates to compounds of formula I, where Y is a chemical bond, and to their pharmaceutically acceptable salts and tautomers. In another embodiment, Y is selected from the group consisting of O, S, S(O)2and NH. In another such embodiment, i.e. Y represents O, S, S(O)2or NH, X preferably represents a covalent bond.

The preferred implementation of the present invention relates to compounds of formula I, where a is a CRaRbwhere Raand Rbindependently from each other selected from hydrogen, halogen, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, Rbalso may be IT, if Rarepresents hydrogen, C1-C4alkyl or C 1-C4halogenated. Preferably, Raand Rbselected independently of one another from the group consisting of hydrogen, fluorine, methyl, ethyl and methoxy. In particular, Raand Rbrepresent hydrogen, i.e. a represents a CH2.

The preferred implementation of the present invention relates to compounds of formula I where Het is a 5-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where the 5-membered heteroaromatic ring may have a first Deputy R10and optionally 1 or 2 additional substituent R11, R12. Het, in particular, represents a heterocyclic radical selected from Furie, pyrrolyl, teinila, pyrazolyl, thiazolyl, benzothiazolyl, oxazolyl, isoxazolyl, isothiazoline, pyrazolyl, triazolyl and imidazolyl, where the heterocyclic radicals may be the first Deputy R10and optionally 1 or 2 additional substituent R11, R12provided that X represents NH or NRxif Het represents imidazolyl or benzimidazolyl, which may have first Deputy R10and optionally 1 or 2 additional substituent R11, R12. In most predpochtitel the om embodiment of the invention Het in formula I represents pyrazolyl, in particular 4-pyrazolyl, which may have first Deputy R10and additionally may have an additional substituent R11.

In the preferred embodiment of the invention, Het is a radical of the following formula (Het-1)-(Het-7), in particular the following formula (Het-1)-(Het-4):

where R10arepresents hydrogen or has one of the meanings given for R10, R11arepresents hydrogen or one of the meanings given for R11and where the * indicates the location of the joining part Y. In particular, R11arepresents hydrogen. In particular, R10adifferent from hydrogen. Preferably, R10ahas one of the values below as a preferred values for R10. More preferably, R10arepresents a

With1-C8halogenated, in particular, With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical whom or different radicals, selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, and

most preferably,

phenyl, which is unsubstituted or may have 1, 2, 3, 4, or 5 substituents as described above, which are preferably selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular, 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In the first specific embodiment of the present invention R1selected from the group C(=O)-R4C(=O)-OR5, NR6R7C(=O)NR6R7, SO2NR6R7, NR8C(=O)R9, SO2R9and NR8SO2R9where R4, R5, R6, R7, R8and R9are as described in this description. In the first specific embodiment, Ar preferably represents a benzene ring. In the first specific embodiment, R1preferably is in position 3 or 4 of the benzene ring.

<> Among the compounds of the first preferred variant implementation of the preferred compounds where Ar represents a benzene ring, and R1represents C(=O)-R4that is in position 3 or 4 of the benzene ring.

Among the compounds I where R1represents C(=O)-R4concrete option implementation refers to those compounds, where R4selected from the

With3-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, in particular With3-C8of alkyl, C1-C3of alkyl, which is substituted by a radical selected from C1-C4alkoxy or phenyl, which is unsubstituted or substituted as indicated above,

With1-C8halogenoalkane, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl, which is nezame the military or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, in particular of furil, teinila, oxazolyl, thiazolyl, isoxazolyl, isothiazole, 1,2,4-triazolyl, 1,2,3-triazolyl, pyridyl, pyrimidinyl or pyrazinyl where heteroaryl is unsaturated or has 1, 2, 3 or 4 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

Among the compounds I where R1represents C(=O)-R4another particular implementation relates to compounds, where R4together with R2forms With1-C5alkalinity or2-C5alkenylamine fragment, in particular ethane-1,2-dilny or propane-1,2-dilny fragment, where one CH2part may be replaced by oxygen, sulfur or N-R4c-part of, and where C1-C5alkylene and C2-C5albaniles (and ethane-1,2-dilny and propane-1,3-dilny fragment) may be unsubstituted or have 1, 2, 3 or 4 radicals, in particular 0, 1 or 2 radicals selected from halogen, CN, OH, NH With1-C4of alkyl, in particular methyl,3-C6cycloalkyl, in particular cyclopropyl, cyclobutyl or cyclopentyl,1-C4halogenoalkane, in particular diformate or trifloromethyl,1-C4alkylamino, such as methylamino, ethylamino, di(C1-C4alkyl)amino, such as dimethylamino, diethylamino,1-C4alkoxy, such as methoxy or ethoxy, and C1-C4halogenoalkane, such as deformedarse or triptoreline, and where R4cso, as specified in this description. In one embodiment, R4cselected from hydrogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. Preferably, R4cselected from hydrogen, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,3-C6cycloalkylation and benzyl, where the phenyl ring is unsubstituted or may have a Deputy selected from halogen, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4cselected from hydrogen, methyl, ethyl, 2-bromacil, 2,2-deperately, 2,2,2-triptoreline, n-propyl, 3,3,3-cryptochrome, n-butyl, 4,4,4-trifloromethyl, 3-methylbutyl, 2-trifloromethyl, 2-methylprop is a, cyclopentylmethyl, cyclohexylmethyl, benzyl, 4-trifloromethyl and phenyl.

Among the compounds of the first concrete option implementation also preferred are such compounds where Ar is a benzene ring and R1represents C(=O)-OR5that is in position 3 or 4 of the benzene ring. R5preferably represents C1-C4alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl or benzyl.

Among the compounds of the first concrete option implementation also preferred are such compounds where Ar is a benzene ring and R1represents NR6R7that is in position 3 or 4 of the benzene ring. In the radical NR6R7R6represents preferably hydrogen, C1-C4alkyl, C1-C4alkoxy, Cho, or C(O)-C1-C4alkyl, such as acetyl or propionyl. R7represents preferably hydrogen or C1-C4alkyl. Preferred compounds where the fragment NR6R7forms a radical piperidine-1-yl, pyrrolidin-1-yl, morpholine-4-yl, piperazine-1-yl or 4-methylpiperazin-1-yl.

Among the compounds of the first concrete option implementation also preferred are such compounds where Ar, not only is em a benzene ring and R 1represents C(=O)NR6R7that is in position 3 or 4 of the benzene ring. In the radical C(=O)NR6R7R6represents preferably hydrogen, C1-C4alkyl or C1-C4alkoxy. R7represents preferably hydrogen or C1-C4alkyl. Preferred compounds where the fragment NR6R7forms a radical piperidine-1-yl, pyrrolidin-1-yl, morpholine-4-yl, piperazine-1-yl or 4-methylpiperazin-1-yl.

Among the compounds of the first concrete option implementation also preferred are such compounds where Ar is a benzene ring and R1represents the SO2NR6R7that is in position 3 or 4 of the benzene ring. In the radical SO2NR6R7R6preferably represents hydrogen, C1-C4alkyl or C1-C4alkoxy. R7represents preferably hydrogen or C1-C4alkyl. Preferred compounds where the fragment NR6R7forms a radical piperidine-1-yl, pyrrolidin-1-yl, morpholine-4-yl, piperazine-1-yl or 4-methylpiperazin-1-yl.

Among the compounds of the first concrete option implementation also preferred are such compounds where Ar is a benzene ring and R 1represents NR8C(=O)R9that is in position 3 or 4 of the benzene ring. In the radical NR8C(=O)R9R8represents, preferably, hydrogen. R9preferably selected from the group consisting of

hydrogen

With1-C8of alkyl, which is unsaturated or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, in particular With1-C4of alkyl, C1-C4of alkyl, which is substituted by a radical selected from C1-C4alkoxy or phenyl, which is unsubstituted or substituted as above,

With1-C8halogenoalkane, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2al is hydroxy, diformate, trifloromethyl, deformedarse, triptoreline,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, in particular of furil, teinila, oxazolyl, thiazolyl, isoxazolyl, isothiazole, 1,2,4-triazolyl, 1,2,3-triazolyl, pyridyl, pyrimidinyl or pyrazinyl where heteroaryl is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

Among the compounds of the first concrete option implementation also preferred are such compounds where Ar is a benzene ring and R1represents NR8SO2R9that is in position 3 or 4 of the benzene ring. In the radical NR8SO2R9R8represents, preferably, hydrogen. R9preferably selected from the group consisting of

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1- 2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, in particular With1-C4of alkyl, C1-C4of alkyl, which is substituted by a radical selected from C1-C4alkoxy or phenyl, which is unsubstituted or substituted as above,

With1-C8halogenoalkane, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse or triptoreline,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, in particular of furil, teinila, oxazolyl, thiazolyl, isoxazolyl, isothiazole, 1,2,4-triazolyl, 1,2,3-triazolyl, pyridyl, pyrimidinyl or pyrazinyl where heteroaryl is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

Among the compounds of the first competitive advantage is to maintain the option exercise also preferred such compounds, where Ar represents a benzene ring, and R1represents the SO2R9that is in position 3 or 4 of the benzene ring. In the radical SO2R9R9preferably selected from the group consisting of

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, in particular With1-C4of alkyl, C1-C4of alkyl, which is substituted by a radical selected from C1-C4alkoxy or phenyl, which is unsubstituted or substituted as described above

With1-C8halogenoalkane, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, triforma the sludge, deformedarse, triptoreline,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, in particular of furil, teinila, oxazolyl, thiazolyl, isoxazolyl, isothiazole, 1,2,4-triazolyl, 1,2,3-triazolyl, pyridyl, pyrimidinyl or pyrazinyl where heteroaryl is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In the second specific embodiment of the present invention R1selected from the group Het', O-Het', CH2-Het', CH(CH3)-Het', CH(OH)-Het', S-Het', OCH2-Het, where Het' is a 5 - or 6 - membered saturated, unsaturated or aromatic heterocycle having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where the heterocycle may be unsubstituted or may have 1, 2, 3, or 4 substituent selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. In the second specific embodiment, Ar is preferably a benzene ring and R1preferably is in position 3 or 4 of the benzene ring. The second bound is enom embodiment presents such compounds, where R1represents Het'. Het' represents preferably furyl, thienyl, oxazolyl, thiazolyl, isoxazolyl, isothiazole, 1,2,4-triazolyl, 1,2,3-triazolyl, pyridyl, pyrimidinyl or pyrazinyl.

In the third specific embodiment of the present invention R1selected from the group consisting of

With1-C8alkoxy, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and C3-C8cycloalkyl,

With1-C8halogenoalkane,

With3-C8cycloalkane, where the latter two aforementioned radicals are unsubstituted or have 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

O-phenyl, CH2-phenyl, CH(CH3)phenyl, CH(OH)phenyl, S-phenyl and O-CH2-phenyl, where the phenyl ring in the last six above-mentioned radicals may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

In the third specific embodiment, Ar is preferably a benzene ring and R1preferably is in position 3 or 4 of benzene to which ICA.

In the fourth specific embodiment of the present invention R1and R2linked to adjacent carbon atoms and together with atoms to which they are attached, form a 5 - or 6-membered heterocyclic ring condensed with Ar and having 1, 2 or 3 nitrogen atom in the ring or 1 oxygen atom and optionally a further heteroatom selected from O, S and N, in the ring, and where the condensed heterocyclic ring may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, HE, CN, NH2With1-C4of alkyl, C3-C6cycloalkyl,1-C4alkoxy, C1-C4alkylamino, di(C1-C4alkyl)amino, C1-C4halogenoalkane,1-C4halogenoalkane,1-C4alkylsulfonyl,1-C4halogenallylacetic and phenylsulfonyl, where the phenyl ring may be unsubstituted or may have 1, 2, 3, or 4 substituent selected from halogen, CN, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

In the fourth specific embodiment, Ar is preferably a benzene ring and R1and R2preferably located in positions 3 and 4 of the benzene ring. In particular, R1and R2together the benzene ring to form a bicyclic ring, which is attached to the rest of the molecule through the benzene ring, and a bicyclic ring selected from indolyl, benzimidazolyl, benzimidazolyl, benzoxazolyl and benzothiazolyl, where the bicyclic ring is unsubstituted or substituted as described above.

R2preferably selected from hydrogen, halogen, in particular fluorine or chlorine, C1-C4of alkyl, in particular methyl or ethyl, With1-C4halogenoalkane, in particular trifloromethyl,1-C4alkoxy, in particular methoxy or ethoxy, and C1-C4halogenoalkane, in particular deformedarse or triptoreline.

R3preferably selected from hydrogen, halogen, in particular fluorine or chlorine, C1-C4of alkyl, in particular methyl or ethyl, With1-C4halogenoalkane, in particular trifloromethyl,1-C4alkoxy, in particular methoxy or ethoxy, and C1-C4halogenoalkane, in particular deformedarse or triptoreline. In particular, R3represents hydrogen.

In addition, R10preferably selected from the

halogen-free,

cyano,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical and the different radical, selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

With1-C8alkoxy,

With1-C8halogenoalkane,

With1-C8halogenoalkane,

With3-C8croakily, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With3-C8cycloalkane, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

C(=O)-R13,

C(=O)-OR14,

NR15R16,

C(=O)NR15R16,

SO2R17,

phenyl, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

5 - or 6-membered heteroaryl, in particular oxazolyl, thiazolyl, isoxazolyl, isothiazoline, Piras is Lila, imidazolyl, pyridyl, pyrimidinyl or pyrazinyl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, which is unsubstituted or may have 1, 2 or 3 substituent selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1 or 2 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

R11preferably selected from halogen, in particular fluorine or chlorine, C1-C4of alkyl, in particular methyl or ethyl, With1-C4halogenoalkane, in particular trifloromethyl,1-C4alkoxy, in particular methoxy or ethoxy, and C1-C4halogenoalkane, in particular deformedarse or triptoreline.

R12preferably selected from hydrogen, halogen, in particular fluorine or chlorine, C1-C4of alkyl, in particular methyl or ethyl, With1-C4halogenoalkane, in particular trifloromethyl,1-C4alkoxy, in particular methoxy or ethoxy, and C1-C4halogenoalkane, in particular deformedarse or triptoreline. In particular, R12is missing.

In the radical C(O)R13R13preferably selected from the

With1-C4of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse or triptoreline, in particular With1-C4of alkyl, C1-C4of alkyl, which is substituted by a radical selected from C1-C4alkoxy or phenyl, which is unsubstituted or substituted as above,

With1-C8halogenoalkane, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, in particular, furil,teinila, oxazolyl, thiazolyl, isoxazolyl, isothiazole, 1,2,4-triazolyl, 1,2,3-triazolyl, pyridyl, pyrimidinyl or pyrazinyl where heteroaryl is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In the radical C(=O)-OR14R14represents, preferably, With1-C4alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl or benzyl.

In the radical NR15R16R15represents preferably hydrogen, C1-C4alkyl, C1-C4alkoxy, Cho, or C(O)-C1-C4alkyl, such as acetyl or propionyl. R16represents preferably hydrogen or C1-C4alkyl. Preferred compounds where the fragment NR15R16forms a radical piperidine-1-yl, pyrrolidin-1-yl, morpholine-4-yl, piperazine-1-yl or 4-methylpiperazin-1-yl.

In the radical C(=O)NR15R16R15preferably represents hydrogen, C1-C4alkyl or C1-C4alkoxy. R16represents preferably hydrogen or C1-C4alkyl. Preferred are also compounds, where the radical C(=O)NR15R16group NR15 R16forms a radical piperidine-1-yl, pyrrolidin-1-yl, morpholine-4-yl, piperazine-1-yl or 4-methylpiperazin-1-yl.

In the radical SO2R17R17preferably selected from the

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, in particular With1-C4of alkyl, C1-C4of alkyl, which is substituted by a radical selected from C1-C4alkoxy or phenyl, which is unsubstituted or substituted as described above.

With1-C8halogenoalkane, in particular, With1-C2foralkyl,

phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

The preferred embodiment of the invention relates to compounds of formula I and their tautomers and pharmaceutically acceptable salts, where

Ar represents a benzene number of the TSO,

But a CRaRbwhere Raand Rbindependently from each other selected from hydrogen, halogen, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, Rbalso may be IT, if Rarepresents hydrogen, C1-C4alkyl or C1-C4halogenated,

X represents NH or N-Rxand

Y represents a chemical bond.

Another preferred embodiment of the invention relates to compounds of the formula I, their tautomers and pharmaceutically acceptable salts, where

Ar represents a benzene ring,

But a CRaRbwhere Raand Rbindependently from each other selected from hydrogen, halogen, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, Rbalso may be IT, if Rarepresents hydrogen, C1-C4alkyl or C1-C4halogenated,

X represents Oh,

Y represents a chemical bond,

provided that Het is selected from Furie, pyrrolyl, teinila, pyrazolyl, thiazolyl, benzothiazolyl, oxazolyl, isoxazolyl, isothiazoline, pyrazinyl, pyridazinyl, triazolyl, thiadiazolyl, imides Leila, oxazolone, thiazolyl, tetrahydroaminoacridine, tetrahydropyrimidine, isoindolyl, pyridinyl, phthalazine, naphthyridine, khinoksalinona, chinadoll, oxazolopyridine, triazolopyridine, imidazopyridine, oxazolopyridine, triazolopyridine, cinnoline, pteridine, furazane, benzotriazolyl, pyrazolopyrimidine and naphthyridine, where the above heterocyclic radicals may be the first Deputy R10and optionally 1 or 2 additional substituent R11, R12.

Specific preferred implementation relates to compounds of formula I, where the fragmentrepresents the formulawhere R2, R3and R4are as described above. Among these compounds, particularly preferred compounds where R2and R3represent hydrogen, and R4so, as stated above, preferably selected from C3-C8of alkyl, C1-C4halogenoalkane, in particular With1-C4foralkyl,3-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4, and 5 identical or different radicals, selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4represents a C3-C8alkyl, C1-C3alkyl, which is substituted by a radical selected from C1-C4alkoxy and C3-C6cycloalkyl or1-C4halogenated, in particular With1-C4foralkyl.

Similarly, the preferred compounds of this particularly preferred variant implementation, where R3represents hydrogen and R4together with R2form1-C5alkalinity or2-C5alkenylamine fragment, in particular ethane-1,2-dilny fragment, ethen-1,2-dilny fragment, 1,3-provincially fragment or propane-1,3-dilny fragment, where one CH2part may be replaced by oxygen, sulfur or N-R4c-part of, and where C1-C5alkylene and C2-C5albaniles (and similarly, ethane-1,2-dilny fragment, ethen-1,2-dilny fragment, 1,3-provincially fragment and propane-1,3-dilny fragment) can be unsubstituted or have 1, 2, 3 or 4 radicals, in particular 0, 1 or 2 radicals selected from halogen, CN, OH, NH2With1-C4of alkyl, in particular methyl,3-C6cycloalkyl, in particular cyclopropyl, cyclobutyl or Cyclops is ntila, With1-C4halogenoalkane, in particular diformate or trifloromethyl,1-C4alkylamino, such as methylamino, ethylamino, di(C1-C4alkyl)amino, such as dimethylamino, diethylamino,1-C4alkoxy, such as methoxy or ethoxy, and C1-C4halogenoalkane, such as deformedarse or triptoreline, and where R4cso, as specified in this description. Preferably, R4cselected from C1-C6of alkyl, which is unsubstituted or is alkoxy or halogenoacetyl, in particular With1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,3-C6cycloalkylation and benzyl, where the phenyl ring is unsubstituted or has a Deputy selected from halogen, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4cselected from methyl, ethyl, 2-bromacil, 2,2-deperately, 2,2,2-triptoreline, n-propyl, 3,3,3-cryptochrome, n-butyl, 4,4,4-trifloromethyl, 3-methylbutyl, 2-trifloromethyl, 2-methylpropyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and 4-trifloromethyl.

More preferred compounds of this specific preferred option exercise, where the fragmentrepresents the formula where R3and R4care as defined above, and Q represents-C(RQ1RQ2)-, -C(RQ1RQ2)-C(RQ3RQ4)- or-C(RQ1)=C(RQ2)-, where RQ1, RQ2, RQ3, RQ4each independently from each other selected from hydrogen, halogen, CN, OH, NH2C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkylamino, di(C1-C4alkyl)amino, C1-C4alkoxy and C1-C4halogenoalkane. Preferably, Q represents-C(RQ1RQ2)-. Preferably, RQ1, RQ2, RQ3, RQ4each independently from each other selected from hydrogen, halogen, C1-C4of alkyl, C3-C6cycloalkyl and C1-C4halogenoalkane. In particular, Q is a CH2CH2CH2or CH=CH, preferably CH2. More preferably, R3represents hydrogen.

In such preferred embodiments, the implementation of Het, Rx, R1, R2and R3are as defined above, and are, preferably, one of the values of the data as the preferred values.

In such preferred embodiments, the implementation of the Het is particularly preferably 5-membered heteroaromatics, having 1, 2 or 3 heteroatoms in the ring, where the 5-membered heteroaromatic ring may have a first Deputy R10and optionally 1 or 2 additional substituent R11, R12where R10, R11and R12are as defined above, and are, preferably, one of the values of data in the form of preferred values.

Thus, a particular preferred implementation of the present invention relates to compounds of the formula Ia and their pharmaceutically acceptable salts and tautomers.

In the formula Ia, X, Ra, Rb, Het, Rx, R1, R2and R3are as defined herein, and preferably have one of the values of data in the form of preferred values. Preferably, X in formula Ia represents NH or N-Rx. In the formula Ia X can also be preferably About if Het is selected from Furie, pyrrolyl, teinila, pyrazolyl, thiazolyl, benzothiazolyl, oxazolyl, isoxazolyl, isothiazoline, pyrazinyl, pyridazinyl, triazolyl, thiadiazolyl, imidazolyl, oxazolyl, thiazolyl, tetrahydroaminoacridine, tetrahydropyrimidine, isoindolyl, pyridinyl, phthalazine, naphthyridine, khinoksalinona, chinadoll, oxazolopyridine, triazolopyridine, imidazo is ridazine, oxazolopyridine, triazolopyridine, cinnoline, pteridine, furazane, benzotriazolyl, pyrazolopyrimidine and naphthyridine, where the above heterocyclic radicals may be the first Deputy R10and optionally 1 or 2 additional substituent R11, R12.

Preferably, Raand Rbselected independently of one another from the group consisting of hydrogen, fluorine, methyl, ethyl and methoxy. In particular, Raand Rbrepresent hydrogen.

Among the compounds of the compounds Ia, where X represents NRxthe radical Rxpreferably selected from the group consisting of C1-C6of alkyl, C1-C4halogenoalkane,1-C4alkoxy-C1-C4of alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl, benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, and radical SO2-Rx5where Rx5is the same as defined above. Rx5preferably selected from C1-C4of alkyl, C1-C4-foralkyl, in particular CH2CF3A 5 - or 6-membered heteroaryl, the which may contain a condensed benzene ring, in particular pyridyl, pyrimidinyl and chinoline, and phenyl, which is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. Among the compounds preferably the compound of formula Ia, where the radical Rxthe radical SO2-Rx5where Rx5is the same as defined above. Similarly, preferred are the compounds of formula Ia, where the radical Rxrepresents a C1-C6alkyl, C1-C4halogenated,1-C4alkoxy-C1-C4alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl or benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals, selected halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

The preferred implementation of the present invention relates to compounds of formula Ia, where Het represents a 5-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms in the ring, where the 5-membered heteroaromatic ring may have a first Deputy R10and additionally may have 1 or 2 to ovocny Deputy R 11, R12. Het, in particular, represents a heterocyclic radical selected from Furie, pyrrolyl, teinila, pyrazolyl, thiazolyl, benzothiazolyl, oxazolyl, isoxazolyl, isothiazoline, pyrazolyl, triazolyl and imidazolyl, where the heterocyclic radicals may be the first Deputy R10and optionally 1 or 2 additional substituent R11, R12and X represents NH or NRxif Het represents imidazolyl or benzimidazolyl, which may have first Deputy R10and optionally 1 or 2 additional substituent R11, R12. In a more preferred embodiment, compounds of the formula Ia Het is a radical of formula (Het-1)-(Het-7), in particular of the formula Het-1, Het-2, Het-3 and Het-4, as described above, where R10aand R11ahave the meanings given above, in particular the preferred meanings. In the preferred embodiment of the invention Het in formula Ia represents pyrazolyl, in particular 4-pyrazolyl, which may have first Deputy R10and additionally may have an additional substituent R11. More preferably, Het is a radical of formula (Het-1)-(Het-4), as defined above, where R10aand R11ahave the meanings given above, in particular the preferred mn of the treatment.

Among the compounds of formula Ia are particularly preferred such compounds, where the fragmentrepresents the formulawhere R2, R3and R4are as defined above. Among these compounds, particularly preferred compounds where R2and R3represent hydrogen and R4is as defined above and preferably selected from C3-C8of alkyl, C1-C4halogenoalkane, in particular With1-C4-foralkyl,3-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4represents a C3-C8alkyl, C1-C3alkyl, which is substituted by a radical selected from C1-C4alkoxy and C3-C6cycloalkyl or1-C4halogenated, in particular With1-C4foralkyl.

Similarly, the preferred compounds of formula Ia, where R3represents hydrogen and R4in the natural with R 2form1-C5alkalinity or2-C5alkenylamine fragment, in particular ethane-1,2-dilny fragment, ethen-1,2-dilny fragment, 1,3-provincially fragment or propane-1,3-dilny fragment, where one CH2part may be replaced by oxygen, sulfur or N-R4c-part of, and where C1-C5alkylene and C2-C5albaniles (and similarly, ethane-1,2-dilny fragment, ethen-1,2-dilny fragment, 1,3-provincially fragment and propane-1,3-dilny fragment) may be unsubstituted or have 1, 2, 3 or 4 radicals, in particular 0, 1 or 2 radicals selected from halogen, CN, OH, NH2With1-C4of alkyl, in particular methyl,3-C6cycloalkyl, in particular cyclopropyl, cyclobutyl or cyclopentyl,1-C4halogenoalkane, in particular diformate or trifloromethyl,1-C4alkylamino, such as methylamino, ethylamino, di(C1-C4alkyl)amino, such as dimethylamino, diethylamino,1-C4alkoxy, such as methoxy or ethoxy, and C1-C4halogenoalkane, such as deformedarse or triptoreline, and where R4cis the same as defined above. Preferably, R4cselected from C1-C6of alkyl, which is unsubstituted or is alkoxy or halogenoacetyl, in particular With1-C4 alkyl, C3-C6cycloalkyl,1-C4halogenated,3-C6cycloalkylation and benzyl, where the phenyl ring is unsubstituted or may have a Deputy selected from halogen, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4cselected from methyl, ethyl, 2-bromacil, 2,2-deperately, 2,2,2-triptoreline, n-propyl, 3,3,3-cryptochrome, n-butyl, 4,4,4-trifloromethyl, 3-methylbutyl, 2-trifloromethyl, 2-methylpropyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and 4-trifloromethyl.

More preferred compounds of formula Ia, where the fragmentrepresents the formulawhere R3and R4care as defined above, and Q represents-C(RQ1RQ2)-, -C(RQ1RQ2)-C(RQ3RQ4)- or-C(RQ1)=C(RQ2)-, where RQ1, RQ2, RQ3, RQ4each independently from each other selected from hydrogen, halogen, CN, OH, NH2With1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkylamino, di(C1-C4alkyl)amino, C1-C4alkoxy and C1-C4halogenoalkane. Preferably, Q represents-C(RQ1RQ2)-. Preferably, RQ1, RQ2, RQ , RQ4each independently from each other selected from hydrogen, halogen, C1-C4of alkyl, C3-C6cycloalkyl and C1-C4halogenoalkane. In particular, Q is a CH2CH2CH2or CH=CH, preferably CH2. More preferably, R3represents hydrogen.

A particular preferred implementation of the present invention relates to compounds of the formula I.1, their isomers of formula I.2, I.3 and I.4 and to their pharmaceutically acceptable salts:

In the formulae I.1, I.2, I.3 and I.4 X, A, Y, R1, R2and R3are as described herein, and are, preferably, one of the values of data in the form of preferred values. R10arepresents hydrogen or has one of the meanings given for R10, R11arepresents hydrogen or has one of the meanings given for R11.

In particular, R10aselected from the

hydrogen

halogen-free,

cyano,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or R is slichnih radical, selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

With1-C8alkoxy,

With1-C8halogenoalkane,

With1-C8halogenoalkane,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With3-C8cycloalkane, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

C(=O)-R13,

C(=O)-OR14,

NR15R16,

C(=O)NR15R16,

SO2R17,

phenyl, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

5 - or 6-membered heteroaryl, in particular of furil, teinila, oxazolyl, thiazolyl, isoxazolyl from thiazolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl or pyrazinyl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, which is unsubstituted or may have 1, 2 or 3 substituent selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1 or 2 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

More preferably, R10arepresents a

With1-C8halogenated, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse and triptorelin and, and

more preferably,

phenyl, which is unsubstituted or may have 1, 2, 3, 4, or 5 substituents as described above, which are preferably selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In particular, R11arepresents hydrogen or a C-linked moiety, which is preferably selected from CN, C1-C4of alkyl, C1-C4halogenoalkane and phenyl, which is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. More preferably, R11arepresents hydrogen.

R10aand R11atogether with the atoms to which they are attached may also form a condensed pyridine or pyrimidine ring, which is unsubstituted or may have 1, 2 or 3 substituent selected from halogen, CN, IT,1-C4al the sludge, With3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1 or 2 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

A particular preferred implementation of the present invention relates to compounds of the formulae I.1, I.2, I.3 and I.4, where X represents NH or NRxand their pharmaceutically acceptable salts.

Another particular preferred implementation of the present invention relates to compounds of the formulae I.1, I.2, I.3 and I.4, where X represents Oh, and to their pharmaceutically acceptable salts.

Such compounds of the formulae I.1, I.2, I.3 and I.4, where X represents NRxthe radical Rxpreferably selected from the group consisting of C1-C6of alkyl, C1-C4halogenoalkane,1-C4alkoxy-C1-C4of alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl, benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1- 4halogenoalkane, and radical SO2-Rx5where Rx5is the same as defined above. Rx5preferably selected from C1-C4of alkyl, C1-C4-foralkyl, in particular CH2CF3A 5 - or 6-membered heteroaryl, which may contain a condensed benzene ring, in particular pyridyl, pyrimidinyl and chinoline, and phenyl, which is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. Among the compounds preferably a compound of formulas I' and I", where the radical Rxthe radical SO2-Rx5where Rx5is the same as defined above. Similarly, preferred are compounds of formulas I' and I”, where the radical Rxrepresents a C1-C6alkyl, C1-C4halogenated,1-C4alkoxy-C1-C4alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl or benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

the Preferred implementation of the present invention relates to compounds of formula I.1, I.2, I.3 and I.4, where Y is a chemical bond, and to their pharmaceutically acceptable salts.

The preferred implementation of the present invention relates to compounds of the formulae I.1, I.2, I.3 and I.4, where a is a CRaRbwhere Raand Rbindependently from each other selected from hydrogen, halogen, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, Rbalso may be IT, if Rarepresents hydrogen, C1-C4alkyl or C1-C4halogenated. Preferably, Raand Rbselected independently of one another from the group consisting of hydrogen, fluorine, methyl, ethyl and methoxy. In particular, Raand Rbrepresent hydrogen, i.e. a represents a CH2.

Thus, a particular preferred implementation of the present invention relates to compounds of the formula Ia.1, their isomers Ia.2, Ia.3 and Ia.4 and to their pharmaceutically acceptable salts:

In the formulae Ia.1, Ia.2, Ia.3 and Ia.4 Raand Rbare as defined for formula Ia, and have, preferably, one of the values of data in the form of preferred C is acini. X has the meanings as defined above, and preferably O, NH or N-Rxin particular, O or NH. Rx, R1, R2and R3have the meanings as defined above, and are, preferably, one of the values of data in the form of preferred values. R10aand R11have the meanings as defined for formula Ia.2, Ia.3 and Ia.4. In particular, R10aand R11aindependently of one another have one of the meanings given for formula I' and I", in the form of preferred values.

Preferably, Raand Rbin the formulae Ia.1, Ia.2, Ia.3 and Ia.4 selected independently of one another from the group consisting of hydrogen, fluorine, methyl, ethyl and methoxy. In particular, Raand Rbrepresent hydrogen.

Such compounds of the formulae Ia.1, Ia.2, Ia.3 and Ia.4, where X represents NRxthe radical Rxpreferably selected from the group consisting of C1-C6of alkyl, C1-C4halogenoalkane,1-C4alkoxy-C1-C4of alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl, benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, and radical SO2-Rx5, R x5is the same as defined above. Rx5preferably selected from C1-C4of alkyl, C1-C4-foralkyl, in particular CH2CF3A 5 - or 6-membered heteroaryl, which may contain a condensed benzene ring, in particular pyridyl, pyrimidinyl and chinoline, and phenyl, which is unsubstituted or has 1, 2, 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. Among the compounds preferably a compound of the formulae Ia.1, Ia.2, Ia.3 and Ia.4, where the radical Rxthe radical SO2-Rx5where Rx5is the same as defined above. Similarly, preferred are compounds of formulas Ia' and Ia", where the radical Rxrepresents a C1-C6alkyl, C1-C4halogenated,1-C4alkoxy-C1-C4alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl or benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

Particularly preferred variant implementation and the attainment relates to compounds of formula I.1, I.2, I.3 and I.4, Ia.1, Ia.2, Ia.3 and Ia.4 and to their pharmaceutically acceptable salts and tautomers, where R1represents a radical C(O)R4that is in position 3 or, in particular, in position 4 of the benzene ring.

Thus, particularly preferred implementation of the present invention relates to compounds of the formula I.1.a, I.2.a, I.3.a and I.4.a:

And, in particular, to compounds of formula Ia.1.a, Ia.2.a, Ia.3.a and Ia.4.a

and their pharmaceutically acceptable salts.

In the formula I.1.a, I.2.a, I.3.a and I.4.a symbols X, A, Y, R2, R3and R4are as defined herein, and have, preferably, one of the values of data in the form of preferred values. R10aand R11aare as defined for (Het-1)-(Het-7) and formula I.1, I.2, I.3 and I.4. In particular, R10aand R11aindependently of one another have one of the meanings given for the formulae I.1, I.2, I.3, or I.4 as the preferred values.

In formulas Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a, the symbols X, Ra, Rb, R2, R3and R4are as defined in this OPI is assured, and have, preferably, one of the meanings given as preferred meanings. R10aand R11aare as defined for (Het-1)-(Het-7) and formula I.1, I.2, I.3 and I.4. In particular, R10aand R11aindependently of one another have one of the meanings given for the formulae I.1, I.2, I.3 and I.4 in the form of preferred values.

A particular preferred implementation of the present invention relates to compounds of the formula I.1.a, I.2.a, I.3.a or I.4.a, where X represents O, NH or NRxin particular O or NH, and their pharmaceutically acceptable salts.

The preferred implementation of the present invention relates to compounds of the formula I.1.a, I.2.a, I.3.a or I.4.a, where Y is a chemical bond, and to their pharmaceutically acceptable salts.

The preferred implementation of the present invention relates to compounds of the formula I.1.a, I.2.a, I.3.a or I.4.a, where a is a CRaRbwhere Raand Rbindependently from each other selected from hydrogen, halogen, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, Rbalso may be IT, if Rarepresents hydrogen, C1-C4alkyl or C1-C4halogenated. Preferably, Raand Rbselected independently the Rog from one another from the group consisting of hydrogen, fluorine, methyl, ethyl and methoxy. In particular, Raand Rbrepresent hydrogen, i.e. a represents a CH2.

In formulas Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a Raand Rband are as defined for formula Ia, and have, preferably, one of the meanings given as preferred meanings. In particular, Raand Rbrepresent hydrogen. X is preferably O, NH or N-Rxand R10a, R11a, R2, R3and R4are as defined herein, and are preferably one of the meanings given as preferred meanings.

Preferably, Raand Rbin formulas Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a selected independently of one another from the group consisting of hydrogen, fluorine, methyl, ethyl and methoxy. In particular, Raand Rbrepresent hydrogen.

Such compounds of the formula I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a, where X represents NRxthe radical Rxpreferably selected from the group consisting of C1-C6of alkyl, C1-C4halogenoalkane,1-C4alkoxy-C1-C4of alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl, benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals, selected from GoLoG is on, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, and radical SO2-Rx5where Rx5is the same as defined above. Rx5preferably selected from C1-C4of alkyl, C1-C4-foralkyl, in particular CH2CF3A 5 - or 6-membered heteroaryl, which may contain a condensed benzene ring, in particular pyridyl, pyrimidinyl and chinoline, and phenyl, which is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. Among the compounds preferably the compound of the formula I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a, where the radical Rxthe radical SO2-Rx5where Rx5are as defined above. Similarly, preferred are compounds of the formula I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a, where the radical Rxrepresents a C1-C6alkyl, C1-C4halogenated,1-C4alkoxy-C1-C4alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl or benzyl, where the phenyl ring is unsaturated or has 1, 2 or radical, selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

In a particular preferred embodiment, compounds of formula Ia.1.a, Ia.2.a Ia.3.a or Ia.4.a, Raand Rbrepresents hydrogen.

In the formulae I.1, I.2, I.2, I.4, I.1.a, I.2.a, I.3.a, I.4.a Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a, R10apreferably selected from the

hydrogen

halogen-free,

cyano,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

With1-C8alkoxy,

With1-C8halogenoalkane,

With1-C8halogenoalkane,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4and is coxi,

C(=O)-R13,

C(=O)-OR14,

NR15R16,

C(=O)NR15R16,

SO2R17,

phenyl, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, 5 - or 6-membered heteroaryl, in particular of furil, teinila, oxazolyl, thiazolyl, isoxazolyl, isothiazoline, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl or pyrazinyl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, which is unsubstituted or may have 1, 2 or 3 substituent selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1 or 2 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In f is mulah I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a R10amore preferably represents a

With1-C8halogenated, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, and

most preferably,

phenyl, which is unsubstituted or may have 1, 2, 3, 4, or 5 substituents as those mentioned above, which are preferably selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In particular, R11ain the formulae I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a represents hydrogen or a C-linked moiety, which is preferably selected from CN, C1-C4of alkyl, C1-C4halogenoalkane and phenyl, which is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. More preferably, R11ain the formulae I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a represents hydrogen.

Specific preferred implementation relates to compounds of the formulae I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a, where R4preferably selected from the

With3-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, in particular With3-C8of alkyl, C1-C3of alkyl, which is substituted by a radical selected from C1-C4al is hydroxy or phenyl, which is unsubstituted or substituted as above

With1-C8halogenoalkane, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, in particular of furil, teinila, oxazolyl, thiazolyl, isoxazolyl, isothiazole, 1,2,4-triazolyl, 1,2,3-triazolyl, pyridyl, pyrimidinyl or pyrazinyl where heteroaryl is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

More preferably, R4in the formulae I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or AA selected from C3-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, where the very phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, in particular With3-C8of alkyl, C1-C3of alkyl, which is substituted by a radical selected from C1-C4alkoxy or phenyl, which is unsubstituted or substituted as above, With1-C4halogenoalkane, in particular With1-C4-foralkyl,3-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4in the formulae I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a represents a C3-C8alkyl, C1-C3alkyl, which is substituted by a radical selected from C1-C4alkoxy and C3-C6cycloalkyl or1-C4halogenated, in particular With1-C4foralkyl. More preferably, R2and R3fo the mule I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a represent hydrogen.

The following variant of implementation relates to compounds of the formulae I.1, I.2, I.3, I.4, I.1.a, I.2.a, I.3.a, I.4.a, Ia.1.a, Ia.2.a, Ia.3.a or Ia.4.a, where R4together with R2form C1-C5alkalinity or2-C5alkenylamine fragment, in particular ethane-1,2-dilny or propane-1,3-dilny fragment, where one CH2part may be replaced by oxygen, sulfur or N-R4c-part of, and where C1-C5alkylene and C2-C5albaniles (similarly, ethane-1,2-dilny fragment and propane-1,3-dilny fragment) may be unsubstituted or have 1, 2, 3 or 4 radicals, in particular 0, 1 or 2 radicals selected from halogen, CN, OH, NH2With1-C4of alkyl, in particular methyl,3-C6cycloalkyl, in particular cyclopropyl, cyclobutyl or cyclopentyl,1-C4halogenoalkane, in particular diformate or trifloromethyl,1-C4alkylamino, such as methylamino, ethylamino, di(C1-C4alkyl)amino, such as dimethylamino, diethylamino,1-C4alkoxy, such as methoxy or ethoxy, and C1-C4halogenoalkane, such as deformedarse or triptoreline, and where R4cis such as defined in this description. Preferably, R4cselected from C1-C6alkyl is, which is unsubstituted or is alkoxy or halogenoacetyl, in particular With1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,3-C6cycloalkylation and benzyl, where the phenyl ring is unsubstituted or may have a Deputy selected from halogen, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4cselected from methyl, ethyl, 2-bromacil, 2,2-deperately, 2,2,2-triptoreline, n-propyl, 3,3,3-cryptochrome, n-butyl, 4,4,4-trifloromethyl, 3-methylbutyl, 2-trifloromethyl, 2-methylpropyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and 4-trifloromethyl.

The preferred embodiment of the invention relates to compounds of formula Ia.1.a', Ia.2.a', Ia.3.a' or Ia.4.a' and their pharmaceutically acceptable salts

where Q, X, R3, R4c, R11a, R10a, Raand Rbare as defined in this specification.

Preferably, Q represents-C(RQ1RQ2)-. Preferably, RQ1, RQ2, RQ3, RQ4each independently from each other selected from hydrogen, halogen, C1-C4of alkyl, C3-C6cycloalkyl and sub> 1-C4halogenoalkane. In particular, Q is a CH2CH2CH2or CH=CH, preferably CH2.

X preferably represents O, NH or N-Rx.

R3in particular represents hydrogen.

R4cpreferably selected from C1-C6of alkyl, which is unsubstituted or is alkoxy or halogenoacetyl, in particular With1-C4alkyl, C3-C6cycloalkyl,1-C4halogenated,3-C6cycloalkenyl or benzyl, where the phenyl ring is unsubstituted or may have a Deputy selected from halogen, diformate, trifloromethyl, deformedarse, triptoreline. In particular, R4cselected from methyl, ethyl, 2-bromacil, 2,2-deperately, 2,2,2-triptoreline, n-propyl, 3,3,3-cryptochrome, n-butyl, 4,4 .4-trifloromethyl, 3-methylbutyl, 2-trifloromethyl, 2-methylpropyl, cyclopentylmethyl, cyclohexylmethyl, benzyl and 4-trifloromethyl.

Raand Rbmore preferably represent hydrogen.

In formulas Ia.1.a', Ia.2.a', Ia.3.a' or Ia.4.a' R10apreferably, selected from

hydrogen

halogen-free,

cyano,

With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

With1-C8alkoxy,

With1-C8halogenoalkane,

With1-C8halogenoalkane,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

C(=O)-R13,

C(=O)-OR14,

NR15R16,

C(=O)NR15R16,

SO2R17,

phenyl, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline,

5 - or 6-membered heteroaryl, in particular of furil, thienyl is, oxazolyl, thiazolyl, isoxazolyl, isothiazoline, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl or pyrazinyl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, which is unsubstituted or may have 1, 2 or 3 substituent selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1 or 2 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In formulas Ia.1.a', Ia.2.a', Ia.3.a' or Ia.4.a' R10amore preferably, is a

With1-C8halogenated, in particular With1-C2foralkyl,

With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,

With1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C 1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, and

most preferably,

phenyl, which is unsubstituted or may have 1, 2, 3, 4, or 5 substituents as described above, which are preferably selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, in particular 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline.

In formulas Ia.1.a', Ia.2.a', Ia.3.a' or Ia.4.a' R11apreferably selected from hydrogen and C-linked moiety, which is preferably selected from CN, C1-C4of alkyl, C1-C4halogenoalkane and phenyl, which is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, OH, C1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane. More preferably, R11ain formulas Ia.1.a', Ia.2.a', Ia.3.a' or Ia.4.a' represents hydrogen.

Examples of compounds of the present invention include, but are not limited to:

1-{4-[(thiophene-3-ILM is Tyl)amino]phenyl}butane-1-he,

1-(4-{[5-(2-chlorophenyl)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[5-(3-chlorophenyl)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[5-(4-chlorophenyl)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-chlorothiophene-2-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[5-(2-(triptoreline)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[5-(3-triptoreline)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-ethylthiophen-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(benzo[b]thiophene-3-ylmethyl)amino]phenyl}butane-1-he,

(R)-1-{4-[(tetrahydrofuran-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-methyl-1H-indole-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(furan-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(pyridine-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(pyridine-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(pyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-methyl-1H-imidazol-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methylthiophene-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-methylthiophene-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-(hydroxymethylene-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methylfuran-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-methylbenzo[b]thiophene-2-ylmethyl)amino]phenyl}butane-1-he,

5-[(4-butyrylthiocholine)methyl]furan-2-ymetray ether acetic acid,

1-{4-[(1-acetyl-1H-indol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(chinali the-6-ylmethyl)amino]phenyl}butane-1-he,

1-{4-{(thiazol-2-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[1-(toluene-4-sulfonyl)-1H-pyrrol-2-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[5-(piperidine-1-yl)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(4-phenylthiazol-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1H-indol-2-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[1-(toluene-4-sulfonyl)-1H-indol-3-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-methyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[4-bromo-2-(4-chlorbenzyl)-2H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he,

4-{5-[(4-butyrylthiocholine)methyl]furan-2-yl}benzosulfimide,

1-(4-{[5-(2-(trifloromethyl)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[4-(3-bromophenyl)pyridine-3-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[3-(4-methoxyphenyl)-1-(thiophene-2-carbonyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[5-(3-(trifloromethyl)furan-2-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[3-(thiophene-2-yl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-chlorobenzo[b]thiophene-3-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[3-(4-(triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-methyl-3-phenylisoxazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,5-dimethyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methyl-1-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-phenylthiazol-4-ylmethyl)amino]phenyl}Boo is an-1-he,

1-{4-[(4-methyl-2-phenylpyrimidine-5-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[1-(phenylsulfonyl)-1H-indol-3-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[5-(3-chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[5-chloro-1-methyl-3-(phenylthiomethyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[5-chloro-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl]methylamino}phenyl)butane-1-he,

1-(4-{[4-(3-chlorobenzoyl)-1-methyl-1H-pyrrol-2-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-ethyl-5-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-phenyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-tert-butyl-3,5-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl)butane-1-he,

1-{4-[(5-methyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1,5-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1,3-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[3-(5-methylfuran-2-yl)-1-phenyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[1-phenyl-3-(thiophene-2-yl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-ethyl-5-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-ethyl-3-methyl-1H-pyrazol-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-ethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,5-dimethyl-1H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-methyl-1-propyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methyl-1-propyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-methyl-1H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-methyl-5-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl})butane-1-he,

1-{4-[(1,5-dimethyl-1H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-isopropyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[3-(4-hydroxyphenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(3-tert-butyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

N-sensitiza-2-amine,

3-[(3-tert-butyl-1H-pyrazole-4-ylmethyl)amino]phenol,

(4-boutillier)-[1-(2,2,2-cryptogramophone)-3-(4-reformational)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

5-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}indan-1-he,

6-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-3,4-dihydro-2H-naphthalene-1-he,

[4-(2-methoxyphenoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

N-methoxy-N-methyl-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzamide,

4-{[3-tert-butyl-1-(2,2,2-cryptogramophone)-1H-pyrazole-4-ylmethyl]amino}-N-methoxy-N-methylbenzamide,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3(1-methylbutoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)phenylamine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-o-tolylamino,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-m-tolylamino,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-p-tolylamino,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2-methoxyphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-methoxyphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-methoxyphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2-forfinal)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-forfinal)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-forfinal)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2-chlorophenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-chlorophenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-chlorophenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-trifloromethyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-phenoxyphenyl)amine,

N-(3-tert-butyl-1H-pyrazole-4-ylmethyl)-N',N'-xylene-1,3-diamine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-triptoreline)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-triptoreline)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-trifloromethyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-phenoxyphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,3-dimetilfenil)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,4-dimetilfenil)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,5-dimetilfenil)amine,

(3-tert-is util-1H-pyrazole-4-ylmethyl)-(3,4-dimetilfenil)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3, 5dimethylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,3-acid)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,4-acid)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,5-acid)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,4-acid)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,5-acid)amine,

benzo[1,3]dioxol-5-yl(3-tert-butyl-1H-pyrazole-4-ylmethyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,4,5-trimethoxyphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,3-dichlorophenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,4-dichlorophenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,5-dichlorophenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,4-dichlorophenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,5-dichlorophenyl)amine,

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-o-tolylamino,

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-p-tolylamino,

(2-methoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3-methoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(4-methoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2-forfinal)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3-forfinal)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2-chlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3-chlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(4-chlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(4-trifloromethyl)amine,

(3-phenoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

N,N-dimethyl-N'-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)benzene-1,3-diamine,

N,N-dimethyl-N'-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)benzene-1,4-diamine,

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(3-triptoreline)amine,

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(4-triptoreline)amine,

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(3-trifloromethyl)amine,

(4-phenoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2,3-dimetilfenil)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2,4-dimetilfenil)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2.5-dimetilfenil)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3, 5dimethylphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2,3-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2,4-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2,5-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3,4-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3,5-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

benzo[1,3]dioxol-5-yl(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(3,4,5-trimethoxyphenyl)amine,

(2,3-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2,4-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(2,5-dichlorophenyl)-(3-thiophene-2-yl-1H-pee the azole-4-ylmethyl)amine,

(3,4-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

(3,5-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine,

[3-tert-butyl-1-(2,2,2-cryptogramophone)-1H-pyrazole-4-ylmethyl]-[3-(1-methylbutoxy)phenyl]amide 2,2,2-cryptgethashparam acid

2-fluoro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzonitrile,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1,1-dioxo-1λ6-thiomorpholine-4-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-oxazol-5-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-pyridin-4-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-pyridine-2-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-thiophene-3-ylphenyl)amine,

3-fluoro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzonitrile,

2-chloro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzonitrile,

(3-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-ethanolgasoline)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

N,N-dimethyl-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzosulfimide,

(3-benzoylphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-thiophene-2-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-methylpiperazin-1-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4,5-dimethyloxazole-2-yl)phenyl]amine,

o-tolyl[3-(4-triptime ylphenyl)-1H-pyrazole-4-ylmethyl]Amin,

m-tolyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

p-tolyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-forfinal)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-forfinal)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-forfinal)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-chlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-chlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-chlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-trifloromethyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-phenoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-dimethylaminomethylphenol)-[5-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-triptoreline)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-triptoreline)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-trifloromethyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-phenoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,3-dimetilfenil)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,4-dimetilfenil)-[3-(4-shall reformational)-1H-pyrazole-4-ylmethyl]Amin,

(2.5-dimetilfenil)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3,4-dimetilfenil)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3, 5dimethylphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,3-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,4-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,5-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3,4-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3,5-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]-(3,4,5-trimethoxyphenyl)amine,

(2,3-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,4-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,5-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3,4-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3,5-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-boutillier)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide econsultancy acid,

(4-boutillier)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(3-boutillier)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(3-boutillier)-[3-(4-trifloromethyl who yl)-1H-pyrazole-4-ylmethyl]amide econsultancy acid,

[3-(1-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide econsultancy acid,

[3-(1-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide econsultancy acid,

[3-(2-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide econsultancy acid,

[3-(2-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(3-second-butoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(3-second-butoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide econsultancy acid,

(3-second-butoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide econsultancy acid,

(3-second-butoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide 2,2,2-cryptgethashparam acid,

[3-(2-methylbutoxy)phenyl]-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide 2,2,2-cryptgethashparam acid,

[3-(2-methylbutoxy)phenyl]-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide econsultancy acid,

[3-(1-ethylpropoxy)phenyl]-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide econsultancy acid,

[3-(1-methylbutoxy)phenyl]-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide 2,2,2-cryptgethashparam acid,

[3-(1-methylbutoxy)phenyl]-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide econsultancy acid,

(3-boutillier)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide econsultancy acid,

(3-boutillier)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide 2,2,2-cryptgethashparam acid,

(4-boutillier)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide 2,2,2-cryptgethashparam acid,

(4-boutillier)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amide econsultancy acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-boutillier)amide econsultancy acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-boutillier)amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-boutillier)amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-boutillier)amide econsultancy acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1-methylbutoxy)phenyl]amide econsultancy acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1-methylbutoxy)phenyl]amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1-ethylpropoxy)phenyl]amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1-ethylpropoxy)phenyl]amide econsultancy acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl-[3-(2-methylbutoxy)phenyl]amide econsultancy acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(2-methylbutoxy)phenyl]amide 2,2,2-cryptgethashparam acid,

(3-second-butoxyphenyl)-(3-tert-butyl-1H-pyrazole-4-ylmethyl)amide 2,2,2-cryptgethashparam acid,

(3-second-butoxyphenyl)-(3-tert-butyl-1H-pyrazole-4-ylmethyl)amide econsultancy acid,

1-(4-{[3-(4-methoxyphenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(3-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-p-tolyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[3-(3,5-differenl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1H-indazol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-methyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[3-(3,4-acid)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-methyl-1H-indazol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-benzyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[3-(4-forfinal)-1-phenyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-phenyl-3-pyridin-3-yl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methoxy-1H-indazol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3,5-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[4-(4-methoxyphenyl)thiazol-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-methyl-1H-benzoimidazol-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3,5-dimethylisoxazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(1-methyl-1H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-thiophene-2-isoxazol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,3-dimethyl-3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methyl-2-phenyloxazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-furan-2-isoxazol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-methyl-4-phenylthiazol-5-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[2-(4-triptoreline)thiazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[2-(3-chlorophenyl)thiazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-methyl-3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(4-methylthiazole-5-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[5-(4-forfinal)isoxazol-3-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-methylisoxazol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,4-dimethylthiazol-5-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(4-methylthiazole-2-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[2-(2-methoxyphenyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[2-(3-methoxyphenyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[4-(4-forfinal)thiazol-2-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-methyl-2-thiophene-2-yl-oxazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-phenylthiazol-5-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-methyl-3H-imidazol-4-ylmethyl)amino]phenylbutane-1-he,

1-{4-[(thiazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(thiazole-5-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,4-dihlotiazid-5-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(4,5-dimethyl-1H-imidazol-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(oxazol-5-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(oxazol-2-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[3-(3-forfinal)isoxazol-5-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[3-(2-forfinal)isoxazol-5-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[2-(4-chlorophenyl)thiazol-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(2-chlorothiazole-5-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-chloro-2-phenyl-3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[2-(toluene-4-sulfonyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[2-(4-methoxyphenoxy)thiazole-5-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(1-propyl-1H-imidazol-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(imidazo[1,2-a]pyridine-2-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-methylthiazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-methyl-1H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[2-(4-methoxyphenyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[2-(3-forfinal)thiazole-5-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[2-(4-triptoreline)thiazole-5-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(2-isopropylthiazole-4-ylmethyl)amino]phenyl}butane-1-he,

2-{4-[(3-tert-butyl-1H-pyrazole-4-ylmethyl)amino]phenoxy}benzonitrile,

(4-butoxyphenyl)-(3-t the et-butyl-1H-pyrazole-4-ylmethyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-deformational)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-propoxyphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-deformational)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-ethoxyphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2-chlorophenoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-o-tolylacetic)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3,4-dichlorophenoxy)phenyl]amine,

(4-benzyloxyphenyl)-(3-tert-butyl-1H-pyrazole-4-ylmethyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3-chloro-5-triptorelin-2-yloxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(chloroformate)phenyl]amine,

[4-(3,5-bis-triptoreline)phenyl]-(3-tert-butyl-1H-pyrazole-4-ylmethyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2-pertenece)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1-methylpiperidin-4-yloxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(pyridine-2-ylethoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-isobutoxide)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2,3-dimethylphenoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(pyrimidine-2-yloxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-elmet the l)-[4-(2-chlorobenzoyloxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(pyridine-3-yloxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-forbindelse)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(5-triptorelin-2-yloxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3-triptoreline)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-m-tolylacetic)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-pertenece)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-chlorophenoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3-methylbutoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2,4-dichlorophenoxy)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-p-tolylacetic)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-isopropoxyphenyl)amine,

1-{4-[(6-dimethylaminopyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-morpholine-4-espiridion-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-chloropyridin-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,6-dichloropyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-herperidin-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-isopropoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-propoxyphen-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-cyclopentyloxy-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-morpholine-4-espiridion-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-fluoro-2-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-methylpyridin-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,6-dimethoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-herperidin-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(5-herperidin-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2,5-dichloropyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-thiophene-3-espiridion-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-dimethylaminopyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-triptorelin-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-thiophene-2-espiridion-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-furan-2-espiridion-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(4-methylpyridin-3-ylmethyl)amino]phenyl}butane-1-he,

[4-(furan-2-ylethoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[4-(thiophene-2-ylethoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-isopropoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[3-(pyridine-2-yloxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-cyclopentylacetyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-chloro-5-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(6-chloro-4-methylpyridin-3-the l)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(6-chloropyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

phenyl-3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)methanon;

(5-herperidin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(6-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(5-chloropyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4,6-dimethylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(6-methoxypyridine-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(5-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(6-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

pyridine-2-yl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

pyridine-3-yl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3,5-differencein-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(6-chloropyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,6-dimethylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2,6-dimethoxypyridine-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4,6-dimethylpyridin-3 is)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

pyridine-4-yl(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)methanon;

(5-chloropyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

1-(3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}thiophene-2-yl)Etalon,

(6-herperidin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-methoxypyridine-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-herperidin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(6-herperidin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(5-methoxypyridine-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(5-herperidin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-chloro-5-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(5,6-dimethylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-chloro-6-methylpyridin-3-yl)-[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]Amin,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(6-fluoro-5-methylpyridin-3-yl)amine,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(5-fluoro-4-methylpyridin-2-yl)amine,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(6-methoxy-4-methylpyridin-3-yl)amine,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(2-methoxy-4-methylpyridin-3-yl)amine,

N3-[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-N2,N2-dimethyl-5-triptorelin-2,3-diamine,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(4-methoxypyridine-3-yl)amine,

N5-3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-N2,N2-dimethylpyridin-2,5-diamine,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(4-methoxypyridine-2-yl)amine,

3-methyl-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzonitrile,

1-(4-{[1-methyl-3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[1-methyl-5-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

[3-(2-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

(3-second-butoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[3-(1-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-piperidine-4-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-piperazine-1-ylphenyl)amine,

(4-boutillier)pyridine-3-ylmethylene 2,2,2-cryptgethashparam acid,

N,N-dimethyl-N'-pyridine-3-ylmethylene-1,4-diamine,

(4-dimethylaminophenyl)pyridine-3-ylmethylene 2,2,2-cryptgethashparam acid,

1-{3-[(pyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-dimethylaminopyridine-3-ylmethyl)amino]phenyl}butane-1-he,

N,N-dimethyl-N'-pyridine-3-ylmethylene-1,3-diamine,

(3-dimethylaminophenyl)pyridine-3-ylmethylene 2,2,2-cryptgethashparam acid,

(3-boutillier)pyridine-3-ylmethylene 2,2,2-cryptgethashparam is islote,

(4-boutillier)-(6-dimethylaminopyridine-3-ylmethyl)amide 2,2,2-cryptgethashparam acid,

1-(3-{methyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

(5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

[4-(2-methoxyphenoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

N,N-dimethyl-4-{(2,2,2-cryptogramophone)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzosulfimide,

[3-(2-trifloromethyl)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[3-(2-methoxyphenoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

1-(3-chloro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon,

(4-methanesulfonyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

2-methyl-7-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}chromen-4-one,

1-(2-fluoro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4,5-dimethyloxazole-2-yl)phenyl]amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-oxazol-5-ylphenyl)amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-pyridine-2-ylphenyl)amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ilma who yl)-(4-pyridin-4-ylphenyl)amide 2,2,2-cryptgethashparam acid,

[3-(1-ethylpropoxy)phenyl]methyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide econsultancy acid,

N-[3-(1-ethylpropoxy)phenyl]-N-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]methanesulfonamide,

1-(4-{methyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-[4-(methylpyridin-3-ylmethylamino)phenyl]butane-1-he,

(4-boutillier)-[1-methyl-5-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(4-boutillier)-[1-methyl-3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(4-boutillier)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(4-boutillier)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

3-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N,N-dimethylbenzamide,

1-(4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

N-(4-boutillier)-N-pyridin-3-ylmethylphosphonate,

N-[3-(1-ethylpropoxy)phenyl]-N-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]benzosulfimide,

1-[3-(methylpyridin-3-ylmethylamino)phenyl]butane-1-he,

N-(3-boutillier)-N-pyridin-3-ylmethylphosphonate,

N-(3-boutillier)-N-pyridin-3-ylmethylphosphonate,

N-(3-boutillier)-C-phenyl-N-pyridin-3-iletilmesinden the Ministry of foreign Affairs,

1-{4-[4-(pyridine-3-yloxy)butoxy]phenyl}butane-1-he,

(6-dimethylaminopyridine-3-ylmethyl)-[3-(1-ethylpropoxy)phenyl]amide 2,2,2-cryptgethashparam acid,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(1,1-dioxo-2,3-dihydro-1H-benzo[b]thiophene-5-yl)amine,

7-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-3,4-dihydro-2H-naphthalene-1-he,

6-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}indan-1-he,

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-methylbenzenesulfonamide,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-[4-(pyrrolidin-1-sulfonyl)phenyl]amine,

3-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N,N-dimethylbenzenesulfonamide,

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(1,1-dioxo-1H-benzo[b]thiophene-5-yl)amine,

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N,N-determinationand,

N,N-dimethyl-4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzamide,

1-(2-methoxy-4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(2-hydroxy-4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(2-hydroxy-3-propyl-4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon,

1-[4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-(1-ethylpropoxy)phenyl]butane-1-he,

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-methoxy-3-were)Etalon,

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-methoxy-3-propylphenyl)Etalon,

1-(4-{[3-(4-chlorphen the l)-1H-pyrazole-4-ylmethyl]amino}-2-hydroxy-3-methylphenyl)Etalon,

2-phenyl-1-{4-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon,

cyclopentyl{4-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}mechanon,

methyl ester of 4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}benzoic acid,

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)-(4-methylpiperazin-1-yl)methanon,

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)-[4-(1-methylpiperidin-4-yl)piperazine-1-yl]metano,

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)morpholine-4-ylmethanone,

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-methyl-N-propylbenzamide,

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-propylbenzamide,

1-[3-(benzylpyridine-3-ylmethylamino)phenyl]butane-1-he,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1-methylpiperidin-4-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-methyl-4H-[1,2,4]triazole-3-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(5-methylfuran-2-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-cyclopentylacetyl)amine,

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

[3-(1-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(3-second-butoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

[3-(2-methylbutoxy)phenyl]-[3-(4-t is iformatter)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-cyclopentylacetyl)amide 2,2,2-cryptgethashparam acid,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-thiophene-2-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-furan-2-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(4-methylthiazole-2-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(4,5-dimethylthiazol-2-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-oxazol-5-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-thiophene-3-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(4,5-dimethyloxazole-2-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(4-methylpiperazin-1-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-piperazine-1-ylphenyl)amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1,1-dioxo-1λ6-isothiazolin-2-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(2-methylthiazole-4-yl)phenyl]amine,

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-pyridin-2-ylphenyl)amine,

[4-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(2-dimethylaminomethylphenol)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

(3-dimethylaminomethylphenol)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin,

[4-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid,

1-{4-[(3-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-prop is l-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-isopropyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-ethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he,

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)morpholine-4-yl-methanon,

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-methyl-N-propylbenzamide,

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-propylbenzamide,

1-[3-(benzylpyridine-3-ylmethylamino)phenyl]butane-1-he,

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon,

1-{3-chloro-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon,

1-{2-fluoro-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon,

1-{3-fluoro-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon,

1-{2-methyl-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon,

1-{3-methyl-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon,

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}propane-1-he,

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}pentane-1-he,

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}hexane-1-he,

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-elmersolver]phenyl}butane-1-he,

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-elmersolver]phenyl}butane-1-he,

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he,

1-{4-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he,

1-{4-[3-(4-chlorophenyl)-1H-Piras the l-4 ylethoxy]phenyl}butane-1-he,

1-{4-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he,

1-{4-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he,

1-[4-(3-phenyl-1H-pyrazole-4-ylethoxy)phenyl]butane-1-he,

1-{4-[1-(3-phenyl-1H-pyrazole-4-yl)ethoxy]phenyl}butane-1-he,

1-(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon,

1-(3-nitro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon,

1-(3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon,

1-(3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

phenyl-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)methanon,

2,2-dimethyl-1-(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)propane-1-he,

2,2,2-Cryptor-1-(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon,

1-{1-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}Etalon,

1-(4-{[3-(4-forfinal)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[3-(3-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[3-(2-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[3-(3-forfinal)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(3-pyridin-3-yl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[4-(4-methoxyphenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he,

1-(3-{[4-(4-methoxyphenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he,

1-(3-{[4-(4-ethylphenyl)-1H-p is razol-3-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[4-(4-ethylphenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[4-(4-triptoreline)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he,

1-(4-{[4-(4-chlorophenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(5-phenyl)-2H-[1,2,3]triazole-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[4-(4-methoxyphenyl)-1H-pyrazole-3-ylethoxy]phenyl}butane-1-he,

1-{4-[4-(4-ethylphenyl)-1H-pyrazole-3-ylethoxy]phenyl}butane-1-he,

1-[4-(4-bromo-1H-pyrazole-3-ylethoxy)phenyl]butane-1-he,

1-{4-[(4-phenyl-1H-pyrrol-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-phenylpyridine-4-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(4-vinylpyridin-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(2-phenylpyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(6-vinylpyridin-3-ylmethyl)amino]phenyl}butane-1-he,

1-(4-{[6-(4-forfinal)pyridine-2-ylmethyl]amino}phenyl)butane-1-he,

1-{4-[(pyrazole[1,5-a]pyridine-3-ylmethyl)amino]phenyl}butane-1-he,

1-{4-[(3-methyl-5-phenylisoxazol-4-ylmethyl)amino]phenyl}butane-1-he,

2-propyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-propyl-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-he,

5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-he,

5-[3-(3-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-he,

5-[3-(3-forfinal)-1H-pyrazole-4-olmeto the si]-2-propyl-2,3-dihydroindol-1-he,

5-(3-phenyl-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-he,

5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-he,

5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-he,

5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-he,

5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-he,

5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-he,

5-(3-phenyl-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-he,

2-butyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-butyl-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-butyl-5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-butyl-5-[3-(3,4-dichlorophenyl)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-butyl-5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-butyl-5-[3-(3-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-butyl-5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-butyl-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-antiperoxidase acid,

2-(4,4,4-trifloromethyl)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

5-(3-phenyl-1H-shall irsol-4-ylethoxy)-2-(4,4,4-trifloromethyl)-2,3-dihydroindol-1-he,

5-[3-(3,4-dichlorophenyl)-1H-pyrazole-4-ylethoxy]-2-(4,4,4-trifloromethyl)-2,3-dihydroindol-1-he,

2-(3-methylbutyl)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-(3-methylbutyl)-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-he,

5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2-(2-trifloromethyl)-2,3-dihydroindol-1-he,

2-ethyl-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-ethyl-5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-ethyl-5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

5-[3-(3-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-ethyl-2,3-dihydroindol-1-he,

5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-ethyl-2,3-dihydroindol-1-he,

2-ethyl-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-he,

2-(2-bromacil)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-(2-bromacil)-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-(2,2-dottorati)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-(2,2-dottorati)-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-he,

2-(2,2,2-triptorelin)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-(2,2,2-triptorelin)-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

5-[3-(4-forfinal)-1H-pyrazole-4-yl is ethoxy]-2-(2,2,2-triptorelin)-2,3-dihydroindol-1-he,

5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2-(2,2,2-triptorelin)-2,3-dihydroindol-1-he,

5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-methyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-propyl-6-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-3,4-dihydro-2H-isoquinoline-1-he,

2-propyl-5-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-2,3-dihydroindol-1-he,

5-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-he,

5-{[3-(3-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-he,

2-propyl-5-{[3-3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-2,3-dihydroindol-1-he,

5-{[3-(4-forfinal)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-he,

5-{[3-(3-forfinal)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-he,

5-[(3-phenyl-1H-pyrazole-4-ylmethyl)amino]-2-propyl-2,3-dihydroindol-1-he,

2-propyl-5-{[4-(3-triptoreline)-1H-pyrazole-3-ylmethyl]amino}-2,3-dihydroindol-1-he,

2-propyl-5-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}isoindole-1,3-dione,

2-propyl-6-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-2,3-dihydroisoquinoline-1-he,

2-(4-cryptomaterial)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-cyclohexylmethyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-digidroid is indole-1-he,

2-isobutyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-cyclopentyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

2-phenyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he,

5-[(3-methyl-5-phenylisoxazol-4-ylmethyl)amino]-2-propyl-2,3-dihydroindol-1-he

and their pharmaceutically acceptable salts.

Compounds according to the present invention can be obtained by analogy with well-proven in the field by methods of organic synthesis.

The compounds of formula I, where X represents NH or NRxand a represents a fragment of A CRa'H, where A' is a chemical bond or optionally substituted C1-C4alkylene, and Ra'represents hydrogen or C1-C4alkyl, in particular hydrogen, can be obtained by a sequence of reactions represented in scheme 1, including restorative amination of aminoalkylsilane II heteroanalogues III.

Scheme 1

Scheme 1 characters Het, Ar, X, Y, A', Ra', Rx, R1, R2and R3are as defined above. Rxrepresents, in particular, the radical C(=O)-Rx1C(=O)-ORx2C(=O)NRx3Rx4, S(O)2Rx5or S(O)2N x3Rx4or optionally substituted C1-C6alkyl, C3-C8cycloalkyl or1-C6halogenated. Lg is nucleophile replaced the group comprising halogen, in particular chlorine or bromine, and O-S(O)2R, where R represents a C1-C6alkyl, C1-C6halogenated or phenyl which may be substituted With1-C6by alkyl or halogen.

Reductive amination of compound III to compound II can be performed by standard techniques oxidative amination, which are known in the art. In particular, the compounds II and III are subjected to interaction with the regenerating agent, in particular DIBORANE, borohydride, triacetoxyborohydride or cyanoborohydride, such as borohydride alkali metal, cyanoborohydride alkali metal, triacetoxyborohydride alkali metal or deposited on the polymer cyanoborohydride or deposited on the polymer triacetoxyborohydride, for example, macroporous cyanoborohydride.

Interaction of compound II and compound III are usually in an organic solvent comprising an aprotic organic solvents, such as substituted amides, lactams and urea, such as dimethylformamide, dimethylacetamide, N-organic, tetramethylrhodamine, simple circular is Fira, such as dioxane, tetrahydrofuran, halogenated hydrocarbons such as dichloromethane, and mixtures thereof and mixtures with1-C6the alkanols and/or water.

Interaction of compound II and compound III usually should be carried out at temperatures in the range of from -10° to 100°C, depending on the reactivity of the compounds II and III.

Compound I where X represents NH, for example, compound I obtained in the result of the interaction of compound II and compound III can then be subjected to the reaction of alkylation, acylation or sulfonylurea connection Rx-Lg to introduce the radical Rx. Compounds where Rxrepresents a radical C(O=)otherx3can be obtained by the interaction of compound I {X is NH} with isocyanate Rx3-NCO.

The interaction of the compounds I, in which X represents NH, with a compound Rx-Lg can be a standard method of alkylation, acylation or sulfonylurea. Usually the interaction is carried out in an inert solvent in the presence of suitable bases include hydroxides of alkali metals, carbonates of alkali metals such as sodium carbonate or potassium carbonate, or tertiary amine, such as triethylamine or pyridine.

Suitable solvents include, but are not limited to, substituted amides, lactams is urea, such as dimethylformamide, dimethylacetamide, N-organic, tetramethylrhodamine, simple cyclic ethers, such as dioxane, tetrahydrofuran, halogenated hydrocarbons such as dichloromethane, and also tertiary amines, such as trialkylamine or pyridine, and mixtures thereof. The interaction of the compounds I, in which X represents NH, with a compound Rx-Lg usually should be carried out at temperatures in the range from 10°C to 150°C, depending on the reactivity of compounds Rx-Lg.

The compounds of formula I, where X represents O or S, can be obtained by the sequence of reactions shown in the scheme 2, including alkylation reaction hidroxiaril or mercaptoamines compound IIa with heteroeroticism IIIa.

Scheme 2

Figure 2 characters Het, Ar, X, A, R1, R2and R3are as defined above. Lg is nucleophile replaced the group comprising halogen, in particular bromine or iodine, and-S(O)2R, where R represents a C1-C6alkyl, C1-C6halogenated or phenyl which may be substituted With1-C6by alkyl or halogen.

Interaction of compound IIa with a compound IIIa can be performed using standard alkylation. Usually the interaction is carried out in an inert Rast is oricale, optionally in the presence of suitable bases include hydroxides of alkali metals, carbonates of alkali metals such as sodium carbonate or potassium carbonate, or tertiary amine, such as triethylamine or pyridine.

Suitable solvents include, but are not limited to, substituted amides, lactams and urea, such as dimethylformamide, dimethylacetamide, N-organic, tetramethylrhodamine, simple cyclic amines, such as dioxane, tetrahydrofuran, halogenated hydrocarbons such as dichloromethane, and also tertiary amines, such as trialkylamine or pyridine, and mixtures thereof.

The interaction of compounds IIa c compound IIIa usually should be carried out at temperatures in the range from 10°C to 150°C, depending on the reactivity of the leaving group Lg.

The interaction is presented in figure 2, can also be used to obtain compounds I in which X represents NH, NRxor NH-C(O), on the basis of compounds IIa, where HX' represents NH2, Otherxor H2NC(O). The interaction is particularly suitable for preparing compounds I where X represents NRxwhere Rxin particular, represents a radical C(=O)-Rx1C(=O)-ORx2C(=O)NRx3Rx4, S(O)2Rx5or S(O)2NRx3Rx4.

The compounds of formula I, where X submitted is a Oh, you can also get condensation reaction of alcohols IIIb and aromatic alcohols IIb in the presence of esters of azodicarboxylate, such as diethylazodicarboxylate (DEAD), diisopropylcarbodiimide (DIAD) or di-tert-utilisationbased, and triarylphosphine, such as triphenylphosphine, as shown in figure 3 by analogy with the reaction Mizunami.

Scheme 3

Compound I obtained by the above reactions can be extracted and cleaned using standard methods, such as solvent extraction, chromatography, crystallization, distillation and the like.

The applicability of the compounds in accordance with the present invention as modulators of the activity of a metabotropic glutamate receptor, in particular the activity of mGlu2, can be demonstrated by a method known in the art. Compounds of the present invention can be tested, for example, by determining the intracellular concentration of CA++in cells permanently expressing human mGlu receptor, rat glutamate Transporter rGLAST and Galpha16 subunit of G-protein complex under standard conditions in the tablet reader fluorometric image (FLIPR, Molecular Devices, Union City, CA 94587, USA) by measuring the response of cells to the test compound in the absence or in the presence of the tvii glutamate. The FLIPR analysis is a standard functional analysis for monitoring of natural or recombinant Galphaq-coupled receptors and natural and recombinant receptors, normally associated with other cascades by G-protein signal transmission that are associated with calcium through coexpression alpha-subunit disorderly or chimeric G-protein. In the analysis, the increase in intracellular calcium was measured using the calcium-sensitive fluorescent dye (e.g., Fluo-4 AM) in the FLIPR device.

For the purpose of this study cell line permanently expressing human mGlu receptor, such as mGlu2 receptor, rat glutamate Transporter rGLAST and GalphaG16 can be generated by transfection as described in the examples. For the selection of a suitable cell clone and subsequent measurement of the selected clone of cells is placed on a suitable advance tablets in a suitable medium (for example, DMEM Glutamax (GIBCO # 21885-025)/10% detalizirovannoi FCS). Cells can be selected by gentamitsinovoy processing, as described in the examples. The cells are then load the appropriate Ca2+sensitive fluorescent dye, for example, 2 μm Fluo-4 AM (molecular probes F14201). The cells are then washed with a suitable buffer (such as HEPES), and thus treated the tablets is measured in tablet reader fluorometric of the images (for example, FLIPR, Molecular Devices, Union City, CA 94587, USA).

Compounds of the present invention were tested in the above FLIPR analysis using the selected cell clone. Elevated levels of intracellular calcium quantitatively determined following addition of the test compounds (agonism), and subsequent addition of a submaximal concentration of glutamate (potentiation).

To determine the effect of the test compounds (agonism) or by increasing the response to a submaximal concentration (for example, 1 μm) of glutamate (potentiation) the resulting signal was determined by subtracting the background fluorescence from the peak height maximum fluorescence appropriate responses. In the FLIPR device connection serves to the cell and its fluorescent response quantify the FLIPR device (agonism). The concentration at which the connection detects half of its maximum steps, referred to as the 'effective concentration 50' or 'EC50'. The maximum effect caused by the test substance lead (normalize) to the maximum activity detected using 100 μm glutamate (set at 100%).

After adding to the tablet test connection add a submaximal concentration of glutamate (for example, 1 μm CH is tamata). Potentiator enhances the response of the receptor for glutamate. The response to glutamate in the presence of test compounds to determine quantitatively. The concentration at which the test compound is able to show half of his maximum potentiate actions on glutamate, called 'EC50'. The maximum response to a submaximal concentration of glutamate (for example, 1 micromolar glutamate) in the presence of test compounds normalize to maximum effect, show 100 micromolar glutamate (set at 100%). Then draw a least-squares curve if chetyrehkamernoe equations with getting in the curve dose-response to determine the resulting size EU50(Graph Pad Prism).

The control cell line, NECK cells permanently expressing rGLAST and Galpha16, was also placed in advance tablet for parallel testing verified the specificity of the test compounds on mGlu receptor agonism or potentiation.

Compounds of the invention can be further characterized by measuring their effectiveness and possible inhibition of Forskolin-induced camp levels in these cells based on their own agonism or potency of the action of glutamate (potentiial the tion). Levels of camp were determined quantitatively using the method of Alphascreen (PerkinElmer Life and Analytical Sciences, 710 Bridgeport Avenue, Shelton, CT USA)as described by the manufacturer (the author of the method), to determine action Galphai-coupled receptors.

The concentration at which the compound exhibits a half of its maximum steps, referred to as the 'effective concentration 50' or 'EC50'. The maximum effect caused by the test substance, normalize in accordance with the maximum effect that is manifested with 100 μm glutamate (100%). Then draw a curve by the method of least squares in the case chetyrehkamernoe equations, obtained by curve dose-response to determine the resulting size EU50(Graph Pad Prism).

In particular, the compounds of the following examples have activity in potentsiirovannye mGlu2 receptor in the aforementioned assays, generally with EU50not more than approximately 10 microns. Preferred compounds within the scope of the present invention have activity in potentiating mGlu2 receptor in the aforementioned assays with EU50less than 1 μm, in particular less than 0.5 μm, more preferably at most 0.2 μm, at most 0.1 micron. This result indicates a significant activity of the compounds when used as positive modulators active the STI mGlu2 receptor.

As indicated above, the compounds of the present invention are positive modulators of metabotropic glutamate (mGluR) receptor function, in particular, they are positive modulators of mGlu2 receptors. Thus, the compounds of the present invention can be used to treat, prevent, reduce, suppress or reduce the risk of a number of neurological and psychiatric disorders associated with glutamate dysfunction, including one or more of the following conditions or diseases: acute neurological and psychiatric disorders such as cerebral insufficiency resulting from operations with artificial blood circulation and grafting, stroke, cerebral ischemia, spinal cord injury, head trauma, perinatal hypoxia, cardiac arrest, hypoglycemic neuronal damage, dementia (including AIDS-induced dementia), Alzheimer's disease, horey's chorea, amyotrophic lateral sclerosis, ocular damage, retinopathy, cognitive disorders, idiopathic and induced drug for Parkinson's disease, muscular spasms and disorders associated with muscular spasticity including tremor, epilepsy, convulsions, migraine (including headache, migraine, urinary incontinence, Rosstroy the VA, associated with tolerance to substance-related disorders syndrome substances (including substances such as opiates, nicotine, tobacco products, alcohol, benzodiazepines, cocaine, sedatives, sleep AIDS, and so on), psychosis, schizophrenia, anxiety (including common anxiety disorder, panic disorder and obsessive-compulsive disorder), mood disorders (including depression, mania, bipolar disorders), trigeminal neuralgia, hearing loss, noise-related macular degeneration of the eye, emesis, brain edema, pain (including acute and chronic painful conditions, severe pain, nekupiruemy pain, neuropathic pain and post-traumatic pain), late dyskinesia, sleep disorders (including narcolepsy), upset with the lack of attention/hyperactivity disorder and conduct disorder.

From the above disorders is especially important treatment of schizophrenia, anxiety, depression, disorders associated with substance, migraine and epilepsy.

Therefore, the present invention relates to a method for the treatment of painful disorders selected from neurological and psychiatric disorders associated with glutamate dysfunction, which includes the introduction of an effective amount of at least one compound of the present image is etenia needy in this subject.

Compounds of the present invention often exhibit affinity in relation to serotonin NT2Athe receptor. In particular, the compounds of the present invention are antagonist of serotonin NT2Athe receptor. Preferred compounds of the present invention have binding constants Ki(T2Abelow 1 μm, in particular at most 0.5 micron, more preferably at most 250 nm, or, mainly, at most 100 nm. Thus, the compounds of the present invention is particularly suitable for the treatment of the above disorders, in particular mental disorders, such as schizophrenia, psychosis, cognitive disorders, drug abuse (i.e. related disorders portability substances, disorders related to syndrome substances (including substances such as opiates, nicotine, tobacco products, alcohol, benzodiazepines, cocaine, sedatives, sleep AIDS, etc), anxiety (including common anxiety disorder, panic disorder and obsessive-compulsive disorder). The affinity against NTA receptor, and antagonist activity may be defined by the generally accepted methods of screening a specialist in this field who is familiar with the publications (for review, see, for example, D.E Nichols, Hallocinogens, Pharmacology & Therapeutics 101 (2004) 131-181, J.A. Lieberman et al. Biol. Psychiatry 44 (1998) 1099-1117, S. Miyamoto et al., Mol. Psychiatry 10 (2005), 79-104).

The subject being treated in these ways, is usually a mammal, preferably human, man or woman, in the body which you want potentiation of the activity of a metabotropic glutamate receptor. The term "therapeutically effective amount" means the amount of compound that will elicit the biological or medical response of a tissue, system, animal or human, which is determined by the researcher, veterinarian, doctor, physician or other Clinician. It is clear that a specialist in this field of technology can affect neurological and psychiatric disorders by treatment of a patient affected at the moment, disorders, or by prophylactic treatment of a patient affected by disorder, an effective amount of the compounds of the present invention. Used in this description, the terms "treating" and "treatment" refer to all the ways where it can be slow, interruption, delay, suppression or stop the development described in this description of the neurological and mental disorders, but without having to show the complete elimination of all symptoms of the disorder, as well as about lakticheskoj treatment of the above disease conditions, especially in patients who are predisposed to such disease or disorder. Used in this description, the term "composition" refers to the inclusion of a product that contains specific ingredients in the specified amounts, as well as any product that results, directly or indirectly, from combination of the precise set of ingredients in the specified amounts. Such a term in relation to pharmaceutical compositions include product containing the active ingredient(s) and the inert ingredient(s), which is the media, as well as any product that is obtained, directly or indirectly, in the combination, consolidation or aggregation of any two or more ingredients, or as a result of dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more ingredients. Accordingly, the pharmaceutical compositions of the present invention include any composition obtained by mixing the compounds of the present invention and a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable" means a carrier, diluent or excipient, which must be compatible with other ingredients of the drug and not to act negatively on the recipient.

It should be understood that the term the "introduction" and/or "purpose" connections mean providing a compound of the invention or prodrug compound of the invention required treatment to the individual.

The preferred implementation of the present invention provides a method of treating schizophrenia, comprising the administration to a patient in need of treatment an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. In another preferred embodiment of the present invention, a method for preventing or treating anxiety, comprising the administration to a patient in need of treatment an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. Especially preferred anxiety disorders are common anxiety disorder, panic disorder and obsessive-compulsive disorder.

In another preferred embodiment of the present invention, a method for treatment of disorders associated with substance, including introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. In another preferred embodiment of the present invention, a method for treating migraine, comprising an introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. In another preferred embodiment, about what westline of the present invention, a method for treatment of epilepsy, includes introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or a pharmaceutically acceptable salt.

Of neurological and psychiatric disorders associated with glutamate dysfunction, which is subjected to the treatment according to the present invention, particularly preferred is the treatment of schizophrenia, anxiety, depression, migraine, disorders associated with substance, especially the dependence on substances, tolerance, substance withdrawal syndrome substance, and epilepsy. Especially preferred anxiety disorders are common anxiety disorder, panic disorder and obsessive-compulsive disorder.

Thus, in a preferred embodiment, the present invention provides a method of treating schizophrenia, comprising an introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. At present, the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1994, American Psychiatric Association, Washington, D.C.) provides a means of diagnosing schizophrenia and other mental disorders, inclusive. Disorders include disorders with mental symptoms as the defining characteristics. The term psychic is bream, known hallucinations, incoherent speech, destructive or catatonic behavior. The disorder includes paranoid, destructive, catatonic, dedifferentiate and residual schizophrenia, a disorder similar to schizophrenia, schizoaffective disorder, delusion disorder, brief psychotic disorder, joint psychotic disorder, psychotic disorder due to a General morbid condition caused by substance psychotic disorder and psychotic disorder, differently not precisely defined. The person skilled in the art may discover that there are alternative nomenclatures, nosology and classification system for neurological and psychiatric disorders, especially schizophrenia, and that these systems evolve with medical science. Thus, the term "schizophrenia" refers to the inclusion of such disorders, which are described in other diagnostic sources.

In another preferred embodiment, the present invention provides a method of treating anxiety, comprising an introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. At present, the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1994, Ameican Psychiatric Association, Washington, D.C. offers a means of diagnosis of anxiety and similar disorders, inclusive. Disorders include panic disorder with or without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder, disorder in the post-traumatic stress disorder as a result of acute stress, a common anxiety disorder, anxiety disorder due to a General morbid condition caused by substance anxiety disorder and anxiety disorder, differently not precisely defined. Used in this description, the term "anxiety" includes treatment such as an anxiety disorder and similar disorders as described in DSM-IV. The person skilled in the art may discover that there are alternative nomenclatures, nosology and classification system for neurological and psychiatric disorders, especially anxiety, and that these systems evolve with medical science.Thus, the term "anxiety" refers to the inclusion of such disorders, which are described in other diagnostic sources.

In another preferred embodiment, the present invention provides a method of treating depression, comprising an introduction to the needy in e is om the patient an effective amount of the compounds of formula I, his tautomer and/or pharmaceutically acceptable salts. At present, the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1994, American Psychiatric Association, Washington, D.C.) offers a means of diagnosis of depression and similar disorders, inclusive. Depressive disorders include, for example, single episodic or recurrent significant depressive disorders and estimatesa disorders, depressive neurosis and neurotic depression, melancholic depression including anorexia, weight loss, insomnia and early morning waking, and psychomotor delay, atypical depression (or reactive depression)including increased appetite, hypersomnia, psychomotor agitation or irritability, anxiety and phobias; seasonal affective disorder, or bipolar disorder, or banicescu depression, such as bipolar I disorder, bipolar II disorder, and cyclothymic disorder. Used in this description, the term "depression" includes the treatment of major depressive disorder and similar disorders as described in DSM-IV.

In another preferred embodiment, the present invention provides a method of treatment related to substance use disorders, especially dependence on substances, substance abuse, tolerance to the substances and withdrawal syndrome substance, includes introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. At present, the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (1994, American Psychiatric Association, Washington, D.C.) provides a means to diagnose disorders associated with response to drug abuse (including alcohol), side effects of the drug and the effects of toxins. Substances include alcohol, amphetamine and similar sympathomimetic action means, caffeine, marijuana, cocaine, hallucinogens, pharmaceutical forms for inhalation, nicotine, opioids, phencyclidine (PCP) or arylcyclohexylamine similar actions and sedatives, sleeping pills or anxiety. Also included is the dependence of many substances and other unknown associated with substance disorders. The person skilled in the art may discover that there are alternative nomenclatures, nosology and classification systems of neurological and psychiatric disorders, particularly disorders associated with substance, and that these systems evolve with medical science. Thus, the term "associated with substance disorder" implies the inclusion of such disorders, which are described in other diagnostic tool for the sources.

In another preferred embodiment, the present invention provides a method of treating migraine, comprising an introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or pharmaceutically acceptable salts. In one of the available sources of diagnostic methods, Dorland''s Medical Dictionary (23'rd Ed., 1982, W.B.Saunders Company, Philidelphia, PA), migraine is described as a symptom complex of periodic headaches, usually temporal and unilateral, often with irritability, nausea, vomiting, constipation or diarrhea and photophobia. Used in this description, the term "migraine" includes such periodic headaches, as the temporal and unilateral, associated with irritability, nausea, vomiting, constipation or diarrhea, photophobia and other symptoms attached. The person skilled in the art may discover that there are alternative nomenclatures, nosology and classification system for neurological and psychiatric disorders, including migraine, and that these systems evolve with medical science.

In another preferred embodiment, the present invention provides a method of treating epilepsy, comprising an introduction to the needy in this patient an effective amount of the compounds of formula I, its tautomer and/or pharmaceutical is acceptable salt. Currently there are several types and subtypes of seizures associated with epilepsy, including idiopathic, symptomatic and cryptogenic. Such epileptic seizures can be focal (partial) or common. They can also be simple or complex. Epilepsy is described in this field, for example, Epilepsy: A comprehensive textbook. Ed. By Jerome Engel, Jr. and Timithy A. Pedley (Lippincott-Raven, Philadelphia, 1997). Currently, International Classification of Diseases, Ninth Revision, (ICD-9) offers a means of diagnosis of epilepsy and related disorders, inclusive. Disorders include common nestorone epilepsy, common convulsive epilepsy, small epileptic seizure, a large seizures, focal epilepsy with impairment of consciousness, focal epilepsy without impairment of consciousness, infant convulsions, epilepsy focal continuous, other forms of epilepsy, is not precisely defined epilepsy, NOS. Used in this description, the term "epilepsy" includes all these types and subtypes. The person skilled in the art may discover that there are alternative nomenclatures, nosology and classification system for neurological and psychiatric disorders, including epilepsy, and that these systems evolve with medical science.

In the treatment, prevention, suppression, reduces the intensity drop or reduce the risk of painful conditions, which require potentiation of metabotropic activity of glutamate receptor, a suitable dose level will generally be about 0.01 to 500 mg per kg of body weight of the patient per day, which can be entered in single or multiple doses. Preferably, the dose will be from about 0.1 to 250 mg/kg / day; more preferably, from about 0.5 to 100 mg/kg / day. Suitable level doses can range from about 0.01 to 250 mg/kg / day, from about 0.05 to 100 mg/kg / day or from about 0.1 to 50 mg/kg / day. Within this interval, the dose may be from 0.05 to 0.5, from 0.5 to 5 or from 5 to 50 mg/kg / day. For oral administration, the composition preferably offered in the form of tablets containing 1.0 to 1000 milligrams of the active ingredient, particularly, 1,0, 5,0, 10,0, 15,0, 20,0, 25,0, 50,0, 75,0, 100,0, 150,0, 200,0, 250,0, 300,0, 400,0, 500,0, 600,0, 750,0, 800,0, 900,0 and 1000,0 milligrams of the active ingredient for the symptomatic installation doses for the patient being treated. Connection, you can enter the mode from 1 to 4 times a day, preferably once or twice a day. When treating, preventing, suppressing, reducing the intensity or reduce the risk of neurological and psychiatric disorders associated with glutamate dysfunction or other disease for which is shown with the organisations of the present invention, generally, satisfactory results are obtained when the compounds of the present invention is administered at a daily dosage of from about 0.1 milligram to 100 milligrams per kilogram of animal body weight, preferably, administered as a single daily dose or in separate doses two to six times a day, or in a long time released form. For most large mammals the total daily dosage is from about 1.0 milligrams to 1000 milligrams, preferably from about 1 milligram to 50 milligrams, in the case of a 70 kg adult human, the total daily dose will generally be from about 7 mg to 350 mg. This dose can be set for optimal therapeutic response. It should be understood, however, that the specific dose level and frequency of dosage for any particular patient may be changed and will depend on a number of factors including the activity of the applied specific compounds, the metabolic stability and length of action of this compound, the age, body weight, General health, sex, diet, mode and time of administration, rate of excretion, combination drugs, the severity of the particular painful condition and subjected to the treatment of owner.

Compounds according to nastasemarian additionally applicable in the way of warning, treating, suppressing, reducing the intensity or reduce the risk of the aforementioned diseases, disorders and painful conditions in combination with other agents, including mGluR agonist.

The term "potentiate number" refers to the number of mGluR agonist, i.e. the dose of the agonist, which is effective in the treatment described neurological and mental disorders, when introduced in combination with an effective amount of the compounds of the present invention. I believe that potentiate the number is less than the amount required to provide the same effect when mGlup agonist is administered without an effective amount of the compounds of the present invention.

Potentiate the number can be easily determined with the help of assisting diagnostician, as a specialist in this field, by applying conventional methods and observing results obtained under analogous circumstances. When determining potentiate the number of dose mGluR agonist for administration in combination with the compound of the formula I assisting diagnostician discusses a number of factors, including but not limited to them: selected for the introduction of the mGluR agonist, including its effectiveness and selectivity; a compound of formula I for the joint introduction; the species of mammal; its size, age and General health; suppose ageme specific disorder; the extent of injury or the severity of the disorder; the response of the individual patient; the route of administration; the bioavailability characteristics of administered drugs; selected dosing regimens; the use of other additional drug treatment and other relevant cases.

I believe that potentiate the number mGluR agonist for administration in combination with an effective amount of the compounds of formula I varies from about 0.1 milligram per kilogram of body weight per day (mg/kg/day to 100 mg/kg/day and, I believe, is less than the amount required to provide the same steps with the introduction without an effective amount of the compounds of formula I. the Preferred number of simultaneously introduced mGluR agonist is able to determine a specialist in this field. Compounds of the present invention can be used in combination with one or more other drugs in the treatment, prevention, inhibition, reduction in the intensity or reduction of risk of diseases or pathological States for which it is possible to apply the compounds of formula I or other medicines, in cases when the combination of drugs together safer and more effective than any one drug. Therefore, such other drug(s) means the(a) can be administered by and in the quantity accepted in this case, simultaneously or sequentially with the compound of the formula I. When a compound of the formula I is administered with one or more other drugs, preferred is a pharmaceutical composition in unit dosage form containing such other drugs and the compound of formula I. However, combination therapy may also include therapies in which the compound of formula I and one or more other medicines administered on different overlapping schedules. It is also suggested that when used in combination with one or more other active ingredients, the compounds of the present invention and other active ingredients can be used in lower doses than when used separately. In accordance with this pharmaceutical compositions of the present invention include compositions that contain one or more other active ingredients, in addition to the compound of formula I. the above combinations include combinations of compounds of the present invention not only one other active compound, but also with two or more other active compounds.

Similarly, the compounds of the present invention can be used in combination with other drugs is mi, which are used in preventing, treating, suppressing, reducing the intensity or reduction of risk of diseases or pathological States for which the applicable compounds of the present invention. Therefore, these other medicines can be administered by or in the amount accepted in this case, simultaneously or sequentially with the compound of the present invention. When the compound of the present invention is administered with one or more other drugs, preferred is a pharmaceutical composition containing such other drugs in addition to the compound of the present invention. Accordingly, the pharmaceutical composition of the present invention includes a composition that also contains one or more active ingredients, in addition to the compound of the present invention.

The mass ratio of the compounds of the present invention to the second active ingredient may vary and will depend upon the effective dose of each ingredient. Usually, it is necessary to apply an effective dose of each. Thus, for example, when the compound of the present invention is combined with another agent, the mass ratio of the compounds of the present invention to another agent will usually be in the range is roughly from 1000:1 to 1:1000, preferably, from about 200:1 to 1:200. The combination of the compounds of the present invention and other active ingredients will usually be in the aforementioned range, but in each case it is necessary to apply an effective dose of each active ingredient. In combinations of the compound of the present invention and other active agents can be entered separately or in combination. In addition, the introduction of one element may be prior to, simultaneously or sequentially with the introduction of another agent(s).

Compounds of the present invention it is possible to enter the conventional routes of administration, including parenteral (e.g. intramuscular, intraperitoneal, intravenous, ICV, intracavitary injection or infusion, subcutaneous injection, or implant), by inhalation spray, nazalnam, vaginal, rectal, sublingual, or local routes of administration.

Compounds of the present invention can be formulated into the composition of one or together with additional active compounds, a suitable single dose preparations containing conventional non-toxic pharmaceutical excipients. Excipients can be solid, semi-solid or liquid substances, which serve as fillers, carriers or medium for the active connection. Suitable ex is pienty listed in medical books for specialists in this field. In addition, products may include pharmaceutically acceptable carriers or conventional excipients, such as glidant, moisturizing agents; emulsifying and suspendresume agents; preservatives; antioxidants; protivoraketami agents; chelating agents; covering auxiliary agents; emulsion stabilizers; film formers; gel-forming agents; agents for masking odor; korrigentami taste; resins; hydrocolloids; solvents; solubilizing agents; neutralizing agents; accelerators diffusion; dyes; Quaternary ammonium compounds; agents for re-degreasing and excessive degreasing; source materials for ointments, creams or oils; silicone derivatives; auxiliary agents for distribution; stabilizers; sterilizing agents; bases of suppositories; auxiliary agents for tablets, such as binders, fillers, glidant, disintegrators or covering agents; propellants; agents for drying; cloud emulsions; thickeners; waxes; plasticizers and white mineral oil. The drug in this respect is the competence of the person skilled in the art, as described, for example, in Fiedler, H.P., Lexikon der Hilfsstoffe fur Pharmszie, Kosmetik und angrenzende Gebiete [Encyclipedia of fuxillary substances for pharmacy, cosmetics and related fields], 4thedition, Aulendorf: ECV-Editio-Kantor-Verlag, 1996.

Examples under Odesa pharmaceuticals are solid dosage forms, such as powders, granules, tablets, in particular tablets film, lozenges, sachets, starch capsules, covered with sugar pills, capsules such as hard capsules and soft gelatin capsules, suppositories or vaginal dosage forms, semi-solid dosage forms such as ointments, creams, hydrogels, pastes or patches, and liquid dosage forms such as solutions, emulsions, particularly emulsions of the type oil-in-water suspensions, for example, lotions, injectable drugs and infusion preparations, eye drops and ear drops. Implantable disposable device can also be used for injection of the inhibitors according to the present invention. In addition, it is also possible use of liposomes or microspheres.

In the manufacture of compositions of the compounds according to the present invention optionally mixed or diluted with one or more excipients.

The following examples are intended to further illustrate the present invention.

EXAMPLES GET

Abbreviations used in the examples which follow are: DCM dichloromethane, DMA N,N-dimethylacetamide, DMSO, dimethylsulfoxide, MeOH methanol, TFUK triperoxonane acid, MP-CNBH3macroporous cyanoborohydride.

Example 1

1-{4-[(thiophene-3-ylmethyl)amino]enyl}butane-1-he

In 20-ml test tube to a solution of 1-(4-AMINOPHENYL)butane-1-it (19,64 mg, 0.1 mmol) in DCM/MeOH (0.7 ml) was added a solution of thiophene-3-carbaldehyde (of 22.4 mg, 0.2 mmol) in DMA (0.8 ml). Solution was added acetic acid (18 mg, 0.3 mmol) in DCM/MeOH (0.7 ml) followed by the addition of 160 mg of resin MP-CNBH3(3 EQ.; substances 2.25 mmol/g). The tube was closed with a lid and then was heated with shaking over night at 55°C. the Development of the reaction was monitored by monitoring LC/MS. After completion of the reaction, the reaction mixture was concentrated to dryness. The residue was dissolved in 1:1 DMSO/MeOH. Purification HPLC with reversed phase (TFUC method) has been specified in the header of the connection.

N1NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,53-to 1.63 (m, 2H), 2,78 (t, 2H), or 4.31-4,37 (m, 2H), 6,63 is 6.67 (m, 2H), to 7.09 (DD, 1H), 7,31-7,37 (m, 1H), 7,45-7,49 (m, 1H), 7,69 to 7.75 (m, 2H);

MC (ESI) positive ion 260 (M+H)+; negative ion 258 (M-H)-.

Example 2

1-(4-{[5-(2-chlorophenyl)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-(2-chlorophenyl)furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

N1NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,55-of 1.64 (m, 2H), of 2.81 (t, 2H), 4,43-to 4.46 (m, 2H), 6,51 (d, 1H), 6,72-of 6.78 (m, 2H), 7,07 (d, 1H), 7.29 trend was 7.36 (m, 1H), 7,41 was 7.45 (m, 1H), 7,54 (DD, 1H), 7,74 for 7.78 (m, 2H), 7,80 (DD, 1H);

MC (ESI) positive ion 354 (M+H)+; negative ion 352 (M-H) -.

Example 3

1-(4-{[5-(3-chlorophenyl)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following method, analogously to example 1, but using 5-(3-chlorophenyl)furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

N1NMR (500 MHz, DMSO-d6/D2O) δ ppm -0,00 (t, 3H), 0,61 of 0.77 (m, 2H), 1,92 (t, 2H), 3,52 is 3.57 (m, 2H), to 5.58 (d, 1H), 5,85-of 5.89 (m, 2H), 6,07 (m, 1H), 6,41-6,47 (m, 1H), 6,56 (t, 1H), of 6.71-6,74 (m, 1H), 6,79 (t, 1H), 6,85-6,92 (m, 2H);

MC (ESI) positive ion 354 (M+H)+; negative ion 352 (M-H)-.

Example 4

1-(4-{[5-(4-chlorophenyl)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-(4-chlorophenyl)furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,48-of 1.65 (m, 2H), 2,80 (t, 2H), 4,36-of 4.44 (m, 2H), 6,46 (d, 1H), 6,67-PC 6.82 (m, 2H), 6.90 to (d, 1H), 7,41-to 7.50 (m, 2H), 7,62-of 7.70 (m, 2H), 7,73-7,79 (m, 2H);

MC (ESI) positive ion 354 (M+H)+; negative ion 352 (M-H)-.

Example 5

1-{4-[(5-chlorothiophene-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-chlorothiophene-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3 H), 1,48-of 1.64 (m, 2H), and 2.79 (t, 2H), to 4.41-4.53-in (m, 2H), 6,60 to 6.75 (m, 2H), 6,88-of 6.99 (m, 2H), 7,69-7,76 m, 2H);

MC (ESI) positive ion 394 (M+H)+; negative ion 392 (M-H)-.

Example 6

1-(4-{[5-(2-(triptoreline)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-[2-(trifluoromethyl)phenyl]furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,43-1,72 (m, 2H), 2,80 (t, 2H), 4,28-of 4.54 (m, 2H), 6,46-of 6.52 (m, 1H), 6,67-6,77 (m, 3H), 7,47-7,66 (m, 1H), 7,69-7,80 (m, 4H), to 7.84 (d, 1H);

MC (ESI) positive ion 388 (M+H)+; negative ion 386 (M-H)-.

Example 7

1-(4-{[5-(3-triptoreline)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-[3-(trifluoromethyl)phenyl]furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,54-of 1.64 (m, 2H), 2,80 (t, 2H), 4,42-4,47 (m, 2H), of 6.49 (d, 1H), 6,72-of 6.78 (m, 2H), 7,06 (d, 1H), to 7.59-of 7.70 (m, 2H), 7,74-7,79 (m, 2H), 7,88-to 7.93 (m, 1H), 7,95 (d, 1H);

MC (ESI) positive ion 388 (M+H)+; negative ion 386 (M-H)-.

Example 8

1-{4-[(3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 3H-imidazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/sub> /D2O) δ ppm of 0.90 (t, 3H), 1,53-of 1.66 (m, 2H), of 2.81 (t, 2H), 4,43-4,48 (m, 2H), 6,66-6,72 (m, 2H), 7,51-of 7.55 (m, 1H), 7,74-7,80 (m, 2H), 8,95 (d, 1H);

MC (ESI) positive ion 244 (M+H)+; negative ion 242 (M-H)-.

Example 9

1-{4-[(5-ethylthiophen-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-ethylthiophen-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,19 (t, 3H), 1,51-of 1.65 (m, 2H), 2,72 (kV, 2H), of 2.81 (t, 2H), to 4.38-4,50 (m, 2H), 6,60-of 6.73 (m, 3H), 6,86 (d, 1H), 7,66-7,79 (m, 2H);

MC (ESI) positive ion 288 (M+H)+; negative ion 286 (M-H)-.

Example 10

1-{4-[(benzo[b]thiophene-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using benzo[b]thiophene-3-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,51-of 1.65 (m, 2H), 2,78 (t, 2H), 4,57-4,63 (m, 2H), 6,67 to 6.75 (m, 2H), 7,35-7,49 (m, 2H), 7,54-to 7.61 (m, 1H), to 7.67-to 7.77 (m, 2H), of 7.90-8,02 (m, 2H);

MC (ESI) positive ion 310 (M+H)+; negative ion 308 (M-H)-.

Example 11

(R)-1-{4-[(tetrahydrofuran-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using (R)-tetrahydrofuran-2-carbaldehyde instead of thiophene-3-carbaldehyde.

<> 1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,51-to 1.67 (m, 3H), 1,94-to 2.06 (m, 1H), 2,43-2,52 (m, 1H), 2,80 (t, 2H), 3,02-3,13 (m, 2H), 3,38-to 3.52 (m, 1H), 3,59-to 3.67 (m, 1H), 3.75 to of 3.80 (m, 2H), 6,38-6,85 (m, 2H), 7,66-7,80 (m, 2H);

MC (ESI) positive ion 248 (M+H)+; negative ion 246 (M-H)-.

Example 12

1-{4-[(1-methyl-1H-indole-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1-methyl-1H-indole-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,50-of 1.64 (m, 2H), 2,78 (t, 2H), of 3.73-3,74 (m, 3H), 4,50-br4.61 (m, 2H), 6,32-to 6.43 (m, 1H), 6,70-6,77 (m, 2H), 6,95-7,05 (m, 1H), 7,09-7,17 (m, 1H), 7,41 (d, 1H), of 7.48 (d, 1H), 7,70-7,79 (m, 2H);

MC (ESI) positive ion 307 (M+H)+; negative ion 305 (M-H)-.

Example 13

1-{4-[(furan-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using furan-3-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,51 by 1.68 (m, 2H), and 2.79 (t, 2H), 4,30-to 4.38 (m, 2H), 6,30 to 6.35 (m, 1H), 6,38-6,46 (m, 1H), 6,63-of 6.78 (m, 2H), 7,53-EUR 7.57 (m, 1 H), 7.68 per-to 7.77 (m, 2H);

MC (ESI) positive ion 244 (M+H)+; negative ion 242 (M-H)-.

Example 14

1-{4-[(pyridine-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but with the COI is the whether picolinamides instead of thiophene-3-carbaldehyde.

1H-NMR (50 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,47-of 1.65 (m, 2H), and 2.79 (t, 2H), 4,57 with 4.65 (m, 2H), 6,62-6,69 (m, 2H), 7,56-the 7.65 (m, 2H), 7,71 for 7.78 (m, 2H), 8,08-8,16 (m, 1H), 8,60-8,68 (m, 1H);

MC (ESI) positive ion 255 (M+H)+; negative ion 253 (M-H)-.

Example 15

1-{4-[(pyridine-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using isonicotinamide instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,48-of 1.65 (m, 2H), 2,78 (t, 2H), 4,60-4,69 (m, 2H), 6,57 of 6.66 (m, 2H), 7,69-to 7.77 (m, 2H), 7,80-7,88 (m, 2H), 8,69-8,76 (m, 2H);

MC (ESI) positive ion 255 (M+H)+; negative ion 253 (M-H)-.

Example 16

1-{4-[(pyridine-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using nicotinanilide instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,49-of 1.65 (m, 2H), 2,78 (t, 2H), 4,51-br4.61 (m, 2H), 6,61-of 6.71 (m, 2H), 7,70 for 7.78 (m, 2H), 7,81-7,88 (m, 1H), 8,28 (d, 1H), 8,64-to 8.70 (m, 1H), 8,72-8,80 (m, 1H);

MC (ESI) positive ion 255 (M+H)+; negative ion 253 (M-H)-.

Example 17

1-{4-[(1-methyl-1H-imidazol-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1-methyl-1H-imidazole-2-carbaldehyde instead of tio is EN-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,52 by 1.68 (m, 2H), 2,84 (t, 2H), 3,81-a 3.87 (m, 3H), with 4.64-4.80 to (m, 2H), 6,65 to 6.75 (m, 2H), 7,46-of 7.55 (m, 1H), EUR 7.57 to 7.62 (m, 1H), 7,75-to 7.84 (m, 2H);

MC (ESI) positive ion 258 (M+H)+; negative ion 256 (M-H)-.

Example 18

1-{4-[(5-methylthiophene-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-methylthiophene-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.95 (t, 3H), 1,48-of 1.65 (m, 2H), 2,31-to 2.41 (m, 3H), 2,77 (t, 2H), to 4.38-4,50 (m, 2H), 6,56-6,70 (m, 3H), 6,78-6,91 (m, 1H), 7,62-to 7.77 (m, 2H);

MC (ESI) positive ion 274 (M+H)+; negative ion 272 (M-H)-.

Example 19

1-{4-[(3-methylthiophene-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 3-methylthiophene-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,48-of 1.64 (m, 2H), 2,18-of 2.23 (m, 3H), of 2.81 (m, 2H), 4,35-4,43 (m, 2H), 6,57 is 6.67 (m, 2H), PC 6.82-6.89 in (m, 1H), 7,27 (m, 1H), to 7.67 for 7.78 (m, 2H);

MC (ESI) positive ion 274 (M+H)+; negative ion 272 (M-H)-.

Example 20

1-{4-[(5-(hydroxymethylene-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-(hydroxymethyl)wagon is-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,52-of 1.65 (m, 2H), 2,80 (t, 2H), 4,28-to 4.33 (m, 2H), 4,32-4,37 (m, 2H), 6,11-6,34 (m, 2H), 6,55-6,87 (m, 2H), 7,66 for 7.78 (m, 2H);

MC (ESI) positive ion 274 (M+H)+; negative ion 272 (M-H)-.

Example 21

1-{4-[(5-methylfuran-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-methylfuran-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,49 by 1.68 (m, 2H), 2,19-of 2.26 (m, 3H), 2,80 (t, 2H), 4,16-to 4.33 (m, 2H), 5,86-6,05 (m, 1H), 6,12-of 6.26 (m, 1H), 6,60-6,74 (m, 2H), 7,66 for 7.78 (m, 2H);

MC (ESI) positive ion 258 (M+H)+; negative ion 256 (M-H)-.

Example 22

1-{4-[(3-methylbenzo[b]thiophene-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 3-methylbenzo[b]thiophene-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,50-to 1.63 (m, 2H), 2.40 a at 2.45 (m, 3H), 2,78 (t, 2H), 4,59-4,63 (m, 2H), 6,60-of 6.71 (m, 2H), 7.29 trend was 7.36 (m, 1H), 7,37-7,42 (m, 1H), 7,69-7,76 (m, 3H), of 7.82 (d, 1H);

MC (ESI) positive ion 324 (M+H)+.

Example 23

5-[(4-Butyrylthiocholine)methyl]furan-2-ymetray ether acetic acid

Specified in the title compound was obtained following the method similar to example 1, but using (5-formylfuran-2-yl)methyl) - Rev. of Zetta instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,52-of 1.65 (m, 2H), 1,99 e 2.06 (m, 3H), and 2.79 (t, 2H), 4,29-to 4.41 (m, 2H), 4,93-5,02 (m, 2H), 6,28-6,36 (m, 1H), 6,40-of 6.49 (m, 1H), 6,61-6,72 (m, 2H), 7,66 for 7.78 (m, 2H);

MC (ESI) positive ion 316 (M+H)+; negative ion 314 (M-H)-.

Example 24

1-{4-[(1-acetyl-1H-indol-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1-acetyl-indol-3-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.93 (t, 3H), 1,52-of 1.66 (m, 2H), 2,59-of 2.64 (m, 3H), and 2.79 (t, 2H), 4,42-4,55 (m, 2H), 6,66-6,84 (m, 2H), 7.24 to the 7.43 (m, 2H), 7.68 per-7,79 (m, 3H), 7,80-7,89 (m, 1H), compared to 8.26-8.34 per (m, 1H);

MC (ESI) positive ion 335 (M+H)+; negative ion 333 (M-H)-.

Example 25

1-{4-[(quinoline-6-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using quinoline-6-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.87 (t, 3H), 1,52-to 1.61 (m, 2H), 2,77 (t, 2H), with 4.64-and 4.68 (m, 2H), 6,65-of 6.71 (m, 2H), 7,70-7,74 (m, 2H), to $ 7.91-of 7.97 (m, 1H), 8,04-of 8.09 (m, 1H), 8,16-8,21 (m, 2H), to 8.94 (d, 1H), 9,13 (DD, 1H);

MC (ESI) positive ion 305 (M+H)+.

Example 26

1-{4-{(thiazol-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using thiazole-2-carbaldehyde instead of iophen-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,50-of 1.65 (m, 2H), 2,80 (t, 2H), with 4.64-4,71 (m, 2H), 6,63-of 6.73 (m, 2H), EUR 7.57-7,63 (m, 1H), 7,72-7,79 (m, 3H);

MC (ESI) positive ion 261 (M+H)+; negative ion 259 (M-H)-.

Example 27

1-(4-{[1-(toluene-4-sulfonyl)-1H-pyrrol-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1-(p-toluensulfonyl)-1H-pyrrole-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,51-to 1.63 (m, 2H), 2,38-to 2.42 (m, 3H), and 2.79 (t, 2H), 4,32-4,50 (m, 2H), 6,10-6,18 (m, 1H), 6,25-6,32 (m, 1H), 6,33-6,46 (m, 2H), 7,35-the 7.43 (m, 1H), 7,44 is 7.50 (m, 2H), EUR 7.57-of 7.69 (m, 2H), 7,74-7,87 (m, 2H);

MC (ESI) positive ion 397 (M+H)+; negative ion 395 (M-H)-.

Example 28

1-{4-[(1-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1-methyl-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,52 was 1.69 (m, 2H), and 2.79 (t, 2H), of 3.77-of 3.80 (m, 3H), 4,12-to 4.23 (m, 2H), 6,60 of 6.68 (m, 2H), 7,34-7,44 (m, 1H), 7,58-to 7.64 (m, 1H), 7,69-7,76 (m, 2H);

MC (ESI) positive ion 258 (M+H)+; negative ion 256 (M-H)-.

Example 29

1-(4-{[5-(piperidine-1-yl)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-(piperidine-1-yl)furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

Example 30

1-{4-[(4-phenylthiazol-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 4-phenylthiazol-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,45-1,71 (m, 2H), 2,82 (t, 2H), 4,71-rate 4.79 (m, 2H), 6,67-6,74 (m, 2H), 7,34-7,40 (m, 1H), 7,42-7,52 (m, 2H), 7,71-7,80 (m, 2H), of 7.90-7,98 (m, 3H);

MC (ESI) positive ion 337 (M+H)+; negative ion 335 (M-H)-.

Example 31

1-{4-[(1H-indol-2-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1H-indole-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), 1,51-of 1.62 (m, 2H), 2,78 (t, 2H), 4,39-4,58 (m, 2H), 6,28 to 6.35 (m, 1H), 6,62-6,74 (m, 2H), 6.89 in-7,02 (m, 1H), 7,00-7,10 (m, 1H), 7,26-7,37 (m, 1H), 7,40-to 7.50 (m, 1H), 7,62-7,81 (m, 2H).

Example 32

1-(4-{[1-(toluene-4-sulfonyl)-1H-indol-3-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1-[(4-were)sulfonyl]-1H-indole-3-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm were 0.94 (t, 3H), 1,58 was 1.69 (m, 2H), 2,28-of 2.38 (m, 3H), 2,84 (t, 2H), 4,48-4,55 (m, 2H), 6,62-for 6.81 (m, 2H), 7,4-the 7.43 (m, 4H), to 7.67-to 7.84 (m, 6H), 7,94 (d, 1H);

MC (ESI) positive ion 447 (M+H)+; negative ion 445 (M-H)-.

Example 33

1-{4-[(5-methyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 3-methyl-1H-pyrazole-5-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,52 is 1.70 (m, 2H), 2.21 are of 2.25 (m, 3H), 2,80 (t, 2H), 4,24 is 4.36 (m, 2H), 6,05-6,12 (m, 1H), 6,57-6,72 (m, 2H), to 7.67-7,80 (m, 2H);

MC (ESI) positive ion 258 (M+H)+; negative ion 256 (M-H)-.

Example 34

1-(4-{[4-bromo-2-(4-chlorbenzyl)-2H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 4-bromo-1-(4-Chlorobenzyl)-1H-pyrazole-5-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.95 (t, 3H), 1,53-1,72 (m, 2H), and 2.83 (t, 2H), 4,24-or 4.31 (m, 2H), 5,22-5,43 (m, 2H), 6,66 to 6.75 (m, 2H), 7,20-7,33 (m, 2H), 7,37-7,46 (m, 2H), 7,69-of 7.82 (m, 2H), 8,02-8,10 (m, 1H);

MC (ESI) positive ion 448 (M+H)+; negative ion 446 (M-H)-.

Example 35

4-{5-[(4-butyrylthiocholine)methyl]furan-2-yl}benzosulfimide

Specified in the title compound was obtained following the method similar to example 1, but using 4-(5-formylfuran-2-yl)benzosulfimide instead of thiophene-3-carbaldehyde.

1H-NMR(500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,53 by 1.68 (m, 2H), 2.77-to 2,87 (m, 2H), to 4.38-4,51 (m, 2H), of 6.52 (d, 1H), of 6.71-for 6.81 (m, 2H), 7,06 (d, 1H), 7,66-7,74 (m, 1H), 7,74-7,81 (m, 2H), 7,81-7,89 (m, 3H);

MC (ESI) positive ion 399 (M+H)+; negative ion 397 (M-H)-.

Example 36

1-(4-{[5-(2-(trifloromethyl)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-(2-(triptoreline)phenyl)furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,51-of 1.66 (m, 2H), of 2.81 (t, 2H), 4,42-4,50 (m, 2H), 6,53 (d, 1H), 6,70-of 6.78 (m, 2H), 6.82 (d, 1H), 7,39-of 7.55 (m, 3H), 7,72-7,81 (m, 2H), 7,84-of 7.90 (m, 1H);

MC (ESI) positive ion 404 (M+H)+; negative ion 402 (M-H)-.

Example 37

1-(4-{[4-(3-bromophenyl)pyridine-3-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 4-(3-bromophenyl)nicotinanilide instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,87 with 0.93 (m, 3H), 1,51-of 1.65 (m, 2H), of 2.81 (t, 2H), or 4.31-4,51 (m, 2H), 6,41-6,60 (m, 2H), 7,51-7,86 (m, 7H), 8,69-8,83 (m, 2H);

MC (ESI) negative ion 407 (M-H)-.

Example 38

1-(4-{[3-(4-methoxyphenyl)-1-(thiophene-2-carbonyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but with ispolzovaniem-(4-methoxyphenyl)-1-(thiophene-2-carbonyl)-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.95 (t, 3H), 1,60-1,70 (m, 2H), 2,87 (t, 2H), a 3.87-to 3.89 (m, 3H), 4,48-to 4.52 (m, 2H), 6,72-6,77 (m, 2H), 7,14-7,19 (m, 2H), was 7.36-7,41 (m, 1H), 7,80-to 7.84 (m, 2H), 7,87-to $ 7.91 (m, 2H), 8,24 (DD, 1H), 8,44 (DD, 1H), 8,50-charged 8.52 (m, 1H);

MC (ESI) positive ion 460 (M+H)+; negative ion 458 (M-H)-.

Example 39

1-(4-{[5-(3-(trifloromethyl)furan-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-[3-(triptoreline)phenyl]furan-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,87-to 0.96 (m, 3H), 1,55-1,65 (m, 2H), was 2.76-to 2.85 (m, 2H), 4,40-4,47 (m, 2H), 6,45-of 6.52 (m, 1H), 6,72-for 6.81 (m, 2H), 7,00? 7.04 baby mortality (m, 1H), 7.23 percent-7,29 (m, 1H), 7,52-to 7.59 (m, 2H), 7,66-7,72 (m, 1H), 7,75-7,80 (m, 2H);

MC (ESI) positive ion 404 (M+H)+; negative ion 402 (M-H)-.

Example 40

1-(4-{[3-(thiophene-2-yl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 3-(thiophene-2-yl)-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 to 0.96 (m, 3H), 1.56 to its 1.68 (m, 2H), of 2.81 (t, 2H), 4,30-to 4.38 (m, 2H), 6,66-6,76 (m, 2H), 7,11-7,14 (m, 1H), 7,27-7,34 (m, 1H), 7,49-7,52 (m, 1H), 7,71-7,80 (m, 3H);

MC (ESI) positive ion 326 (M+H)+; negative ion 324 (M-H)-.

Example 41

1-{4-[(5-chlorobenzo[b]thiophene-3-ylmethyl)amino]phenyl}Boo is an-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-chlorobenzo[b]thiophene-3-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.93 (t, 3H), 1,54 by 1.68 (m, 2H), 2,84 (t, 2H), br4.61-of 4.66 (m, 2H), 6,69-for 6.81 (m, 2H), 7,42-7,52 (m, 1H), 7,72-a 7.85 (m, 3H), 7,98-8,13 (m, 2H);

MC (ESI) positive ion 344 (M+H)+.

Example 42

1-(4-{[3-(4-(triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 3-(4-(trifluoromethyl)phenyl)-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 to 0.94 (m, 3H), 1,53 was 1.69 (m, 2H), of 2.81 (t, 2H), or 4.31-4,39 (m, 2H), 6,63-6,69 (m, 2H), 7,73 for 7.78 (m, 3H), 7,79-to 7.84 (m, 2H), 7,87-to 7.93 (m, 2H);

Example 43

1-{4-[(5-methyl-3-phenylisoxazol-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-methyl-3-phenylisoxazol-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (50 MHz, DMSO-d6/D2O) δ ppm 0,80-0,90 (m, 3H), 1,44-to 1.61 (m, 2H), 2,39 at 2.45 (m, 3H), 2,72-and 2.79 (m, 2H), 4,06 is 4.13 (m, 2H), 6,52-of 6.61 (m, 2H), 7,43-7,49 (m, 3H), EUR 7.57-to 7.64 (m, 2H), to 7.67-7,73 (m, 2H);

MC (ESI) positive ion 335 (M+H)+; negative ion 333 (M-H)-.

Example 44

1-{4-[(2,5-dimethyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he

Specify the OU in the title compound was obtained, following the method similar to example 1, but using 1,3-dimethyl-1H-pyrazole-5-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.92 (t, 3H), 1,51 by 1.68 (m, 2H), 2,07 with 2.14 (m, 3H), of 2.81 (t, 2H), 3,69-of 3.77 (m, 3H), or 4.31 was 4.42 (m, 2H), 5,97-between 6.08 (m, 1H), 6,63 to 6.75 (m, 2H), 7,72-7,79 (m, 2H);

MC (ESI) positive ion 272 (M+H)+; negative ion 270 (M-H)-.

Example 45

1-{4-[(5-methyl-1-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.92 (t, 3H), 1,55 was 1.69 (m, 2H), 2,30-of 2.36 (m, 3H), 2,82 (t, 2H), 4,17-of 4.25 (m, 2H), 6,69-of 6.78 (m, 2H), 7,43-to 7.59 (m, 5H), 7,62-7,66 (m, 1H), 7,74-7,81 (m, 2H);

MC (ESI) positive ion 334 (M+H)+; negative ion 332 (M-H)-.

Example 46

1-{4-[(2-phenylthiazol-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 2-phenylthiazol-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,89-0,98 (m, 3H), 1,55-1,71 (m, 2H), 2,84 (t, 2H), 4,51-4,58 (m, 2H), 6,69-to 6.80 (m, 2H), 7,49-to 7.67 (m, 4H), 7,74-a 7.85 (m, 2H), 7,94-with 8.05 (m, 2H).

Example 47

1-{4-[(4-methyl-2-phenylpyrimidine-5-ylmethyl)amino]phenyl}butane-1-he

Specified in the header of connection produces and, following the method similar to example 1, but using 4-methyl-2-phenylpyrimidine-5-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,57-1,72 (m, 2H), 2,61-2,69 (m, 3H), 2,85 (t, 2H), to 4.41-4,51 (m, 2H), 6,62-6,77 (m, 2H), 7,50 to 7.62 (m, 3H), 7,74-to 7.84 (m, 2H), 8,28-8,46 (m, 2H), 8,60-8,68 (m, 1H);

MC (ESI) positive ion 346 (M+H)+; negative ion 344 (M-H)-.

Example 48

1-(4-{[1-(phenylsulfonyl)-1H-indol-3-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 1-(phenylsulfonyl)-1H-indole-3-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm were 0.94 (t, 3H), 1,59 by 1.68 (m, 2H), and 2.83 (t, 2H), 4,50-of 4.54 (m, 2H), 6,69 to 6.75 (m, 2H), 7,28-7,34 (m, 1H), 7,37-7,44 (m, 1H), 7,54-to 7.61 (m, 2H), 7,66-7,71 (m, 1H), 7,73-7,79 (m, 3H), 7,81-7,83 (m, 1H), of 7.90-7,98 (m, 3H);

MC (ESI) positive ion 433 (M+H)+; negative ion 431 (M-H)-.

Example 49

1-(4-{[5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,87-of 0.95 (m, 3H), 1,55-of 1.66 (m, 2H), 2,16-2,19 (m, 3H), 2,78 (t, 2H), 3.46 in is 3.57 (m, 3H), 3,84-of 3.94 (m, 2H), 6,44-6,59 (m, 2H), 6,91? 7.04 baby mortality (m, 2H), 7,29-7,44 (m, 2H), 7,58-7,72 (m, 2H);

C (ESI) positive ion 398 (M+H) +; negative ion 396 (M-H)-.

Example 50

1-(4-{[5-(3-chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-(3-chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,86-of 0.95 (m, 3H), 1,50-to 1.67 (m, 2H), 2,16-of 2.21 (m, 3H), 2,75-of 2.81 (m, 2H), 3,48-of 3.53 (m, 3H), 3,88-3,93 (m, 2H), 6,47-is 6.54 (m, 2H), 6,95 (DD, 1H), 6,98-7,02 (m, 1H), 7,13-7,20 (m, 1H), 7,37 (t, 1H), to 7.61-7,72 (m, 2 H);

MC (ESI) positive ion 398 (M+H)+; negative ion 396 (M-H)-.

Example 51

1-{4-[(5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm were 0.94 (t, 3H), 1,54-1,71 (m, 2H), 2.26 and-of 2.34 (m, 3H), 2,85 (t, 2H), 4,18-4,27 (m, 2H), 6,65-to 6.80 (m, 2H), of 7.48-the 7.65 (m, 5H), 7,74-7,87 (m, 2H);

MC (ESI) positive ion 368 (M+H)+.

Example 52

1-(4-{[5-chloro-1-methyl-3-(phenylthiomethyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-chloro-1-methyl-3-(phenylthiomethyl)-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 is Hz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,54-of 1.66 (m, 2H), 2,70-to 2.85 (m, 2H), 3.72 points-3,74 (m, 3H), 4,11-4,16 (m, 2H), 4,17-is 4.21 (m, 2H), 6,62-6,69 (m, 2H), 7,16-of 7.23 (m, 1H), 7,27-to 7.32 (m, 2H), 7,33-7,38 (m, 2H), 7,71-7,80 (m, 2H);

MC (ESI) positive ion 414 (M+H)+; negative ion 412 (M-H)-.

Example 53

1-(4-{[5-chloro-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-yl]methylamino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 5-chloro-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.95 (t, 3H), 1,58 is 1.70 (m, 2H), 2,84 (t, 2H), 3,89-4,01 (m, 3H), 4,19-to 4.33 (m, 2H), 6,62-6,74 (m, 2H), 7,74-a 7.85 (m, 2H);

MC (ESI) positive ion 361 (M+H)+.

Example 54

1-(4-{[4-(3-chlorobenzoyl)-1-methyl-1H-pyrrol-2-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 1, but using 4-(3-chlorobenzoyl)-1-methyl-1H-pyrrole-2-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,82 is 0.99 (m, 3H), 1,53-of 1.66 (m, 2H), 2,78-to 2.85 (m, 2H), 3,68-3,70 (m, 3H), 4,33-and 4.40 (m, 2H), 6,51-6,55 (m, 1H), 6,60 of 6.66 (m, 1H), of 6.71-6,77 (m, 2H), 7,41-7,47 (m, 1H), of 7.64-7,80 (m, 5H);

MC (ESI) positive ion 395 (M+H)+; negative ion 393 (M-H)-.

Example 55

1-{4-[(1-ethyl-5-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following method, which is similar to ogino example 1, but using 1-ethyl-5-methyl-1H-pyrazole-4-carbaldehyde instead of thiophene-3-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 to 0.94 (m, 3H), of 1.29 (t, 3H), 1,55-of 1.66 (m, 2H), 2.26 and-of 2.28 (m, 3H), 2.77-to 2,85 (m, 2H), 4,01-4.09 to (m, 2H), 4,10-to 4.15 (m, 2H), 6,57-6,76 (m, 2H), 7,37 was 7.45 (m, 1H), 7.68 per-7,79 (m, 2H);

MC (ESI) positive ion 284(M+H)+; negative ion 286 (M-H)-.

Example 56

1-{4-[(3,5-dimethyl-1-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

In 20-ml test tube to a solution of 1-(4-AMINOPHENYL)butane-1-she (46 mg, 0.28 mmol)dissolved in DCM/MeOH (0.6 ml), was added a solution of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde (112 mg, 0,56 mmol) in DMA (1.8 ml). Then the solution was added acetic acid (50 mg, 0.84 mmol) in DCM/MeOH (0.6 ml) followed by addition of 361 mg of the resin Mr-CNBH3(3 EQ.; substances 2.34 mmol/g). The tube was closed with a lid and then was heated with shaking over night at 55°C. the Development of the reaction was monitored by monitoring LC/MS. After completion of the reaction, the reaction mixture was concentrated to dryness. The resulting residue was dissolved in DMSO/Meon 1:1. Purification HPLC with reversed phase (method TFUC) has been specified in the header of the connection.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,53 is 1.70 (m, 2H), 2,18-2,22 (m, 3H), 2.26 and is 2.33 (m, 3H), and 2.79 (t, 2H), 4,07-to 4.14 (m, 2H), 6,62-6,74 (m, 2H), was 7.36-7,49 (m, 3H), 7,49-of 7.55 (m, 2H), 7,71-7,81 (m, 2H);

MC (ESI) positive ion 348 (M+H)+; negative ion 346 (M-H) -.

Example 57

1-{4-[(2-phenyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-phenyl-1H-pyrazole-5-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,53-of 1.64 (m, 2H), and 2.79 (t, 2H), 4,37-4,47 (m, 2H), 6,36-6,41 (m, 1H), 6,53-of 6.61 (m, 2H), 7,41-7,51 (m, 1H), 7,51-to 7.59 (m, 4H), to 7.61-7,66 (m, 1H), 7,66-7,76 (m, 2H);

MC (ESI) positive ion 320 (M+H)+; negative ion 318 (M-H)-.

Example 58

1-{4-[(1-tert-butyl-3,5-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-tert-butyl-3,5-dimethyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,87 with 0.93 (m, 3H), 1,52-of 1.56 (m, 9H), 1.56 to of 1.64 (m, 2H), 2.06 to a 2.12 (m, 3H), 2,33-of 2.38 (m, 3H), 2,75-and 2.83 (m, 2H), 3,90-4,01 (m, 2H), 6,61-6,74 (m, 2H), 7,70 for 7.78 (m, 2H);

MC (ESI) positive ion 328 (M+H)+; negative ion 326 (M-H)-.

Example 59

1-{4-[(5-methyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 3-methyl-1H-pyrazole-5-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6 2O) δ ppm 0,84-of 0.95 (m, 3H), 1,50-of 1.66 (m, 2H), 2,17-2,22 (m, 3H), and 2.79 (t, 2H), 4,24-or 4.31 (m, 2H), 5,99-6,05 (m, 1H), 6,58-of 6.73 (m, 2H), 7,65-7,80 (m, 2H);

MC (ESI) positive ion 258 (M+H)+; negative ion 256 (M-H)-.

Example 60

1-{4-[(1,5-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1,5-dimethyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,54-of 1.65 (m, 2H), 2,22 was 2.25 (m, 3H), 2,75-2,82 (m, 2H), 3,65-and 3.72 (m, 3H), 4,01-to 4.15 (m, 2H), 6,60 of 6.66 (m, 2H), 7,26 and 7.36 (m, 1H), 7,63-to 7.84 (m, 2H);

MC (ESI) positive ion 272 (M+H)+.

Example 61

1-{4-[(1,3-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1,3-dimethyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 0,85-0,95 (m, 3H), 1,52-of 1.66 (m, 2H), 2,09-of 2.16 (m, 3H), and 2.79 (t, 2H), 3,65-3,71 (m, 3H), 4,01-4,11 (m, 2H), 6,61 of 6.68 (m, 2H), 7,51-7,53 (m, 1H), 7,70-7,76 (m, 2H);

MC (ESI) positive ion 272 (M+H)+; negative ion 270 (M-H)-.

Example 62

1-{4-[(1-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-methyl-1H-pyrazol-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,49 by 1.68 (m, 2H), and 2.79 (t, 2H), of 3.77-of 3.80 (m, 3H), 4,10-4,20 (m, 2H), 6,57-of 6.71 (m, 2H), 7,34-the 7.43 (m, 1H), 7,58-to 7.64 (m, 1H), 7,66-7,79 (m, 2H);

MC (ESI) positive ion 258 (M+H)+; negative ion 256 (M-H)-.

Example 63

1-(4-{[3-(5-methylfuran-2-yl)-1-phenyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 3-(5-methylfuran-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,52-to 1.67 (m, 2H), 2,31-is 2.37 (m, 3H), 2,80 (t, 2H), 4,35-of 4.44 (m, 2H), to 6.19-of 6.26 (m, 1H), 6,65 (d, 1H), 6,68-6,77 (m, 2H), 7.24 to 7,37 (m, 1H), 7,46-to 7.61 (m, 2H), 7,69-7,87 (m, 4H), of 8.37-8,48 (m, 1H);

MC (ESI) negative ion 398 (M-H)-.

Example 64

1-(4-{[1-phenyl-3-(thiophene-2-yl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-phenyl-3-(thiophene-2-yl)-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.91 (t, 3H), 1,53-of 1.66 (m, 2H), of 2.81 (t, 2H), 4,37-4,43 (m, 2H), 6,70-6,76 (m, 2H), 7,14-7,19 (m, 1H), 7,32-7,37 (m, 1H), 7,41 (DD, 1H), 7,50-of 7.60 (m, 3H), 7,74-a 7.85 (m, 4H), 8,50-8,54 (m, 1H);

MC (ESI) positive ion 402 (M+H)+; negative ion 400 (M-H)-.

Example 65

1-{4-[(1-ethyl-5-methyl-1H-pyrazole-4-ilma who yl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-ethyl-5-methyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), of 1.27 (t, 3H), 1,54-of 1.64 (m, 2H), 2,20-of 2.27 (m, 3H), and 2.79 (t, 2H), a 4.03 (q, 2H), 4,07-4,10 (m, 2H), to 6.43-6,83 (m, 2H), 7,25-7,49 (m, 1H), 7,58-7,86 (m, 2H);

MC (ESI) positive ion 286 (M+H)+; negative ion 284 (M-H)-.

Example 66

1-{4-[(1-ethyl-3-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-ethyl-3-methyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), of 1.32 (t, 3H), 1,52-of 1.65 (m, 2H), 2,11-2,17 (m, 3H), and 2.79 (t, 2H), 3,98 (kV, 2H), 4,06-4,12 (m, 2H), 6,57-of 6.71 (m, 2H), 7,52-to 7.61 (m, 1H), 7,69-to 7.77 (m, 2H);

MC (ESI) positive ion 286 (M+H)+; negative ion 284 (M-H)-.

Example 67

1-{4-[(1-ethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-ethyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), of 1.34 (t, 3H), 1,51-of 1.66 (m, 2H), and 2.79 (t, 2H), 4,07 (kV, 2H), 4,13-is 4.21 (m, 2H), 6,63-of 6.71 (m, 2H), 7,35-7,47 (m, 1H), ,63-7,70 (m, 1H), 7,70-to 7.77 (m, 2H);

MC (ESI) positive ion 272(M+H)+; negative ion 270 (M-H)-.

Example 68

1-{4-[(1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,50-to 1.67 (m, 2H), and 2.79 (t, 2H), 4,14-4,27 (m, 2H), 6,55-6,72 (m, 2H), 7,53-to 7.59 (m, 2H), 7,66 for 7.78 (m, 2H);

MC (ESI) positive ion 244 (M+H)+; negative ion 242 (M-H)-.

Example 69

1-{4-[(2,5-dimethyl-1H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 2,5-dimethyl-2H-pyrazole-3-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,49-of 1.65 (m, 2H), 2,04 is 2.10 (m, 3H), 2,80 (t, 2H), 3,63-and 3.72 (m, 3H), 4.26 deaths-of 4.38 (m, 2H), 5,94-6,00 (m, 1H), 6,60 to 6.75 (m, 2H), 7,65-7,79 (m, 2H);

MC (ESI) positive ion 272 (M+H)+; negative ion 270 (M-H)-.

Example 70

1-{4-[(3-methyl-1-propyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 3-methyl-1-propyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-I Is R (500 MHz, DMSO-d6/D2O) δ ppm of 0.79 (t, 3H), of 0.90 (t, 3H), 1,53-of 1.65 (m, 2H), from 1.66 to 1.76 (m, 2H), 2,11-to 2.18 (m, 3H), 2,78 (t, 2H), 3,91 (t, 2H), 4,06-4,12 (m, 2H), 6,61 of 6.68 (m, 2H), 7,56 to 7.62 (m, 1H), 7.68 per-7,76 (m, 2H);

MC (ESI) positive ion 300 (M+H)+; negative ion 298 (M-H)-.

Example 71

1-{4-[(5-methyl-1-propyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 5-methyl-1-propyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.82 (t, 3H), of 0.90 (t, 3H), 1,53-to 1.63 (m, 2H), 1,65-to 1.77 (m, 2H), 2,18-of 2.28 (m, 3H), 2,78 (t, 2H), 3,95 (t, 2H), 4,06-4,12 (m, 2H), 6,61 is 6.67 (m, 2H), 7,32-7,39 (m, 1H), to 7.67-to 7.77 (m, 2H);

MC (ESI) positive ion 300 (M+H)+; negative ion 298 (M-H)-.

Example 72

1-{4-[(1-methyl-1H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-methyl-1H-pyrazole-3-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,53-of 1.66 (m, 2H), and 2.79 (t, 2H), 3,78-of 3.80 (m, 3H), 4,24-4,27 (m, 2H), x 6.15 (d, 1H), 6,63-6,69 (m, 2H), EUR 7.57 (d, 1H), 7,69-7,76 (m, 2H);

MC (ESI) positive ion 258 (M+H)+; negative ion 256 (M-H)-.

Example 73

1-{4-[(1-methyl-5-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl})butane-1-he

Specified in the header connect the tion was received, following the method similar to example 56, but using 1-methyl-5-phenyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,48-of 1.66 (m, 2H), 2,78 (t, 2H), 3.72 points-to 3.73 (m, 3H), 4,00-4,06 (m, 2H), of 6.49 return of 6.58 (m, 2H), 7,38-to 7.59 (m, 6H), to 7.64-7,72 (m, 2H);

MC (ESI) positive ion 334 (M+H)+; negative ion 332 (M-H)-.

Example 74

1-{4-[(1,5-dimethyl-1H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1,5-dimethyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,51-of 1.66 (m, 2H), 2.05 is is 2.10 (m, 3H), 2,80 (t, 2H), 3,68-and 3.72 (m, 3H), 4,25 is 4.36 (m, 2H), 5,76-of 6.20 (m, 1H), of 6.49-6,77 (m, 2H), of 7.64-of 7.82 (m, 2H);

MC (ESI) positive ion 272 (M+H)+; negative ion 270 (M-H)-.

Example 75

1-{4-[(1-isopropyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 1-isopropyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm from 0.88 (t, 3H), of 1.37 (d, 6H), 1,52 by 1.68 (m, 2H), 2,80 (t, 2H), 4,12-4,20 (m, 2H), 4,37 figure-4.49 (m, 1H), 6,63-6,69 (m, 2H), 7,37-7,44 (m, 1H), 7,66 for 7.78 (m, 3H);

MC (ESI) positive ion 286 (M+H)+; tricatel the hydrated ion 284 (M-H) -.

Example 76

1-(4-{[3-(4-hydroxyphenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 3-(4-hydroxyphenyl)-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm of 0.90 (t, 3H), 1,52-to 1.67 (m, 2H), and 2.79 (t, 2H), 4,18-4,27 (m, 2H), 6,56 of 6.68 (m, 2H), for 6.81-6.90 to (m, 2H), 7,39-of 7.48 (m, 2H), EUR 7.57-to 7.64 (m, 1H), 7,70 for 7.78 (m, 2H);

MC (ESI) positive ion 334 (M+H)+.

Example 77

1-{4-[(3-tert-butyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

Specified in the title compound was obtained following the method similar to example 56, but using 3-tert-butyl-1H-pyrazole-4-carbaldehyde instead of 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carbaldehyde.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm to 0.89 (t, 3H), 1,28-of 1.36 (m, 9H), 1,53-to 1.67 (m, 2H), and 2.79 (t, 2H), 4,20-4.26 deaths (m, 2H), 6,60-of 6.71 (m, 2H), 7,37-7,41 (m, 1H), 7.68 per for 7.78 (m, 2H);

MC (ESI) positive ion 300 (M+H)+; negative ion 298 (M-H)-.

Example 78

N-sensitiza-2-amine

In 20-ml test tube to a solution of benzaldehyde (40 mg, 0.38 mmol) in DCM/MeOH (1.4 ml) was added a solution of thiazole-2-amine (47 mg, 0.47 mmol) in DMA (1.8 ml). Then the solution was added acetic acid (66 mg, 1.1 mmol) in DCM/MeOH (1.4 ml) followed by addition of 470 mg of the resin Mr-CNBH3(3 EQ.; substance 2.36 mmol/g). The tube was closed with a lid and then load the Vali with shaking over night at 65°C. The development of the reaction was monitored by monitoring LC/MS. After completion of the reaction, the reaction mixture was concentrated to dryness. The residue was dissolved in DMSO/Meon. Purification HPLC with reversed phase (method TFUC) has been specified in the header of the connection.

1H-NMR (500 MHz, DMSO-d6/D2O) δ ppm 4,47-of 4.67 (m, 2H), 6,83-6,93 (m, 1H), 7,19-7,30 (m, 1H), 7,30-7,46 (m, 5H);

MC (ESI) positive ion 191 (M+H)+.

The new compounds of examples 79 and 81-482 received, following the method similar to example 1 or 56.

Example 79

3-[(3-tert-butyl-1H-pyrazole-4-ylmethyl)amino]phenol

MC (ESI) 246,15 (M+H)+.

Example 79

3-[(3-tert-butyl-1H-pyrazole-4-ylmethyl)amino]phenol

MS (ESI) 246,15 (M+N)+.

Example 80

(4-boutillier)-[1-(2,2,2-cryptogramophone)-3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid

The solution triftormetilfullerenov (2 EQ.) in dichloromethane (5 ml) was added dropwise at 0°C (ice bath) to a solution of 1-(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-it (50.0 mg, 0.13 mmol) and pyridine (0.15 ml). After complete addition, the ice bath was removed and the solution was stirred for an additional 12 h, the Solution washed with aqueous hydrochloric acid (2n, approximately 50 ml) and then with water and saturated aqueous sodium chloride. The organic phase was dried over sodium sulfate and then chromatographia is whether on silica gel (suirable 10-20% ethyl acetate in heptane). Yield 70 mg, 80%.

1H-NMR (400 MHz, CDCl3) δ ppm of 8.06 (s, 1H), 7,86 (d, 2H), 7,63 (d, 1H), 7,55 (d, 1H), 7,21 (d, 1H), 5,02 (s, 2H), 4.26 deaths (kV, 2H), and 3.72 (q, 2H), 2,87 (t, 2H), 1,76 (kV, 2H), and 1.00 (t, 3H);

MC (ESI) 680,15 (M+H)+.

Example 81

5-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}indan-1-he

1H-NMR (500 MHz, DMSO-d6) δ ppm 8,02-7,73 (user. m, 5H), 7,38 (d, 1H),? 7.04 baby mortality (m, 1H), 6,72 (d, 1H), 6,64 (user. s, 1H), 4,39 (user. S., 2H), equal to 2.94 (m, 2H), 2.49 USD (m, 2H);

MC (ESI) 372,10 (M+H)+.

Example 82

6-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-3,4-dihydro-2H-naphthalene-1-he

1H-NMR (500 MHz, DMSO-d6) δ ppm 13,16 (user. s, 1H), 8,00 (d, 2H), to 7.93 (s, 1H), to 7.84 (d, 2H), 7,73 (d, 1H), 6,92 (user. s, 1H), to 6.67 (d, 1H), 6,52 (user. s, 1H), 4,42 (user. s, 2H), 2,83 (user. s, 2H), 2.49 USD (m, 2H), 2,02 (Quint, 2H);

MC (ESI) 386,15 (M+H)+.

Example 83

[4-(2-methoxyphenoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

1H-NMR (500 MHz, CDCl3) δ ppm to 7.77 (d, 2H), to 7.61 (m, 3H), 7,08-of 6.78 (m, 6H), 6,60 (d, 2H), 4,25 (user. s, 2H), a 3.87 (user. s, 3H);

MC (ESI) 440,15 (M+H)+.

Example 84

N-methoxy-N-methyl-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzamide

MC (ESI) 405,1 (M+H)+.

Example 85

4-{[3-tert-butyl-1-(2,2,2-cryptogramophone)-1H-pyrazole-4-ylmethyl]amino}-N-methoxy-N-methylbenzamide

1H-NMR (500 MHz, CDCl3) δ ppm 7,86 (s, 1H), 7,66 (d, 2H), 6,55 (d, 2H), 4,37-the 4.29 (m, 3H), 4,20 (kV, 2H), to 3.58 (s, 3H), 3,34 (s, 3H), of 1.39 (s, 9H);

MM (ESI) 463,10 (M+H)+.

Example 86

(3-tert-butyl-1H-Piras the l-4-ylmethyl)-[3-(1-methylbutoxy)phenyl]amine

1H-NMR (500 MHz, CDCl3) δ ppm 7,51 (s, 1H), 7,07 (t, 1H), 6.30-in-6,17 (m, 3H), 4,33 (m, 1H), 4,23 (s, 2H), 1.77 in-1,36 [m, 13H incl. of 1.40 (s, 9H)], of 1.28 (d, 3H), of 0.93 (t, 3H);

MC (ESI) 316,20 (M+H)+.

Example 87

(3-tert-butyl-1H-pyrazole-4-ylmethyl)phenylamine; connection with triperoxonane acid

MC (ESI) 230,0 (M+H)+.

Example 88

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-o-tolylamino; connection with triperoxonane acid

MC (ESI) to 244.1 (M+H)+.

Example 89

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-m-tolylamino; connection with triperoxonane acid

MC (ESI) to 244.1 (M+H)+.

Example 90

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-p-tolylamino; connection with triperoxonane acid

MC (ESI) to 244.1 (M+H)+.

Example 91

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2-methoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 260,1 (M+H)+.

Example 92

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-methoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 260,1 (M+H)+.

Example 93

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-methoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 260,1 (M+H)+.

Example 94

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2-forfinal)amine; compound with triperoxonane acid

MC (ESI) 248,0 (M+H)+.

Example 95

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-forfinal)amine; compound with triperoxonane acid

MC (ESI) 248,0 (M+H)+./p>

Example 96

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-forfinal)amine; compound with triperoxonane acid

MC (ESI) 248,0 (M+H)+.

Example 97

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2-chlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 264,0 (M+H)+.

Example 98

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-chlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 264,0 (M+H)+.

Example 99

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-chlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 264,0 (M+H)+.

Example 100

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-trifloromethyl)amine; compound with triperoxonane acid

MC (ESI) 314,0 (M+H)+.

Example 101

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-phenoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) was 322.3 (M+H)+.

Example 102

N-(3-tert-butyl-1H-pyrazole-4-ylmethyl)-N',N'-xylene-1,3-diamine; compound with triperoxonane acid

MC (ESI) 273,1 (M+H)+.

Example 103

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-triptoreline)amine; compound with triperoxonane acid

MC (ESI) 298,1 (M+H)+.

Example 104

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-triptoreline)amine; compound with triperoxonane acid

MC (ESI) 298,3 (M+H)+.

Example 105

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-trifloromethyl)amine; compound with referencesee acid

MC (ESI) 314,3 (M+H)+.

Example 106

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-phenoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 322,1 (M+H)+.

Example 107

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,3-dimetilfenil)amine; compound with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 108

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,4-dimetilfenil)amine; compound with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 109

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,5-dimetilfenil)amine; compound with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 110

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,4-dimetilfenil)amine; compound with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 111

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3, 5dimethylphenyl)amine; compound with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 112

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,3-acid)amine; compound with triperoxonane acid

MC (ESI) 290,3 (M+H)+.

Example 113

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,4-acid)amine; compound with triperoxonane acid

MC (ESI) 290,3 (M+H)+.

Example 114

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,5-acid)amine; compound with triperoxonane acid

MC (ESI) 290,1 (M+H)+.

Example 115

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,4-dimethoxy the Nile)amine; connection with triperoxonane acid

MC (ESI) 290,2 (M+H)+.

Example 116

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,5-acid)amine; compound with triperoxonane acid

MC (ESI) 290,4 (M+H)+.

Example 117

benzo[1,3]dioxol-5-yl(3-tert-butyl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 274,1 (M+H)+.

Example 118

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,4,5-trimethoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 320,1 (M+H)+.

Example 119

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,3-dichlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 298,0 (M+H)+.

Example 120

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,4-dichlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 298,0 (M+H)+.

Example 121

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(2,5-dichlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 299,8 (M+H)+.

Example 122

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,4-dichlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 298,0 (M+H)+.

Example 123

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3,5-dichlorophenyl)amine; compound with triperoxonane acid

MC (ESI) 297,9 (M+H)+.

Example 124

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-o-tolylamino; connection with triperoxonane acid

MC (ESI) of 270.0 (M+H)+.

Example 125

(3-thiophene-2-yl-1H-p is razol-4-ylmethyl)-p-tolylamino; connection with triperoxonane acid

MC (ESI) of 270.0 (M+H)+.

Example 126

(2-methoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 286,0 (M+H)+.

Example 127

(3-methoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 286,0 (M+H)+.

Example 128

(4-methoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 286,0 (M+H)+.

Example 129

(2-forfinal)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 274,0 (M+H)+.

Example 130

(3-forfinal)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 274,1 (M+H)+.

Example 131

(2-chlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

Example 132

(3-chlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 290,2 (M+H)+.

Example 133

(4-chlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 290,0 (M+H)+.

Example 134

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(4-trifloromethyl)amine; compound with triperoxonane acid

MC (ESI) 339,9 (M+H)+.

Example 135

(3-phenoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine;compound with triperoxonane acid

MC (ESI) 348,0 (M+H)+.

Example 136

N,N-dimethyl-N'-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)benzene-1,3-diamine; compound with triperoxonane acid

MC (ESI) 299,0 (M+H)+.

Example 137

N,N-dimethyl-N'-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)benzene-1,4-diamine; compound with triperoxonane acid

MC (ESI) to 298.9 (M+H)+.

Example 138

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(3-triptoreline)amine; compound with triperoxonane acid

MC (ESI) 323,9 (M+H)+.

Example 139

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(4-triptoreline)amine; compound with triperoxonane acid

Example 140

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(3-trifloromethyl)amine; compound with triperoxonane acid

MC (ESI) 340,0 (M+H)+.

Example 141

(4-phenoxyphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

Example 142

(2,3-dimetilfenil)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid.

MS (ESI) 284.0 (M+H)+.

Example 143

(2,4-dimetilfenil)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid.

MS (ESI) 284.0 (M+H)+.

Example 144

(2.5-dimetilfenil)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 284,0 (M+H)+.

Example 145

(3, 5dimethylphenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with three terukuni acid

MC (ESI) 284,2 (M+H)+.

Example 146

(2,3-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) was 316.0 (M+H)+.

Example 147

(2,4-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) was 316.0 (M+H)+.

Example 148

(2,5-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) was 316.0 (M+H)+.

Example 149

(3,4-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) was 316.0 (M+H)+.

Example 150

(3,5-acid)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) was 316.0 (M+H)+.

Example 151

benzo[1,3]dioxol-5-yl(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 299,9 (M+H)+.

Example 152

(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)-(3,4,5-trimethoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 346,0 (M+H)+.

Example 153

(2,3-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

Example 154

(2,4-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

Example 155

(2,5-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane what isatou

Example 156

(3,4-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

Example 157

(3,5-dichlorophenyl)-(3-thiophene-2-yl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

Example 158

[3-tert-butyl-1-(2,2,2-cryptogramophone)-1H-pyrazole-4-ylmethyl]-[3-(1-methylbutoxy)phenyl]amide 2,2,2-cryptgethashparam acid

MC (ESI) 608,10 (M+H)+;

1H-NMR (500 MHz, CDCl3) δ ppm 7,83 (user. s, 1H), 7,30-of 7.23 (m, 1H), 6.90 to-to 6.80 (m, 3H), 4,94 (user. s, 2H), or 4.31 (q, 1H), 4,13 (kV, 2H), 3,80 (kV, 2H), 1,74-1,61 (user. m, 2H), 1,57 is 1.48 (user. m, 1H), 1,48-1,18 [m, 14H incl. of 1.29 (s, 9H)], to 0.92 (t, 3H).

Example 159

2-fluoro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzonitrile; connection with triperoxonane acid

1H-NMR (500 MHz, DMSO-d6) δ ppm 13,41 and 13,10 (2× of user. S., NH), 7,86 (kV, 3H), of 7.75 (t, 2H), 7,46 (t, 1H), 7,30 (user. s, NH), 6,62-of 6.52 (m, 2H), 4,37-of 4.25 (m, 2H).

Example 160

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1,1-dioxo-1λ6-thiomorpholine-4-yl)phenyl]amine

MC (ESI) 362,1 (M).

Example 161

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-oxazol-5-Altenrhein)Amin

MC (ESI) 297,15 (M+H)+.

Example 162

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-pyridin-4-ylphenyl)Amin

MC (ESI) 307,20 (M+H)+.

Example 163

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-pyridine-2-ylphenyl)amine; compound with triperoxonane acid

MC (ESI) 307,20 (M+H)+.

Example 164

(3-tert-butyl-1H-shall irsol-4-ylmethyl)-(4-thiophene-3-ylphenyl)Amin

MC (ESI) 312,10 (M+H)+.

Example 165

3-fluoro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzonitrile

MC (ESI) 597,4, 402,1, 361,1 (M+H), 288,3, 101,1.

Example 166

2-chloro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzonitrile

MC (ESI) 418,1, 377,0 (M+H)+, 101,0.

Example 167

(3-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 348,10 (M+H)+.

Example 168

(4-ethanolgasoline)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 634,1, 410,1 (M+H)+.

Example 169

N,N-dimethyl-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzosulfimide

MC (ESI) 425,10 (M+H)+.

Example 170

(3-benzoylphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 408,05 (M+H)+.

Example 171

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-thiophene-2-ylphenyl)Amin

MC (ESI) 312,10 (M+H)+.

Example 172

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-methylpiperazin-1-yl)phenyl]amine

1H-NMR (400 MHz, DMSO-d6) δ ppm 12,19 (user. s, NH), 7,35 (user. s, 1H), 6.73 x (d, 2H), 6,55 (d, 2H), 5,11 (m, 1H), 4,06 (d, 2H), 2,90 (t, 4H), 2,42 (t, 4H), of 2.20 (s, 3H), of 1.30 (s, 9H).

Example 173

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4,5-dimethyloxazole-2-yl)phenyl]amine

1H-NMR (400 MHz, CDCl3) δ ppm to 7.93 (d, 2H), to 7.64 (s, 1H), to 6.67 (d, 2H), 2,35 (s, 3H), 2,24 (s, 3H), of 1.46 (s, 9H);

MC (ESI) 325,20 (M+H)+.

Example 174

o-tolyl[3-(4-triptoreline)1H-pyrazole-4-ylmethyl]amine; connection with triperoxonane acid

MC (ESI) 332,0 (M+H)+.

Example 175

m-tolyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 332,1 (M+H)+.

Example 176

p-tolyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 332,2 (M+H)+.

Example 177

(2-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 348,0 (M+H)+.

Example 178

(3-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 348,0 (M+H)+.

Example 179

(4-methoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 348,1 (M+H)+.

Example 180

(2-forfinal)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 358,2 (M+Na)+.

Example 181

(3-forfinal)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 182

(4-forfinal)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 336,0 (M+H)+.

Example 183

(2-chlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 184

(3-CHL is henyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; connection with triperoxonane acid

Example 185

(4-chlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 186

(4-trifloromethyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 187

(3-phenoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 410,1 (M+H)+.

Example 188

(3-dimethylaminomethylphenol)-[5-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 361,1 (M+H)+.

Example 189

(3-triptoreline)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 190

(4-triptoreline)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 191

(3-trifloromethyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 402,0 (M+H)+.

Example 192

(4-phenoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 410,1 (M+H)+.

Example 193

(2,3-dimetilfenil)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 194

(2,4-dimetilfenil)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; soedinenie triperoxonane acid

MC (ESI) 346,0 (M+H)+.

Example 195

(2.5-dimetilfenil)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 346,0 (M+H)+.

Example 196

(3,4-dimetilfenil)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 346,0 (M+H)+.

Example 197

(3, 5dimethylphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 346,1 (M+H)+.

Example 198

(2,3-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 378,1 (M+H)+.

Example 199

(2,4-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 378,1 (M+H)+.

Example 200

(2,5-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 378,1 (M+H)+.

Example 201

(3,4-acid)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 378,1 (M+H)+.

Example 202

(3,5-dimethoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 378,1 (M+H)+.

Example 203

[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]-(3,4,5-trimethoxyphenyl)amine; compound with triflorum what usnei acid

MC (ESI) 408,1 (M+H)+.

Example 204

(2,3-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 205

(2,4-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 206

(2,5-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 207

(3,4-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 208

(3,5-dichlorophenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

Example 209

1-(4-{[3-(4-methoxyphenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 350,1 (M+H)+

Example 210

1-{4-[(3-phenyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 320,1 (M+H)+.

Example 211

1-{4-[(1,3,5-trimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 286,3 (M+H)+.

Example 212

1-{4-[(3-p-tolyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 334,1 (M+H)+.

Example 213

1-(4-{[3-(3,5-deformity)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 356,1 (MH) +.

Example 214

1-{4-[(1-phenyl-3-pyridin-4-yl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 397,2 (M+H)+.

Example 215

1-{4-[(1H-indazol-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 294,3 (M+H)+.

Example 216

1-{4-[(2-methyl-2H-pyrazole-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 217

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 354,0 (M+H)+.

Example 218

1-(4-{[3-(3,4-acid)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 380,1 (M+H)+.

Example 219

1-{4-[(1-methyl-1H-indazol-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 308,4 (M+H)+.

Example 220

1-{4-[(1-benzyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 334,1 (M+H)+.

Example 221

1-(4-{[3-(4-forfinal)-1-phenyl-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 414,1 (M+H)+.

Example 222

1-{4-[(1-phenyl-3-pyridin-3-yl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 397,1 (M+H)+.

Example 223

1-{4-[(5-methoxy-1H-indazol-3-ILM is Tyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 324,1 (M+H)+.

Example 224

1-{4-[(3,5-dimethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 272,1 (M+H)+.

Example 225

1-(4-{[4-(4-methoxyphenyl)thiazol-2-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 367,0 (M+H)+.

Example 226

1-{4-[(1-methyl-1H-benzimidazole-2-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 308,1 (M+H)+.

Example 227

1-{4-[(3,5-dimethylisoxazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 273,3 (M+H)+.

Example 228

1-{4-[(1-methyl-1H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 229

1-{4-[(5-thiophene-2-isoxazol-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 327,0 (M+H)+.

Example 230

1-{4-[(2,3-dimethyl-3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 272,4 (M+H)+.

Example 231

1-{4-[(5-methyl-2-phenyloxazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 335,1 (M+H)+.

Example 232

1-{4-[(5-furan-2-isoxazol-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 311,0 (M+H)+.

the example 233

1-{4-[(2-methyl-4-phenylthiazol-5-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 351,1 (M+H)+.

Example 232

1-(4-{[2-(4-triptoreline)thiazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 405,1 (M+H)+.

Example 235

1-(4-{[2-(3-chlorophenyl)thiazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 371,0 (M+H)+.

Example 236

1-{4-[(5-methyl-3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 237

1-{4-[(4-methylthiazole-5-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 275,1 (M+H)+.

Example 238

1-(4-{[5-(4-forfinal)isoxazol-3-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 339,0 (M+H)+.

Example 239

1-{4-[(5-methylisoxazol-3-ylmethyl)amino]phenyl}butane-1-it;

connection with triperoxonane acid

MC (ESI) 259,1 (M+H)+.

Example 240

1-{4-[(2,4-dimethylthiazol-5-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 289,3 (M+H)+.

Example 241

1-{4-[(4-methylthiazole-2-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 275,3 (M+H)+.

Example 242

1-(4-{[2-(2-methoxyphenyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he; connection with tripto the acetic acid

MC (ESI) 367,1 (M+H)+.

Example 243

1-(4-{[2-(3-methoxyphenyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 367,1 (M+H)+.

Example 244

1-(4-{[4-(4-forfinal)thiazol-2-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 355,0 (M+H)+.

Example 245

1-{4-[(5-methyl-2-thiophene-2-isoxazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 341,0 (M+H)+.

Example 246

1-{4-[(2-phenylthiazol-5-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 337,0 (M+H)+.

Example 247

1-{4-[(3-methyl-3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 258,1 (M+H)+.

Example 248

1-{4-[(thiazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 261,0 (M+H)+.

Example 249

1-{4-[(thiazole-5-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 261,0 (M+H)+.

Example 250

1-{4-[(2,4-dihlotiazid-5-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 329,3 (M)+.

Example 251

1-{4-[(4,5-dimethyl-1H-imidazol-2-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 272,1 (M+H)+.

Example 252

1-{4-[(oxazol-5-ylmethyl)amino]phenyl}butane-1-it; the connection with trifero ssnoi acid

MC (ESI) 245,0 (M+H)+.

Example 253

1-{4-[(oxazol-2-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 245,0 (M+H)+.

Example 254

1-(4-{[3-(3-forfinal)isoxazol-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 339,0 (M+H)+.

Example 255

1-(4-{[3-(2-forfinal)isoxazol-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 339,0 (M+H)+.

Example 256

1-(4-{[2-(4-chlorophenyl)thiazol-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 371,0 (M+H)+.

Example 257

1-{4-[(2-chlorothiazole-5-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 294,9 (M)+.

Example 258

1-{4-[(5-chloro-2-phenyl-3H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 354,1 (M+H)+.

Example 259

1-(4-{[2-(toluene-4-sulfonyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 415,1 (M+H)+.

Example 260

1-(4-{[2-(4-methoxyphenoxy)thiazole-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 383,1 (M+H)+.

Example 261

1-{4-[(1-propyl-1H-imidazol-2-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 286,1 (M+H)+.

Example 262

1-{4-[(imidazo[1,2-a]pyridine-2-ylmethyl)am is but]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 294,1 (M+H)+.

Example 263

1-{4-[(2-methylthiazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 275,0 (M+H)+.

Example 264

1-{4-[(2-methyl-1H-imidazol-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 258,0 (M+H)+.

Example 265

1-(4-{[2-(4-methoxyphenyl)thiazole-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 367,1 (M+H)+.

Example 266

1-(4-{[2-(3-forfinal)thiazole-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 355,1 (M+H)+.

Example 267

1-(4-{[2-(4-triptoreline)thiazole-5-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 405,1 (M+H)+.

Example 268

1-{4-[(2-isopropylthiazole-4-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 303,1 (M+H)+.

Example 269

2-{4-[(3-tert-butyl-1H-pyrazole-4-ylmethyl)amino]phenoxy}benzonitrile; connection with triperoxonane acid

MC (ESI) 347,1 (M+H)+.

Example 270

(4-butoxyphenyl)-(3-tert-butyl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 302,1 (M+H)+.

Example 271

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 346,1 (M+H)+ .

Example 272

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-deformational)amine; compound with triperoxonane acid

MC (ESI) 296,1 (M+H)+.

Example 273

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-propoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) grass 288,1 (M+H)+.

Example 274

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-deformational)Amin connection with triperoxonane acid

MC (ESI) 296,1 (M+H)+.

Example 275

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-ethoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 274,1 (M+H)+.

Example 276

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2-chlorophenoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 356,1 (M+H)+.

Example 277

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-o-tolylacetic)amine; compound with triperoxonane acid

MC (ESI) 336,1 (M+H)+.

Example 278

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3,4-dichlorophenoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 390,1 (M)+.

Example 279

(4-benzyloxyphenyl)-(3-tert-butyl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 336,1 (M+H)+.

Example 280

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3-chloro-5-triptorelin-2-yloxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 425,1 (M+H)+.

Example 281

(3-tert-butyl-1H-feast of the ol-4-ylmethyl)-[4-(chloroformate)phenyl]amine; connection with triperoxonane acid

MC (ESI) 330,1 (M+H)+.

Example 282

[4-(3,5-bis-triptoreline)phenyl]-(3-tert-butyl-1H-pyrazole-4-ylmethyl)amine; compound with triperoxonane acid

MC (ESI) 458,2 (M+H)+.

Example 283

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2-pertenece)phenyl]amine; compound with triperoxonane acid

MC (ESI) 340,1 (M+H)+.

Example 284

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1-methylpiperidin-4-yloxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 343,6 (M+H)+.

Example 285

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(pyridine-2-ylethoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) sauce 337,1 (M+H)+.

Example 286

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-isobutoxide)amine; compound with triperoxonane acid

MC (ESI) 302,1 (M+H)+.

Example 287

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2,3-dimethylphenoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 350,2 (M+H)+.

Example 288

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(pyrimidine-2-yloxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 324,1 (M+H)+.

Example 289

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 346,1 (M+H)+.

Example 290

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2-chlorobenzoyloxy)phenylamine; connection with triperoxonane acid

MC (ESI) 370,1 (M+H)+.

Example 291

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(pyridine-3-yloxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 323,1 (M+H)+.

Example 292

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-forbindelse)phenyl]amine; compound with triperoxonane acid

MC (ESI) 354,1 (M+H)+.

Example 293

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(5-triptorelin-2-yloxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) to € 391.1 (M+H)+.

Example 294

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3-triptoreline)phenyl]amine; compound with triperoxonane acid

MC (ESI) 390,2 (M+H)+.

Example 295

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-m-tolylacetic)amine; compound with triperoxonane acid

MC (ESI) 336,1 (M+H)+.

Example 296

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-pertenece)phenyl]amine; compound with triperoxonane acid

MC (ESI) 340,1 (M+H)+.

Example 297

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-chlorophenoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 356,1 (M+H)+.

Example 298

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(3-methylbutoxy)phenyl]amine; compound with triperoxonane acid

MC (ESI) 316,2 (M+H)+.

Example 299

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(2,4-dichlorophenoxy)phenyl]amine; connected the e triperoxonane acid

MC (ESI) 390,1 (M)+.

Example 300

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-p-tolylacetic)amine; compound with triperoxonane acid

MC (ESI) 336,1 (M+H)+.

Example 301

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-isopropoxyphenyl)amine; compound with triperoxonane acid

MC (ESI) 288,3 (M+H)+.

Example 302

1-{4-[(6-dimethylaminopyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 298,1 (M+H)+.

Example 303

1-{4-[(6-morpholine-4-espiridion-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 340,1 (M+H)+.

Example 304

1-{4-[(6-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 285,4 (M+H)+.

Example 305

1-{4-[(6-chloropyridin-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 289,1 (M+H)+.

Example 306

1-{4-[(2-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 285,1 (M+H)+.

Example 307

1-{4-[(2,6-dichloropyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 322,9 (M)+.

Example 308

1-{4-[(2-herperidin-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 273,3 (M+H)+.

Example 309

1-{4-[(5-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-it; is connected with triperoxonane acid

MC (ESI) 285,1 (M+H)+.

Example 310

1-{4-[(2-isopropoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 313,1 (M+H)+.

Example 311

1-{4-[(2-propoxyphen-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 313,2 (M+H)+.

Example 312

1-{4-[(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 338,2 (M+H)+.

Example 313

1-{4-[(6-cyclopentyloxy-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 3391 (M+H)+.

Example 314

1-{4-[(2-morpholine-4-espiridion-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 340,1 (M+H)+.

Example 315

1-{4-[(5-fluoro-2-methoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 303,1 (M+H)+.

Example 316

1-{4-[(5-methylpyridin-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

M (ESI) 269,1 (M+H)+.

Example 317

1-{4-[(2,6-dimethoxypyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 315,1 (M+H)+.

Example 318

1-{4-[(6-herperidin-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 273,1 (M+H)+.

Example 319

1-{4-[(5-herperidin-3-ylmethyl)the Mino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 273,1 (M+H)+.

Example 320

1-{4-[(2,5-dichloropyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 323,0 (M)+.

Example 321

1-{4-[(2-thiophene-3-espiridion-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) sauce 337,1 (M+H)+.

Example 322

1-{4-[(2-dimethylaminopyridine-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 298,1 (M+H)+.

Example 323

1-{4-[(6-triptorelin-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 323,3 (M+H)+.

Example 324

1-{4-[(6-thiophene-2-espiridion-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) sauce 337,1 (M+H)+.

Example 325

1-{4-[(6-furan-2-espiridion-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 321,1 (M+H)+.

Example 326

1-{4-[(4-methylpyridin-3-ylmethyl)amino]phenyl}butane-1-he; connection with triperoxonane acid

MC (ESI) 269,1 (M+H)+.

Example 327

[4-(furan-2-ylethoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 414,1 (M+H)+.

Example 328

[4-(thiophene-2-ylethoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI 430,1 (M+H) +.

Example 329

(3-isopropoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 376,1 (M+H)+.

Example 330

[3-(pyridine-2-yloxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 411,1 (M+H)+.

Example 331

(4-cyclopentylacetyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 402,2 (M+H)+.

Example 332

(2-chloro-5-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 367,0 (M+H)+.

Example 333

(6-chloro-4-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 367,0 (M+H)+.

Example 334

(4-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 333,0 (M+H)+.

Example 335

(6-chloropyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 353,0 (M+H)+.

Example 336

phenyl-3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)methanon; connection with triperoxonane acid

MC (ESI) 422,1 (M+H)+.

Example 337

(5-herperidin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; connect the s with triperoxonane acid

MC (ESI) 337,0 (M+H)+.

Example 338

(2-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 333,0 (M+H)+.

Example 339

(6-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 333,0 (M+H)+.

Example 340

(5-chloropyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 353,0 (M+H)+.

Example 341

(4,6-dimethylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 347,0 (M+H)+.

Example 342

(6-methoxypyridine-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 349,0 (M+H)+.

Example 343

(5-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 333,0 (M+H)+.

Example 344

(6-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 333,0 (M+H)+.

Example 345

pyridine-2-yl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 319,0 (M+H)+.

Example 346

pyridine-3-yl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triflorus the second acid

MC (ESI) 319,0 (M+H)+.

Example 347

(3,5-differencein-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 354,9 (M+H)+.

Example 348

(4-methylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 333,0 (M+H)+.

Example 349

(6-chloropyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 352,9 (M)+.

Example 350

(2,6-dimethylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 347,0 (M+H)+.

Example 351

(2,6-dimethoxypyridine-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 379,0 (M+H)+.

Example 352

(4,6-dimethylpyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 347,0 (M+H)+.

Example 353

pyridine-4-yl(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)methanon; connection with triperoxonane acid

MC (ESI) 423,1 (M+H)+.

Example 354

(5-chloropyridin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 352,9 (M)+.

Example 355

1-(3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}thiophene-2-yl)is the Thanon; connection with triperoxonane acid

MC (ESI) 366,0 (M+H)+.

Example 356

(6-herperidin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 337,0 (M+H)+.

Example 357

(2-methoxypyridine-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 349,0 (M+H)+.

Example 358

(2-herperidin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 337,0 (M+H)+.

Example 359

(6-herperidin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 337,0 (M+H)+.

Example 360

(5-methoxypyridine-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 349,0 (M+H)+.

Example 361

(5-herperidin-3-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 337,0 (M+H)+.

Example 362

(3-chloro-5-methylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 367,0 (M+H)+.

Example 363

(5,6-dimethylpyridin-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 347,1 (M+H)+.

Example 364

(2-chloro-6-methylpyridin-3-yl)-[3-(4-CHL is henyl)-1H-pyrazole-4-ylmethyl]amine; connection with triperoxonane acid

MC (ESI) 333,0 (M)+.

Example 365

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(6-fluoro-5-methylpyridin-3-yl)amine; compound with triperoxonane acid

MC (ESI) 317,0 (M)+.

Example 366

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(5-fluoro-4-methylpyridin-2-yl)amine; compound with triperoxonane acid

MC (ESI) 316,9 (M)+.

Example 367

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(6-methoxy-4-methylpyridin-3-yl)amine; compound with triperoxonane acid

MC (ESI) 329,0 (M)+.

Example 368

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(2-methoxy-4-methylpyridin-3-yl)amine; compound with triperoxonane acid

MC (ESI) 329,0 (M)+.

Example 369

N3-[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-N2,N2-dimethyl-5-triptorelin-2,3-diamine; compound with triperoxonane acid

MC (ESI) 396,0 (M)+.

Example 370

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(4-methoxypyridine-3-yl)amine; compound with triperoxonane acid

MC (ESI) 315,0 (M)+.

Example 371

N5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-N2,N2-dimethylpyridin-2,5-diamine; compound with triperoxonane acid

MC (ESI) 328,0 (M)+.

Example 372

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(4-methoxypyridine-2-yl)amine; compound with triperoxonane acid

MC (ESI) 315,0 (M)+.

Example 373

3-methyl-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}b is sonitrol; connection with triperoxonane acid

MC (ESI) 357,10 (M+H)+.

Example 374

1-(4-{[1-methyl-3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

MC (ESI) 424,05 (M+Na)+.

Example 375

1-(4-{[1-methyl-5-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

MC (ESI) 424,05 (M+Na)+.

Example 376

[3-(2-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 404,20 (M+H)+.

Example 377

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 354,15 (M+H)+.

Example 378

(3-second-butoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 390,10 (M+H)+.

Example 379

[3-(1-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 404,15 (M+H)+.

Example 380

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 404,15 (M+H)+.

Example 381

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-piperidine-4-ylphenyl)amine (hydrochloride)

MC (ESI) 313,20 (M+H)+.

Example 382

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-piperazine-1-ylphenyl)amine (hydrochloride)

Example 383

(4-boutillier)pyridine-3-ylmethylene 2,2,2-cryptgethashparam acid

MC (ESI) 401,10 (M+H)+.

Example 384

N,N-dimethyl-N'-pyridine-3-ylmethylene-1,4-diamine

MC (ESI) 228,15 (M+H)+.

Example 38

(4-dimethylaminophenyl)pyridine-3-ylmethylene 2,2,2-cryptgethashparam acid

MC (ESI) 374,10 (M+H)+.

Example 386

1-{3-[(pyridine-3-ylmethyl)amino]phenyl}butane-1-he

MC (ESI) 255,05 (M+H)+.

Example 387

1-{4-[(6-dimethylaminopyridine-3-ylmethyl)amino]phenyl}butane-1-he

MC (ESI) 298,15 (M+H)+.

Example 388

N,N-dimethyl-N'-pyridine-3-ylmethylene-1,3-diamine

MC (ESI) 228,10 (M+H)+.

Example 389

(3-dimethylaminophenyl)pyridine-3-ylmethylene 2,2,2-cryptgethashparam acid

1H-NMR (500 MHz, CDCl3) δ ppm 8,51 (m, 1H), scored 8.38 (s, 1H), 7,69 (d, 1H), 7.23 percent (SIM. m, 1H), 7,18 (t, 1H), 6,62 (d, 1H), 6,55 (d, 1H), 6,41 (s, 1H), to 4.87 (s, 2H), 3,83 (kV, 2H), 2,88 (s, 6H).

Example 390

(3-boutillier)pyridine-3-ylmethylene 2,2,2-cryptgethashparam acid

MC (ESI) 401,15 (M+H)+.

Example 391

(4-boutillier)-(6-dimethylaminopyridine-3-ylmethyl)amide 2,2,2-cryptgethashparam acid

MC (ESI) 444,15 (M+H)+.

Example 392

1-(3-{methyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

MC (ESI) 402,15 (M+H)+.

Example 393

(5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 532,10 (M+H)+.

Example 394

[4-(2-methoxyphenoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 586,05 (M+H)+ .

Example 395

N,N-dimethyl-4-{(2,2,2-cryptogramophone)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzosulfimide (hydrochloride)

MC (ESI) 571,10 (M+H)+.

Example 396

[3-(2-trifloromethyl)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 476,15 (M+H)+.

Example 397

[3-(2-methoxyphenoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 440,15 (M+H)+.

Example 398

1-(3-chloro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon; connection with triperoxonane acid

MC (ESI) 394,25 (M+H)+.

Example 399

(4-methanesulfonyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine; compound with triperoxonane acid

MC (ESI) 396,25 (M+H)+.

Example 400

2-methyl-7-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}chromen-4-one; compound with triperoxonane acid

MC (ESI) 400,25 (M+H)+.

Example 401

1-(2-fluoro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon; connection with triperoxonane acid

MC (ESI) 378,25 (M+H)+.

Example 402

(3-tert-butyl-1H-pyrazole-ylmethyl)-[4-(4,5-dimethyloxazole-2-yl)phenyl]amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 471,15 (M+H)+.

Example 401

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-oxazol-5-ylphenyl)amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 443,15 (M+H)+ .

Example 404

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-pyridine-2-ylphenyl)amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 453,15 (M+H)+.

Example 405

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(4-pyridin-4-ylphenyl)amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 453,15 (M+H)+.

Example 406

[3-(1-ethylpropoxy)phenyl]methyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amine (hydrochloride)

MC (ESI) 418,35 (M+H)+.

Example 407

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide econsultancy acid (hydrochloride)

MC (ESI) 496,35 (M+H)+.

Example 408

N-[3-(1-ethylpropoxy)phenyl]-N-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]methanesulfonamide (hydrochloride)

MC (ESI) 482,35 (M+H)+.

Example 409

1-(4-{methyl[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

MC (ESI) 402,20 (M+H)+.

Example 410

1-[4-(methylpyridin-3-ylmethylamino)phenyl]butane-1-he

MC (ESI) 269,25 (M+H)+.

Example 411

(4-boutillier)-[1-methyl-5-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid

MC (ESI) 548,35 (M+H)+.

Example 412

(4-boutillier)-[1-methyl-3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid

MC (ESI) 548,35 (M+H)+.

Example 413

(4-butylphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC ESI) 374,15 (M+H) +.

Example 414

(4-boutillier)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid

MC (ESI) 534,10 (M+H)+.

Example 415

3-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N,N-dimethylbenzamide

MC (ESI) 355,10 (M+H)+.

Example 416

1-(4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

MC (ESI) 388,10 (M+H)+.

Example 417

N-(4-boutillier)-N-pyridin-3-ylmethylphosphonate

MC (ESI)395,15 (M+H)+.

Example 418

N-[3-(1-ethylpropoxy)phenyl]-N-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]benzosulfimide (hydrochloride)

MC (ESI) 544,15 (M+H)+.

Example 419

1-[3-(methylpyridin-3-ylmethylamino)phenyl]butane-1-he; connection with triperoxonane acid

MC (ESI) 269,15 (M+H)+.

Example 420

N-(3-boutillier)-N-pyridin-3-ylmethylphosphonate; connection with triperoxonane acid

MC (ESI) 395,10 (M+H)+.

Example 421

N-(3-boutillier)-N-pyridin-3-ylmethylphosphonate; connection with triperoxonane acid

MC (ESI) 333,05 (M+H)+.

Example 422

N-(3-boutillier)-C-phenyl-N-pyridin-3-ylmethylphosphonate

MC (ESI) 409,20 (M+H)+.

Example 423

1-{4-[4-(pyridine-3-yloxy)butoxy]phenyl}butane-1-he

MC (ESI) 314,10 (M+H)+.

Example 424

(6-dimethylaminopyridine-3-ylmethyl)-[3-(1-ethylpropoxy)phenyl]amide 2,2,2-cryptgethashparam acid; soybean is inania with triperoxonane acid

MC (ESI) 460,20 (M+H)+.

Example 425

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(1,1-dioxo-2,3-dihydro-1H-benzo[b]thiophene-5-yl)amine; compound with triperoxonane acid

MC (ESI) 374,00 (M+H)+.

Example 426

7-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-3,4-dihydro-2H-naphthalene-1-he

MC (ESI) 352,10 (M+H)+.

Example 427

6-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}indan-1-he

MC (ESI) 677,20(2M+H)+.

Example 428

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-methylbenzenesulfonamide; connection with triperoxonane acid

MC (ESI) 377,05 (M+H)+.

Example 429

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-[4-(pyrrolidin-1-sulfonyl)phenyl]amine

MC (ESI) 417,10 (M+H)+.

Example 430

3-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N,N-dimethylbenzenesulfonamide

MC (ESI) 391,10 (M+H)+.

Example 431

[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]-(1,1-dioxo-1H-benzo[b]thiophene-5-yl)Amin

MC (ESI) 372,00 (M+H)+.

Example 432

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N,N-determinationand

MC (ESI) 419,10 (M+H)+.

Example 433

N,N-dimethyl-4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}benzamide

MC (ESI) 389,20 (M+H)+.

Example 434

1-(2-methoxy-4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 418,10 (M+H)+.

Example 435

1-(2-hydroxy-4-{[3-(3-triptoreline)-1-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he; connection with triperoxonane acid

MC (ESI) 404,20 (M+H)+.

Example 436

1-(2-hydroxy-3-propyl-4-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)Etalon; connection with triperoxonane acid

MC (ESI) 418,20 (M+H)+.

Example 437

1-[4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-(1-ethylpropoxy)phenyl]butane-1-he

MC (ESI) 440,20 (M+H)+.

Example 438

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-methoxy-3-were)alanon

MC (ESI) 370,20 (M+H)+.

Example 439

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-methoxy-3-propylphenyl)Etalon; connection with triperoxonane acid

MC (ESI) 398,10 (M+H)+.

Example 440

1-(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-hydroxy-3-were)Etalon; connection with triperoxonane acid

MC (ESI) 356,1 (M+H)+.

Example 441

2-phenyl-1-{4-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}Etalon; connection with triperoxonane acid

MC (ESI) 437,10 (M+H)+.

Example 442

cyclopentyl{4-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}meanon; connection with triperoxonane acid

MC (ESI) 415,20 (M+H)+.

Example 443

methyl ester of 4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}benzoic acid

MC (ESI) 342,10 (M+H)+.

Example 444

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)-(4-methylpiperazin-1-yl)methanon

MC (ESI) 410,20 (M+H)+ .

Example 445

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)-[4-(1-methylpiperidin-4-yl)piperazine-1-yl]metano; connection with triperoxonane acid

MC (ESI) 493,30 (M)+.

Example 446

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)morpholine-4-ylmethanone; connection with triperoxonane acid

MC (ESI) 397,10 (M+H)+.

Example 447

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-methyl-N-propylbenzamide; connection with triperoxonane acid

MC (ESI) 383,20 (M+H)+.

Example 448

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-propylbenzamide; connection with triperoxonane acid

MC (ESI) 369,20 (M+H)+.

Example 449

1-[3-(benzylpyridine-3-ylmethylamino)phenyl]butane-1-he; connection with triperoxonane acid

MC (ESI) 345,20 (M+H)+.

Example 450

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(1-methylpiperidin-4-yl)phenyl]amine

MC (ESI) 327,20 (M+H)+.

Example 451

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(4-methyl-4H-[1,2,4]triazole-3-yl)phenyl]amine

MC (ESI) 311,20 (M+H)+.

Example 452

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[4-(5-methylfuran-2-yl)phenyl]amine

MC (ESI) 310,20 (M+H)+.

Example 453

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-cyclopentylacetyl)Amin

MC (ESI) 314,15 (M+H)+.

Example 454

[3-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid (hydrochlor the e)

MC (ESI) 550,10 (M+H)+.

Example 455

[3-(1-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 550,10 (M+H)+.

Example 456

(3-second-butoxyphenyl)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 536,10 (M+H)+.

Example 457

[3-(2-methylbutoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 550,15 (M+H)+.

Example 458

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-cyclopentylacetyl)amide 2,2,2-cryptgethashparam acid (hydrochloride)

MC (ESI) 460,15 (M+H)+.

Example 459

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-thiophene-2-ylphenyl)Amin

MC (ESI) 312,15 (M+H)+.

Example 460

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-furan-2-ylphenyl)Amin

MC (ESI) 296,20 (M+H)+.

Example 461

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(4-methylthiazole-2-yl)phenyl]amine

MC (ESI) 327,20 (M+H)+.

Example 462

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(4,5-dimethylthiazol-2-yl)phenyl]amine

MC (ESI) 341,20 (M+H)+.

Example 463

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-oxazol-5-ylphenyl)Amin

MC (ESI) 297,20 (M+H)+.

Example 464

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-thiophene-3-ylphenyl)Amin

MC (ESI) 312,15 (M+H)+.

Example 465

(3-tert-butyl-1H-pyrazole-4-yl is ethyl)-[3-(4,5-dimethyloxazole-2-yl)phenyl]amine

MC (ESI) 325,20 (M+H)+.

Example 466

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(4-methylpiperazin-1-yl)phenyl]amine

MC (ESI) 328,25 (M+H)+.

Example 467

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-piperazine-1-ylphenyl)amine (hydrochloride)

MC (ESI) 314,25 (M+H)+.

Example 468

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(1,1-dioxo-1(lambda6-isothiazolin-2-yl)phenyl]amine

MC (ESI) 349,15 (M+H)+.

Example 469

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-[3-(2-methylthiazole-4-yl)phenyl]amine

MC (ESI) 327,15 (M+H)+.

Example 470

(3-tert-butyl-1H-pyrazole-4-ylmethyl)-(3-pyridin-2-ylphenyl)Amin

MC (ESI) 307,15 (M+H)+.

Example 471

[4-(1-ethylpropoxy)phenyl]-[3-(4-trifloromethyl)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 404,35 (M+H)+.

Example 472

(2-dimethylaminomethylphenol)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 375,20 (M+H)+.

Example 473

(3-dimethylaminomethylphenol)-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]Amin

MC (ESI) 375,20 (M+H)+.

Example 474

[4-(1-ethylpropoxy)phenyl]-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amide 2,2,2-cryptgethashparam acid

MC (ESI) 550,15 (M+H)+.

Example 475

1-{4-[(3-methyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

MC (ESI) 258,35 (M+H)+.

Example 476

1-{4-[(3-propyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

MC (ESI) 286,20 (M+H)+.

Example 477

1-{4-[(3-isopropyl-1H-piraso the-4-ylmethyl)amino]phenyl}butane-1-he

MC (ESI) 286,15 (M+H)+.

Example 478

1-{4-[(3-ethyl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

MC (ESI) 272,25 (M+H)+.

Example 479

(4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)morpholine-4-ylmethanol

Example 480

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-methyl-N-propylbenzamide

Example 481

4-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-N-propylbenzamide

Example 482

1-[3-(benzylpyridine-3-ylmethylamino)phenyl]butane-1-he

Connection examples 483-499 was obtained by the methods provided in the following diagrams I, II and III:

Scheme I

Scheme II

Ms: Methylsulfonylamino,

Et3N: triethylamine,

TFUCK: triperoxonane acid

Scheme III

Example 483

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}alanon

ESI-MS: 361,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 8,05 (user. s, 1H); to 7.95 (m, 4H); to 7.75 (m, 2H); to 7.15 (d, 2H); 5,20 (s, 2H); 2.50 each (s, 3H).

Example 484

1-{3-chloro-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}ethanetricarboxylate acid

ESI-MS: 395,00 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (m, 3H); of 7.90 (d, 1H); of 7.75 (d, 2H); was 7.45 (d, 1H); and 5.30 (s, 2H); 2.50 each (s, 3H).

Example 485

1-{2-fluoro-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}ethnorussia acid

ESI-MS: 40,10 [M+Na] +.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,20 (user. s, 1H); with 8.05 (s, 1H); of 7.90 (d, 2H); to 7.75 (m, 4H); 7,05 (d, 1H); to 6.95 (d, 1H); 5,20 (m, 2H); 2.50 each (s, 3H).

Example 486

1-{3-fluoro-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}ethanetricarboxylate acid

ESI-MS: 379,15 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); of 7.90 (d, 2H); to 7.75 (m, 3H); of 7.70 (d, 1H); was 7.45 (t, 1H); 5.25 in (s, 2H); 2.50 each (s, 3H).

Example 487

1-{2-methyl-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}ethanetricarboxylate acid

ESI-MS: 375,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); of 7.90 (d, 2H); a 7.85 (d, 1H); 7,80 (d, 2H); 7,00 (d, 1H); to 6.95 (s, 1H); the 5.65 (s, 2H); 2.50 each (s, 3H); of 2.45 (s, 3H).

Example 488

1-{3-methyl-4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}ethanetricarboxylate acid

ESI-MS: 375,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (d, 2H); 7,80 (d, 1H); to 7.75 (m, 3H); to 7.25 (d, 1H); 5.25 in (s, 2H); 2.50 each (s, 3H); 2,10 (s, 3H).

Example 489

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}propane-1-antiperoxidase acid

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (m, 4H); of 7.75 (d, 2H); to 7.15 (d, 2H); 5,20 (s, 2H); 2.95 and (m, 2H); of 1.05 (t, 3H).

Example 490

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}pentane-1-antiperoxidase acid

ESI-MS: 403,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,20 (user. s, 1H); with 8.05 (s, 1H); to 7.95 (m, 3H); a 7.85 (m, 1H); the 7.65 (d, 2H); to 7.15 (d, 2H); 5,20 (s, 2H); 2.95 and (m, 2H)and 1.60 (m, H); of 1.35 (m, 2H); from 0.90 (t, 3H).

Example 491

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}hexane-1-antiperoxidase acid

ESI-MS: 417,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (m, 4H); 7,80 (d, 2H); to 7.15 (d, 2H); 5,20 (s, 2H); 2,90 (t, 2H)and 1.60 (m, 2H); of 1.30 (m, 4H); of 0.85 (t, 3H).

Example 492

tert-butyl ester 4-(4-butyrylthiocholine)-3-(4-triptoreline)pyrazole-1-carboxylic acid

ESI-MS: 405,10 [M+H-Boc]+.

Example 492

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-elmersolver]phenyl}butane-1-antiperoxidase acid

ESI-MS: 405,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.95 (d, 2H); a 7.85 (d, 2H); 7,80 (m, 3H); 7,40 (d, 2H); however, 4.40 (s, 2H); 2.95 and (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 493

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-elmersolver]phenyl}butane-1-antiperoxidase acid

ESI-MS: 437,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (d, 2H); the 7.65 (m, 3H); of 7.60 (m, 4H); at 4.75 (s, 2H); 2.95 and (t, 2H); of 1.65 (m, 2H); of 0.95 (t, 3H).

Example 494

1-{4-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he

ESI-MS: 389,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,20 (user. s, 1H); 8,05 (user. s, 1H); to 7.95 (m, 4H); to 7.75 (m, 2H); to 7.15 (d, 2H); 5,20 (s, 2H); 2,90 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 495a

tert-butyl ester 4-(4-butyraldoxime)-3-(4-forfinal)pyrazole-1-carboxylic acid

ESI-MS: 339,10 [M+H-Boc]+.

Example 495

1-{4-[3-(4-forfinal)-1H-pyrazole-4-is metoxi]phenyl}butane-1-antiperoxidase acid

ESI-MS: 339,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm to 7.95 (m, 3H); to 7.75 (m, 2H); 7,25 (m, 2H); to 7.15 (d, 2H); further 5.15 (s, 2H); 2.95 and (t, 2H); of 1.65 (m, 2H); from 0.90 (t, 3H).

Example 496

1-{4-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he, salt triperoxonane acid

ESI-MS: 355,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,10 (user. s, 1H); 8,05 (user. s, 1H); to 7.95 (d, 2H); of 7.70 (m, 2H); was 7.45 (m, 2H); to 7.15 (d, 2H); further 5.15 (s, 2H); 2.95 and (t, 2H); of 1.65 (m, 2H); from 0.90 (t, 3H).

Example 497a

tert-butyl ester 4-(4-butyraldoxime)-3-(3-tryptophanyl)pyrazole-1-carboxylic acid

ESI-MS: 339,10 [M+H-Boc]+.

Example 497

1-{4-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he, salt triperoxonane acid

ESI-MS: 339,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,15 (user. s, 1H); 8,05 (user. s, 1H); to 7.95 (d, 2H); to 7.50 (m, 3H); to 7.15 (m, 3H); further 5.15 (s, 2H); 2.95 and (t, 2H); of 1.65 (m, 2H); from 0.90 (t, 3H).

Example 498

1-{4-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]phenyl}butane-1-he

ESI-MS: 389,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,20 (user. s, 1H); 8,10 (user. s, 1H); with 8.05 (m, 2H); to 7.95 (d, 2H); of 7.70 (m, 2H); to 7.15 (d, 2H); 5,20 (s, 2H); 2.95 and (t, 2H); of 1.65 (m, 2H); from 0.90 (t, 3H).

Example 499

1-[4-(3-phenyl-1H-pyrazole-4-ylethoxy)phenyl]butane-1-antiperoxidase acid

ESI-MS: 321,15 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm to 7.95 (m, 3H); of 7.70 (d, 2H); was 7.45 (m, 2H); 7,35 (m, 1H); to 7.15 (d, 2H); further 5.15 (s, 2H); 2.95 and (t, 2H); of 1.65 (m, 2H); from 0.90 (t, 3H).

Connection example 500 received by way pok is related to the following scheme IV:

Scheme IV

Example 500

1-{4-[1-(3-phenyl-1H-pyrazole-4-yl)ethoxy]phenyl}butane-1-he

ESI-MS: 357,20 [M+Na]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 13,0 (user. s, 1H); a 7.85 (m, 2H); 7,70-7,30 (m, 6H); to 6.95 (m, 2H); 5,70 (m, 1H); 2,90 (t, 2H)and 1.60 (m, 5H); from 0.90 (t, 3H).

Connection examples 501-512 was obtained by the methods provided in the following diagrams V and VI:

Scheme V

Scheme VI

Example 501

1-(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)alanon

Example 502

1-(3-nitro-4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)ethanetricarboxylate acid

ESI-MS: 405,15 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm to 8.70 (m, 1H); at 8.60 (s, 1H); to 7.95 (d, 1H); a 7.85 (d, 2H); of 7.70 (m, 3H); 7,05 (d, 1H); 4.75 in (m, 2H); 2.50 each (s, 3H).

Example 502

1-(3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)alanon

ESI-MS: 361,00 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 13.05 (user. s, 1H); to 7.95 (m, 2H); 7,80 (m, 3H); 7,20 (m, 3H); 6.90 to (d, 1H); of 6.20 (m, 1H); 4,30 (m, 2H); 2.50 each (s, 3H).

Example 503

1-(3-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-antiperoxidase acid

ESI-MS: 388,00 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 7.95 (d, 2H); 7,80 (m, 3H); 7,20 (m, 3H); 6.90 to (d, 1H); of 5.75 (s, 1H); 4,30 (s, 2H); 2,90 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 504

phenyl(4-{[3-(4-triptoreline)-1H-pyrazole-ylmethyl]amino}phenyl)metano

ESI-MS: 422,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (d, 2H); 7,80 (s, 1H); of 7.75 (d, 2H); of 7.60 (m, 5H); to 7.50 (m, 2H); 6.75 in (d, 2H); of 4.35 (s, 2H).

Example 505

2,2-dimethyl-1-(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)propane-1-antiperoxidase acid

ESI-MS: 402,20 [M+H]+.

1H-NMR (400 MHz, CDCl3): δ ppm a 7.85 (d, 2H); to 7.75 (m, 2H); of 7.70 (m, 3H); 6,60 (d, 2H); however, 4.40 (s, 2H); of 1.40 (s, 9H).

Example 506

2,2,2-Cryptor-1-(4-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}phenyl)ethanetricarboxylate acid

ESI-MS: 414,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (d, 2H); of 7.70 (m, 6H); 6,70 (d, 2H); of 4.45 (s, 2H).

Example 507

1-{1-[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]-2,3-dihydro-1H-indol-5-yl}ethanetricarboxylate acid

ESI-MS: 386,10 [M+H]+.

Example 508

1-(4-{[3-(4-forfinal)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 338,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,10 (user. s, 1H); of 7.70 (m, 5H); 7,30 (m, 2H); 6,85 (m, 1H); of 6.65 (d, 2H); 4.25 in (m, 2H); 2,80 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 509

1-(4-{[3-(3-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 354,15 [M+H]+.

Example 510

1-(4-{[3-(2-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-antiperoxidase acid

ESI-MS: 354,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.70 (m, 3H); of 7.60 (d, 1H); was 7.45 (m, 3H); 6,55 (d, 2H); of 4.05 (s, 2H); to 2.75 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 511

1-(4-{[3-(3-perfe who yl)-1H-pyrazole-4-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 338,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,10 (user. s, 1H); to 7.75 (m, 3H); to 7.50 (m, 3H); to 7.15 (t, 1H); 6,85 (s, 1H); of 6.65 (d, 2H); 4,30 (m, 2H); 2,80 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 512

1-{4-[(3-pyridin-3-yl-1H-pyrazole-4-ylmethyl)amino]phenyl}butane-1-he

ESI-MS: 321,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm cent to 8.85 (s, 1H); 8,55 (d, 1H); with 8.05 (d, 1H); 7,80 (s, 1H); of 7.75 (d, 2H); 7,45 (m, 1H); 6,85 (m, 1H); of 6.65 (d, 2H); 4,30 (m, 2H); 2,80 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Connection examples 513-532 received similar methods are presented in schemes I, II, V and VI, on the basis of suitable heteroaromatic carbaldehyde.

Example 513

1-(4-{[4-(4-methoxyphenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 350,15 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 7.75 (m, 2H); at 7.55 (m, 2H); 7,00 (m, 2H); to 6.80 (s, 1H); of 6.65 (m, 2H); 4,20 (m, 2H); of 3.80 (s, 3H); 2,80 (m, 2H)and 1.60 (m, 2H); from 0.90 (m, 3H).

Example 514

1-(3-{[4-(4-methoxyphenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 350,15 [M+H]+.

Example 515

1-(3-{[4-(4-ethylphenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 348,15 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 12,80 (m, 1H); the 7.65 (s, 1H); at 7.55 (d, 2H); to 7.25 (d, 2H); to 7.15 (m, 3H); 6,85 (d, 1H); x 6.15 (m, 1H); 4,20 (m, 2H); 2,90 (t, 2H); to 2.65 (m, 2H)and 1.60 (m, 2H); of 1.20 (t, 3H); from 0.90 (t, 3H).

Example 516

1-(4-{[4-(4-ethylphenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 348,15 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 12,90 (m, 1H); of 7.75 (d, 2H); 7,70 (users, 1H); at 7.55 (d, 2H); to 7.25 (d, 2H); to 6.80 (m, 1H); of 6.65 (d, 2H); 4.25 in (m, 2H); 2,80 (t, 2H); to 2.65 (m, 2H)and 1.60 (m, 2H); of 1.20 (t, 3H); from 0.90 (t, 3H).

Example 517

1-(4-{[4-(4-triptoreline)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 388,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 8,10 (s, 1H); 7,80 (m, 2H); of 7.75 (d, 2H); of 7.60 (m, 2H); 6,70 (d, 2H); however, 4.40 (s, 2H); 2,80 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 518

1-(4-{[4-(4-chlorophenyl)-1H-pyrazole-3-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 354,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.75 (m, 3H); 7,50 (d, 2H); 7,40 (d, 2H); 6,70 (m, 2H); however, 4.40 (s, 2H); 2,80 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 519

1-{4-[(5-phenyl)-2H-[1,2,3]triazole-4-ylmethyl)amino]phenyl}butane-1-he

ESI-MS: 321,25 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.75 (m, 4H); to 7.50 (m, 2H); 7,40 (m, 1H); 6,70 (d, 2H); 4,50 (s, 2H); 2,70 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 520

1-{4-[4-(4-methoxyphenyl)-1H-pyrazole-3-ylethoxy]phenyl}butane-1-antiperoxidase acid

ESI-MS: 351,20 [M+H]+.

Example 521

1-{4-[4-(4-ethylphenyl)-1H-pyrazole-3-ylethoxy]phenyl}butane-1-antiperoxidase acid

ESI-MS: 371,20 [M+Na]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 7.95 (d, 2H); of 7.90 (s, 1H); of 7.60 (d, 2H); to 7.25 (d, 2H); to 7.15 (d, 2H); further 5.15 (s, 2H); 2,90 (m, 2H); to 2.65 (m, 2H); of 1.65 (m, 2H); of 1.20 (t, 3H); from 0.90 (t, 3H).

Example 522

1-[4-(4-bromo-1H-pyrazole-3-ylethoxy)phenyl]butane-1-he

ESI-MS: 322,00/324,00 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 13,10 (user. s, 1H); of 7.75 (d, 2H); 6.90 to (s, 1H); 6,70 (d, 2H); 4.25 in (user. s, 2H); 2,80 (m, 2H); 1,60 (who, 2H); from 0.90 (t, 3H).

Example 523

1-{4-[(4-phenyl-1H-pyrrol-3-ylmethyl)amino]phenyl}butane-1-he

ESI-MS: 319,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 10,90 (s, 1H); of 7.75 (d, 2H); was 7.45 (d, 2H); 7,30 (m, 2H); to 7.15 (t, 1H); 7,05 (s, 1H); 6,85 (s, 1H); 6,70 (s, 1H); of 6.65 (d, 2H); 4,20 (d, 2H); 2,80 (t, 2H)and 1.60 (m, 2H); from 0.90 (t, 3H).

Example 524

1-{4-[(3-phenylpyridine-4-ylmethyl)amino]phenyl}butane-1-antiperoxidase acid

ESI-MS: 331,20 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 8,65 (s, 1H); of 7.70 (d, 2H); of 7.60 (d, 1H); at 7.55 (m, 5H); 7,25 (user. s, 1H); 6,45 (d, 2H); however, 4.40 (s, 2H); to 2.75 (t, 2H); of 1.55 (m, 2H); from 0.90 (t, 3H).

Example 525

1-{4-[(4-vinylpyridin-3-ylmethyl)amino]phenyl}butane-1-antiperoxidase acid

ESI-MS: 331,10 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm to 8.70 (s, 1H); 8,65 (d, 1H); of 7.70 (d, 2H); 7,55 (user. s, 6H); 7,10 (m, 1H); 6,50 (d, 2H); of 4.35 (s, 2H); to 2.75 (t, 2H); of 1.55 (m, 2H); from 0.90 (t, 3H).

Example 526

1-{4-[(2-phenylpyridine-3-ylmethyl)amino]phenyl}butane-1-he

ESI-MS: 331,20 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 8,55 (d, 1H); 7,80 (d, 1H); the 7.65 (d, 2H); of 7.60 (d, 2H); was 7.45 (m, 3H); 7,40 (m, 1H); to 7.15 (m, 1H); 6,45 (d, 2H); of 4.35 (d, 2H); to 2.75 (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 527

1-{4-[(6-vinylpyridin-3-ylmethyl)amino]phenyl}butane-1-he

ESI-MS: 331,20 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 8,65 (s, 1H); with 8.05 (d, 2H); to 7.95 (d, 1H); 7,80 (d, 1H); of 7.75 (d, 2H); was 7.45 (m, 3H); 7,20 (m, 1H); of 6.65 (d, 2H); of 4.45 (d, 2H); 2,80 (t, 2H); of 1.55 (m, 2H); from 0.90 (t, 3H).

Example 528

1-(4-{[6-(4-forfinal)pyridine-2-ylmethyl]amino}phenyl)butane-1-he

ESI-MS: 349,20 [M+H] +.

1H-NMR (400 MHz, d6-DMSO): δ ppm 8,15 (m, 2H); a 7.85 (d, 2H); of 7.75 (d, 2H); 7,30 (m, 4H); of 6.65 (d, 2H); 4,55 (d, 2H); to 2.75 (t, 2H); of 1.55 (m, 2H); from 0.90 (t, 3H).

Example 529

1-{4-[(pyrazolo[1,5-a]pyridine-3-ylmethyl)amino]phenyl}butane-1-he

1H-NMR (500 MHz, d6-DMSO): δ ppm 8,65 (d, 1H); with 8.05 (s, 1H); of 7.75 (d, 1H); of 7.70 (d, 2H); 7,20 (m, 1H); to 6.95 (m, 1H); 6,85 (t, 1H); 6,70 (d, 2H); of 4.45 (s, 2H); to 2.75 (t, 2H); of 1.55 (m, 2H); from 0.90 (t, 3H).

Example 530

1-{4-[(3-methyl-5-phenylisoxazol-4-ylmethyl)amino]phenyl}butane-1-antiperoxidase acid

ESI-MS: 335,10 [M+H]+.

Connection examples 531-590 received similar methods are presented in schemes I, II, V and VI, on the basis of suitable heteroaromatic carbaldehyde and compounds of the following formulas, where X represents NH or O, and R4cand Q are as specified in this case:

Example 531a

tert-butyl ester 4-(1-oxo-2-propyl-2,3-dihydro-1H-isoindole-5-intoximeter)-3-(4-triptoreline)pyrazole-1-carboxylic acid

ESI-MS: 516,20 [M+H]+.

Example 531

2-propyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 416,35 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (d, 2H); of 7.75 (d, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); 5,20 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H)and 1.60 (m, 2H); of 0.85 (t, 3H).

Example 532

2-propyl-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 416,20 [M+H]+

1H-NMR (400 MHz, d6-DMSO): δ ppm 13,20 (user. s, 1H); 8,10 (s, 1H); with 8.05 (m, 2H); of 7.70 (m, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H)and 1.60 (m, 2H); of 0.85 (t, 3H).

Example 533

5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 366,20 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 7.95 (s, 1H); of 7.70 (m, 2H); at 7.55 (d, 1H); 7,25 (m, 3H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H)and 1.60 (m, 2H); of 0.85 (t, 3H).

Example 534

5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MSC 382,10 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 7.95 (s, 1H); of 7.70 (d, 2H); of 7.60 (d, 1H); 7,50 (d, 2H); to 7.25 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H)and 1.60 (m, 2H); of 0.85 (t, 3H).

Example 535

5-[3-(3-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 382,20 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); of 7.75 (s, 1H); the 7.65 (d, 1H); of 7.60 (d, 1H); was 7.45 (t, 1H); 7,40 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H)and 1.60 (m, 2H); of 0.85 (t, 3H).

Example 536a

tert-butyl ether 3-(3-forfinal)-4-(1-oxo-2-propyl-2,3-dihydro-1H-isoindole-5-intoximeter)pyrazole-1-carboxylic acid

ESI-MS: 466,20 [M+H]+.

Example 536

5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2-propyl-2,3-dihydroindol-1-he

ESI-MS: 366,10 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm 13,15 (user. s, 1H); 8,00 (s, 1H); of 7.60 (m, 2H); to 7.50 (m, 2H; of 7.25 (s, 1H); 7,20 (m, 1H); to 7.15 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); to 3.45 (m, 2H)and 1.60 (m, 2H); of 0.85 (t, 3H).

Example 537

5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 348,20 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 7.90 (s, 1H); of 7.70 (d, 2H); of 7.60 (d, 1H); was 7.45 (m, 2H); 7,35 (m, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); to 3.45 (m, 2H)and 1.60 (m, 2H); of 0.85 (t, 3H).

Example 538

5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 470,10 [M+H]+.

1H-NMR (500 MHz, MeOD): δ ppm with 8.05 (s, 1H); to 7.95 (d, 1H); of 7.90 (s, 1H); of 7.70 (d, 1H); the 7.65 (d, 1H); of 7.60 (t, 1H); 7,20 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); 4,50 (s, 2H); of 3.85 (t, 2H); 2,60 (m, 2H).

Example 539

5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 436,10 [M+H]+.

1H-NMR (500 MHz, MeOD): δ ppm a 7.85 (s, 1H); the 7.65 (m, 3H); 7,40 (d, 2H); to 7.15 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); of 4.45 (s, 2H); of 3.85 (t, 2H); 2,60 (m, 2H).

Example 540

5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 420,10 [M+H]+.

1H-NMR (500 MHz, MeOD): δ ppm a 7.85 (s, 1H); of 7.70 (m, 3H); to 7.15 (m, 3H); 7,10 (d, 1H); 5,10 (s, 2H); of 4.45 (s, 2H); of 3.85 (t, 2H); 2,60 (m, 2H).

Example 541

5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 420,10 [M+H]+.

1H-NMR (500 MHz, MeOD): δ ppm a 7.85 (s, 1H; of 7.70 (d, 1H); 7,50 (d, 1H); was 7.45 (m, 2H); 7,20 (s, 1H); 7,10 (m, 2H); further 5.15 (s, 2H); of 4.45 (s, 2H); of 3.85 (t, 2H); 2,60 (m, 2H).

Example 542

5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 470,10 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm with 8.05 (s, 1H); to 7.95 (d, 2H); 7,80 (d, 2H); of 7.60 (d, 1H); 7,30 (s, 1H); to 7.15 (d, 1H); 5,20 (s, 2H); of 4.45 (s, 2H); 3.75 to (m, 2H); to 2.65 (m, 2H).

Example 543

5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2-(3,3,3-cryptochromes)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 402,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 7.95 is (user. s, 1H); of 7.70 (d, 2H); of 7.60 (d, 1H); was 7.45 (m, 2H); 7,35 (m, 1H); to 7.25 (d, 1H); to 7.15 (m, 2H); 5,10 (s, 2H); of 4.45 (s, 2H); 3.75 to (m, 2H); to 2.65 (m, 2H).

Example 544

2-butyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 430,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm with 8.05 (s, 1H); to 7.95 (d, 2H); 7,80 (d, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); to 7.15 (d, 1H); 5,20 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H); of 1.55 (m, 2H); 1,25 (m, 2H); 0,9 (t, 3H).

Example 545

tert-butyl ester 4-(2-butyl-1-oxo-2,3-dihydro-1H-isoindole-5-intoximeter)-3-(3-triptoreline)pyrazole-1-carboxylic acid

ESI-MS: 530,30 [M+H]+.

Example 545

2-butyl-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 430,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm with 8.05 (m, 3H); of 7.70 (m, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); 3,50 (m, 2H); of 1.55 (m, 2H); of 1.30 (m, 2H); 0,9 (t, 3H)./p>

Example 546a

tert-butyl ester 4-(2-butyl-1-oxo-2,3-dihydro-1H-isoindole-5-intoximeter)-3-(4-chlorophenyl)pyrazole-1-carboxylic acid

ESI-MS: 496,20 [M+H]+.

Example 546

2-butyl-5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 396,20 [M+H]+.

Example 547

2-butyl-5-[3-(3,4-dichlorophenyl)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 430,10/432,10 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (s, 1H); of 7.70 (m, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); 3,50 (m, 2H); of 1.55 (m, 2H); of 1.30 (m, 2H); from 0.90 (t, 3H).

Example 548

2-butyl-5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 380,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (s, 1H); of 7.70 (m, 2H); of 7.60 (d, 1H); 7,25 (m, 3H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H); of 1.55 (m, 2H); 1,25 (m, 2H); of 0.85 (t, 3H).

Example 549

2-butyl-5-[3-(3-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 396,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 8,00 (user. s, 1H); of 7.75 (s, 1H); the 7.65 (d, 1H); of 7.60 (d, 1H); was 7.45 (t, 1H); 7,40 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H); of 1.55 (m, 2H); 1,25 (m, 2H); 0,9 (t, 3H).

Example 550

2-butyl-5-[3-(3-trifluoromethyl)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 380,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); at 7.55 (m, 2H); to 7.4 (m, 2H); to 7.25 (s, 1H); to 7.15 (t, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); of 4.35 (s, 2H); of 3.45 (t, 2H); of 1.55 (m, 2H); 1,25 (m, 2H); 0,9 (t, 3H).

Example 551

2-butyl-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 362,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 9,50 (user. s, 2H); of 7.90 (s, 1H); the 7.65 (d, 2H); at 7.55 (d, 1H); was 7.45 (m, 2H); to 7.35 (t, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); of 3.45 (t, 2H); of 1.55 (m, 2H); of 1.30 (m, 2H); 0,9 (t, 3H).

Example 552

2-(4,4,4-trifloromethyl)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 484,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); of 7.90 (d, 2H); 7,80 (d, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); of 4.45 (s, 2H); 3,55 (t, 2H); 2,30 (m, 2H); of 1.80 (m, 2H).

Example 553

5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2-(4,4,4-trifloromethyl)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 416,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (s, 1H); of 7.70 (d, 2H); of 7.60 (d, 1H); was 7.45 (m, 2H); 7,35 (m, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); of 4.45 (s, 2H); 3,55 (t, 2H); 2,30 (m, 2H); of 1.80 (m, 2H).

Example 554

5-[3-(3,4-dichlorophenyl)-1H-pyrazole-4-ylethoxy]-2-(4,4,4-trifloromethyl)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 484,10/486,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); of 7.90 (s, 1H); of 7.70 (m, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); of 4.45 (s, 2H); 3,55 (t, 2H); 2,30 (m, 2H); of 1.80 (m, 2H).

Example 555

2-(3-methylbutyl)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-Digue is drosendahl-1-antiperoxidase acid

ESI-MS: 444,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm with 8.05 (s, 1H); to 7.95 (d, 2H); 7,80 (d, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); 3,50 (m, 2H); 1,50 (m, 2H); 0,9 (d, 6H).

Example 556

2-(3-methylbutyl)-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 376,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (user. s, 1H); of 7.70 (d, 2H); at 7.55 (d, 1H); was 7.45 (t, 1H); to 7.35 (t, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); 3,50 (m, 2H); to 1.45 (m, 2H); 0,9 (d, 6H).

Example 557

5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2-(2-trifloromethyl)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 418,15 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (s, 1H); of 7.70 (d, 2H); of 7.60 (d, 1H); was 7.45 (m, 2H); to 7.35 (t, 1H); 7,30 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); of 4.45 (s, 2H); 4,30 (m, 2H); of 3.80 (m, 2H).

Sample 558a

tert-butyl ester 4-(2-ethyl-1-oxo-2,3-dihydro-1H-isoindole-5-intoximeter)-3-(3-triptoreline)pyrazole-1-carboxylic acid

ESI-MS: 502,20 [M+H]+.

Example 558

2-ethyl-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 402,10 [M+H]+.

Example 559

2-ethyl-5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 352,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (s, 1H); of 7.70 (m, 2H); at 7.55 (d, 1H); 7,25 (m, 3H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); to 3.45 (m, 2H); to 1.15 (t, 3H).

Example 560

2-ethyl-5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

SI-MC: 352,20 [M+H] +.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.95 (s, 1H); of 7.60 (d, 1H); at 7.55 (d, 1H); was 7.45 (m, 2H); to 7.25 (s, 1H); to 7.15 (t, 1H); 7,10 (d, 1H); of 5.05 (s, 2H); however, 4.40 (s, 2H); to 3.45 (m, 2H); to 1.15 (t, 3H).

Example 561

5-[3-(3-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-ethyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 368,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); of 7.75 (s, 1H); the 7.65 (d, 1H); of 7.60 (d, 1H); was 7.45 (t, 1H); 7,40 (d, 1H); to 7.25 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H); 3,50 (m, 2H); to 1.15 (t, 3H).

Example 562

5-[3-(4-chlorophenyl)-1H-pyrazole-4-ylethoxy]-2-ethyl-2,3-dihydroindol-1-he

ESI-MS: 368,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,15 (user. s, 1H); 8,00 (user. s, 1H); of 7.70 (m, 2H); of 7.60 (d, 1H); was 7.45 (m, 2H); to 7.25 (s, 1H); 7,10 (d, 1H); 5,10 (s, 2H); however, 4.40 (s, 2H); 3,50 (m, 2H); to 1.15 (t, 3H).

Example 563

2-ethyl-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 334,10 [M+H]+.

Example 564

2-(2-bromacil)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 480,10/482,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (m, 3H); of 7.70 (m, 3H); 7,20 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); 4,55 (s, 2H); 4,00 (t, 2H); 3,70 (t, 3H).

Example 565

2-(2-bromacil)-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 480,10/482,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm with 8.05 (s, 1H); to 7.95 (d, 1H); of 7.90 (s, 1H); of 7.70 (d, 1H); the 7.65 (d, 1H); of 7.60 (t, 1H); 7,20 (s, 1H); 710 (d, 1H); further 5.15 (s, 2H); 4,55 (s, 2H); 4,00 (t, 2H); 3,70 (t, 3H).

Example 566

2-(2,2-dottorati)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 438,10 [M+H]+.

1H-NMR (500 MHz, MeOD): δ ppm of 7.90 (s, 1H); a 7.85 (d, 2H); of 7.70 (m, 3H); 7,20 (s, 1H); to 7.15 (d, 1H), 6,10 (t,J=70 Hz, 1H); further 5.15 (s, 2H); 4,55 (s, 2H); of 3.95 (t, 2H).

Example 567

2-(2,2-dottorati)-5-(3-phenyl-1H-pyrazole-4-ylethoxy)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 370,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 7,80 (s, 1H); of 7.70 (d, 1H); the 7.65 (d, 2H); 7,40 (m, 2H); to 7.35 (d, 1H); 7,10 (s, 1H); 7,05 (d, 1H); 6,10 (t,J=70 Hz, 1H); 5,10 (s, 2H); 4,50 (s, 2H); of 3.95 (t, 2H).

Example 568

2-(2,2,2-triptorelin)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 456,10 [M+H]+.

Example 569

2-(2,2,2-triptorelin)-5-[3-(3-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 456,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm with 8.05 (m, 3H); the 7.65 (m, 3H); to 7.35 (s, 1H); to 7.15 (d, 1H); further 5.15 (s, 2H); 4,55 (s, 2H); of 4.35 (m, 2H).

Example 570

5-[3-(4-forfinal)-1H-pyrazole-4-ylethoxy]-2-(2,2,2-triptorelin)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 406,10 [M+H]+.

Example 571

5-[3-(3-forfinal)-1H-pyrazole-4-ylethoxy]-2-(2,2,2-triptorelin)-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 406,10 [M+H]+.

1H-NMR (500 MHz, d -DMSO): δ ppm of 8.00 (s, 1H); of 7.70 (d, 1H); at 7.55 (d, 1H); was 7.45 (m, 2H); to 7.35 (s, 1H); 7,20 (m, 2H); further 5.15 (s, 2H); 4,55 (s, 2H); of 4.35 (m, 2H).

Example 572

5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 374,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (m, 3H); of 7.70 (m, 3H); 7,20 (s, 1H); 7,10 (d, 1H); further 5.15 (s, 2H); however, 4.40 (s, 2H).

Example 573

2-methyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 388,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 7,80 (m, 4H); of 7.70 (d, 2H); 7,05 (d, 1H); 7,00 (s, 1H); 5,10 (s, 2H); of 4.35 (s, 2H); 3,20 (s, 3H).

Example 574a

tert-butyl ester 4-(1-oxo-2-propyl-1,2,3,4-tetrahydroisoquinoline-6-intoximeter)-3-(4-triptoreline)pyrazole-1-carboxylic acid

Example 574

2-propyl-6-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-3,4-dihydro-2H-isoquinoline-1-antiperoxidase acid

ESI-MS: 430,10 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (d, 2H); 7,80 (m, 3H); 7,00 (d, 1H); to 6.95 (s, 1H); further 5.15 (s, 2H); 3.50 for each (t, 2H); 3.40 in (t, 2H); 2,90 (m, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 575a

tert-butyl ester 4-[(1-oxo-2-propyl-2,3-dihydro-1H-isoindole-5-ylamino)methyl]-3-(4-triptoreline)pyrazole-1-carboxylic acid

ESI-MS: 515,20 [M+H]+.

Example 575

2-propyl-5-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 415,20 [M+H]+.

1/sup> H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (m, 2H); 7,80 (m, 3H); to 7.35 (d, 1H); 6.75 in (m, 2H); 4,30 (m, 4H); 3.40 in (m, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 576

5-{[3-(4-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 381,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.75 (s, 1H); of 7.70 (d, 2H); 7,50 (d, 2H); to 7.35 (d, 1H); 6,70 (m, 2H); 4,30 (s, 2H); 4.25 in (s, 2H); at 3.35 (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 577

5-{[3-(3-chlorophenyl)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 381,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.75 (s, 1H); of 7.70 (s, 1H); the 7.65 (d, 1H); was 7.45 (t, 1H); 7,40 (d, 1H); to 7.35 (d, 1H); 6.75 in (m, 2H); 4.25 in (m, 4H); 3.40 in (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 578

2-propyl-5-{[3-(3-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 415,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); to 7.95 (d, 1H); 7,80 (s, 1H); of 7.70 (m, 2H); to 7.35 (d, 1H); 6.75 in (m, 2H); 4,30 (s, 4H); 3.40 in (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 579

5-{[3-(4-forfinal)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 365,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.75 (s, 1H); of 7.70 (m, 2H); to 7.35 (d, 1H); 7,25 (m, 2H); 6,70 (m, 2H); 4.25 in (s, 2H); 4,20 (s, 2H); 3.40 in (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 580

5-{[3-(3-forfinal)-1H-pyrazole-4-ylmethyl]amino}-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 365,20 [M+H]+/sup> .

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.75 (s, 1H); at 7.55 (d, 1H); was 7.45 (d, 1H); to 7.35 (d, 1H); to 7.15 (t, 1H); 6.75 in (m, 2H); 4,30 (m, 4H); 3.40 in (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 581

5-[(3-phenyl-1H-pyrazole-4-ylmethyl)amino]-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 347,20 [M+H]+.

1H-NMR (400 MHz, d6-DMSO): δ ppm of 7.70 (s, 1H); the 7.65 (d, 2H); was 7.45 (m, 2H); 7,35 (m, 2H); 6.75 in (m, 2H); 4,30 (s, 2H); 4.25 in (s, 2H); 3.40 in (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 582

2-propyl-5-{[4-(3-triptoreline)-1H-pyrazole-3-ylmethyl]amino}-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 415,20 [M+H]+.

Example 583

2-propyl-5-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}isoindole-1,3-dentrificans acid

ESI-MS: 429,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (d, 2H); 7,80 (s, 1H); of 7.75 (d, 2H); at 7.55 (d, 1H); 7,30 (user. s, 1H); 7,00 (s, 1H); 6.90 to (d, 1H); however, 4.40 (s, 2H); of 3.45 (t, 2H); of 1.55 (m, 2H); of 0.85 (t, 3H).

Example 584

2-propyl-6-{[3-(4-triptoreline)-1H-pyrazole-4-ylmethyl]amino}-2,3-dihydroisoquinoline-1-antiperoxidase acid

ESI-MS: 427,15 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.90 (m, 3H); a 7.85 (s, 1H); 7,80 (d, 2H); to 7.25 (d, 1H); 6,85 (d, 1H); 6,55 (s, 1H); 6.30-in (d, 1H); of 4.35 (s, 2H); of 3.80 (m, 2H); of 1.65 (m, 2H); of 0.85 (t, 3H).

Example 585

tert-butyl ester 4-[1-oxo-2-(4-cryptomaterial)-2,3-dihydro-1H-isoindole-5-intoximeter]-3-(4-triptoreline)pyrazole-1-carboxylic acid

ESI-MS: 648,20 [M+H]+.

Example 585

2-(4-triform oxybenzyl)-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 548,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 8.00 (s, 1H); of 7.90 (d, 2H); 7,80 (d, 2H); the 7.65 (d, 1H); 7,40 (d, 2H); to 7.35 (d, 2H); to 7.25 (s, 1H); to 7.15 (d, 1H); further 5.15 (s, 2H); 4.75 V (s, 2H); of 4.35 (s, 2H).

Example 586

2-cyclohexylmethyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 470,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm with 8.05 (s, 1H); to 7.95 (d, 2H); 7,80 (d, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); to 7.15 (d, 1H); 5,20 (s, 2H); however, 4.40 (m, 1H); 3,30 (d, 2H); of 1.65 (m, 3H)and 1.60 (m, 3H); to 1.15 (m, 3H), of 0.90 (m, 2H).

Example 587

2-isobutyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 430,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm with 8.05 (s, 1H); to 7.95 (d, 2H); 7,80 (d, 2H); of 7.60 (d, 1H); to 7.25 (s, 1H); to 7.15 (d, 1H); 5,20 (s, 2H); however, 4.40 (m, 1H); 3,30 (d, 2H); 2,00 (m, 1H); of 0.85 (d, 6H).

Example 588

2-cyclopentyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 442,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,25 (user. s, 1H); 8,10 (user. s, 1H); to 7.95 (m, 2H); 7,80 (m, 2H); at 7.55 (d, 1H); to 7.25 (s, 1H); to 7.15 (d, 1H); 5,20 (s, 2H); 4,55 (m, 1H); however, 4.40 (s, 2H); of 1.85 (m, 2H); to 1.75 (m, 2H); of 1.65 (m, 4H).

Example 589

tert-butyl ester 4-(1-oxo-2-phenyl-2,3-dihydro-1H-isoindole-5-intoximeter)-3-(4-triptoreline)pyrazole-1-carboxylic acid

ESI-MS: 550,20 [M+H]+.

Example 589

2-phenyl-5-[3-(4-triptoreline)-1H-pyrazole-4-ylethoxy]-2,3-dihydroindol-1-he

ESI-MS: 550,10 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm 13,30 (user. s, 1H); 8,05 (user. s, 1H); to 7.95 (m, 2H); of 7.90 (d, 2H); 7,80 (m, 2H); of 7.70 (d, 1H); was 7.45 (m, 2H); to 7.35 (s, 1H); to 7.15 (m, 2H); 5,20 (s, 2H); of 4.95 (s, 2H).

Example 590

5-[(3-methyl-5-phenylisoxazol-4-ylmethyl)amino]-2-propyl-2,3-dihydroindol-1-antiperoxidase acid

ESI-MS: 362,20 [M+H]+.

1H-NMR (500 MHz, d6-DMSO): δ ppm of 7.70 (d, 2H); at 7.55 (m, 3H); to 7.35 (d, 1H); 6,70 (d, 1H); of 6.65 (s, 1H); 4.25 in (s, 2H); 4,20 (s, 2H); at 3.35 (t, 2H); 2,30 (s, 3H); of 1.55 (m, 2H); of 0.85 (m, 3H).

Examples intended for the introduction of the galenical forms

A) Tablets

Tablets of the following composition is extruded on the press for tablets in the usual way:

40 mg of the product of example 4

120 mg of corn starch

13.5 mg of gelatin

45 mg of lactose

2.25 mg Aerosil (chemically pure silicic acid in the form of submicroscopic small dispersion)

of 6.75 mg of potato starch (6% paste)

C) Covered sugar pills

20 mg of the substance according to example 4

60 mg of the composition of the nucleus

70 mg Osharova composition

The composition of the core consists of 9 parts of corn starch, 3 parts of lactose and 1 part of a copolymer 60:40 vinyl pyrrolidone/vinyl acetate. Osharova composition consists of 5 parts sugar, 2 parts of corn starch, 2 parts of calcium carbonate and 1 part of talc. Covered sugar pills, which are obtained in this manner is then supplied to sustainable zheludochno the Moo juice coating.

Biological tests

Generation NEC cell clones permanently expressing mGlu receptors, and functional assessment of cells

a) mGlu receptor

For the purpose of this study cell line permanently expressing human mGlu2 receptor, rat glutamate Transporter rGLAST and alpha-subunit G16, generated by transfection. Briefly, NEC cells were sown in Petri dishes (15 cm diameter) with a density of 2×106cells in DMEM with glutamax (Invitrogen, GIBCO#21885-025), 10% detalizirovannoi fetal calf serum (Invitrogen, GIBCO#26400-044) and incubated at 37°C over night. The next day, the cells were transfusional lipofectamine (Invitrogen, GIBCO#18324-012), as recommended by the manufacturer, using the linearized rdnk (V5/His)-hmGlu2 receptor (Scal) and rdnc Zeo-Ga16 IRES rGLAST (Sspl). After transfection cells were selected in DMEM Glutamax (Invitrogen, GIBCO#21885-025)containing 10% detalizirovannoi fetal calf serum (FCS; (Invitrogen, GIBCO#26400-044), antibiotic/antimycotic agent, 800 μg/ml of geneticin (G418) and 250 μg/ml cesina. Individual clones were isolated manually and additional subclinical serial dilution.

The function of the mGlu2 receptor was determined by assessing intracellular concentrations of CA+2under standard conditions in fluorimetric tablet-image reader (FLIPR, Molecular Devices, Union City, CA 94587, USA) by MEAs is the measured response of the cells to the test compound. FLIPR analysis is a standard functional analysis and monitoring of natural or recombinant Glphaq-coupled receptors and natural or recombinant receptors, usually associated with other G-protein cascades of the transmission signal, which is correlated with the calcium through co-expression of alpha-subunit mixed or chimeric G-protein. In the analysis, the increase in intracellular calcium was measured using the calcium-sensitive fluorescent dye (e.g., Fluo-4 AM) in the FLIPR device.

For the selection of a suitable cell clone and subsequent measurement of the selected clone, 4×104cells/well were placed on coated with poly-D-lysine 96-well Biocoat tablets in DMEM Glutamax (GIBCO#21885-025)/10% detalizirovannoi FCA during the night. The next day the medium was aspirated and replaced besplatnoe with DMEM (GIBCO#21969-035)without FCS or glutamine containing 50 μg/ml gentamicin (GIBCO#15750). The cells are again incubated overnight. Before measurement, the cells were loaded with 2 μm Fluo-4 AM (molecular probes, F14201; the original solution of 1 mm in DMSO) and 0.02% Pluronic F127 (molecular probes, R; the source solution 10% DMSO) in DMEM (GIBCO#21969-035) for 45 minutes at 37°C with a final volume of 100 μl per well. In conclusion, the tablets were washed in a device for washing cells BioTec with HBSS containing 20 mm HEPES. The final volume in each well was 100 the class. Then the tablets were measured by fluorimetric tablet-image reader (FLIPR, Molecular Devices, Union City, CA 94587, USA).

Compounds of the present invention were tested in the above analyzer FLIPR using selected cell clone. Increased levels of intracellular calcium quantitatively determined after addition of test compounds (agonism), and the subsequent addition of a submaximal concentration of 1 micromolar (1 μm) of glutamate (potentiation).

To determine the effect of the test compounds (agonism) or increased response to a submaximal concentration (for example, 1 μm) of glutamate (potentiation) the resulting signal was determined by subtracting the background fluorescence from the maximum height of the fluorescence peak of the corresponding response. In the FLIPR device connection was filed in the cell and its fluorescent response was quantitatively determined using devices FLIPR (agonism). The concentration at which the compound exhibits a half of its maximum action, called 'effective concentration 50' or 'EC50'. The maximum effect caused by the test compound was standardized in accordance with the maximum effect shown by 100 μm glutamate (set at 100%).

Ten minutes after addition of the test compounds is the tablet was added to 1 μm glutamate. Potentiator enhances the response of the receptor for glutamate. The response to glutamate in the presence of test compounds were determined quantitatively. The concentration at which the test compound is able to show half of his maximum potentiate actions on glutamate, called 'EC50'. The maximum response to 1 micromolar glutamate in the presence of test compounds standardized in accordance with the maximum effect shown by 100 μm glutamate (set at 100%). Built on the points of the curve using the method of least squares and chetyrehkamernoe equations were then applied to the resulting curve dose-response to determine the resultant values of the EU50(Graph Pad Prism). The control cell line, NECK cells permanently expressing rGLAST, and Glpha 16 is also placed in the microplate 4×104cells/well for parallel testing to confirm the specificity of the test compounds to the mGlu2 receptor agonism or potenzirovania. Values EU50are given in table 1.

High-efficiency or key connections are additionally characterized by measuring their effectiveness and activity against inhibition of Forskolin-induced levels of camp in these cells relative to their own (level) (agonism) or potentsiirovannye really is glutamate (potentiation). Levels of cyclic AMR quantitatively determined using the method of Alphascreen (PerkinElmer Life and Analytical Science, 710 Bridgeport Avenue, Shelton, CT USA)as described by the manufacturer, to determine action Galphai-coupled receptors. The concentration at which the compound exhibits a half of its maximum activity. called the 'effective concentration 50' or 'EC50'. Maximum efficiency caused by the test substance, standardized in accordance with the maximum effect shown by 100 μm glutamate (100%). Curve built from points using the method of least squares and chetyrehkamernoe equations were then applied to the resulting curve dose-response to determine the resultant values of the EU50(Graph Pad Prism).

Compounds of the following examples had activity against the potentiation mGlu2 receptor in the aforementioned assays, generally with the EU50not more than approximately 10 microns. Preferred compounds of the present invention had activity against the potentiation mGlu2 receptor in the aforementioned assays with EU50less than about 1 μm. This result is the indication of the intrinsic activity of the compounds in use as potentiators activity mGlu2 receptor.

td align="center"> 483
Table 1
The values of the EU50potentiate the actions on glutamate
Connection example#EC501)
9++
13++
16++
23++
25++
35++
37++
40+++
42+++
43++
46++
45++
49++
50++
++
53++
55++
56++
57++
58++
60++
68++
71++
73+++
75++
76+++
77+++
81++
82+++
83+++
82++
116 ++
117++
169++
209+++
210+++
211++
212+++
213+++
214++
215++
216++
217+++
218+++
219++
220++
221++
222++
223224++
226++
227++
228++
232++
233++
242++
243++
245++
246++
250++
255++
260++
268++
273++
281++
284++
285++
286++
298++
307++
310++
311++
312++
313++
317++
321++
340++
341++
349++
351++
355++
363++
374+++
375+++
378++
379++
380++
383++
385++
386++
387++
389++
390+++
391++
392++
399++
400++
401++
416++
423++
430++
433++
434+++
436++
437++
440+++
442+++
443++
454++
455++
456++
457++
458++
475++
476++
477++
478++
++
485++
487++
488++
489+++
490+++
491+++
492++
494+++
495+++
496+++
497+++
498+++
499+++
501++
502++
503++
504++
506++
507++
508+++
509+++
510+++
511+++
513+++
514++
515++
516+++
517+++
518++
519++
520+++
521+++
522++
523++
524++
525+++
526++
529++
531+++
532+++
533+++
534+++
535+++
536+++
537+++
538+++
539+++
540+++
541+++
542+++
543+++
544+++
545+++
546+++
547+++
548+++
549+++
550+++
551+++
552+++
553+++
554+++
558+++
559+++
560+++
562+++
563+++
564+++
565+++
566+++
567+++
568+++
569+++
570+++
571+++
573+++
574+++
576+++
577+++
578+++
579+++
580+++
581+++
582++
584+++
585+++
586+++
587+++
588+++
589++
590+++
+++: EU50<1 μm
++: 1 µm≤EC50≤10 ám

b) mGlu3 receptor

For the purpose of this study was generated by transfection of the cell line permanently expressing human mGlu3 receptor, rat glutamate Transporter rGLAST and the alpha subunit of G16. Briefly, NEC cells were sown in Petri dishes (15 cm diameter) with a density of 2×106cells in DMEM with glutamax (Invitrigen, GIBCO#21885-025), 10% detalizirovannoi fetal bovine serum (Invitrigen, GIBCO#26400-044) and incubated at 37°C over night. The next day, the cells were transfusional lipofectamine (Invitrigen, GIBCO#18324-012), as recommended by the manufacturer, using the linearized rdnk (V5/His)-hmGlu3 receptor (Scal) and rdnc Zeo-Ga16 IRES rGLAST (Sspl). After transfection cells were selected in DMEM is glutamax (Invitrigen, GIBCO#21885-025)containing 10% detalizirovannoi fetal calf serum (FCS; (Invitrigen, GIBCO#264-044), antibiotic/antimycotic agent, 800 μg/ml of geneticin (G418) and 250 μg/ml cesina. Individual clones were isolated manually and then subclinically serial dilution. Function tested FLIPR, as described above.

C) mGlu4 receptor

For the purpose of this study was generated by transfection of the cell line permanently expressing human mGlu4 receptor, rat glutamate Transporter rGLAST and the alpha subunit of G15. Briefly, NEC cells were sown in Petri dishes (15 cm diameter) with a density of 2×106cells in DMEM glutamax (Invitrigen, GIBCO#21885-025), 10% detalizirovannoi FCS and incubated at 37°C over night. The next day, the cells were transfusional lipofectamine (Invitrogen, Karlsruhe, Germany)as recommended by the manufacturer, using the linearized rdnk-hmGlu4 (Sspl) and rdnc(+) Hygro-rGLAST IRES Ga15 (Sspl). After transfection cells were cultured in DMEM glutamax (Invitrogen)containing 10% detalizirovannoi fetal calf serum (FCS; Invitrogen), antibiotic/antimycotic agent, 800 μg/ml of geneticin (G418) and 150 μg/ml of hygromycin, individual clones were isolated manually and subclinically serial dilution. Function tested FLIPR, as described above.

d) mGlu7 receptor

For the purpose of this research generirouyushaya cell line, permanently expressing human mGlu7a receptor, rat glutamate Transporter rGLAST and the alpha subunit of G15. Briefly, NEC cells were sown in Petri dishes (15 cm diameter) with a density of 2×106cells in DMEM glutamax, 10% detalizirovannoi FCS and incubated at 37°C over night. The next day, the cells were transfusional lipofectamine (Invitrogen, Karlsruhe, Germany)as recommended by the manufacturer, using the linearized rdnk-hmGlu7a (Sspl). After transfection cells were cultured in DMEM Glutamax (Invitrogen)containing 10% detalizirovannoi fetal calf serum (FCS; Invitrogen), antibiotic/antimycotic agent (Invitrogen), 800 μg/ml of geneticin (G418). Individual clones were isolated manually tested in a decrease in cellular camp (alpha screening) and subclinically FACS. Individual cell clones was re-tested in the reduction of camp and transfusional rdnk(+) Hygro rGLAST IRES Ga15 (Sspl). The transfection was performed as described above. Cells were selected in DMEM Glutamax, 10% detalizirovannoi FCS and antibiotic/antimycotic agent, 800 μg/ml G418 and 150 μg/ml of hygromycin. Individual clones were isolated by serial dilution and tested FLIPR, as described above.

e) mGlu1 and 5 receptors

For the purpose of this study was generated by transfection of the cell line permanently expressing human mGlu5a and rat glutamate the second conveyor rGLAST. Briefly, cells were transfusional lipofectamine (Invitrogen, Karlsruhe, Germany) using the linearized rdnk-hmGlu5a (Sspl) and plRES-rGlast (Sspl). After transfection cells were cultured in DMEM Glutamax (Invitrogen)containing 10% detalizirovannoi fetal calf serum (FCS; Invitrogen), antibiotic/antimycotic agent, 800 μg/ml of geneticin (G418) and 150 μg/ml of hygromycin, and individual clones were isolated manually. Similarly generate a cell line expressing mGlu1a. Functional clones were selected using measurements of intracellular CA2+using fluorescent tablet-image reader (FLIPR) under standard conditions as described above.

f) research NCAndreceptor binding

f.1 Radioligand binding to the cloned human 5-HT2A

Cho-K1 cells stably expressing the human 5-HT2Areceptor (Euroscreen-ES-313-C, protein ID NP 036679), were cultured in UltraCHO mediumTMwith glutamine (Cambrex Bio Science, Walkersville, Inc., USA), and added with 1% fetal calf serum. Received the "shadow" of the cell. For studies of inhibition of 0.4 nm [3H]-ketanserin and "shadow" cells (6,5-8,5 μg of protein/assay) were incubated in the presence of various concentrations of test compounds in a total volume of 200 μl. Nonspecific binding was determined using 1 μm meanse the ina. The binding reaction was carried out for 1 h at room temperature and stopped by filtration on Packard Unifilter GF/C (with 0.3% PEI) tablets with header Tomtec Machill U 96-well plate. After the tablets were dried for 2 h at 55°C in a drying chamber, was added to the scintillation mixture (BetaPlate Scint; PerkinElmer). Radioactivity was measured in a Microbeta Trilux two hours after addition of scintillation mixture.

f.2 Determination of antagonistic activity mobilization of intracellular CA2+

The increase in intracellular CA2+measured device FLIPR384 (Molecular Devices). Cells were sown on black 96-well plates to cell cultures and cultured in 100 μl of growth medium overnight at 37°C, 5% CO2. The next day cells were incubated overnight in serum-free medium. On the day of experiment, cells were loaded with 100 μl of a reagent kit for analysis Sa (as described by the manufacturer, Molecular Devices, Ismaning/münchen, Germany), incubated for 1-2 h at 37°C and 5% CO2in the dark, with subsequent 30-60 min incubation at room temperature before the tablet was transferred into a device.

Curves of the concentration response after adding substances used to calculate the values of the EU50using GraphPadPrism. For antagonists values IC50was calculated using curves Concentratio the nogo response after addition of 50 nm 5-HT. The values of the IC50were converted into apparent value of Kbusing functional equivalent equation of Cheng-Prusoff.

Compounds of working examples often had the binding constants Ki(5-HT2Abelow 1 μm, in particular at most 0.5 micron, more preferably at most 250 nm or especially at most 100 nm. Compounds demonstrate antagonistic behavior.

1. The compound of formula Ia.1.a, AA, AA or Ia.4.a

where
Raand Rbindependently from each other selected from hydrogen, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, Rbalso may be IT, if Rarepresents hydrogen, C1-C4alkyl or C1-C4halogenated, X represents O, NH or N-Rx, R10arepresents hydrogen or has one of the meanings given for R10, R11arepresents hydrogen or has one of the meanings given for R11;R2represents hydrogen, CN, IT, halogen, C1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C3-C6cycloalkyl and C1-C4alkoxy,
With3-C6cycloalkyl,1-C8halogenated,1-C8ALCO is si and C 1-C8halogenoalkane; R3represents hydrogen, halogen, C1-C4alkyl, which is unsubstituted or carries one radical selected from HE, and1-C4alkoxy, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane,
With3-C8cycloalkyl, which is unsubstituted or has 1,
2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;
R4selected from
With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy, C3-C8cycloalkyl and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4a,
With1-C8halogenoalkane,
With2-C8alkenyl,
With2-C8the quinil,
With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy, and phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4band
5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where heteroaryl is unsubstituted or has 1, 2, 3 or odinakovyh or different radicals R 4bor
R4together with R2forms With1-C5alkalinity or3-C5alkenylamine fragment, where one CH2part may be replaced by oxygen, sulfur or N-R4c-part of, and where C1-C5alkylene and C2-C5albaniles can be unsubstituted or have 1, 2, 3 or 4 radicals selected from halogen, CN, HE, NH2With1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkylamino, di(C1-C4alkyl)amino, C1-C4alkoxy and C1-C4halogenoalkane; R4aselected from the group consisting of halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane; R4bselected from the group consisting of halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane; R4cselected from the group consisting of hydrogen, CN, IT,1-C8of alkyl, which is unsubstituted or is a radical selected from C1-C4alkoxy, C1-C4alkylthio,1-C4halogenoalkane,1-C4allogenicity,3-C6cycloalkyl that the C is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from halogen and C1-C4of alkyl,
phenyl or benzyl, where the very phenyl ring in the last two radicals is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane,
With3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;
R10selected from halogen, cyano,
With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4a,
With1-C8alkoxy, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R4a,
With1-C8halogenoalkane,
With1-C8halogenoalkane,
With2-C8alkenyl,
With1-C6the quinil,
With3-C8cycloalkyl, which is unsubstituted or have the t 1, 2, 3 or 4 radicals selected their halogen, C1-C4the alkyl and C1-C4alkoxy,
With3-C8cycloalkane, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,
C(=O)-R13C(=O)-OR14, NR15R16C(=O)NR15R16, SO2R17,
phenyl, O-phenyl, CH2-phenyl, CH(CH3)-phenyl, CH(OH)phenyl, S-phenyl and O-CH2-phenyl, where the phenyl ring in the last seven following radicals may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, which is unsubstituted or has 1, 2, 3, 4 or 5 substituents selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;
R11represents a CN, IT, halogen, C1-C8alkyl, which is unsubstituted or carries one radical selected from HE, and1-C4alkoxy, C1-C8halogen is Qila, With1-C8alkoxy, C1-C8halogenoalkane or phenyl which may be unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, C1-C4of alkyl,
With1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;
R13selected from hydrogen,
With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R13a,
With1-C8halogenoalkane,
With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,
phenyl and 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where phenyl and heteroaryl are unsubstituted or have 1, 2, 3, 4 or 5 identical or different radicals R13b;
R13aselected from the group consisting of halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane;
R13bselected from the group consisting of halogen, CN, IT,1-C4of alkyl, sub> 3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane; R14selected from
With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R13a,
With1-C8halogenoalkane and
With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;
R15selected from hydrogen,
With1-C8of alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R13aand
With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy;
R16selected from hydrogen and C1-C8the alkyl or
R15and R16together with the nitrogen atom to which they are linked, form a heterocyclic radical selected from pyrrolidinyl, piperidinyl, piperazinil, N-alkylpiperazine, N-penilee is azinil and morpholinyl;
R17represents a C1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3, 4 or 5 identical or different radicals R17a,
With1-C8halogenated,
With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl or C1-C4alkoxy, phenyl and 5 - or 6-membered heteroaryl having 1, 2 or 3 heteroatoms in the ring, the heteroatoms selected from O, S and N, where phenyl and heteroaryl are unsubstituted or have 1, 2, 3, 4 or 5 identical or different radicals R17bwhere R17ais the same as defined for R13aand R17bis the same as defined for R13b;
Rxrepresents a C1-C6alkyl, C1-C4halogenated,1-C4alkoxy-C1-C4alkyl, C3-C6cycloalkyl,3-C6cycloalkenyl, benzyl, where the phenyl ring is unsubstituted or has 1, 2 or 3 radicals selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4-halogenoalkane,1-C4-alkoxy and C1-C4-halogenoalkane, and radical SO2-Rsup> x5where Rx5represents a C1-C4alkyl, C1-C4-foralkyl, in particular, 5 - or 6-membered heteroaryl, which may contain a condensed benzene ring and phenyl, which is unsubstituted or has 1, 2, 3 radicals selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane and their pharmaceutically acceptable salts.

2. The compound according to claim 1, where Raand Rbrepresent hydrogen.

3. The compound according to claim 1 or 2, where Rllarepresents hydrogen.

4. The compound according to claim 1 or 2, where R2and R3represent hydrogen.

5. The compound according to claim 1, where X represents O or NH.

6. The compound according to claim 1, where R10arepresents a
With1-C8halogenated,
With3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,
With1-C8alkyl, which is unsubstituted or carries one radical selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1 2of alkyl, C1-C2alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, or
phenyl, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

7. The compound according to claim 1 or 2, where R3represents a hydrogen, and where R4together with R2form1-C5alkalinity or2-C5alkenylamine fragment, where one CH2part may be replaced by oxygen, sulfur or N-R4c-part of, and where C1-C5alkylene and C2-C5albaniles can be unsubstituted or have 1, 2, 3 or 4 radicals selected from halogen, CN, HE, NH2With1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkylamino, di(C1-C4alkyl)amino, C1-C4alkoxy and C1-C4halogenoalkane, and where R4cis such as defined in claim 1.

8. The connection according to claim 7, where R4cselected from C1-C6of alkyl, which is unsubstituted or is alkoxy or halogenoalkane radical, With3-C6cycloalkyl,1-C4halogenoalkane,3-C6cycloalkylation is the benzyl, where the phenyl ring is unsubstituted or has a Deputy selected from halogen, diformate, trifloromethyl, deformedarse, triptoreline.

9. The compound according to claim 1, where R4represents a C3-C8alkyl, C1-C3alkyl, which is substituted by a radical selected from C1-C4alkoxy and C3-C6cycloalkyl or1-C4halogenated.

10. The compound according to claim 1, which has the formula Ia', Ia', AA' or Ia.4.a'

where-Q - is-C(RQ1RQ2)-, -C(RQ1RQ2)-C(RQ3RQ4)- or-C(RQ1)=C(RQ2)-, where RQ1, RQ2, RQ3, RQ4each independently from each other selected from hydrogen, halogen, CN, HE, NH2With1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkylamino, di(C1-C4alkyl)amino, C1-C4alkoxy and C1-C4halogenoalkane; Raand Rbindependently from each other selected from hydrogen, halogen, C1-C4of alkyl, C1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane, Rbalso may be IT, if Rarepresents hydrogen, C1-C4alkyl or C1-C4halogenated, X represents O, NH and the N-R xwhere R4cand R3are as defined in claim 1, R10arepresents hydrogen or has one of the meanings given for R10, Rllarepresents hydrogen or has one of the meanings given for R11and its pharmaceutically acceptable salts.

11. The connection of claim 10, where Raand Rbrepresent hydrogen.

12. The compound of claim 10 or 11, where Rllarepresents hydrogen.

13. The compound of claim 10 or 11, where Q represents CH2.

14. The connection section 12, where Q represents CH2.

15. The connection of claim 10, where X represents O or NH.

16. The connection of claim 10, where R4cselected from C1-C6of alkyl, which is unsubstituted or is alkoxy or halogenoalkane radical, With3-C6cycloalkyl,1-C4halogenoalkane,3-C6cycloalkylation and benzyl, where the phenyl ring is unsubstituted or has a Deputy selected from halogen, diformate, trifloromethyl, deformedarse, triptoreline.

17. The connection of claim 10, where R10arepresents a
With1-C8halogenated,3-C8cycloalkyl, which is unsubstituted or has 1, 2, 3 or 4 radicals selected from halogen, C1-C4the alkyl and C1-C4alkoxy,
With1-C8alkyl, cat is which is unsubstituted or carries one radical, selected from HE, C1-C4alkoxy and phenyl, itself where the phenyl ring is unsubstituted or has 1, 2, 3 or 4 identical or different radicals selected from the group consisting of fluorine, chlorine, CN, C1-C2of alkyl, C1-C2-alkoxy, diformate, trifloromethyl, deformedarse, triptoreline, or
phenyl, which is unsubstituted or may have 1, 2, 3, 4 or 5 substituents selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

18. The compound according to claim 1 or 10, where R10arepresents phenyl, which is unsubstituted or has 1, 2, 3, 4 or 5 substituents selected from halogen, CN, IT,1-C4of alkyl, C3-C6cycloalkyl,1-C4halogenoalkane,1-C4alkoxy and C1-C4halogenoalkane.

19. Pharmaceutical composition for treatment of painful disorders associated with glutamate dysfunction, containing at least one compound according to claim 1 or 10, optionally together with at least one physiologically acceptable carrier or auxiliary substance.

20. The use of compounds according to claim 1 or 10 to obtain the pharmaceutical composition according to claim 19.

21. The compound according to claim 1 or 10 for the change in the treatment of painful disorders, associated with glutamate dysfunction selected from neurological disorders and psychiatric disorders.

22. The compound according to claim 1 or 10 for the treatment, control, suppress or reduce the risks associated with glutamate dysfunction, such as
the risk of anxiety in a mammal;
the risk of depression in a mammal;
the risk of migraine in a mammal;
the risk of schizophrenia in a mammal;
the risk of epilepsy in a mammal.

23. Compounds according to claim 1 or 10 for use in treating or reducing the intensity of symptoms associated with disorders related to substance in a mammal.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or use thereof to prepare a medicine for treating depression, anxiety or both: or pharmaceutically acceptable salts thereof, where m is 0-3; n is 0-2; Ar is: optionally substituted indolyl; optionally substituted indazolyl; azaindolyl; 2,3-dihydro-indolyl; 1,3-dihydro-indol-2-one-yl; optionally substituted benzothiophenyl; benzothiazolyl; benzisothiazolyl; optionally substituted quinolinyl; 1,2,3,4-tetrahydroquinolinyl; quinolin-2-one-yl; optionally substituted naphthalenyl; optionally substituted pyridinyl; optionally substituted thiophenyl or optionally substituted phenyl; R1 is: C1-6alkyl; hetero-C1-6alkyl; halo-C1-6alkyl; halo-C2-6alkenyl; C3-7cycloalkyl; C3-7cycloalkyl-C1-6alkyl; C1-6alkyl-C3-6cycloalkyl-C1-6alkyl; C1-6alkoxy; C1-6alkylsulphonyl; phenyl; tetrahydropyranyl-C1-6alkyl; phenyl-C1-3alkyl, where the phenyl part is optionally substituted; heteroaryl-C1-3alkyl; R2 is: hydrogen or C1-6alkyl; and each Ra and Rb is independently: hydrogen; C1-6alkyl; C1-6alkoxy; halo; hydroxy or oxo; or Ra and Rb together form C1-2alkylene; under the condition that, when m is 1, n is 2, and Ar is an optionally substituted phenyl, then R1 is not methyl or ethyl, and where optionally substituted denotes 1-3 substitutes selected from alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, amino, acylamino, monoalkylamino, dialkylamino, hydroxyalkyl, alkoxyalkyl, pyrazolyl, -(CH2)q-S(O)rRf; -(CH2)q-C(=O)-NRgRh; -(CH2)q-N(Rf)-C(=O)-Ri or -(CH2)q-C(=O)-Ri; where q is 0, r is 0 or 2, each Rf, Rg and Rh is independently hydrogen or alkyl, and each Ri is independently alkyl, and where "heteroaryl" denotes a monocyclic radical having 5-6 ring atoms, including 1-2 ring heteroatoms selected from N or S, wherein the rest of the ring atoms are C atoms, "heteroalkyl" denotes an alkyl radical, including a branched C4-C7-alkyl, where one hydrogen atom is substituted by substitutes selected from a group consisting of -ORa, -NRbH, based on the assumption that the bonding of heteroalkyl radical occurs through a carbon atom, where Ra is hydrogen or C1-6alkyl, Rb is C1-6alkyl. Pharmaceutical compositions based on said compound are also disclosed.

EFFECT: obtaining novel compounds which can be used in medicine to treat depression, anxiety or both.

14 cl, 1 tbl, 28 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new derivatives of ((phenyl)imidazolyl)methylheteroaryl of formula wherein A represents pyridyl or thienyl having 0 or 1 substitute; B represents phenyl having 0, 1 or 2 substitutes; wherein each substitute independently represents alkyl having 1 to 8 carbon atoms, -F, -Cl, -Br or -CF3. Also, the invention refers to the use of the declared compounds for the purpose of preparing a therapeutic agent, a pharmaceutical composition on the basis of the declared compounds, and to a kit containing the pharmaceutical composition above.

EFFECT: there are prepared new derivatives of ((phenyl)imidazolyl)methylheteroaryl effective in pain management.

10 cl, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts wherein r represents 1; Ar is specified in and , R1 is specified in -COOR1a, -NHSO2R1b, -SO2NHR1d, -SO2OH, -O-CH(R1e)-COOH and tetrazol-5-yl, R1a represents H, -C1-6alkyl, -C1-3alkylenaryl, -C1-3alkyleneheteroaryl, - C3-7cycloalkyl, -CH(C1-4alkyl)OC(O)R1aa, or R1aa represents -O-C1-6alkyl or -O-C3-7cycloalkyl; R1b represents R1c; R1d represents -C1-6alkyl or -C0-4alkylenaryl; R1d represents -C(O)R1c or -C(O)NHR1c; R1e represents -C1-4alkyl; Y represents -C(R3)-, Z represents -N-, Q represents -C(R2)-, and W represents a bond; Y represents -N-, Z represents -C(R3)-, Q represents -C(R2)-, and W represents a bond; Y represents -C(R3)-, Z represents -N-, Q represents -N-, and W represents a bond; or Y represents -C(R3)-, Z represents -CH-, Q represents -C(R2)-, and W represents -C(O)-; R2 is specified in H, halogen, -C1-6alkyl, -C3-6dicloalkyl, and -C0-5alkylene-OR2b; wherein R2b is specified in H and -C1-6alkyl; R3 is specified in -C1-10alkyl and -C0-5alkylene-O-C0-5alkylene-R3b; and R3b represents -C1-6alkyl; X represents -C1-12alkylene-, where at least one group -CH2- in alkylene is substituted by the group -NR4a-C(O)- or -C(O)-NR4a-, wherein R4a is specified in H, -OH, and -C1-4aalkyl; R5 is specified in -C0-3 alkylene-SR5a, -C0-3alkylene-C(O)NR5bR5c, -C0-3alkylene-NR5b-C(O)R5d, -NH-C0-1alkylene-P(O)(OR5e)2, -C0-2alkylene-CHR5g-COOH and -C0-3alkylene-C(O)NR5h-CHR5i-COOH; R5a represents H or -C(O)-R5aa; R5aa represents -C1-6alkyl, -C0-6alkylene-C3-7cycoalkyl, -C0-6alkylenaryl, or -C0-6alkylenemorpholine; R5b represents -OH, -OC(O)R5ba, -CH2COOH or -OC(S)NR5bbR5bc; R5ba represents -C1-6alkyl, -OCH2-aryl or -CH2O-aryl; R5bb and R5bc independently represents -C1-4alkyl; R5c represents H; R5d represents H; R5e represents H; R5g represents H or -CH2-O-(CH2)2-O-CH3; R5h represents H; R5i represents -C0-3alkylenaryl; R6 is specified in -C1-6alkyl, -C0-3alkylenaryl, -C0-3alkyleneheteroaryl and -C0-3alkylene-C3-7cycloalkyl; and R7 represents H or together with R6 to form -C3-7cycloalkyl; where each ring in Ar and each aryl and heteroaryl in R1-3 and R5-6 are optionally substituted by 1-3 substitutes optionally specified in -C1-6alkyl, -CN, halogen, -O-C1-6alkyl, -phenyl, -NO2, wherein each alkyl is optionally substituted by 1-5 fluorine atoms; each carbon atom in X is optionally substituted by one or more groups R4b, and one group -CH2- in X may be substituted by -C4-8cycloalkylene- and -CH=CR4d-; where R4b is specified in -C0-5alkylene-COOR4c and benzene, where R4c represents H; and R4d represents -CH2-thiophen; each alkyl and each aryl in R1-3, R4a-4d and R5-6 are optionally substituted by 1-7 fluorine atoms; where aryl represents monovalent aromatic hydrocarbon having one ring or condensed rings, and contains 6-10 carbon atoms in the ring; and heteroaryl represents a monovalent aromatic group having one ring or two condensed rings, and having 5-10 atoms in large in the ring with one atom of the ring represents a heteroatom specified in nitrogen, oxygen and sulphur. Besides, the invention refers to a pharmaceutical composition based on the compound of formula

,

to a method for preparing the compound of formula (I), to intermediate compounds used in synthesis of the compound of formula (I), to the use of the compounds of formula (I).

EFFECT: there are prepared new compounds possessing activity of a type 1 angiotensin II (AT1) receptor antagonist and activity of neprilysin inhibition.

38 cl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula in which: X denotes S, N-R5 or O; R denotes H; alkyl; heteroaryl, which is a thienyl optionally substituted with alkyl; R1 denotes alkyl; aryl, optionally substituted with a halogen; heteroaryl which is a thienyl optionally substituted with an alkyl, a a halogen, a methoxy group; R2 denotes heteroaryl which is 2-, 3- or 4-pyridyl; R3 denotes H; aryl, optionally substituted with a halogen, a methoxy group; heteroaryl, which is a thienyl optionally substituted with a halogen; alkyl, optionally substituted with oxytetrahydropyranyl; R4 denotes H; R5 denotes H; alkyl; or salt thereof.

EFFECT: invention also relates to a method of producing said compounds, which can be used as antifungal agents for crops, as well as agents against other pests, such as insects or mites and weeds which can harm crops.

10 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: compounds can be used to treat such diseases as hypertension, congestive heart failure, cardiac hypertrophy and others. In formula I R1 denotes a) cyclohexyl or trifluoromethyl; or b) phenyl, 2-thienyl, 3-thienyl, 2-pyridyl, 2-imidazolyl, 2-thiazolyl, 2-benzothienyl, 4-benzofuryl, 4-benzothienyl, 7-benzofuryl, 2,3-dihydro-7-benzofuryl, 7-benzothienyl, 1,3-benzodioxol-4-yl, 7-indazolyl, or 8-quinolinyl, optionally substituted with 1-3 substitutes, and X and Y each denotes a single bond; R2 denotes methyl, ethyl, propyl, butyl, pentyl, hexyl, 5-pentenyloxy, 3,33-trifluoropropyl, 4,4-difluoropentyl, 3-(cyclopropyl)propyl, 4-(cyclopropyl)butyl, 3-hydroxypropyl, 4-hydroxybutyl, 4-hydroxypentyl, 4-hydroxyhexyl, 5-hydroxyhexyl, 2-hydroxyethoxy etc, given in the claim; R3 denotes H, F, OH, methoxy, ethoxy, 3-hydroxypropoxy, acetylamino, propionylamino, (2-methylpropionyl)amino, or butanoylamino; A denotes 2,4-disubstituted morpholine with R1XCR2R3Y, bonded on the second position and Q bonded on the fourth position, 1,3-disubstituted piperidine with R1XCR2R3Y bonded on the third position and Q bonded on the first position, 1,3-dibustituted-3-methylpiperidine with R1XCR2R3Y bonded on the third position and Q bonded on the first position, 1,3-disubstituted benzene or 1,3-disubstituted cyclohexane; Q denotes Q1, Q2, Q4, Q5, Q9, or Q10 given in the claim, to which A and N are bonded on cut-off bonds, R4 denotes H or methyl.

EFFECT: obtaining novel compounds having aspartic protease inhibitor properties, particularly renin inhibitor.

10 cl, 1 tbl, 166 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1) (lb) in which A denotes a benzene ring; Ar denotes naphthalenyl which optionally contains 1-3 substitutes independently selected from a group comprising C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, hydroxy group, C1-C6alkoxy group, halogen, heteroalkyl, heteroalkoxy group, nitro group, cyano group, amino- and mono- or di- C1-C6alkyl-substuted amino group; R1 denotes hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy group, carboxy group, heteroalkyl, hydroxy group optionally substituted with heterocyclylcarbonyl-C1-C6alkyl or R1 denotes N(R')(R")-C1-C6alkyl or N(R')(R")-carbonyl- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, heteroalkyl, phenyl-C1-C6alkyl; or R1 denotes R'-CO-N(R")-C1-C6alkyl, R'-O-CO-N(R")- C1-C6alkyl- or R'-SO2-N(R")- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cyclalkyl, C3-C7cycloalkyl- C1-C6alkyl or optionally substituted phenyl; R2, R2' and R2" independently denote hydrogen, halogen, cyano group, C1-C6alkyl, halogenated C1-C6alkyl or C1-C6alkoxy group; n equals 1; and pharmaceutically acceptable salts thereof. The invention also relates to use of compounds in any of claims 1-9, as well as to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds with chymase inhibiting activity.

14 cl, 128 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing α,ω-bis-[2-(N,N-dimethylamino)thien-5-yl]alkanes, which involves reaction of α,ω-bis-[2-(N,N-dimethylaminomethyl)ethynyl]alkane, where (alkane = propyl, butyl, hexyl), with excess elementary sulphur (S8) in the presence of a three-component catalyst consisting of cobalt acetylacetonate Co(acac)2, triphenylphosphine Ph3P and triethylaluminium Et3Al, taken in molar ratio α,ω-bis-[2-(N,N-dimethylaminomethyl)ethynyl]alkane:S8:Co(acac)2:Ph3P:Et3Al=10:(40-60):(0.3-0.7):(0.6-1.4):(0.9-2.1), preferably 10:50:0.5:1.0:1.5, at temperature 125-135°C and atmospheric pressure for 5-7 hours.

EFFECT: obtaining novel compounds which can be used as biologically active compounds, additives to oil and process lubricants and in fine organic synthesis.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazoline derivatives of formula (I), where n equals 0 or 1, R1 denotes a saturated branched or straight unsubstituted C1-C4alkyl, saturated unsubstituted C3-C8cycloalkyl or unsubstituted phenyl bonded through a C1-C3alkyl chain, R2 denotes an unsubstituted or halogen atom-monosubstituted phenyl or thiophenyl, or unsubstituted phenyl bonded through a C1-C3alkyl chain, R3 denotes a saturated branched or straight C1-C8alkyl which is not substituted or contains one substitute selected from a group comprising -COO-methyl, thiomethyl or thiobenzyl, or a phenyl which is mono-substituted with a halogen atom and bonded through a C1-C3alkyl chain, R4 denotes a C1-C4alkyl, R5 and R6 independently denote a saturated branched or straight C1-C6alkyl, in form of a racemate, enantiomers, diastereomers, mixture of enantiomers or diastereomers or a separate enantiomer or diastereomer, bases and/or salts with physiologically compatible acids. The invention also relates to a method for synthesis of the compound of formula (I), intermediate compounds of formula B , a medicinal agent based on the compound of formula (I) or formula B and use of compounds of formula (I) or formula B to prepare a medicinal agent.

EFFECT: novel derivatives of imidazoline and substituted aldehyde of formula B, having µ-opiate receptor affinity, are obtained.

16 cl, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general structural formula:

or to pharmaceutically acceptable salts, where Z denotes -O- or -CH2- or -CH2-CH2-; X1 denotes a covalent bond or -O-; Y1 denotes a covalent bond or C1-C10 alkylene, provided that Y1 is a covalent bond only when X1 denotes a covalent bond; R1 denotes a) (C3-C7)cycloalkyl or b) phenyl or heteroaryl, which is a monovalent heteroatomatic monocyclic radical ring containing 1-2 heteroatoms, independently selected from nitrogen and sulphur, possibly substituted with 1-3 groups, independently selected from fluorine, chlorine, bromine, (C1-C6)alkyl or (C1-C6)-alkoxy; R2 denotes -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9, -C(O)R9, -C(O)(NH2), -C(O)(NHR9) or -NHC(O)H, where R9 denotes a linear or branched C1-C5 alkyl or a linear or branched (C1-C5)alkoxyalkyl; R3 denotes H, C1-C5 alkyl, -NHC(O)R10 or OH, where R10 denotes C1-C3 alkyl, provided that when R3 denotes -OH, X1 is not O and R2-Y1-X1 is not -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9 or -NHC(O)H; -Q denotes

, where N and N are bonded by bonds denoted by a wavy line; R4 denotes H; R5 and R6 independently denote: a) H, (C1-C10)alkyl, (C4-C10)cycloalkylalkyl, hydroxylated (C4-C10)cycloalkylalkyl, halo(C4-C10)cycloalkylalkyl, (C1-C2)alkyl(C4-C10)cycloakylalkyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl(C1-C3)alkyl, where the saturated heterocyclic ring is selected from 5-, 6- or 7-member heterocyclic rings which contain 1 heteroatom independently selected from N and O; or b) phenyl(C1-C2)alkyl, phenoxymethyl, each of which is possibly with 1-3 groups independently selected from fluorine, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy; provided that both R5 and R6 are not H; G denotes NH2 or NHR7; R7 denotes (C1-C6)alkyl; or R5 and R7 together denote -CH2, -(CH2)2 or -(CH2)3, possibly substituted with 1-2 groups independently selected from (C1-C8)-alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C2)alkyl or (C1-C8)alkoxy. The invention also relates to compounds selected from the group, pharmaceutical compositions, a method for antagonising one or more aspartate proteases, as well as methods of treating aspartate protease-mediated disorders.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

35 cl, 33 ex, 4 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described compounds of 3-cyanonaphthalene-1-carboxylic acid and perhydroxyalkylmethylpiperazine of formula

, where R1 means C1-C4alkyl, R2 and R3 mean halogen, R4 is selected from the group consisting of 2-furanyl, 3-furanyl, 2-thiophen, 3-thiophen, phenyl, benzyl, 2-benzofuranyl, etc., R5 is selected from the group consisting of hydrogen and R6, R6 means a subgroup of general formula

which are antagonists of tachykinin receptors. Also, there are described pharmaceutical compositions containing such compounds, and methods for making such compounds and intermediate products for making the compounds according to said methods.

EFFECT: preparation of new compounds.

FIELD: chemistry.

SUBSTANCE: invention relates to organic synthesis and specifically to a method of producing 2-(2-thienyl)-3-alkyl pyrroles and N-vinyl derivatives thereof of general formula and , where Alk denotes any linear alkyl substitute. The method is a single-reactor three-component reaction of 2-acylthiophene, hydroxylamine chloride and excess acetylene in the presence of an alkali metal hydroxide with adding sodium bicarbonate to DMSO in an autoclave under acetylene pressure for 1-3 hours at temperature of 80-120°C in a wide range of molar concentration of reactants; molar ratio of reactants acylthiophene: hydroxylamine chloride: acetylene: MOH: DMSO varies in the range of 1:1.0-1.5:2-25:1.5-2.5:30-50.

EFFECT: method of obtaining novel compounds which can be used as monomers for producing electroconductive polymers, particularly as active components of electrodes of polymer rechargeable batteries and electrochromic devices.

2 cl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are presented nitrogen-containing heterocyclic compounds presented by the following formula wherein the radical values are specified in the description. These compounds or their pharmaceutically acceptable salts possess strong EP1 activity if introduced in a human or an animal; they are used as an effective component of a pharmaceutical agent, e.g. for preventing and/or treating overactive bladder.

EFFECT: compounds are used as an effective component of the pharmaceutical agent for preventing and/or treating the symptoms including frequent urination, heavy urination demand accompanied by fear of involuntary urination, and urinary incontinence.

24 cl, 145 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to a piperidine derivative of general formula (I)

,

where R1 denotes hydrogen or a substitute selected from the following (b)-(i): b) acrylic acid (including alkyl ester and hydroxyalkyl amide), (c) ureide, (d) alkenyl, (e) aminoalkyl which can be substituted with alkyl carbonyl or aminocarbonyl, (f) carbonyl alkyl, substituted with hydroxy, alkoxy or hydroxyalkylamino, (g) carbonyl, substituted with hydroxy, morpholino, alkoxy, hydroxyalkyl aminoalkoxy or cyclohexyloxy carbonyloxyalkoxy, (h) carbonylamino, substituted with alkyl or alkoxy, (i) aminocarbonyl which can be substituted with one or two substitutes selected from amino, hydroxy, alkoxy, alkenyl and alkyl (which can be substituted with halogen, thiol, piperidino, amino, alkoxy, alkoxycarbonyl, aminocarbonyl or one or two hydroxy); R2 denotes hydrogen or a substitute selected from the following (j)-(r): (j) cyano, (k) acrylic acid, (l) alkyl, substituted with hydroxy or piperidino, (m) carbonyl alkyl, substituted with hydroxy, alkoxy (which can be substituted with cyclohexyloxy carbonyloxy) or hydroxyalkylamino, (n) carbonyl, substituted with hydroxy or alkoxy, (o) carbonyl alkoxy, substituted with alkoxy, (p) carbonyl alkyl sulphanyl, substituted with hydroxy or alkoxy, (q) alkoxy, (r) halogen; and R3 denotes hydrogen or a substitute selected from the following (s)-(w): (s) alkyl which can be substituted with carboxy, cyano, pyrrolidyl, piperidino, alkoxy, alkyl sulphanyl or one or two hydroxy, (t) carbonyl, substituted with alkyl or alkoxy, (u) carbonyl alkoxyalkyl, substituted with hydroxy or alkoxy, (v) carbonyl alkyl, substituted with alkyl, alkoxy or alkylphenyl, (w) aminoalkyl, substituted with aminocarbonyl or alkane sulphonyl, where one of said R1 and R2 denotes a substitute other than hydrogen, A is unsubstituted or is an oxo, B denotes carbon or oxygen, one of X and Y denotes carbon and the other denotes sulphur, the dotted line denotes a single bond or a double bond, under the condition that when R2 denotes halogen or alkoxy, A is unsubstituted, R1 denotes a substitute other than hydrogen and B denotes oxygen. The invention also relates to an antihistamine which contains a compound of formula I and use of the described compound for treatment and production of a medicinal agent.

EFFECT: novel compounds having antagonistic action on histamine receptors are obtained and described and can be suitable as active ingredients of a pharmaceutical composition, especially an antihistamine composition.

17 cl, 40 ex, 21 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the use of compounds of formula (wherein R1, R2, X, Y and n have the values specified in the patent claim) or their pharmaceutically acceptable salts for treating the diseases related to the biological function of the trace amine associated receptors, namely depression, anxiety disorders, bipolar disorders, attention deficit/hyperactivity disorder, stress-induced disorders, schizophrenia, neurological disorders, Parkinson's disease, neurodegenerative disorders, Alzheimer's disease, epilepsy, migraine, addictions, metabolic disorders, eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, energy consumption and assimilation disorders, thermal homeostasis disorders and disturbances, sleeping and circadian rhythm disorders, and cardiovascular diseases. Besides, the invention refers to compounds of formulas I-A, I-B, I-C, I-D, l-E, l-F, I-G, I-H (structural formulas of which are presented in the patent claim) and to a pharmaceutical composition based on the compounds of formula (I) for treating the diseases related to the biological function of the trace amine associated receptors.

EFFECT: use of the compounds of formula 1 in preparing the drugs for treating the diseases related to the biological function of the trace amine associated receptors.

45 cl, 9 dwg, 1 tbl, 379 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of 2-heteroaryl-substituted benzothiophene and benzofuran, precursors thereof and therapeutic use of said compounds, having structural formula (1a) where R1, R2, X9 and Q assume values given in the description, and pharmaceutically acceptable salts thereof, which are suitable for imaging amyloid deposits in living patients. The invention also relates to pharmaceutical compositions based on compounds of formula 1a, use and methods of producing said compounds. More specifically, the present invention relates to a method of imaging brain amyloid deposits in vivo for intravital diagnosis of Alzheimer's disease, and measuring clinical efficiency of therapeutic agents against Alzheimer's disease.

EFFECT: high efficiency of using said compounds.

15 cl, 1 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel disubstituted phenylpyrrolidines of formula , any stereoisomers thereof or any mixtures of stereoisomers thereof, or N-oxides thereof, or pharmaceutically acceptable salts thereof, where Ar denotes phenyl; R1 denotes F, Cl; R2 denotes F and Cl; R3 denotes H, Me, Et, n-Pr, iso-Pr, n-Bu, iso-Bu, sec-Bu, tert-Bu, cyclopropylmethyl, CFH2CH2CH2-, CF2HCH2CH2-, CF3CH2CH2-, allyl and CH3OCH2CH2-; X denotes F, OH; under the condition that X denotes OH, R3 does not denote H.

EFFECT: compounds are capable of increasing levels of dopamine, norepinephrine and serotonin, which enables their use in treating central nervous system disorders.

16 cl, 21 dwg, 69 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3-alkyl(aryl)-2,2'-bithiophene-5-carboxylic acids and esters thereof of general formula I where R = C1-C10-alkyl or aryl; R1 = hydrogen atom or C1-C4 alkyl, involving reaction of 2-acyl thiophenes of general formula II with dimethyl formamide and phosphoryl chloride, and the formed 2-alkyl(aryl)-3-chloro-3-(2-thienyl)acrylaldehyde of general formula III reacts with thioglycolic ester in the presence of a base, and by hydrolysis of the obtained esters of general formula I, where R assumes values given above and R1=C1-C4 alkyl, 3-alkyl-2,2'-bithiophene-5-carboxylic acids are obtained, where R1 = hydrogen atom.

EFFECT: simpler method of producing compounds of formula I, which can be used in synthesis of solvatochromic and thermochromic dendrimers, oligothiophenes with adjustable electrical and optical properties.

1 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to indole derivatives or pharmaceutically acceptable salts thereof of general formula (1): , where values of R1, R2, m are given in claim 1.

EFFECT: compounds have inhibiting activity on IKKβ, which enables their use as a preventive or therapeutic agent for treating IKKβ mediated diseases.

26 cl, 1 tbl, 29 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2,3-disubstituted indoles of general formula (I): , where the method involves the following steps: a) reaction of bromine diol (i): with dialkoxyborane in the presence of a ligand, a palladium catalyst, preferably selected from Pd(OAc)2, PdCl2, PdBr2, Pd2(dba)3, Pd2(dba)3.CHCl3, [Pd(ally)Cl]2,- Pd(CH3CN)2Cl2, Pd(PhCN)2Cl2, Pd/C and encapsulated Pd and a base to obtain a compound of general formula or, alternatively, reaction of compound (i) with a magnesium compound containing 3 alkyl groups, with subsequent treatment with a borate to obtain a compound of general formula ii given above; b) reaction of the product from step (a) with R2-Hal to obtain a compound of general formula I; where: R denotes (C1-C6)alkyl; R2 denotes: , , , , ,

, , , , ;

R3 denotes cyclopentyl: X denotes carboxymethyl; Hal denotes Br or I; or pharmaceutically acceptable salt thereof.

EFFECT: higher efficiency.

12 cl, 4 dwg, 2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: described are novel 1,2,4-triazolones of general formula (I):

, where A denotes N and values of other radicals are given in the claim, which are vasopressin receptor inhibitors, synthesis method thereof and use thereof to prepare medicinal agents for treating and/or preventing diseases, particularly for treating and/or preventing cardiovascular diseases.

EFFECT: high efficiency of using said derivatives.

6 cl, 512 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (II-A) or pharmaceutically acceptable salt thereof: [in which symbols denote the following: R10-R12: are identical or different and each denotes halogen, lower alkyl, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, R13: R0, halogen, halogen-lower alkyl, -OR0, -O-halogen-lower alkyl or -CN, ring B: benzene ring or a 5-6-member heteroaromatic ring containing 1-2 heteroatoms selected from O, S and N, R14: R0, halogen or -OR0, R0: are identical or different and each denotes H or lower alkyl, Y1: a single bond, lower alkylene, lower alkenylene or O-lower alkylene-, and Z1: -CO2R0 or -C0-NH-SO2-lower alkyl]. The invention also relates to a pharmaceutical composition based on the said compound, having antagonistic effect on the EP1 receptor.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in a medicinal agent for treating lower urinary tract symptoms.

6 cl, 56 tbl, 231 ex

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