Aminotetraline derivatives containing their pharmaceutical compositions and using them in therapy


FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new aminotetraline derivatives of formula (I) and their physiologically tolerable salts. In formula

,

A means a benzene ring or a ring specified in a group consisting of a 5-merous ring

,

R means the group R1-W-A1-Q-Y-A2-X1-; R1 means hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, halogenated C1-C6-alkyl, tri-(C1-C4-alkyl)-silyl-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl, an optionally substituted phenyl, C1-C6-alkoxy, di-C1-C6-alkylamino, an optionally substituted 5 or 6-merous heterocyclyl containing 1-3 heteroatoms specified in nitrogen and/or oxygen or sulphur; W means a bond; A1 means a bond; Q means -S(O)2- or -C(O)-; Y means -NR9- or a bond; A2 means C1-C4-alkylene, or a bond; X1 means -O-, C1-C4-alkylene, C2-C4-alkynylene; R2 means hydrogen, halogen, or two radicals R2 together with the ring atom to which they are attached form a benzene ring; R3 means hydrogen. The other radical values are specified in the patent claim. The invention also refers to intermediate products for preparing the compounds of formula (I).

EFFECT: compounds possess the properties of glycine transporter inhibitors, particularly GlyT1 and can find application in treating neurological and psychiatric disorders, such as dementia, bipolar disorder, schizophrenia, etc or for managing pain related to glycerinergic or glutamatergic neurotransmission dysfunction.

20 cl, 2 tbl, 326 ex

 

The prior art inventions

The present invention relates to aminotetraline derivatives, pharmaceutical compositions containing such aminotetraline derivatives and to the use of such aminotetraline derivatives for therapeutic purposes. Aminotetraline derivatives are inhibitors of GlyT1.

The dysfunction of glutamatergic pathways involved in the development of a number of illnesses of the Central nervous system (CNS) of a person, including, without limitation, schizophrenia, cognitive disorders, dementia, Parkinson's disease, Alzheimer's disease and bipolar disorder. A large number of studies in animal models confirm the hypothesis about the involvement of NMDA hypofunction in the development of schizophrenia.

The function of the NMDA receptor can be modulated by changing the accessibility of the co-agonist glycine. This approach has the important advantage of maintaining the activity-dependent activation of the NMDA receptor, since the increase synaptic concentration of glycine does not cause activation of NMDA receptors in the absence of glutamate. Because the synaptic levels of glutamate are supported mainly by the mechanisms of high-affinity transport, increased activation of the glycine site only increases the level of the NMDA component in activated synapses.

Identific�are arranged two specific glycine Transporter, GlyT1 and GlyT2, which belong to the Na/Cl-dependent family of transporters of neurotransmitters, including transporters of taurine, gamma-aminobutyric acid (GABA), Proline, monoamines and orphan. It is shown that GlyT1 and GlyT2, which were isolated from different species, have only 50% identity at the amino acid level. They are characterized by different expression patterns in the Central nervous system of mammals, and GlyT2 is expressed in the spinal cord, the brain stem and the cerebellum, and GlyT1, in addition to these sites, is present in such sections of the forebrain, the cerebral cortex, the hippocampus, the septa and the thalamus. It is shown that at the cellular level GlyT2 is expressed glycinergic nerve endings in the spinal cord of rats, whereas GlyT1 is expressed predominantly by glial cells. These expression studies suggest that GlyT2 is primarily responsible for the uptake of glycine in glycinergic synapses, whereas GlyT1 is involved in the regulation of the concentration of glycine in the area of synapses expressing NMDA receptor. Recent on rats functional studies demonstrate that blockade of GlyT1 effective inhibitor (N-[3-(4'-fluorophenyl)-3-(4'-phenyleneoxy)propyl])sarcosine (NFPS) increases the activity of the NMDA receptor and causes an NMDA receptor-dependent long potentsiirovannye� in rats.

Using the methods of molecular cloning revealed the existence of three variants of GlyT1, named GlyT-1a, GlyT-1b and GlyT-1c, each of which is characterized by a unique distribution in the brain and peripheral tissues. Options result from different splicing and use of different exons, and differ in the N-terminal region.

Physiological effects of GlyT1 in forebrain areas along with clinical reports showing the beneficial effects of GlyT1 inhibitor of sarcosine, leading to improvement of symptoms in patients with schizophrenia, suggest that selective GlyT1 inhibitors represent a new class of antipsychotic drugs.

Inhibitors of the glycine Transporter known in this field and include, for example:

(�. also Hashimoto K., Recent Patents on CNS Drug Discovery, 2006, 1, 43-53; Harsing L. G. et al., Current Medicinal Chemistry, 2006, 13, 1017-1044; Javitt D. C, Molecular Psychiatry (2004) 9, 984-997; Lindsley, CW. et al., Current Topics in Medicinal Chemistry, 2006, 6, 771-785; Lindsley CW. et al., Current Topics in Medicinal Chemistry, 2006, 6, 1883-1896).

The aim of the present invention is to provide other inhibitors of the glycine Transporter.

Summary of the invention

The present invention relates to aminotetraline derivative of formula (I)

where

A denotes a 5 - or 6-membered ring;

R denotes the R1-W-A1-Q-Y-A2-X1-;

R1denotes hydrogen, alkyl, cycloalkyl, halogenated alkyl, trialkylsilyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, acylaminoalkyl, dialkylaminoalkyl, alkylcarboxylic, allyloxycarbonyl, alkylaminocarbonyl, dialkylaminoalkyl, alkylsulfonyl, (optionally substituted arylalkyl), aminoalkyl, optionally substituted arylalkyl, optionally substituted geterotsiklicheskie, cycloalkyl, alkylaryl, alkoxycarbonyl, halogenated alkoxycarbonyl, aryloxyalkyl, aminocarbonyl, alkylaminocarbonyl, (halogenated alkyl)aminocarbonyl, allumination, alkenyl, alkinyl, optionally substituted aryl, hydroxy, alkoxy, halogenated alkoxy, hydroxyalkoxy and�kocialski, aminoethoxy, acylaminoalkyl, dialkylaminoalkyl, alkylcarboxylic, arylcarboxylic, alkoxycarbonylmethyl, Allakaket, alkylsulfonamides, (halogenated alkyl)sulfonilamidami, arylsulfonamides, (arylalkyl)sulfonilamidami, , geterotsiklicheskikh, aryloxy, heterocyclic, alkylthio, the halogenated alkylthio, alkylamino, (halogenated alkyl)amino, dialkylamino, di(halogenated alkyl)amino, alkylcarboxylic, (halogenated alkyl)carbylamine, arylcarboxamide, alkylsulfonamides, (halogenated alkyl)sulfonylamino, arylsulfonyl or optionally substituted heterocyclyl;

W represents-NR8or communication;

A1denotes optionally substituted alkylene or communication;

Q represents-S(O)2- or-C(O)-;

Y represents-NR9or communication;

A2denotes optionally substituted alkylen, alkylen-CO-, -CO-alkylene, alkylene-O-alkylene, alkylene-NR10-alkylen, optionally substituted albaniles, optionally substituted akinyan, optionally substituted, Allen, optionally substituted, heteroaryl or communication;

X1denotes-O-, -NR11-, -S-, optionally substituted alkylene, optionally substituted albaniles, neobythites�but substituted akinyan;

R2denotes hydrogen, halogen, alkyl, halogenated alkyl, hydroxyalkyl, -CN, alkenyl, alkynyl, optionally substituted aryl, hydroxy, alkoxy, halogenated alkoxy, alkoxycarbonyl, alkenylacyl, Allakaket, alkylcarboxylic, alkylthio, alkylsulfonyl, alkylsulfonyl, aminosulfonyl, amino, alkylamino, alkynylamino, nitro or optionally substituted heterocyclyl, or two radicals R2together with the ring atoms of A to which they are attached, form a 5 - or 6-membered ring;

R3denotes hydrogen, halogen, alkyl or alkoxy, or two radicals R3together with the carbon atom to which they are attached, form a carbonyl group;

R4adenotes hydrogen, alkyl, cycloalkyl, halogenated alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, CH2CN, -CHO, alkylsulphonyl, (halogenated alkyl)carbonyl, arylcarbamoyl, alkoxycarbonyl, aryloxyalkyl, alkylaminocarbonyl, alkenyl, -C(=NH)NH2, -C(=NH)NHCN, alkylsulfonyl, arylsulfonyl, amino, -NO or heterocyclyl;

R4bdenotes hydrogen, alkyl, halogenated alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, CH2CN, -CHO, alkylsulphonyl, (halogenated alkyl)carbonyl, arylcarbamoyl, alkoxycarbonyl, aryloxyalkyl, alkylaminocarbonyl, alkenyl, -C(=NH)NH2, -C(=NH)NHCN, alkylsulfonyl�, arylsulfonyl, amino, -NO or heterocyclyl; or

R4a, R4btogether represent optionally substituted alkylene, where one-CH2- alkylene may be replaced by oxygen atom or-NR16;

X2denotes-O-, -NR6-, -S -, > CR12aR12bor communication;

X3denotes-O-, -NR7-, -S -, > CR13aR13bor communication;

R5denotes optionally substituted aryl, optionally substituted cycloalkyl or optionally substituted heterocyclyl;

n is 0, 1 or 2;

R6denotes hydrogen or alkyl;

R7denotes hydrogen or alkyl;

R8denotes hydrogen or alkyl;

R9denotes hydrogen, alkyl, cycloalkyl, aminoalkyl, optionally substituted arylalkyl or heterocyclyl; or

R9, R1together denote alkylene; or

R9is file alkylen associated with the carbon atom A2where A2is file alkylen, or to a carbon atom of X1where X1is file alkylen;

R10denotes hydrogen, alkyl or alkylsulfonyl;

R11denotes hydrogen or alkyl, or

R9, R11together denote alkylene,

R12adenotes hydrogen, optionally substituted alkyl, acylaminoalkyl, dialkylaminoalkyl, geterotsiklicheskie, optionally substituted aryl or hydroxy;

12bdenotes hydrogen or alkyl, or

R12a, R12btogether denote a carbonyl or optionally substituted alkylene, where one-CH2- alkylene may be replaced by oxygen atom or-NR14-;

R13adenotes hydrogen, optionally substituted alkyl, acylaminoalkyl, dialkylaminoalkyl, geterotsiklicheskie, optionally substituted aryl or hydroxy;

R13bdenotes hydrogen or alkyl, or

R13a, R13btogether denote a carbonyl or optionally substituted alkylene, where one-CH2- alkylene may be replaced by oxygen atom or-NR15-;

R14denotes hydrogen or alkyl;

R15denotes hydrogen or alkyl; and

R16denotes hydrogen or alkyl, or

to their physiologically tolerated salts.

Thus, the present invention relates to aminotetraline derivative having the formula (Ia)

where A, R1, W, A1, Q, Y, A2, X1, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

In addition, the present invention relates to aminotetraline derivative of formula (I), where R is-CN, i.e., to aminotetraline derivative having the formula (Ib)

where A, R2, R3 , R4a, R4b, X2, X3, R5n have the values listed in this document.

Thus, the term "aminotetraline derivative" is used herein to denote in particular, aminotetraline (n=1) and paired cyclohexanol (n=1), where the benzene ring is substituted 5 - or 6-membered heterocycle, and is homologous to bicyclic compounds where n is 0 or 2.

These compounds of formula (I), i.e., aminotetraline derivatives of formula (I) and their physiologically tolerated acid-additive salts, are inhibitors of the glycine Transporter, and therefore can be used as pharmaceuticals.

Therefore, the present invention further relates to compounds of formula (I), intended for use in therapy.

The present invention also relates to pharmaceutical compositions containing a carrier and a compound of formula (I).

In particular, these compounds, i.e., aminotetraline derivatives and their physiologically tolerated acid-additive salts, are inhibitors of the glycine Transporter GlyT1.

Therefore, the present invention further relates to compounds of formula (I) suitable for inhibiting the glycine Transporter.

The present invention also relates to the use of compounds�s of formula (I) in the manufacture of a medicament for inhibiting the glycine Transporter GlyT1 and to corresponding methods of inhibiting the glycine Transporter GlyT1.

It is known that inhibitors of glycine transport, in particular inhibitors of the glycine Transporter GlyT1, can be used to treat a number of neurological and psychiatric disorders.

Therefore, the present invention further relates to compounds of formula (I) intended for the treatment of neurological or psychiatric disorders.

The present invention also relates to compounds of formula (I) intended for the treatment of pain.

The present invention also relates to the use of compounds of formula (I) in the manufacture of a medicine for the treatment of neurological or psychiatric disorders and to corresponding methods of treatment of these disorders. The present invention also relates to the use of compounds of formula (I) in the manufacture of medicinal products for the treatment of pain and related methods of pain treatment.

The present invention also relates to aminotetraline derivative of the formula (II)

where L denotes an amino-protective group, Y represents NR9and A2, X1, R2, R3, R4a, R4b, X2, X3, R5n and R9have the above values.

Aminotetraline derivatives of the formula (II) can be used as intermediate compounds for obtaining in�of autorov GlyT1, in particular, compounds of formula (I).

Detailed description of the invention

If aminotetraline derivatives of formula (I) or (II) with concrete structure may exist in different spatial configurations, for example, if they contain one or more centers of asymmetry, polyamidine rings or double bonds, or as different tautomers, it is possible to use a mixture of enantiomers, in particular, racemate, mixtures of diastereoisomers and mixtures of tautomers, but preferably use the respective substantially pure enantiomers, diastereomers and tautomers of the compounds of formula (I) or (II) and/or their salts.

In accordance with one embodiment of the enantiomer aminotetraline derivative of the present invention has the following formula:

where A, R, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

In accordance with another embodiment of the enantiomer aminotetraline derivative of the present invention has the following formula:

where A, R, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

In accordance with one embodiment of the enantiomer aminotetraline derivative of the present invention has�t the following formula:

where A, R, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

In accordance with another embodiment of the enantiomer aminotetraline derivative of the present invention has the following formula:

where A, R, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

Physiologically tolerated salts aminotetraline derivatives of formula (I) or (II) are mainly acid-additive salts with physiologically portable acids. Examples of suitable physiologically tolerated organic and inorganic acids are hydrochloric acid, Hydrobromic acid, phosphoric acid, sulfuric acid, C1-C4-alkylsulfonate acids such as methanesulfonic acid, cycloaliphatic sulfonic acids such as S-(+)-10-camphorsulfonic acid, aromatic sulfonic acids such as a mixture of Benzenesulfonic acid and toluensulfonate acid, di - and tricarboxylic acids and hydroxycarbonate acid containing from 2 to 10 carbon atoms, such as oxalic acid, malonic acid, maleic acid, fumaric acid, lactic acid, tartaric sour�and, citric acid, glycolic acid, adipic acid and benzoic acid. Other suitable acids are described in Fortschritte der Arzneimittelforschung [Advances in drug research], Volume 10, pages 224 ff., Birkhäuser Verlag, Basel and Stuttgart, 1966.

The present invention also relates to compounds of formula (I) or (II) described herein, where at least one of the atoms is replaced by its stable, non-radioactive isotope (e.g., hydrogen by deuterium,12C13C,14N15N,16O18O), preferably where at least one hydrogen atom is replaced by a deuterium atom.

Of course, in such compounds, the concentration of the respective isotope is higher than in nature and, therefore, usually in compounds (I) or (II).

Stable isotopes (e.g., deuterium,13C,15N,18O) are nonradioactive isotopes which contain additional neutrons compared to the most abundant isotope of the respective atom. Deuterated compounds are used in pharmaceutical research to study the metabolism of compounds by determining the mechanism of action and metabolic pathway Mediterraneo the parent compound (Blake et al. J. Pharm. Sci. 64, 3, 367-391 (1975)). Such metabolic studies are important in the development of safe, effective Thera�viteska funds because either enter patient active in vivo connection, or the metabolites formed from the parent compound, can be toxic or carcinogenic (Foster et al., Advances in Drug Research Vol. 14, pp. 2-36, Academic press, London, 1985; Kato et al., J. Labelled Comp. Radiopharmaceut, 36(10):927-932 (1995); Kushner et al., Can. J. Physiol. Pharmacol., 77, 79-88 (1999).

The introduction of a heavy atom, in particular, the replacement of hydrogen by deuterium, can lead to the isotopic effect on the pharmacokinetics of the drug. This effect is usually negligible if the label is metabolically inert position of the molecule.

The drug labeling with a stable isotope can alter its physicochemical properties such as pKa and solubility in lipids. These changes can affect the metabolism of the drug at different stages, including its passage through the body. Changes can be observed in absorption, distribution, metabolism or excretion. Absorption and distribution are processes that primarily depend on the size of the molecule and the lipophilicity of the substance. These effects and alterations can affect the pharmacodynamic characteristics of the molecule medicines, if replacement of the isotope affects the area that is involved in ligand-receptor interaction.

The metabolism of drugs� may cause significant isotope effect, if cleavage of a chemical bond with the deuterium atom is a step limiting the rate of the process. Although some physical properties of a molecule labeled with a stable isotope, differ from the physical properties of the unlabeled molecules, chemical and biological properties of these molecules may be the same, except for one important aspect: since the heavy isotope has a higher mass, any relationship formed with the heavy isotope and another atom is stronger than the bond between the light isotope and the specified atom. Any reaction in which the gap of such a connection is a step limiting the rate of the process is slower in the case of molecules containing the heavy isotope due to "kinetic isotope effect". Reactions involving cleavage of C-D, can proceed in a 700 percent slower than a similar reaction involving the cleavage of C-H. If link C-D is not involved in one of the stages leading to the formation of the metabolite, it has no effect on the behavior of the drug. If the deuterium is in the position of participating in the metabolism of the drug, an isotope effect is observed only if the cleavage of the C-D stage is limiting the speed. There are data suggesting that in all cases where PR�comes the splitting of the aliphatic C-H bonds, as a rule, in the oxidation catalyzed by multifunctional oxidase, replacement of hydrogen by deuterium leads to the observed isotope effect. It is important to understand that the introduction of deuterium into a position that is involved in the metabolism, slows down your metabolism so that formation of another metabolite in the attack on a carbon atom not substituted by deuterium, becomes the primary process, which is called "metabolic switching".

Healthy people of all ages, including newborns and pregnant women, it is also possible to enter deuterated markers such as deuterium-labeled drugs and deuterated water in doses, in some cases, multiple constituting a thousand milligrams, in the absence of confirmed side effects (e.g. Pons g and Rey E, Pediatrics 1999 104: 633; Coward W A, et al., Lancet 1979 7: 13; Schwarcz H P, Control. Clin. Trials 1984 5(Suppl 4): 573; Rodewald L E et al., J. Pediatr. 1989 1 14: 885; Butte N F et al. Br. J. Nutr. 1991 65: 3; A H MacLennan et al. Am. J. Obstet Gynecol. 1981 139: 948). Thus, it is obvious that the release of any amounts of deuterium, for example, in the metabolism of compounds of this invention, is not harmful to health.

On the basis of mass percentage of hydrogen in the body of a mammal (about 9%) and occurrence of deuterium in nature (approximately 0,015%) we can calculate that the human� weight of 70 kg is usually contains about one gram of deuterium. In addition, in mammals, including rodents and dogs, conducted replace up to about 15% of ordinary hydrogen to deuterium, which was maintained for a period of from several days to several months, watching with minimal side effects (Czajka D M and Finkel A J, Ann. N. Y. Acad. Sci. 1960 84: 770; Thomson J F, Ann. New York Acad. Sci 1960 84: 736; Czakja D M et al., Am. J. Physiol. 1961 201: 357). Higher concentration of deuterium, for example, exceeding the rate of 20%, can be toxic to animals. However, found that short-term replacement up to 15% -23% of hydrogen in the fluids of the human body for deuterium does not cause toxicity (Blagojevic N et al. in "Dosimetry &Treatment Planning for Neutron Capture Therapy", Zamenhof R, Solares G and Harling O Eds. 1994. Advanced Medical Publishing, Madison Wis. pp.125-134; Diabetes Metab. 23: 251 (1997)).

Increasing the amount of deuterium in the compound above the level found in nature, known as enrichment or the enrichment of deuterium. Examples of enrichment include the values that make up approximately 0,5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96 to 100 molar %.

The hydrogen atoms contained in the specific organic compound, characterized by different ability to the replacement by deuterium. Some of the hydrogen atoms are easily exchangeable under physiological conditions and, in the case of replacement by deuterium atoms, it can be assumed that they will be easily replaced by protons after �of reference of the patient. Some of the hydrogen atoms can be replaced by deuterium atoms by the impact of deuterated acids, such as D2SO4/D2O. Alternatively, deuterium atoms can be entered in different combinations in the process of synthesis of compounds of this invention. Some of the hydrogen atoms are difficult to be replaced with deuterium atoms. However, in the rest position of the deuterium atoms can be entered by use of deuterated starting materials or intermediates in obtaining compounds of this invention.

Deuterated and deuterium-enriched compounds of this invention can be obtained by known methods described in the literature. Such methods include obtaining compounds described herein using the corresponding deuterated and optionally containing other isotopes of reagents and/or intermediates, or known in the field of standard synthetic methods of introducing isotopic atoms to a chemical structure of the compounds. Relevant procedures and intermediates are described, for instance, in Lizondo, J et al., Drugs Fut, 21 (11), 1116 (1996); Brickner, S J et al., J Med Chem, 39(3), 673 (1996); Mallesham, B et al., Org Lett, 5(7), 963 (2003); publications PCT WO1997010223, WO2005099353, WO1995007271, WO2006008754; U.S. patents№№ 7538189; 7534814; 7531685; 7528131; 7521421; 7514068; 7511013; and publications of patent applications U.S.№№ 20090137457; 20090131485; 20090131363; 2009011238; 20090111840; 20090105338; 20090105307; 20090105147; 20090093422; 20090088416; 20090082471, thus, these methods are included in this description by reference.

Organic fragments referred to in the above definitions, are - like the term halogen - collective terms for individual lists of the separate group members. The prefix Cn-Cmindicates in each case the possible number of carbon atoms in the group.

Unless otherwise indicated, the term "substituted" means that a radical is substituted with 1, 2 or 3 substituents, mainly 1 Deputy, which, in particular, can be selected from the group including halogen, C1-C4-alkyl, hydroxy-C1-C4-alkyl, C3-C12-geterotsiklicheskie, S1-C4-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C4-alkenyl, OH, SH, CN, CF3,- CF3, COOH, O-CH2-COOH, C1-C6-alkoxy, C1-C6-alkylthio, C3-C7-cycloalkyl, COO-C1-C6-alkyl, CONH2, CONH-C1-C6-alkyl, - SO2NH-C1-C6-alkyl, CON-(C1-C6-alkyl)2, SO2N-(C1-C6-alkyl)2NH2NH-C1-C6-alkyl, N-(C1-C6-alkyl)2NH-(C1-C4-alkyl-C6-C12-aryl), NH-CO-C1-C6-alkyl, NH-SO2-C1-C6- �Kil, SO2-C1-C6-alkyl, C6-C12-aryl, O-(C6-C12-aryl, O-CH2-C6-C12-aryl, CONH-C6-C12-aryl, - SO2NH-C6-C12-aryl, CONH-C3-C12-heterocyclyl, SO2NH-C3-C12-heterocyclyl, SO2-C6-C12-aryl, NH-SO2-C6-C12-aryl, NH-CO-C6-C12-aryl, NH-SO2-C3-C12-heterocyclyl, NH-CO-C3-C12-heterocyclyl and C3-C12-heterocyclyl, where aryl and heterocyclyl, in turn, can be unsubstituted, or they may be substituted with 1, 2 or 3 substituents selected from the group consisting of halogen, C1-C4-alkyl, C1-C4-halogenoalkane, S1-C4-alkoxy and C1-C4-halogenoalkane.

The term "halogen" in each case denotes fluorine, bromine, chlorine or iodine, preferably fluorine or chlorine.

With1-C4-Alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms. Examples of alkyl groups are methyl, C2-C4-alkyl, such as ethyl, n-propyl, ISO-propyl, n-butyl, 2-butyl, ISO-butyl or tert-butyl. C1-C2-Alkyl is methyl or ethyl, C1-C3-alkyl additionally includes n-propyl or isopropyl.

C1-C6-Alkyl is a linear or �osvetleniyu alkyl group, containing from 1 to 6 carbon atoms. Examples include methyl, C2-C4-alkyl, as defined herein, as well as the pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, 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-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl "and 1-ethyl-2-methylpropyl".

Halogenated C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms, such as halogenmethyl, dehalogenation, trihalomethyl, (R)-1-halogenated, (S)-1-halogenated, 2-halogenated, 1,1-dehalogenated, 2,2-dehalogenated, 2,2,2-trihalomethyl, (R)-1-halogenfrei, (S)-1-halogenfrei, 2-halogenfrei, 3-halogenfrei, 1,1-dialogerror, 2,2-dialogerror, 3,3-dialogerror, 3,3,3-trihalomethyl, (R)-2-halogen-1-methylethyl, (S)-2-halogen-1-methylethyl, (R)-2,2-dihalogen-1-methylethyl, (S)-2,2-dihalogen-1-methylethyl, (R)-1,2-dihalogen--methylethyl, (S)-1,2-dihalogen-1-methylethyl, (R)-2,2,2-trihalogen-1-methylethyl, (S)-2,2,2-trihalogen-1-methylethyl, 2-halogen-1-(halogenmethyl)ethyl, 1-(dehalogenated)-2,2-dehalogenation, (R)-1-halogenmethyl, (S)-1-halogenated, 2-halogenmethyl, 3-halogenmethyl, 4-halogenmethyl, 1,1-dehalogenated, 2,2-dehalogenated, 3,3-dehalogenated, 4,4-dehalogenated, 4,4,4-trihalomethyl, etc. Specific examples include fluorinated C1-C4the alkyl groups defined above, such as trifluoromethyl.

C6-C12-Aryl-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom substituted C6-C12-aryl, such as benzyl.

Hydroxy-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, where one or two hydrogen atoms substituted with one or two hydroxyl groups, such as gidroximetil, (R)-1-hydroxyethyl, (S)-1-hydroxyethyl, 2-hydroxyethyl, (R)-1-hydroxypropyl, (S)-1-hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, (R)-2-hydroxy-1-methylethyl, (S)-2-hydroxy-1-methylethyl, 2-�hydroxy-1-(gidroximetil)ethyl, (R)-1-hydroxybutyl, (S)-1-hydroxybutyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl.

C1-C6-Alkoxy-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, where one or two hydrogen atoms substituted with one or two alkoxylic one groups containing from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms, such as methoxymethyl, (R)-1-methoxyethyl, (S)-1-methoxyethyl, 2-methoxyethyl, (R)-1-methoxypropyl, (S)-1-methoxypropyl, 2-methoxypropyl, 3-methoxypropyl, (R)-2-methoxy-1-methylethyl, (S)-2-methoxy-1-methylethyl, 2-methoxy-1-(methoxymethyl)ethyl, (R)-1-methoxybutyl, (S)-1-methoxybutyl, 2-methoxybutyl, 3-methoxybutyl, 4-methoxybutyl, ethoxymethyl, (R)-1-ethoxyethyl, (S)-1-ethoxyethyl, 2-ethoxyethyl, (R)-1-ethoxypropan, (S)-1-ethoxypropan, 2-ethoxypropan, 3-ethoxypropan, (R)-2-ethoxy-1-methylethyl, (S)-2-ethoxy-1-methylethyl, 2-ethoxy-1-(ethoxymethyl)ethyl, (R)-1-ethoxymethyl, (S)-1-ethoxymethyl, 2-ethoxymethyl, 3-ethoxymethyl, 4-ethoxymethyl.

Amino-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two atoms arc�kind, where one hydrogen atom substituted with amino group, such as aminomethyl, 2-aminoethyl.

C1-C6-Alkylamino-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom substituted C1-C6-alkylamino, in particular, C1-C4-alkylaminocarbonyl such as methylaminomethyl, ethylaminomethyl, n-propylaminoethyl, ISO-propylaminoethyl, n-butylaminoethyl, 2-butylaminoethyl, ISO-butylaminoethyl or tert-butylaminoethyl.

Di-C1-C6-Alkylamino-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom is substituted with di-C1-C6-alkylamino, in particular, di-C1-C4-alkylaminocarbonyl, such as dimethylaminomethyl.

C1-C6-Alkylcarboxylic-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferred�tive 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom substituted C1-C6-alkylcarboxylic, in particular, C1-C4-alkylcarboxylic such as methylcarbamoylmethyl, ethylcarbodiimide, n-profilerviewer, ISO-profilerviewer, n-butylcarbamoyl, 2-butylcarbamoyl, ISO-butylcarbamoyl or tert-butylcarbamoyl.

C1-C6-Alkylaminocarbonyl-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom substituted C1-C6-alkylaminocarbonyl, in particular, C1-C4-alkylaminocarbonyl such as methylaminoanthraquinone, ethylaminoethanol, n-propylenecarbonate, ISO-propylenecarbonate, n-buylamisilonline, 2-buylamisilonline, ISO-buylamisilonline or tert-buylamisilonline.

Di-C1-C6-alkylaminocarbonyl-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 atoms coal�ode, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom is substituted with di-C1-C6-alkylaminocarbonyl, in particular, di-C1-C4-alkylaminocarbonyl such as dimethylaminocarbonylmethyl, dimethylaminocarbonylmethyl, dimethylaminocarbonylmethyl-n-propyl.

C1-C6-Alkylsulfonyl-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom substituted C1-C6-alkylsulfonamides, in particular, C1-C4-alkylsulfonamides such as methylsulfonylamino, ethylsulfinylmethyl, n-propylsulfonyl, ISO-propylsulfonyl, n-butylsulfonyl, 2-butylsulfonyl, ISO-butylsulfonyl or tert-butylsulfonyl.

(C6-C12-Aryl-C1-C6-alkyl)amino-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more predpochtitel�but 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one atom of hydrogen is replaced by (C6-C12-aryl-C1-C6-alkyl)amino group, in particular, (C6-C12-aryl-C1-C2-alkyl)amino group, such as benzylamine.

C3-C12-Heterocyclyl-C1-C4-alkyl is a linear or branched alkyl group containing from 1 to 4 carbon atoms, preferably from 1 to 3 carbon atoms, more preferably 1 or 2 carbon atoms, in particular 1 or two carbon atoms, where one hydrogen atom substituted C3-C12-heterocyclyl, such as N-pyrrolidinyl, N-piperidinylmethyl, N-morpholinylmethyl.

C3-C12-Cycloalkyl represents a cycloaliphatic radical containing from 3 to 12 carbon atoms. In particular, 3-6 carbon atoms form a cyclic structure such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The cyclic structure may be unsubstituted or may carry 1, 2, 3 or 4 C1-C4-alkyl radicals, preferably one or more methyl radicals.

The carbonyl represents >C=O.

C1-C6-Alkylsulphonyl represents a radical of the formula R-C(O)-, where R is an alkyl radical containing from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms as defined�but in this document. Examples include acetyl, propionyl, n-butyryl, 2-methylpropionyl, a pivaloyl.

Halogenated C1-C6-alkylsulphonyl represents C1-C6-alkylsulphonyl defined herein, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms. Examples include formatieren, deformational, triftormetilfullerenov. Other examples include 1,1,1-cryptonet-2-ylcarbonyl, 1,1,1-Cryptocom-3-ylcarbonyl.

C6-C12-Arylcarbamoyl represents a radical of the formula R-C(O)-, where R is an aryl radical containing from 6 to 12 carbon atoms as defined herein. Examples include benzoyl.

C1-C6-Alkoxycarbonyl represents a radical of the formula R-O-C(O)-, where R is an alkyl radical containing from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms as defined herein. Examples include methoxycarbonyl and tert-butyloxycarbonyl.

Halogenated C1-C6-alkoxycarbonyl represents C1-C6-alkoxycarbonyl defined in this document where at least one, e.g. 1, 2, 3, 4 or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different atoms halog�on.

C6-C12-Aryloxyalkyl represents a radical of the formula R-O-C(O)-, where R is an aryl radical containing from 6 to 12 carbon atoms as defined herein. Examples include phenoxycarbonyl.

Cyano is a-C≡N.

Aminocarbonyl represents NH2C(O)-.

C1-C6-Alkylaminocarbonyl represents a radical of the formula R-NH-C(O)-, where R is an alkyl radical containing from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms as defined herein. Examples include methylaminomethyl.

(Halogenated C1-C4-alkyl)aminocarbonyl represents C1-C4-alkylaminocarbonyl defined in this document where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different hydrogen atoms.

C6-C12-Allumination represents a radical of the formula R-NH-C(O)-, where R is an aryl radical containing from 6 to 12 carbon atoms as defined herein. Examples include phenylenecarbonyl.

C2-C6The alkenyl is a singly unsaturated hydrocarbon radical containing 2, 3, 4, 5 or 6 carbon atoms, e.g. vinyl, allyl (2-propene-1-yl), 1-propene-1-yl, 2-propene-2-yl, IU�allyl(2-methylprop-2-EN-1-yl), etc. C3-C5The alkenyl is, in particular, allyl, 1-methylprop-2-EN-1-yl, 2-butene-1-yl, 3-butene-1-yl, methallyl, 2-penten-1-yl, 3-penten-1-yl, 4-penten-1-yl, 1-methylbut-2-EN-1-yl or 2-itelpop-2-EN-1-yl.

C2-C6-Alkenyl is a singly unsaturated hydrocarbon radical containing 2, 3, 4, 5 or 6 carbon atoms, for example, ethinyl, 2-propen-1-yl, 1-propen-1-yl, 2-propen-2-yl, etc., C3-C5-Alkynyl represents, in particular, 2-propen-1-yl, 2-Butin-1-yl, 3-butyn-1-yl, 2-Pentin-1-yl, 3-Pentin-1-yl, 4-Pentin-1-yl.

C1-C4-Alkylene represents a linear or branched alkylenes group containing from 1 to 4 carbon atoms. Examples include methylene and ethylene. Another example is propylene.

C2-C4-Albaniles represents a linear or branched alkenylamine group containing 2 to 4 carbon atoms.

C2-C4-Akinyan represents a linear or branched alkynylamino group containing 2 to 4 carbon atoms. Examples include propylen.

C6-C12Aryl represents a 6-12-membered, in particular, 6-10-membered aromatic cyclic radical. Examples include phenyl and naphthyl.

C3-C12-Aralen represents an aryl diradical. Examples include Hairdryer-1,4-ilen and Hairdryer-1,3-ilen.

Hydroxypentanal a-OH.

C1-C6-Alkoxy represents a radical of the formula R-O-, where R represents a linear or branched alkyl group containing from 1 to 6, in particular 1 to 4 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, butoxy, 2-butoxy, ISO-butoxy (2 methylpropoxy), tert-butoxy, pentyloxy, 1 methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-DIMETHYLPROPANE, 1 ethylpropoxy, hexyloxy, 1,1-DIMETHYLPROPANE, 1,2-DIMETHYLPROPANE, 1 methylpentylamine, 2-methylpentane, 3-methylpentane, 4-methylpentylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,2-dimethylbutylamino, 2,3-dimethylbutylamino, 3,3-dimethylbutylamino, 1 ethylbutylamine, 2-ethylbutyrate, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy.

Halogenated C1-C6-alkoxy is a linear or branched alkoxylic one group containing from 1 to 6, preferably from 1 to 4, in particular 1 or 2 carbon atoms, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms, such as halogenerators, dehalogenate, trihalomethane, (R)-1-halogenations, (S)-1-halogenations, 2-halogenations, 1,1-dehalogenate, 2,2-dehalogenate, 2,2,2-trihalomethane, (R)-1-ha�openproxy, (S)-1-halogenerators, 2-halogenerators, 3-halogenerators, 1,1-dialoginterface, 2,2-dialoginterface, 3,3-dialoginterface, 3,3,3-trialgenericsi, (R)-2-halogen-1-methylethoxy, (S)-2-halogen-1-methylethoxy, (R)-2,2-dihalogen-1 methylethoxy, (S)-2,2-dihalogen-1 methylethoxy, (R)-1,2-dihalogen-1 methylethoxy, (S)-1,2-dihalogen-1 methylethoxy, (R)-2,2,2-trihalogen-1 methylethoxy, (S)-2,2,2-trihalogen-1 methylethoxy, 2-halogen-1-(halogenmethyl)ethoxy, 1-(dehalogenated)-2,2-dehalogenate, (R)-1-halogenates, (S)-1-halogenates, 2-halogenates, 3-halogenates, 4-halogenates, 1,1-dehalogenate, 2,2-dehalogenate, 3,3-dehalogenate, 4,4-dehalogenate, 4,4,4-trihalomethane, etc. Specific examples include fluorinated C1-C4-alkoxylic one group defined in this document, such as triptoreline.

C1-C6-Hydroxyalkoxy alkoxylic one is a radical, containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein where one or two hydrogen atoms substituted by a hydroxyl group. Examples include 2-hydroxyethoxy, 3-hydroxypropoxy, 2-hydroxypropoxy, 1-methyl-2-hydroxyethoxy, etc.

C1-C6-Alkoxy-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4 carbon atoms, predpochtitelno 1 or 2 carbon atoms, ka� defined in this document where one or two hydrogen atoms substituted by one or two alkoxylic one radicals containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methoxyethoxy, 2-methoxyethoxy, 1 methoxyethoxy, 3-methoxypropane, 2-methoxypropene, 1-methyl-1-methoxyethoxy, ethoxyethoxy, 2-ethoxyethoxy, 1 ethoxyethoxy, 3-ethoxypropane, 2-ethoxypropane, 1-methyl-1-ethoxyethoxy, etc.

Amino-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom substituted with amino group. Examples include 2-aminoethoxy.

C1-C6-Alkylamino-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom is substituted by alkylamino containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylaminomethyl, ethylaminomethyl, propylaminoethyl, ISO-propylaminoethyl, butylaminoethyl, 2-butylaminoethyl, ISO-butylaminoethyl, tert-butylaminoethyl, 2-(methylamino)ethoxy, 2-(ethylamino)ethoxy, 2-(n-propylamino)ethoxy, 2-(ISO-propylamino)ethoxy, 2-(n-butylamino)ethoxy, -(2-butylamino)ethoxy, 2-(ISO-butylamino)ethoxy, 2-(tert-butylamino)ethoxy.

Di-C1-C6-alkylamino-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom is substituted with di-alkylamino containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include dimethylaminoethoxy, diethylaminoethoxy, N-methyl-N-ethylamino)ethoxy, 2-(dimethylamino)ethoxy, 2-(diethylamino)ethoxy, 2-(N-methyl-N-ethylamino)ethoxy.

C1-C6-Alkylcarboxylic-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom is substituted by alkylcarboxylic, where the alkyl group contains from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylcarbanilate, ethylcarbodiimide, propellerblades, ISO-propylmalonate, BUTYLCARBAMATE, 2-BUTYLCARBAMATE, ISO-butylcarbamoyl, tert-BUTYLCARBAMATE, 2-(methylcarbanilate)ethoxy, 2-(ethylcarbodiimide)ethoxy, 2-(n-propelleronline)ethoxy, 2-(ISO-propylmalonate�o)ethoxy, 2-(n-butylcarbamoyl)ethoxy, 2-(2-butylcarbamoyl)ethoxy, 2-(ISO-butylcarbamoyl)ethoxy, 2-(tert-butylcarbamoyl)ethoxy.

C6-C12-Arylcarboxamide-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom substituted C6-C12-arylcarbamoyl, as defined in this document. Examples include 2-(benzoylamino)ethoxy.

C1-C6-Alkoxycarbonyl-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom is substituted by alkoxycarbonylmethyl, and alkoxylic one group contains from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methoxycarbonylamino, ethoxycarbonylmethoxy, propoxycarbonyl, ISO-propoxycarbonyl, butoxycarbonylamino, 2-butoxycarbonylamino, ISO-butoxycarbonylamino, tert-butoxycarbonylamino, 2-(methoxycarbonylamino)ethoxy, 2-(ethoxycarbonyl)ethoxy, 2-(n-propoxycarbonyl)ethoxy, 2-(ISO-propoxycarbonyl)ethoxy, 2-(n-butoxycarbonylamino�)ethoxy, 2-(2-butoxycarbonylamino)ethoxy, 2-(ISO-butoxycarbonylamino)ethoxy, 2-(tert-butoxycarbonylamino)ethoxy.

C2-C6-Alkenylacyl represents a radical of the formula R-O-, where R is a linear or branched alkenyl group containing from 2 to 6, in particular 2 to 4 carbon atoms. Examples include vinyloxy, allyloxy (2-propene-1-yloxy), 1-propene-1-yloxy, 2-propene-2-yloxy, metalliance (2-methylprop-2-ene-1-yloxy) and T. p. (C3-C5-Alkenylacyl represents, in particular, allyloxy, 1-methylprop-2-ene-1-yloxy, 2-butene-1-yloxy, 3-butene-1-yloxy, metalliance, 2-penten-1 yloxy, 3-penten-1 yloxy, 4-penten-1 yloxy, 1-methylbut-2-ene-1-yloxy or 2-itelpop-2-ene-1-yloxy.

C6-C12-Aryl-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom substituted C6-C12-aryl group, as defined herein. Examples include benzyloxy.

C1-C6-Alkylsulfonyl-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom is substituted by alkylsulfonamides containing from 1 to 6, preferably from 1 to 4 ATO�s carbon as defined in this document. Examples include 2-(methylsulfonylamino)ethoxy, 2-(ethylsulfonyl)ethoxy, 2-[(2-methylpropyl") sulfonylamino]ethoxy.

(Halogenated C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom is substituted by alkylsulfonamides containing from 1 to 6, preferably from 1 to 4 carbon atoms, as defined in this document, where the alkyl group is halogenated. Examples include 2-(triftormetilfullerenov)ethoxy.

C6-C12-Arylsulfonamides-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom substituted C6-C12-arylsulfonamides, as defined in this document. Examples include 2-(phenylcarbonylamino)ethoxy, 2-(naphthylaniline)ethoxy.

(C6-C12-Aryl-C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom is substituted (C6-C12-�RIL-C 1-C6-alkyl)sulfonylamino, preferably (C6-C12-aryl-C1-C2-alkyl)sulfonylamino. Examples include 2-(benzylmethylamine)ethoxy.

C3-C12-Geterotsiklicheskie-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom substituted C3-C12- defined in this document. Examples include 2-(pyridin-3-yl-sulfonylamino)ethoxy.

C3-C12-Heterocyclyl-C1-C4-alkoxy alkoxylic one is a radical, containing from 1 to 4, preferably 1 or 2 carbon atoms as defined herein wherein one hydrogen atom substituted C3-C12-heterocyclyl group defined in this document. Examples include 2-(N-pyrrolidinyl)ethoxy, 2-(N-morpholinyl)ethoxy and 2-(N-imidazolyl)ethoxy.

C1-C2-Alkylenedioxy represents a radical of the formula-O-R-O-, where R is a linear or branched alkylenes group containing 1 or 2 carbon atoms as defined herein. Examples include methylenedioxy.

C6-C12-Aryloxy represents a radical of the formula R-O-, where R is a aryl group, sod�Rasul from 6 to 12, in particular 6 carbon atoms as defined herein. Examples include phenoxy.

C3-C12-Heterocyclics represents a radical of the formula R-O-, where R is a C3-C12-heterocyclyl group containing from 3 to 12, in particular from 3 to 7 carbon atoms as defined herein. Examples include pyridine-2-yloxy.

C1-C6-Alkylthio represents a radical of the formula R-S-, where R is an alkyl radical containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylthio, ethylthio, propylthio, butylthio, pentylthio, 1 methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1 utilproperties, hexylthio, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1 methylphenylthio, 2-methylphenylthio, 3-methylphenylthio, 4-methylphenylthio, 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-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl "and 1-ethyl-2-methylpropyl".

Halogenated C1-C6-alkylthio represents a radical of the formula R-S-, where R is a halogenated alkyl radical containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. �reamers include halogenmethyl, dehalogenation, trigalogenmetany, (R)-1-halogenation, (S)-1-halogenation, 2-halogenation, 1,1-dehalogenation, 2,2-dehalogenation, 2,2,2-trigalogenmetany, (R)-1-halogenfrei, (S)-1-halogenfrei, 2-halogenfrei, 3-halogenfrei, 1,1-dehalogenation, 2,2-dehalogenation, 3,3-dehalogenation, 3,3,3-trigonocephaly, (R)-2-halogen-1-metalicity, (S)-2-halogen-1-metalicity, (R)-2,2-dihalogen-1 metalicity, (S)-2,2-dihalogen-1 metalicity, (R)-1,2-dihalogen-1 metalicity, (S)-1,2-dihalogen-1 metalicity, (R)-2,2,2-trihalogen-1 metalicity, (S)-2,2,2-trihalogen-1 metalicity, 2-halogen-1-(halogenmethyl)ethylthio, 1-(dehalogenated)-2,2-dehalogenation, (R)-1-halogenation, (S)-1-halogenation, 2-halogenmethyl, 3-halogenmethyl, 4-halogenation, 1,1-dehalogenation, 2,2-dehalogenation, 3,3-dehalogenation, 4,4-dehalogenation, 4,4,4-trigalogenmetany, etc. Specific examples include fluorinated C1-C4-allylthiourea, as defined, such as triptoreline.

C1-C6-Alkylsulfonyl represents a radical of the formula R-S(O)-, where R is an alkyl radical containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylsulfinyl, ethylsulfinyl, propylsulfonyl, butylsulfonyl, pentasulfide, 1-methylbutyl�Neal, 2-methylbutylamine, 3-methylbutylamine, 2,2-dimethylpropylene, 1-ethylpropylamine, exisulind, 1,1-dimethylpropylene, 1,2-dimethylpropylene, 1-methylphenylsulfonyl, 2-methylphenylsulfonyl, 3-methylphenylsulfonyl, 4-methylphenylsulfonyl, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,2-dimethylbutylamino, 2,3-dimethylbutylamino, 3,3-dimethylbutylamino, 1-ethylbutylamine, 2-ethylbutylamine, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl "and 1-ethyl-2-methylpropyl".

C1-C6-Alkylsulfonyl represents a radical of the formula R-S(O)2-, where R is an alkyl radical containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methyl-sulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, intercultural, 1-methylbutylamine, 2-methylbutylamine, 3-methylbutanoyl, 2,2-dimethylpropanoyl, 1-ethylpropylamine, hexylsilane, 1,1-dimethylpropylene, 1,2-dimethylpropylene, 1-methylphenylsulfonyl, 2-methylphenylsulfonyl, 3-methylphenylsulfonyl, 4-methylphenylsulfonyl, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,2-dimethylbutylamino, 2,3-dimethylbutylamino, 3,3-DIMET�butylsulfonyl, 1-ethylbutylamine, 2-ethylbutylamine, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl "and 1-ethyl-2-methylpropyl".

(Halogenated C1-C6-alkyl)sulfonyl is a C1-C6-alkylsulfonyl, as defined in this document, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C6-C12-Arylsulfonyl represents a radical of the formula R-S(O)2-, where R is an aryl radical containing from 6 to 12 carbon atoms as defined herein. Examples include phenylsulfonyl.

(C6-C12-Aryl-C1-C4-alkyl)sulfonyl is a radical of the formula R-S(O)2-, where R is a C6-C12-aryl-C1-C4-alkyl radical, in particular, C6-C12-aryl-C1-C2is an alkyl radical, as defined herein. Examples include benzolsulfonat.

C3-C12-Heterocyclisation represents a radical of the formula R-S(O)2-, where R is a C3-C12-heterocyclyl defined in this document.

Aminosulfonyl represents NH2-S(O)2-.

C1-C6-Alkylaminocarbonyl represents a radical of the formula R-NH-S() 2-, where R is an alkyl radical containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include methylaminomethyl, ethylaminomethyl, n-propylaminosulfonyl, ISO-propylaminosulfonyl, n-butylaminoethyl, 2-butylaminoethyl, ISO-butylaminoethyl, tert-butylaminoethyl.

Di-C1-C6-alkylaminocarbonyl represents a radical of the formula RR'N-S(O)2-, where R and R' independently from each other represent an alkyl radical containing from 1 to 6, preferably from 1 to 4 carbon atoms as defined herein. Examples include dimethylaminomethyl, diethylaminomethyl, N-methyl-N-ethylaminomethyl.

C6-C12-Arylamination represents a radical of the formula R-NH-S(O)2-, where R is an aryl radical containing from 6 to 12, preferably 6 carbon atoms as defined herein.

Amino represents NH2.

C1-C6-Alkylamino represents a radical of the formula R-NH-, where R is an alkyl radical containing from 1 to 6, in particular 1 to 4 carbon atoms as defined herein. Examples include methylamino, ethylamino, propylamino, ISO-propylamino, n-butylamino, 2-butylamino, ISO-butylamino, tert-butylamino.

(Halogenated C 1-C6-alkyl)amino is a C1-C6-alkylamino, as defined in this document, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

Di-C1-C6-alkylamino represents a radical of the formula RR'N-, where R and R' independently from each other represent an alkyl radical containing from 1 to 6, in particular 1 to 4 carbon atoms as defined herein. Examples include dimethylamino, diethylamino, N-methyl-N-ethylamino.

Di-(halogenated C1-C6-alkyl)amino, represents di-(C1-C6-alkylamino, as defined in this document, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C1-C6-Alkylcarboxylic represents a radical of the formula R-C(O)-NH-, where R is an alkyl radical containing from 1 to 6, in particular 1 to 4 carbon atoms as defined herein. Examples include atsetamido (methylcarbanilate), propionamido, butyramide, 2-methylpropionamide (isopropylcarbonate), 2,2-dimethylpropanamide, etc.

(Halogenated C1-C6-alkyl)carbylamine represents C1-C6-alkyl�ebonyline, as defined in this document, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C6-C12-Arylcarboxamide represents a radical of the formula R-C(O)-NH-, where R is an aryl radical containing from 6 to 12 carbon atoms as defined herein. Examples include phenylcarbonylamino.

C2-C6-Alkenylamine represents a radical of the formula R-NH-, where R is a linear or branched alkenyl group containing from 2 to 6, in particular 2 to 4 carbon atoms. Examples include vinylamine, allylamine (2-propene-1-ylamino), 1-propene-1-ylamino, 2-propene-2-ylamino, metalaluminum (2-methylprop-2-ene-1-ylamino) and T. p. (C3-C5-Alkenylamine represents, in particular, allylamine, 1-methylprop-2-ene-1-ylamino, 2-butene-1-ylamino, 3-butene-1-ylamino, metalaluminum, 2-penten-1 ylamino, 3-penten-1 ylamino, 4-penten-1 ylamino, 1-methylbut-2-ene-1-ylamine or 2-itelpop-2-ene-1-ylamino.

C1-C6-Alkylsulfonamides represents a radical of the formula R-S(O)2-NH-, where R is an alkyl radical containing from 1 to 6, in particular 1 to 4 carbon atoms as defined herein. Examples include methylsulfonylamino, ethylsulfonyl, propylsulfonyl, and�about propylsulfonyl, n-butylsulfonyl, 2-butylsulfonyl, ISO-butylsulfonyl, tert-butylsulfonyl.

(Halogenated C1-C6-alkyl)sulfonylamino represents C1-C6-alkylsulfonyl, as defined in this document, where at least one, e.g. 1, 2, 3, 4, or all of the hydrogen atoms substituted with 1, 2, 3, 4 or a corresponding number of identical or different halogen atoms.

C6-C12-Arylsulfonamides represents a radical of the formula R-S(O)2-NH-, where R is an aryl radical containing from 6 to 12 carbon atoms as defined herein. Examples include phenylcarbonylamino.

Nitro is a-NO2.

C3-C12-Heterocyclyl is a 3-12-membered heterocyclic radical including a saturated heterocyclic radical, which generally has 3, 4, 5, 6 or 7, the loop-forming atoms (circular members), unsaturated non-aromatic heterocyclic radical, which generally has 5, 6 or 7, the loop-forming atoms, and a heteroaromatic radical (heteroaryl), which typically contains 5, 6 or 7, the loop-forming atoms. Heterocyclic radicals can be joined to the rest of the molecule via a carbon atom (C-bound) or a nitrogen atom (N-linked). Preferred heterocycle�die radicals contain 1 nitrogen atom as the cyclic atom and, optional, 1, 2 or 3 other heteroatoms as circular members, which can be selected independently from one another from O, S and N. in this way the preferred heterocyclic radicals contain 1 heteroatom as a circular member that can be selected from O, S and N, and optionally 1, 2 or 3 nitrogen atoms as the cyclic members.

Examples of C3-C12-heterocyclyl include:

C - or N-linked 3 to 4 membered saturated cycles, such as 2-oxiranyl, 2-oxetanyl, 3-oxetanyl, 2-aziridinyl, 3-titanyl, 1-azetidine, 2-azetidine, 3-azetidinol;

C-linked, 5-membered saturated cycles, such as tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothieno-2-yl, tetrahydrothieno-3-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyranol-3-yl, tetrahydropyranol-4-yl, tetrahydrocarbazol-3-yl, tetrahydrocarbazol-4-yl, tetrahydrocarbazol-5-yl, 1,2-oxathiolan-3-yl, 1,2-oxathiolan-4-yl, 1,2-oxathiolan-5-yl, tetrahydrocortisol-3-yl, tetrahydrocortisol-4-yl, tetrahydrocortisol-5-yl, 1,2-dithiolan-3-yl, 1,2-dithiolan-4-yl, tetrahydroimidazo-2-yl, tetrahydroimidazo-4-yl, tetrahydrooxazolo-2-yl, tetrahydrooxazolo-4-yl, tetrahydrooxazolo-5-yl, tetrahydrocarbazol-2-yl, tetrahydrothieno-4-yl, tetrahydrocarbazol-5-yl, 1,3-dioxolan-2-yl, 1,3-dioxolan-4-yl, 1,3-oxathiolan-2-yl, 1,3-oxathiolan-4-yl, 1,3-ox�iolan-5-yl, 1,3-dithiolan-2-yl, 1,3-dithiolan-4-yl, 1,3,2-dioxathion-4-yl;

C-linked 6-membered saturated cycles, such as tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, piperidine-2-yl, piperidine-3-yl, piperidine-4-yl, tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, 1,3-dioxan-2-yl, 1,3-dioxane-4-yl, 1,3-dioxan-5-yl, 1,4-dioxane-2-yl, 1,3-dition-2-yl, 1,3-dition-4-yl, 1,3-dition-5-yl, 1,4-dition-2-yl, 1,3-occation-2-yl, 1,3-occation-4-yl, 1,3-occation-5-yl, 1,3-occation-6-yl, 1,4-occation-2-yl, 1,4-occation-3-yl, 1,2-dition-3-yl, 1,2-dicyan-4-yl, hexahydropyridine-2-yl, hexahydroazepin-4-yl, hexahydroazepin-5-yl, hexahydropyrazino-2-yl, hexahydropyridine-3-yl, hexahydropyridine-4-yl, tetrahydro-1,3-oxazine Serie-2-yl, tetrahydro-1,3-oxazine Serie-4-yl, tetrahydro-1,3-oxazine Serie-5-yl, tetrahydro-1,3-oxazine Serie-6-yl, tetrahydro-1,3-thiazin-2-yl, tetrahydro-1,3-thiazin-4-yl, tetrahydro-1,3-thiazin-5-yl, tetrahydro-1,3-thiazin-6-yl, tetrahydro-1,4-thiazin-2-yl, tetrahydro-1,4-thiazin-3-yl, tetrahydro-1,4-oxazine Serie-2-yl, tetrahydro-1,4-oxazine Serie-3-yl, tetrahydro-1,2-oxazine Serie-3-yl, tetrahydro-1,2-oxazine Serie-4-yl, tetrahydro-1,2-oxazine Serie-5-yl, tetrahydro-1,2-oxazine Serie-6-yl;

N-linked, 5-membered saturated cycles, such as tetrahydropyrrole-1-yl (pyrrolidin-1-yl), tetrahydropyrazin-1-yl, tetrahydrocarbazol-2-yl, tetrahydrocortisol-2-yl, tetrahydroimidazo-1-yl, tetrahydrooxazolo-3-yl, Tetra�kotesol-3-yl;

N-linked 6-membered saturated cycles, such as piperidine-1-yl, hexahydroazepin-1-yl, hexahydroazepin-1-yl (piperazine-1-yl), hexahydropyridine-1-yl, tetrahydro-1,3-oxazine Serie-3-yl, tetrahydro-1,3-thiazin-3-yl, tetrahydro-1,4-thiazin-4-yl, tetrahydro-1,4-oxazine Serie-4-yl (morpholine-1-yl), tetrahydro-1,2-oxazine Serie-2-yl;

C-linked, 5-membered partially unsaturated cycles, such as 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,5-dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl, 4,5-dihydrofuran-2-yl, 4,5-dihydrofuran-3-yl, 2,3-dihydrothieno-2-yl, 2,3-dihydrothieno-3-yl, 2,5-dihydrothieno-2-yl, 2,5-dihydrothieno-3-yl, 4,5-dihydrothieno-2-yl, 4,5-dihydrothieno-3-yl, 2,3-dihydro-1H-pyrrol-2-yl, 2,3-dihydro-1H-pyrrol-3-yl, 2,5-dihydro-1H-pyrrol-2-yl, 2,5-dihydro-1H-pyrrol-3-yl, 4,5-dihydro-1H-pyrrol-2-yl, 4,5-dihydro-1H-pyrrol-3-yl, 3,4-dihydro-2H-pyrrol-2-yl, 3,4-dihydro-2H-pyrrol-3-yl, 3,4-dihydro-5H-pyrrol-2-yl, 3,4-dihydro-5H-pyrrol-3-yl, 4,5-dihydro-1H-pyrazol-3-yl, 4,5-dihydro-1H-pyrazol-4-yl, 4,5-dihydro-1H-pyrazol-5-yl, 2,5-dihydro-1H-pyrazol-3-yl, 2,5-dihydro-1H-pyrazol-4-yl, 2,5-dihydro-1H-pyrazol-5-yl, 4,5-dihydroisoxazole-3-yl, 4,5-dihydroisoxazole-4-yl, 4,5-dihydroisoxazole-5-yl, 2,5-dihydroisoxazole-3-yl, 2,5-dihydroisoxazole-4-yl, 2,5-dihydroisoxazole-5-yl, 2,3-dihydroisoxazole-3-yl, 2,3-dihydroisoxazole-4-yl, 2,3-dihydroisoxazole-5-yl, 4,5-dihydroisoxazole-3-yl, 4,5-dihydrothiazolo-4-yl, 4,5-dihydroisoxazole-5-yl, 2,5-dihydroisoxazole-3-yl, 2,5-DIH�drastical-4-yl, 2,5-dihydroisoxazole-5-yl, 2,3-dihydroisoxazole-3-yl, 2,3-dihydrothiazolo-4-yl, 2,3-dihydroisoxazole-5-yl, 4,5-dihydro-1H-imidazol-2-yl, 4,5-dihydro-1H-imidazol-4-yl, 4,5-dihydro-1H-imidazol-5-yl, 2,5-dihydro-1H-imidazol-2-yl, 2,5-dihydro-1H-imidazol-4-yl, 2,5-dihydro-1H-imidazol-5-yl, 2,3-dihydro-1H-imidazol-2-yl, 2,3-dihydro-1H-imidazol-4-yl, 4,5-dihydro-oxazol-2-yl, 4,5-dihydrooxazolo-4-yl, 4,5-dihydrooxazolo-5-yl, 2,5-dihydrooxazolo-2-yl, 2,5-dihydrooxazolo-4-yl, 2,5-dihydrooxazolo-5-yl, 2,3-dihydrooxazolo-2-yl, 2,3-dihydrooxazolo-4-yl, 2,3-dihydrooxazolo-5-yl, 4,5-dihydrothiazolo-2-yl, 4,5-dihydrothiazolo-4-yl, 4,5-dihydrothiazolo-5-yl, 2,5-dihydrothiazolo-2-yl, 2,5-dihydrothiazolo-4-yl, 2,5-dihydrothiazolo-5-yl, 2,3-dihydrothiazolo-2-yl, 2,3-dihydrothiazolo-4-yl, 2,3-dihydrothiazolo-5-yl, 1,3-dioxol-2-yl, 1,3-dioxol-4-yl, 1,3-dithiol-2-yl, 1,3-dithiol-4-yl, 1,3-oxalyl-2-yl, 1,3-oxalyl-4-yl, 1,3-axetil-5-yl;

C-linked 6-membered partially unsaturated cycles, such as 2H-3,4-dihydropyran-6-yl, 2H-3,4-dihydropyran-5-yl, 2H-3,4-dihydropyran-4-yl, 2H-3,4-dihydropyran-3-yl, 2H-3,4-dihydropyran-2-yl, 2H-3,4-dihydrocoumarin-6-yl, 2H-3,4-dihydrothieno-5-yl, 2H-3,4-dihydrothieno-4-yl, 2H-3,4-dihydrothiophene-3-yl, 2H-3,4-dihydrothieno-2-yl, 1,2,3,4-tetrahydropiridine-6-yl, 1,2,3,4-tetrahydropiridine-5-yl, 1,2,3,4-tetrahydropiridine-4-yl, 1,2,3,4-tetrahydropiridine-3-yl, 1,2,3,4-tetrahydropiridine-2-yl, 2H-5,6-dihydropyran-2-yl, 2H-5,6-dihydropyran-3-yl, 2H-5,6-dihydropyran-4-yl, 2H-5,6-�gidropony-5-yl, 2H-5,6-dihydropyran-6-yl, 2H-5,6-dihydrothieno-2-yl, 2H-5,6-dihydrothiophene-3-yl, 2H-5,6-dihydrothieno-4-yl, 2H-5,6-dihydrothieno-5-yl, 2H-5,6-dihydrothieno-6-yl, 1,2,5,6-tetrahydropiridine-2-yl, 1,2,5,6-tetrahydropiridine-3-yl, 1,2,5,6-tetrahydropiridine-4-yl, 1,2,5,6-tetrahydropiridine-5-yl, 1,2,5,6-tetrahydropiridine-6-yl, 2,3,4,5-tetrahydropiridine-2-yl, 2,3,4,5-tetrahydropiridine-3-yl, 2,3,4,5-tetrahydropiridine-4-yl, 2,3,4,5-tetrahydropiridine-5-yl, 2,3,4,5-tetrahydropiridine-6-yl, 4H-Piran-2-yl, 4H-Piran-3-yl-, 4H-Piran-4-yl, 4H-thiopyran-2-yl, 4H-thiopyran-3-yl, 4H-thiopyran-4-yl, 1,4-dihydropyridine-2-yl, 1,4-dihydropyridines-3-yl, 1,4-dihydropyridines-4-yl, 2H-Piran-2-yl, 2H-Piran-3-yl, 2H-Piran-4-yl, 2H-PYRAN-5-yl, 2H-PYRAN-6-yl, 2H-thiopyran-2-yl, 2H-thiopyran-3-yl, 2H-thiopyran-4-yl, 2H-thiopyran-5-yl, 2H-thiopyran-6-yl, 1,2-dihydropyridine-2-yl, 1,2-dihydropyridine-3-yl, 1,2-dihydropyridines-4-yl, 1,2-dihydropyridine-5-yl, 1,2-dihydropyridine-6-yl, 3,4-dihydropyridine-2-yl, 3,4-dihydropyridine-3-yl, 3,4-dihydropyridine-4-yl, 3,4-dihydropyridine-5-yl, 3,4-dihydropyridine-6-yl, 2,5-dihydropyridine-2-yl, 2,5-dihydropyridine-3-yl, 2,5-dihydropyridine-4-yl, 2,5-dihydropyridine-5-yl, 2,5-dihydropyridine-6-yl, 2,3-dihydropyridine-2-yl, 2,3-dihydropyridine-3-yl, 2,3-dihydropyridine-4-yl, 2,3-dihydropyridine-5-yl, 2,3-dihydropyridine-6-yl, 2H-5,6-dihydro-1,2-oxazine Serie-3-yl, 2H-5,6-dihydro-1,2-oxazine Serie-4-yl, 2H-5,6-dihydro-1,2-oxazine Serie-5-yl, 2H-5,6-dihydro-1,2-oxazine Serie-6-yl, 2H-5,6-dihydro-1,2-thiazin-3-yl, 2H-5,6-dihydro-1,2-TIA�in-4-yl, 2H-5,6-dihydro-1,2-thiazin-5-yl, 2H-5,6-dihydro-1,2-thiazin-6-yl, 4H-5,6-dihydro-1,2-oxazine Serie-3-yl, 4H-5,6-dihydro-1,2-oxazine Serie-4-yl, 4H-5,6-dihydro-1,2-oxazine Serie-5-yl, 4H-5,6-dihydro-1,2-oxazine Serie-6-yl, 4H-5,6-dihydro-1,2-thiazin-3-yl, 4H-5,6-dihydro-1,2-thiazin-4-yl, 4H-5,6-dihydro-1,2-thiazin-5-yl, 4H-5,6-dihydro-1,2-thiazin-6-yl, 2H-3,6-dihydro-1,2-oxazine Serie-3-yl, 2H-3,6-dihydro-1,2-oxazine Serie-4-yl, 2H-3,6-dihydro-1,2-oxazine Serie-5-yl, 2H-3,6-dihydro-1,2-oxazine Serie-6-yl, 2H-3,6-dihydro-1,2-thiazin-3-yl, 2H-3,6-dihydro-1,2-thiazin-4-yl, 2H-3,6-dihydro-1,2-thiazin-5-yl, 2H-3,6-dihydro-1,2-thiazin-6-yl, 2H-3,4-dihydro-1,2-oxazine Serie-3-yl, 2H-3,4-dihydro-1,2-oxazine Serie-4-yl, 2H-3,4-dihydro-1,2-oxazine Serie-5-yl, 2H-3,4-dihydro-1,2-oxazine Serie-6-yl, 2H-3,4-dihydro-1,2-thiazin-3-yl, 2H-3,4-dihydro-1,2-thiazin-4-yl, 2H-3,4-dihydro-1,2-thiazin-5-yl, 2H-3,4-dihydro-1,2-thiazin-6-yl, 2,3,4,5-tetrahydropyridine-3-yl, 2,3,4,5-tetrahydropyridine-4-yl, 2,3,4,5-tetrahydropyridine-5-yl, 2,3,4,5-tetrahydropyridine-6-yl, 3,4,5,6-tetrahydropyrimidin-3-yl, 3,4,5,6-tetrahydropyrimidin-4-yl, 1,2,5,6-tetrahydropyridine-3-yl, 1,2,5,6-tetrahydropyrimidin-4-yl, 1,2,5,6-tetrahydropyrimidin-5-yl, 1,2,5,6-tetrahydropyrimidin-6-yl, 1,2,3,6-tetrahydropyrimidin-3-yl, 1,2,3,6-tetrahydropyrimidin-4-yl, 4H-5,6-dihydro-1,3-oxazine Serie-2-yl, 4H-5,6-dihydro-1,3-oxazine Serie-4-yl, 4H-5,6-dihydro-1,3-oxazine Serie-5-yl, 4H-5,6-dihydro-1,3-oxazine Serie-6-yl, 4H-5,6-dihydro-1,3-thiazin-2-yl, 4H-5,6-dihydro-1,3-thiazin-4-yl, 4H-5,6-dihydro-1,3-thiazin-5-yl, 4H-5,6-dihydro-1,3-thiazin-6-yl, 3,4,5,6-tetrahydropyrimidin-2-yl, 3,4,5,6-tetrahydropyrimidin-4-yl, ,4,5,6-tetrahydropyrimidin-5-yl, 3,4,5,6-tetrahydropyrimidin-6-yl, 1,2,3,4-tetrahydropyrazin-2-yl, 1,2,3,4-tetrahydropyrazin-5-yl, 1,2,3,4-tetrahydropyrimidin-2-yl, 1,2,3,4-tetrahydropyrimidin-4-yl, 1,2,3,4-tetrahydropyrimidin-5-yl, 1,2,3,4-tetrahydropyrimidin-6-yl, 2,3-dihydro-1,4-thiazin-2-yl, 2,3-dihydro-1,4-thiazin-3-yl, 2,3-dihydro-1,4-thiazin-5-yl, 2,3-dihydro-1,4-thiazin-6-yl, 2H-1,3-oxazine Serie-2-yl, 2H-1,3-oxazine Serie-4-yl, 2H-1,3-oxazine Serie-5-yl, 2H-1,3-oxazine Serie-6-yl, 2H-1,3-thiazin-2-yl, 2H-1,3-thiazin-4-yl, 2H-1,3-thiazin-5-yl, 2H-1,3-thiazin-6-yl, 4H-1,3-oxazine Serie-2-yl, 4H-1,3-oxazine Serie-4-yl, 4H-1,3-oxazine Serie-5-yl, 4H-1,3-oxazine Serie-6-yl, 4H-1,3-thiazin-2-yl, 4H-1,3-thiazin-4-yl, 4H-1,3-thiazin-5-yl, 4H-1,3-thiazin-6-yl, 6H-1,3-oxazine Serie-2-yl, 6H-1,3-oxazine Serie-4-yl, 6H-1,3-oxazine Serie-5-yl, 6H-1,3-oxazine Serie-6-yl, 6H-1,3-thiazin-2-yl, 6H-1,3-oxazine Serie-4-yl, 6H-1,3-oxazine Serie-5-yl, 6H-1,3-thiazin-6-yl, 2H-1,4-oxazine Serie-2-yl, 2H-1,4-oxazine Serie-3-yl, 2H-1,4-oxazine Serie-5-yl, 2H-1,4-oxazine Serie-6-yl, 2H-1,4-thiazin-2-yl, 2H-1,4-thiazin-3-yl, 2H-1,4-thiazin-5-yl, 2H-1,4-thiazin-6-yl, 4H-1,4-oxazine Serie-2-yl, 4H-1,4-oxazine Serie-3-yl, 4H-1,4-thiazin-2-yl, 4H-1,4-thiazin-3-yl, 1,4-dihydropyridin-3-yl, 1,4-dihydropyridin-4-yl, 1,4-dihydropyridin-5-yl, 1,4-dihydropyridin-6-yl, 1,4-dihydropyridin-2-yl, 1,2-dihydropyridin-2-yl, 1,2-dihydropyridin-3-yl, 1,2-dihydropyridin-5-yl, 1,2-dihydropyridin-6-yl, 1,4-dihydropyrimidine-2-yl, 1,4-dihydropyrimidine-4-yl, 1,4-dihydropyrimidine-5-yl, 1,4-dihydropyrimidine-6-yl, 3,4-dihydropyrimidine-2-yl, 3,4-dihydropyrimidine-4-yl, 3,4-dihydropyrimidine-5-yl or 3,4-dihydropyrimidine-6-yl;

N-linked, 5-membered �aztechno unsaturated cycles, such as 2,3-dihydro-1H-pyrrol-1-yl, 2,5-dihydro-1H-pyrrol-1-yl, 4,5-dihydro-1H-pyrazol-1-yl, 2,5-dihydro-1H-pyrazol-1-yl, 2,3-dihydro-1H-pyrazol-1-yl, 2,5-dihydroisoxazole-2-yl, 2,3-dihydroisoxazole-2-yl, 2,5-dihydrothiazolo-2-yl, 2,3-dihydroisoxazole-2-yl, 4,5-dihydro-1H-imidazol-1-yl, 2,5-dihydro-1H-imidazol-1-yl, 2,3-dihydro-1H-imidazol-1-yl, 2,3-dihydrooxazolo-3-yl, 2,3-dihydrothiazolo-3-yl;

N-linked 6-membered partially unsaturated cycles, such as 1,2,3,4-tetrahydropiridine-1-yl, 1,2,5,6-tetrahydropiridine-1-yl, 1,4-dihydropyridine-1-yl, 1,2-dihydropyridine-1-yl, 2H-5,6-dihydro-1,2-oxazine Serie-2-yl, 2H-5,6-dihydro-1,2-thiazin-2-yl, 2H-3,6-dihydro-1,2-oxazine Serie-2-yl, 2H-3,6-dihydro-1,2-thiazin-2-yl, 2H-3,4-dihydro-1,2-oxazine Serie-2-yl, 2H-3,4-dihydro-1,2-thiazin-2-yl, 2,3,4,5-tetrahydropyridine-2-yl, 1,2,5,6-tetrahydropyrimidin-1-yl, 1,2,5,6-tetrahydropyrimidin-2-yl, 1,2,3,6-tetrahydropyrimidin-1-yl, 3,4,5,6-tetrahydropyrimidin-3-yl, 1,2,3,4-tetrahydropyrazin-1-yl, 1,2,3,4-tetrahydropyrimidin-1-yl, 1,2,3,4-tetrahydropyrimidin-3-yl, 2,3-dihydro-1,4-thiazin-4-yl, 2H-1,2-oxazine Serie-2-yl, 2H-1,2-thiazin-2-yl, 4H-1,4-oxazine Serie-4-yl, 4H-1,4-thiazin-4-yl, 1,4-dihydropyridin-1-yl, 1,4-dihydropyridin-1-yl, 1,2-dihydropyridin-1-yl, 1,4-dihydropyrimidine-1-yl or 3,4-dihydropyrimidine-3-yl;

C-linked, 5-membered heteroaromatic cycles, such as 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, pyrrol-2-yl, pyrrol-3-yl, pyrazol-3-yl, pyrazol-4-yl, isoxazol-3-yl, izocsazol-4-yl, isoxazol-5-yl,� - thiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, imidazol-2-yl, imidazol-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 1,2,3-oxidiazol-4-yl, 1,2,3-oxidiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,3-thiadiazole-4-yl, 1,2,3-thiadiazole-5-yl, 1,2,4-thiadiazole-3-yl, 1,2,4-thiadiazole-5-yl, 1,3,4-thiadiazolyl-2-yl, 1,2,3-triazole-4-yl, 1,2,4-triazole-3-yl, tetrazol-5-yl;

C-linked 6-membered heteroaromatic cycles, such as pyridin-2-yl, pyridin-3-yl, pyridin-4-yl (4-pyridyl), pyridin-3-yl, pyridazin-4-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyrimidine-5-yl, pyrazine-2-yl, 1,3,5-triazine-2-yl, 1,2,4-triazine-3-yl, 1,2,4-triazine-5-yl, 1,2,4-triazine-6-yl, 1,2,4,5-tetrazin-3-yl;

N-linked, 5-membered heteroaromatic cycles, such as pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, 1,2,3-triazole-1-yl, 1,2,4-triazole-1-yl, tetrazol-1-yl.

Heterocyclyl also includes bicyclic heterocycles, which contain one of the 5 - or 6-membered heterocycles fused with a saturated, unsaturated or aromatic carbocycle, such as benzene, cyclohexane, cyclohexanone or cyclohexadiene ring, or 5 - or 6-membered heterocycle which may be saturated, unsaturated or aromatic. Examples heterocyclyl are chinoline, ethenolysis, indole, indolizine, isoindole, indazole, benzofuran, benzothiazyl, benzo�[b]thiazolyl, benzoxazolyl, benzothiazolyl and benzimidazolyl. Examples of 5 - or 6-membered heteroaromatic compounds containing condensed cycloalkenyl include dihydroindole, dihydroartemisinin, dihydroisoquinolyl, dihydroquinoline, dihydroisoquinoline, bromanil and bromanil.

C3-C12-Heteroaryl represents a heteroaryl diradical. Examples include pyrid-2,5-yl and pyrid-2,4-ilen.

In compounds capable of inhibiting glycine Transporter 1, the variables A, R, R1, W, A1, Q, Y, A2, X1, R2, R3, R4, X2, X3, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16n preferably have the following values, which individually or in combination, represent particular embodiments aminotetraline derivatives of formula (I), (II) or any other formula disclosed herein.

In the above formulas (I) or (II) may be present one or more of the substituents R, R2and/or R3. More specifically, may contain up to 3 substituents R2and up to 6 substituents R3. Preferably there is one substituent R and 1, 2 or 3 substituent R2. Therefore, the formula (I) can be represented as follows:

where a is 1, 2 �whether 3, b is 1, 2, 3, 4, 5 or 6, and c is 1. If there are several radicals R2they may be the same or different. If there are several radicals R3they may be the same or different.

A represents A 5 - or 6-membered ring which comprises the two carbon atoms from cyclopentane, cyclohexane or Cycloheptane fragment, which condenses A. A may be homolliella or heterocyclic ring. The ring may be saturated, unsaturated, non-aromatic or aromatic. In accordance with a specific embodiment A represents a benzene ring. If a is A heterocyclic ring, it may contain 1, 2 or 3 heteroatom as ring atoms, which may be selected, independently of one another, from N, S and O. Preferred heterocyclic rings contain 1 nitrogen atom as ring atom and optionally 1 or 2 further heteroatoms as ring members, which can be chosen, independently from one another from O, S and N. in this way, preferred heterocyclic radicals contain 1 heteroatom as a ring atom, which may be selected from O, S and N, and optionally 1 or 2 additional nitrogen atom as ring members. In accordance with a specific embodiment, A performance�possessing a heterocyclic ring, selected from the group comprising the following 5 - or 6-membered heterocycles:

In these formulas, the hydrogen atoms are not shown. This means that the free valence of the carbon atom or nitrogen may be occupied by a hydrogen atom, R or R2. Accordingly, R and R2can be linked with C or N at any position of the ring A.

An experienced specialist will be clear that some of the above rings may be present in the form of other structures in which the hydrogen atoms are located in positions other than the provisions of the above structures, for example, as shown below:

Preferably, A represents heterocycle selected from the group comprising the following 5 - or 6-membered heterocycles:

In accordance with another specific embodiment, A represents heterocycle selected from the group comprising the following 5 - or 6-membered heterocycles:

In accordance with a preferred embodiment A represents heterocycle selected from the group comprising the following 5 - or 6-membered heterocycles:

If the ring A represents A 5-membered heterocycle, preferably R is associated with G1or G2in particular, with G2 :

In the formulae (G1G2and G3independently represent-CH=, -CH2-, -N=, -NH-, S or O, the dotted line indicates that the bond may be single or double, and R3, R4, X2, X3, R5have the values listed in this document.

If the ring A represents a 6-membered heterocycle, preferably R is associated with G1or G2in particular, with G2:

In the formulae (G1G2G3and G4independently represent-CH=, -CH2-, -N=, -NH-, S or O, the dotted line indicates that the bond may be single or double, and R3, R4, X2, X3, R5have the values listed in this document.

Heterocyclic compounds containing the following partial structures are preferred:

Heterocyclic compounds containing the following partial structure are particularly preferred:

In the above formulas, R and R2have the values listed in this document. If there are several radicals R2they may be the same or different.

In �accordance with the specific embodiment, pictured above is an incomplete structure condensed with cyclohexanebis fragment (i.e., n is equal to 1). This applies to preferred and specific embodiments of ring A.

In accordance with one embodiment R represents cyano.

Preferably, R denotes the R1-W-A1-Q-Y-A2-X1-, and A, R1, W, A1, Q, Y, A2, X1, R2, R3, R4a, R4b, X2, X3, R5have the values listed in this document.

R1denotes hydrogen, C1-C6-alkyl (e.g., methyl, ethyl, n-propyl, isopropyl or sec-butyl, another example is n-butyl or n-pentyl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopentylmethyl or cyclohexylmethyl, is another example cyclopropylmethyl), halogenated C1-C6-alkyl (e.g. 3-forprom-1-yl, 3-chlorpro-1-yl or 3,3,3-Cryptocom-1-yl), hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl (e.g. ethoxyethyl), amino-C1-C4-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6-alkylcarboxylic-C1-C4-alkyl, C1-C6-allyloxycarbonyl-C1-C4-alkyl, C1-C6-alkylaminocarbonyl-C1-C4-alkyl, �and-C 1-C6-alkylaminocarbonyl-C1-C4-alkyl, C1-C6-alkylsulfonyl-C1-C4-alkyl, (optionally substituted C6-C12-aryl-C1-C6-alkyl)amino-C1-C4-alkyl, optionally substituted C6-C12-aryl-C1-C4-alkyl, optionally substituted C3-C12-heterocyclyl-C1-C4-alkyl, C3-C12-cycloalkyl (e.g., cyclopropyl or cyclobutyl), C1-C6-alkylsulphonyl, C1-C6-alkoxycarbonyl, halogenated C1-C6-alkoxycarbonyl, C6-C12-aryloxyalkyl, aminocarbonyl, C1-C6-alkylaminocarbonyl, (halogenated C1-C4-alkyl)aminocarbonyl, C6-C12-allumination, C2-C6-alkenyl (e.g. prop-1,2-EN-1-yl), C2-C6-alkynyl, optionally substituted C6-C12-aryl (e.g., phenyl, another example is 2-methylphenyl), hydroxy, C1-C6-alkoxy (e.g. tert-bucalossi), halogenated C1-C6-alkoxy, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, amino-C1-C4-alkoxy, C1-C6-alkylamino-C1-C4-alkoxy, di-C1-C6-alkylamino-C1-C4-alkoxy, C1-C6-alkylarene�amino-C 1-C4-alkoxy, C6-C12-arylcarboxamide-C1-C4-alkoxy, C1-C6-alkoxycarbonyl-C1-C4-alkoxy, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylsulfonyl-C1-C4-alkoxy, (halogenated C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C6-C12-arylsulfonamides-C1-C4-alkoxy, (C6-C12-aryl-C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C3-C12-geterotsiklicheskie-C1-C4-alkoxy, C3-C12-heterocyclyl-C1-C4-alkoxy, C6-C12-aryloxy, C3-C12-heterocyclics, C1-C6-alkylthio, halogenated C1-C6-alkylthio, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-(C1-C6-alkylamino (e.g., dimethylamino), di-(halogenated C1-C6-alkyl)amino, C1-C6-alkylcarboxylic, (halogenated C1-C6)-alkyl)carbylamine, C6-C12-arylcarboxamide, C1-C6-alkylsulfonyl, (halogenated C1-C6-alkyl)sulfonylamino, C6-C12-arylsulfonyl or optionally substituted C3-C12-heterocyclyl (e.g., 3-pyridyl, 2-�Anil, 4-methyl-2-thienyl, 5-methyl-2-thienyl, 5-chloro-2-thienyl, 2,5-dimethyl-3-thienyl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-ethyl-1,2-diazol-4-yl, 1-deformity-1,2-diazol-4-yl, 2-methyl-1,3-diazol-4-yl, 1-methyl-1,3-diazol-4-yl, 2-methyl-1,3-thiazol-5-yl, 2,4-dimethyl-1,3-thiazol-5-yl or 3-pyrrolidinyl, other examples are 1-methyl-pyrrol-3-yl, 2-pyridyl, 1-methyl-1,2-diazol-3-yl, 1-methyl-3-trifluoromethyl-1,2-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 5-methylisoxazol-3-yl or 1-methyl-1,2,4-triazole-3-yl). In addition, R1it can also mean the three-(C1-C4-alkyl)-silyl-C1-C4-alkyl (e.g. trimethylsilylmethyl). Preferably, R1represents C1-C6-alkyl (e.g., methyl, ethyl, n-propyl, isopropyl or sec-butyl, another example is n-butyl or n-pentyl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopentylmethyl or cyclohexylmethyl, is another example cyclopropylmethyl), halogenated C1-C6-alkyl (e.g. 3-forprom-1-yl, 3-chlorpro-1-yl or 3,3,3-Cryptocom-1-yl), C1-C6-alkoxy-C1-C4-alkyl (e.g. ethoxyethyl), amino-C1-C4-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6-allyloxycarbonyl-C1-C4-alkyl, C1-C6-alkylaminocarbonyl-C -C4-alkyl, C6-C12-aryl-C1-C4-alkyl, C3-C12-cycloalkyl (e.g., cyclopropyl or cyclobutyl), C2-C6-alkenyl (e.g. prop-1,2-EN-1-yl), optionally substituted C6-C12-aryl (e.g. phenyl), hydroxy, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-(C1-C6-alkylamino or optionally substituted C3-C12-heterocyclyl (e.g., 3-pyridyl, 2-thienyl, 4-methyl-2-thienyl, 5-methyl-2-thienyl, 5-chloro-2-thienyl, 2,5-dimethyl-3-thienyl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-ethyl-1,2-diazol-4-yl, 1-deformity-1,2-diazol-4-yl, 2-methyl-1,3-diazol-4-yl, 1-methyl-1,3-diazol-4-yl, 2-methyl-1,3-thiazol-5-yl, 2,4-dimethyl-1,3-thiazol-5-yl or 3-pyrrolidinyl). More preferably, R1denotes tri-(C1-C4-alkyl)-silyl-C1-C4-alkyl (e.g. trimethylsilylmethyl).

In particular, R1represents C1-C6-alkyl (e.g., methyl, ethyl, n-propyl, isopropyl or sec-butyl, another example is n-butyl or n-pentyl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopentylmethyl or cyclohexylmethyl, is another example cyclopropylmethyl), halogenated C1-C6-alkyl (e.g. 3-forprom-1-yl, 3-chlorpro-1-yl or 3,3,3-Cryptocom-1-yl), C3-C12-cycloalkyl (for example, Cyclops�drank or cyclobutyl), C2-C6-alkenyl (e.g. prop-1,2-EN-1-yl), optionally substituted C6-C12-aryl (e.g., phenyl), or optionally substituted C3-C12-heterocyclyl (e.g., 3-pyridyl, 2-thienyl, 4-methyl-2-thienyl, 5-methyl-2-thienyl, 5-chloro-2-thienyl, 2,5-dimethyl-3-thienyl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-ethyl-1,2-diazol-4-yl, 1-deformity-1,2-diazol-4-yl, 2-methyl-1,3-diazol-4-yl, 1-methyl-1,3-diazol-4-yl, 2-methyl-1,3-thiazol-5-yl, 2,4-dimethyl-1,3-thiazol-5-yl or 3-pyrrolidinyl). In particular, R1it can also mean the three-(C1-C4-alkyl)silyl-C1-C4-alkyl (e.g. trimethylsilylmethyl).

In relation to R1substituted C6-C12-aryl in particular includes C6-C12-aryl, such as phenyl or naphthyl, substituted 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl, C1-C4-halogenated, cyano, C1-C4-alkoxy, C1-C4-halogenoalkane, amino, C1-C4-alkylamino, C1-C4-dialkylamino, morpholino and piperidinyl. This relates to substituted C6-C12the aryl included in the substituted C6-C12-aryl-C1-C4-alkyl.

In relation to R1substituted C3-C12-heterocyclyl, in particular, includes the C3-C12-heterocyclyl, such as pyridyl, thienyl, �azolyl, chinoline, piperidinyl, piperazinyl or morpholinyl (other examples of such C3-C12-heterocyclyl are pyrrolyl, isoxazolyl and triazolyl), substituted 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl, C1-C4-halogenated, C1-C4-alkoxycarbonyl, cyano, C1-C4-alkoxy, C1-C4-halogenoalkane, C1-C4-alkylsulfonyl, amino, C1-C4-alkylamino, C1-C4-dialkylamino, C6-C12-arylamino and C3-C12-heterocyclyl (for example, morpholino or piperidinyl). This relates to substituted C3-C12-heteroaryl included in the substituted C3-C12-heteroaryl-C1-C4-alkyl.

In accordance with one embodiment W represents-NR8-, and Y represents a bond. In accordance with an alternative embodiment W represents a bond and Y represents-NR9-. In accordance with another alternative embodiment W represents a bond and Y represents a bond, especially if R1denotes a radical linked to the nitrogen atom, for example, associated with the nitrogen atom heterocyclyl, such as piperazinyl or morpholinyl.

In accordance with one embodiment Q represents-S(O)2-. In accordance with an alternative embodiment Q represents-C(O)-.

According to�a particular embodiment,- W-A 1-Q-Y - represents-W-A1-S(O)2-NR9-, -NR8-S(O)2-, -A1-S(O)2- or-S(O)2-. In accordance with another specific embodiment-W-A1-Q-Y - represents-W-A1-CO-NR9- or-NR8-CO-.

A1denotes optionally substituted C1-C4-alkylen or link. When applied to A1substituted C1-C4-alkylene, in particular, includes the C1-C4-alkylene substituted with 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl and cyano. Preferably, A1is file link. If (A1represents C1-C4-alkylen, W preferably denotes-NR8-.

A2denotes optionally substituted C1-C4-alkylene (for example, 1,2-ethylene or 1,3-propylene), C1-C4-alkylen-CO-, -CO-C1-C4-alkylen, C1-C4-alkylen-O-C1-C4-alkylen, C1-C4-alkylen-NR10-C1-C4-alkylen, optionally substituted C6-C12-Allen, optionally substituted C6-C12-heteroaryl or link. In addition, A2may represent an optionally substituted C2-C4-albaniles or optionally substituted C2-C4-akinyan. Preferably, A2denotes optionally substituted C1-C4-alkyl�h (e.g., 1,2-ethylene or 1,3-propylene). More preferably, A2represents C1-C4-alkylene (for example, 1,2-ethylene or 1,3-propylene). Alternatively, A2preferred designates optionally substituted C6-C12-Allen, in particular, C6-C12-aralen selected from the group including dryer-1,4-ilen and Hairdryer-1,3-yl, or optionally substituted C6-C12-heteroaryl, in particular, C6-C12-heteroaryl selected from the group consisting of pyrid-2,5-yl and pyrid-2,4-ilen. If (A2denotes a bond, X1preferably represents optionally substituted C1-C4-alkylen. Alternatively, if A2denotes a bond, X1denotes, in particular, optionally substituted C2-C4-albaniles or optionally substituted C2-C4-akinyan.

When applied to A2substituted C1-C4-alkylene, in particular, includes the C1-C4-alkylene substituted with 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl, C1-C4-halogenated and cyano.

When applied to A2substituted C2-C4-albaniles or substituted C2-C4-akinyan, in particular, includes the C2-C4-albaniles or C2-C4-akinyan substituted with 1, 2 or 3 substituents, selected and� group, comprising halogen, (C1-C4-alkyl, C1-C4-halogenated and cyano.

When applied to A2substituted C6-C12-Allen, in particular, includes the C6-C12-aralen substituted with 1, 2 or 3 substituents selected from the group comprising C1-C4-alkyl, C1-C4-halogenated, C1-C4-alkoxycarbonyl, cyano, C1-C4-alkoxy, C1-C4-halogenoalkane, C1-C4-alkylsulfonyl, amino, C1-C4-alkylamino, C1-C4-dialkylamino, C6-C12arylamino and C3-C12-heterocyclyl (for example, morpholino or piperidinyl).

When applied to A2substituted C6-C12-heteroaryl, in particular, includes the C6-C12-heteroaryl substituted with 1, 2 or 3 substituents selected from the group comprising C1-C4-alkyl, C1-C4-halogenated, C1-C4-alkoxycarbonyl, cyano, C1-C4-alkoxy, C1-C4-halogenoalkane, C1-C4-alkylsulfonyl, amino, C1-C4-alkylamino, C1-C4-dialkylamino, C6-C12-arylamino and C3-C12-heterocyclyl (for example, morpholino or piperidinyl).

X1denotes-O-, -NR11-, -S - or optionally substituted C1-C4-alkylene (e.g., -CH2-, another example�m is 1,2-ethylene and 1,3-propylene). In relation to X1substituted C1-C4-alkylene, in particular, includes the C1-C4-alkylene substituted with 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl, C1-C4-halogenated and cyano. In addition, X1may represent an optionally substituted C2-C4-albaniles or optionally substituted C2-C4-akinyan (e.g. propylen). In relation to X1substituted C2-C4-albaniles or substituted C2-C4-akinyan, in particular, includes the C2-C4-albaniles or C2-C4-akinyan substituted with 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl, C1-C4-halogenated and cyano. Preferably, X1denotes-O-, -NR11, -S-. More preferably, X1denotes-O-. Alternatively, X1preferably represents optionally substituted C1-C4-alkylene (e.g., -CH2-, 1,2-ethylene and 1,3-propylene).

In accordance with a specific embodiment of A2denotes a bond, and X1denotes optionally substituted C1-C4-alkylen, optionally substituted C2-C4-albaniles or optionally substituted C2-C4-akinyan.

In accordance with the specific waples�of R 1-W-A1-Q-Y-A2-X1denotes R1-S(O)2-NH-A2-X1-, R1-NH-S(O)2-A2-X1-, R1-C(O)-NH-A2-X1or R1-NH-C(O)-A2-X1-.

In accordance with a specific embodiment of the structural element-Y-A2-X1- contains at least 2, 3 or 4 atoms in the main chain. In accordance with another specific embodiment of the structural element-Y-A2-X1- contains up to 4, 5 or 6 atoms in the main chain, for example, from 2 to 6, 2 to 5 or from 2 to 4 atoms in the main chain, preferably 2, 3 or 4 atoms in the main chain.

In accordance with another particular embodiment,- Y-A2-X1- represents C1-C4-alkylen-O - or-NR9-C1-C4-alkylen-O-, and-Y-A2-X1preferably contains from 2 to 6, 3 to 5, particularly preferably 4 atoms in the main chain. Specific examples of-Y-A2-X1include -(CH2)3-O - and-NR9-(CH2)2-O-. In this particular embodiment, R9has the values defined herein and preferably R9denotes hydrogen, C1-C6-alkyl (e.g. methyl or ethyl) or C3-C12-cycloalkyl (e.g., cyclopropyl), or R9represents C1-C4-alkylen associated with the carbon atom A2that means C1-C -alkylen.

In accordance with another particular embodiment,- Y-A2-X1- denotes-NR9-C1-C4-alkylene- (e.g.-NH-CH2-, another example is-NH-(CH2)2- or-NH-(CH2)3-), wherein-Y-A2-X1preferably contains from 2 to 6, 2 to 5, 2 to 4, particularly preferably 2, 3 or 4 atoms in the main chain. In this particular embodiment, R9has the values defined herein and preferably R9denotes hydrogen, C1-C6-alkyl (e.g. methyl or ethyl) or C3-C12-cycloalkyl (e.g., cyclopropyl); or R9represents C1-C4-alkylen associated with the carbon atom of X1that means C1-C4-alkylen. If A represents heterocycl specified embodiment-Y-A2-X1- is especially preferred.

In accordance with another particular embodiment,- Y-A2-X1- denotes-NR9-C2-C4-albaniles - or-NR9-C2-C4-akinyan- (e.g.-NH-CH2-C≡C-), wherein-Y-A2-X1preferably contains from 2 to 6, 3 to 5, and particularly preferably 4 atoms in the main chain. In this particular embodiment, R9has the values defined herein and preferably R9denotes hydrogen, C1 6-alkyl (e.g. methyl or ethyl) or C3-C12-cycloalkyl (e.g., cyclopropyl or cyclobutyl). If A denotes heterocycl, this embodiment-Y-A2-X1- is especially preferred.

In accordance with another particular embodiment,- Y-A2-X1- represents C1-C4-alkylene- (e.g., -(CH2)2-), wherein-Y-A2-X1preferably contains from 2 to 6, 2 to 5, from 2 to 4 and particularly preferably 2 atoms in the main chain. If A denotes heterocycl, this embodiment-Y-A2-X1- is especially preferred.

In accordance with another specific embodiment of the structural motif-Y-A2-X1-, disclosed in this description, is linked to Q to form-S(O)2- or-C(O)-. Specific examples of this embodiment include heterocyclic compounds of the present invention, where R denotes R1-S(O)2-Y-A2-X1or R1-C(O)-Y-A2-X1.

The radical R and, in particular, the radical R1-W-A1-Q-Y-A2-X1- basically can be associated with 5, 6, 7 or 8 position aminotetraline skeleton:

In the above formulas, R1, W, A1, Q, Y, A2, X1, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document�.

Other specific examples include heterocyclic compounds of the above formulas, where the radical R1-W-A1-Q-Y-A2-X1- replaced by the radical-CN.

Aminotetraline derivatives containing the radical R1-W-A1-Q-Y-A2-X1- (or the radical-CN) in 5, 6, 7-position, are preferred.

Especially preferred are aminotetraline derivatives containing the radical R1-W-A1-Q-Y-A2-X1- (or the radical-CN) in the 7-position.

In addition to the radical R1-W-A1-Q-Y-A2-X1- (or the radical-CN) aminotetraline derivatives of this invention can contain one or more other substituents linked to the ring A. in these positions, the skeleton aminotetraline derivatives may be substituted by one or more radicals R2. If there are several radicals R2they may be the same or different. In particular, 5, 6, 7 and/or 8 position aminotetraline skeleton may be substituted by one or more radicals R2. Thus, aminotetraline derivatives of this invention can be represented by one of the following formulas:

or relevant formulas, �de radical, R 1-W-A1-Q-Y-A2-X1- replaced by the radical-CN,

where R2a, R2b, R2c, R2dindependently have one of the meanings defined for R2and R1, W, A1, Q, Y, A2, X1, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

R2denotes hydrogen, halogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, -CN, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C2-C6-alkenylacyl, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylcarboxylic, C1-C6-alkylthio, C1-C6-alkylsulfonyl, C1-C6-alkylsulfonyl, aminosulfonyl, amino, C1-C6-alkylamino, C2-C6-alkenylamine, nitro or optionally substituted C3-C12-heterocyclyl, or two radicals R2together with the ring atoms of A to which they are attached, form a 5 - or 6-membered ring.

Optionally substituted 5 - or 6-membered ring formed by the two radicals R2together with the ring atoms of A to which they are linked, p�establet a, for example, a benzene ring.

In relation to R2substituted C6-C12-aryl in particular includes C6-C12-aryl, such as phenyl, substituted by 1, 2 or 3 substituents selected from the group comprising halogen and (C1-C4-alkyl, C1-C4-halogenated, cyano, C1-C4-alkoxy and C1-C4-halogenoalkane.

In relation to R2substituted C3-C12-heterocyclyl, in particular, includes the C3-C12-heterocyclyl, such as morpholinyl, pyrrolidinyl and piperidinyl substituted with 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl, C1-C4-halogenated, cyano, C1-C4-alkoxy and C1-C4-halogenoalkane.

Preferably, R2denotes hydrogen, halogen or C1-C6-alkoxy. In particular, R2denotes hydrogen.

In accordance with a specific embodiment, aminotetraline derivatives of this invention have one of the following formulas:

or they can be represented by formulas, where the radical R1-W-A1-Q-Y-A2-X1- replaced by the radical-CN,

where R1, W, A1, Q, Y, A2, X1, R2, R3, R4a, R4b, X2, X3, R5/sup> n have the values listed in this document.

1, 2, 3, 4 and/or 5 position aminotetraline derivatives of this invention can be substituted by one or more radicals R3. If there are several radicals R3they may be the same or different. Thus, aminotetraline derivatives of this invention can be represented by the following formula:

where R3a, R3b, R3c, R3d, R3e, R3findependently have one of the meanings defined for R3and A, R, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

In accordance with a specific embodiment, aminotetraline derivatives of this invention have one of the following formulas:

where R3a, R3b, R3findependently have the meaning as defined for R3and A, R, R2, R3, R4a, R4b, X2, X3, R5n have the values listed in this document.

R3denotes hydrogen, halogen, C1-C6-alkyl, C1-C6-alkoxy, or two radicals R3together with the carbon atom to which they are attached, form a carbonyl group.

Preferably, R3denotes hydrogen or C1- 6-alkyl. In particular, R3denotes hydrogen.

R4adenotes hydrogen, C1-C6-alkyl (e.g., methyl, ethyl, n-propyl or isopropyl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopropylmethyl), halogenated C1-C4-alkyl (e.g. 2-fluoroethyl or 2,2,2-trifluoroethyl), hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, -CHO, C1-C4-alkylsulphonyl (e.g. methylcarbamyl or isopropylcarbonate, another example is ethylcarbazole), (halogenated C1-C4-alkyl)carbonyl (e.g., formational, deformational or triftormetilfullerenov, another example is 1,1,1-cryptonet-2-ylcarbonyl or 1,1,1-Cryptocom-3-ylcarbonyl), C6-C12-arylcarbamoyl (e.g. phenylcarbamoyl), C1-C4-alkoxycarbonyl (e.g. ethoxycarbonyl or tert-butyloxycarbonyl), C6-C12-aryloxyalkyl (e.g. phenoxycarbonyl), C1-C6-alkylaminocarbonyl, C2-C6-alkenyl, -C(=NH)NH2, -C(=NH)NHCN, C1-C6-alkylsulfonyl, C6-C12-arylsulfonyl, amino, -NO or C3-C12-heterocyclyl.

Preferably, R4adenotes hydrogen, C1-C6-alkyl (e.g., methyl, ethyl, n-propyl or isopro�yl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopropylmethyl), halogenated C1-C4-alkyl (e.g. 2-fluoroethyl or 2,2,2-trifluoroethyl), amino-C1-C4-alkyl, CH2CN, C1-C4-alkylsulphonyl (e.g. methylcarbamyl or isopropylcarbonate), (halogenated C1-C4-alkyl)carbonyl (e.g., formational, deformational or triftormetilfullerenov), C6-C12-arylcarbamoyl (e.g. phenylcarbamoyl), C1-C4-alkoxycarbonyl (e.g. ethoxycarbonyl or tert-butyloxycarbonyl), C6-C12-aryloxyalkyl (e.g. phenoxycarbonyl), -C(=NH)NH2, -C(=NH)NHCN, C1-C6-alkylsulfonyl, amino, -NO or C3-C12-heterocyclyl. More preferably, if R1refers to-CHO.

In particular, R4adenotes hydrogen, C1-C6-alkyl (e.g., methyl, ethyl, n-propyl or isopropyl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopropylmethyl), halogenated C1-C4-alkyl (e.g. 2-fluoroethyl or 2,2,2-trifluoroethyl), C1-C4-alkylsulphonyl (e.g. methylcarbamyl or isopropylcarbonate), (halogenated C1-C4-alkyl)carbonyl (e.g., formational, deformational or triftormetilfullerenov), C6-C12-arylcarbamoyl (e.g.�measures phenylcarbinol), C1-C4-alkoxycarbonyl (e.g. ethoxycarbonyl or tert-butyloxycarbonyl), C6-C12-aryloxyalkyl (e.g. phenoxycarbonyl). In particular, R4ait can also mean-CHO.

R4bdenotes hydrogen, C1-C6-alkyl (e.g., methyl, is another example ethyl), halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, -CHO, C1-C4-alkylsulphonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbamoyl, C1-C4-alkoxycarbonyl, C6-C12-aryloxyalkyl, C1-C6-alkylaminocarbonyl, C2-C6-alkenyl, -C(=NH)NH2, -C(=NH)NHCN, C1-C6-alkylsulfonyl, C6-C12-arylsulfonyl, amino, -NO or C3-C12-heterocyclyl.

Preferably, R4bdenotes hydrogen, C1-C6-alkyl (e.g., methyl, is another example ethyl).

Alternatively, R4a, R4btogether represent optionally substituted C1-C6-alkylene (for example, 1,4-butylene, another example is 1,3-propylene, 2-Forbot-1,4-yl or 1-exabot-1,4-ilen), where one-CH2- C1-C4-alkylene may be replaced by oxygen atom (e.g., -CH2CH 2-O-CH2-CH2-) or-NR16.

X2denotes-O-, -NR6-, -S -, > CR12aR12bor a link. Preferably, X2represents the >CR12aR12b.

X3denotes-O-, -NR7-, -S -, > CR13aR13bor a link. Preferably, X3denotes the connection.

Thus, preferably, if X2represents the >CR12aR12band X3denotes the connection.

R12adenotes hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy. Preferably, R12adenotes hydrogen or C1-C6-alkyl.

R13adenotes hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy. Preferably, R13adenotes hydrogen or C1-C6-alkyl.

In relation to R12aand R13asubstituted C1-C6-alkyl in particular includes C1-C6-alkyl, Samedan�1, 2 or 3 substituents selected from the group comprising halogen, hydroxy, C1-C4-alkoxy and amino.

In relation to R12aand R13asubstituted C6-C12-aryl in particular includes C6-C12-aryl, such as phenyl, substituted by 1, 2 or 3 substituents selected from the group comprising C1-C4-alkyl, C1-C4-halogenated, cyano, C1-C4-alkoxy and C1-C4-halogenoalkane.

R12bdenotes hydrogen or C1-C6-alkyl. In accordance with a specific embodiment R12bdenotes hydrogen.

R13bdenotes hydrogen or C1-C6-alkyl. In accordance with a specific embodiment R13bdenotes hydrogen.

Alternatively, R12aand R12bor R13aand R13btogether denote carbonyl or, preferably, optionally substituted C1-C4-alkylene (e.g. 1,3-propylene), wherein one-CH2- C1-C4-alkylene may be replaced by oxygen atom or-NR14-.

In relation to R12aand R12bor R13aand R13bsubstituted C1-C4-alkylene, in particular, includes the C1-C4-alkylene substituted with 1, 2 or 3 substituents selected from the group comprising halogen, (C1-C4-alkyl, C1-C4-halogenated, cyano, C1-C4-alkoxy C 1-C4-halogenoalkane.

In accordance with a specific embodiment R12arepresents C1-C6-alkyl, and R12bdenotes hydrogen or C1-C6-alkyl, or R13arepresents C1-C6-alkyl, and R13bdenotes hydrogen or C1-C6-alkyl.

In accordance with another specific embodiment, R12adenotes hydrogen, and R12bdenotes hydrogen, or R13adenotes hydrogen, and R13bdenotes hydrogen.

In accordance with another specific embodiment R12aand R12btogether denote an optionally substituted 1,3-propylene, or R13aand R13btogether denote an optionally substituted 1,3-propylene.

R5denotes optionally substituted C6-C12-aryl (e.g. phenyl, 3-chlorophenyl, 3,4-dichlorophenyl or 2,4-dichlorophenyl, another example is 2-fluorophenyl, 2-chlorophenyl, 3-fluorophenyl, 3-chlorophenyl; 3-cyanophenyl, 3-methylphenyl, 3-triptoreline, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methoxyphenyl, 3,4-differenl, 3.5-differenl, 3-fluoro-5-chlorophenyl, 3-chloro-4-fluorophenyl), optionally substituted C3-C12-cycloalkyl (e.g., cyclohexyl) or optionally substituted C3-C12-heterocyclyl.

In relation to R5substituted C3-C12-cycloalkyl, in particular, includes the C3-C121-C6-alkyl, halogenated C1-C6-alkyl, CN, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, amino, C1-C6-alkylamino, di-C1-C6-alkylamino and C3-C12-heterocyclyl.

In relation to R5substituted C6-C12-aryl in particular includes C6-C12-aryl, such as phenyl, substituted by 1, 2 or 3 substituents selected from the group comprising halogen (e.g., F, Cl, Br), optionally substituted C1-C6-alkyl (e.g. methyl), halogenated C1-C6-alkyl (e.g. trifluoromethyl), CN, hydroxy, C1-C6-alkoxy (e.g., methoxy), halogenated C1-C6-alkoxy, amino, C1-C6-alkylamino, di-C1-C6-alkylamino and C3-C12-heterocyclyl.

In relation to R5substituted C3-C12-heterocyclyl, in particular, includes the C3-C12-heterocyclyl substituted with 1, 2 or 3 substituents selected from the group comprising halogen, optionally substituted C1-C6-alkyl, halogenated C1-C6-alkyl, CN, hydroxy, C1-C6-alkoxy, halogenated C1-Csub> 6-alkoxy, amino, C1-C6-alkylamino, di-C1-C6-alkylamino and C3-C12-heterocyclyl.

In relation to R5, C3-C12-heterocyclyl, in particular, represents C3-C12-heteroaryl.

Preferably, R5denotes optionally substituted C6-C12-aryl, in particular, as in aminotetraline derivatives of the formula:

where A, R, R2, R3, R4a, R4b, X2, X3n have the values listed in this document, and R15a, R15b, R15c, R15d, R15eindependently denote hydrogen, halogen (e.g. F, Cl or Br), optionally substituted C1-C6-alkyl (e.g. methyl), halogenated C1-C6-alkyl (e.g. trifluoromethyl), CN, hydroxy, C1-C6-alkoxy (e.g. methoxy), amino, C1-C6-alkylamino, di-C1-C6-alkylamino or C3-C12-heterocyclyl.

In accordance with a specific embodiment of the present invention relates to aminotetraline derivative of the formula:

where A, R, R2, R3, R4a, R4b, R5n have the values listed in this document, and R5preferably represents optionally substituted aryl, in particular optionally salmenniemi, as described in this document.

In relation to R5or R15a, R15b, R15c, R15d, R15esubstituted C1-C6-alkyl in particular includes C1-C6-alkyl, especially C1-C4-alkyl, substituted 1, 2 or 3 substituents selected from the group comprising hydroxy, C1-C6-alkoxy, amino, C1-C6-alkylamino, di-C1-C6-alkylamino and C3-C12-heterocyclyl (e.g. morpholinyl or piperidinyl).

In accordance with a specific embodiment R15a, R15b, R15d, R15edenote hydrogen, and R15cdifferent from hydrogen (para-mono-substitution).

In accordance with another specific embodiment R15a, R15c, R15d, R15edenote hydrogen, and R15bdifferent from hydrogen (meta-mono-substitution).

In relation to R15a, R15b, R15c, R15d, R15e, C3-C12-heterocyclyl, in particular, includes morpholinyl, imidazolyl and pyrazolyl.

The index n is 0, 1 or 2. In accordance with a particular embodiment n is 1.

R6denotes hydrogen or C1-C6-alkyl. Preferably, R6denotes hydrogen.

R7denotes hydrogen or C1-C6-alkyl. Preferably, R7denotes hydrogen.

R8denotes hydrogen or C1-C 6-alkyl. Preferably, R8denotes hydrogen.

R9denotes hydrogen, C1-C6-alkyl (e.g. methyl or ethyl), C3-C12-cycloalkyl (e.g., cyclopropyl), amino-C1-C6-alkyl, optionally substituted C6-C12-aryl-C1-C4-alkyl or C3-C12-heterocyclyl (for example, 3-azetidinol). Preferably, R9denotes hydrogen or C1-C6-alkyl (e.g. methyl or ethyl).

In accordance with a specific embodiment R9and R1together denote C1-C4-alkylene (for example, 1,3-propylene, another example is 1,2-ethylene), so that R9and R1together with the atom Q is linked to R1and the nitrogen atom is linked to R9form a heterocyclic ring containing, in particular, 4, 5 or 6 ring atoms (including the nitrogen atom and Q). Considering the fact that W and A1both represent a bond, such a ring may be represented by the following partial structure:

where Q has the values defined in this document (e.g., a represents S(O)2), and n is 0, 1, 2, 3, or 4.

In accordance with another specific embodiment R9represents C1-C4-alkylene (e.g. methylene or 1,3-propylene) that is bound to a carbon atom of A2and A2denotes Csub> 1-C4-alkylen, so that R9and at least part of A2together with the nitrogen atom, is linked to R9form a N-containing heterocyclic ring consisting of, in particular, 4, 5, 6 or 7 ring atoms (including the nitrogen atom). Such a ring may be represented by the following partial structure:

where R1, W, A1, Q and X1have the values listed in this document, p is 1 or 2, r is 0, 1 or 2, and q is 0, 1 or 2. In this particular embodiment X1preferably denotes-O-. Specific combinations of p, r and q include p=1, r=0, q=1; and p=1, r=0, q=0. Alternative p is 0, r is 3 and q is 1, and X1preferably denotes-O-.

In accordance with another specific embodiment R9represents C1-C4-alkylene (e.g. methylene or 1,3-propylene) that is bound to a carbon atom of X1and X1represents C1-C4-alkylene (e.g. 1,2-ethylene), so that R9and at least part of the X1together with the nitrogen atom, is linked to R9form a N-containing heterocyclic ring consisting of, in particular, 4, 5, 6 or 7 ring atoms (including the nitrogen atom). Given the fact that A2means a connection, such a ring may be represented by the following partial structure:

�de R 1, W, A1, Q and X1have the values listed in this document, p is 1 or 2, r is 0, 1 or 2, and q is 0, 1 or 2. Specific combinations of p, r and q include p=1, r=0, q=0.

R10denotes hydrogen, C1-C6-alkyl or C1-C6-alkylsulfonyl. Preferably, R10denotes hydrogen.

R11denotes hydrogen or C1-C6-alkyl. Preferably, R11denotes hydrogen.

Alternatively, R9, R11together denote C1-C4-alkylene (e.g., ethylene).

R14denotes hydrogen or C1-C6-alkyl. Preferably, R14denotes hydrogen.

R15denotes hydrogen or C1-C6-alkyl. Preferably, R15denotes hydrogen.

R16denotes hydrogen or C1-C6-alkyl. Preferably, R16denotes hydrogen.

In specific embodiments aminotetraline derivatives of the invention

A denotes a 5 - or 6-membered ring;

R denotes the R1-W-A1-Q-Y-A2-X1- or-CN;

R1denotes hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl-C1-C4-alkyl, halogenated C1-C6-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C6-Ala�lamino-C 1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6-alkylcarboxylic-C1-C4-alkyl, C1-C6-allyloxycarbonyl-C1-C4-alkyl, C1-C6-alkylaminocarbonyl-C1-C4-alkyl, di-C1-C6-alkylaminocarbonyl-C1-C4-alkyl, C1-C6-alkylsulfonyl-C1-C4-alkyl, (optionally substituted C6-C12-aryl-C1-C6-alkyl)amino-C1-C4-alkyl, optionally substituted C6-C12-aryl-C1-C4-alkyl, optionally substituted C3-C12-heterocyclyl-C1-C4-alkyl, C3-C12-cycloalkyl, C1-C6-alkylsulphonyl, C1-C6-alkoxycarbonyl, halogenated C1-C6-alkoxycarbonyl, C6-C12-aryloxyalkyl, aminocarbonyl, C1-C6-alkylaminocarbonyl, (halogenated C1-C4-alkyl)aminocarbonyl, C6-C12-allumination, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, amino-C1-C4-alkoxy, C1-C -alkylamino-C1-C4-alkoxy, di-C1-C6-alkylamino-C1-C4-alkoxy, C1-C6-alkylcarboxylic-C1-C4-alkoxy, C6-C12-arylcarboxamide-C1-C4-alkoxy, C1-C6-alkoxycarbonyl-C1-C4-alkoxy, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylsulfonyl-C1-C4-alkoxy, (halogenated C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C6-C12-arylsulfonamides-C1-C4-alkoxy, (C6-C12-aryl-C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C3-C12-geterotsiklicheskie-C1-C4-alkoxy, C3-C12-heterocyclyl-C1-C4-alkoxy, C6-C12-aryloxy, C3-C12-heterocyclics, C1-C6-alkylthio, halogenated C1-C6-alkylthio, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-(C1-C6-alkylamino, di-(halogenated C1-C6-alkyl)amino, C1-C6-alkylcarboxylic, (halogenated C1-C6-alkyl)carbylamine, C6-C12-arylcarboxamide, C1-C6-alkylsulfonyl, (halogenated C1-C6-alkyl)sulfonylamino, C6- 12-arylsulfonyl or optionally substituted C3-C12-heterocyclyl;

W represents-NR8or communication;

A1denotes optionally substituted C1-C4-alkylen or communication;

Q represents-S(O)2- or-C(O)-;

Y represents-NR9or communication;

A2denotes optionally substituted C1-C4-alkylen, C1-C4-alkylen-CO-, -CO-C1-C4-alkylen, C1-C4-alkylen-O-C1-C4-alkylen, C1-C4-alkylen-NR10-C1-C4-alkylen, optionally substituted C6-C12-Allen, optionally substituted C6-C12-heteroaryl or communication;

X1denotes-O-, -NR11-, -S-, optionally substituted C1-C4-alkylen;

R2denotes hydrogen, halogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, -CN, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C2-C6-alkenylacyl, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylcarboxylic, C1-C6-alkylthio, C1-C6-alkylsulfonyl, C1-C6-Alki�sulfonyl, aminosulfonyl, amino, C1-C6-alkylamino, C2-C6-alkenylamine, nitro or optionally substituted C3-C12-heterocyclyl, or two radicals R2together with the ring atoms of A to which they are attached, form a 5 - or 6-membered ring;

R3denotes hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy, or two radicals R3together with the carbon atom to which they are attached, form a carbonyl group;

R4adenotes hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl-C1-C4-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, -CHO, C1-C4-alkylsulphonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbamoyl, C1-C4-alkoxycarbonyl, C6-C12-aryloxyalkyl, C1-C6-alkylaminocarbonyl, C2-C6-alkenyl, -C(=NH)NH2, -C(=NH)NHCN, C1-C6-alkylsulfonyl, C6-C12-arylsulfonyl, amino, -NO or C3-C12-heterocyclyl;

R4bdenotes hydrogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C -alkyl, amino-C1-C4-alkyl, CH2CN, -CHO, C1-C4-alkylsulphonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbamoyl, C1-C4-alkoxycarbonyl, C6-C12-aryloxyalkyl, C1-C6-alkylaminocarbonyl, C2-C6-alkenyl, -C(=NH)NH2, -C(=NH)NHCN, C1-C6-alkylsulfonyl, C6-C12-arylsulfonyl, amino, -NO or C3-C12-heterocyclyl; or

R4a, R4btogether represent optionally substituted C1-C6-alkylene, where one-CH2- included in the C1-C4-alkylene may be replaced by oxygen atom or-NR16;

X2denotes-O-, -NR6-, -S -, > CR12aR12bor communication;

X3denotes-O-, -NR7-, -S -, > CR13aR13bor communication;

R5denotes optionally substituted C6-C12-aryl, optionally substituted C3-C12-cycloalkyl or optionally substituted C3-C12-heterocyclyl;

n is 0, 1 or 2;

R6denotes hydrogen or C1-C6-alkyl;

R7denotes hydrogen or C1-C6-alkyl;

R8denotes hydrogen or C1-C6-alkyl;

R9denotes hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl, amino-C1-C6-alkyl, n�necessarily substituted C 6-C12-aryl-C1-C4-alkyl; or

R9, R1together denote C1-C4-alkylen; or

R9represents C1-C4-alkylen associated with the carbon atom A2where A2represents C1-C4-alkylen, or to a carbon atom of X1where X1represents C1-C4-alkylen;

R10denotes hydrogen, C1-C6-alkyl or C1-C6-alkylsulfonyl;

R11denotes hydrogen or C1-C6-alkyl, or

R9, R11together denote C1-C4-alkylen,

R12adenotes hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy;

R12bdenotes hydrogen or C1-C6-alkyl, or

R12a, R12btogether denote a carbonyl or optionally substituted C1-C4-alkylene, where one-CH2- included in the C1-C4-alkylene may be replaced by oxygen atom or-NR14-;

R13adenotes hydrogen, optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C 1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy;

R13bdenotes hydrogen or C1-C6-alkyl, or

R13a, R13btogether denote a carbonyl or optionally substituted C1-C4-alkylene, where one-CH2- included in the C1-C4-alkylene may be replaced by oxygen atom or-NR15-;

R14denotes hydrogen or C1-C6-alkyl;

R15denotes hydrogen or C1-C6-alkyl; and

R16denotes hydrogen or C1-C6-alkyl,

or in this description can be specified more accurately determining one or more of the variables A, R, R1, W, A1, Q, Y, A2, X1, R2, R3, R4, X2, X3, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16n.

In other specific embodiments aminotetraline derivatives of the invention

A stands for a benzene ring;

R denotes the R1-W-A1-Q-Y-A2-X1-;

R1represents C1-C6-alkyl (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, n-pentyl), C3-C12-cycloalkyl-C1-C 4-alkyl (e.g. cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl), halogenated C1-C6-alkyl (e.g. 3-forprom-1-yl, 3-chlorpro-1-yl, 3,3,3-Cryptocom-1-yl), tri-(C1-C4-alkyl)silyl-C1-C4-alkyl (e.g. trimethylsilylmethyl), C1-C6-alkoxy-C1-C4-alkyl (e.g. ethoxyethyl), C3-C12-cycloalkyl (e.g., cyclopropyl, cyclobutyl, cyclohexyl), C2-C6-alkenyl (e.g. prop-1,2-EN-1-yl), optionally substituted C6-C12-aryl (e.g., phenyl, 2-methylphenyl) or optionally substituted C3-C12-heterocyclyl (for example, 1-methylpyrrole-3-yl, 2-pyridyl, 3-pyridyl, 2-thienyl, 4-methyl-2-thienyl, 5-methyl-2-thienyl, 5-chloro-2-thienyl, 2,5-dimethyl-3-thienyl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-3-yl, 1-methyl-1,2-diazol-4-yl, 1-ethyl-1,2-diazol-4-yl, 1-deformity-1,2-diazol-4-yl, 1-methyl-3-trifluoromethyl-1,2-diazol-4-yl, 2-methyl-1,3-diazol-4-yl, 1-methyl-1,3-diazol-4-yl, 1,2-dimethyl-1,3-diazol-4-yl, 5-methylisoxazol-3-yl, 2-methyl-1,3-thiazol-5-yl, 2,4-dimethyl-1,3-thiazol-5-yl, 1-methyl-1,2,4-triazole-3-yl, 3-pyrrolidinyl);

W represents a bond;

A1identifies a relationship;

Q represents-S(O)2- or-C(O)-;

Y represents-NR9or communication;

A2represents C1-C4-alkylene (for example, 1,2-ethylene, 1,3-propylene) or a bond;

X1denotes-O - or optionally Zam�by C 1-C4-alkylene (for example, methylene, 1,2-ethylene, 1,3-propylene) or C2-C4-akinyan (e.g. prop-1,2-in-1,3-ilen);

R2denotes hydrogen;

R3denotes hydrogen;

R4adenotes hydrogen, C1-C6-alkyl (e.g., methyl, ethyl, n-propyl, isopropyl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopropylmethyl), halogenated C1-C4-alkyl (e.g. 2-fluoroethyl, 2,2,2-trifluoroethyl), -CHO, C1-C4-alkylsulphonyl (e.g. methylcarbamoyl, ethylcarbonate, isopropylcarbonate), (halogenated C1-C4-alkyl)carbonyl (e.g., formational, deformational, triftormetilfullerenov, 1,1,1-cryptonet-2-ylcarbonyl, 1,1,1-Cryptocom-3-ylcarbonyl), C6-C12-arylcarbamoyl (e.g. phenylcarbamoyl), C1-C4-alkoxycarbonyl (e.g. ethoxycarbonyl, tert-butyloxycarbonyl), C6-C12-aryloxyalkyl (e.g. phenoxycarbonyl);

R4bdenotes hydrogen or C1-C6-alkyl (e.g. methyl, ethyl); or

R4a, R4btogether represent optionally substituted C1-C6-alkylene (for example, 1,3-propylene, 1,4-butylene, 2-Forbot-1,4-yl, 1-oxo-but-1,4-ilen), where one-CH2- included in the C1-C4-alkylene may be replaced by oxygen atom (e.g., -CH2-C 2-O-CH2-CH2-);

X2denotes a CR12aR12b;

X3identifies a relationship;

R5denotes optionally substituted phenyl (e.g. phenyl, 2-fluorophenyl, 2-chlorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-cyanophenyl, 3-methylphenyl, 3-triptoreline, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methoxyphenyl, 3,4-differenl, 3.5-differenl, 3-fluoro-5-chlorophenyl, 3-chloro-4-fluorophenyl, 3,4-dichlorophenyl, 2,4-dichlorophenyl) or optionally substituted C3-C12-cycloalkyl (e.g., cyclohexyl);

n is 1;

R9denotes hydrogen, C1-C6-alkyl (e.g. methyl, ethyl) or C3-C12-cycloalkyl (cyclopropyl), or

R9, R1together denote C1-C4-alkylene (e.g. 1,3-propylene); or

R9represents C1-C4-alkylene (for example, methylene, 1,3-propylene) that is bound to a carbon atom of A2where A2represents C1-C4-alkylene (for example, 1,2-ethylene, 1,3-propylene), or to a carbon atom of X1where X1represents C1-C4-alkylene (e.g. 1,2-ethylene);

R12adenotes hydrogen; and

R12bdenotes hydrogen.

In other specific embodiments aminotetraline derivatives of the invention

A stands for a benzene ring;

R denotes the R1-W-A1-Q-Y-A2-X1-;

R1 1-C6-alkyl (e.g., methyl, ethyl, n-propyl, isopropyl or sec-butyl), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopentylmethyl or cyclohexylmethyl), halogenated C1-C6-alkyl (e.g. 3-forprom-1-yl, 3-chlorpro-1-yl or 3,3,3-Cryptocom-1-yl), C3-C12-cycloalkyl (e.g., cyclopropyl or cyclobutyl), C2-C6-alkenyl (e.g. prop-1,2-EN-1-yl), optionally substituted C6-C12-aryl (e.g., phenyl), or optionally substituted C3-C12-heterocyclyl (e.g., 3-pyridyl, 2-thienyl, 4-methyl-2-thienyl, 5-methyl-2-thienyl, 5-chloro-2-thienyl, 2,5-dimethyl-3-thienyl, 1,2-diazol-4-yl, 1-methyl-1,2-diazol-4-yl, 1-ethyl-1,2-diazol-4-yl, 1-deformity-1,2-diazol-4-yl, 2-methyl-1,3-diazol-4-yl, 1-methyl-1,3-diazol-4-yl, 2-methyl-1,3-thiazol-5-yl, 2,4-dimethyl-1,3-thiazol-5-yl or 3-pyrrolidinyl);

W represents a bond;

A1identifies a relationship;

Q represents-S(O)2- or-C(O)-;

Y represents-NR9or communication;

A2represents C1-C4-alkylene (e.g. methylene or 1,3-propylene) or a bond;

X1denotes-O - or optionally substituted C1-C4-alkylene (e.g., methylene);

R2denotes hydrogen;

R3denotes hydrogen;

R4adenotes hydrogen, C1-C6-alkyl (e.g., methyl, ethyl, n-propyl or isopropyl�), C3-C12-cycloalkyl-C1-C4-alkyl (e.g. cyclopropylmethyl), halogenated C1-C4-alkyl (e.g. 2-fluoroethyl or 2,2,2-trifluoroethyl), C1-C4-alkylsulphonyl (e.g. methylcarbamyl or isopropylcarbonate), (halogenated C1-C4-alkyl)carbonyl (e.g., formational, deformational or triftormetilfullerenov), C6-C12-arylcarbamoyl (e.g. phenylcarbamoyl), C1-C4-alkoxycarbonyl (e.g. ethoxycarbonyl or tert-butyloxycarbonyl), C6-C12-aryloxyalkyl (e.g. phenoxycarbonyl);

R4bdenotes hydrogen or C1-C6-alkyl (e.g., methyl);

X2denotes a CR12aR12b;

X3identifies a relationship;

R5denotes optionally substituted phenyl (e.g. phenyl, 3-chlorophenyl, 3,4-dichlorophenyl or 2,4-dichlorophenyl);

n denotes 1;

R6denotes hydrogen;

R7denotes hydrogen;

R8denotes hydrogen;

R9denotes hydrogen or alkyl (e.g. methyl or ethyl); or

R9, R1together denote C1-C4-alkylene (e.g. 1,3-propylene); or

R9represents C1-C4-alkylene (e.g. methylene or 1,3-propylene) that is bound to a carbon atom of A2where A2represents C1-C4-alkylen;

R10denotes hydrogen;

R11denotes hydrogen;

R12adenotes hydrogen; and

R12bdenotes hydrogen.

A specific compound of the present invention are aminotetraline derivatives disclosed in the examples of the preparation, and to their physiologically tolerated acid-additive salt. They include compound shown in each example as corresponding to the free base and any other physiologically tolerated acid-additive salts of the free base (if given in the example, the compound is a salt), or any physiologically tolerated acid-additive salt of the free base (if given in the example, the compound is a free base). It also includes the enantiomers, diastereomers, tautomers, and any other isomeric form of these compounds, regardless of whether they are opened in explicit or implicit form.

Compounds of formula (I) can be obtained using techniques similar to well known in this field. Suitable methods for obtaining compounds of formula (I) described in the following schema.

The method depicted in scheme 1, can be used to obtain aminotetraline where X1denotes-O - or-S-.

As shown nashama 1, the compound of the General formula 1 is susceptible raminosoa the alkylation with a compound of the General formula 3.

In scheme 1 the variables X2, X3, R5have the values listed in this document, and L denotes a suitable protective group (e.g. L = Me). The method depicted in scheme 1, can also be used to obtain aminotetraline in which X represents optionally substituted alkylene. In this case, L denotes a group, which is a desired side chain R1-W-A1-Q-Y-A2- or may develop in it.

Alternatively, compounds of formula 3 can be obtained according to the method described in scheme 2.

As shown in scheme 2, the compound of the General formula 4 is susceptible to alkylation with a compound of the General formula 5. The conversion to the acid chloride and subsequent closure ring with ethylene in the presence of a Lewis acid (e.g., AlCl3) gives compound 3 (for example, J. Het. Chem., 23 (2), 343, 1986 and Bioorg. Med. Chem. Let, 17 (22), 6160, 2007).

The variables X2, X3, R5have the values listed in this document, and L, L1oboznachayut suitable protective groups (for example, L, L1= Me). Then, compound 3 can be converted into compounds of the General formula (I).

The method depicted in scheme 3, can be used to obtain �of aminotetraline, in which X1denotes - O-or-S-, A2denotes optionally substituted alkylene, Y represents-NR9-, and Q represents-S(O)2.

In scheme 3, the variables R1, W, A1, R2, R3, R4a, R4b, R5, R9, X2, X3have the values listed in this document, and L2denotes a suitable protective group (for example, L2= COOEt).

The method depicted in scheme 4, can be used to obtain aminotetraline where X1denotes methylene, A2denotes a bond, Y is-NR9-, and Q represents-S(O)2.

To produce compound 20 instead of triflate 19 you can use the corresponding bromide or iodide.

In scheme 4, the variables R1, W, A1, R2, R3, R4a, R4b, R5, R9, X2, X3have the values listed in this document, and L3denotes a suitable protective group (for example, L3= COOtBu).

The method depicted in scheme 5, can be used to obtain aminotetraline where X1denotes optionally substituted alkylen, A2denotes optionally substituted alkylene or bond, Y represents-NR9-, and Q represents-S(O)2.

DL� produce compound 26 instead of tricorporate 66 you can use the corresponding 9-borabicyclo[3.3.1]non-9-yl derivative.

In scheme 5, the variables R1, W, A1, R2, R3, R4a, R4b, R5, R9, X2, X3, A2have the values listed in this document, and L3denotes a suitable protective group (for example, L3= COOtBu).

The method depicted in scheme 6, can be used to obtain aminotetraline in which X represents-NR11-, A2denotes optionally substituted alkylene, Y represents-NR9-, and Q represents-S(O)2.

In scheme 6, the variables R1, W, A1, R2, R3, R4a, R4b, R5, R9, X2, X3, A2have the values listed in this document, and L4denotes a suitable protective group.

The method depicted in the following diagrams can be used to obtain compounds of the General formula (I) in which A denotes heterocycl.

As shown in scheme 7, the compound of the General formula 34 easily undergoes condensation with dimethylacetal dimethylformamide to produce a compound of the General formula 35.

As shown in the above scheme 8, the intermediate compound of the General formula 35 interacts with different nucleophile of the General formula H2N-NH-R in an alcoholic solvent, predpochtitel�but in methanol or ethanol, at a temperature from about 20° to 80°C with obtaining compounds of General formulas 36 and 37. In the case of monosubstituted hydrazines are formed regioisomeric products. Compounds 36 and 37 can be converted into compounds of the General formula (I) according to the method depicted in scheme 9.

Figure 8 variable R has the values specified in this specification.

Alkylation of compound 38 can flow through enamin, as shown in figure 1, or via the enolate. Reductive amination of compound 39 gives compound 40. After alkylation or acylation of compound 40 compound 41. In scheme 9, the variables R, R4a, R4b, R5, X2, X3have the values listed in this document.

As illustrated in figure 10, the interaction of the compounds of the General formula 34 with the hydroxyl(tosyloxy)odensala gives compound of formula 42. The interaction of the compounds of the General formula 42 with 1,3-nucleophile in suitable conditions gives compound of General formula 43. The subsequent conversion into compounds of General formula 46 is carried out according to the method depicted in scheme 9.

In scheme 10, the variables R, R4a, R4b, R5, X2, X3have the values listed in this document.

As shown in scheme 11, condensing techniques�tion of the compounds of the General formula 35 with a reagent of the General formula 49 and ammonium acetate in boiling to reflux acetic acid gives compound of General formula 47, which then can be converted into compounds of General formula 48.

In scheme 11, the variables R, R4a, R4b, R5, X2, X3have the values listed in this document.

As shown in figure 12, cyclocondensation intermediate compounds of the General formula 35 with a 1.3-nucleophile of the General formula 50 in the presence of suitable organic or inorganic bases, such as KOH, NaOH, NaHCO3ethoxide sodium, sodium methoxide, triethylamine and diisopropylethylamine, in an alcoholic solvent, preferably in ethanol or methanol, at a temperature from about 20° to 80°C gives compound of General formula 51, which subsequently can be converted into compounds of General formula 52.

In scheme 12, the variables R, R4a, R4b, R5, X2, X3have the values listed in this document.

As shown in scheme 13, an intermediate compound of General formula 53 can easily undergo condensation with dimethylacetal dimethylformamide to produce a compound of the General formula 54, which can interact with different nucleophile of the General formula H2N-NH-R in an alcoholic solvent, preferably methanol or ethanol, at temperatures from about 20° to 80°C with obtaining compounds of General formula 55 and 56. Compounds 55 and 56 can turn�ü in compounds of the General formula (I), according to the method shown in the previous schemes. Figure 13 variables R, R4a, R4b, R5, X2, X3have the values listed in this document.

As shown in figure 14, the interaction of the compounds of the General formula 53 with a hydroxyl(tosyloxy)odensala gives compound of formula 59, which may interact with 1,3-nucleophile in suitable conditions to produce a compound of the General formula 60. The subsequent conversion into compounds of General formula 62 is carried out according to the methods described in the previous schemes.

In figure 14 the variables R, R4a, R4b, R5, X2, X3have the values listed in this document.

As shown in scheme 15, cyclocondensation intermediate compounds of General formula 54 with a 1.3-nucleophile of the General formula 50 in the presence of suitable organic or inorganic bases, such as KOH, NaOH, NaHCO3ethoxide sodium, sodium methoxide, triethylamine and diisopropylethylamine, in an alcoholic solvent, preferably in ethanol or methanol, at a temperature from about 20° to 80°C gives compound of General formula 63, which then can be converted into compounds of the General formula 65 using the methods described in the previous schemes.

In scheme 15, the variables R, R4a, R4b, R5, X2, 3have the values listed in this document.

Acid-additive salts aminotetraline derivatives of formula (I) is prepared in a standard way by mixing the free base with a corresponding acid, optionally in solution in an organic solvent, e.g. a lower alcohol, such as methanol, ethanol or propanol, simple ether, such as methyl tert-butyl ether or diisopropyl ether, a ketone, such as acetone or methyl ethyl ketone, or ester, such as ethyl acetate.

Aminotetraline derivatives of the formula (II)

where L denotes an amino-protective group, Y represents NR9and A2, X1, R2, R3, R4a, R4b, X2, X3, R5n have the above values, can be used as intermediate compounds for obtaining of GlyT1 inhibitors, in particular having the formula (I).

Suitable amino-protective groups are well known in the art and described, for example, in Protective Groups in Organic Chemistry, ed. J. F. W. McOmie, Plenum Press, 1973; and T. W. Greene &P. G. M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 1991.

In accordance with a specific embodiment, L denotes an optionally substituted alkylsulphonyl (for example, tert-butylcarbamoyl), optionally substituted arylcarbamoyl, optionally substituted arylalkylamines (�reamer, benzylcarbamoyl), optionally substituted alkoxycarbonyl (for example, methoxycarbonyl or tert-butyloxycarbonyl), optionally substituted aryloxyalkyl (e.g. phenoxycarbonyl) or optionally substituted arylalkanolamine.

Compounds of formula (I) are capable of inhibiting the activity of glycine Transporter, in particular, glycine Transporter 1 (GlyT1).

The suitability of compounds of the present invention for inhibiting the activity of glycine Transporter, in particular, GlyT1 activity can be demonstrated using known in the field methods. For example, to measure the absorption of glycine and its inhibition (IC50under the action of a compound of formula (I) recombinant cells hGlyT1c_5_CHO expressing human GlyT1c.

Preferred are compounds of formula (I) which are able to provide effective inhibition at low concentrations. Particularly preferred are compounds of formula (I) capable of inhibiting the glycine Transporter 1 (GlyT1) with IC50<1 μmol, more preferably with an IC50<0.5 mol, particularly preferably with IC50<0.2 μmol and most preferably with an IC50<0.1 µmol.

Thus, the compounds of formula (I) of the present invention can be used as pharmaceuticals./p>

Therefore, the present invention also relates to pharmaceutical compositions that contain an inert carrier and a compound of formula (I).

The present invention also relates to the use of compounds of formula (I) in the manufacture of a medicament for inhibiting the glycine Transporter GlyT1, and to corresponding methods of inhibiting the glycine Transporter GlyT1.

The NMDA receptor plays a key role in a wide range of processes in the CNS, and, as shown, is involved in the development of several diseases in humans and animals of other species. The GlyT1 inhibitors slow down the removal of glycine from the synapse, which leads to increased levels of synaptic glycine. This, in turn, increases the filling of the glycine-binding sites of the NMDA receptor and enhances NMDA receptor activation with subsequent release of glutamate from presynaptic endings. Thus, it is known that inhibitors of glycine transport, and in particular inhibitors of the glycine Transporter GlyT1, can be used to treat a number of neurological and psychiatric disorders. In addition, the glycine receptor A is involved in the development of several diseases in humans and animals of other species. Increased extracellular concentrations of glycine as a result of inhibition of glycine transport may lead to increased activity of receptors g�of Irina A. Therefore, inhibitors of glycine transport, and in particular inhibitors of the glycine Transporter GlyT1, can be used to treat a number of neurological and psychiatric disorders.

Thus, the present invention also relates to the use of compounds of formula (I) in the manufacture of a medicine for the treatment of neurological or psychiatric disorders, and to corresponding methods of treatment of these disorders.

In accordance with a specific embodiment, the disorder is associated with dysfunction of glycinergic or glutamatergic neurotransmission.

In accordance with another specific embodiment, the disorder includes one or more of the following conditions and diseases: schizophrenia or psychotic disorder, including schizophrenia (paranoid, disorganized, catatonic or undifferentiated), adulthood schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, collective psychotic disorder, psychotic disorder due to General health status and psychotic disorder, drug-induced, including both positive and negative symptoms of schizophrenia and other psychoses; cognitive disorders including dementia (dementia, assotsiirovanna� with Alzheimer's disease, ischemia, multi-infarct dementia, dementia associated with trauma, vascular disorders or stroke, HIV infection, Parkinson's disease, Huntington disease, disease of the Peak, disease Creutzfeldt-Jacob disease, perinatal hypoxia, other General health conditions or drug abuse); delirium, amnestic disorders or cognitive disturbance, including age-related deterioration in cognitive functions; anxiety disorders including acute stress disorder, agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, panic disorder, posttraumatic stress disorder, separation anxiety disorder, social phobia, specific phobia, drug-induced anxiety disorder and anxiety due to General medical conditions; drug-related disorders and behavior, exhibiting a tendency to drug use (including drug-induced delirium, persistent dementia, persistent amnestic disorder, psychotic disorder or anxiety disorder; tolerance, dependence or withdrawal from chemical substances including alcohol, amphetamines, cannabis, cocaine, hallucinogens means for inhalation, nicotine, opioids, phenylcyclidine, sedatives, hypnotics or anxiolytics); obesity, bulimia nervosa and compulsive eating disorders; bipolar disorders, affective disorders, including depressive disorders; depression including unipolar depression, seasonal depression and postpartum depression, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PDD), mood disorders due to General health status, and drug-induced affective disorders; cognitive disorders, General disorders of psychological development, including autistic disorder, syndrome, attention disorders, including the syndrome of attention deficit and hyperactivity disorder (ADHD) and conduct disorder; movement disorders, including akinesia and akinetic rigid syndromes (including Parkinson's disease, drug-induced parkinsonism, postencephalitic parkinsonism, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, comprehensive dementia associated with parkinsonism-ALS and calcification of the basal nuclei of the brain), Parkinson's disease, caused by medications (such as parkinsonism, induced neuro�aticama, neuroleptic malignant syndrome induced by antipsychotics acute dystonia induced by neuroleptic acute akathisia induced by neuroleptics tardive dyskinesia and is caused by medications postural tremor), the syndrome of Gilles de La Tourette's, epilepsy, muscular spasms and disorders associated with muscular spasticity or weakness including tremors; dyskinesias [including tremor (such as rest tremor, postural tremor and intention tremor), chorea (such as Sydenham chorea, Huntington's disease, benign hereditary chorea, neuroacanthocytosis, symptomatic wittow chorea, drug-induced chorea and hemiballism), myoclonus (including generalized myoclonus and focal myoclonus), tics (including simple tick, integrated tick and symptomatic tics), and dystonia (including generalized dystonia such as idiopathic dystonia, drug-induced dystonia, symptomatic dystonia and proximally dystonia, and focal dystonia such as blepharospasm, oromandibular dystonia, spasmodic dysphonia, spasmodic torticollis, axial dystonia, dystonic graphospasm and hemiplegic dystonia)]; urinary incontinence; loss of neurons, including the defeat of vision, retinopathy or macular degeneration VC�wow spot of the eye, tinnitus, impaired and hearing loss, and brain edema; emesis; and sleep disorders including insomnia and narcolepsy.

In accordance with another specific embodiment the disorder is a pain, particularly chronic pain, especially neuropathic pain.

The pain can be divided into acute and chronic pain. Acute and chronic pain differ in their etiology, pathophysiology, diagnosis and treatment.

Sharp pain that occurs after tissue damage is self-limiting, indicates ongoing tissue damage and after the restoration of tissue usually subsides. There is a minimum of psychological symptoms associated with acute pain, except for moderate anxiety. Acute pain is nociceptive in nature and occurs as a result of chemical, mechanical and thermal stimulation of A-Delta and C-polymodal pain receptors.

On the other hand, chronic pain serves a protective biological function. Rather, it is a symptom of tissue damage and some diseases. Chronic pain continues unabated, is not samoogranichivatsja and can last for years, possibly decades, after the initial damage. Chronic pain can be resistant to various treatment regimes. Psychological symptoms associated with chronic b�Lew, include chronic anxiety, fear, depression, insomnia and worsening of social interaction. Chronic benign pain is predominantly neuropathic in nature and includes the defeat of the peripheral and Central nervous system.

Acute and chronic pain caused by different neuro-physiological processes and therefore tend to respond to different types of treatment. Acute pain can be somatic or visceral in nature. Somatic pain is often quite localized, constant pain and is described as sharp, aching, throbbing or gnawing pain. On the other hand, visceral pain may have an uncertain distribution, it is often paroxysmal in nature and is usually described as deep, aching, squeezing, or colicky. Examples of acute pain include post-operative pain, pain associated with trauma, and arthritic pain. Acute pain usually responds to treatment with opioids or nonsteroidal anti-inflammatory drugs.

Chronic pain, unlike acute pain, described as burning, electric, tingling and shooting. It can be continuous or paroxysmal. The hallmark signs of chronic pain include chronic allodynia and guy�analgesia. Allodynia is a pain arising due to a stimulus that normally does not cause pain response, such as a light touch. Hyperalgesia is an increased sensitivity to normal painful stimuli. Primary hyperalgesia occurs directly in the area of damage. Secondary hyperalgesia occurs in the undamaged area surrounding the damage. Examples of chronic pain include complex regional pain syndrome, pain resulting from peripheral neuropathy, postoperative pain, pain associated with chronic fatigue syndrome, tension headache, pain arising from mechanical nerve damage, and severe pain associated with diseases such as cancer, metabolic disease, infection neurotropic virus, neurotoxicity, inflammation, multiple sclerosis or any pain that occurs due to stress or depressive syndrome, or associated with stress or depressive syndrome.

Although opioids are cheap and effective, their use is having serious side effects that may pose a threat to life, that is basically due to respiratory depression and muscle rigidity. In addition, the input dose of opioids is limited by nausea, vomiting,�stipula, the pruritus and delayed urinary output, which often lead to the fact that patients prefer to receive insufficient suppression of pain than to endure these distressing side effects. In addition, these side effects often lead to prolonged hospitalization of patients. Opioids are highly addictive and in many areas their use is strictly regulated.

Compounds of formula (I) particularly suitable for treatment of diseases such as schizophrenia, bipolar disorder, depression including unipolar depression, seasonal depression and postpartum depression, premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PDD), disorders of learning ability, General development disorder, which includes autistic disorder, syndromes, attention disorders including attention deficit disorder with hyperactivity, tick disorders, including Tourette syndrome, anxiety disorders including phobia and post-traumatic stress disorder, cognitive disorders associated with dementia, AIDS-related dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, spastic condition of the muscles, myoclonus, muscle spasm, tinnitus and impairment and hearing loss.

Specific cognitive p�straitway are dementia, the delirium, amnestic disorders, and cognitive disturbance, including age-related deterioration of cognitive function.

Specific anxiety disorders are generalized anxiety disorder, obsessive-compulsive disorder and panic disorder.

Specific schizophrenic or psychotic pathologies are paranoid, disorganized, catatonic or undifferentiated schizophrenia and drug-induced psychotic state.

Specific neurological disorders that can be treated by the compounds of formula (I) include, in particular, cognitive disorder such as dementia, worsening cognitive function, attention deficit disorder with hyperactivity.

Specific psychiatric disorders that can be treated by the compounds of formula (I) include, in particular, anxiety disorder, affective disorder, such as depression or bipolar disorder, schizophrenia, psychotic disorder.

In the context of treatment, the use of compounds of formula (I) of this invention includes a method. In this method, an effective amount of one or more compounds of formula (I), as determined in accordance with pharmaceutical and veterinary practice, is administered to a subject, Podles�the present treatment, preferably to a mammal, especially man. The purpose of such treatment and its form varies from case to case and is attributable to medical assessment (diagnosis) given the present signs, symptoms and/or dysfunctions, risk of developing certain signs, symptoms and/or dysfunctions, and other factors.

Typically, the treatment is carried out by one or more injections per day, as needed simultaneously or sequentially with other drugs or preparations containing the drug.

The invention also relates to the industrial production of pharmaceutical compositions for the treatment of a subject, preferably a mammal, in particular humans. Thus, compounds of formula (I) is generally administered in pharmaceutical compositions, which contain an inert carrier (e.g., pharmaceutically acceptable excipient) along at least one compound of the present invention and, if necessary, other drugs. These compositions can be administered, e.g., orally, rectally, percutaneously, subcutaneously, intravenously, intramuscularly or intranasally.

Examples of suitable pharmaceutical compositions are solid dosage forms such as powders, granules, tablets, in particular film tablets, PL�weave for resorption, sachets, cachets, sugar-coated tablets, capsules such as hard gelatin capsules and soft gelatin capsules, suppositories or vaginal pharmaceutical forms, semisolid pharmaceutical forms such as ointments, creams, hydrogels, pastes or patches, and liquid dosage forms such as solutions, emulsions, particularly emulsions of oil in water, suspensions, for example lotions, preparations for injection and infusion, eye drops and ear drops. For the introduction of inhibitors of the present invention can also be used implantable devices, ensuring their release. It is also possible to use liposomes or microspheres.

To obtain compositions of the compounds of this invention optionally mixed with one or more carriers (excipients), or diluted with one or more carriers (excipients). Media (excipient) can be a solid, semi-solid or liquid substances that are used as bases, carriers or medium for the active connection.

Suitable carrier materials (excipient) are listed in specialized medical monographs. In addition, the compositions may contain pharmaceutically acceptable auxiliary substances, such as moisturizing agents; emulsifying and suspendresume agents; preservatives; anti�xianti; protivoraketami agent; chelating agent; auxiliary means for applying coatings; emulsion stabilizers; film-forming agents; gel-forming means; means for masking the smell; means, correcting the taste; resin; hydrocolloids; solvents; soljubilizatory; neutralizing means; fast diffusion; pigments; Quaternary ammonium compounds; means providing re degreasing degreasing and increased; the source materials for ointments, creams or oils; silicone derivatives; subsidiary means for the distribution; stabilizers; sterilizing agent; the basis for candles; supporting means for tablets, such as binders, fillers, to contribute to a slide, dezintegriruetsja funds or coatings; propellants; desiccants; cloud emulsions; thickeners; waxes; plasticizers and light mineral oil. Methods of obtaining compositions known in this field and are described, for example, in Fiedler, H. P., Lexikon der Hilfsstoffe fűr Pharmazie, Kosmetik und angrenzende Gebiete [Encyclopedia of auxiliary substances for pharmacy, cosmetics and related fields], 4th edition, Aulendorf: ECV-Editio-Cantor-Verlag, 1996.

Compounds of formula (I) can also be used in combination with other therapeutic agents.

Therefore, the present invention also offers:

(i) a combination of a compound of formula (I) from about�him or more other therapeutic agents;

ii) a pharmaceutical composition containing the combined product specified above in paragraph (i), and at least one carrier, diluent or excipient;

(iii) the application of a combination as specified above in paragraph (i), to manufacture a drug for the treatment or prophylaxis of a disorder, disease or condition as defined in this document;

(iv) a combination as defined above in paragraph (i), for the treatment or prophylaxis of a disorder, disease or condition as defined in this document;

(v) set for the treatment of a disorder, disease or condition as defined in this document, which includes a first dosage form containing the compound of formula (I), and one or more other dosage forms, each of which contains one or more other therapeutic agents, for simultaneous therapeutic administration,

vi) a combination as defined above in paragraph (i), for use in therapy;

vii) a method for the treatment or prophylaxis of a disorder, disease or condition as defined herein comprising administering an effective amount of a combination as specified above in paragraph (i);

(viii) a combination as defined above in paragraph (i), for the treatment or prophylaxis of a disorder, disease or condition as defined in this document.

Combined tera�AI of this invention can be entered separately. Under the introduction of additional means adjoining or overlapping the introduction of all the components in the form of separate pharmaceutical compositions or devices. This mode is therapeutic introduction of two or more therapeutic agents in the field and in the present description referred to as the introduction of additional therapeutic; it is also known as incremental therapeutic introduction. Each and every therapeutic modes that include separate but adjacent or overlapping therapeutic administration of compounds of formula (I) and at least one other therapeutic agent, included in the scope of the present invention. In one embodiment described herein, additional therapeutic administration, the patient is usually administered one or more components within a certain period of time and then introduce another component.

The combination therapy of this invention can also be administered simultaneously. Under the simultaneous introduction of the mean mode of treatment in which the individual components are administered together, either in a single pharmaceutical composition or device containing or containing both components, or as part of different compositions or devices, each of which contains one of the components that is administered at the same time. Such combinations of individual com�of onenow for simultaneous administration may be provided as a set.

In another aspect the invention provides a method of treatment of a psychotic disorder by the introduction of additional therapeutic compounds of the formula (I) to a patient receiving therapeutic introduction of at least one antipsychotic medication. In another aspect the invention provides the use of compounds of formula (I) in the manufacture of a medicine for additional therapeutic administration for the treatment of a psychotic disorder in a patient receiving therapeutic introduction of at least one antipsychotic medication. The invention also provides compounds of formula (I) for additional therapeutic administration for the treatment of a psychotic disorder in a patient receiving therapeutic introduction of at least one antipsychotic medication.

In another aspect the invention provides a method of treating psychotic disorders by therapeutic administration of at least one antipsychotic medication to a patient receiving therapeutic administration of compounds of formula (I). In another aspect the invention provides the use of at least one antipsychotic medication in the manufacture of a medicine for additional therapeutic administration for the treatment psychotic�who disorders the patient has, receiving therapeutic administration of compounds of formula (I). The invention also provides at least one antipsychotic agent for additional therapeutic administration for the treatment of a psychotic disorder in a patient receiving therapeutic administration of compounds of formula (I).

In another aspect the invention provides a method of treatment of a psychotic disorder by simultaneous therapeutic administration of a combination of compounds of formula (I) with at least one antipsychotic agent. The invention also provides the use of combinations of compounds of formula (I) with at least one antipsychotic agent in the manufacture of a medicament for simultaneous therapeutic administration for the treatment of a psychotic disorder. The invention also provides a combination of compounds of formula (I) with at least one antipsychotic agent for simultaneous therapeutic administration for the treatment of a psychotic disorder. Further, the invention provides the use of compounds of formula (I) in the manufacture of a medicament for simultaneous therapeutic administration with at least one antipsychotic agent for the treatment of a psychotic disorder. The invention also provides compounds of formula (I) for �odnovremenno therapeutic injection, at least one antipsychotic agent for the treatment of a psychotic disorder. The invention also provides the use of at least one antipsychotic medication in the manufacture of a medicament for simultaneous therapeutic administration with compounds of formula (I) for the treatment of a psychotic disorder. In addition, the invention provides at least one antipsychotic agent for simultaneous therapeutic administration with compounds of formula (I) for the treatment of a psychotic disorder.

In other aspects the invention provides a method of treatment of a psychotic disorder by simultaneous therapeutic administration of a pharmaceutical composition containing the compound of formula (I) and at least one agent, stabilizing mood, or antigenically agent, pharmaceutical compositions containing the compounds of formula (I) and at least one agent, stabilizing mood, or antigenically tool, the use of pharmaceutical compositions containing compounds of formula (I) and at least one agent, stabilizing mood, or antigenically the means to manufacture a drug for the treatment of psychotic disorders, and pharmaceutical compositions containing the compounds�in termination of formula (I) and, at least one means, stabilizing mood, or antigenically remedy for the treatment of psychotic disorders.

Antipsychotics include both typical and atypical antipsychotics. Examples of antipsychotic drugs that are suitable for use in the present invention include, without limitation: the butyrophenones, such as haloperidol, pimozide, and droperidol; phenothiazines, such as chlorpromazine, thioridazine, mesoridazine, trifluoperazine, perphenazine, fluphenazine, triflupromazine, prochlorperazine and acetophenazine; thioxanthenes, such as thiothixene and chlorprothixene; thienobenzodiazepine; dibenzodiazepine; benzisoxazole; dibenzothiazepine; imidazolidinone; benzisothiazolinone; triazine such as lamotrigine; dibenzoxazepine, such as loxapine; dihydroindole, such as molindone; aripiprazole; and derivatives thereof that have antipsychotic activity.

Listed below are examples of trade names and suppliers of some antipsychotic drugs: clozapine (available under the trade name CLOZARIL®, Mylan, Zenith Goldline, UDL, Novartis); olanzapine (available under the trade name ZYPREX®, Lilly); ziprasidone (available under the trade name GEODON®, Pfizer); risperidone (available under the trade name RISPERDAL®, Janssen); quetiapine fumarate (available �od trade name SEROQUEL®, AstraZeneca); haloperidol (available under the trade name HALDOL®, Ortho-McNeil); chlorpromazine (available under the trade name THORAZINE®, SmithKline Beecham (GSK)); fluphenazine (available under the trade name PROLIXIN®, Apothecon, Copley, Schering, Teva, and American Pharmaceutical Partners, Pasadena); thiothixene (available under the trade name NAVANE®, Pfizer); trifluoperazine (10-[3-(4-methyl-1-piperazinyl)propyl]-2-(trifluoromethyl)phenothiazine dihydrochloride, available under the trade name STELAZINE®, Smith Klein Beckman); perphenazine (available under the trade name TRILAFON®, Schering); thioridazine (available under the trade name MELLARIL®; from Novartis, Roxane, HiTech, Teva, and Alpharma); molindone (available under the trade name MOBAN®, Endo); and loxapine (available under the trade name LOXITANE®, Watson). In addition, you can use benperidol (Glianimon®), perazine (Taxilan®) or melperone (Eunerpan®). Other antipsychotic drugs include promazine (available under the trade name SPARINE®), triflupromazine (available under the trade name VESPRIN®), chlorprothixene (available under the trade name TARACTAN®), droperidol (available under the trade name INAPSINE®), acetophenazine (available under the trade name TINDAL®), prochlorperazine (available under the trade name COMPAZINE®), methotrimeprazine (available under the trade name NOZINAN®), pipotiazine (available under t�rhovyl name PIPOTRIL®), the ziprasidone and gueridon.

In another aspect the invention provides a method of treatment of neurodegenerative disorders such as Alzheimer's disease, by the introduction of additional therapeutic compounds of the formula (I) to a patient receiving therapeutic introduction of at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease. In another aspect the invention provides the use of compounds of formula (I) in the manufacture of a medicine for additional therapeutic administration for the treatment of neurodegenerative disorders such as Alzheimer's disease, in a patient receiving therapeutic introduction of at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease. The invention also provides compounds of formula (I) for additional therapeutic administration for the treatment of neurodegenerative disorders such as Alzheimer's disease, in a patient receiving therapeutic introduction of at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease.

In another aspect the invention provides a method of treating neurodegenerative disorders, such as illness Alzh�of ymer, by additional therapeutic administration of at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, a patient receiving therapeutic administration of compounds of formula (I). In another aspect the invention provides the use of at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, in the production of medicines for additional therapeutic administration for the treatment of neurodegenerative disorders such as Alzheimer's disease, in a patient receiving therapeutic administration of compounds of formula (I). The invention also provides at least one agent suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, additional therapeutic administration for the treatment of neurodegenerative disorders such as Alzheimer's disease, in a patient receiving therapeutic administration of compounds of formula (I).

In another aspect the invention provides a method of treatment of neurodegenerative disorders such as Alzheimer's disease, by simultaneous therapeutic administration of a combination of compounds of formula (I) with at least one substance suitable for the treatment of neurode�enerating disorders such as Alzheimer's disease. The invention also provides the use of combinations of compounds of formula (I) and at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, in the manufacture of a medicament for simultaneous therapeutic administration for the treatment of neurodegenerative disorders such as Alzheimer's disease. The invention also provides a combination of compounds of formula (I) and at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, for simultaneous therapeutic administration for the treatment of neurodegenerative disorders such as Alzheimer's disease. The invention also provides the use of compounds of formula (I) in the manufacture of a medicament for simultaneous therapeutic administration with at least one substance suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, for the treatment of neurodegenerative disorders such as Alzheimer's disease. The invention also provides compounds of formula (I) for simultaneous therapeutic administration with at least one substance suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease�of Amara, for the treatment of neurodegenerative disorders such as Alzheimer's disease. The invention also provides the use of at least one product suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, in the manufacture of a medicament for simultaneous therapeutic administration with compounds of formula (I) for the treatment of neurodegenerative disorders such as Alzheimer's disease. The invention also provides at least one agent suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, for simultaneous therapeutic administration with compounds of formula (I) for the treatment of neurodegenerative disorders such as Alzheimer's disease.

Examples of tools suitable for the treatment of neurodegenerative disorders such as Alzheimer's disease, which can be used in the present invention include, without limitation: cholinesterase inhibitors, the funds allocated to nicotinic or muscarinic acetylcholine receptors, NMDA receptors, the formation of amyloid, mitochondrial dysfunction associated with disease activity calpain, inflammation of nerves, receptors of tumor necrosis factor, NF-kappaB, receptor gamma activator of proliferation of peroxisome, apolipoprotein�E option 4 (ApoE4), illness-related increase in the activity of the hypothalamic-pituitary-adrenal (HPA) system, epileptic discharges, vascular dysfunction, vascular risk factors and oxidative stress.

Cholinesterase inhibitors, which are suitable for use in combination with compounds of this invention include, for example, tacrine, donepezil, galantamine and rivastigmine.

Funds aimed at NMDA receptors, which are suitable for use in combination with compounds of this invention include, for example, memantine.

Agents that increase the activity of the hypothalamic-pituitary-adrenal (HPA) system, suitable for use in combination with compounds of this invention include, for example, antagonists of CRF1 or V1b antagonists.

Therefore, in another aspect, the invention provides a method of treating pain by the introduction of additional therapeutic compounds of the formula (I) to a patient receiving therapeutic introduction of at least one product suitable for the treatment of pain. In another aspect the invention provides the use of compounds of formula (I) in the manufacture of a medicine for additional therapeutic administration for the treatment of pain in a patient receiving therapeutic introduction of at least one product suitable for the treatment of pain. Invent�the Oia also provides compounds of formula (I) for additional therapeutic administration for the treatment of pain in the patient, receiving therapeutic introduction of at least one product suitable for the treatment of pain.

In another aspect the invention provides a method of treating pain by additional therapeutic administration of at least one product suitable for the treatment of pain, a patient receiving therapeutic administration of compounds of formula (I). In another aspect the invention provides the use of at least one product suitable for the treatment of pain, in the manufacture of a medicine for additional therapeutic administration for the treatment of pain in a patient receiving therapeutic administration of compounds of formula (I). The invention also provides at least one agent suitable for the treatment of pain, for additional therapeutic administration for the treatment of pain in a patient receiving therapeutic administration of compounds of formula (I).

In another aspect the invention provides a method of treating pain by simultaneous therapeutic administration of compounds of formula (I) in combination with at least one substance suitable for the treatment of pain. The invention also provides the use of combinations of compounds of formula (I) and at least one product suitable for the treatment of pain, in the manufacture of a medicament for simultaneous terapeuticas�th injection for treatment of pain. The invention also provides a combination of compounds of formula (I) and at least one product suitable for the treatment of pain, for simultaneous therapeutic administration for the treatment of pain. The invention also provides the use of compounds of formula (I) in the manufacture of a medicament for simultaneous therapeutic administration with at least one substance suitable for the treatment of pain, for the treatment of pain. The invention also provides compounds of formula (I) for simultaneous therapeutic administration with at least one substance suitable for the treatment of pain, for the treatment of pain. The invention also provides the use of at least one product suitable for the treatment of pain, in the manufacture of a medicament for simultaneous therapeutic administration with a compound of formula (I) for the treatment of pain. The invention also provides at least one agent suitable for the treatment of pain, for simultaneous therapeutic administration with compounds of formula (I), for the treatment of pain.

Examples of tools suitable for the treatment of pain, which can be used in the present invention include, without limitation: NSAID (nonsteroidal anti-inflammatory drugs), anticonvulsant drugs such as carbamazepine and GABA�Entin, the sodium channel blockers, antidepressants, cannabinoids and anaesthetics local action.

Agents suitable for use in combination with compounds of this invention include, for example, celecoxib, etoricoxib, lumiracoxib, paracetamol, tramadol, methadone, venlafaxine, imipramine, DULOXETINE, bupropion, gabapentin, pregabalin, lamotrigine, fentanyl, parecoxib, nefopam, Remifentanil, pethidine, diclofenac, rofecoxib, nalbuphine, Sufentanil, pethidine, diamorphine and butorphanol.

For specialists in this field will be obvious that the compounds of this invention can be successfully used in conjunction with one or more other therapeutic agents such as antidepressants, for example, 5HT3 antagonists, serotonin agonists, antagonists of NK-1 selective inhibitors of serotonin reuptake (SSRI), inhibitors of reuptake of norepinephrine (SNRI), tricyclic antidepressants, dopaminergic antidepressants, H3 antagonists, 5ht1 (a) antagonists, 5HT1B antagonists, antagonists, 5ht1 (d), D1 agonists, M1 agonists and/or protivogololednye funds, as well as a means of enhancing cognitive function.

5HT3 antagonists suitable for use in combination with compounds of this invention include, for example, ondansetron, granisetron, metoclopramide.

Agonists gray�onine, suitable for use in combination with compounds of this invention include sumatriptan, rauwolscine, yohimbine, metoclopramide.

SSRI, which are suitable for use in combination with compounds of this invention include fluoxetine, citalopram, femoxetine, fluvoxamine, paroxetine, indalpine, sertraline, zimeldine.

SNRI, which are suitable for use in combination with compounds of this invention include venlafaxine and reboxetine.

Tricyclic antidepressants, which are suitable for use in combination with compounds of this invention include imipramine, amitriptyline, clomipramine and nortriptyline.

Dopaminergic antidepressants, which are suitable for use in combination with compounds of this invention include bupropion and amineptine.

Protivogololednye agents suitable for use in combination with compounds of this invention include, for example, divalproex, carbamazepine and diazepam.

The following examples serve to explain the invention without limiting it.

Compounds characterized by using mass spectrometry, typically HPLC-MS, using a fast gradient on C18 media (electrospray ionization (ESI)).

Examples of preparation

Unless otherwise specified, all target compounds have the CIS-configuration in tetrahydronaphtalene the kernel.

Example 1: [7-(2-tert-butoxycarbonylamino)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

1.1 1-(3,4-Dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalene-2(1H)-he

15 g (85 mmol) of 7-methoxy-3,4-dihydronaphthalene-2(1H)-it was dissolved in 200 ml of dry MeOH under an atmosphere of nitrogen. Then dropwise slowly added to 6.66 g (94 mmol) of pyrrolidine, thus there is a color change. The mixture is stirred for one hour. The solvent is evaporated in vacuo, and the residue dissolved in MeCN. At 5°C is added to 22.5 g (94 mmol) of 4-(methyl bromide)-1,2-dichlorobenzene dissolved in MeCN, and the mixture was stirred over night at room temperature. The solvent is evaporated in vacuo, the residue was mixed with MeOH/CH2Cl2/H2O 1:1:1 (50 ml, 50 ml, 50 ml) and add 10 ml of glacial acetic acid. The mixture was stirred over night. Treatment: the Reaction mixture was placed in ice water and extracted with 3× CH2Cl2. The combined organic layers were washed 1× with a solution of NaHCO3and 1× with saturated NaCl solution. The organic phase is dried over MgSO4, and the solvent evaporated. The residue (31,5 g) purified flash chromatography on silica gel, elwira a mixture of heptane/EtOAc 2:1. Get 24,1 g (71,7 mmol, 84%) of product.

ESI-MS [M+H+]=335,1 calculated for C18H16Cl2O2=334,05.

1.2 1-(3,4 Dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride

To 1-(3,4-dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalene-2(1H)-ONU, 5.2 g (15.5 mmol) in MeOH under an atmosphere of nitrogen was added a reagent ammonium acetate (12.0 g, 155 mmol) and cyanoborohydride sodium (1,46 g, with 23.3 mmol). The mixture was stirred for 4 days at room temperature. The solvent was evaporated in vacuo and after adding water, extracted with EtOAc. The organic layer was washed with NaCl, dried over MgSO4and the solvent removed. The residue was dissolved in iPrOH and added HCl in iPrOH (6N). After crystallization overnight HCl salt is separated from the mother liquor and converted into the free base using NaOH (1N). Get the oil, which after treatment with HCl and crystallization gives the CIS-product (1.95 g, 5,80 mmol, 37.4 per cent). The mother liquor contains a mixture of CIS/TRANS products.

ESI-MS [M+H+]=is 336.2 calculated for C18H19Cl2NO=336,26.

1.3 Ethyl 1-(3,4-dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate

To 1-(3,4-dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride (1.95 g, 5,80 mmol) in pyridine (10 ml) in a nitrogen atmosphere, slowly add ethylchloride (1.00 g, 9,28 mmol). The mixture is stirred over night at room temperature. The solvent was evaporated in vacuo and after addition of HCl (1 N), extracted with CH2Cl2. The organic layer was washed with HCl (1N), a solution of NaHCO3and NaCl, then �tub over MgSO 4and the solvent removed. The product is obtained in the form of an orange oil which is deposited in a few hours (2.10 g, 5,14 mmol, 89%).

ESI-MS [M+H+]=408,2 calculated for C21H23ClN2O3=407,11.

1.4 Ethyl 1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate

Ethyl 1-(3,4-dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (2.1 g, 5,14 mmol) was dissolved in CH2Cl2(50 ml) and added BBr3(a 3.87 g, to 15.4 mmol) at -10°C. the Reaction mixture was slowly heated to room temperature and stirred for 2 h. the Reaction mixture was added to ice water and extracted with CH2Cl2. The organic layer was washed with a solution of NaHCO3and NaCl, then dried over MgSO4and the solvent removed. The product was obtained as a brown oil (2.05 g, 5,14 mmol, 100%).

ESI-MS [M+H+]=394,1 calculated for C20H21Cl2NO3=393,09.

1.5 7-(2-tert-butoxycarbonylamino)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

NaH (55% in paraffin to 34.5 mmol) suspended in DMA (80 ml) and added ethyl 1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (6,80 g, 17.3 mmol) dissolved in DMA (40 ml). The mixture was stirred for another hour. ZAT�m portions add bromide, and the mixture was stirred for 3 days at room temperature. The reaction mixture was added to prokonsultirovatsia solution of NaCl and extracted with EtOAc. The organic layer was washed with H2O, NaCl, then dried over MgSO4and the solvent removed. A certain amount of DMA was removed on the oil pump. The residue is purified flash chromatography on silica gel, elwira a mixture of CH2Cl2/MeOH 98:2. The product was obtained as a yellow oil (9.27 g, 17.3 mmol, 100%), which becomes solid after a few hours.

ESI-MS [M+H+]=481,1 calculated for C27H34Cl2N2O5=536,18.

Example 2Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate

2.1 Ethyl 7-(2-aminoethoxy)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate hydrochloride

[7-(2-tert-Butoxycarbonylamino)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester (9.27 g, 17.3 mmol), example 1, was dissolved in CH2Cl2(200 ml) and add HCl in iPrOH (6N). The reaction mixture was stirred at room temperature overnight, after which the precipitated solid. To the reaction mixture is added diethyl ether, and the precipitated HCl salt is separated by filtration, obtaining the final product in the form of solids (5,85 g, 123 mmol, 72%).

ESI-MS [M+H+]=437,1 calculated for C22H26Cl2N2O3=436,13.

2.2 Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate

Ethyl 7-(2-aminoethoxy)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate hydrochloride (100 mg, 0,229 mmol) and DMAP (27,9 mg, 0,229 mmol) was dissolved in CH2Cl2(15 ml) and added with 1-methyl-1H-imidazol-4-sulphonylchloride (41,3 mg, 0,229 mmol) dissolved in CH2Cl2(15 ml). The reaction mixture was stirred over night at room temperature. After addition of H2O the phases were separated, and the aqueous phase extracted with CH2Cl2. The organic layer was washed with HCl (1N), a solution of NaHCO3and NaCl, then dried over MgSO4and the solvent removed. The residue was added EtOAc/diethyl ether (1:1), stirred, and the precipitate is separated by filtration, receiving the product as a brown solid (100 mg).

ESI-MS [M+H+]=581,5 calculated for C26H30Cl2N4O5S=580,13.

Example 3: N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (1.00 g, 1,72 mmol), n�emer 2, was heated to reflux in 25 g of a mixture EtOH/20% KOH for 2 h. To the reaction mixture add prokonsultirovalis NaCl solution, and the mixture was extracted with ethyl acetate. The organic layers are combined and washed with NaCl solution, then dried over MgSO4and the solvent removed. Discovered that a significant amount remains on MgSO4so spend an extra stage of separation/extraction H2O/CH2Cl2, dried over Na2SO4and receives a yellow oil (830 mg). The remaining residue is dissolved in a small amount of MeOH, was added HCl (1N), and the final product (650 mg, 1,19 mmol, 69%) is separated by filtration.

ESI-MS [M+H+]=509,1 calculated for C23H26Cl2N4O3S=508,11.

Example 4: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using 1-methyl-1H-pyrazol-4-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=509,1 calculated for C23H26Cl2N4O3S=508,11.

Example 5: Pyridine-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphtyl�n-2-yloxy]ethyl}amide hydrochloride

Pyridine-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using pyridyl-3-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=506,1 calculated for C24H25Cl2N3O3S=505.

Example 6:

N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)propane-1-sulfonamide (example 8) (66,0 mg, 0,140 mmol), paraformaldehyde (7,63 mg, 0,254 mmol), and formic acid (21.6 mg, 0,469 mmol) was dissolved in ethanol (5 ml) and heated to reflux for 4 h. the Solvent was evaporated and the residue was added NaOH (1N). After extraction with CH2Cl2the organic layers are washed with water and saturated NaCl solution, dried over Na2SO4, filtered, and the solvent removed. Balance purify separated by column chromatography (CH2Cl2/MeOH 97:7→95:5). The final product (15,0 mg, 0,028 mmol, 20%) was obtained as a brown solid HCl salt from isopropanol after treatment with HCl in isopropanol (6N).

ESI-MS [M+H+]=499,1 calculated for C24H32Cl2N2O3S=498.

Example 7: 1-(3,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

{1-(3,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 3, using propane-1-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=543,2 calculated for C25H32Cl2N2O5S=542.

Example 8: Propane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Propane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using propane-1-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=of 471.1 calculated for C22H28Cl2N2O3S=470.

Example 9: {1-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

{1-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 3, using 1-methyl-1H-pyrazol-4-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=581,2 calculated for C26H30Cl2N4O5S=580.

<> Example 10: {1-(3,4-Dichlorobenzyl)-7-[2-(pyridin-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

{1-(3,4-Dichlorobenzyl)-7-[2-(pyridin-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 3, using pyridine-3-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=to 578.2 calculated for C27H29Cl2N3O5S=577.

Example 11: N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-methylpropan-1-sulfonamide hydrochloride

11.1 N-(1-(3,4-Dichlorobenzyl)-7-(2-(propylsulfonyl)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl)-2,2,2-triptorelin

N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)propane-1-sulfonamide (example 3, 150 mg, 0,318 mmol) and triethylamine (32,2 mg, 0,318 mmol) was dissolved in THF (10 ml) and add trifluoroacetic anhydride (or 66.8 mg, 0,318 mmol). The mixture was stirred at room temperature for 48 h. Add ethyl acetate, the mixture was extracted with water and then washed with a solution of NaHCO3and a saturated solution of NaCl. After drying over MgSO4and removal of the solvent the residue is purified by chromatography on silica gel using CH2Cl2/MeOH 98:2, and finish the product in �IDA colorless oil, which after some time becomes solid (80.0 mg, 0,141 mmol, 44%).

11.2 N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-methylpropan-1-sulfonamide hydrochloride

NaH (3,38 mg, 0,078 mmol, 55% in oil) are suspended in DMA (5 ml) and added dropwise N-(1-(3,4-dichlorobenzyl)-7-(2-(propylsulfonyl)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl)-2,2,2-trifurcated (40 mg, 0.07 mmol) dissolved in DMA (4 ml). After stirring for 1 h was added itmean (10.5 mg, between 0.074 mmol) dissolved in DMA (1 ml). After stirring for 14 h, the reaction mixture was added to prokonsultirovatsia solution of NaCl. After extraction with ethyl acetate, washing the organic layer with water and saturated NaCl solution and drying over Na2SO4a residue which is washed with diisopropyl ether. Cleavage of the amide bond is carried out by mixing the residue with concentrated NaOH solution in water, followed by extraction with ethyl acetate. The organic layer is dried over MgSO4and evaporated. The residue was purified by the method of preparative HPLC (RP-18, acetonitrile/water with 0.01% TFA). After conversion of product to HCl salt receives a yellow solid (11.0 mg, 0,021 mmol, 30%).

ESI-MS [M+H+]=485,2 calculated for C23H30Cl2N2O3S=484.

Example 12: [1-(3,4-Dichlorobenzyl)-7-(2-methanol�parilamentary)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

[1-(3,4-Dichlorobenzyl)-7-(2-methanesulfonylaminoethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester receive according to the method of example 3, using methylsulfonylamino instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=515.1 calculated for C23H28Cl2N2O5S=514.

Example 13: [7-(2-Benzolsulfonat)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

[7-(2-Benzolsulfonat)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester receive according to the method of example 3, using phenylsulfonyl instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=577,2 calculated for C28H30Cl2N2O5S=576.

Example 14: {1-(3,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

{1-(3,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 3, using phenylsulfonyl instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=583,1 calculated for C26H28Cl2N2O5S2=582./p>

Example 15: N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide hydrochloride

N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide receive according to the method of example 3, using methylsulfonylamino instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=443,1 calculated for C20H24Cl2N2O3S=442.

Example 16: N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}benzosulfimide hydrochloride

N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}benzolsulfonat receive according to the method of example 3, using phenylsulfonyl instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=505,1 calculated for C25H26Cl2N2O3S=504.

Example 17: Thiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

The thiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide receive according to the method of example 3, using thiophenesulfonyl instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=511,1 calculated for C23H24Cl2N2O3/sub> S2=510.

Example 18: N-{1-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}-2,2,2-triptorelin

N-{1-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}-2,2,2-trifurcated receive according to the method of example 11 using the product of example 3 instead of the product of example 8.

ESI-MS [M+H+]=605,1 calculated for C25H25Cl2F3N4O4S=604.

Example 19: Pyrrolidin-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Pyrrolidin-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using benzyl 3-(chlorosulfonyl)pyrrolidin-1-carboxylate (synthesis described in WO2008075070) instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=498,2 calculated for C23H29Cl2N3O3S=497.

Example 20: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-formylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (example 3, 60,0 mg, 0,103 mmol) Sol�critics in THF (5 ml) at room temperature is added LiAlH 4(7,83 mg, 0,206 mmol). The residue was added to 2N NaOH and extracted with dichloromethane. The organic layer was washed with saturated solution of NaHCO3and then with saturated NaCl solution, dried and evaporated. The product precipitated as HCl salt from a solution of 6N HCl in isopropanol and isopropyl ether to give product as a white salt (36 mg, 61%).

ESI-MS [M+H+]=537,1 calculated for C24H26Cl2N4O4S=536.

Example 21: 1-(3,4-Dichlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

1-(3,4-Dichlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 3, using 4-methylthiophene-2-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=597,1 calculated for C27H30Cl2N2O5S2=596.

Example 22: {1-(3,4-Dichlorobenzyl)-7-[2-(3-forproper-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

{1-(3,4-Dichlorobenzyl)-7-[2-(3-forproper-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 3, using 3-forproper-1-sulphonylchloride instead of 1-methyl-1H-�midazol-4-sulphonylchloride.

ESI-MS [M+H+]=561,2 calculated for C25H31Cl2FN2O5S=560.

Example 23: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (example 3, 60,0 mg, 0,103 mmol) was dissolved in dichloromethane (5 ml) and acetaldehyde (5,45 mg, 0,124 mmol µl), was added molecular sieves 3 E, and the mixture was stirred for 3 h. Add acetic acid (7,07 mg, the amount of 0.118 mmol), and the mixture was stirred for another 3 h. MeOH was Then added (5 ml) and cyanoborohydride sodium (14,8 mg of 0.236 mmol) and stirring was continued for 14 h. After adding water, the mixture extracted with dichloromethane. The organic layer was washed with saturated solution of NaHCO3, washed and evaporated. Balance purify separated by column chromatography using SiO2and CH2Cl2/MeOH 95:5→90:10. The product precipitated as HCl salt from 6N HCl solution in isopropanol and isopropyl ether to obtain white salt (17 mg, 25%).

ESI-MS [M+H+]=537,2 calculated for C25H30Cl2N4O3S=536.

Example 24: 4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using 4-methylthiophene-2-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=RUB 525.1 calculated for C24H26Cl2N2O3S2=524.

Example 25: N'-(2-{[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N,N-dimethylcarbinol acid diamide hydrochloride

N'-(2-{[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N,N-dimethylcarbinol acid diamide hydrochloride receive according to the method of example 3, using di - methylsulfinylpropyl instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=472,1 calculated for C21H27Cl2N3O3S=471.

Example 26: {1-(3,4-Dichlorobenzyl)-7-[2-(3,3,3-cryptochrome-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

{1-(3,4-Dichlorobenzyl)-7-[2-(3,3,3-cryptochrome-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 3, using dimethylsulphamoyl instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=597,1 calculated for C25H29Cl2F3Nsub> 2O5S=596.

Example 27: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using 1-methyl-1H-imidazol-4-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride and 4-(methyl bromide)-1-dichlorobenzene instead of 4-(methyl bromide)-1,2-dichlorobenzene.

ESI-MS [M+H+]=475,1 calculated for C23H27ClN4O3S=474.

Example 28: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using 1-methyl-1H-pyrazol-4-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride and 4-(methyl bromide)-1-dichlorobenzene instead of 4-(methyl bromide)-1,2-dichlorobenzene.

ESI-MS [M+H+]=475,1 calculated for C23H27ClN4O3S=474.

Example 29: 7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-carbonitrile triptorelin

29.1 8-(3,4-Dichlorobenzyl)-7-[(ethoxycarbonyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl Tr�formeasurement

Ethyl 1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (700 mg, 1,775 mmol, see example 3d) and 1,1,1-Cryptor-N-phenyl-N-(triftormetilfullerenov)methanesulfonamide (761 mg, 2,13 mmol) was dissolved in dichloromethane (30 ml). The reaction mixture was cooled to 0°C and dropwise added a solution of triethylamine (0,495 ml, 3,55 mmol) in dichloromethane (5 ml). The reaction mixture is allowed to warm to room temperature, and stirring was continued over night. The solvent is evaporated under vacuum, and the crude product is purified flash chromatography (dichloro methane, silica gel). Output: 934 mg (100%).

ESI-MS [M+H+]=526 calculated for C21H20Cl2F3NO5S=525.

29.2 Ethyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

8-(3,4-Dichlorobenzyl)-7-[(ethoxycarbonyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov (250 mg, 0.475 mmol), zinc cyanide (139 mg, 1,187 mmol) and tetracationic palladium (82 mg, 0,071 mmol) in dimethylformamide (5 ml) was heated in a microwave at 120°C (100 W) with stirring for 35 min. the Solvent is evaporated under vacuum, and the crude product partitioned between ethyl acetate (40 ml) and water (30 ml). The aqueous layer was extracted with ethyl acetate (20 ml) and the combined organic extracts are dried (Na2SO 4) and concentrated in vacuo. The crude product (460 mg) is purified flash chromatography (dichloromethane to dichloro methane:methanol = 100:1, silica gel). Yield: 109 mg (0,270 mmol, 57%, colorless solid).

ESI-MS [M+H+]=403, calculated for C21H20Cl2N2O2=402.

29.3 7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-carbonitrile triptorelin

Ethyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (50 mg, 0,124 mmol) was dissolved in a 10% solution of potassium hydroxide in ethanol (1.5 ml) and the reaction mixture was stirred at 80°C for 2.5 h. the Solvent is evaporated in vacuum. To the crude product add saturated salt solution (5 ml) and 2N hydrochloric acid until a pH of 7. The aqueous layer was extracted with dichloromethane three times. The combined organic extracts are dried (Na2SO4) and concentrated in vacuo. The crude product (60 mg) purified by the method of preparative HPLC (column xTerra prep MS C18, C mm, 5 μm; gradient: water, acetonitrile containing 0.,1% trifluoroacetic acid, flow rate: 20 ml/min). Yield: 6 mg (0,013 mmol, 11%).

ESI-MS [M+H+]=331, calculated for C18H16Cl2N2=330.

Example 30: 7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-carbonitrile hydrochloride

30.1 7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-te�residronate-2-ol

1-(4-Chlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine (13,18 g, 43,7 mmol, obtained analogously to 1-(3,4-dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine, see also example 3) was dissolved in dichloromethane (200 ml). The solution was cooled to -10°C and slowly added 1 M solution of borontrifluoride in dichloromethane (131 ml, 131 mmol). The reaction mixture is allowed to warm to room temperature, and stirring was continued for 2 h. the Reaction mixture was poured in iced water and add sodium hydroxide until pH 8. The aqueous layer was extracted with dichloromethane. The combined organic extracts are dried (Na2SO4) and concentrated in vacuo. The crude product was used for next step without further purification. Output: 8,89 g (of 30.9 mmol, 71%, colorless solid).

ESI-MS [M+H+]=288, calculated for C17H18ClNO=287.

30.2 Tert-butyl [1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-ol (2.0 g, to 6.95 mmol) was dissolved in dry tetrahydrofuran and added di-tert-BUTYLCARBAMATE (1,517 grams of 6.95 mmol) and triethylamine (2,91 ml of 20.85 mmol). The reaction mixture was stirred at room temperature for 3 h. the Solvent is evaporated in vacuum. Water was added, and the aqueous layer extra�are dichloromethane. The combined organic extracts are dried (Na2SO4) and concentrated in vacuo. The crude product was recrystallized from n-hexane. Yield: 2.2 g (5,67 mmol, 82%).

ESI-MS [M-isobutene+H+]=332, calculated for C22H26ClN2O3=387.

30.3 7-[(Tert-butoxycarbonyl)amino]-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov

Tert-butyl [1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (850 mg, 2,191 mmol) and 1,1,1-Cryptor-N-phenyl-N-(triftormetilfullerenov)methanesulfonamide (939 mg, 2,63 mmol) was dissolved in dichloromethane (45 ml). Pale yellow solution was cooled to 0°C and dropwise added a solution of triethylamine (0,611 ml, of 4.38 mmol) in dichloromethane (5 ml). The reaction mixture is allowed to warm to room temperature, and stirring was continued over night. The solvent is evaporated under vacuum, and the crude product is purified flash chromatography (dichloro methane, silica gel). Yield: 1.03 g (1,981 mmol, 90%, colorless solid).

ESI-MS [M-isobutene+CH3CN+H+]=505, calculated for C23H25ClF3NO5S=519.

30.4 Tert-butyl [1-(4-Chlorobenzyl)-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

DPPF (8,1 mg, 0.015 mmol) and Pd2dba3(3,35 mg, 0,00365 mmol) suspended in dimethylformamide (0.4 ml), and after p�of remesiana at room temperature in an inert atmosphere of nitrogen for 20 min add 7-[(tert-butoxycarbonyl)amino]-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov (38 mg, 0,073 mmol) and zinc cyanide (12,87 mg, 0,110 mmol). The reaction mixture was stirred at 90°C for 1 h. the Solvent is evaporated in vacuum. To the crude product is added water (10 ml) and the aqueous layer was extracted with ethyl acetate (twice 10 ml). The combined organic extracts are dried (Na2SO4) and concentrated in vacuo. The crude product is purified flash chromatography (dichloro methane, silica gel). Yield: 16 mg (0.040 mmol, 55%).

ESI-MS [M-isobutene+CH3CN+H+]=382, calculated for C23H25ClN2O2=396.

30.5 7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-carbonitrile hydrochloride

Tert-butyl [1-(4-Chlorobenzyl)-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (15 mg, 0,038 mmol) was dissolved in dichloromethane (1.5 ml) and added 5 M hydrochloric acid solution in isopropanol (0.3 ml). The reaction mixture was stirred for 3 h at room temperature. The solvent and excess hydrochloric acid is evaporated in a vacuum. Yield: 11 mg (0,033 mmol, 87%, colorless solid).

ESI-MS [M+H+]=297 calculated for C18H17ClN2=296.

Example 31: N-[(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-3-forproper-1-sulfonamida triptorelin

31.1 Tert-butyl [7-(aminomethyl)-1-benzyl-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

Tert-butyl [1-(4-Chlorobenzyl)-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (52 mg, 0,131 mmol, see also example 30d) was dissolved in methanol (5 ml). Add Raney Nickel (about 30 mg) and the reaction mixture was stirred at room temperature for 4 hours in hydrogen atmosphere. The catalyst is removed by filtration. The solvent is evaporated in vacuum. The crude product was used for next step without further purification. Yield: 32 mg (0,087 mmol, 67%).

ESI-MS [M-isobutene+H+]=311, calculated for C23H30N2O2=366.

31.2 Tert-butyl [1-benzyl-7-({[(3-forproper)sulfonyl]amino}methyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

Tert-butyl [7-(aminomethyl)-1-benzyl-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (32 mg, 0.87 mmol) was dissolved in dichloromethane (15 ml) and 4-dimethylaminopyridine (12 mg, 0,096 mmol) and add 3-forproper-1-sulphonylchloride (14 mg, 0,087 mmol). The reaction mixture was stirred at room temperature over night. A solution of crude product in dichloromethane was washed successively 1N aqueous solution of hydrochloric acid and an aqueous solution of NaHCO3, dried (Na2SO4) and concentrated in vacuo. The crude product is purified flash chromatography (dichloro methane, methanol, silica gel). Output: 9,3 mg is 0.019 mmol, 22%).

ESI-MS [M-isobutene+H+]=435, calculate how muc�Tano for C 26H35FN2O4S=490.

31.3 N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-forproper-1-sulfonamida triptorelin

Tert-butyl [1-benzyl-7-({[(3-forproper)sulfonyl]amino}methyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (9,3 mg, is 0.019 mmol) was dissolved in dichloromethane (10 ml) and add trifluoroacetic acid (excess). The reaction mixture was stirred at room temperature for 4 h. the Solvent was evaporated in vacuo, and the crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 4 mg (0,0079 mmol, 42%).

ESI-MS [M+H+]=391 calculated for C21H27FN2O2S =390.

Example 32Ethyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

Cm. example 29b.

ESI-MS [M+H+]=403, calculated for C21H20Cl2N2O2=402.

Example 33: 1-(3-Chlorobenzyl)-7-[2-(1,1-dioxothiazolidine-2-yl)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride

ESI-MS [M+H+]=435, calculated for C22H27ClN2O3S=434.

Example 34: tert-Butyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

34.1 7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-ol

1-(3,4-Dichlorobenzyl-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine (10 g, at 26.8 mmol, see also example 3.2) was dissolved in dichloromethane (240 ml). The suspension was cooled to -10°C and add 1 M solution of bartered in dichloromethane (80 ml, 80 mmol). The solution was allowed to warm to room temperature, and stirring was continued for 3 h. the Reaction mixture was poured onto ice (1 l). The aqueous layer made basic (pH 10) 2N solution of sodium hydroxide. The layers were separated. The aqueous layer was extracted with dichloromethane, and the combined organic layers washed with saturated solution of NaHCO3and water. The organic layers are dried (Na2SO4) and concentrated in vacuo. The crude product was used without additional purification in the next step. Yield: 10.8 g

ESI-MS [M+H+]=322, calculated for C17H17Cl2NO=321.

34.2 tert-Butyl [1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-ol (10.8 g) and triethylamine (14,01 ml, 101 mmol) was dissolved in dry tetrahydrofuran (200 ml). Di-tert-butyl carbonate (7,31 g of 33.5 mmol) was added in small portions at room temperature. The reaction mixture was stirred over night. The solvent is evaporated in vacuum. The residue was dissolved in ethyl acetate (300 ml) and washed with water (CH ml). A solution of crude product in ethyl acetate was dried (Na2SO4). The solvent in�arevut in vacuum, and the crude product used for next step without further purification. Output: 12,2.

ESI-MS [M-isobutene+CH3CN+H+]=407, calculated for C22H25Cl2NO3=421.

34.3 7-[(tert-butoxycarbonyl)amino]-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov

tert-Butyl [1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (4,06 g, 9.66 as per mmol) and 1,1,1-Cryptor-N-phenyl-N-(triftormetilfullerenov)methanesulfonamide (4.14 g, 11,59 mmol) was dissolved in dichloromethane (190 ml). The light brown solution was cooled to 0°C and dropwise added a solution of triethylamine (2,69 ml, for 19.32 mmol) in dichloromethane (10 ml). The reaction mixture is allowed to warm to room temperature, and stirring was continued over night. The solvent is evaporated under vacuum, and the crude product is purified flash chromatography (dichloro methane, silica gel). Yield: 3.2 g (5,77 mmol, 60%).

34.4 tert-Butyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

Diphenylphosphinite (100 mg, 0.18 mmol) and diplodia tridimensionale (41 mg, or 0.045 mmol) suspended in an argon atmosphere in dry dimethylformamide (5 ml). After stirring at room temperature for 40 min add 7-[(tert-butoxycarbonyl)amino]-8-(3,4-dichlorobenzyl)-5,6,7,8-�tetrahydronaphthalen-2-yl triftormetilfullerenov (0.5 g, 0,902 mmol) and the reaction mixture heated to 90°C. After 30 min in small portions is added zinc cyanide (159 mg, 1,353 mmol). After completion of the addition stirring was continued at 90°C for 2 h. the Reaction mixture was cooled to room temperature, diluted with dichloromethane (50 ml) and washed with saturated solution of NaHCO3(CH ml). The organic layer was dried (MgSO4) and concentrated in vacuo. The crude product is purified flash chromatography (dichloro methane, silica gel). Yield: 97 mg (0,225 mmol, 25%).

ESI-MS [M+Na+]=453, calculated for C23H24Cl2N2O2=430.

Example 35: 7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-ol triptorelin (salt)

Cm. also the example 34a.

ESI-MS [M+H+]=322, calculated for C17H17Cl2NO=321.

Example 36: 1-(4-Chlorobenzyl)-7-(deformedarse)-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride

36.1 tert-Butyl [1-(4-Chlorobenzyl)-7-(deformedarse)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

Tert-butyl [1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (180 mg, 0,464 mmol, obtained analogous to tert-butyl [1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate, see also example 34.2) and potassium hydroxide (1.4 g, 25 mmol) suspended in acetonitrile (4 ml). After paramashiva�Oia two-phase system for 45 min at room temperature, the reaction mixture was cooled to -15°C and added dropwise a solution of 2-chloro-2,2-debtor-1-phenylethanone (442 mg, 2,32 mmol) in acetonitrile (1 ml) for 30 min. the Reaction mixture was heated to room temperature and then heated at 80°C for 2 h. the Reaction mixture was cooled to room temperature and diluted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined extracts are dried (MgSO4) and concentrated in vacuo. The crude product is purified flash chromatography (dichloro methane, silica gel). Yield: 30 mg (0,069 mmol, 15%).

ESI-MS [M-isobutene+CH3CN+H+]=423, calculated for C23H26ClF2NO3=437.

36.2 1-(4-Chlorobenzyl)-7-(deformedarse)-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride

tert-Butyl [1-(4-Chlorobenzyl)-7-(deformedarse)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (30 mg, 0,069 mmol) was dissolved in dichloromethane (2 ml). Added 5N hydrochloric acid in isopropanol (0.3 ml) and the reaction mixture was stirred at room temperature for 3 h. the Solvent is evaporated in vacuum. Yield: 26 mg (0,069 mmol, 100%, colorless solid).

ESI-MS [M+H+]=338 calculated for C18H18ClF2NO=337.

Example 37: Benzyl [1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

tert-Butyl [1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (2 g, to 6.95 mmol, obtained similarly t�et-butyl [1-(3,4-dichlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate, see also example 34.2) suspended in dimethylformamide (40 ml). Add triethylamine (0,969 ml of 6.95 mmol) and benzylcarbamoyl (1,186 g, to 6.95 mmol). The reaction mixture was stirred at room temperature over night. The solvent is evaporated in vacuum. To the crude product is added ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layers are dried (MgSO4) and concentrated in vacuo. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Output: 393 mg (0,931 mmol, 13.4 per cent, colorless foam).

ESI-MS [M+H+]=422, calculated for C25H24ClNO3=421.

Example 38: tert-Butyl [7-(aminomethyl)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

tert-Butyl [7-cyano-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (30 mg, 0.07 mmol, see also example 34d) was dissolved in methanol (3 ml). Add Raney Nickel (10 mg) and the reaction mixture was stirred at room temperature in hydrogen atmosphere for 4 h. the Catalyst was removed by filtration, and the methanol is evaporated in vacuum. Yield: 18 mg (0,041 mmol, 59%).

ESI-MS [M+H+]=435, calculated for C23H28Cl2N2O2=434.

Example 39: tert-Butyl [1-(3,4-dichlorobenzyl)-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

tert-Butyl [7-(aminomethyl)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (120 mg, 0.276 mmol, see example 38) was dissolved in dichloromethane (5 ml). Add 4-dimethylaminopyridine (35 mg, 0,289 mmol). After stirring at room temperature for 5 min add propane-1-sulphonylchloride (39 mg, 0.031 inch mmol), and stirring was continued over night. The reaction mixture was diluted with dichloromethane and washed successively with 0.5 N hydrochloric acid (CH ml) and a saturated solution of NaHCO3(CH ml). The organic phase was dried (MgSO4) and concentrated in vacuo. The crude product was used for next step without further purification. Yield: 125 mg (0,231 mmol, 84%).

ESI-MS [M+Na+]=563 calculated for C26H34Cl2N2O4S=540.

Example 40: N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

Tert-butyl [1-(3,4-dichlorobenzyl)-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (120 mg, 0,222 mmol, see example 39) was dissolved in 5N Rasbora hydrochloric acid in isopropanol (2 ml). The reaction mixture was stirred at room temperature for 1 h. the Solvent was evaporated, and the product was dried in vacuum. Yield: 101 mg (0,211 mmol, 95%).

ESI-MS [M+H+]=441, scheduled for�about for C 21H26Cl2N2O2S=440.

Example 41: N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-forproper-1-sulfonamide hydrochloride

Connection receive according to the method of example 40, using 3-forproper-1-sulphonylchloride instead of n-propane-1-sulphonylchloride.

ESI-MS [M+H+]=459, calculated for C21H25Cl2FN2O2S=458.

Example 42: N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide triptorelin

N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride (40 mg, 0,084 mmol, see example 40) was dissolved in methanol (4 ml) and is hydrogenated on H-cube (1 h, 40°C, 30 bar, 20% Pd/C). The solvent was evaporated, and the crude product was then purified by the method of preparative HPLC (column xTerra prep MS C18, C mm, 5 μm; gradient: water-acetonitrile containing 0.1% trifluoroacetic acid, flow rate: 20 ml/min). Output: 4,9 mg (0,0102 mmol, 12%).

ESI-MS [M+H+]=373, calculated for C21H28N2O2S=372.

Example 43: N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine hydrochloride

Connection receive according to the method of example 40, using cyclobutylamine instead of n-propane-1-sulfonyl�lorida.

ESI-MS [M+H+]=385, calculated for C22H28N2O2S=384.

Example 44: N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanecarboxamide hydrochloride

Connection receive according to the method of example 40, using cyclopropanesulfonyl instead of n-propane-1-sulphonylchloride.

ESI-MS [M+H+]=385, calculated for C22H28N2O2S=384.

Example 45: N-{[CIS-7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamide hydrochloride

Tert-butyl-1-benzyl-7-(propylsulfonyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (35 mg, between 0.074 mmol, obtained according to the method of example 40) was dissolved in acetonitrile (1 ml). Added sequentially cesium carbonate (29 mg, 0.09 mmol)) and methyliodide (12 μl, 0,19 mmol) and the reaction mixture was heated in a microwave at 100°C for 3 h. the Solvent is evaporated in vacuum. The residue was treated with dichloromethane and washed with water. The organic layer was dried (MgSO4) and concentrated. The crude product is dissolved in isopropanol and treated with 5 M hydrochloric acid solution in isopropanol. The solvent is evaporated under vacuum to give the final product as colorless solids. Yield: 18 mg (0,043 mmol, 58%).

ESI-MS [M+H+]=387, �Asciano for C 22H30N2O2S=386.

Example 46: {1-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

46.1 7-(2-tert-Butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

7-(2-tert-Butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester receive according to the method of example 1, using 1-methyl bromide-3-chlorobenzene instead of 4-(methyl bromide)-1,2-dichlorobenzene.

ESI-MS [M+H+]=503 calculated for C27H35ClN2O5=502.

46.2 {1-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

{1-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester receive according to the method of example 2, using as starting substances 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester obtained in the previous phase and 1-methyl-1H-pyrazol-4-sulphonylchloride instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=547, calculated for C26H31ClN4O5=546.

When�EP 47 : 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using as starting substances {1-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 46).

ESI-MS [M+H+]=475, calculated for C23H27ClN4O3S=474.

Example 48: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride get in three steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 47, using 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=475, calculated for C23H27ClN4O3S=474.

Example 49: {1-(3-Chlorobenzyl)-7-[2-(2,4-dimethylthiazol-5-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using 2,4-dimethylthiazol-5-sulphonylchloride.

ESI-MS [M+H+]=578 calculated for C27H32ClN3O5S2=577.

Example 50: {1-(3-Chlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using thiophene-2-sulphonylchloride.

ESI-MS [M+H+]=549 calculated for C26H29ClN2O5S2=548.

Example 51: {1-(3-Chlorobenzyl)-7-[2-(5-chlorothiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46 using 5-chlorothiophene-2-sulphonylchloride.

ESI-MS [M+H+]=583 calculated for C26H28Cl2N2O5S2=582.

Example 52: {1-(3-Chlorobenzyl)-7-[2-(2-methyl-3H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-t�traditionellen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using 2-methyl-3H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=547, calculated for C26H31ClN4O5S=546.

Example 53: {1-(3-Chlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46 using 5-methylthiophene-2-sulphonylchloride.

ESI-MS [M+H+]=563 calculated for C27H31ClN2O5S2=562.

Example 54: {1-(3-Chlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using 4-methylthiophene-2-sulphonylchloride.

ESI-MS [M+H+]=563 calculated for C27H31ClN2O5S2=562.

Example 55: Propane-1-sulfonic acid {2-[7-AMI�about-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in three stages from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 48, using propane-1-sulphonylchloride.

ESI-MS [M+H+]=437, calculated for C22H29ClN2O3S=436.

Example 56: Thiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

Get in one step from {1-(3-Chlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester according to the method of example 48.

ESI-MS [M+H+]=477 calculated for C23H25ClN2O3S2=476.

Example 57: 2,4-Dimethylthiazol-5-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

Get in one step from {1-(3-Chlorobenzyl)-7-[2-(2,4-dimethylthiazol-5-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 49) according to the method of example 48.

ESI-MS [M+H+]=506, calculated for C24H28ClN3O3S2=505.

Example 58: 2-Methyl-3H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

Get in on�well stage from {1-(3-Chlorobenzyl)-7-[2-(2-methyl-3H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 52) by the method of example 48.

ESI-MS [M+H+]=475, calculated for C23H27ClN4O3S=474.

Example 59: 5-Chlorothiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

Get in one step from {1-(3-Chlorobenzyl)-7-[2-(5-chloro-thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 51) by the method of example 48.

ESI-MS [M+H+]=511, calculated for C23H24Cl2N2O3S2=510.

Example 60: {1-(3-Chlorobenzyl)-7-[2-(2,5-dimethylthiophene-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using 2,5-dimethylthiophene-3-sulphonylchloride.

ESI-MS [M+H+]=577 calculated for C28H33ClN2O5S2=576.

Example 61: {1-(3-Chlorobenzyl)-7-[2-(1-ethyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method in�EPA 46, using 1-Ethyl-1H-pyrazol-4-sulphonylchloride.

ESI-MS [M+H+]=561 calculated for C27H33ClN4O5S=560.

Example 62: {1-(2,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Receive according to the method of example 46, using 1-methyl bromide-2,4-dichlorobenzene instead of 4-(methyl bromide)-3-chlorobenzene.

ESI-MS [M+H+]=581 calculated for C26H30Cl2N4O5S=580.

Example 63: {1-(2,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Receive according to the method of example 62, using thiophene-2-sulphonylchloride instead of 1-methyl-1H-pyrazol-4-sulphonylchloride.

ESI-MS [M+H+]=583 calculated for C26H28Cl2N4O5S2=582.

Example 64: {1-(2,4-Dichlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Receive according to the method of example 62, using 5-methylthiophene-2-sulphonylchloride instead of 1-methyl-1H-pyrazol-4-sulphonylchloride.

ESI-MS [M+H+]=597 calculated for C27H30Cl2N2O5S2=596.

Example 65: [1-(3-Chlorobenzyl)-7-(2-ethanolamine�si)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using ethanolgasoline.

ESI-MS [M+H+]=495 calculated for C24H31ClN2O5S=494.

Example 66: 1-Ethyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from {1-(3-Chlorobenzyl)-7-[2-(1-ethyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 61) according to the method of example 48.

ESI-MS [M+H+]=489, calculated for C24H29ClN4O3S=488.

Example 67: 4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from {1-(3-Chlorobenzyl)-7-[2-(2-methyl-3H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 53) according to the method of example 48.

ESI-MS [M+H+]=491 calculated for C24H27ClN2O3S2=490.

Example 68: 5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide of hydrochlori�

Get in one step from {1-(3-Chlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 53) according to the method of example 48.

ESI-MS [M+H+]=491 calculated for C24H27ClN2O3S2=490.

Example 69: 2,5-Dimethylthiophene-3-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from {1-(3-Chlorobenzyl)-7-[2-(2,5-dimethylthiophene-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 60) according to the method of example 48.

ESI-MS [M+H+]=505, calculated for C25H29ClN2O3S2=504.

Example 70: Econsultancy acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from [1-(3-Chlorobenzyl)-7-(2-ethanolamines)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester (example 65) according to the method of example 48.

ESI-MS [M+H+]=423, calculated for C21H27ClN2O3S=422.

Example 71: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from {1-(2,4-dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 62) according to the method of example 48.

ESI-MS [M+H+]=509 calculated for C23H26Cl2N4O3S=508.

Example 72: Thiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from {1-(2,4-dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 63) according to the method of example 48.

ESI-MS [M+H+]=511, calculated for C23H24Cl2N2O3S2=510.

Example 73: 5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from {1-(2,4-dichlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 64) by the method of example 48.

ESI-MS [M+H+]=525, calculated for C24H26Cl2N2O3S2=524.

Example 74: {1-(2,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Receive according to the method of example 62, using propane-1-sulphonylchloride instead of 1-methyl-1H-pyrazol-4-sulphonylchloride.

ESI-MS [M+H+]=543 calculated for C25H32Cl2N2O5S=542.

Example 75: Propane-1-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get in one step from {1-(2,4-dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester (example 74) by the method of example 48.

ESI-MS [M+H+]=471, calculated for C22H28Cl2N2O3S=470.

Example 76: (1-(4-Chlorobenzyl)-7-{2-[methyl-(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester

76.1 2-(N-methylpropanesulfonate)ethyl propane-1-sulfonate

To the cooled solution (0-5°C) 2-(methylamino)ethanol (of 8.56 ml, 107 mmol) in 100 ml of DCM is added dropwise a solution of propane-1-sulphonylchloride (13,1 ml, 117 mmol) in 50 ml of DCM for 1 h. the resulting mixture was stirred at room temperature over night. Add water and 10% citric acid and then extracted with DCM, dried over MgSO4, filtered and evaporated, yielding a yellow-orange oil (13.6 g). After chromatography gain of 2.75 g of the product.

76.2 (1-(4-Chlorobenzyl)-7-{-[methyl-(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester

A solution of ethyl 1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (of 0.128 g, 0,355 mmol) in DMF in an atmosphere of N2treated with sodium hydride (0,014 g, 0,568 mmol) and the reaction mixture was stirred for 30 minutes at room temperature. Added a solution of 2-(N-methylpropanesulfonate)ethyl propane-1-sulfonate (is 0.102 g, 0,355 mmol) (see stage 1) in DMF, and the reaction mixture was stirred at ambient temperature overnight. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water, dried (MgSO4), filtered and evaporated, yielding a brown/white crystals. After adding a few drops of the mixture ethyl acetate/cyclohexane (1:4) a white precipitate is formed. Yield 43 mg.

ESI-MS [M+H+]=523 calculated for C26H35ClN2O5S=522.

Example 77: Propane-1-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamine hydrochloride

Get in one step from (1-(4-Chlorobenzyl)-7-{2-[methyl-(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester (example 76) by the method of example 48.

ESI-MS [M+H+]=451, calculated for C23H31ClN2O3S=450.

Example 78: (1-(3-Chlorobenzyl)-7-{2-[methyl-(propane-1-sulfonyl)amino]ethoxy}-1,2,,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester

Prepared from [1-(3-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 77.

ESI-MS [M+H+]=523 calculated for C26H35ClN2O5S=522.

Example 79: Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamine hydrochloride

Get in one step from (1-(3-Chlorobenzyl)-7-{2-[methyl-(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester (example 78) according to the method of example 48.

ESI-MS [M+H+]=451, calculated for C23H31ClN2O3S=450.

Example 80: {1-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=547, calculated for C26H31ClN4O5S=546.

Example 81: {1-(3-Chlorobenzyl)-7-[2-(1-deformity-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared in two steps from 7-(2-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 46, using 1-deformity-1H-pyrazol-4-sulphonylchloride.

ESI-MS [M+H+]=583 calculated for C26H29ClF2N4O5S=582.

Example 82: 1-(3-Chlorobenzyl)-7-[(R)-1-(propane-1-sulfonyl)pyrrolidin-2-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

82.1 (Propane-1-sulfonic acid (R)-1-(propane-1-sulfonyl)-pyrrolidin-2-ymetray ether

Receive according to the method described for 2-(N-methylpropanesulfonate)ethyl propane-1-sulfonate (example 76, step 1), using (R)-1-pyrrolidin-2-ylmethanol instead of 2-(methylamino)of ethanol.

82.2 1-(3-Chlorobenzyl)-7-[(R)-1-(propane-1-sulfonyl)-pyrrolidin-2-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Prepared in two steps from (propane-1-sulfonic acid (R)-1-(propane-1-sulfonyl)pyrrolidin-2-Eletropaulo ether (see previous stage) and ethyl 1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate as described in example 77.

ESI-MS [M+H+]=477 calculated for C25H33ClN2O3S=476.

Example 83: 1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yloxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

To the cooled solution (0-5°C) of azetidin-3-ol hydrochloride (1 g, 9,13 mmol) in 10 ml of dichloromethane containing diisopropylethylamine (2,391 ml 13,69 mmol), was added dropwise a solution of propane-1-sulphonylchloride (1,126 ml, 10,04 mmol) in 5 ml of dichloromethane for 1 h. the Mixture is allowed to warm to room temperature and stirred over night. Add citric acid (10%), extracted with dichloromethane, dried over MgSO4, filtered and the solvent evaporated, yielding 597 mg of a yellow oil which is purified by chromatography (yield 470 mg).

83.2 Methanesulfonic acid 1-(propane-1-sulfonyl)azetidin-3-silt ether

To a solution of 1-(propane-1-sulfonyl)azetidin-3-ol (236 mg, 1,317 mmol) in pyridine is added dropwise methanesulfonanilide (205 µl, 2,63 mmol) at 0°C. the Mixture is allowed to warm to room temperature and stirred for 3 h. dichloro methane is Added. The mixture was sequentially washed with water, saturated solution of NaHCO3and saturated salt solution, dried (MgSO4) and filtered. The solvent was evaporated, yielding 293 mg of crude product used without further purification.

83.3 1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yloxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Get� in two stages from methanesulfonic acid 1-(propane-1-sulfonyl)azetidin-3-silt ether (see previous stage) and ethyl 1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate as described in example 77.

ESI-MS [M+H+]=449 calculated for C23H29ClN2O3S=448.

Example 84: 1-(3-Chlorobenzyl)-7-(3-econsultancy)-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Prepared in two steps from 1-chloro-3-ethanolgasoline (see: Synthetic Communications, 19(9-10), 1583-91; 1989) and ethyl 1-(4-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate according to the method of example 77.

ESI-MS [M+H+]=422, calculated for C22H28ClNO3S=421.

Example 85: Cyclohexanesulfamic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Cyclohexanesulfamic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3, using cyclohexylsulfamate instead of 1-methyl-1H-imidazol-4-sulphonylchloride.

ESI-MS [M+H+]=511, calculated for C25H32Cl2N2O3S=510.

Example 86: 2-Trimethylsilylamodimethicone acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

2-Trimethylsilylamodimethicone acid {2-[7-amino-8-(3,4-dichloran�yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=529, calculated for C24H34Cl2N2O3SSi=528.

Example 87: N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-(5-methylisoxazol-3-yl)-methanesulfonamide hydrochloride

N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-(5-methylisoxazol-3-yl)methanesulfonamide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=524, calculated for C24H27Cl2N3O4S=523.

Example 88: Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

88.1 1-(1-(3,4-Dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)pyrrolidin

1-(3,4-Dichlorobenzyl)-7-methoxy-3,4-dihydronaphthalene-2(1H)-he (5.5 g, 16.4 mmol, example 1), pyrrolidine (1.40 g, of 19.7 mmol), and p-toluensulfonate acid monohydrate (31,0 mg, 0,164 mmol) was dissolved in toluene (100 ml) and heated to reflux for 2 h, using a condenser, Dean stark. The solvent was removed, and after adding MeOH (50 ml) and cyanohydrine sodium (1,57 g, at 24.6 mmol) the mixture was stirred for 4 days at room temperature in a nitrogen atmosphere. Water was added, the organic phase was separated and the aqueous phase extracted with ethyl acetate. About�yedinenye organic layers washed with saturated NaCl solution, dried over MgSO4and concentrate, receiving the remainder, which is purified flash chromatography (silica gel, MeOH/CH2Cl23:97→5:95). After deposition from a mixture of ethyl acetate/diisopropyl ether (1:1) receive solid beige product (1.6 g, 25%).

88.2 8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol

1-(1-(3,4-Dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)pyrrolidine (1.6 g, 4.10 mmol) was dissolved in CH2Cl2(100 ml) and added BBr3(1-molar solution in CH2Cl2, of 12.3 ml, 12.3 mmol) at -10°C. was Stirred for 2 h, after which the temperature was raised to room. Add ice water, the organic phase was separated and the aqueous phase extracted with CH2Cl2. The combined organic layers washed with saturated solution of NaHCO3and NaCl, dried over Na2SO4and concentrate, receiving the remainder. After precipitation from ethyl acetate receive solid beige product (1.2 g, 78%).

88.3 tert-Butyl 2-(8-(3,4-dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethylcarbamate

NaH in paraffin (0,278 g, 6,38 mmol, 55% in paraffin) was washed with n-hexane and suspended in DMA (30 ml). Add 8-(3,4-dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol (1.2 g, 3,19 mmol) in DMA (20 ml). After stirring the�Linux 1 h at room temperature add portions of tert-butyl 2-bramatelecom (2.14 g, at 6.38 mmol) and the mixture was stirred for 48 h. water was Added, and the aqueous phase extracted with ethyl acetate. The combined organic layers washed with saturated NaCl solution, dried over Na2SO4and concentrate, receiving the remainder, which is purified flash chromatography (silica gel, MeOH/CH2Cl23:97). The product (1.6 g, 97%) was obtained as a yellow oil.

88.4 2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethanamine hydrochloride

tert-Butyl 2-(8-(3,4-dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethylcarbamate (1.6 g, is 3.08 mmol) was dissolved in CH2Cl2(70 ml) and add HCl in iPrOH. Stirred for 14 h at room temperature, after which the temperature was raised to room. The solvent was removed, yielding a white salt (1.2 g, 85%).

88.5 Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethanamine (120 mg, 0,286 mmol), para-(N,N-dimethylamino)pyridine (1.40 g, of 19.7 mmol) and cyclobutanemethanol (46,5 mg, 0,30 mmol) was dissolved in CH2Cl2(20 ml) and stirred for 14 h at room temperature. Add 0.5 N HCl, the organic phase was separated, and the aqueous phase EC�tracerout CH 2Cl2. The combined organic layers washed with water, a solution of NaHCO3and a saturated solution of NaCl, dried over Na2SO4and concentrate, receiving the remainder, which is purified flash chromatography (silica gel, MeOH/CH2Cl23:97→5:95). The solid white product (164 mg, 32%) are converted to HCl salt and precipitated from diisopropyl ether.

ESI-MS [M+H+]=537 calculated for C27H34Cl2N2O3S=536.

Example 89: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamine hydrochloride

N-(2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride (41 mg, 0,068 mmol, example 91), itmean (11,6 mg, 0,082 mmol), cesium carbonate (49,0 mg, 0,150 mmol) was dissolved in acetonitrile (3 ml) and stirred for 1 h at 100°C in a microwave oven. After adding another portion of iodomethane (11,6 mg, 0,082 mmol) and cesium carbonate (49,0 mg, 0,150 mmol) the mixture was stirred another 1 h at 100°C in a microwave oven. Add water and CH2Cl2, the organic phase was separated, and the aqueous phase extracted with CH2Cl2. The combined organic layers washed with saturated NaCl solution, dried over Na2SO4and concentrate, receiving the remainder, which�th purified flash chromatography (silica gel, MeOH/CH2Cl23:97→5:95). The solid white product (42 mg, 38%) are converted to HCl salt and precipitated from diisopropyl ether.

ESI-MS [M+H+]=577 calculated for C28H34Cl2N4O3S=576.

Example 90: Butane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Butane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=485, calculated for C23H30Cl2N2O3S=484.

Example 91: Propane-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Propane-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=471, calculated for C22H28Cl2N2O3S=470.

Example 92: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

1-Methyl-1H-pyrazol-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide of hydrochlori� receive according to the method of example 88. ESI-MS [M+H+]=563 calculated for C27H32Cl2N4O3S=562.

Example 93: 2-Ethoxyethanol acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

2-Ethoxyethanol acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=501 calculated for C23H30Cl2N2O4S=500.

Example 94: Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamine hydrochloride

Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide hydrochloride is prepared from N-(2-(8-(3,4-dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)cyclobutanemethanamine hydrochloride (example 88) according to the method of example 89.

ESI-MS [M+H+]=551 calculated for C28H36Cl2N2O3S=550.

Example 95: N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl hydrochloride

N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl of hydrochl�Reid receive according to the method of example 3.

ESI-MS [M+H+]=483 calculated for C23H28Cl2N2O3S=482.

Example 96: Propane-1-sulfonic acid {2-[7-amino-8-(4-methoxybenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Propane-1-sulfonic acid {2-[7-amino-8-(4-methoxybenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=433 calculated for C23H32N2O4S2=432.

Example 97: N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methanesulfonamide hydrochloride

N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)methanesulfonamide hydrochloride (50.0 mg, 0.104 mmol), Pd-C 10% (1,10 mg) and hydrazine monohydrate (522 mg, 10.4 mmol) suspended in ethanol (5 ml) and stirred for 4 hours under heating to reflux. Add water and CH2Cl2the mixture was filtered, and the filtrate was extracted with CH2Cl2. The combined organic layers washed with water, saturated NaCl, dried over Na2SO4and concentrate, receiving the remainder, which is purified by precipitation from diisopropyl ether. The residue was converted into HCl salt, and the product comes in the form of a white solid (31 mg, 72%).

ESI-MS [M+H+]=375, calculated for C20H26N 2O3S=374.

Example 98: 1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide hydrochloride

1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide hydrochloride receive according to the method of example 3 and 89.

ESI-MS [M+H+]=455, calculated for C24H30N4O3S=454.

Example 99: N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]benzosulfimide hydrochloride

N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]benzosulfimide hydrochloride is prepared from N-{2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}benzosulfimide hydrochloride (example 16) according to the method of example 3 and 97.

ESI-MS [M+H+]=437, calculated for C25H28N2O3S=436.

Example 100: 3,3,3-Cryptochrome-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide hydrochloride

3,3,3-Cryptochrome-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide hydrochloride receive according to the method of example 3 and 97.

ESI-MS [M+H+]=457, calculated for C22H27F3N2O3S=456.

Example 101: 1-Methyl-1H-imidazol-4-�Lanovoy acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide hydrochloride

N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N,1-dimethyl-1H-imidazole-4-sulfonamide hydrochloride (98), 1,4-dibromobutane accounting for 49.9 mg, 0,231 mmol) and triethylamine (31,2 mg, 0,308 mmol) was dissolved in acetonitrile (3 ml) and stirred for 2 h at 130°C in a microwave oven. Add water and ethyl acetate, and the organic phase was separated. After extraction of the aqueous phase with ethyl acetate the combined organic layers washed with saturated NaCl solution, dried over Na2SO4and concentrate, receiving the remainder, which is purified flash chromatography (silica gel, MeOH/CH2Cl25:95). The residue was converted to HCl salt and get the product as a white solid (8.5 mg, 10%) after precipitation from diisopropyl ether.

ESI-MS [M+H+]=509 calculated for C28H36N4O3S=508.

Example 102: Cyclopropanemethanol acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide hydrochloride

Cyclopropanemethanol acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide hydrochloride receive according to the method of example 3 and 97.

ESI-MS [M+H+]=401, calculated for C22H28N2O3S=400.

Example 103: N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]propionamide hydrochloride

Ethyl 7-(2-aminoethoxy)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate hydrochloride (example 2.1, 100 mg, 0,229 mmol) and N,N-dimethylaminopyridine (to 30.7 mg, 0,252 mmol) was dissolved in CH2Cl2(20 ml) at room temperature was added propionitrile (to 30.7 mg, 0,252 mmol). After stirring at room temperature for 14 h added 0.5 N HCl and the mixture extracted with CH2Cl2. The combined organic layers washed with saturated solution of NaHCO3and NaCl, dried over Na2SO4and concentrate, receiving the remainder. After precipitation from ethyl acetate, a white solid ethyl 1-(3,4-dichlorobenzyl)-7-(2-propionamido)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (98 mg, 87%). As a result of subsequent transformation according to the method of example 2 and get 97 N-[2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]propionamide hydrochloride.

ESI-MS [M+H+]=353, calculated for C22H28N2O2=352.

Example 104: 1-Methyl-1H-[1,2,4]triazole-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

1-Methyl-1H-[1,2,4]triazole-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide receive according to the method of example 3.

ESI-MS [M+H+]=510, calculated for C22H25Cl2N5O3S=509.

Example 105: 1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide

1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide receive according to the method of example 101.

ESI-MS [M+H+]=495 calculated for C27H34N4O3S=494.

Example 106: N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclobutanemethanamine hydrochloride

N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclobutanemethanamine hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=497 calculated for C24H30Cl2N2O3S=496.

Example 107: Propane-1-sulfonic acid {2-[7-amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Propane-1-sulfonic acid {2-[7-amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=421, calculated for C22H29FN2O3S=420.

Example 108: N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropyl-N-methylmethanesulfonamide hydrochloride

N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropyl-N-methylmethanesulfonamide hydrochloride receive according to the method of example 11.

ESI-MS [M+H+]=497 calculated for C24H30Cl2N2O3S=496.

Example 109: 1-Methyl-1H-pyrazol-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide

1-Methyl-1H-pyrazol-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide receive according to the method of example 3 and 89.

ESI-MS [M+H+]=455, calculated for C24H30N4O3S=454.

Example 110: N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide

N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide receive according to the method of example 11.

ESI-MS [M+H+]=537 calculated for C25H30Cl2N4O3S=536.

Example 111: 1-Methyl-1H-pyrazol-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide hydrochloride

1-Methyl-1H-pyrazol-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide hydrochloride get JV�soba example 50.

ESI-MS [M+H+]=509 calculated for C28H36N4O3S=508.

Example 112: 1-Methyl-1H-pyrazol-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide hydrochloride

1-Methyl-1H-pyrazol-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide hydrochloride receive according to the method of example 50.

ESI-MS [M+H+]=495 calculated for C27H34N4O3S=494.

Example 113: N-(2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride

N-(2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride receive according to the method of example 3 and 89.

ESI-MS [M+H+]=469, calculated for C25H32N4O3S=468.

Example 114: N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)pentane-1-sulfonamide hydrochloride

N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)pentane-1-sulfonamide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=499, calculated for C24H32Cl2N2O3S=498.

Example 115: N-(2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphtyl�len-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-(2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride synthesized according to the method of example 88.

ESI-MS [M+H+]=536, calculated for C27H32Cl2N4O3S=535.

Example 116: N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride is prepared from N-(2-(8-(3,4-dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide (example 115) according to the method of example 97.

ESI-MS [M+H+]=495 calculated for C27H34N4O3S=494.

Example 117, 118 (Enantiomers 1 and 2 of the compound of example 116)

The racemate of N-(2-(8-benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride (example 116) separated by the method of chiral chromatography on a Chiracel AD (n-heptane/ethanol 35:65, about 0.1% TEA, 9 ml/min) to give (after conversion to a salt form) (-)-N-(2-(8-benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride ([α]=-76,0° in MeOH, c=1,040 g/100 ml [example 117]) and (+)-N-(2-(8-Ben�Il-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride ([α]=-77,7° in MeOH, c=equation (0.382 g/100 ml [example 118]).

ESI-MS [M+H+]=495 calculated for C27H34N4O3S=494.

Example 119: N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride

N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride is prepared from N-(2-(8-(3,4-dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-pyrazole-4-sulfonamide (example 114) according to the method of example 97.

ESI-MS [M+H+]=495 calculated for C27H34N4O3S=494.

Example 120: N-(2-{[7-Amino-8-(3-chloro-4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide hydrochloride

N-(2-{[7-Amino-8-(3-chloro-4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=455, calculated for C22H28ClFN2O3S=454.

Example 121: N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=415, calculated for C23H 30N2O3S=414.

Example 122: N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetic hydrochloride

N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetic hydrochloride synthesized according to the method of example 103.

ESI-MS [M+H+]=447, calculated for C24H28Cl2N2O2=446.

Example 123: N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)benzamide derivative hydrochloride

N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)benzamide derivative hydrochloride synthesized according to the method of example 103.

ESI-MS [M+H+]=469, calculated for C26H26Cl2N2O2=468.

Example 124: N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride

N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride synthesized from N-(2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride (example 113) by way of example 97.

ESI-MS [M+H+]=523 calculated for C29H38N4O3S=522.

Example 125: N-(2-{[7-amine�-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylethanol hydrochloride

N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylethanol hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=497 calculated for C24H30Cl2N2O3S=496.

Example 126: C-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-N-methylmethanesulfonamide hydrochloride

C-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-N-methylmethanesulfonamide hydrochloride synthesized according to the methods of examples 89, 97, 101.

ESI-MS [M+H+]=551 calculated for C28H36Cl2N2O3S=550.

Example 127: N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride

N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride synthesized from 1-cyclopropyl-N-(2-{[8-(3,4-dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N-methylmethanesulfonamide hydrochloride according to the method of example 97.

ESI-MS [M+H+]=483 calculated for C28H38N2O3S=482.

Example 128: N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ox�}ethyl)-1-cyclopropanesulfonyl hydrochloride

N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=449 calculated for C23H29ClN2O3S=448.

Example 129: N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride

N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride receive according to the method of example 3, N-methylation is carried out according to the method of example 89.

ESI-MS [M+H+]=463 calculated for C24H31ClN2O3S=462.

Example 130: N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]-C-cyclopropyl-N-methylmethanesulfonamide hydrochloride

N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]-C-cyclopropyl-N-methylmethanesulfonamide hydrochloride is prepared from N-(2-{[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride (example 108) according to the method of example 97.

ESI-MS [M+H+]=429, calculated for C24H32N2O3S=428.

Example 131: N-(2-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropylmethyl�of ifosamide hydrochloride

N-(2-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride receive according to the method of example 3.

ESI-MS [M+H+]=451, calculated for C23H28F2N2O3S=450.

Example 132: C-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide hydrochloride

C-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide hydrochloride receive according to the method of example 88.

ESI-MS [M+H+]=537 calculated for C27H34Cl2N2O3S=536.

Example 133: N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride is prepared from C-cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide hydrochloride (example 132) by way of example 97.

ESI-MS [M+H+]=469, calculated for C27H36N2O3S=468.

Example 134: 1-Cyclopropyl-N-[2-({8-(3,4-dichlorobenzyl)-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]m�consultame

7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-ol (691 mg, 2,146 mmol, example 34), 2 EQ. 1,4-dibrom-2-verboten and 3 EQ. of triethylamine dissolved in acetonitrile (10 ml) and heated in a microwave for 2 h. After adding water with ethyl acetate, washing the organic phase with saturated solution of NaHCO3NaCl, drying over Na2SO4and flash chromatography (silica gel, CH2Cl2/MeOH 95:5) 8-(3,4-dichlorobenzyl)-7-(3-ftorpirimidinu-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol (330 mg, 39%). Atelocollagen side chain is added by the method of examples 1, 7, 8, yielding 1-cyclopropyl-N-[2-({8-(3,4-dichlorobenzyl)-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]methanesulfonamide.

ESI-MS [M+H+]=555, calculated for C27H33Cl2FN2O3S=554.

Example 135: N-(2-{[7-(Azetidin-1-yl)-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl

N-(2-{[7-(Azetidin-1-yl)-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl receive according to the method of example 320.

ESI-MS [M+H+]=523 calculated for C26H32Cl2N2O3S=522.

Example 136: N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-cyclopropanesulfonyl guide�klorid

N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-cyclopropanecarboxamide hydrochloride synthesized from 1-cyclopropyl-N-[2-({8-(3,4-dichlorobenzyl)-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]methanesulfonamide (example 134) by way of example 97.

ESI-MS [M+H+]=487 calculated for C27H35FN2O3S=486.

Example 137: N-(2-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

The synthesis was carried out using as starting substances, ethyl 1-benzyl-7-(2-(cyclopropanesulfonyl)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (synthesized according to the method of example 3) was dissolved in THF (50 ml), after which at room temperature is added LiAlH4and the mixture was stirred for 8 h under heating to reflux. Then added 2N aqueous NaOH, extracted with CH2Cl2organic layers washed with saturated solution of NaHCO3and saturated NaCl solution, the solvent is evaporated and get the remainder, which is treated with iPrOH/HCl, whereupon the product is precipitated. After filtration get a white salt (287 mg, 58%).

ESI-MS [M+H+]=429, calculated for C24H32N2O3S=428.

Example 138: -Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide hydrochloride

1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide hydrochloride synthesized according to the methods of examples 264/88.

ESI-MS [M+H+]=487, C27H35FN2O3S=486.

Example 139: N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride synthesized according to the method of example 320.

ESI-MS [M+H+]=473, C26H33FN2O3S=472.

Example 140: N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride synthesized according to the methods of examples 264/88.

ESI-MS [M+H+]=513, C27H33FN4O3S=512.

Example 141: N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazol-4-sulfonmethane synthesized according to the method of example 320.

ESI-MS [M+H+]=499 C26H31FN4O3S=498.

Example 142: N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride synthesized according to the method of example 320.

ESI-MS [M+H+]=455 C26H34N2O3S=454.

Examples 143, 144 (Enantiomers 1 and 2 of the compound of example 142)

The racemate of N-(2-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanecarboxamide hydrochloride (example 142) are separated by chiral chromatography on a Chiracel AD (n-heptane/ethanol 35:65, about 0.1% TEA, 9 ml/min), receiving (after conversion to a salt form) (-)-N-(2-(7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-cyclopropanesulfonyl ([α]=-103,0° in MeOH, c=0,461 g/100 ml [example 143]) and (+)-N-(2-(7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-cyclopropanesulfonyl succinate ([α]=+57,0° in MeOH, c=0,508 g/100 ml [example 144]).

ESI-MS [M+H+]=455, C26H34N2O3S=454.

Example 145: N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide

N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-Tetra�adrenalin-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide synthesized according to the method of example 320.

ESI-MS [M+H+]=481, C26H32N4O3S=480.

Example 146:

The racemate of N-(2-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide (145) can be divided by chiral chromatography to obtain (after conversion to a salt form) (-)-N-(2-((7S,8R)-7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide fumarate ([α]=-81,4° in MeOH, c=0,409 g/100 ml).

ESI-MS [M+H+]=481, calculated for C27H34N4O3S=480.

Example 147: N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)cyclobutanemethanamine

N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)cyclobutanemethanamine synthesized according to the method of example 320.

ESI-MS [M+H+]=455, C26H34N2O3S=454.

Example 148: Propane-1-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide

Propane-1-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide is synthesized according to the method of example 320.

ESI-MS [M+H+]=443, C25H34N2O3S=442.

Example 149: N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-su�of ifosamide hydrochloride

N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide hydrochloride synthesized according to the methods of examples 264/88.

ESI-MS [M+H+]=512, C28H34FN3O3S=511.

Example 150: N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride synthesized according to the method of example 3.

ESI-MS [M+H+]=467, C23H28ClFN2O3S=466.

Example 151: N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride synthesized according to the method of example 3.

ESI-MS [M+H+]=493, C23H26ClFN4O3S=492.

Example 152: N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-methyl-1H-imidazole-4-sulfonamide hydrochloride Shin�Airout by way of example 264/88.

ESI-MS [M+H+]=513, C27H33FN4O3S=512.

Example 153: N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide

N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide synthesized according to the method of example 264/88.

ESI-MS [M+H+]=520, C28H33N5O3S=519.

Example 154: N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride synthesized according to the method of example 88.

ESI-MS [M+H+]=508, C27H33N5O3S=507.

Example 155: N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride synthesized according to the methods of examples 264/88.

ESI-MS [M+H+]=494, C28H35N3O3S=493.

Example 156: N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-�of eloprofessional hydrochloride

N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride synthesized according to the method of example 88.

ESI-MS [M+H+]=482, C27H35N3O3S=481.

Example 157: N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide hydrochloride

N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide hydrochloride synthesized from propane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride (example 8) according to the method of example 97.

ESI-MS [M+H+]=403, C22H30N2O3S=402.

Example 158: N-(2-{[8-(3-Chloro-5-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

The synthesis was carried out using as starting substances, ethyl 1-(3-chloro-5-terbisil)-7-(2-(cyclopropanesulfonyl)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (synthesized according to the method of example 3) was dissolved in THF (50 ml), after which at room temperature is added LiAlH4and the mixture was stirred for 8 h under heating to reflux. After adding 2N aqueous NaOH, extraction with CH2 Cl2washing the organic layer with saturated solution of NaHCO3and saturated NaCl solution and evaporation of the solvent gave a residue which is treated with iPrOH/HCl, whereupon the product is precipitated. After filtration a white salt (134 mg, 39%).

ESI-MS [M+H+]=481, calculated for C24H30ClFN2O3S=480.

Example 159: N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl (2E)-but-2-entiat

N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl (2E)-but-2-entiat synthesized according to the method of example 320.

ESI-MS [M+H+]=507, C26H32ClFN2O3S=506.

Example 160: N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide (2E)-but-2-entiat

N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide (2E)-but-2-entiat synthesized according to the method of example 320.

ESI-MS [M+H+]=533, C26H30ClFN4O3S=532.

Example 161: 1-Cyclopropyl-N-(2-{[8-(4-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide

Synthesis of wire�t, using as starting substances, ethyl 7-(2-(cyclopropanesulfonyl)ethoxy)-1-(4-terbisil)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (synthesized according to the method of example 3) was dissolved in THF (50 ml), then added LiAlH4at room temperature, and the mixture was stirred for 8 h under heating to reflux. Added 2N aqueous NaOH, extracted with CH2Cl2organic layers washed with saturated solution of NaHCO3and saturated NaCl solution, and the solvent is evaporated, obtaining a residue that is treated with iPrOH/HCl, whereupon the product is precipitated. After filtration a white salt (89 mg, 76%).

ESI-MS [M+H+]=447, C24H31FN2O3S=446.

Example 162: (-)-N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

The synthesis was carried out using as starting substances of (-)ethyl 1-benzyl-7-(2-(cyclopropanesulfonyl)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (137), which was dissolved in THF (50 ml), then added LiAlH4at room temperature, and the mixture was stirred for 8 h under heating to reflux. Added 2N aqueous NaOH, extracted with CH2Cl2organic layers washed with saturated solution NHCO 3and saturated NaCl solution, and the solvent is evaporated, obtaining a residue that is treated with iPrOH/HCl, whereupon the product is precipitated. After filtration a white salt (102 mg, 79%). The racemate is separated by the method of chiral chromatography on a Chiracel AD (n-heptane/ethanol/tert-butanol 800:150:50), receiving (after conversion to a salt form) (-)-N-(2-(8-benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride ([α]=-80,5° in MeOH, c=0,191 g/100 ml).

ESI-MS [M+H+]=429, C24H32N2O3S=428.

Example 163: 1-Methyl-N-(2-{[8-(3-methylbenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1H-imidazole-4-sulfonamide

1-Methyl-N-(2-{[8-(3-methylbenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1H-imidazole-4-sulfonamide synthesized according to the methods of examples 264/88.

ESI-MS [M+H+]=509, C28H36N4O3S=508.

Example 164: N-(2-{[8-(3-Methoxybenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

N-(2-{[8-(3-Methoxybenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride synthesized according to the methods of examples 264/88.

ESI-MS [M+H+]=525, C28H36N4O4S=524.

Example 165: 1-�ethyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-triptoreline)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-triptoreline)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride synthesized according to the method of example 3.

ESI-MS [M+H+]=509, C24H27F3N4O3S=508.

Compounds of the following examples receive according to the method of example 40:

Example 166: N-{[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=407, calculated for C24H27ClN2O2S=406.

Example 167: N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]methanesulfonamide hydrochloride

ESI-MS [M+H+]=345, calculated for C19H24N2O2S=344.

Example 168: N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]benzosulfimide hydrochloride

ESI-MS [M+H+]=407, calculated for C24H26N2O2S=406.

Example 169: Enantiomer 2 of N-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

The compound obtained after chiral chromatography (Chiralpak AD-H, 30 mm ID × 250 mm, n-hexane/EtOH/MeOH/diethylamine = 20/40/40/0,1) from the racemic compound (example 42) in the form of a peak, which is eluated �Erwin. Optical rotation = -50° (589 nm, 25°C, c=0.1 in methanol).

ESI-MS [M+H+]=373, calculated for C21H28N2O2S=372.

Example 170: Enantiomer 1 of N-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

The compound obtained after chiral chromatography (Chiralpak AD-H 30 mm ID × 250 mm, n-hexane/EtOH/MeOH/diethylamine=20/40/40/0,1) from the racemic compound (example 42) in the form of a peak, which is eluated second. Optical rotation = +49° (589 nm, 25°C, c=0.1 in methanol).

ESI-MS [M+H+]=373, calculated for C21H28N2O2S=372.

Example 171: N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=391 calculated for C21H27FN2O2S=390.

Example 172: N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=411 calculated for C22H26N4O2S=410.

Example 173: N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=411 calculated for C22H26N4O2S=410.

Example 174: N-{[7-Amino-8-(4-terbisil)-5,6,7,8-Tetra�adrenalin-2-yl]methyl}cyclobutanemethanamine hydrochloride

ESI-MS [M+H+]=403, calculated for C22H27FN2O2S=402.

Example 175: N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=391 calculated for C21H27FN2O2S=390.

Example 176: N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=429, calculated for C22H25FN4O2S=428.

Example 177: N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=429, calculated for C22H25FN4O2S=428.

Example 178: N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=429, calculated for C22H25FN4O2S=428.

Example 179: N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-methylbenzenesulfonamide hydrochloride

ESI-MS [M+H+]=421, calculated for C25H28N2O2S=420.

Example 180: N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-me�yl-1H-pyrrol-3-sulfonamide hydrochloride

ESI-MS [M+H+]=410 calculated for C23H27N3O2S=409.

Example 181: N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-3-sulfonamide dihydrochloride

ESI-MS [M+H+]=408 calculated for C23H25N3O2S=407.

Example 182: N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=479 calculated for C23H25F3N4O2S=478.

Example 183: N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazol-3-sulfonamide hydrochloride

ESI-MS [M+H+]=411 calculated for C22H26N4O2S=410.

Example 184: N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine hydrochloride

ESI-MS [M+H+]=403, calculated for C22H27FN2O2S=402.

Example 185: N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanecarboxamide hydrochloride

ESI-MS [M+H+]=421, calculated for C22H26F2N2O2S=420.

Example 186: N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-Tetra�adrenalin-2-yl]methyl}cyclobutanemethanamine hydrochloride

ESI-MS [M+H+]=421, calculated for C22H26F2N2O2S=420.

Example 187: N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

tert-Butyl [1-benzyl-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate, obtained by the method of example 39 (1240 mg, 2,62 mmol) was dissolved in tetrahydrofuran (50 ml). At room temperature was added, dropwise, a solution of aluminum lithium hydride (1 M in tetrahydrofuran, a 7.87 ml, a 7.87 mmol). Then the reaction mixture was heated at 60°C for 1 h. After the treatment of water, purification of extracted product flash chromatography (silica gel, dichloro methane, methanol) and processing of a 1.25 M solution of hydrochloric acid in ethanol, followed by concentration under vacuum gave the desired product. Yield: 590 mg (1,4 mmol, 53%).

ESI-MS [M+H+]=425, calculated for C22H30N2O2S=424.

According to the method of example 187 receive connections the following examples:

Example 188: N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine hydrochloride

ESI-MS [M+H+]=400 calculated for C23H30N2O2S=399.

Example 189: N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-�l]methyl}-3-methylbenzenesulfonamide hydrochloride

ESI-MS [M+H+]=435, calculated for C26H30N2O2S=434.

Example 190: N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide hydrochloride

ESI-MS [M+H+]=424 calculated for C24H29N3O2S=423.

Example 191: N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazol-3-sulfonamide hydrochloride

ESI-MS [M+H+]=425, calculated for C23H28N4O2S=424.

Example 192: Enantiomer 1 of N-{[8-benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

For synthesis using chiral structural element, i.e., the enantiomer of tert-butyl (1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate.

tert-Butyl (1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate can be obtained according to the method used to obtain the dichloro-derivative described in example 34. CIS-isomer can be separated into the enantiomers by the method of chiral chromatography (Daicel, Chiralpak IC, C,6 mm ID, 5 µm, a mixture of n-heptane/ethanol=1/9 containing 0.1% triethylamine). Enantiomer, eluruumist second, used for synthesis described above.

ESI-MS [M+H+ ]=387, calculated for C22H30N2O2S=386.

Example 193: Enantiomer 1 of N-{[8-benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine hydrochloride

Enantiomer of tert-butyl (1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate as described in example 192, is used for the synthesis as chiral structural element.

ESI-MS [M+H+]=399, calculated for C23H30N2O2S=398.

Example 194: N-{[TRANS-8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

Prepared from TRANS-derivative, formed as by-product during recrystallization

(see also example 1).

ESI-MS [M+H+]=387, calculated for C22H30N2O2S=386.

Example 195: N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=425, calculated for C23H28N4O2S=424.

Example 196: N-(1-Benzyl-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide

N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide (see example 42) �will catilium in dichloromethane by acetylchloride in the presence of ethyldiethanolamine at room temperature.

ESI-MS [M+H+]=415, calculated for C23H30N2O3S=414.

Example 197: N-[(1-(4-Terbisil)-7-({[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}methyl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide

The specified connection receive according to the method of example 196.

ESI-MS [M+H+]=471, calculated for C24H27FN4O3S=470.

Example 198: N-{[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide hydrochloride

N-(1-Benzyl-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide (example 196, 153 mg, of 0.37 mmol) was dissolved in tetrahydrofuran (5 ml). Add a 1 M solution of a complex of borane-dimethyl sulfide in tetrahydrofuran (852 μl 8,52 mmol) and the reaction mixture was stirred at room temperature over night. Water was added, and the mixture was extracted with dichloromethane (three times). The combined organic extracts are dried (MgSO4) and concentrated in vacuo. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Add an excess of 6 M hydrochloric acid solution in isopropanol. The solvent was evaporated, and the product was dried in vacuum. Yield: 70 mg (0,16 mmol, 36%).

ESI-MS [M+H+]=401, calculated for C23H32N2O2S=400.

Compounds of the following examples Paul�prepared according to the method of example 198:

Example 199: 1-Methyl-1H-imidazole-4-sulfonic acid [7-ethylamino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide hydrochloride

ESI-MS [M+H+]=457, calculated for C24H29FN4O2S=456.

Example 200: 1-Methyl-1H-pyrazol-4-sulfonic acid [7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide hydrochloride

ESI-MS [M+H+]=457, calculated for C24H29FN4O2S=456.

Example 201: N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

201.1 tert-Butyl [1-(4-Chlorobenzyl)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

To a solution of 9-BBN (0.5 M in tetrahydrofuran, of 8.85 ml, 4,42 mmol) was added dropwise a solution of N-allylprodine-1-sulfonamida (1152 mg, 7,06 mmol) in tetrahydrofuran (1 ml) at 0°C. After stirring at a temperature from 0°C to 5°C for 3.5 hours added dioxane (25 ml) and then 7-(tert-butoxycarbonylamino)-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov (1000 mg, 1,923 mmol, obtained by the method of example 34.3), palladium acetate (to 43.2 mg, 0,192 mmol), triphenylphosphine (101 mg, 0,385 mmol) and cesium carbonate (1253 mg, of 3.85 mmol). The yellow reaction mixture was heated to reflux in �of Directors for 3 hours. The reaction mixture is diluted with ethyl acetate (60 ml) and washed with water (CH ml). The organic layer was dried and concentrated in vacuo. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Output: 854 mg (1,596 mmol, 83%).

201.2 N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

tert-Butyl [1-(4-Chlorobenzyl)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (150 mg, 0,281 mmol) was dissolved in dichloromethane (3 ml) and add hydrochloric acid (0.5 ml, 5 M in isopropanol). After stirring at room temperature for 2 hours the solvent was removed under vacuum. Add water (15 ml) and the pH adjusted to 9 using saturated aqueous sodium bicarbonate solution, whereupon the mixture was extracted with dichloromethane (3×15 ml). The combined organic extracts dried and concentrated in vacuo. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). The product was dissolved in dichloromethane (2 ml) and add hydrochloric acid in ethanol (1,25 M). The solvent was removed under vacuum. Output: 31,4 mg (0,187 mmol, 36%).

ESI-MS [M+H+]=435, calculated for C23H31ClN2O2S=434.

Compounds of the following examples receive according to the method of example 201:

PR�measures 202 : N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanecarboxamide hydrochloride

ESI-MS [M+H+]=447, calculated for C24H31ClN2O2S=446.

Example 203: N-{3-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=469, calculated for C23H30Cl2N2O2S=468.

Example 204: N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-C-cyclopropanesulfonyl hydrochloride

ESI-MS [M+H+]=449 calculated for C24H30F2N2O2S=448.

Example 205: N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=401, calculated for C23H32N2O2S=400.

Example 206: N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=437, calculated for C23H30F2N2O2S=436.

Example 207: N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl triptorelin

ESI-MS [M+H+]413, calculated for C24H32N2O2S=412.

Example 208: N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanecarboxamide hydrochloride

ESI-MS [M+H+]=431 calculated for C24H31FN2O2S=430.

Example 209: N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=419, calculated for C23H31FN2O2S=418.

Example 210: N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanecarboxamide hydrochloride

ESI-MS [M+H+]=431 calculated for C24H31FN2O2S=430.

Example 211: N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=435, calculated for C23H31ClN2O2S=434.

Example 212: N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-C-cyclopropanesulfonyl hydrochloride

ESI-MS [M+H+]=447, calculated for C24H31ClN2O2S=446.

Example 213: N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=419, calculated for C23H31FN2O2S=418.

Example 214: N-[1-(3-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide

N-(3-(7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl)propyl)propane-1-sulfonamide (see also example 209: 45 mg, 0,108 mmol) and triethylamine (15 μl, 0,108 mmol) was dissolved in dichloromethane (2 ml). Add acetyl chloride (of 7.64 μl 0,108 mmol). The reaction mixture was stirred for 12 hours at room temperature. The reaction mixture was diluted with dichloromethane and successively washed with hydrochloric acid, water and saturated sodium chloride solution. The organic layer was dried and concentrated in vacuo. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 37 mg (0.08 mmol, 75%).

ESI-MS [M+H+]=461, calculated for C25H33FN2O3S=460.

By way of example 214 receive connections the following examples:

Example 215: N-[1-(4-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide

ESI-MS [M+H+]=461, calculated for C25H33FN2O3S=460.

Example 216: N-[1-Benzyl-7-(3-{[(cyclopropylmethyl)sulfonyl]amino}propyl)-1,2,3,4-tetrahydronaphthalen�-2-yl]acetamide

ESI-MS [M+H+]=455, calculated for C26H34N2O3S=454.

Example 217: N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide

ESI-MS [M+H+]=443 calculated for C25H34N2O3S=442.

Example 218: N-[7-(3-{[(the Cyclopropylmethyl)sulfonyl]amino}propyl)-1-(3-terbisil)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide

ESI-MS [M+H+]=473 calculated for C26H33FN2O3S=472.

Example 219: Propane-1-sulfonic acid {3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide hydrochloride

N-(1-(3-Terbisil)-7-(3-(propylsulfonyl)propyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide (see also example 214, to 19.5 mg, 0,042 mmol) was dissolved in tetrahydrofuran (1 ml) and added porandamaterjalid (106 μl, 0,212 mmol). The reaction mixture was stirred for 5 hours at 50°C. After cooling to room temperature, add aqueous solution of hydrochloric acid. The mixture was made alkaline by adding sodium bicarbonate and extracted with dichloromethane several times. The combined organic extracts are dried (MgSO4), concentrated in vacuo, and the crude product is purified flash chromatography (silica�gel, dichloro methane, methanol). To a purified product added excess 1 M hydrochloric acid in ether and the ether distilled off. Yield: 7 mg (0,016 mmol, 37%).

ESI-MS [M+H+]=447, calculated for C25H35FN2O2S=446.

Compounds of the following examples receive according to the method of example 219:

Example 220: N-{3-[7-(Ethylamino)-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=447, calculated for C25H35FN2O2S=446.

Example 221: C-Cyclopropyl-N-{3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide hydrochloride

ESI-MS [M+H+]=459, calculated for C26H35FN2O2S=458.

Example 222: Propane-1-sulfonic acid {3-[8-(2-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide hydrochloride

ESI-MS [M+H+]=463 calculated for C25H35ClN2O2S=462.

Example 223: N-{3-[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

ESI-MS [M+H+]=429, calculated for C25H36N2O2S=428.

Example 224: N-{3-[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cycloprop�of methansulfonate hydrochloride

ESI-MS [M+H+]=441, calculated for C26H36N2O2S=440.

Example 225: N-{3-[8-(3,4-Diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide triptorelin

ESI-MS [M+H+]=465, calculated for C25H34F2N2O2S=464.

Example 226: 1-Cyclopropyl-N-{3-[8-(3,4-diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide triptorelin

ESI-MS [M+H+]=477 calculated for C26H34F2N2O2S=476.

Example 227: N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide hydrochloride

tert-Butyl (1-(3-terbisil)-7-(3-(propylsulfonyl)propyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (see also 209 201a, 65 mg, 0.125 mmol) was dissolved in acetonitrile (800 μl) and add methyliodide (24 μl 0,376 mmol) and cesium carbonate (is 0.102 g, 0,313 mmol). The reaction mixture was heated for 24 hours in a tightly closed vessel at 80°C. the Reaction mixture is diluted with ethyl acetate. Ethylacetate the solution was sequentially washed with water and saturated sodium chloride solution. The organic phase was dried (MgSO4) and concentrated in vacuo. The crude product is purified drugs�active thin layer chromatography (silica gel, dichloro methane, methanol). Obtained tert-butyl 1-(3-terbisil)-7-(3-(N-methylpropanesulfonate)propyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (65 mg, 0,122 mmol) was dissolved in 4 M hydrochloric acid in isopropanol and stirred at room temperature for 4 hours. The solvent was removed under vacuum. Add diethyl ether and the precipitate is removed by filtration, and dried. Yield: 22 mg (0,047 mmol, 38%).

ESI-MS [M+H+]=433 calculated for C24H33FN2O2S=432.

Compounds of the following examples get by way of example 227:

Example 228: N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-propyl}-C-cyclopropyl-N-methylmethanesulfonamide hydrochloride

ESI-MS [M+H+]=461, calculated for C25H33ClN2O2S=460.

Example 229: Propane-1-sulfonic acid {3-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methylamine hydrochloride

ESI-MS [M+H+]=449 calculated for C24H33ClN2O2S=448.

Example 230: N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride

ESI-MS [M+H+]=445, calculated for C25H33FN2O2S=444.

Example 231: N-{3-[7-Amino-8-(4-terbisil)-56,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride

ESI-MS [M+H+]=445, calculated for C25H33FN2O2S=444.

Example 232: N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide hydrochloride

ESI-MS [M+H+]=433 calculated for C24H33FN2O2S=432.

Example 233: N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide hydrochloride

ESI-MS [M+H+]=461, calculated for C25H33ClN2O2S=460.

Example 234: N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide hydrochloride

ESI-MS [M+H+]=449 calculated for C24H33ClN2O2S=448.

The compound of example 235 receive according to the method of example 47:

N-(2-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl hydrochloride

ESI-MS [M+H+]=433 calculated for C23H29FN2O3S=432.

Compounds of the following examples receive according to the method of example 46:

Example 236Ethyl [1-(3,5-diferensial)-7-(2-{[(1-methyl-1H-pyrrol-3-yl)sulfonyl]amino}ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

ESI-MS [M+H+]=548 calculated for C27H31F2N3O5S=547.

Example 237Ethyl [7-(2-{[(cyclopropylmethyl)sulfonyl]amino}ethoxy)-1-(3,5-diferensial)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

ESI-MS [M+H+]=523 calculated for C26H32F2N2O5S=522.

The compound of example 238 receive according to the method of example 47:

Enantiomer 1 of N-(2-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

The specified connection can be allocated by chiral chromatography of the final or intermediate connection.

ESI-MS [M+H+]=441, calculated for C23H28N4O3S=440.

Compounds of the following examples receive according to the method of example 137:

Example 239: Enantiomer 2 C-cyclopropyl-N-{2-[8-(3-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide hydrochloride

C-Cyclopropyl-N-{2-[8-(3-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide (Daicel, Chiralpak IC, C,6 mm ID, 5 µm, methyl tert-butyl ether/dichloro methane/methanol/triethylamine=900/50/50/1). Enantiomer, which is eluated second, used for the synthesis of the final compounds.

ESI-MS [M+H+]=447, calculated for C24H31 FN2O3S=446.

Example 240: Enantiomer 1 of 1-cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide hydrochloride

Ethyl 7-(2-(cyclopropanesulfonyl)ethoxy)-1-(3-terbisil)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate isolated by chiral chromatography (Daicel, Chiralpak IC, C,6 mm ID, methyl tert-butyl ether/dichloro methane/methanol/triethylamine = 900/50/50/1). Enantiomer, which is eluated first used for the synthesis of the final compounds.

ESI-MS [M+H+]=447, calculated for C24H31FN2O3S=446.

Example 241: Enantiomer 1 of N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide hydrochloride

Ethyl 1-(3,5-diferensial)-7-(2-(1-methyl-1H-pyrrol-3-sulfonamide)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate isolated by chiral chromatography (Daicel, Chiralpak AD, 250×20 mm ID, 10 µm, n-heptane/ethanol/triethylamine=35/65/1). Enantiomer, which is eluated second, used for the synthesis of the final compounds. It is possible to allocate by chiral chromatography of the final or intermediate connection.

ESI-MS [M+H+]=490, calculated for C25H29F2N3O3S=489.

Example 242: Enantiomer 2 of N-(2-{[8-(3,5-diferensial)-7-(metiram�but)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide hydrochloride

Ethyl 1-(3,5-diferensial)-7-(2-(1-methyl-1H-pyrrol-3-sulfonamide)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate isolated by the method of chiral chromatography (Daicel, Chiralpak AD, 250×20 mm ID, 10 µm, n-heptane/ethanol/triethylamine=35/65/1). For the synthesis of the final compound, enantiomer, which is eluated first.

ESI-MS [M+H+]=490, calculated for C25H29F2N3O3S=489.

Example 243: 1-Cyclopropyl-N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide hydrochloride

ESI-MS [M+H+]=465, calculated for C24H30F2N2O3S=464.

Example 244: Enantiomer 2 of 1-cyclopropyl-N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide hydrochloride

Ethyl 7-(2-(cyclopropanesulfonyl)ethoxy)-1-(3,5-diferensial)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate isolated by the method of chiral chromatography (Daicel, Chiralpak AD, 250×20 mm ID, 10 µm, n-heptane/ethanol/tert-butanol=800/150/50). For the synthesis of the final compound, enantiomer, eluruumist first.

ESI-MS [M+H+]=465, calculated for C24H30F2N2O3S=464.

Example 245: Enantiomer 1 of 1-cyclopropyl-N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetras�hereafter-2-yl]oxy}ethyl)methanesulfonamide hydrochloride

Ethyl 7-(2-(cyclopropanesulfonyl)ethoxy)-1-(3,5-diferensial)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate isolated by the method of chiral chromatography (Daicel, Chiralpak AD, 250×20 mm ID, 10 µm, n-heptane/ethanol/tert-butanol=800/150/50). For the synthesis of the final compound, enantiomer, which is eluated second.

ESI-MS [M+H+]=465, calculated for C24H30F2N2O3S=464.

Example 246: N-(2-{[8-(3,5-Diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide hydrochloride

ESI-MS [M+H+]=490, calculated for C25H29F2N3O3S=489.

Example 247: 1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide hydrochloride

ESI-MS [M+H+]=447, calculated for C24H31FN2O3S=446.

Example 248: N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide

248.1 7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-carbonitril

Tert-butyl 1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (1.1 g, 3.03 mmol) was dissolved in dichloromethane (20 ml) and added 5 M hydrochloric acid solution in isopropanol (2 ml). Reactionary cm�camping stirred for 12 h at room temperature and then 4 h at 35°C. The solvent is evaporated in vacuum. Add water (30 ml) and pH adjusted to pH 9 using saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with dichloromethane. The combined extracts are dried (MgSO4), and the solvent evaporated in vacuum. Yield: 790 mg (3.03 mmol, 100%).

248.2 7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-carbonitril

7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-carbonitrile (790 mg, 3.03 mmol), 1,3-dibromopropane (0.4 ml, 3,93 mmol) and triethylamine (0,914 ml, 6,56 mmol) was dissolved in acetonitrile (8 ml) and the reaction mixture heated at 120°C in microwave oven for 2 h. the Solvent is evaporated in vacuum. Add water (30 ml) and ethyl acetate (40 ml). The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts are dried (MgSO4), and the solvent evaporated in vacuum. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 346 mg (1,14 mmol, 37.6 per cent).

248.3 1-[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methanamine

7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-carbonitrile (340 mg, 1.12 mmol) was dissolved in dry methanol (20 ml) in a nitrogen atmosphere. Add Raney Nickel (900 mg, 3,36 mmol) in a nitrogen atmosphere, and the reaction mixture was stirred at room temperature in tech�of 48 h in the hydrogen atmosphere. Add methanol (20 ml) and dichloro methane (30 ml). After stirring at room temperature for 20 minutes, the catalyst is removed by filtration, and the solvent evaporated in vacuum. Yield: 338 mg (1.10 mmol, 98%).

248.4 N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide

(7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methanamine (250 mg, 0,816 mmol) and N,N-dimethyl-4-aminopyridin (199 mg, 1,632 mmol) was dissolved in dichloromethane (18 ml). Add dropwise 1-methyl-1H-imidazol-4-sulphonylchloride (147 mg, 0,816 mmol) dissolved in dichloromethane (2 ml). The reaction mixture was stirred at room temperature for 12 h. Then the reaction mixture was diluted with dichloromethane (20 ml) and washed sequentially with a saturated solution of ammonium chloride (CH ml) and water (CH ml). The organic phase was dried (MgSO4), and the solvent evaporated in vacuum. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 64 mg (0,142 mmol, 17%).

ESI-MS [M+H+]=451, calculated for C25H30N4O2S=450.

Compounds of the following examples receive according to the method of example 248:

Example 249: N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide

ESI-MS [M+H+]=413, scheduled for�about for C 24H32N2O2S=412.

Example 250: N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide

ESI-MS [M+H+]=451, calculated for C25H30N4O2S=450.

Example 251: N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamida triptorelin

ESI-MS [M+H+]=450, calculated for C26H31N3O2S=449.

Example 252: Enantiomer 1 of N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide

Enantiomer of tert-butyl (1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate as described in example 192, is used for the synthesis as chiral structure element.

ESI-MS [M+H+]=451, calculated for C25H30N4O2S=450.

Example 253: Enantiomer 1 of N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-2-sulfonamide

Enantiomer of tert-butyl (1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate as described in example 192, is used for the synthesis as chiral structure element.

ESI-MS [M+H+]=448, calculated for C26H29N3O2S=447.

Example 254: Enantiomer 1N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide

Enantiomer of tert-butyl (1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate as described in example 192, is used for the synthesis as chiral structure element.

ESI-MS [M+H+]=451, calculated for C25H30N4O2S=450.

Example 255: Enantiomer 1 of N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}thiophene-2-sulfonamide

Enantiomer of tert-butyl (1-benzyl-7-cyano-1,2,3,4-tetrahydronaphthalen-2-yl)carbamate as described in example 192, is used for the synthesis as chiral structure element.

ESI-MS [M+H+]=453, calculated for C25H28N2O2S2=452.

Example 256: N-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide hydrochloride

ESI-MS [M+H+]=469, calculated for C25H29FN4O2S=468.

Example 257: N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide

The specified connection receive according to the method of example 248, using 1-bromo-2-(2-bromoethoxy)ethane instead of 1,3-dibromopropane.

ESI-MS [M+H+]=481, calculated for C26H32N4O3S=480.

Compounds of the following examples get in the way �reamer 257:

Example 258: N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide

ESI-MS [M+H+]=481, calculated for C26H32N4O3S=480.

Example 259: N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl

ESl-MS [M+H+]=455, calculated for C26H34N2O3S=454.

Example 260: N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide

ESl-MS [M+H+]=443 calculated for C25H34N2O3S=442.

Example 261: N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine

ESI-MS [M+H+]=455, calculated for C26H34N2O3S=454.

Example 262: N-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide

The specified connection receive according to the method of example 248, using 1,4-dibromobutane instead of 1,3-dibromopropane.

ESI-MS [M+H+]=465, calculated for C26H32N4O2S=464.

Example 263: N-{[8-Benzyl-7-(2-oxopyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide

N-((7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl)-1-methyl-1H-imidazole-4-sulfonamide (271 mg, 0,66 mmol, see also 173) was dissolved in dichloromethane (10 ml). Add pyridine (0,191 ml 2,357 mmol). Then added dropwise 4-chlorobutanol chloride (0,116 ml, 1,038 mmol). After 2 h was added N,N-dimethyl-4-aminopyridin (46 mg, 0,378 mmol), and stirring was continued over night. Add 1N solution of sodium hydroxide, and the mixture was extracted with dichloromethane. The combined organic extracts are dried (MgSO4) and concentrated in vacuo. The crude product is suspended in dry tetrahydrofuran, is added a suspension of sodium hydride (60% in oil, 179 mg, twice before adding washed with pentane) in tetrahydrofuran (3 ml). The reaction mixture was heated at 45°C for 1 h. water was Added, and the mixture was extracted with dichloromethane (CH ml). The combined organic extracts are dried (MgSO4) and concentrated in vacuo. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 98 mg (0,205 mmol, 46%).

ESI-MS [M+H+]=479 calculated for C26H30N4O3S=478.

Example 264: N-{3-[8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

264.1 1-[1-(3-Chlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]pyrrolidin

1-(3�orbenin)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine (6 g, 19,88 mmol) was dissolved in acetonitrile (150 ml). Add 1,4-dibromobutane (2,61 ml 21,87 mmol) and triethylamine (6.1 ml, 43,7 mmol), after which the reaction mixture was heated to reflux for 3 h. the Reaction mixture was poured on ice and extracted with dichloromethane. The combined organic extracts are successively washed with water and saturated salt solution, dried (MgSO4), and the solvent evaporated in vacuum. The crude product (6.6 g) used in next step without further purification.

264.2 8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol

1-(1-(3-Chlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)pyrrolidine (6.6 g, 18,54 mmol) was dissolved in dichloromethane (100 ml). Added dropwise 1 M solution of bartered in dichloromethane (55,6 ml, at 55.6 mmol) under cooling, maintaining the temperature of the reaction mixture at the level of the room. The reaction mixture was stirred at room temperature for 2 h. Then the reaction mixture was poured on ice, made basic with sodium hydroxide. The aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed successively with sodium bicarbonate solution and saturated salt solution. The combined extracts are dried (MgSO4), and the solvent evaporated in vacuum. The crude product (5.5 g) use inherits stage without further purification.

264.3 8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov

8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol (5.5 g, 16,09 mmol) was dissolved in dichloromethane (150 ml). At 0°C was added 1,1,1-Cryptor-N-phenyl-N-(triftormetilfullerenov)methanesulfonamide (6.9 g, 19,31 mmol) and then a solution of triethylamine (4,48 ml, to 32.2 mmol) in dichloromethane (50 ml). The reaction mixture is allowed to warm to room temperature, and stirring was continued over night. The reaction mixture was poured on ice and extracted with dichloromethane. The combined extracts was washed successively with aqueous ammonium chloride, water and saturated salt solution. The extracts were dried (Na2SO4), and the solvent evaporated in vacuum. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Output: 6,33 g (13,36 mmol, 83%).

264.4 N-{3-[8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

N-allylprodine-1-sulfonamide (0,238 g, 1,456 mmol) was added to a solution of 9-borabicyclo[3.3.1]nonane (0,185 g, 1,519 mmol) in tetrahydrofuran (4 ml). The reaction mixture was stirred for 2 h at room temperature. (7R,8S)-8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-silt triftormetilfullerenov� (0.3 g, 0,633 mmol) was dissolved in tetrahydrofuran (2 ml) and add sodium hydroxide (0,063 g, 1,582 0.06 mmol ml water) and tetranitroaniline palladium (0,073 g, 0,063 mmol). The reaction mixture was heated to reflux over night. The reaction mixture is diluted with ethyl acetate and washed with 1 M sodium hydroxide solution. The aqueous phase is extracted two more times with ethyl acetate. The combined organic extracts washed with saturated salt solution, dried (MgSO4), and the solvent evaporated in vacuum. The crude product is purified preparative thin layer chromatography (silica gel, dichloro methane, methanol). The product was dissolved in dichloromethane. Add an excess of 5N hydrochloric acid in ethanol. The solvent was evaporated, and the product was dried in vacuum. Yield: 53 mg (0,108 mmol, 17%).

ESI-MS [M+H+]=489, calculated for C27H37ClN2O2S=488.

Compounds of the following examples receive according to the method of example 264:

Example 265: Propane-1-sulfonic acid [3-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yl)propyl]amide hydrochloride

ESI-MS [M+H+]=455, calculated for C27H38N2O2S=454.

Example 266: N-{3-[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanecarboxamide hydrochloride

ESI-MS [M+H+]=467, calculated for C28H38N2O2S=466.

Example 267: N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide

267.1 8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol

8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol get in the way of obtaining 8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol (see also 264).

267.2 2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethanamine

2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethanamine receive according to the method of examples 1 and 2 from 8-(3-terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol.

267.3 N-(2-{[8-(3-terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide

2-(8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethanamine (50 mg, 0,136 mmol) was dissolved in dichloromethane (2 ml). Sequentially added N,N-dimethyl-4-aminopyridin (49,7 mg, 0,407 mmol) and 1-methyl-1H-pyrrol-3-sulphonylchloride (24,4 mg, 0,136 mmol). The reaction mixture was stirred at room temperature over night. Then the reaction mixture is diluted with dichloromethane and washed with water. Organic�s phase was dried (MgSO 4), and the solvent evaporated in vacuum. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 31 mg (0,061 mmol, 45%).

ESI-MS [M+H+]=512, calculated for C28H34FN3O3S=511.

Compounds of the following examples receive according to the method of example 267:

Example 268: N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide

ESI-MS [M+H+]=480, calculated for C27H33N3O3S=479.

Example 269: 1-Methyl-1H-pyrrol-3-sulfonic acid {2-[7-azetidin-1-yl-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

ESI-MS [M+H+]=498 calculated for C27H32FN3O3S=497.

Example 270: Enantiomer 1 of N-{1-benzyl-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}propionamide

N-{1-Benzyl-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}-propionamide receive according to the method of example 2, using propionitrile instead of ethylchloride. The specified connection can be allocated by chiral chromatography of the final or intermediate connection.

ESI-MS [M+H+]=497 calculated for C26H32N4O4S=496.

Example 271: N-(2-[8-(3,5-Diferensial)-7-(formylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide

271.1 Ethyl [1-(3,5-diferensial)-7-(2-{[(1-methyl-1H-pyrrol-3-yl)sulfonyl]amino}ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate

Ethyl[1-(3,5-diferensial)-7-(2-{[(1-methyl-1H-pyrrol-3-yl)sulfonyl]amino}ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate receive according to the method of example 2.

271.2 N-(2-{[8-(3,5-Diferensial)-7-(formylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide

Ethyl[1-(3,5-diferensial)-7-(2-{[(1-methyl-1H-pyrrol-3-yl)sulfonyl]amino}ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate (200 mg, 0,365 mmol) was dissolved in tetrahydrofuran (16 ml). At room temperature was added, dropwise 1 M solution of aluminum lithium hydride in tetrahydrofuran (0,73 ml, 0,73 mmol). The reaction mixture was heated at 50°C for 2 h. Upon cooling, added dropwise 2N sodium hydroxide solution (3 ml). Then add water (30 ml) and ethyl acetate (30 ml). The aqueous phase was extracted with ethyl acetate twice. The combined extracts are dried (MgSO4), and the solvent evaporated in vacuum. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 61 mg (0,116 mmol, 32%).

ESI-MS [M+H+]=504, calculated for C25H27F2N3O4S=503.

Example 272: N-{3-[8-(3,4-Dichlorobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfon�Mead

272.1 1-(3,4-Dichlorobenzyl)-7-methoxy-N-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-amine

1-(3,4-Dichlorobenzyl)-7-methoxy-N-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-amine is released in the form of a minor by-product of recrystallization of 1-(3,4-dichlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-amine hydrochloride from isopropanol.

272.2 N-{3-[8-(3,4-Dichlorobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide

N-{3-[8-(3,4-Dichlorobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide receive according to the method of example 264, using 1-(3,4-dichlorobenzyl)-7-methoxy-N-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-amine instead of 1-[1-(3-Chlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]pyrrolidine.

ESI-MS [M+H+]=511, calculated for C25H32Cl2N2O3S=510.

Example 273: N-{3-[8-Benzyl-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide hydrochloride

N-{3-[8-(3,4-Dichlorobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide (70 mg, 0,137 mmol) was dissolved in methanol (1.5 ml) and add palladium hydroxide (30 mg, 0,214 mmol). The reaction mixture was heated to reflux in an atmosphere of hydrogen for 6 h. the Catalyst was removed fil�radio, and the crude product is purified flash chromatography (silica gel, dichloro methane, methanol). The obtained amine was dissolved in dichloromethane (2 ml) and added 5N hydrochloric acid in isopropanol (0.3 ml). The solvent was evaporated, and the product was dried in vacuum. Yield: 30 mg (0,63 mmol, 46%).

ESI-MS [M+H+]=443 calculated for C26H38N2O2S=442.

Example 274: N-{3-[8-(4-Chlorobenzyl)-7-(diethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanecarboxamide hydrochloride

274.1 N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl

N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl (see 202).

274.2 N-{3-[8-(4-Chlorobenzyl)-7-(diethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanecarboxamide hydrochloride

N-(3-(7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl)propyl)-1-cyclopropanesulfonyl (49 mg, 0.11 mmol) was dissolved in dichloromethane (2 ml). Add acetic acid (7 μl, 0.11 mmol) and acetaldehyde (18 μl, 0,322 mmol) in dichloromethane (2 ml) and triacetoxyborohydride sodium (34 mg, 0,16 mmol). The reaction mixture was stirred at room temperature for 2 h. Then the reaction mixture was diluted with dichloromethane (20 ml) and washed�Ute water (CH ml). The organic layer was dried (MgSO4), and the solvent evaporated in vacuum. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Amine was dissolved in dichloromethane (3 ml) and add an excess of hydrochloric acid in ethanol. The solvent was evaporated, and the product was dried in vacuum. Yield: 22 mg (0,041 mmol, 38%).

ESI-MS [M+H+]=503 calculated for C28H39ClN2O2S=502.

Example 275: N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamida triptorelin

The specified connection can be obtained according to the method of example 227 using tert-butyl [(1S,2R)-1-benzyl-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate instead of tert-butyl 1-(3-terbisil)-7-(3-(propylsulfonyl)propyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (alkylation of the sulfonamide). Then tert-BUTYLCARBAMATE is possible to recover the aluminum lithium hydride according to the method of example 187.

ESI-MS [M+H+]=401, calculated for C23H32N2O2S=400.

Example 276: N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]prop-1-yn-1-yl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide

7-Atsetamido-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov (100 mg, 0,234 mmol; obtained according to the method of obtaining 8-(3,4-dichlorobenzyl)-7-[(et�xianbei)amino]-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov, example 29), N-(prop-2-inyl)propane-1-sulfonamide (75 mg, 0,468 mmol), tetranitroaniline palladium (54 mg, 0.047 mmol), copper iodide(I) (35,6 mg, 0,187 mmol) and triethylamine (65 µl, 0,468 mmol) in dioxane (3 ml) was heated to reflux for 16 hours Then add water (15 ml) and the mixture was extracted with dichloromethane (CH ml). The combined organic extracts are dried (MgSO4), and the solvent evaporated in vacuum. The crude product is purified flash chromatography (silica gel, dichloro methane, methanol). Yield: 56 mg (0,132 mmol, 57%).

ESI-MS [M+H+]=439, calculated for C25H30N2O3S=438.

Example 277: N-(2-(8-Benzyl-7-(oxetan-3-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-cyclopropanesulfonyl

N-(2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-cyclopropanesulfonyl (50 mg, equal to 0,121 mmol) was dissolved in methanol. At 0°C was added oxetan-3-one (87 mg, to 1.21 mmol), zinc chloride (66 mg, 0,482 mmol) and cyanoborohydride sodium (23 mg, 0,362 mmol). Then the reaction mixture was heated at 40°C for 5 h. Add aqueous solution of ammonium chloride, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts washed with saturated salt solution, dried (MgSO4) and concentrated in vacuo. The crude product is purified flash chromatography (silica gel, dichloro�n, the methanol). Yield: 3 mg (6,4 mmol, 5%).

ESI-MS [M+H+]=471, calculated for C26H34N2O4S=470.

Example 278: Propane-1-sulfonic acid (8-benzyl-7-cyclopropylamino-5,6,7,8-tetrahydronaphthalen-2-ylmethyl)amide hydrochloride

N-((7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl)propane-1-sulfonamide (51 mg, 0,137 mmol), (1 amoxilcompare)trimethylsilane (26 mg, 0,151 mmol), acetic acid (0,078 ml, 1.37 mmol), cyanoborohydride sodium (26 mg, 0,411 mmol) and molecular sieve (50 mg) in methanol (1.5 ml) was heated in a microwave at 100°C for 25 min. the Solvent was evaporated, the crude product is purified flash chromatography (silica gel, dichloro methane, methanol) and converted to the hydrochloride salt. Yield: 18 mg (0.04 mmol, 29%).

ESI-MS [M+H+]=413, calculated for C24H32N2O2S=412.

Example 279: (1-(4-Chlorobenzyl)-7-{2-[methyl-(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester

279.1 Propane-1-sulfonic acid cyclopropylamine

To a solution of cyclopropylamine (1.2 ml, 17.5 mmol) in 100 ml of CH2Cl2and DMAP (2.4 g, 17.5 mmol) was added dropwise a solution of propane-1-sulphonylchloride (2.3 ml, 19.2 mmol) in 50 ml of CH2Cl2. The resulting mixture was stirred at room temperature over night and once�ablaut 50 ml of CH 2Cl2. The mixture is extracted successively with water, 1 M HCl and saturated brine, dried over Na2SO4, filtered, and the solvent was evaporated, yielding 2.8 g of product (oil), which is used for next step without further purification.

279.2 Acetic acid 2-[cyclopropyl(propane-1-sulfonyl)amino]ethyl ester

A mixture of propane-1-sulfonic acid cyclopropylamine (1.3 g, 8 mmol), K2CO3(2.4 g, 14.4 mmol) and acetic acid 2-bromo-ethyl ester (9.5 g, 16 mmol) in 10 ml of acetone was heated for 6 h at 120°C in a microwave oven (biotage AB). After cooling, the mixture was filtered and the solvent was evaporated, yielding 1.7 g of product as an oil, which was used without additional purification in the next step.

279.3 Propane-1-sulfonic acid cyclopropyl(2-hydroxyethyl)amide

A mixture of acetic acid 2-[cyclopropyl(propane-1-sulfonyl)amino]ethyl ester (1.7 g, 6.8 mmol) and KOH (0,57 g, 10.2 mmol) in 30 ml of methanol was stirred over night at room temperature. The solvent was evaporated, the residue dissolved in ethyl acetate and successively extracted with water and 1 M KOH, dried over Na2SO4, and the solvent was evaporated, yielding 0.46 g of product, which is used after purification by chromatography (253,5 mg of a colorless oil)

279.4 P�opan-1-sulfonic acid 2-[cyclopropyl(propane-1-sulfonyl)amino]ethyl ester

To a solution of propane-1-sulfonic acid cyclopropyl-(2-hydroxyethyl)amide (150 mg, 0.8 mmol) in CH2Cl2and DMAP (97 mg, 0.8 mmol) was added dropwise a solution of propane-1-sulphonylchloride (97 mg, 0.8 mmol) in CH2Cl2. The resulting mixture was stirred at room temperature over night, diluted with 50 ml of CH2Cl2, is extracted successively with water, 1 M HCl and saturated brine, dried over Na2SO4and filtered , and the solvent is evaporated, receiving 197,5 mg of product, which is used for next step without further purification.

279.5 1-(3-Chlorobenzyl)-7-{2-[cyclopropyl(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester

Get in one step from ethyl 1-(3-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (obtained by the method of example 1d) and propane-1-sulfonic acid 2-[cyclopropyl(propane-1-sulfonyl)amino]ethyl ester according to the method of example 76.

ESI-MS [M+H+]=549 calculated for C28H37ClN2O5S=548.

Example 280: 1-Benzyl-7-{2-[cyclopropyl-(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester

Get in one step from ethyl 1-benzyl-7-hydroxy-1,2,3,4-tetrahy�ronfalin-2-ylcarbamate (obtained by the method of example 1d) and propane-1-sulfonic acid 2-[cyclopropyl(propane-1-sulfonyl)amino]ethyl ester according to the method of example 76.

ESI-MS [M+H+]=515 calculated for C28H38N2O5S=514.

Example 281: Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}cyclopropylamine hydrochloride

Get in one step from 1-(3-Chlorobenzyl)-7-{2-[cyclopropyl(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester (example 279) according to the method of example 3.

ESI-MS [M+H+]=477 calculated for C25H33ClN2O3S=476.

Example 282: Propane-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]cyclopropylamine hydrochloride

Get in one step from 1-benzyl-7-{2-[cyclopropyl(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester (example 280) according to the method of example 3.

ESI-MS [M+H+]=443 calculated for C25H34N2O3S=442.

Example 283: 1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

283.1 3-[8-(3-Chlorobenzyl)-7-ethoxycarbonyl-5,6,7,8-tetrahydronaphthalen-2-yl]-azetidin-1-carboxylic acid tert-butyl ester

A suspension of zinc powder (152 mg, 2.3 mmol) in 1 ml of DMA in a dry flask is heated in an atmosphere of N2to 65-70°C. Add dropwise a mixture of TMS-Cl (28 mg, 0,26 mmol) and 1,2-dibromoethane (49 mg, 0,26 mmol), stirred for 30 min and then slowly (15 min) was added 3-iodo-azetidine-1-carboxylic acid tert-butyl ester (510 mg, 1.8 mmol) in 1 ml of DMA. The reaction mixture was slowly cooled (3 h) to room temperature, added to a mixture of 8-(3,4-Chlorobenzyl)-7-[(ethoxycarbonyl)amino]-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov (633 mg, 1.3 mmol, obtained according to the method of example 29), CuI (74 mg, 0,39 mmol) and PdCl2(dppf) (63 mg, 0,08 mmol) in 4 ml of DMA, pre-heated to 70°C, stirred for 7 h at 70°C, add water and MTB (1:1 20 ml) and the resulting mixture was filtered. The organic layer is separated, dried (Na2SO4), and the solvent evaporated. After purification by chromatography receiving 560 mg of product (white foam).

283.2 1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Get in three stages from 3-[8-(3-Chlorobenzyl)-7-ethoxycarbonyl-5,6,7,8-tetrahydronaphthalen-2-yl]-azetidin-1-carboxylic acid tert-butyl ester according to the method of examples 46/47. Cleavage of the Boc group is carried out in formic acid.

ESI-MS [M+H+]=433 calculated for C23H29ClN2O2S=432.

Example 284: 1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochlori�

Receive according to the method of example 283.

ESI-MS [M+H+]=399, calculated for C23H30N2O2S=398.

Example 285: {1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

285.1 1-(Propane-1-sulfonyl)azetidin-3-carboxylic acid methyl ester

Get a standard way from azetidin-3-carboxylic acid methyl ester and propane-1-sulphonylchloride (see, e.g., example 279).

285.2 [1-(Propane-1-sulfonyl)azetidin-3-yl]methanol

Produced by reducing 1-(propane-1-sulfonyl)azetidin-3-carboxylic acid methyl ester under the action of LiAlH4in THF at a temperature from ambient to 50°C (for example, example 300).

285.3 Methanesulfonic acid 1-(propane-1-sulfonyl)azetidin-3-ymetray ether

Get a standard way of [1-(propane-1-sulfonyl)azetidin-3-yl]methanol and methane-1-sulphonylchloride (for example, example 40)

285.4 {1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared from 1-(3-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate and methanesulfonic acid -(propane-1-sulfonyl)azetidin-3-Eletropaulo ether according to the method of example 315.

ESI-MS [M+H+]=536, calculated for C27H35ClN2O5S=535.

Example 286: 1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Prepared from {1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester according to the method of example 3.

ESI-MS [M+H+]=463 calculated for C24H31ClN2O3S=462.

Example 287: [1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

Receive according to the method of example 3.

ESI-MS [M+H+]=521, calculated for C26H33ClN2O5S=520.

Example 288: N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl hydrochloride

Prepared from [1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 3.

ESI-MS [M+H+]=449 calculated for C23H29ClN2O3S=448.

Example 289: [1-(3-Chlorobenzyl)-7-(1--3-ylethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

Prepared from 1-(3-Chlorobenzyl)-7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate and methanesulfonic acid 1--3-Eletropaulo ester (obtained according to the method of example 285) according to the method of example 315.

ESI-MS [M+H+]=547, calculated for C28H35ClN2O5S=546.

Example 290: {1-(3-Chlorobenzyl)-7-[2-()ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Prepared from [1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 45.

ESI-MS [M+H+]=535, calculated for C27H35ClN2O5S=534.

Example 291: N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropyl-N-methylmethanesulfonamide

Prepared from {1-(3-Chlorobenzyl)-7-[2-()ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester according to the method of example 3.

ESI-MS [M+H+]=463 calculated for C24H31ClN2O3S=462.

Example 292: 1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Receive according to the method of example 46.

ESI-MS [M+Hsup> +]=429, calculated for C24H31ClN2O3S=428.

Example 293: Propane-1-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 3.

ESI-MS [M+H+]=437, calculated for C22H29ClN2O3S=436.

Example 294: Cyclopropanemethanol acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 3.

ESI-MS [M+H+]=435, calculated for C22H27ClN2O3S=434.

Example 295: N-{2-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl hydrochloride

Receive according to the method of example 3.

ESI-MS [M+H+]=449 calculated for C23H29ClN2O3S=448.

Example 296: N-{3-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-C-cyclopropanesulfonyl hydrochloride

296.1 [7-(3-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

A solution of tert-butyl allylcarbamate (297 mg, 1.9 mmol) in dry THF under nitrogen is added dropwise at 0°C to 9-BBN dissolved in THF (0.5 M, 2.3 ml, 1.2 MMO�ü) and stirred for 4 h. The resulting mixture was sequentially treated with 8-(3,4-Chlorobenzyl)-7-[(ethoxycarbonyl)amino]-5,6,7,8-tetrahydronaphthalen-2-silt triftormetilfullerenov (250 mg, 0.5 mmol), palladium acetate(II) (11.5 mg, 0.05 mmol), triphenylphosphine (27 mg, 0.1 mmol) and cesium carbonate (333 mg, 1 mmol), after which the mixture was heated to reflux for 2 h. the Solvent was evaporated, the residue dissolved in ethyl acetate, extracted with water and dried (Na2SO4). After evaporation of the solvent produced a 0.51 g of a brown oil which is treated with diisopropyl ether, yielding 91 mg of a brownish powder.

296.2 N-{3-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]-propyl}-C-cyclopropanesulfonyl hydrochloride

Prepared from [7-(3-tert-butoxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 3.

ESI-MS [M+H+]=447, calculated for C24H31ClN2O2S=446.

Example 297: Propane-1-sulfonic acid {3-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide hydrochloride

Receive according to the method of example 296.

ESI-MS [M+H+]=435, calculated for C23H31ClN2O2S=434.

Example 298: {1-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Receive according to the method of example 3.

ESI-MS [M+H+]=547, calculated for C26H31ClN4O5S=546.

Example 299: {1-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

Receive according to the method of example 3.

ESI-MS [M+H+]=547, calculated for C26H31ClN4O5S=546.

Example 300: N-{2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl hydrochloride

A solution of LiAlH4in THF (1 M, 1.5 ml, 1.5 mmol) was added dropwise to [1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ether (523 mg, 1 mmol, example 287), dissolved in 100 ml dry THF. The mixture was heated to reflux for 1 h, treated with 2N NaOH and extracted with CH2Cl2. The organic layer was extracted with saturated solution of NaHCO3and saturated salt solution, dried (Na2SO4), filtered and the solvent evaporated. After purification by chromatography get 324 mg of product as a colorless oil which was converted to the hydrochloride salt by addition of HCl in isopropanol. (325 mg, white powder)

ESI-MS [M+H+]=463, rasschitandlya C 24H31ClN2O3S=462.

Example 301: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 3.

ESI-MS [M+H+]=475, calculated for C23H27ClN4O3S=474.

Example 302: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 3/300.

ESI-MS [M+H+]=489, calculated for C24H29ClN4O3S=488.

Example 303: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 3/300.

ESI-MS [M+H+]=489, calculated for C24H29ClN4O3S=488.

Example 304: Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide hydrochloride

304.1 [7-(2-Benzyloxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

A mixture of potassium (2-(benzyloxycarbonylamino)ethyl)tricorporate (1,130 g, with 3.96 mmol), cesium carbonate (2,58 g, of 7.93 mmol), 8-(3-Chlorobenzyl)-7-(taxicab�ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov (1.3 g, 2,64 mmol), Pd(OAc)2(0.030 g, 0,132 mmol) and 2-dicyclohexylphosphino-2',6'-di-ISO-propoxy-1,1'-biphenyl (0,130 g, 0,264 mmol) in an atmosphere of N2in a mixture of toluene/water 3:1 (15 ml) was heated to reflux for 13 h. Then the reaction mixture was filtered, the solvent was evaporated, and the residue purified by chromatography, yielding 1.04 g of product as a colorless oil.

304.2 [7-(2-Aminoethyl)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

[7-(2-benzyloxycarbonylamino)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ether (500 mg, 0,960 mmol) was added at room temperature 8 ml of 33% HBr in acetic acid. After 2 h the mixture was diluted with CH2Cl2, washed twice with NaHCO3, dried and filtered. The solvent is evaporated, receiving the product as a yellow oil (392 mg), used without further purification.

304.3 Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide hydrochloride

Prepared from [7-(2-amino-ethyl)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester according to the method of example 3.

ESI-MS [M+H+]=421, calculated for C22H29ClN2O2S=420.

Example 305: 1-Methyl-1H-imidazole-4-sulfonic keys�located the whereabouts of {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 3.

ESI-MS [M+H+]=475, calculated for C23H27ClN4O3S=474.

Example 306: N-[1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide

Receive according to the method of example 214.

ESI-MS [M+H+]=491 calculated for C25H31ClN2O4S=490.

Example 307: N-{2-[8-(3-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl hydrochloride

Receive according to the method of example 300.

ESI-MS [M+H+]=477 calculated for C25H33ClN2O3S=476.

Example 308: Propane-1-sulfonic acid {3-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide hydrochloride

Get examples of ways 297/300.

ESI-MS [M+H+]=449 calculated for C24H33ClN2O2S=448.

Example 309: Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide

Get examples of ways 304/300.

ESI-MS [M+H+]=435, calculated for C23H31ClN2O2S=434.

Example 310: N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}-C-cyclopropyl�of econsultameri hydrochloride

Receive according to the method of example 304.

ESI-MS [M+H+]=433 calculated for C23H29ClN2O2S=432.

Example 311: Propane-1-sulfonic acid {2-[8-(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get examples of ways 3/300.

ESI-MS [M+H+]=435, calculated for C23H31FN2O3=434.

Example 312: C-Cyclopropyl-N-{2-[8-(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide hydrochloride

Get examples of ways 3/300.

ESI-MS [M+H+]=447, calculated for C24H31FN2O3S=446.

Example 313: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide

Get examples of ways 304/300.

ESI-MS [M+H+]=473 calculated for C24H29ClN4O2S=472.

Example 314: Propane-1-sulfonic acid [2-(8-cyclohexylmethyl-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide triptorelin

Get examples of ways 3/300.

ESI-MS [M+H+]=423, calculated for C23H38N2O3S=422.

Example 315: 1-Methyl-1H-imidazol-4-Sultanova� acid {2-[8-(2-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

315.1 1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-(2-oxopyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide

Receive according to the method of example 263.

315.2 1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Prepared from the compound obtained in the previous phase through the rehabilitation of LiAlH4by way of example 300.

ESI-MS [M+H+]=529, calculated for C27H33ClN4O3S=528.

Example 316: 1,2-Dimethyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 3.

ESI-MS [M+H+]=489, calculated for C24H29ClN4O3S=488.

Example 317: N-{2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl hydrochloride

Get examples of ways 264/88.

ESI-MS [M+H+]=503 calculated for C27H35ClN2O3S=502.

Example 318: 1-Methyl-1H-pyrazol-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

ESI-MS [M+H+]=529, calculated for C27H33ClN4O3S=528.

Example 319: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get examples of ways 264/88.

ESI-MS [M+H+]=529, calculated for C27H33ClN4O3S=528.

Example 320: N-{2-[7-Azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl

320.1 1-[1-(3-Chlorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl]azetidin

Receive according to the method of example 264, using 1,3-dibromopropane instead of 1,4-dibromobutane.

320.2 N-{2-[7-Azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl

Prepared from the compound obtained in the previous stage, according to the method of example 88.

ESI-MS [M+H+]=489, calculated for C26H33ClN2O3S=488.

Example 321: 1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 320.

ESI-MS [M+H+]=515 calculated for C26H31ClN4O3S=514.

Example 322: 1-Methyl-1H-pyrazol-4-su�honowai acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Receive according to the method of example 320.

ESI-MS [M+H+]=515 calculated for C26H31ClN4O3S=514.

Example 323: Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide hydrochloride

Get examples of ways 264/88.

ESI-MS [M+H+]=491 calculated for C26H35ClN2O3S=490.

Example 324: 1-Methyl-1H-pyrazol-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide hydrochloride

Receive according to the method of example 320.

ESI-MS [M+H+]=481, calculated for C26H32N4O3S=480.

Example 325: 1-Benzyl-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

325.1 [1-(3-Chlorobenzyl)-7-vinyl-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

The synthesis is carried out by analogy with the Organic Letters; 2002, Vol 4; p.107-109. A solution of trifter(vinyl)borate potassium (1,000 g, of 7.46 mmol), adduct PdCl2(dppf)-CH2Cl2(is 0.102 g, 0,124 mmol), 8-(3-Chlorobenzyl)-7-(ethoxycarbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl triftormetilfullerenov (3,06 g, from 6.22 mmol) and triethylamine (0,867 ml, from 6.22 mmol) in 100 ml n-BuOH was stirred in an atmosphere of N2at 85-90°C for 4 h and ZAT�m was cooled to room temperature. Add water and extracted with ether. The ethereal solution is washed with saturated salt solution, dried, filtered and evaporated, yielding a brown oil. After chromatography receive 1.55 g of product as pale yellow solids.

325.2 [1-(3-Chlorobenzyl)-7-(2-hydroxyethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

BH3·DMS (1 M in THF, 0,838 ml 0,838 mmol) was added a solution of ethyl 1-(3-Chlorobenzyl)-7-vinyl-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (1.55 g, 4,19 mmol) in 20 ml dry THF. The reaction mixture was stirred at 60°C for 1 h and cooled to room temperature. Add a little water to destroy the excess boranova complex, and the resulting mixture was heated to reflux for 1 h in the presence of 30% H2O2(of 8.56 ml, 84 mmol) and 2N NaOH (9,74 ml, 19,49 mmol). The reaction mixture was extracted with CH2Cl2, washed with water and saturated salt solution, dried, filtered and the solvent was evaporated, yielding a pale brown solid (1.7 g) which is purified by chromatography, getting 854 mg of product as a white solid.

325.3 [7-(2-Bromo-ethyl)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

To a solution of [1-(3-Chlorobenzyl)-7-(2-hydroxyethyl)-1,2,3,4-tetrahydronaphtyl�EN-2-yl]his carbamino acid ethyl ester (554 mg, 1,428 mmol) in 15 ml dry CH2Cl2cooled to 0°C, add triphenylphosphine (562 mg, 2,142 mmol) and tetrabromide carbon (0,208 ml 2,142 mmol). The mixture was stirred for 1 h, after which the solvent is evaporated. The residue is purified by chromatography, yielding 277 mg of product as a white solid.

325.4 [1-(3-Chlorobenzyl)-7-(2-propylsulfonyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

To a suspension of NaH (4,73 mg, 0,177 mmol) in 3 ml dry DMF in an atmosphere of N2add 1-propanethiol (0,012 ml of 0.133 mmol, dissolved in 1 ml dry DMF). The reaction mixture was stirred at room temperature for 2 hours, then add triethylamine is 0.019 ml of 0.133 mmol) and ethyl 7-(2-bromacil)-1-(3-chlorbenzyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (40 mg, 0,089 mmol, dissolved in 2 ml dry DMF). The mixture was stirred at room temperature overnight, the solvent was evaporated, the residue pererastayut in ethyl acetate, washed with water, citric acid, NaHCO3saturated salt solution and filtered. The solvent was evaporated, yielding 31 mg of an off-white solid which was used without further purification.

325.5 {1-(3-Chlorobenzyl)-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester

� cooled mixture (0°C) ethyl 1-(3-Chlorobenzyl)-7-(2-(propylthio)ethyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (31,4 mg, 0,070 mmol) in 2 ml of ethyl acetate is added m-CPBA (33,4 mg, 0,155 mmol). The reaction mixture was stirred for 2 h allowing it to warm to room temperature. The mixture is then diluted with ethyl acetate, washed with NaHCO3, water and saturated salt solution, dried, filtered and the solvent was evaporated, yielding a white solid which is purified by chromatography (27 mg).

325.6 [1-Benzyl-7-(2-propylsulfonyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester

Ethyl 1-(3-Chlorobenzyl)-7-(2-(propylsulfonyl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate (27,1 mg, 0,057 mmol) and ammonium formate (71,5 mg, 1,134 mmol) was dissolved in 5 ml of MeOH. Add Pd/C (0,845 mg, 7,94 mmol) and stirred at 80°C for 4 h. the Mixture was filtered, the solvent was evaporated, the residue pererastayut in ethyl acetate and sequentially washed with water, NaHCO3and saturated salt solution, dried, filtered. The solvent was evaporated, yielding a white solid which is purified by chromatography with obtaining a 12.7 mg of product as a white solid.

325.7 1-Benzyl-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Receive according to the method of example 3 from [1-benzyl-7-(2-propylsulfonyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester�.

ESI-MS [M+H+]=372, calculated for C22H29NO2S=371.

Example 326: 1-(3-Chlorobenzyl)-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine hydrochloride

Receive according to the method of example 325, skipping the stage of dechlorination.

ESI-MS [M+H+]=406, calculated for C22H28ClNO2S=405.

Biological testing

1. The uptake of [3H]-glycine recombinant CHO cells expressing human GlyT1:

Recombinant cells hGlyT1c_5_CHO expressing human GlyT1c, placed in a 96-well scintillation microtitre plates Cytostar-T (Amersham Biosciences) in the amount of 20000 cells per well and cultivated almost to confluence within 24 h. to analyze the absorption of glycine, the culture medium is aspirated and cells are washed once with 100 ál of HBSS (Gibco BRL, #14025-050) containing 5 mm L-alanine (Merck #1007). Add 80 μl of HBSS buffer, then 10 μl of inhibitor or vehicle (10% DMSO) and 10 µl of [3H]-glycine (TRK71, Amersham Biosciences) to a final concentration of 200 nm to initiate the absorption of glycine. Tablets are placed in a Wallac Microbeta (PerkinElmer) and continuously counted by the method of solid-phase scintillation spectrometry in the period up to 3 hours. Nonspecific uptake is determined in the presence of 10 μm Org24598. IC50calculated by the method of four-parametric Logar�pricheski nonlinear regression (GraphPad Prism), using values in the range of linear increase of the incorporation of [3H]-glycine in the range from 60 to 120 min.

2. Analysis of binding radiochango ligand with membranes of recombinant CHO cells expressing human GlyT1:

Binding radiochango ligand with membranes expressing the human Transporter GlyT1c, carried out according to the method described in Mezler et al., Molecular Pharmacology 74:1705-1715, 2008.

Below are the results of analysis of compounds disclosed in the examples:

Table 1
The absorption of glycineBinding radiochango ligand
ExampleIC50[µmol]Kiapp[µmol]
1≤1000≤10
2≤1≤0,1

3≤0,01≤0,01
4≤0,01≤0,01
5≤1≤1
6≤1≤0,1
7≤10≤10
8≤0,1≤0,1
9≤1≤1
10≤100≤10
11≤1≤0,1
12≤100≥10
13≤1000≤100
14≤1000≤100
15≤1≤1
16≤10≤10
17≤10≤1
18≤0,1≤0,01
19≤100≤10
20≤0,1≤0,01
21≤1000≤100
22≤1000≤10
23≤100≤10
24≤10≤0,1
25≤1≤0,1
26≤1000≤10
27≤0,01≤0,01

28≤0,01≤0,01
29≤100≤10
30≤100≤100
31≤1≤0,1
32 ≤100≤10
33≤1≤1
34≤1000≤10
35≤100≥100
36≤10≤100
37≤100≤10
38≤100≤100
39≤1000≤10
40≤100≤10
41≤100≤10
42≤0,1≤0,1
43≤1≤0,1
44≤0,1≤0,1
45≤0,1≤0,1
46 ≤1≤1
47≤0,01≤0,01
48≤0,01≤0,01
49≤100≤100
50≤10≤1
51≤1000≤100
52≤10≤10

53≤1000≤10
54≥100≤10
55≤0,1≤0,01
56≤1≤0,1
57≤10≤1
58≤10≤1
59≤10 ≤1
60>100≤10
61≤1000≤10
62≤1000≤10
63≥100≤10
64≤1000≤10
65≤100≥10
66≤1≤0,1
67≤1≤0,1
68≤10≤1
69≤10≤1
70≤1≤0,1
71≤0,1≤0,01
72≤10≤10
73≤10 ≤1
74≤100≥10
75≤10≤1
76≤1000≤100
77≤1≤0,1

78≤10≤10
79≤1≤0,1
80≤1≤1
81>1000≤10
82≤1≤0,1
83≤10≤1
84≤10≤10
85-≤1
86-≤10
-≤10
88-≤0,1
89-≤0,1
90-≤1
91-≤0,1
92--
93-≤1
94-≤0,1
95-≤0,01
967-≤1
98-≤1
99-≤0,1
100-≤1
100-≤10
101 -≤0,1
102-≤1

103-≤10
104-≤1
105-≤0,1
106-≤1
107-≤0,1
108-≤0,01
109-≤0,1
110-≤1
111-≤0,1
112-≤0,1
113-≤0,1
114-≤1
115--
116-≤0,01
117-≤0,01
118-≤0,1
119-≤0,01
120-≤0,1
121-≤0,01
122-≤10
123-≤10
124-≤1
125-≤1
126-≤0,01
127-≤0,1

128-129-≤0,01
130-≤0,01
131-≤0,1
132-≤0,1
133-≤0,1
134-≤1
135-≤0,1
136-≤0,1
137-≤0,01
138-≤0,01
139-≤0,01
140-≤0,01
141-≤0,01
142-�0,1
143-≤0,01
144-≤1
145-≤0,01
146-≤0,01
147-≤0,1
148-≤0,1
149-≤0,1
150-≤0,01
151-≤0,01
152-≤0,01

153-≤0,1
154-≤0,1
155-≤1
156 -≤1
157-≤0,1
158-≤0,01
159-≤0,1
160-≤0,01
161-≤0,01
162-≤0,01
163-≤0,01
164-≤0,01
165-≤0,01
166-≤0,1
167-≤10
168-≤10
169-≤0,01
170- >10
171-≤0,1
172-≤0,01
173-≤0,01
174-≤1
175-≤1
176-≤0,1
177-≤0,01

178-≤0,01
179-≤1
180-≤0,01
181-≤0,1
182-≤0,1
183-≤1
184-≤0,1
185-≤1
186-≤1
187-≤0,01
188-≤0,1
189-≤10
190-≤0,01
191-≤1
192--
193-≤0,01
194--
195--
196-≤10
197-≤10
198 -≤0,1
199-≤0,1
200-≤0,1
201-≤0,1
202-≤0,1
203-≤0,01

204-≤0,1
205-≤0,1
206-≤0,1
207-≤0,1
208-≤0,1
209-≤0,1
210-≤0,1
211-≤1
212-≤1
213-≤0,1
214-≤10
215-≤10
216-≤10
217-≤10
218-≤10
219-≤0,1
220-≤1
221-≤0,1
222-≤1
223-≤0,1
224-≤0,1
225-≤0,1
226 -≤0,1
227-≤0,1
228-≤0,1

229-≤1
230-≤0,01
231-≤0,01
232-≤0,1
233-≤0,1
234-≤0,1
235-≤0,01
236-≤1
237-≤10
238-≤0,01
239-≤1
240-≤0,01
241-≤0,1
242-≤0,01
243-≤0,01
244-≤0,01
245-≤1
246-≤0,01
247-≤0,01
248-≤0,01
249-≤0,1
250-≤0,01
251-≤0,1
252-≤0,01
253-≤1

254-≤0,01
255-≤1
256-≤0,1
257-≤0,1
258-≤0,1
259-≤1
260-≤1
261-≤1
262-≤0,1
263-≤1
264-≤1
265-≤1
266-≤1
267-≤0,1
268-≤0,01
269-≤0,01
270-≤0,1
271-≤0,1
272-≤0,1
273-≤1
274-≤0,1
275-≤0,1
276-≤10
277-
278-

279-≤10
280-≤10
281- ≤0,1
282-≤0,1
283-≤1
284-≤1
285-≤10
286-≤10
287-≤10
288-≤0,01
289->10
290-≤10
291-≤0,01
292-≤1
293-≤1
294-≤10
295-≤1
296-≤0,1
297-≤0,1
298-≤10
299->10
300-≤0,01
301-≤0,01
302-≤0,1
303-≤0,1

304-≤1
305-≤0,1
306-≤0,1
307-≤0,01
308-≤0,01
309≤0,1
310-≤1
311-≤0,1
312-≤0,1
313-≤0,1
314-≤1
315-≤1
316-≤1
317-≤0,1
318-≤0,01
319-≤0,1
320-≤0,1
321-≤0,01
322-≤0,01
323- ≤1
324-≤0,01
325-≤1
326-≤1

ADDITIONAL DATA ON the BIOLOGICAL ACTIVITY

PR. No.FormulaBinding radiochango ligand | Kiapp[µmol]
E-1.≤1
E-2.≤10
E-3.≤0,1
E-4.≤10
E-5.≤0,01
E-6.≤0,1
E-7. ≤0,1
E-8.≤0,01

E-9.≤0,1
E-10.≤0,1
E-11.≤0,1
E-12.≤0,1
E-13.≤1
E-14.≤0,01
E-15.≤0,01

All compounds have a CIS-configuration at indenbom ring

PR. No.FormulahGlyT1 Ki[µm�l]
E-1≤1
E-2≤1
E-3≤1
E-4≤10
E-5≤10
E-6≤10
E-7≤10

PR. No.FormulahGlyT1 Ki[µmol]
E-8≤10
E-9≤10
E-10 ≤10
E-11≤10
E-12≤10
E-13≤10
E-14≤10

PR. No.FormulahGlyT1 Ki[µmol]
E-15≤0,1
E-16≤0,1
E-17≤1
E-18≤1
E-19≤1
E-20≤1
E-21≤1

PR. No.FormulahGlyT1 Ki[µmol]
E-22≤10
E-23≤10
E-24≤10
E-25≤10
E-26≤10
E-27≤10
E-28≤10
E-29 ≤10

PR. No.FormulahGlyT1 Ki[µmol]
E-30≤10
E-31≤10
E-32≤10
E-33≤10
E-34≤10
E-35≤10
E-36≤10
E-37≤10

PR. No.FormulahGlyT1 Ki[µmol]
E-38≤10
E-39≤10
E-40≤10
E-41≤10
E-42≤10
E-43≤10
E-44≤10
E-45≤10

PR. No.FormulahGlyT1 Ki[µmol]
E-46≤10
E-47≤10
E-48≤1
E-49≤0.1
E-50≤0.01
E-51≤0.01
E-52≤0.01

PR. No.FormulahGlyT1 Ki[µmol]
E-53 ≤0.01
E-54≤0.01
E-55≤0.1
E-56≤0.1
E-57≤0.1
E-58≤0.1
E-59≤0.1
E-60≤0.1

PR. No.FormulahGlyT1 Ki[µmol]
E-61 ≤1
E-62≤1
E-63≤1
E-64≤1

1. Aminotetraline derivatives of formula (I)

where
A denotes a benzene ring or a ring selected from the group consisting of 5-membered ring:

R denotes the R1-W-A1-Q-Y-A2-X1-;
R1denotes hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, halogenated C1-C6-alkyl, tri-(C1-C4-alkyl)-silyl-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl, optionally substituted phenyl, C1-C6-alkoxy, di-C1-C6-alkylamino, optionally substituted 5 or 6-membered heterocyclyl containing 1-3 heteroatom selected from nitrogen and/or oxygen or sulfur;
W denotes a link;
A 1denotes a link;
Q represents-S(O)2- or-C(O)-;
Y represents-NR9or a link;
A2represents C1-C4-alkylen, or a link;
X1denotes-O-, C1-C4-alkylen, C2-C4-akinyan;
R2denotes hydrogen, halogen, or two radicals R2together with the ring atoms of A to which they are attached, form a benzene ring;
R3denotes hydrogen;
R4adenotes hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl-C1-C4-alkyl, halogenated C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, Cho, C1-C4-alkylsulphonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbamoyl, C1-C4-alkoxycarbonyl, C6-C12-aryloxyalkyl, or C3-C5-heterocyclic containing an oxygen atom;
R4bdenotes hydrogen, C1-C6-alkyl, C1-C4-alkoxycarbonyl;
or
R4a, R4btogether denote C3-C6-alkylene, where one-CH2- may be replaced by oxygen atom;
X2represents the >CR12aR12b;
X3denotes a link;
R5denotes optionally substituted phenyl, optionally substituted C3-C12-cycloalkyl or the optional samewe�tion pyridyl;
n is 0 or 1;
R9denotes hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl; or
R9, R1together denote C1-C4-alkylen; or
R9represents C1-C4-alkylen associated with the carbon atom A2and A2represents C1-C4-alkylen, or to a carbon atom of X1and X1represents C1-C4-alkylen;
R12adenotes hydrogen;
R12bdenotes hydrogen or
R12a, R12btogether denote C2-C4-alkylen;
where the term "substituted" means that a radical is substituted with 1 or 2 substituents which are selected from the group comprising halogen, (C1-C4-alkyl, halogenated C1-C4-alkyl, CN, C1-C6-alkoxy,
or their physiologically-tolerated salts.

2. The compound according to claim 1, where A denotes a benzene ring.

3. The compound of claim 1, wherein-Y-A2-X1- contains at least 2, 3 or 4 atoms in the main chain.

4. The compound according to claim 1 or 2, where R1represents C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, halogenated C1-C6-alkyl, C3-C6-cycloalkyl, optionally substituted 5 or 6-membered heterocyclyl containing 1-3 heteroatom selected from nitrogen and/or oxygen or sulfur.

5. A connection on p is 1 or 2, g�e A 1denotes a bond, or A1represents C1-C4-alkylen,

6. The compound according to claim 1 or 2, where A2represents C1-C4-alkylen.

7. The compound according to claim 1 or 2, where X1denotes-O-, or X1represents C1-C4-alkylen, And2denotes the connection.

8. The compound according to claim 1 or 2, where R1-W-A1-Q-Y-A2-X1denotes R1-S(O)2-NH-A2-X1-, R1-C(O)-NH-A2-X1-..

9. The compound according to claim 1 or 2, having one of formulas
where R1, W, A1, Q, Y, A2, X1, R2, R3, R4a, R4b, X2, X3, R5n have the meanings given in one of the PP. 1-8.

10. The compound according to claim 1 or 2, where R4adenotes hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl-C1-C4-alkyl, halogenated C1-C4-alkyl, -CHO, C1-C4-alkylsulphonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbamoyl, C1-C4-alkoxycarbonyl, C6-C12-aryloxyalkyl, or C3-C5-heterocyclyl,
containing an oxygen atom, and R4bdenotes hydrogen or C1-C6-alkyl, or R4a, R4btogether represent optionally substituted C3-C6-alkylene, where one-CH2- can be replaced �volume of oxygen.

11. The compound according to claim 1 or 2, where R5denotes optionally substituted phenyl.

12. The compound according to claim 11, having the formula

where A, R, R2, R3, R4a, R4b, X2, X3n have the meanings given in one of the paragraphs 1-11; and
R15a, R15b, R15c, R15d, R15eindependently represent hydrogen, halogen, C1-C6-alkyl, halogenated C1-C6-alkyl, C1-C6-alkoxy.

13. The compound according to claim 1 or 2, where R9denotes hydrogen, C1-C6-alkyl or C3-C12-cycloalkyl, or R9and R1together denote C1-C4-alkylen; or R9represents C1-C4-alkylen associated with the carbon atom A2and A2represents C1-C4-alkylen, or to a carbon atom of X1and X1represents C1-C4-alkylen.

14. The compound according to claim 1, where
A stands for a benzene ring;
R denotes the R1-W-A1-Q-Y-A2-X1-;
R1represents C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, halogenated C1-C6-alkyl, tri-(C1-C4-alkyl)-silyl-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl, phenyl or neobyazatel� substituted 5 - or 6-membered heterocyclyl, containing 1-3 heteroatom selected from nitrogen and/or oxygen or sulfur;
W denotes a link;
A1denotes a link;
Q represents-S(O)2- or-C(O)-;
Y represents-NR9or a link;
A2represents C1-C4-alkylen or link;
X1denotes-O - or C1-C4-alkylene or C2-C4-akinyan;
R2denotes hydrogen;
R3denotes hydrogen;
R4adenotes hydrogen, C1-C6-alkyl, C3-C12-cycloalkyl-C1-C4-alkyl, halogenated C1-C4-alkyl, -CHO, C1-C4-alkylsulphonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbamoyl, C1-C4-alkoxycarbonyl, C6-C12-aryloxyalkyl;
R4bdenotes hydrogen or C1-C6-alkyl; or
R4a, R4btogether represent optionally substituted C3-C6-alkylene, where one-CH2- may be replaced by oxygen atom;
X2denotes a CR12aR12b;
X3denotes a link;
R5denotes optionally substituted phenyl or optionally substituted C3-C12-cycloalkyl;
n is 1;
R9denotes hydrogen, C1-C6-alkyl or C3-C6-cycloalkyl; or
R9, R1together denote C1-C4-Ala�len; or
R9represents C1-C4-alkylen associated with the carbon atom A2and A2represents C1-C4-alkylen, or to a carbon atom of X1and X1represents C1-C4-alkylen;
R12adenotes hydrogen; and
R12bdenotes hydrogen.

15. Compound selected from the group including:
[7-(2-tert-butoxycarbonylamino)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Pyridine-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-dimethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-(3,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{l-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-and�}carbamino acid ethyl ester;
{1-(3,4-Dichlorobenzyl)-7-[2-(pyridin-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-methylpropan-1-sulfonamide;
[1-(3,4-Dichlorobenzyl)-7-(2-methanesulfonylaminoethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
[7-(2-Benzolsulfonat)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
{l-(3,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}benzolsulfonat;
The thiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{1-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}-2,2,2-triptorelin;
Pyrrolidin-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-formylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-(3,4-Dichlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acids� ethyl ester;
{l-(3,4-Dichlorobenzyl)-7-[2-(3-forproper-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N'-(2-{[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N,N-dimethylcarbinol acid diamide;
{1-(3,4-Dichlorobenzyl)-7-[2-(3,3,3-cryptochrome-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-3-forproper-1-sulfonamide;
1-(3-Chlorobenzyl)-7-[2-(1,1-dioxothiazolidine-2-yl)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-amine;
tert-Butyl [1-(3,4-dichlorobenzyl)-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-forproper-1-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]meth�l}propane-1-sulfonamide;
N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[CIS-7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamide;
{l-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{l-(3-Chlorobenzyl)-7-[2-(2,4-dimethylthiazol-5-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(chlorothiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-(5-chlorothiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(2-methyl-3H-imidazole-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydro�ftolen-2-yl } carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
The thiophene-2-sulfonic acid {2- [7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2,4-Dimethylthiazol-5-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Methyl-3H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Chlorothiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{1-(3-Chlorobenzyl)-7-[2-(2,5-dimethylthiophene-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-(1-ethyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(2,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(2,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(2,4-Dichlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
[1-(3-Chlorobenzyl)-7-(2-ethanolamines)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
1-Ethyl-1H-pyrazol-4-sulfonic acid {2[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2,5-Dimethylthiophene-3-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Econsultancy acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazol-4-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
The thiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{1-(2,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
(1-(4-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
(1-(3-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl EF�R;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
{l-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(1-deformity-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-(3-Chlorobenzyl)-7-[(R)-1-(propane-1-sulfonyl)pyrrolidin-2-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yloxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-(3-Chlorobenzyl)-7-(3-econsultancy)-1,2,3,4-tetrahydronaphthalen-2-ylamine;
Cyclohexanesulfamic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Trimethylsilylamodimethicone acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-(5-methylisoxazol-3-yl)methanesulfonamide;
Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazol-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
Butane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazol-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Ethoxyethanol acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {2-[7-amino-8-(4-methoxybenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methanesulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]benzolsulfonat;
3,3,3-Cryptochrome-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
Cyclopropanemethanol acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]propionamide;
1-Methyl-1H-[1,2,4]triazole-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]�Teal}amide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclobutanecarbonitrile;
Propane-1-sulfonic acid {2-[7-amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropyl-N-methylmethanesulfonamide;
1-Methyl-1H-pyrazol-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy) ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide;
1-Methyl-1H-pyrazol-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
1-Methyl-1H-pyrazol-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-(2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)pentane-1-sulfonamide;
N-(2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tet�Aeronavale-2-yloxy)ethyl)-1-methyl-1H-pyrazole-4-sulfonamide;
N-(2-{[7-Amino-8-(3-chloro-4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide;
N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetic;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)benzamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetylene;
C-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-N-methylmethanesulfonamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide;
N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]-s-cyclopropyl-N-methylmethanesulfonamide;
N-(2-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
C-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide�;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
1-Cyclopropyl-N-[2-({8-(3,4-dichlorobenzyl)-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]methanesulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl
N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-cyclopropanesulfonyl;
N-(2-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)cyclobutanemethanamine;
Propane-1-sulfonic acid [2-(7-azetidin-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide;
N-(2-{[8-(3-Chloro-5-terbisil)-7-(methylamino)-5,6,7,8-
tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-N-(2-{[8-(4-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
(-)-N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-N-(2-{[8-(3-methylbenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Methoxybenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide/
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-triptoreline)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]methanesulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]benzolsulfonat;
N-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-pyrazole-4-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahy�ronfalin-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-methylbenzenesulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-3-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazol-3-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-methylbenzenesulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazol-3-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-IMID�Zol-4-sulfonamide;
N-(1-Benzyl-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide;
N-[(1-(4-Terbisil)-7-({[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}methyl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-{[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid [7-ethylamino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide;
1-Methyl-1H-pyrazol-4-sulfonic acid [7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-C-cyclopropanesulfonyl;
N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3-ferb�nil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-C-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-[1-(3-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-(4-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-Benzyl-7-(3-{[(cyclopropylmethyl)sulfonyl]amino}propyl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[7-(3-{[(the Cyclopropylmethyl)sulfonyl]amino}propyl)-1-(3-terbisil)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
Propane-1-sulfonic acid {3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
N-{3-[7-(Ethylamino)-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
S-Cyclopropyl-N-{3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide;
Propane-1-sulfonic acid {3-[8-(2-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
N-{3-[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3[8-(3,4-Diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
1-Cyclopropyl-N-{3-[8-(3,4-diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropyl-N-methylmethanesulfonamide;
Propane-1-sulfonic acid {3-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methylamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-(2-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
Ethyl[1-(3,5-diferensial)-7-(2-{[(1-methyl-1H-pyrrol-3-yl)sulfonyl]amino}ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
Ethyl[7-(2-{[(cyclopropylmethyl)sulfonyl]amino}ethoxy)-I-(3,5-diferensial)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
N-(2-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[8-(3,5-Diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-2-sulfonamide;
N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}thiophene-2-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-Tetra�adrenalin-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(2-oxopyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{3-[8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
Propane-1-sulfonic acid [3-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yl)propyl]amide;
N-{3-[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
1-Methyl-1H-pyrrol-3-sulfonic acid {2-[7-azetidin-1-yl-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{1-benzyl-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}propionamide;
N-(2-{[8-(3,5-Diferensial)-7-(formylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-{3-[8-(3,4-Dichloro�ensil)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-Benzyl-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-(4-Chlorobenzyl)-7-(diethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamide;
N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]prop-1-yn-1-yl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-(2-(8-Benzyl-7-(oxetan-3-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-cyclopropanesulfonyl;
Propane-1-sulfonic acid (8-benzyl-7-cyclopropylamino-5,6,7,8-tetrahydronaphthalen-2-ylmethyl)amide;
(1-(4-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
1-Benzyl-7-{2-[cyclopropyl(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}cyclopropylamino;
Propane-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]cyclopropylamine;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
{l-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino to�slots ethyl ester;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;372
[1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
[1-(3-Chlorobenzyl)-7-(1--3-ylethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-()ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-s-cyclopropyl-N-methylmethanesulfonamide;
1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
Propane-1-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Cyclopropanemethanol acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropanesulfonyl;
Propane-1-sulfonic acid {3-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
{1-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-imides�l-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-{2-[8-(3-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {3-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {2-[8(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
S-Cyclopropyl-N-{2-[8-(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
Propane-1-sulfonic acid [2-(8-cyclohexylmethyl-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1,2-Dimethyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Benzyl-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine; or
1-(3-Chlorobenzyl)-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine
or its physiologically tolerated salt.

16. Pharmaceutical composition for inhibiting the activity of glycine Transporter, in particular, GlyT1 activity containing the carrier and a therapeutically effective amount of a compound according to any one of claims. 1-15.

17. A method of treating a neurological or psychiatric disorder or pain associated with dysfunction glycinergic or glutamatergic neurotransmission in need, comprising administering to the patient a therapeutically effective amount of a compound according to any one of claims. 1-15, where
neurological disorder is a dementia, worsening cognitive function, or a syndrome of attention deficit and hyperactivity disorder, and psychiatric disorder is an anxiety disorder, affective disorder, bipolar disorder, schizophrenia, or psychotic disorder.

18. Pharmaceutical composition for inhibiting the activity of glycine Transporter, in particular, GlyT1 activity containing the carrier and a therapeutically effective amount Conn�tion, selected from the group including:
[7-(2-tert-butoxycarbonylamino)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Pyridine-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-dimethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-(3,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{l-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3,4-Dichlorobenzyl)-7-[2-(pyridin-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-methylpropan-1-sulfonamide;
[1-(3,4-Dichlorobenzyl)-7-(2-methanesulfonyl�ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
[7-(2-Benzolsulfonat)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
{l-(3,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}benzolsulfonat;
The thiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;378
N-{l-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}-2,2,2-triptorelin;
Pyrrolidin-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-formylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-(3,4-Dichlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3,4-Dichlorobenzyl)-7-[2-(3-forproper-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tet�Aeronavale-2-yloxy]ethyl}amide;
N'-(2-{[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N,N-dimethylcarbinol acid diamide;
{l-(3,4-Dichlorobenzyl)-7-[2-(3,3,3-cryptochrome-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-3-forproper-1-sulfonamide;
1-(3-Chlorobenzyl)-7-[2-(1,1-dioxothiazolidine-2-yl)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-amine;
tert-Butyl[1-(3,4-dichlorobenzyl)-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-forproper-1-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[CIS-7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamide;
{l-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4 tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{1-(3-Chlorobenzyl)-7-[2-(2,4-dimethylthiazol-5-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(chlorothiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(5-chlorothiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(2-methyl-3H-imidazole-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
The thiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2,4-Dimethylthiazol-5-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Methyl-3H-imidazole-4-sulfones�th acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Chlorothiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{1-(3-Chlorobenzyl)-7-[2-(2,5-dimethylthiophene-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(1-ethyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(2,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(2,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(2,4-Dichlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
[1-(3-Chlorobenzyl)-7-(2-ethanolamines)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
1-Ethyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2,5-Dimethylthiophene-3-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Econsultancy acid {2 to 7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
The thiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{l-(2,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
(1-(4-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
(1-(3-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
{l-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(1-deformity-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-(3-Chlorobenzyl)-7-[(R)-1-(propane-1-sulfonyl)�irreligion-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yloxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-(3-Chlorobenzyl)-7-(3-econsultancy)-1,2,3,4-tetrahydronaphthalen-2-ylamine;
Cyclohexanesulfamic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Trimethylsilylamodimethicone acid {2-[7-amino-8-(dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-(5-methylisoxazol-3-yl)methanesulfonamide;
Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
Butane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Ethoxyethanol acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
N-{2-[7-Amino-8-(3,4-di�Lorenzi)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {2-[7-amino-8-(4-methoxybenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methanesulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]benzolsulfonat;
3,3,3-Cryptochrome-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
Cyclopropanemethanol acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]propionamide;
1-Methyl-1H-[1,2,4]triazole-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclobutanecarbonitrile;
Propane-1-sulfonic acid {2-[7-amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-s-cyclopropyl-N-methylmethanesulfonamide;
1-Methyl-1H-�irasol-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide;
1-Methyl-1H-pyrazole-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
1-Methyl-1H-pyrazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-(2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)pentane-1-sulfonamide;
N-(2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-pyrazole-4-sulfonamide;
N-(2-{[7-Amino-8-(3-chloro-4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide;
N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetic;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)benzamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N-ethyl-1-methyl-1H-pyrazol-4-sulfones�;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetylene;
S-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-N-methylmethanesulfonamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide;
N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]-s-cyclopropyl-N-methylmethanesulfonamide;
N-(2-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
S-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
1-Cyclopropyl-N-[2-({8-(3,4-dichlorobenzyl)-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]methanesulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-cyclopropanesulfonyl;
N-(2-{[8-Benzyl-7-(metelli�o)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)cyclobutanemethanamine;
Propane-1-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydro�naphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide;
N-(2-{[8-(3-Chloro-5-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8 tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(4-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
(-)-N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-N-(2-{[8-(3-methylbenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Methoxybenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-triptoreline)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-yl]methyl}propane-1-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]methanesulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]benzolsulfonat;
N-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-Sul fonemed;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-pyrazole-4-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-methylbenzenesulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-3-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahy�ronfalin-2-yl]methyl}-1-methyl-1H-pyrazole-3-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-methylbenzenesulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-3-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-(1-Benzyl-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide;
N-[(1-(4-Terbisil)-7-({[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}methyl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-{[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid [7-ethylamino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide;
1-Methyl-1H-pyrazole-4-sulfonic acid [7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide;
N-{3-[7-Amino-8-(4-�Lorenzi)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropanesulfonyl;
N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-[1-(3-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-(4-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-Benzyl-7-(3-{[(cyclopropylmethyl)sulfonyl]am�but}propyl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[7-(3-{[(the Cyclopropylmethyl)sulfonyl]amino}propyl)-1-(3-terbisil)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
Propane-1-sulfonic acid {3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
N-{3-[7-(Ethylamino)-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
S-Cyclopropyl-N-{3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide;
Propane-1-sulfonic acid {3-[8-(2-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
N-{3-[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-Benzyl-7-(ethylamino)-5,6 J,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[8-(3,4-Diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
1-Cyclopropyl-N-{3-[8-(3,4-diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropyl-N-methylmethanesulfonamide;
Propane-1-sulfonic acid {3-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methylamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]�ropyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-(2-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
Ethyl[1-(3,5-diferensial)-7-(2-{[(1-methyl-1H-pyrrol-3-yl)sulfonyl]amino}ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
Ethyl[7-(2-{[(cyclopropylmethyl)sulfonyl]amino}ethoxy)-1-(3,5-diferensial)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
N-(2-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
S-cyclopropyl-N-{2-[8-(3-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
l-cyclopropyl-N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[8-(3,5-Diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-IU�yl-1H-pyrrol-3-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-2-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}thiophene-2-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-B�nil-7-(2-oxopyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{3-[8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
Propane-1-sulfonic acid [3-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yl)propyl]amide;
N-{3-[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
1-Methyl-1H-pyrrol-3-sulfonic acid {2-[7-azetidin-1-yl-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{1-benzyl-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}propionamide;
N-(2-{[8-(3,5-Diferensial)-7-(formylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-{3-[8-(3,4-Dichlorobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-Benzyl-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-(4-Chlorobenzyl)-7-(diethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamide;
N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]prop-1-yn-1-yl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-(2-(8-Benzo�l-7-(oxetan-3-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-cyclopropanesulfonyl;
Propane-1-sulfonic acid (8-benzyl-7-cyclopropylamino-5,6,7,8-tetrahydronaphthalen-2-ylmethyl)amide;
(1-(4-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
1-Benzyl-7-{2-[cyclopropyl(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}cyclopropylamino;
Propane-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]cyclopropylamine;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
{l-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
[1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
[1-(3-Chlorobenzyl)-7-(1--3-ylethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
1-(3-Chlorobenzyl)-7-[2-()ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-s-cyclopropyl-N-methylmethanesulfonamide;
1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
Propane-1-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Cyclopropanemethanol acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropanesulfonyl;
Propane-1-sulfonic acid {3-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
{l-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid�you {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-{2-[8-(3-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {3-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-yl]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {2-[8-(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
S-Cyclopropyl-N-{2-[8-(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
Propane-1-sulfonic acid [2-(8-cyclohexylmethyl-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1,2-Dimethyl-1H-imidazole-4-sulfonic acid {2-[7-amino-(3-CL�benzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Benzyl-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine; or
1-(3-Chlorobenzyl)-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
or its physiologically tolerated salt.

19. A method of treating a neurological or psychiatric disorder or pain associated with dysfunction glycinergic or glutamatergic neurotransmission in need, comprising administering PA�Ianto therapeutically effective amount of at least one connection selected from the group including:
[7-(2-tert-butoxycarbonylamino)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
Ethyl 1-(3,4-dichlorobenzyl)-7-(2-(1-methyl-1H-imidazol-4-sulphonamido)ethoxy)-1,2,3,4-tetrahydronaphthalen-2-ylcarbamate;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(3 dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Pyridine-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-dimethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-(3,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{1-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3,4-Dichlorobenzyl)-7-[2-(pyridin-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-methylpropan-1-sulfonamide;
[1-(3,4-Dichlorobenzyl)-7-(2-methanesulfonamido�oxy)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
[7-(2-Benzolsulfonat)-1-(3,4-dichlorobenzyl)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
{l-(3,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}benzolsulfonat;
The thiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{1-(3,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}-2,2,2-triptorelin;
Pyrrolidin-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-formylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-(3,4-Dichlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3,4-Dichlorobenzyl)-7-[2-(3-forproper-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-Tetra�adrenalin-2-yloxy]ethyl}amide;
N'-(2-{[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N,N-dimethylcarbinol acid diamide;
{1-(3,4-Dichlorobenzyl)-7-[2-(3,3,3-cryptochrome-1 sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-3-forproper-1-sulfonamide;
1-(3-Chlorobenzyl)-7-[2-(1,1-dioxothiazolidine-2-yl)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-amine;
tert-Butyl[1-(3,4-dichlorobenzyl)-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-forproper-1-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[CIS-7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[CIS-7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamide;
{l-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4 tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{1-(3-Chlorobenzyl)-7-[2-(2,4-dimethylthiazol-5-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-(chlorothiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-(5-chlorothiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(2-methyl-3H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{1-(3-Chlorobenzyl)-7-[2-(4-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
The thiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2,4-Dimethylthiazol-5-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Methyl-ZN-imidazole-4-sulfones�th acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Chlorothiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{1-(3-Chlorobenzyl)-7-[2-(2,5-dimethylthiophene-3-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(1-ethyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(2,4-Dichlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(2,4-Dichlorobenzyl)-7-[2-(thiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(2,4-Dichlorobenzyl)-7-[2-(5-methylthiophene-2-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
[1-(3-Chlorobenzyl)-7-(2-ethanolamines)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
1-Ethyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
4-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2,5-Dimethylthiophene-3-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Econsultancy acid {2 to 7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
The thiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
5-Methylthiophene-2-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
{l-(2,4-Dichlorobenzyl)-7-[2-(propane-1-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(2,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
(1-(4-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
(1-(3-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
{l-(3-Chlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(3-Chlorobenzyl)-7-[2-(1-deformity-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-(3-Chlorobenzyl)-7-[(R)-1-(propane-1-sulfonyl)�irreligion-2-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yloxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-(3-Chlorobenzyl)-7-(3-econsultancy)-1,2,3,4 - tetrahydronaphthalen-2-ylamine;
Cyclohexanesulfamic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Trimethylsilylamodimethicone acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-(5-methylisoxazol-3-yl)methanesulfonamide;
Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
Butane-1-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-2-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
2-Ethoxyethanol acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Cyclobutanemethanol acid {2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methylamide;
N-{2-[7-Amino-8-(3,4-�chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {2-[7-amino-8-(4-methoxybenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methanesulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]benzolsulfonat;
3,3,3-Cryptochrome-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
Cyclopropanemethanol acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]propionamide;
1-Methyl-1H-[1,2,4]triazole-3-sulfonic acid {2-[7-amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclobutanecarbonitrile;
Propane-1-sulfonic acid {2-[7-amino-8-(3-terbisil)-
5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-s-cyclopropyl-N-methylmethanesulfonamide;
1-Methyl�-1H-pyrazole-4-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide;
1-Methyl-1H-pyrazole-4-sulfonic acid [2-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
1-Methyl-1H-pyrazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]methylamide;
N-(2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-N-ethyl-1-methyl-1H-pyrazole-4-sulfonamide;
N-(2-(7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)pentane-1-sulfonamide;
N-(2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-pyrazol-4-
the sulfonamide;
N-(2-{[7-Amino-8-(3-chloro-4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide;
N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetic;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)benzamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-N-ethyl-1-methyl-1H-pyrazol-4-sulfon�MFA;
N-(2-{[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-2-cyclopropylacetylene;
S-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-N-methylmethanesulfonamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide;
N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropyl-N-methylmethanesulfonamide;
N-[2-(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]-s-cyclopropyl-N-methylmethanesulfonamide;
N-(2-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
S-Cyclopropyl-N-{2-[8-(3,4-dichlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
N-(2-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
l-Cyclopropyl-N-[2-({8-(3,4-dichlorobenzyl)-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]methanesulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-cyclopropanesulfonyl;
N-(2-{[8-Benzyl-7-(metelli�o)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
l-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)cyclobutanemethanamine;
Propane-1-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-[2-({8-Benzyl-7-[3-ftorpirimidinu-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl}oxy)ethyl]-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahed�naphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Cyanobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Cyanobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)propane-1-sulfonamide;
N-(2-{[8-(3-Chloro-5-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
N-(2-{[7-(Azetidin-1-yl)-8-(3-chloro-5-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(4-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
(-)-N-(2-(8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-N-(2-{[8-(3-methylbenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1H-imidazole-4-sulfonamide;
N-(2-{[8-(3-Methoxybenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-triptoreline)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]methanesulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]benzolsulfonat;
N-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-pyrazole-4-sulfonamide;
N-[(7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl)methyl]-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-methylbenzenesulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-3-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonamide;
N-{[7-Amino-8-benzyl-5,6,7,8-tetrahy�ronfalin-2-yl]methyl}-1-methyl-1H-pyrazole-3-sulfonamide;
N-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-3-methylbenzenesulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-3-sulfonamide;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-(1-Benzyl-7-{[(propylsulfonyl)amino]methyl}-1,2,3,4-tetrahydronaphthalen-2-yl)acetamide;
N-[(1-(4-Terbisil)-7-({[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}methyl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-{[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid [7-ethylamino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide;
1-Methyl-1H-pyrazole-4-sulfonic acid [7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylmethyl]amide;
N-{3-[7-Amino-8-(4-�Lorenzi)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3,4-dichlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropanesulfonyl;
N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3,4-diferensial)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-[1-(3-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-(4-Terbisil)-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-Benzyl-7-(3-{[(cyclopropylmethyl)sulfonyl]am�but}propyl)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]propyl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-[7-(3-{[(the Cyclopropylmethyl)sulfonyl]amino}propyl)-1-(3-terbisil)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
Propane-1-sulfonic acid {3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
N-{3-[7-(Ethylamino)-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
S-Cyclopropyl-N-{3-[7-ethylamino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide;
Propane-1-sulfonic acid {3-[8-(2-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
N-{3-[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-Benzyl-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{3-[8-(3,4-Diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
1-Cyclopropyl-N-{3-[8-(3,4-diferensial)-7-(ethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methanesulfonamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-{3-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropyl-N-methylmethanesulfonamide;
Propane-1-sulfonic acid {3-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}methylamide;
N-{3-[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-ylpropyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropyl-N-methylmethanesulfonamide;
N-{3-[7-Amino-8-(4-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-N-methylpropan-1-sulfonamide;
N-(2-{[7-Amino-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-cyclopropanesulfonyl;
Ethyl[1-(3,5-diferensial)-7-(2-{[(1-methyl-1H-pyrrol-3-yl)sulfonyl]amino}ethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
Ethyl[7-(2-{[(cyclopropylmethyl)sulfonyl]amino}ethoxy)-1-(3,5-diferensial)-1,2,3,4-tetrahydronaphthalen-2-yl]carbamate;
N-(2-{[7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-imidazole-4-sulfonamide;
S-cyclopropyl-N-{2-[8-(3-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(3,5-diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-(2-{[8-(3,5-Diferensial)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-IU�yl-1H-pyrrol-3-sulfonamide;
1-Cyclopropyl-N-(2-{[8-(3-terbisil)-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)methanesulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrrol-3-sulfonamide;
N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}pyridine-2-sulfonamide;
N-{[7-(azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}thiophene-2-sulfonamide;
N-{[7-(Azetidin-1-yl)-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-pyrazole-4-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-cyclopropanesulfonyl;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}propane-1-sulfonamide;
N-{[8-Benzyl-7-(morpholine-4-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}cyclobutanemethanamine;
N-{[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{[8-Be�ZIL-7-(2-oxopyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide;
N-{3-[8-(3-Chlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
Propane-1-sulfonic acid [3-(8-benzyl-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yl)propyl]amide;
N-{3-[8-Benzyl-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-(2-{[8-(3-Terbisil)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-(2-{[7-(Azetidin-1-yl)-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
1-Methyl-1H-pyrrol-3-sulfonic acid {2-[7-azetidin-1-yl-8-(3-terbisil)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{1-benzyl-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}propionamide;
N-(2-{[8-(3,5-Diferensial)-7-(formylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy}ethyl)-1-methyl-1H-pyrrol-3-sulfonamide;
N-{3-[8-(3,4-Dichlorobenzyl)-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-Benzyl-7-(propan-2-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}propane-1-sulfonamide;
N-{3-[8-(4-Chlorobenzyl)-7-(diethylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-1-cyclopropanesulfonyl;
N-{[8-Benzyl-7-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-N-methylpropan-1-sulfonamide;
N-[1-Benzyl-7-{3-[(propylsulfonyl)amino]prop-1-yn-1-yl}-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-(2-(8-Benzo�l-7-(oxetan-3-ylamino)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-cyclopropanesulfonyl;
Propane-1-sulfonic acid(8-benzyl-7-cyclopropylamino-5,6,7,8-tetrahydronaphthalen-2-ylmethyl)amide;
(1-(4-Chlorobenzyl)-7-{2-[methyl - (propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
1-Benzyl-7-{2-[cyclopropyl(propane-1-sulfonyl)amino]ethoxy}-1,2,3,4-tetrahydronaphthalen-2-yl)carbamino acid ethyl ester;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}cyclopropylamino;
Propane-1-sulfonic acid [2-(7-amino-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]cyclopropylamine;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
{l-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
1-(3-Chlorobenzyl)-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
[1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
[1-(3-Chlorobenzyl)-7-(1--3-ylethoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]his carbamino acid ethyl ester;
{-(3-Chlorobenzyl)-7-[2-()ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-s-cyclopropyl-N-methylmethanesulfonamide;
1-Benzyl-7-[1-(propane-1-sulfonyl)azetidin-3-ylethoxy]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
Propane-1-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Cyclopropanemethanol acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
N-{3-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}-s-cyclopropanesulfonyl;
Propane-1-sulfonic acid {3-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
{1-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-imidazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
{l-(2-Chlorobenzyl)-7-[2-(1-methyl-1H-pyrazol-4-sulfonylamino)ethoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}carbamino acid ethyl ester;
N-{2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid�you {2-[8-(2-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[7-amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(2-Chlorobenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-[1-(3-Chlorobenzyl)-7-(2-)-1,2,3,4-tetrahydronaphthalen-2-yl]acetamide;
N-{2-[8-(3-Chlorobenzyl)-7-ethylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {3-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]propyl}amide;
Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
N-{2-[7-Amino-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}-C-cyclopropanesulfonyl;
Propane-1-sulfonic acid {2-[8-(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
S-Cyclopropyl-N-{2-[8-(2-terbisil)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}methanesulfonamide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yl]ethyl}amide;
Propane-1-sulfonic acid [2-(8-cyclohexylmethyl-7-methylamino-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(2-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1,2-Dimethyl-1H-imidazole-4-sulfonic acid {2-[7-amino-8-(3-�Lorenzi)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-pyrazole-4-sulfonic acid(2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
N-{2-[7-Azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}-C-cyclopropanesulfonyl;
1-Methyl-1H-imidazole-4-sulfonic acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid {2-[7-azetidin-1-yl-8-(3-chlorbenzyl)-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
Propane-1-sulfonic acid {2-[8-(3-Chlorobenzyl)-7-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-2-yloxy]ethyl}amide;
1-Methyl-1H-pyrazole-4-sulfonic acid [2-(7-azetidin-1-yl-8-benzyl-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl]amide;
1-Benzyl-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine; or
1-(3-Chlorobenzyl)-7-[2-(propane-1-sulfonyl)ethyl]-1,2,3,4-tetrahydronaphthalen-2-ylamine;
or its physiologically tolerated salt,
where neurological disorder is a dementia, worsening cognitive function, or a syndrome of attention deficit and hyperactivity disorder, and psychiatric disorder is an anxiety� disorder, affective disorder, bipolar disorder, schizophrenia, or psychotic disorder.

20. Aminotetraline derivatives of the formula (II)

where L represents C1-C6alkylsulphonyl, S1-C6alkoxycarbonyl,
Y represents NR9and
And2, X1, R2, R3, R4a, R4b, X2, X3, R5, n, R9have the meanings given in one of the PP. 1-15.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a method of obtaining (S)-2-methoxy-3-{4[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]benzo[b]thiophen-7-yl}propionic acid of formula (I) or its salts, in which formula (II) compound or its salt is hydrated in the presence of an iridium-including catalyst, in which the catalyst includes iridium and formula (III) compound, in which R1 stands for hydrogen, isopropyl, phenyl or benzyl and in which R2 stands for phenyl, 3,5-dimethylphenyl or 3,5-di-tert-butylphenyl. The invention also relates to the application of a complex of the catalyst, containing iridium and the formula (III) compound for obtaining the formula (I) compound.

EFFECT: obtaining the formula (I) compound with a high degree of conversion and enantiomeric purity.

6 cl, 4 tbl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula I, or their racemic mixture, or their individual optic isomers, or pharmaceutically acceptable salts possessing the properties of TGR bile acid receptor agonist. The invention also refers to methods for preparing the compounds. In general formula I , X represents amino group R'R"N, wherein the substitutes R' and R" can be optionally identical, or represents hydrogen, C1-C6alkyl, C3-C6cycloalkyl; substituted C1-C6alkyl, wherein the substitute is specified in phenyl or phenoxy, each of which can be substituted by halogen in turn, C1-C3alkyl, C1-C3alkoxy, phenyloxy, C3-C6cycloalkyl, 5-6-merous heteroaryl with 1 nitrogen atom; aryl specified in phenyl optionally substituted by fluorine, C1-C3alkyl, C1-C3 alkoxy; 5-6-merous heteroaryl with nitrogen atom as heteroatom; C2-C4alkenyl, acyl specified in C1-C6alkylcarbonyl or C3-C6cycloalkylcarbonyl; or substituted oxygroup, which represents hydroxy group, wherein hydrogen is substituted by C1-C6alkyl optionally substituted by hydroxy, di(C1-C3alkyl)amino, phenyl, which can be substituted by halogen in turn, C1-C3alkyl, C1-C3alkoxy; C2-C4alkenyl; and 5-6-merous heterocyclyl with nitrogen atom, or sulphur atom, or oxygen atom as heteroatom; R1a and R1b represents hydrogen, C1-C3alkyl, or R1a and R1b together form methylene chain -(CH2)n-, wherein n=2-5; R1c and R1d represents hydrogen, C1-C3alkyl; R2 represents acyl group specified in C1-C6alkylcarbonyl, wherein alkyl can be substituted by phenyl or phenoxy, each of which can be substituted by halogen in turn, C1-C3alkyl, C1-C3alkoxy; C3-C6cycloalkylcarbonyl; phenylcarbonyl, which can be substituted by halogen, C1-C3alkyl, C1-C3alkoxygroup, oxygroup, C1-C3alkylene dioxygroup; 5-6-merous heteroarylcarbonyl with nitrogen atom, or oxygen atom, or sulphur atom as heteroatom, optionally substituted by carboxy, halogen or C1-C3alkoxycarbonyl, substituted aminocarbonyl group, wherein the substitute can be specified in C1-C6alkyl optionally substituted by C1-C3alkoxycarbonyl, halogen, 5-6-merous heteroaryl together with nitrogen atom, or oxygen atom or nitrogen atom as heteroatom; C3-C6cycloalkyl; phenyl optionally substituted by halogen, C1-C3alkyl, C1-C3alkoxy, C1-C3alkoxycarbonyl, C1-C3alkylenedioxygroup; 5-6-merous heteroarym with nitrogen atom, or oxygen atom or nitrogen atom as heteroatom optionally substituted by carboxy, C1-C3alkoxycarbonyl; aminocarbonyl group substituted by C1-C3alkyl; sulphonyl group specified in alkylsuphonyl optionally substituted by hydroxyl group, cyano group, phenyl, which is optionally substituted by C1-C3alkyl, halogen, C1-C3alkoxy group; henylsulphonyl oprtionally substituted by C1-C3alkyl, halogen, C1-C3alkoxy group, cyano group, C1-C3alkylene dioxygroup, or 5-6-merous heteroarylsulphonyl with nitrogen atom, or sulphur atom, or oxygen atom as heteroatom optionally substituted by halogen, C1-C3alkyl, C1-C3alkoxy group; R3 represents hydrogen.

EFFECT: compounds can be used for preparing the pharmaceutical composition applicable in treating or preventing metabolic diseases, such as diabetes, obesity, diabetic obesity, metabolic syndrome, hypercholesterolemia, dislipidemia.

14 cl, 17 dwg, 8 tbl, 16 ex

Antiviral compounds // 2541571

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula I, such as below, or its pharmaceutically acceptable salts. What is described is a method for preparing them.

,

wherein: A independently from B means phenyl,

, or ,

and B independently from A means phenyl,

, or ,

and the values Z, Y, D, L1, L2, L3, Z1, Z2 are presented in the patent claim.

EFFECT: compounds are effective for hepatitis C virus (HCV) replication inhibition.

17 cl, 3 tbl, 8 dwg, 177 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining di-{ 4-[(tetrahydro -4H-1,4-oxazin-4-yl)-methylsulphanyl]-phenyl} ether oxalate of formula

as water-soluble substance with fungicidal activity. Essence of method consists in interaction of di-{ 4-[(tetrahydro -4H-1,4-oxazin-4-yl)-methylsulphanyl]-phenyl} ether with equimolar quantity of oxalic acid (COOH)2 at room (~20°C) temperature for 15 min.

EFFECT: output constitutes 99%.

2 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to field of organic chemistry, namely to heterocyclic compounds of formula I

and to their pharmaceutically acceptable salts, where A is selected from CH or N; R1 is selected from the group, consisting of C3-6-cycloalkyl, C3-6-cycloalkyl-C1-7-alkyl, C1-7-alkoxy-C1-7-alkyl, halogen-C1-7-alkyl; R2 and R6 independently on each other represent hydrogen of halogen; R3 and R5 independently on each other are selected from the group, consisting of hydrogen, C1-7-alkyl and halogen; R4 is selected from the group, consisting of hydrogen, C1-7-alkyl, halogen and amino; R7 is selected from the group, consisting of C1-7-alkyl, C1-7alkoxy-C1-7-alkyl, C1-7-alkoxyimino-C1-7-alkyl, 4-6-membered heterocyclyl, containing one heteroatom O, phenyl, with said phenyl being non-substituted or substituted with one hydroxy group, and 5-10-membered heteroaryl, containing 1-3 heteroatoms, selected from N, S and O, said heteroaryl is not substituted or is substituted with one or two groups, selected from the group, consisting of C1-7-alkyl, hydroxy, C1-7-alkoxy, cyano, C1-7-alkylaminocarbonyl and halogen. Invention also relates to pharmaceutical composition based on formula I compound and to method of obtaining formula I compound.

EFFECT: obtained are novel heterocyclic compounds, which are agents, increasing level of LDLP.

17 cl, 2 tbl, 89 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to isoxazoline FAAH inhibitors of formula (I) or their pharmaceutically acceptable forms, wherein each of G, Ra, Rb, Rc and Rd has a value described in the present application, to pharmaceutical compositions, and methods of treating a FAAH-mediated condition.

EFFECT: developing the method of treating the FAAH-mediated condition.

32 cl, 22 tbl, 351 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of structural formula

possessing inhibitory activity on BTK, TEC, BMX, ITK, ErbB1, ErbB4 and/or JAK3 kinases. In formula (I-b), ring A and ring B represents phenyl; Ry represents -CN, -CF3, C1-4 aliphatic group, C1-4 halogenaliphatic group, -OR, -C(O)R or -C(O)N(R)2; each group R independently represents hydrogen or a group specified in C1-6 aliphatic group optionally containing a substitute presented by halogen, -(CH2)0-4R°, -(CH2)0-4OR°, -(CH2)0-4N(R°)2, -(CH2)0-4N(R°)C(O)OR°, -(CH2)0-4C(O)R°, -(CH2)0-4S(O)2R°, or 5-6-merous substituted or aryl ring containing 1-2 heteroatoms independently specified in nitrogen or oxygen optionally substituted by group =O, -(CH2)0-4R°, -(CH2)0-4N(R°)2 or -(CH2)0-4OR°; phenyl; 5-6-merous heterocyclic ring containing 1-2 heteroatoms independently specified in nitrogen, oxygen or sulphur optionally substituted by group -(CH2)0-4R°, -(CH2)0-4OR° or =O; or 6-merous monocyclic heteroaryl ring containing 1 nitrogen atom; W1 and W2 represent -NR2-; R2 represents hydrogen, C1-6aliphatic group or -C(O)R; m and p are independently equal to 0, 1, 2, 3 or 4; Rx is independently specified in -R, -OR, -O(CH2)qOR or halogen, wherein q=2; Rv is independently specified in -R or halogen; R1 and R° radical values are presented in the patent claim. The invention also refers to a pharmaceutical composition containing the above compounds.

EFFECT: preparing the compounds possessing the inhibitory activity on BTK, TEC, BMX, ITK, ErbB1, ErbB4 and/or JAK3 kinases.

17 cl, 25 dwg, 20 tbl, 286 ex

Amide derivative // 2536409

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) , where R1 is a hydrogen atom or a C1-C6-alkyl group, substituted with one or two substitutes selected from C1-C6-alkoxy group, hydroxyl group, which can be substituted with a C1-C6-alkylcarbonyl group (substituted with one or two substitutes γ), and a 4-6-member saturated monocyclic heterocyclic carbonyl group containing a N atom; γ is a hydroxyl group, amino group, di(C1-C6-alkyl)amino group and carbamoyl group; R2 is a H atom or a C1-C6alkyl group, which can be substituted with a hydroxyl group; or R1 and R2, together with the nitrogen atom with which they are bonded, can be combined to form an azetidine group, a pyrrolidine group or morpholine group, which can be substituted with one hydroxyl group or a hydroxy-C1-C6-alkyl group; R3 and R4 is a C1-C6-alkyl group; R5 is a halogen atom or a C1-C6-alkyl group; R6 is a halogen atom; m and n denote an integer from 0 to 1; V and W are CH; X, Y and Z each independently can be CH or N. The invention also relates to a pharmaceutical composition containing a compound of formula (I), use of the compound of formula (I) and a method of treating sugar diabetes a disease associated with diabetes.

EFFECT: compounds of formula (I), having hypoglycemic activity.

21 cl, 6 tbl, 72 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and (II), which possess the blocking activity on voltage-sensitive sodium channels, such as TTX-S channels, and their pharmaceutically salts. In general formula (I) and (II), R1 represents -CF3, -CHF2, -OCF3, -OCHF2, -OCH2CHF2/ -OCH2CF3, -OCF2CHF2; -OCF2CF3, -OCH2CH2CF3, -OCH(CH3)CF3, -OCH2C(CH3)F2, -OCH2CF2CHF2, -OCH2CF2CF3, OCH2CH2OCH2CF3, -NHCH2CF3, -SCF3, -SCH2CF3, -CH2CF3 -CH2CH2CF3, -CH2OCH2CF3 and -OCH2CH2OCF3; R2 is specified in (1) hydrogen, (2) halogen (3) -On-C1-6 alkyl, (4) -On-C3-6 cycloalkyl, (5) -On-phenyl, (6) -On-heterocyclic group, (7) -NR7 (C=O)R8; wherein n is equal to 0 or 1, p is equal to 1, 2; R3 and R4 represents hydrogen or C1-6 alkyl, X represents carbon atom; Y represents hydrogen or C1-6 alkyl; Ar represents 4-pyridyl, 4-pyrimidyl or 6-pyrimidyl, which is substituted in the 2nd position by a substitute, which is independently specified in (1) -(C=O)-NR7R8, (2) -NR7(C=O)R8; R9 is specified in: (1) hydrogen, (2) halogen, (3) -On-C1-6 alkyl, wherein alkyl is unsubstituted or substituted by hydroxyl; q is equal to 1, 2 or 3; R10 independently represents hydrogen, C1-6 alkyl, C2-6alkenyl, C3-7 cycloalkyl or phenyl, which is unsubstituted or substituted by one or substitutes independently specified in hydroxyl, -On-C1-6 alkyl and -C3-7 cycloalkyl.

EFFECT: preparing the compounds possessing the blocking activity on voltage-sensitive sodium channels.

7 cl, 2 tbl, 1281 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula

,

where values A, R1-R6 are given in i.1 of the invention formula. Methods of obtaining the formula (I) compound are described.

EFFECT: compounds demonstrate an inhibiting activity of the cathepsin enzyme, which makes it possible to use them for the preparation of a pharmaceutical composition and for the preparation of a medication.

38 cl, 12 dwg, 495 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds with structural formulas , as follows and their stereoisomers, wherein Y represents or and using them for an agent for treating and/or preventing glaucoma and/or ocular hypertension.

EFFECT: treating and/or preventing glaucoma and/or ocular hypertension.

7 cl, 32 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutically acceptable salts specified in a group consisting of sodium salt, lithium salt, potassium salt, calcium salt, magnesium salt, arginine salt, lysine salt, methanamine salt, dimethylamine salt, trimethylamine salt, ethylamine salt, diethylaminte salt, triethylamine salt, ethanolamine salt, piperazine salt, dibenzylethylene diamine salt, methyl glucamine salt, tromethamine salt, quaternary tetramethylammonium salt, quaternary tetraethylammonium salt and choline salt, bicyclosubstituted azopyrazole derivatives of general formula

.

The invention also refers to a method for preparing them, a pharmaceutical composition containing them, and using them as a therapeutic agent, particularly as thrombopoietin (TPO) mimetics, using them as TPO agonists. In general formula (I), Het is specified in a group consisting of phenyl, furanyl and thienyl; each R1, R2, R3 andR4 are independently specified in a group consisting of hydrogen and alkyl; n is equal to 0, 1 or 2.

EFFECT: improving the pharmokinetic properties of the compound of formula (I) ensured by better solubility.

19 cl, 1 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula or its therapeutically acceptable salts, wherein A1 represents furyl, imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, pyrrolyl, thiazolyl, thiadiazolyl, thienyl, triazolyl, piperidinyl, morpholinyl, dihydro-1,3,4-thiadiazol-2-yl, benzothien-2-yl, banzothiazol-2-yl, tetrahydrothien-3-yl, [1,2,4]triazolo[1,5-a]pyrimidin-2-yl or imidazo[2,1-b][1,3]-thiazol-5-yl; wherein A1 is unsubstituted or substituted by one, or two, or three, or four, or five substitutes independently specified in R1, OR1, C(O)OR1, NHR1, N(R1)2, C(N)C(O)R1, C(O)NHR1, NHC(O)R1, NR1C(O)R1, (O), NO2, F, Cl, Br and CF3; R1 represents R2, R3, R4 or R5; R2 represents phenyl; R3 represents pyrazolyl or isoxazolyl; R4 represents piperidinyl; R5 represents C1-C10alkyl or C2-C10alkenyl each of which is not specified or specified by substitutes specified in R7, SR7, N(R7)2, NHC(O)R7, F and Cl; R7 represents R8, R9, R10 or R11; R8 represents phenyl; R9 represents oxadiazolyl; R10 represents morpholinyl, pyrrolidinyl or tetrahydropyranyl; R11 represents C1-C10alkyl; Z1 represents phenylene; Z2 represents piperidine unsubstituted or substituted by OCH3, or piperazine; both Z1A and Z2A are absent; L1 represents C1-C10alkyl or C2-C10alkenyl each of which is unsubstituted or substituted by R37B; R37B represents phenyl; Z3 represents R38 or R40; R38 represents phenyl; R40 represents cyclohexyl or cyclohexenyl; wherein phenylene presented by Z1 is unsubstituted or substituted by the group OR41; R41 represents R42 or R43; R42 represents phenyl, which is uncondensed or condensed with pyrrolyl, imidazolyl or pyrazole; R43 represents pyridinyl, which is uncondensed or condensed with pyrrolyl; wherein each cyclic fragment presented by R2, R3, R4, R8, R9, R10, R38, R40, R42 and R43 is independently unsubstituted or substituted by one or more substitutes independently specified in R57, OR57, C(O)OR57, F, Cl CF3 and Br; R57 represents R58 or R61; R58 represents phenyl; R61 represents C1-C10alkyl; and wherein phenyl presented by the group R58 is unsubstituted or substituted by one or more substitutes independently specified in F and Cl.

EFFECT: invention refers to a pharmaceutical composition containing the above compounds, and to a method of treating diseases involving the expression of anti-apoptotic Bcl-2 proteins.

7 cl, 2 tbl, 48 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to quinoxaline derivatives of general formula

,

a based pharmaceutical composition, using them as therapeutic agents, as well as to a based therapeutic agent for treating tumour diseases. In general formula I X represents: oxygen or sulphur; R1 represents hydrogen, R2/R3 represents hydrogen, R4 represents: (i) C1-C12-alkyl, (ii) saturated C3-C8-cycloalkyl, optionally substituted by C6-aryl, (iii) unsaturated C3-C8-cycloalkyl, (iv) heterocyclyl substituted by C(O)CF3, (v) C1-C6-alkyl substituted by C6-aryl, the above C6-aryl can be substituted by F, Cl, Br, I, -O-C1-C6-alkyl, C1-C6-alkyl, C6-aryl or hydroxy, (vi) C1-C6-alkyl substituted by C5-heteroaryl, (vii) C1-C8-alkylene, (viii) 1-adamantyl, (ix) C1-C6-alkyl substituted by C6-heterocyclyl containing a nitrogen atom and an oxygen atom, (x) C1-C6-alkyl substituted by C3-C6-cycloalkyl, or (xi) C1-C6-alkyl substituted by C6-heteroaryl; R5 represents hydrogen, R6 represents (i) aryl optionally substituted by C1-C6-alkyl, -O-C1-C6-alkyl, hydroxy, F, Cl, Br, I or amino, or (ii) C5-heteroaryl containing 2 nitrogen atoms optionally substituted by C1-C6-alkyl, R7 and R8 represent hydrogen.

EFFECT: producing the therapeutic agent for treating the tumour diseases.

7 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: described are novel heteroaryl-N-aryl-carbamates of general formula , where: Ar1 is phenyl, probably substituted with C1-C6halogenalkyl or C1-C6halogenalkoxy; Het is triazolyl; Ar2 is phenyl; X1 represents O or S; X2 - O; R4 - H or C1-C6alkyl; n=0, 1 or 2; and R1, R2 and R3 are independently selected from H, CN, C1-C6alkyl, C1-C6halogenalkyl, C3-C6cycloalkyl, C2-C6alkenyl, C2-C6alkinyl, C(=O)O(C1-C6alkyl), phenyl and Het-1, where Het-1 is a 5-membered unsaturated heterocyclic ring, containing one heteroatom, selected from sulphur or hydrogen, or a 6-membered unsaturated heterocyclic ring, containing one nitrogen atom as a heteroatom, and Het-1 can be substituted with F, Cl, C1-C6alkyl, C1-C6halogenalkyl or C1-C6alkoxy, and a method of fighting pest insects Lepidoptera or Homoptera with the application of the said compounds as insecticides and acaricides.

EFFECT: increased efficiency.

5 cl, 2 tbl, 80 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to a compound of Formula

,

where Y represents a group of formula -(CR9R10)-; X is selected from the group, consisting of -C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)- and -S(-O)2-; Z represents a group of formula -(CR13R14)q-; R1 is selected from the group, consisting of C1-C12alkyl, optionally substituted with one substituent, selected from naphthyl, indole and biphenyl; C2-C12alkenyl, substituted with a substituent, selected from thienyl, naphthyl and phenyl, with the said phenyl being optionally substituted with 1-2 substituents; selected from halogen, trifluoroalkyl, C1-C6alkyl, methoxy and hydroxy; C3-C6cycloalkyl; C6-C10aryl, optionally substituted with 1-2 substituents, selected from halogen, phenyl, amino, phenoxy, C1-C6alkyl, methoxy, hydroxyl and carboxy; and C4-C9heteroaryl, selected from indole, quinoline, quinoxaline, benzofuranyl, benzothiophene, benzimidazole, benzotriazole, benzodioxin, benzothiasole, pyrazole, furyl and isoxazole, optionally substituted with a substituent, selected from C1-C6alkyl and phenyl; R2 and R3 each is independently selected from the group, consisting of H and C1-C12alkyl; R4a is selected from the group, consisting of H, C1-C12alkyl, optionally substituted with phenyl; C2-C12alkenyl, C3-C6cycloalkyl, C6aryl, C(=O)R15, C(=O)NR15R16, C(=O)OR15, SO2R15 and -C(=NR15)-NR16R17; R4d represents hydrogen or R4a and R4b, taken together with a nitrogen atom, which they are bound to, form an optionally substituted heterocyclic fragment, selected from piperidine, morpholine, pyrrolidine and azetidine, where the substituent is selected from C1-C12alkyl, hydroxy, halogen, carboxy and oxo; each R5a and R5b represents H, or R6, R7 and R8 each is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6-C10aryl, optionally substituted with halogen, or taken together with a carbon atom, which they are bound to, two or more of R6, R7 and R8 form a fragment, selected from the group, consisting of C2-C12alkenyl; C3-C6cycloalkyl, optionally substituted with C1-C6alkyl; C6aryl, optionally substituted with 2 substituents, selected from halogen; each R9 and R10 represents H or C1-C12alkyl, substituted with naphthyl; each R11 and R12 represents H; R13 and R14 represent H, or each R15, R16 and R17 is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6aryl, substituted with one substituent, selected from C1-C6alkyl; and C5-heteroaryl, additionally containing one nitrogen atom, with the said heteroaryl representing pyridyl; q represents an integer number, selected from the group, consisting of 2, 3 and 4; r represents 1; or its pharmaceutically acceptable salt. The invention also relates to particular compounds of 1,4-diazepan-2-one derivatives.

EFFECT: obtaining 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists.

21 cl, 7 tbl, 110 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a novel derivative of N-acylanthranilic acid, represented by the following general formula 1, or to its pharmaceutically acceptable salt, in which R1, R2, R3, X1, X2, X3, X4 and A are determined in the invention formula.

EFFECT: invention relates to an inhibitor of collagen production, a medication for treating diseases, associated with the excessive production of collagen, containing N-acylanthranilic acid derivative Formula 1.

FIELD: chemistry.

SUBSTANCE: invention relates to a photoinitiator, a method for production and use thereof and a coating composition. The photoinitiator is a compound of formula: (PI-Sp)n-BB (I), where PI is a thioxanthone group, optionally including additional substitutes in the Sp group; Sp is a spacer link selected from a group consisting of or , BB is a backbone chain link selected from a group consisting of

The method of producing the photoinitiator includes the following steps: (a) optionally substituted thioxanthone, containing at least one hydroxy group, reacts with epichlorohydrin or haloacetic acid ester; (b) the compound from step (a) reacts with the corresponding backbone chain link containing a functional group, or the compound from step (a) reacts with a compound containing a functional group, and the obtained intermediate then reacts with the corresponding backbone chain link; optionally (c) obtaining derivatives of the compounds from step (b). The photoinitiator is used to cure a coating composition, preferably printing ink containing a polymerisable component.

EFFECT: invention enables to obtain a photoinitiator with good curing activity, faint odour and good compatibility with other components of the composition.

10 cl, 1 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula

,

wherein: each of R1, R2, R4, R5, R6, R7, R8 R9, R10, R11, R12, R13, R14, R15 R16 and R17 is independently specified in a group consisting of deuterium or hydrogen; and R3 is independently specified in a group consisting of CD3 and CH3; provided R3 represents CH3, at least one of the groups R1, R2, R4, R5, R6, R7, R8 R9, R10, R11, R12, R13, R14, R15 R16 and R17 represents deuterium; and R18 represents hydrogen. The invention also refers to a drug on the basis of the above compound for treating a condition causing pain.

EFFECT: there are prepared new compounds inhibiting MMPs (metalloproteinases) which show the high activity, metabolic stability and/or lower toxicity in relation to the currently known MMP inhibitors for treating pain and other diseases, such as cancer.

16 cl, 2 dwg, 14 tbl, 136 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 6-substituted isoquinoline and isoquinolinone derivatives of formula or to its stereoisomer and/or tautomer forms and/or a pharmaceutically acceptable salt, wherein R1 represents H, OH or NH2; R3 represents H; R4 represents H, a halogen atom, CN or (C1-C6)alkylene-(C6-C10)aryl; R5 represents H, a halogen atom, (C1-C6)alkyl; R7 represents H, a halogen atom, (C1-C6)alkyl, O-(C1-C6)alkyl; R8 represents H; R9 and R6 are absent; R10 represents (C1-C6)alkyl, (C1-C8)heteroalkyl, (C3-C8)cycloalkyl, (C6)hetrocycloalkyl, (C1-C6)alkylene-(C3-C8)cycloalkyl, (C1-C6)alkylene-(C6-C10)aryl, (C1-C6)alkylene-(C6)heterocycloalkyl; R11 represents H; R12 represents (C1-C6)alkyl, (C3-C8)cycloalkyl, (C5)heteroaryl or (C6-C10)aryl; R13 and R14 independently represent H, (C1-C6)alkyl, (C1-C6)alkylene-R'; n is equal to 0; m is equal to 2 or 3; s is equal to 1 or 2; r is equal to 1; L represents O or NH; R' represents (C3-C8)cycloalkyl, (C6-C10)aryl; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more OCH3; wherein in the rests, R10, R12-R14 alkyl or alkylene are unsubstituted or optionally substituted by one or more halogen atoms; wherein (C1-C8)heteroaryl group means (C1-C8)alkyl groups, wherein at least one carbon atom is substituted by O;. (C6)heterocycloalkyl group means a monocyclic carbon ring system containing 6 ring atoms wherein one carbon atom can be substituted by 1 oxygen atom or 1 sulphur atom which can be optionally oxidated; (C5)heteroaryl means a monoring system wherein one or more carbon atoms can be substituted by 1 nitrogen atom or 1 sulphur atom or a combination of various heteroatoms. Also, the invention refers to using the compound of formula (I) and to a therapeutic agent based on the compound of formula (I).

EFFECT: there are prepared new compounds effective for treating and/or preventing diseases associated with Rho-kinase and/or mediated by Rho-kinase by phosphorylation of myosin light chain phosphatase, and the compositions containing these compounds.

32 cl, 111 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to pyrazine derivatives of formula I, as well as to their enanthiomers, diastereomers and pharmaceutically acceptable salts, wherein R1 is specified in a group consisting of ii) pyridinyl optionally having one substitute specified in a group consisting of C1-4alkoxy and cyano; and iii) pyrimidin-5-yl; or R1 optionally represents methoxymethyl, when Y represents ethinyl; Y represents ethinyl or a bond; R2 represents phenyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxol-5-yl, indolyl or pyridinyl substituted by methyl, phenyl has one to two substitutes independently specified in a group consisting of C1-4alkyl, C1-4alkoxy, fluorine, chlorine, cyano, cyanomethyl, difluoromethyl, trifluoromethyl and hydroxy; or R2 represents phenyl having one C1-4alkylcarbonylamino or 1H-imidazol-1-yl substitute; X represents O or CH2; L is absent, and R3 represents 4-aminocyclohexyl, or L represents methylene, while R3 is specified in a group consisting of i) pyrrolidin-2-yl; ii) 1-aminoeth-1-yl; and iii) 1-aminocyclopent-1-yl; or R3 is combined into one cycle with L nitrogen atom to which L is attached to form piperazinyl. Besides, the invention refers to specific compounds, a pharmaceutical compound based on a compound of formula I, a method of treating pain and some neurodegenerative diseases.

EFFECT: there are produced new pyrazine derivative effective in treating pain and some neurodegenerative diseases.

21 cl, 3 tbl, 13 ex

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