Substituted aminoindans and analogues thereof to be used in pharmaceutics


FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula , wherein A means a six-merous aryl radical or a five-merous heteroaryl radical which contains one heteroatom specified in oxygen and sulphur; one or more hydrogen atoms in the above aryl or heteroaryl radicals can be substituted by substituting groups R1 which are independently specified in a group consisting of: F, Cl, Br, I, (C1-C10)-alkyl-, (C1-C10)-alkoxy-, -NR13R14; B means a radical with mono- or condensed bicyclic rings specified in a group consisting of: six-ten-merous aryl radicals, five-ten-merous heteroaryl radicals and nine-fourteen-merous cycloheteroalkylaryl radicals, wherein cycloheteroalkyl links can be saturated or partially unsaturated, while the heterocyclic groups can contain one or more heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, one or more hydrogen atoms in the radical groups B can be substituted by substituting groups R5 (as specified in the patent claim), L means a covalent bond, X means the group -O-, R2 is absent or means one or more substitutes specified in F and (C1-C4)-alkyl radical; R3 and R4 independently mean (C1-C10)-alkyl, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkylalkyl, (C2-C19)-cycloheteroalkyl, (C3-C19)-cycloheteroalkylalkyl, (C6-C10)-aryl, (C7-C20)-arylalkyl, (C1-C9)-heteroaryl, (C2-C19)-heteroarylalkyl radicals, or R3 and R4 together with nitrogen attached whereto can form a four-ten-merous saturated, unsaturated or partially unsaturated heterocyclic compound which can additionally contain one or more heteroatoms among -O-, -S(O)n-, =N- and -NR8-; other radicals are such as specified in the patient claim. Also, the invention refers to using the compound of formula I for preparing a drug.

EFFECT: compounds of formula (I) as Na+/H+ metabolism inhibitors NHE3.

22 cl, 27 dwg, 1 tbl, 756 ex

 

The invention relates to substituted aminoindane, and their analogs and their use as pharmaceuticals. Pharmaceutical preparations containing compounds of this type, applicable to the prevention or treatment of various diseases.

Known inhibitors of NHE3 receive, for example, from compounds of the type acylhalides (EP 0825178), norbornanamine (WO 01/44164), 2-guanidino-hintline (WO 01/79186, WO 03/051866), benzamidine (WO 01/21582, WO 01/72742), 4-vinyltetrahydrofuran (WO 06/074813) or benzimidazole (WO 03/101984). Squalamine, also known as inhibitor of NHE3 (.Donowitz and others, Am. J. Physiol. 276 (Cell Physiol. 45): C136-C144), there is probably not a direct and indirect mechanism of action, and, accordingly, its effect reaches its maximum power only after one hour.

Based on this, it was unexpectedly found that the compounds of formula I are excellent inhibitors of the sodium-hydrogen exchanger (NHE), in particular the sodium-hydrogen exchanger of subtype 3 (NHE3). Accordingly, in the proposed invention the compounds of formula I:

in which:

And indicates the six-deletechannel aryl radical or a five-deletechannel heteroaryl radical, with aryl and heteroaryl radicals may be mono - or bicyclic, heteroaryl radical may contain one or more heteroatoms selected from the group including the cabbage soup nitrogen, oxygen and sulphur,

when one or more hydrogen atoms in the above-mentioned mono - or bicyclic aryl or heteroaryl radicals can be substituted for the placeholder groups R1 are independently from each other selected from the group comprising F, Cl, Br, I, (C1-C10)-alkyl, (C2-C10)-alkenyl-, (C2-C10)-quinil-, (C3-C14-cycloalkyl-, (C4-C20-cycloalkenyl-, (C4-C20)-cycloalkylation-, (C1-C10)-alkoxy, (C1-C10)-alkylthio-, (C6-C14)-aryl-, (C2-C13-heteroaryl, -CN, -NR13R14, -C(O)R12, -SF5, -S(O)nR12, -C(O)OR12, -C(O)NR13R14, -S(O)nNR13R14,

two adjacent radical groups R1 may also form a saturated or partially unsaturated (C5-C10)-cycloalkyl radical or a saturated or partially unsaturated (C2-C9)-cyclogeranyl radical, with cyclogeranyl radical can contain 1, 2 or 3 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or 1 sulfur atom,

mentioned alkyl, alkeline, alkyline, cycloalkyl, cycloalkenyl, cycloalkylation, cycloheptadiene, alkoxy and alliteratively can be independently of one another once or several times substituted by F, HE or (C1-C10 )-alkoxy,

In denotes the radical with mono - or articulated bicyclic ring selected from the group including:

six-desyatiletnie aryl radicals,

five-desyatiletnie heteroaryl radical

three-desyatiletnie cycloalkyl radicals

nine-chetyrnadcatiletnie cycloalkenyl radicals

eight-chetyrnadcatiletnie cycloalkylcarbonyl radicals

three-desyatiletnie cyclogeranyl radicals

nine-chetyrnadcatiletnie cyclohexanemethylamine radicals and

eight-chetyrnadcatiletnie cyclohexanoltramadol radicals

this cycloalkyl or cyclogeranyl groups can be saturated or partially unsaturated, and heterocyclic groups can contain one or more heteroatoms selected from the group comprising nitrogen, oxygen and sulphur,

one or more hydrogen atoms in the radical groups may be replaced by replacing the groups R5, which are independently from each other selected from the group comprising (C1-C10)-alkyl radicals, (C2-C10)-alkeline radicals, (C2-C10)-alkyline radicals, (C1-C10)-alkoxy radicals, (C1-C10-alkylthiomethyl, (C3-C14)-cycloalkyl radicals, (C4-C20)-cycloalkylation Radik the crystals, (C4-C20)-cycloalkylation, (C2-C19)-cyclogeranyl radicals, (C3-C19)-cyclohexanediamine radicals, (C3-C11)-cycloalkane radicals, (C2-C11)-cyclohexaneacetic radicals, (C6-C10)-aryl radicals, (C1-C9)-heteroaryl radicals, (C9-C14)-cycloalkenyl radicals, (C5-C13)-cycloalkylcarbonyl radicals, (C7-C13)-cycloheptatriene radicals, (C4-C12)-cyclohexanecarbonitrile radicals

cycloalkyl and cyclogeranyl groups can be saturated or partially unsaturated, and one or more hydrogen atoms in the above-mentioned radical groups R5 may be substituted by further radicals, which are independently from each other selected from the group consisting of radical groups R11,

R5 may also represent one or more radicals independently from each other selected from the group including AN (=O)NH2, F, Cl, Br, I, CN, NO2, -NR17R18, -NR16COR17, -NR16COOR17, -NR16CONR17R18, -NR16-S(O)2-R17, -NR16-S(O)2-NR17R18, -COOR16, -COR16, -CO(NR17R18), S(O)nR16, -S(O)2NR17R18,

R16, R17 and R18 independently of one another may represent a radical selected from the group comprising H, (C2-C19)-cycloheptatriene, (C3-C14 )-cycloalkyl, (C6-C10)-aryl, (C1-C10)-alkyl radicals,

all of which can be independently from each other substituted by an Oh, (=O), F, Cl, Br, I, CN, NO2, -NR13R14, -NR13COR12, -NR13COOR12, -NR12CONR13R14, -NR13-S(O)2-R12, -NR12-S(O)2-R13R14, -COOR12, -COR12, -CO(NR13R14), -S(O)nR12, -S(O)2NR13R14, (C3-C14-cycloalkyl, (C4-C20-cycloalkenyl, (C2-C19-cyclogeranyl, (C3-C19-cyclohexanoltramadol, (C6-C10)-aryl and (C1-C9-heteroaryl, and

R17 and R18 together with the nitrogen to which they are bound, may form a four-semiline saturated, unsaturated or partially unsaturated heterocyclic compound containing 1 to 13 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-,=N -, and-NR15-,

formed heterocyclic compound may be one or more times independently from each other substituted with F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy, (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-quinil, (C3-C14-cycloalkyl, (C4-C20-cycloalkenyl, (C2-C20-cyclogeranyl, (C3-C19-cyclohexanoltramadol, each of which independently on the angle from each other, in turn, may contain one or more radicals F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy,

L denotes a covalent bond or alkilinity bridge communication containing 1-10 carbon atoms, which may independently of one another can contain one or more substituents from the group comprising (C1-C10)-alkyl, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkenyl radicals, -COR12, -CO(NR13R14), S(O)nR12, -S(O)2NR13R14, (=O) and F,

while alkyl, cycloalkyl and cycloalkenyl radicals can be one or more substituted by F,

X denotes the group-N(R6)-, -O-, -S(O)nor alkylene containing 1-5 carbon atoms, in which R6 may be a hydrogen or (C1-C10)-alkyl, (C3-C14)-cycloalkenyl, (C4-C20)-cycloalkylcarbonyl radical, it is independently of one another one or more times can be replaced by F, or R6 may be a-COR12, -CO(NR13R14), S(O)nR12, -S(O)2NR13R14,

R2 is absent or represents one or more substituents, which independently of one another may be selected from the group comprising F, (C1-C10)-alkyl and (C1-C10)-alkoxy radical, this alkyl and alkoxy radicals may be independently of one another one or bore is only replaced by F,

R3 and R4 independently from each other represent a hydrogen radical or a radical selected from the group comprising (C1-C10)-alkyl radicals, (C2-C10)-alkeline radicals, (C2-C10)-alkyline radicals, (C3-C14)-cycloalkyl radicals, (C4-C20)-cycloalkenyl radicals, (C2-C19)-cyclogeranyl radicals, (C3-C19)-cyclohexanediamine radicals, (C6-C10)-aryl radicals, (C7-C20)-arylalkyl radicals, (C1-C9)-heteroaryl radicals, (C2-C19)-heteroarylboronic radicals

while the radicals R3 and R4 independently of one another one or more times may be substituted by a radical from the group comprising HE, NH2, (=O), F, Cl, Br, I, CN, NO2, -NR13R14, -NR13COR12, -NR13COOR12, -NR12CONR13R14, -NR13-S(O)2-R12, -NR13 - S(O)2-NR13R14, -COOR12, -C0R12, -CO(NR13R14), S(O)nR12, -S(O)2R13R14, or

R3 and R4 together with the nitrogen to which they are attached, form a four-desatino saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-, =N -, and-NR8-,

where heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group R7 is R9, and

heterocyclic radicals can be connected in bridge connection, saturated or unsaturated (C1-C10)-alkyl or (C1-C9)-heteroalkyl chain or-NR15-, -O-, -S-, with alkyl or heteroalkyl chain can also be a system of spirocycles ring formed by R3 and R4, and alkyl or heteroalkyl bridge connection independently of one another one or more times can be replaced by radicals selected from the group of R7 and R9,

R8 group NR8 may form with the ring formed by R3 and R4, additional saturated, unsaturated or partially unsaturated heterocyclic compound, which independently of one another one or more times may be substituted by radicals selected from the group of R7 and R9, and can optionally contain one or more heteroatoms from among-O-, -S(O)n-, -N= and-NR19-,

R7 denotes (C1-C10)-alkyl radical or (C1-C14)-cycloalkenyl radical, this alkyl radical can be, independently of one another once or several times substituted by R9,

R8 denotes H, (C1-C10)-alkyl radical or (C1-C14)-cycloalkenyl radical, COR12, -CO(NR13R14), S(O)nR12, -S(O)2NR13R14, this alkyl radical can be, independently of one another one or more times during the Eden on R10,

R9 denotes a radical selected from the group comprising HE, (=O), F, Cl, Br, I, CN, NO2, -NR13R14, -NR13COR12, -NR13COOR12, -NR12CONR13R14, -NR13-S(O)2-R12, -NR13-S(O)2-NR13R14, -COOR12, -COR12, -CO(NR13R14), S(O)nR12, -S(O)2NR13R14, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkenyl, (C1-C10)-alkoxy, (C2-C19)-cycloheptatriene, (C3-C19)-cyclohexanediamine, (C6-C10)-aryl, (C1-C9)-heteroaryl radicals,

R10 represents a radical selected from the group comprising F, IT, CN, (C1-C10)-alkoxy, (C1-C10)-alkylthio, NO2, -NR13R14, -NR13COR12, -NR13COOR12, -NR13CONR13R14, -NR13-S(O)2-R12, -NR12-S(O)2-NR13R14, -COOR12, -COR12, -CO(NR13R14), S(O)nR12, -S(O)2NR13R14,

R11 represents a radical selected from the group comprising (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-quinil, (C1-C10)-alkoxy, (C1-C20)-alkylthio, (C3-C14-cycloalkyl, (C4-C10-cycloalkenyl, (C2-C13-cyclogeranyl, (C4-C19-cyclohexanoltramadol, (C3-C14)-cycloalkane, (C2-C13)-cyclohexaneacetic, independently of one another one or more times may be substituted by R10, (=0), Cl, Br, I, and R10,

R12, R13 and R14 are independently from each other denote H, (C1-C 10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-quinil, (C3-C14-cycloalkyl, (C4-C10-cycloalkenyl, (C2-C13)-cyclogeranyl, (C3-C19-cyclohexanoltramadol, (C6-C10)-aryl, each of which may be independently of one another once or several times substituted by F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy, or

R13 and R14 together with the nitrogen to which they are bound, may form a four-semiline saturated, unsaturated or partially unsaturated heterocyclic compound containing 1 to 13 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-, =N -, and-NR15-,

thus formed heterocyclic compound may be independently of one another once or several times substituted by F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy, (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-quinil, (C3-C14-cycloalkyl, (C4-C20-cycloalkenyl, (C2-C20-cyclogeranyl, (C3-C19-cyclohexanoltramadol, each of which can in turn independently from each contain about the Jn or more radicals, including F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy,

R15 denotes a radical selected from the group comprising H1 (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-quinil, (C3-C14-cycloalkyl, (C4-C20-cycloalkenyl, (C2-C13)-cyclogeranyl, (C3-C19-cyclohexanoltramadol, each of which may be independently of one another once or several times substituted by F, IT, CN or (C1-C10)-alkoxy,

R19 represents H, and (C1-C10)-alkyl radical or (C1-C14)cycloalkenyl radical, COR12, -CO(NR13R14), S(O)nR12, -S(O)2NR13R14, this alkyl radical can be, independently of one another once or several times substituted by R10,

n denotes 0, 1 or 2,

p denotes 1 or 2, and

q denotes 0 or 1, and

their pharmaceutically acceptable salt,

in which:

i) where And denotes phenyl, represents phenyl or benzodioxolyl, X denotes-O - or-S-, L denotes a bond, a, R3 and R4 represent H, (C1-C10)-alkyl, (C3-C14-cycloalkyl, (C7-C20-arylalkyl or R3 and R4 together represent unsubstituted pyrrolidinyl, morpholinyl, piperidinyl or piperazinilnom radical or 4-methylpiperazine radical, the debtor shall be present at least one radical R5, which is not (C1-C10)-alkyl, (C1-C10)-alkoxy, HE, CF3, F, Cl, Br or I, a radical

(ii) where And denotes phenyl, X represents-O-, -S - or-NH-, and R3 and R4 represent (C1-C10)-alkyl, (C3-C14)-cycloalkenyl or (C4-C20)-cycloalkylcarbonyl radical must be present at least one radical R5 that is not F, Cl, Br, I, (C1-C4)-alkyl, (C1-C4)-alkoxy, CF3, OCF3, CN, NO2, NH2, -NH((C1-C10)-alkyl), -N((C1-C10)-alkyl)2, unsubstituted or substituted benzoline or unsubstituted or substituted phenyl -(CH2)r-Y-(CH2)s- radical, in which Y represents a bond or oxygen, and r and s is equal to from 0 to 4, wherein r+s is not larger than 4.

In one of the preferred embodiments are compounds and their pharmaceutically acceptable salts of formula I, in which L denotes a covalent bond, X represents a group-O-, and q is 0.

Preferred substances according to the invention are compounds and their pharmaceutically acceptable salts of formula Ia:

,

in which:

And denotes phenyl or a five or six-membered heteroaryl radical, which as heteroatoms may contain 1, 2 or 3 nitrogen atom and 1 oxygen atom 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or 1 sulfur atom, one or more hydrogen atoms in the above-mentioned phenyl or heteroaryl radical may be independently of each other replaced by a radical R1 and / or

In denotes the six-decatizing aryl group mono - or articulated bicyclic rings, five-decatizing heteroaryl group with mono - or articulated bicyclic rings, nine-chetyrnadtsatiletnyuyu cycloalkylcarbonyl group with articulated bicyclic rings, eight-chetyrnadtsatiletnyuyu cycloalkylcarbonyl group with articulated bicyclic rings, nine-chetyrnadtsatiletnyuyu cyclohexanoltramadol group with articulated bicyclic rings or eight-chetyrnadtsatiletnyuyu cyclohexanoltramadol group with articulated bicyclic rings, each of which may be independently of one another once or several times substituted by R5,

cycloalkyl and cyclogeranyl groups can be saturated or partially unsaturated,

cyclohexanemethylamine group as heteroatoms may contain 1 or 2 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom,

heteroaryl and cycloalkylcarbonyl group with whom to hold 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or sulfur or 1 oxygen atom and 1 sulfur atom,

cyclohexanoltramadol group as heteroatoms may contain 1, 2, 3 or 4 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1, 2 or 3 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom, and(or)

X denotes the group-N(R6)-, -O - or-S(O)n-while R6 denotes H or (C1-C5)-alkyl, and n is 1 or 2, and(or)

R2 is absent or represents one or more substituents, which may be independently from each other selected from the group comprising F, and (C1-C6)-alkyl radicals, with the alkyl radicals independently of one another one or more times can be replaced by F, and(or)

L denotes a covalent bond, -C(O)-bridge bond or a methylene bridge the connection, in which one or two hydrogen atoms may be replaced by F,

and the radicals R1, R3, R4 and R5 have the above value.

In one of the preferred embodiments are compounds and their pharmaceutically acceptable salts of formula Ia, in which:

L denotes a covalent bond, and

X denotes the group-O-.

Particularly preferred compounds according to the invention are tetrahydronaphthalene and their pharmaceutically p is ielemia salt of the formula Ib:

,

in which:

In may denote a phenyl group, naftalina group, pyridinyl group, hyalinella group, athinodorou group, indolenine group, benzothiophene group, benzodithiophene group, benzofuranyl group, benzodithiophene group, salesdipyridamole group, benzopyranyl group, benzoimidazolyl group, benzimidazolyl group, benzothiazolyl group, benzothiazolyl group, pentoxifylline group, indolinyl group, benzodioxolyl group, tetrahydroisoquinoline group, tetrahydropyranyloxy group in which one, two, three or four of the hydrogen atom in the group may be substituted by radicals from the group R5,

each radical R5 independently from each other selected from the group including:

(C1-C4)-alkyl, which may be fully or partially fluorinated, or in which hydrogen may be replaced by CN, NH2HE, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-alkoxy,

(C1-C4)-alkoxy, which may be partially or fully fluorinated,

(C1-C4)-alkylthio, which may be partially or fully fluorinated,

(C2-C5-cyclogeranyl and

(C2-C5-cyclohe aralkyl-(C 1-C4)-alkyl, which

cycloheptatriene ring may be a monocyclic, bicyclic, saturated or partially unsaturated ring, and may contain 1 or 2 nitrogen atom and 1 oxygen atom, 1 nitrogen atom and 1 sulfur atom or 1 nitrogen atom and 1 oxygen atom

cycloheptatriene ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-alkoxy, -CN, (C1-C4)-alkyl, (C3-C10-cycloalkyl, phenyl, naphthyl, (C1-C6-heteroaryl,

heteroaryl ring may be monocyclic or articulated bicyclic ring which may contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or sulfur, and

heteroaryl ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -OH, -NH2, NH(C1-C4)-alkyl, N((Cr C4)-alkyl)2, (C1-C4)-alkoxy, -CN, (C1-C4)-alkyl, (C3-C10-cycloalkyl, -C(O)O-(C1-C4)-alkyl, N, HE (=O), F, Cl, Br, CN, NO2, -NR17R18, -NR16COR17, -NR16COOR17, -NR16CONR17R18, -NR16-S(O)2-R17, -NR16-S(O)2-NR17R18, -COOR16, -COR16, -CO(NR17R18), -S(O)nR16, where n=1 or 2, -S(O)2NR17R18,

R16, R17 and R18 independently of one another may denote hydrogen radical sludge is radical, selected from the group comprising unsubstituted or substituted (C1-C4)-alkyl radicals,

when the substituents alkyl radicals selected from F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, -CN or (C1-C10)-alkoxy,

R17 and R18 together with the nitrogen to which they are bound, may form a five or six-membered saturated, unsaturated or partially unsaturated heterocyclic compound containing 1-5 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N-, -NH - and-N((C1-C4)-alkyl), while the formed heterocyclic compound independently of one another one or more times may be substituted (C1-C10)-alkyl, (C3-C14-cycloalkyl, (C4-C20-cycloalkylation, (C2-C20-cyclogeraniol, (C3-C19-cyclohexanoltramadol, each of which can in turn independently from each other to contain one or more radicals F, HE (=O) or (C1-C10)-alkoxy,

R1 is absent or represents one, two or three radicals, which are independently from each other selected from the group comprising F, Cl, Br, I, (C1-C6)-alkyl, (C1-C6)-alkoxy, with the alkyl and alkoxy radicals can be Emesene one or several times, and(or)

L represents a bond or-CH2-and(or)

R3 and R4 independently of one another denote a radical selected from the group comprising H, (C1-C4)-alkyl, (C3-C7-cycloalkyl-, (C3-C6-cyclogeranyl, phenyl, phenyl-(C1-C4)-alkyl, (C1-C5-heteroaryl, and the radicals R3 and R4 may be independently of one another once, twice or three times substituted radical from the group comprising HE, (=O), F, Cl, Br, CN, NO2, -NR13R14, -NR13COR12, -NR13COOR12, -NR12CONR13R14, -NR13-S(O)2-R12, -NR13-S(O)2-NR13R14, -COOR12, -COR12, -CO(NR13R14), S(O)nR12, -S(O)2NR13R14, in which R12, R13 and R14 represent H or (C1-C4)-alkyl, or

R3 and R4 together with the nitrogen to which they are attached, form a four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-, while the heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group of R7 and R9,

heterocyclic radicals can be connected in bridge connection, (C1-C7)-alkyl, saturated or unsaturated (C1-C6)-heteroalkyl chains or-NH-, N((C1-C4)-alkyl)-, and alkyl or heteroalkyl chain also may represent the system spiritlessly rings, which is formed by R3 and R4, and

R8 ring that can form radicals R3 and R4 may form a more saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or two heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N-, -NH - and-N((C1-C4)-alkyl),

a R7, R8 and R9 have the above value.

In one of the preferred embodiments are compounds and their pharmaceutically acceptable salts of formula Ib, in which L denotes a covalent bond.

One additional group of preferred compounds are compounds and their pharmaceutically acceptable salts of formula Ic:

,

in which:

In denotes the six-decatizing aryl group mono - or articulated bicyclic rings, five-decatizing heteroaryl group with mono - or articulated bicyclic rings, nine-chetyrnadcatiletnie cycloalkylcarbonyl group with articulated bicyclic rings, eight-chetyrnadcatiletnie cycloalkylcarbonyl group with articulated bicyclic rings, nine-chetyrnadtsatiletnyuyu cyclohexanoltramadol group with articulated bicyclic rings or eight-chetyrnadtsatiletnyuyu cyclohexanoltramadol group with cleanname bicyclic rings, each of which may be independently of one another once or several times substituted by R5,

this cycloalkyl and cyclogeranyl groups can be saturated or partially unsaturated

cyclohexanemethylamine group as heteroatoms may contain 1 or 2 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom,

heteroaryl and cycloalkylcarbonyl groups can contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom, and

cyclohexanoltramadol group as heteroatoms may contain 1, 2, 3 or 4 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1, 2 or 3 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom and(or)

X denotes the group-N(R6)-, -O - or-S(O)n-, in which R6 denotes H or (C1-C5)-alkyl, and n is 1 or 2, and(or)

R2 is absent or represents one or more substituents, which independently of one another may be selected from the group comprising F, and (C1-C6)-alkyl radicals which, independently of one another one or more times can be replaced by F, and(or)

L denotes a covalent bond, -(C(O)-Nosticova the bond or methylene bridge connection, which, independently of one another one or more times can be replaced by F,

q is 0 or 1,

and the radicals A, R1, R3, R4 and R5 have the above value.

Particularly preferred compounds and their pharmaceutically acceptable salts of formula Ic, in which:

And denotes phenyl or a five or six-membered heteroaryl radical, which as heteroatoms may contain 1, 2 or 3 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or 1 sulfur atom, one or more hydrogen atoms in the phenyl or heteroaryl radical is independently from each other may be substituted by a radical R1 and / or

In denotes the six-decatizing aryl group mono - or articulated bicyclic rings, five-decatizing heteroaryl group with mono - or articulated bicyclic rings, nine-chetyrnadcatiletnie cycloalkylcarbonyl group with articulated bicyclic rings, eight-chetyrnadtsatiletnyuyu cycloalkylcarbonyl group with articulated bicyclic rings, nine-chetyrnadtsatiletnyuyu cyclohexanoltramadol group with articulated bicyclic rings or eight-chetyrnadtsatiletnyuyu cyclohexanoltramadol group with articulated bicyclic rings, each of which independently of one another one or more times may bytesmessage on R5,

this cycloalkyl and cyclogeranyl groups can be saturated or partially unsaturated,

cyclohexanemethylamine group as heteroatoms may contain 1 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom,

heteroaryl and cycloalkylcarbonyl groups can contain 1, 2 or 3 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 nitrogen atom and 1 oxygen atom or sulfur or 1 oxygen atom and one sulfur atom,

cyclohexanoltramadol group as heteroatoms may contain 1, 2, 3 or 4 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom, and(or)

X denotes the group-N(R6)-, -O - or-S(O)n-, in which R6 denotes H or (C1-C5)-alkyl, and n is 1 or 2, and(or)

R2 is absent or represents one or more substituents, which independently of one another may be selected from the group comprising F, and (C1-C6)-alkyl radicals which, independently of one another one or more times can be replaced by F, and(or)

L denotes a covalent bond, -C(O)-bridge bond or a methylene bridge connection, which once or twice may be replaced by F,

q is 0 or 1,

as mentioned radicals R1, R3, R4 and R5 have the above value.

In one of the preferred embodiments are compounds and their pharmaceutically acceptable salts of the formula Id, in which:

L denotes a covalent bond,

X denotes the group-O-and

q is 0.

Particularly preferred are aminoindane and their pharmaceutically acceptable salts of formula Id:

,

in which:

In may denote a phenyl group, naftalina group, pyridinyl group, hyalinella group, athinodorou group, indolenine group, benzothiophene group, benzodithiophene group, benzofuranyl group, benzodithiophene group, salesdipyridamole group, benzopyranyl group, benzoimidazolyl group, benzimidazolyl group, benzothiazolyl group, benzothiazolyl group, pentoxifylline group, indolinyl group, benzodioxolyl group, tetrahydroisoquinoline group, tetrahydropyranyloxy group in which one, two, three or four of the hydrogen atom in the group may be substituted by radicals from the group R5,

each radical R5 independently from each other selected from the group including:

(C1-C4)-alkyl, which may be partially or fully fluorinated and which one is that hydrogen may be replaced by CN, NH2HE, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-alkoxy,

(C1-C4)-alkoxy, which may be partially or fully fluorinated,

(C1-C4)-alkylthio, which may be partially or fully fluorinated,

(C2-C5-cyclogeranyl and

(C2-C5-cyclogeranyl-(C1-C4)-alkyl, which

cycloheptatriene ring may be saturated or partially unsaturated and may contain 1 or 2 nitrogen atom and 1 oxygen atom, 1 nitrogen atom and 1 sulfur atom or 1 nitrogen atom and 1 oxygen atom, and

cycloheptatriene ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -NH2, -CN, (C1-C4)-alkyl, (C3-C10-cycloalkyl, HE, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C10)-alkoxy,

phenyl, naphthyl,

(C1-C6-heteroaryl, which

heteroaryl ring may be monocyclic or articulated bicyclic ring which may contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or sulfur, and

heteroaryl ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -NH2, -CN, (C1-C4)-alkyl,(C 3-C10-cycloalkyl, HE, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C10)-alkoxy, -C(O)O-(C1-C4)-alkyl,

H, HE (=O), F, Cl, Br, CN, NO2, -NR17R18, -NR16COR17, -NR16COOR17, -NR16CONR17R18, -NR16-S(O)2-R17, -NR16-S(O)2-NR17R18, -COOR16, -COR16, CO(NR17R18), S(O)nR16, where n=1 or 2, -S(O)2NR17R18,

R16, R17 and R18 independently of one another may denote a hydrogen radical or a radical selected from the group comprising unsubstituted or substituted (C1-C4)-alkyl radicals in which the substituents are alkyl radicals selected from F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy,

R17 and R18 together with the nitrogen to which they are bound, may form a five or six-membered saturated, unsaturated or partially unsaturated heterocyclic compound containing 1-5 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N-, -NH - and-N((C1-C4)-alkyl)-, while the formed heterocyclic compound independently of one another one or more times substituted (C1-C10)-alkyl, (C3-C14-cycloalkyl, (C4-C20-cycloalkylation, (C2-C20-cyclogeraniol, (C3-C19-cyclohexanoltramadol, kardys which can in turn independently from each other to contain one or more radicals F, HE (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy,

R1 is absent or represents one, two or three radicals, which are independently from each other selected from the group comprising F, Cl, Br, I, (C1-C6)-alkyl, (C1-C6)-alkoxy, where alkyl and alkoxyalkyl substituted one or more times can be F, and(or)

R3 and R4 independently of one another denote a radical selected from the group comprising H, (C1-C4)-alkyl, (C3-C7-cycloalkyl-, (C3-C7-cycloalkyl-(C1-C4)-alkyl, (C3-C6-cyclogeranyl-, phenyl-, phenyl-(C1-C4)-alkyl, (C1-C5-heteroaryl,

R3 and R4 independently of one another once, twice or three times may be substituted by a radical from the group comprising HE, (=O), F, Cl, Br, CN, NO2, -NR13R14, -NR13COR12, -NR13COOR12, -NR12CONR13R14, -NR13-S(O)2-R12, -NR13-S(O)2-NR13R14, -COOR12, -COR12, -CO(NR13R14), -S(O)nR12, -S(O)2NR13R14, in which R12, R13 and R14 represent H or (C1-C4)-alkyl,

R3 and R4 together with the nitrogen to which they are attached, form a four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-,

heterocyclic shall adically independently of one another one or more times can be substituted radical, selected from the group comprising the radicals R7 and R9,

heterocyclic radicals can be connected in bridge connection, (C1-C7)-alkyl, saturated or unsaturated (C1-C6)-heteroalkyl chains or-NH-, N((C1-C4)-alkyl)-, and alkyl or heteroalkyl chain can also be a system of spirocycles ring formed by R3 and R4, and

R8 group NR8 may form with the ring formed by R3 and R4, additional saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or two heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N - and-NR19-, where R1 denotes H or (C1-C4)-alkyl,

and R7, R8 and R9 have the above value.

In another embodiment, particularly preferred are the compounds of formula I, Ia, Ib, Ic and Id, in which:

R3 and R4 together with the nitrogen to which they are attached, form a four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-,

where heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group on the waiting radicals R7 and R9,

R8 ring formed by R3 and R4, together with the neighboring atom, may form an articulated triazole or pyrolidine ring

and R7, R8 and R9 have the above value.

In another embodiment, preferred are compounds of formula I, Ia, Ib, Ic and Id, in which:

R3 and R4 independently from each other represent a hydrogen radical or a radical selected from the group comprising (C1-C10)-alkyl radicals, (C2-C10)-alkeline radicals, (C2-C10)-alkyline radicals, (C3-C14)-cycloalkyl radicals, (C4-C20)-cycloalkenyl radicals, (C2-C19)-cyclogeranyl radicals, (C3-C19)-cyclohexanediamine radicals, (C6-C10)-aryl radicals, (C7-C20)-arylalkyl radicals, (C1-C9)-heteroaryl radicals, (C2-C19)-heteroarylboronic radicals

while the radicals R3 and R4 independently of one another one or more times may be substituted by a radical from the group comprising AN NH2, (=O), F, Cl, Br, I, CN, NO2, -NR13R14, -NR13COR12, -NR13COOR12, -NR12CONR13R14, -NR13-S(O)2-R12, -NR13-S(O)2-NR13R14, -COOR12, -COR12, -CO(NR13R14), S(O)nR12, -S(O)2R13R14,

a R12, R13 and R14 have the above value.

In another embodiment, particularly preferred are compounds form the s I, Ia, Ib, Ic and Id, in which:

R3 and R4 independently of one another denote a radical selected from the group comprising H, (C1-C5)-alkyl-, phenyl-(C1-C4)-alkyl, NH2-(C1-C4)-alkyl, N((C1-C4)-alkyl)2-(C1-C4)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, (C3-C7-cycloalkyl-(C1-C4)-alkyl -, and (C4-C6-cyclogeranyl, which contains a-NH-, -O - and-S - group.

The presence of rings in the context of the present invention denotes the number of atoms of the ring, forming an appropriate system of rings or articulated rings.

Six-desyatiletnimi aryl radicals, which may indicate cyclic radicals a and b are, in particular, phenyl and naphthyl.

Preferred five-desyatiletnie heteroaryl radical, which may denote a cyclic radical And selected from the group including furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazoles, hinely, ethanolic, phthalazine, honokalani, hintline and cinnoline. Particularly preferred heteroaryl radical And is thiophenyl.

In one of the embodiments of the invention And refers to phenyl or five - or six-membered g is thereally radical, in another embodiment, And denotes phenyl or thiophenyl, in another embodiment, And denotes phenyl, and in yet another embodiment, And indicates thiophenyl, all of which can be substituted as indicated above.

Five-deletechannel heteroaryl radical, which may denote a cyclic radical, selected from the group including furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, hinely, ethanolic, phthalazine, honokalani, hintline, cinnoline, benzothiophene, isobenzofuranyl, benzofuranyl, isobenzofuranyl, benzoimidazolyl, benzimidazolyl, benzotriazolyl, benzoxazolyl, samesexual, benzothiazolyl, isobenzofuranyl.

The preferred three-desyatiletnie cycloalkyl radicals, which may denote a cyclic radical, selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctyl, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctene and norbornene.

Preferred nine-chetyrnadcatiletnie cycloalkenyl radicals, which may denote a cyclic radical, selected from the group including systemisation rings, having cycloalkyl ring and an aryl ring. Particularly preferred cycloalkenyl radicals are indenyl, dihydronaphtho, tetrahydronaphthyl and indanyl.

Preferred eight-chetyrnadcatiletnie cycloalkylcarbonyl radicals, which may denote a cyclic radical, selected from the group including a system of coupled rings with cycloalkene ring and heteroaryl ring.

The preferred three-desyatiletnie cyclogeranyl radicals, which may denote a cyclic radical, selected from the group including oxiranyl, thiiranes, aziridinyl, oxetanyl, titanyl, azetidine, pyrrolidine, dihydropyrrole, dihydroimidazole, dihydropyrazolo, tetrahydropyrazolo, oxolane, dihydrofurane, DIOXOLANYL, tylenol, dihydrothiophene, oxazolyl, dihydrooxazolo, isoxazolyl, dihydroisoxazole, diazolidinyl, dihydrothiazolo, isothiazolinones, dihydroisoxazole, oxathiolane, 2H-pyranyl, 4H-pyranyl, tetrahydropyranyl, 2H-teerasil, 4H-teerasil, di-, tetrahydrothiopyran, piperidinyl, di-, tetrahydropyranyl, piperazinil tetrahydropyranyl, di-, Tetra-, hexahydropyridine, di-, Tetra-, hexahydropyridine, morpholinyl, thiomorpholine, dioxane, dithienyl, azepane, tiapamil and examiner, with two of these heterocyclic number is C can also form a system saturated or partially unsaturated articulated bicyclic rings. Examples of such systems bicyclic rings are octahedral[1,2-a]pyrazinyl, octahedral[3,4-b]pyrrolyl, hexahydrofuro[3,4-C]pyrrolyl and octahedral[3,4-C]pyrrolyl.

Preferred nine-chetyrnadcatiletnie cyclohexanemethylamine radicals, which may denote a cyclic radical, selected from the group including a system of coupled rings with cycloheptatriene ring and an aryl ring. Particularly preferred cyclohexanemethylamine radicals are benzodithiophene, benzodithiophene, benzodioxolyl, benzodithiol, benzodithiol, benzodithiol, benzofurazanyl, benzodithiol, benzomorphans, benzodiapines, benzodithiol, dihydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, tetrahydroquinoline, benzoxadiazole, isobenzofuranyl and benzodioxolyl.

Preferred eight-chetyrnadcatiletnie cyclohexanoltramadol radicals, which may denote a cyclic radical, selected from the group including a system of coupled rings with cycloheptatriene ring and heteroaryl ring.

Particularly preferred mono - or bicyclic radicals, which may denote a cyclic radical, selected from the group comprising phenyl, naphthyl, Piri is Il, chinoline, ethenolysis, indolyl, benzodiapines, benzodithiophene, benzothiophene, benzodithiophene, benzofuranyl, benzothiophenes, benzodithiophene, benzoimidazolyl, benzimidazolyl, benzotriazolyl, thiazolyl, benzothiazolyl, benzoxadiazole, benzodioxolyl, tetrahydroisoquinoline or tetrahydroquinolines. Accordingly, the radicals may be associated with a group-LX-such as pyrid-2,3 or 4-yl, China-1,2,3,4,5,6,7 or 8-yl, ethanol-1,2,3,4,5,6,7 or 8-yl, indol-1,2,3,4,5,6 or 7-yl, isoindole-1,2,3,4,5,6 or 7-yl, benzo[b]thiophene-2,3,4,5,6 or 7-yl, benzo[C]thiophene-1,3,4,5,6 or 7-yl, benzo[b]dihydrothiophene-2,3,4,5,6 or 7-yl, benzo[C]dihydrothiophene-1,3,4,5,6 or 7-yl, benzo[b]furan-2,3,4,5,6 or 7-yl, benzo[C]furan-1,3,4,5,6 or 7-yl, benzo[b]dihydrofuran-2,3,4,5,6 or 7-yl, benzo[C]dihydrofuran-1,3,4,5,6 or 7-yl, benzo[b]pyrrolidin-1,2,3,4,5,6 or 7-yl, benzo[C]pyrrolidin-1,2,3,4,5,6 or 7-yl, benzoimidazol-1,2,3,4,5,6 or 7-yl, benzimidazol-1,2,3,4,5,6 or 7-yl, benzotriazol-1,2,4,5,6 or 7-yl, tiaso-2,4 or 5-yl, benzothiazol-2,3,4,5,6 or 7-yl, benzoxadiazole-2,4,5,6-or 7-yl, benzodioxan-2,4,5,6-or 7-yl, tetrahydrothieno-1,2,3,4,5,6,7 or 8-yl, or tetrahedronal-1,2,3,4,5,6,7 or 8-Il.

One, two, three or four of the hydrogen atom in the group preferably may be replaced by radicals, which are independently from each other selected from the group R5. In one of the embodiments of the invention one, two or the ri of a hydrogen atom, in another embodiment, one or two hydrogen atoms may be replaced by radicals, which are independently from each other selected from the group R5.

Particularly preferred are In the following groups:

in which the substituents R5 systems bicyclic rings may be in both rings. In one of the embodiments of the invention are selected from the group comprising phenyl, naphthyl, pyridyl, chinoline or ethenolysis, in another embodiment from the group comprising phenyl and pyridyl, in another embodiment, In denotes phenyl, and in yet another embodiment, In denotes pyridyl, all of which can be substituted as indicated above.

L preferably denotes a single covalent bond, -C(O)-bridge bond or a methylene bridge connection.

In one of the embodiments of the invention L denotes a covalent single bond, in another embodiment, the wasp is estline denotes-C(O)-bridge link, and in yet another embodiment, - methylene bridge connection.

X preferably represents a group-N(R6)-, -O - or-S(O)n-.

In one of the embodiments of the invention X represents a group-N(R6)-, in another embodiment, the group-O-, in another embodiment, a group S(O)n-.

In one of the embodiments of the invention one, two or three hydrogen atoms, in another embodiment, one or two hydrogen atoms in the aryl or heteroaryl radicals, indicating And can be substituted for the placeholder groups R1.

Preferred radicals R1 are selected from the group comprising F, Cl, Br, I, (C1-C6)-alkyl, (C1-C6)-alkoxy, where alkyl and alkoxy radicals one or more times can be replaced by F. Particularly preferred R1 radicals are selected from the group comprising F, Cl, methyl, ethyl, propyl, butyl, methoxy, ethoxy, trifluoromethyl, pentafluoroethyl, triptorelin, in particular-CH2-CF3defloratin, in particular-CH2-CHF2monitorate, in particular-CH2-CH2F, methoxy, ethoxy, triptoreline, pentaborate, triptoreline, in particular-O-CF2-CF3diflorasone, in particular-O-CH2-CHF2monitorate, in particular O-CH2-CH2F.

Preferred radicals R2 are selected from the group of the s, including F, (C1-C6)-alkyl in which the alkyl radicals independently of one another one or more times can be replaced by F, and particularly preferred radicals are F, methyl, ethyl, propyl, butyl, trifluoromethyl, triptorelin, for example, -CF2-CF3, -CH2-CHF2, -CH2-CH2F.

Preferred R3 and R4 radicals independently from each other selected from the group including:

hydrogen, (C1-C4)-alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl,

in which the alkyl radical may be substituted by one or two radicals from the group comprising-N(C1-C4-alkyl)2and-O-(C1-C4-alkyl), especially-N(CH3)2, -N(C2CH5)2with education, for example radicals-CH2-N(CH3)2, -CH2-CH2-N(CH3)2, -CH2-CH2-CH2-N(CH3)2, -CH2-Och3or or-CH2-CH2-Och3,

(C3-C7-cycloalkyl, as, for example, cyclopropyl, cyclobutyl, cyclopentenyl, cyclohexenyl or cycloheptenyl,

(C3-C7-cycloalkyl-(C1-C4)-alkyl, such as, for example, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclopentylmethyl, cyclohexylmethyl or cycle is exanimate,

(C3-C6-cyclogeranyl, as, for example, piperidinyl, piperazinil, hexahydropyridine, hexahydropyridine, morpholinyl, thiomorpholine, pyrrolidine, tetrahydrofuranyl or tetrahydrothiophene,

phenyl, phenyl-(C1-C4)-alkyl, such as, for example, phenylmethyl, phenylethyl, phenylpropyl or phenylbutyl,

(C1-C5-heteroaryl, as, for example, furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, pyridyl, pyrazinyl, pyrimidinyl or pyridazinyl.

The radicals R3 and R4 and the nitrogen atom to which they are bound preferably form the following groups:

In particular, the radicals R3 and R4 preferably form a four-to eight ichinoe rich, unsaturated or partially unsaturated heterocyclic compound. Four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound may optionally contain one or more heteroatomic groups selected from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-. -NR8 -, and an adjacent carbon atom may form an articulated triazole or pyrolidine ring, for example, octahedral[1,2-a]pyrazinyl and tetrahydro-[1,2,4]triazolo[4,3-a]pyrazinyl.

Preferred heterocyclic compounds formed by the radicals R3 and R4, are selected from the group including azetidinol, pyrrolidinyl, piperidinyl, piperazinil, morpholinyl, thiomorpholine, Osotimehin, diocletianopolis, azepane, 1,4-diazepan, pyrrolyl, pyrazolyl and imidazolyl. Heterocyclic rings may be linked covalent bond, (C1-C7)-alkalinous bridge connection or (C1-C6)-heterouncinata bridge bond or-NH-bridge bond or-N(C1-C4)-alkalinous bridge connection, resulting in a system dump or bridged bicyclic rings. (C1-C7)-Allenova bridge connection or (C1-C6)-heterouncinata bridge connection can also be a system of spirocycles rings that education is avana radicals R3 and R4. Examples of such system spiritlessly, articulated or bridged rings formed by the radicals R3 and R4 are diazabicyclo[3.2.1]octenyl, especially 3,8-diazabicyclo[3.2.1]octenyl, diazabicyclo[2.2.1]heptenyl, in particular 2,5-diazabicyclo[2.2.1]heptenyl, octahedral[3,4-b]pyrrolyl, hexahydrofuro[3,4-C]pyrrolyl, octahedral[3,4-C]pyrrolyl and diazepinones, particularly 2,7-diazaspiro[4.4]nonanal.

In one of the embodiments of the invention R3 and R4 and the nitrogen atom to which they are linked, form a heterocyclic radical selected from the group comprising azetidinol, pyrrolidinyl, piperidinyl, piperazinil, morpholinyl, thiomorpholine, azepane and 1,4-diazepan, in another embodiment, the heterocyclic radical selected from the group comprising azetidinol, pyrrolidinyl, piperidinyl and morpholinyl, in another embodiment, the heterocyclic radical selected from the group comprising azetidinol, pyrrolidinyl, piperidinyl, in another embodiment, azetidinone radical, in another embodiment, pyrrolidinyloxy radical, in another embodiment implementation piperidinyloxy radical, in another embodiment, morpholinyl radical, all of which can be substituted as indicated above.

Heterocyclic group formed by the radicals R3 and R4 can sod is neigh additional substituents, independently from each other selected from the group of R7 and R9.

Preferred substituents of the group are:

F, Cl, Br, I,

(C1-C4)-alkyl, where the alkyl radicals one or more times can be replaced by F, as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, -CF3, -CH2-CF3, -CH2-CH2-CF3, -CH2-CH2-CH2-CF3, -CH2F, -CH2-CH2F, -CH2-CH2-CH2-CH2F,

(C3-C7-cycloalkyl, as, for example, cyclopropyl, cyclopentyl,

HE, hydroxy-(C1-C4)-alkyl, such as, for example, -CH2-OH, -CH2-CH2-OH, -CH2-CH2-CH2HE

(C1-C4)-alkyl-O-, such as-och3,

(C1-C4)-alkoxy-(C1-C4)-alkyl, such as, for example, -CH2-Och3, -CH2-CH2-Och3, -CH2-CH2-CH2-Och3,

-SO2-(C1-C4)-alkyl, such as, for example, -SO2-CH3,

-NH2N((C1-C4)-alkyl)2-as, for example, -N(CH3)2, -N(C2H5)2,

NH2(C1-C4)-alkyl, N((C1-C4)-alkyl)2-(C1-C4)-alkyl, such as, for example, -CH2-NH2, -CH2-CH2-NH2, -CH2-CH2-CH2-NH2,

-CN, NC-(C1-C4 )-alkyl-, such as-CH2-CN, -CH2-CH2-CN, -CH2-CH2-CH2-CN

-NH-(C1-C4)-alkyl, in which alkyl group one or more times can be replaced by F, such as-NH-CH2-F, -NH-CH2-CH2-F, -NH-CH2-CF3,

-NH-CH2-CH2-CF3, -NH-(C1-C4)-alkyl-HE,

-NH-(C1-C4)-alkyl-O-(C1-C4)-alkyl, such as-NH-CH2-OH, -NH-CH2-CH2HE

-NH-(C1-C4)-alkyl-CN, as, for example, -NH-CH2-CN, -NH-CH2-CH2-CN, -NH-(C1-C4)-alkyl-O-(C1-C4)-alkyl-HE, as, for example, -NH-CH2-CH2-O-CH2-CH2-OH,

-NH-C(O)-(C1-C4)-alkyl, in which alkyl group one or more times can be replaced by F, as, for example, -NH-C(O)-CH3, -NH-C(O)-CF3,

pyrrolidinyl, pyrrolidinyl-(C1-C4)-alkyl, such as N-pyrrolidinyl-CH2-pyrimidinyl, as, for example, the pyrimidine-2-yl.

In one variant of the invention, the heterocyclic group formed by the radicals R3 and R4 and the nitrogen atom to which they relate, can contain the substituents R7 and R9 are independently from each other selected from the group comprising methyl, ethyl, CF3, F, Cl, CN, NH2N(CH3)2HE co3, SO2CH3in another embodiment, - zamestitel R9, are independently from each other selected from the group comprising F, Cl, CN, NH2N(CH3)2HE co3, SO2CH3. In one variant of the invention, the heterocyclic group formed by the radicals R3 and R4 and the nitrogen atom with which they are associated, may contain one, two or three substituent R7 and R9, in another embodiment, one or two Deputy, in another embodiment, one Deputy.

The radicals R3 and R4 radicals together with the nitrogen to which they relate, particularly preferably comprise one of the following heterocyclic rings systems:

Preferred radicals R5 independently from each other selected from the group including:

F, Cl, Br, I, =0, -CN, -OH, -NH2, -NO2,

(C1-C4)-alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, in which alkylene the radical one or more times can be replaced by F, as, for example,- CF3, -CF2H,

(C1-C4)-alkoxy, such as-och3, -OC2H5in which the alkyl radicals one or more times can be replaced by F, as, for example, -OCF3, -OCHF2, -OCH2F,

-S-(C1-C4)-alkyl, such as-SCH3in which the alkyl radicals one or more times can be replaced by F, as, for example, SCF3,

(C1-C4)-alkoxy-(C1-C4)-alkyl, such as, for example, -CH2-Och3, -CH2-CH2-Och3

NC-(C1-C4)-alkyl-, such as-CH2-CN

NH2-(C1-C4)-alkyl-, such as-CH2-NH2,

N((C1-C4)-alkyl)2-(C1-C4)-alkyl-, such as-CH2-N(CH3)2,

(C1-C4)-alkyl-C(O)-NH-(C1-C4)-alkyl-, such as-CH2-NH-C(O)CH3,

N((C1-C4)-alkyl)2-C(O)-(C1-C4)-alkyl-, such as-CH2-C(O)-N(CH3)2,

-SO2-(C1-C4)-alkyl, such as, for example, -SO2CH3in which alkyl group one or more times can be replaced by F, as, for example,- SO2CF3,

-SO2NH2, -SO2N((C1-C4)-alkyl)2as, for example, -SO2N(CH3)2, -SO2N(C2H5 2,

-SO2-NH-(C1-C4)-alkyl, such as, for example, -SO2-NH-CH3, -SO2-NH-CH2-CH3, -SO2-NH-CH2-CH2-CH3in which the alkyl radicals one or more times can be replaced by F, as, for example,- SO2-NH-CH2-CF3, -SO2-NH-CH2-CH2-CF3,

-NH-C(O)-(C1-C4)-alkyl, such as-NH-C(O)-CH3,

-NH-C(O)-NH2, -NH-C(O)-N((C1-C4)-alkyl)2as, for example, -NH-C(O)-N(CH3)2,

-NH-C(O)-O-(C1-C4-alkylphenyl, as, for example, -NH-C(O)-O-CH2-C6H6,

-NH-C(O)-O-(C1-C4)-alkyl-COOH, as, for example, -NH-C(O)-O-CH2-COOH,

-NH-C(O)-O-(C1-C4)-alkyl-COO(C1-C4)-alkyl, such as-NH-C(O)-O-CH2SOON3,

-NH-SO2-(C1-C4)-alkyl, such as-NH-SO2CH3,

-N((C1-C4)-alkyl)-SO2-(C1-C4)-alkyl, such as-N(CH3)-SO2CH3,

-C(O)-(C1-C4)-alkyl), such as, for example, -C(O)-CH3-C(O)-CH2-CH3,

-C(O)-NH2-C(O)-N((C1-C4)-alkyl)2as, for example, -C(O)-N(CH3)2-C(O)-N(C2H5)2,

-C(O)-O(C1-C4)-alkyl, such as-C(O)-och3,

-C(O)phenyl,

-O-phenyl,

-COOH, -COO(C1-C4)-alkyl, such as-sub> 3-OS2H5,

(C1-C4)-alkyl-(C3-C7-cyclogeranyl-C(O)-, such as, for example, (C1-C4)-alkyl-piperazinil or pyrimidinyl or piperidinyl or tetrahydropyridine-C(O)-, in particular, 4-methylpiperazin-1-yl-C(O)-,

(C3-C7-cyclogeranyl-C1-C4)-alkyl, such as, for example, piperidinyl or piperazinil or pyrimidinyl or tetrahydropyridine-(C1-C4)-alkyl-, in particular piperidine-1-yl-methyl.

Preferred aryl radical R5 is phenyl.

More preferred radicals R5 is heteroaryl radicals, in particular selected from the group comprising pyrrole-1,2, or 3-yl, pyrazole-1,3,4 or 5-yl, imidazol-1,2,4 or 5-yl, 1,2,3-triazole-1,2,4 or 5-yl, 1,2,4-triazole, 3-or 4-yl, tetrazol-1,2 or 5-yl, 1,3,4-oxadiazol-3 or 4-yl, 1,2-isoxazol-2,3,4, or 5-yl, oxazol-2,3,4, or 5-yl, thiazol-2,3,4 or 5-yl, isothiazol-2,3,4, or 5-yl, thiadiazole-2,3,4, or 5-yl of pyrid-2,3 or 4-yl, benzo[b]furan-2,3,4,5,6 or 7-yl, benzo[b]thiophene-2,3,4,5,6 or 7-yl, indol-1,2,3,4,5,6 or 7-yl, isoindole-1,2,3,4,5,6 or 7-yl, benzothiazol-2,4,5,6-or 7-yl, benzothiazol-3,4,5,6 or 7-yl, benzoxazol-2,4,5,6-or 7-yl, benzisoxazol-3,4,5,6 or 7-yl, benzodithiol-1,2,4,5,6 or 7-yl, and benzothiadiazole-1,2,3,4,5,6 or 7-Il.

Preferred cyclogeranyl radicals R5 are selected from the group including piperidine-1,2,3 or 4-yl,piperazine-1, 2 or 3-yl, pyrimidine-1,2,4 or 5-yl, tetrahydropyrimidin-1,3 or 4-yl, 2H-pyridine-1,2,3,4,5 or 6-yl, 4H-pyridine-1,2,3 or 4-yl, morpholine-2,3 or 4-yl, thiomorpholine-2,3 or 4-yl, pyrrolidin-1,2 or 3-yl, dihydropyridin-1,2 or 3-yl, imidazolidin-1,2 or 4-yl, dihydroimidazole-1,2 or 4-yl, thiazolidin-2,3,4, or 5-yl, isothiazolin-2,3,4, or 5-yl, and oxazolin-2,3,4, or 5-yl.

Preferred cyclohexanemethylamine radicals R5 are selected from the group consisting of benzo[b]dihydrofuran-2,3,4,5,6 or 7-yl, benzo[C]dihydrofuran-1,3,4,5,6 or 7-yl, benzo[b]dihydrofuran-2,3,4,5,6 or 7-yl, benzo[C]dihydrothiophene-1,3,4,5,6 or 7-yl, benzo[b]dihydrothiophene-1,2,3,4,5,6 or 7-yl, benzo[C]dihydropyrrol-1,2,3,4,5,6 or 7-yl, benzodioxan-2,4,5,6-or 7-yl, and benzoxadiazole-2,4,5,6-or 7-yl, tetrahedronal-2,3,4,5,6,7 or 8-yl, and ethanol-1,3,4,5,6,7 or 8-Il.

Preferred aryl, heteroaryl, cycloheptadiene, cycloheptatriene and cyclohexanoltramadol radicals can contain one or more, preferably one, two, three or four additional substituent which is independently from each other selected from the group comprising the radicals R11. Particularly preferred R11 radicals chosen from the group comprising F, Cl, Br, I, -CN, NH2HE, =O,

(C1-C4)-alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and

(C1-C4)-alkyloxy-as, for example, -och3 , -OS2H5in which alkyl and alkoxy radicals one or more times can be replaced by F,

-SO2CH3, -SO2NH2, -NH-C(O)-CH3, -C(O)-NH2and-NH-C(O)-NH2-SOON3-OS2H5.

Particularly preferred aryl, heteroaryl, cyclogeranyl, cyclohexanemethylamine and cyclohexanoltramadol radicals R5 are:

In one of the embodiments of the invention, the radicals R5 independently of one another may be selected from the group comprising F, Cl, Br, CN, methyl, ethyl, propyl, tert-butyl, NH2, OCH3, SO2CH3, SO2NH2C(O)NH2, -NH-C(O)-CH3the pyrazole-1,2 or 3-yl, imidazol-1, 2 or 3-yl, 1,2,3-triazole-1 or 2-yl, 1,2,4-triazole-1,3 or 4-yl, tetrazol-1,2 or 5-yl, thiazole-2,3 or 4-yl, 1,3,4-oxadiazol - 3 or 4-yl, oxazol-2 or 3-yl, isoxazol-2 or 3-yl, triazole-1 or 2-yl, piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, oxazolidin-3-yl, isoxazolidine-2-yl, tetrahydroimidazo-1-yl, dihydroimidazole-1-yl, isothiazol-1-yl and morpholine-4-yl, with the cyclic radicals R5 may contain additional cover is eating R11. In another embodiment, one of the radicals R5 are selected from the group comprising F, Cl, CN, methyl, ethyl, tert-butyl, co3, SO2CH3, SO2NH2C(O)NH2and-NH-C(O)-CH3. In another embodiment, one of the radicals R5 are selected from the group including pyrazole-1,2 or 3-yl, imidazol-1-yl, 1,2,3-triazole-1 or 2-yl, 1,2,4-triazole-1,3 or 4-yl, thiazol-2-or 4-yl, oxazol-2 or 3-yl, isoxazol-2 or 3-yl, triazole-1 or 2-yl, tetrazol-1-yl, all of which can contain additional substituents from the group comprising methyl, ethyl cyclopropyl, methoxy, CN, HE, NH2N(CH3)2or choose from a group comprising piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, oxazolidin-3-yl, isoxazolidine-2-yl, tetrahydroimidazo-1-yl, all of which can contain additional substituents R11 from the group comprising methyl, ethyl, cyclopropyl, methoxy, CN, (=0), HE, NH2and N(CH3)2.

In one of the embodiments of the invention one of the radicals R5 are selected from the group comprising F, Cl, Br, CN, methyl, ethyl, propyl, tert-butyl, NH2The co3, SO2CH3, SO2NH2C(O)NH2, -NH-C(O)-CH3and one of the radicals R5 are selected from the group including pyrazole-1,2 or 3-yl, imidazol-1, 2 or 3-yl, 1,2,3-triazole-1 or 2-yl, 1,2,4-triazole-1,3 or 4-yl, thiazole-2,3 or 4-yl, 1,3,4-oxadiazol-3 or 4-yl, oxazol-2 or 3-yl, from Sasol-2 or 3-yl, triazole-1 or 2-yl, tetrazol-1-yl, all of which may contain substituents R11 is selected from the group comprising methyl, ethyl, cyclopropyl, methoxy, CN, HE, NH2N(CH3)2or choose from a group comprising piperidine-1-yl, piperazine-1-yl, pyrrolidin-1-yl, oxazolidin-3-yl, isoxazolidine-2-yl, tetrahydroimidazo-1-yl, dihydroimidazole-1-yl, isothiazol-1-yl and morpholine-4-yl, all of which may contain substituents R11 is selected from the group comprising methyl, ethyl, cyclopropyl, methoxy, CN, (=0), HE, NH2and N(CH3)2.

In one of the embodiments of the invention, the substituents R11 is chosen from the group comprising methyl, ethyl, cyclopropyl, methoxy, CN, (=0), HE, NH2N(CH3)2, SO2Me and CO2Me.

(C1-C10)-alkyl radicals in the context of the present invention may be compounds with a non-branched chain or branched chain. This also applies to the case when they contain substituents or are substituents of other radicals, for example, in the alkyl fluoride radicals or alkoxy radicals. Examples of alkyl radicals are methyl, ethyl, n-propyl, isopropyl (= 1-methylethyl), n-butyl, isobutyl (= 2-methylpropyl), sec-butyl (= 1-methylpropyl), tert-butyl (= 1,1-dimethylethyl), n-pentyl, isopentyl, tert-pentyl, neopentyl and hexyl. Preferred alkyl radicals I have are methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl.

(C2-C10)-alkeline radicals in the context of the present invention may also be compounds with a non-branched chain or branched chain. This also applies to the case when they contain substituents or are substituents of other radicals. Examples alkenyl radicals are ethynyl, propenyl and butenyl.

(C2-C10)-alkyline radicals in the context of the present invention may also be compounds with a non-branched chain or branched chain. This also applies to the case when they contain substituents or are substituents of other radicals. Examples etkinlik radicals are ethinyl, PROPYNYL and butynyl.

(C3-C14)-cycloalkyl radicals in the context of the present invention may be saturated or partially unsaturated compounds. This also applies to the case when they contain substituents or are substituents of other radicals. Preferred are cycloalkyl radicals containing 3, 4, 5, 6, 7 or 8 carbon atoms. Examples cycloalkyl radicals are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

(C2-C19)-cyclogeranyl radicals in the context of the present invention can avlat the Xia saturated or partially unsaturated compounds. This also applies to the case when they contain substituents or are substituents of other radicals. Cyclogeranyl radicals preferably contain heteroatoms selected from the group comprising nitrogen, oxygen and sulfur. Preferred are cyclogeranyl radicals containing 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms as the heteroatoms may contain 1 or 2 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom. Cyclogeranyl radicals may be attached in any position. Examples of such heterocyclic compounds are selected from the group including oxiranyl, thiiranes, aziridinyl, oxetanyl, titanyl, azetidine, diazetidine, pyrrolidinyl, dihydropyrrole, dihydroimidazole, dihydropyrazolo, tetrahydropyrazolo, oxolane, dihydrofurane, DIOXOLANYL, tylenol, dihydrothiophene, oxazolyl, dihydrooxazolo, isoxazolyl, dihydroisoxazole, diazolidinyl, dihydrothiazolo, isothiazolinones, dihydroisoxazole, oxacillin, 2H-pyranyl, 4H-pyranyl, tetrahydropyranyl, 2H-dipiradol, 4H-teerasil, tetrahydrothiopyran, piperidinyl, di-, tetrahydropyranyl, piperazinil, di-, tetrahydropyranyl, di-, Tetra-hexahydropyridine, di-, Tetra-, hexahydropyridine, morphol the Nile, thiomorpholine, azepane, tiapamil and examiner, with two of these heterocyclic rings can also form the system is saturated or partially unsaturated articulated bicyclic rings. Examples of such systems bicyclic rings are octahedral[1,2A]pyrazinyl, octahedral[3,4b]pyrrolyl, hexahydrofuro[3,4-C]pyrrolyl and octahedral[3,4-C]pyrrolyl.

Examples of preferred (C6-C10)-aryl radicals are phenyl and naphthyl. This also applies to the case when they contain substituents or substituents are the radicals.

(C1-C9)-heteroaryl radicals are containing aromatic ring compounds in which one or more ring atoms are oxygen atoms, sulfur atoms or azoty atoms, for example, 1, 2 or 3 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom or the combination of different heteroatoms. This also applies to the case when they contain substituents or are substituents of other radicals. Heteroaryl radicals may be attached in all positions. Heteroaryl means, for example, furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolin, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazoles, hinely, ethanolic,phthalazine, honokalani, hintline and cinnoline.

Particularly preferred heteroaryl radicals are 2 - or 3-thiophenyl, 2 - or 3-furyl, 1-, 2 - or 3-pyrrolyl, 1-, 2-, 4 - or 5-imidazolyl, 1-, 3-, 4 - or 5-pyrazolyl, 1,2,3-triazole-1-, -4 - or-5-yl, 1,2,4-triazole-1-, -3 - or-5-yl, 1 - or 5-tetrazolyl, 2-, 4 - or 5-oxazolyl, 3-, 4 - or 5-isoxazolyl, 1,2,3-oxadiazol-4 - or-5-yl, 1,2,4-oxadiazol-3 - or-5-yl, 1,3,4-oxadiazol-2-yl or-5-yl, 2-, 4 - or 5-thiazolyl, 3-, 4 - or 5-isothiazole, 1,3,4-thiadiazole-2 - or-5-yl, 1,2,4-thiadiazole-3-or-5-yl, 1,2,3-thiadiazole-4- or-5-yl, 2-, 3 - or 4-pyridyl, 2-, 4-, 5 - or 6-pyrimidinyl, 3 - or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6 - or 7-indolyl, 1-, 2-, 4 - or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6 - or 7-indazole, 2-, 3-, 4-, 5-, 6-, 7 - or 8-chinolin, 1-, 3-, 4-, 5-, 6-, 7 - or 8-ethanolic, 2-, And-, 5-, 6-, 7 - or 8-hintline, 3-, A-, 5-, 6-, 7 - or 8-indolinyl, 2-, 3-, 5-, 6-, 7 - or 8-honokalani, 1-, 4-, 5-, 6-, 7 - or 8-phthalazine.

(C9-C14)-cycloalkenyl radicals preferably selected from the group including a system of coupled rings with cycloalkene ring and an aryl ring, particularly phenyl ring. Particularly preferred cycloalkenyl radicals are indenyl, dihydronaphtho, tetrahydronaphthyl and indanyl.

(C5-C13)-cycloalkylcarbonyl radicals preferably selected from the group including a system of coupled rings with cycloalkyl ring is heteroaryl ring.

(C7-C13)-cycloheptatriene radicals preferably represent a system of coupled rings with cycloheptatriene ring and an aryl ring, particularly phenyl ring. Particularly preferred cyclohexanemethylamine radicals are benzodithiophene, benzothiophene, benzodithiophene, benzooxazol, benzodioxolyl, benzodiapines, benzodithiol, benzodiapines, benzodithiol, benzofurazanyl, benzodithiol, benzomorphans benzodithiol, dihydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline and tetrahydroquinolines.

(C4-C12)-cyclohexanecarbonitrile radicals preferably selected from the group including a system of coupled rings with cycloheptatriene ring and heteroaryl ring.

In one of the embodiments of the invention p is 1, and in another embodiment, p is 2. In one of the embodiments of the invention, q is 0, and in another embodiment, q is 1.

If the compounds of formula I have one or more centers of asymmetry, they are independently of each other can have the S configuration or R Compounds may represent optical isomers, diastereomers, racemates or mixtures in any ratio. To the ome, the compounds of formula I can be a rotary isomers.

Particularly preferred are the stereoisomers of the formula I in which the radical XLBR5 attached in position 1, is directed downwards, and the radical -(CH2)qNR3R4 attached in position 2, is directed upwards when the direction is determined proceeding from the plane, which is formed by three carbon atoms in positions 1, 2 and 3, and the following adopted by the molecule orientation (formula Ie):

Preferred are the compounds of formula I with the configuration of TRANS-1S,2S in position 1 and 2.

In the present invention includes all possible tautomeric forms of the compounds of formula I.

Particularly preferred compounds of formula I are selected from the group including:

ExampleConfigurationName
1TRANS-1S,2S-3'R-((R)-1-{TRANS-(1S,2S)-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}piperidine-3-yl)-(3,3,3-cryptochromes)Amin
2TRANS-1S,2S-3-[TRANS-(1S,2S)-4,6-dichloro-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]-3,8-diazabicyclo[3.2.1]octane
3TRANS-1S,2S-2-[rat-TRANS-(1,2)-1-(2,4-dichloro-3-methylphenoxy)indan-2-yl]octahedral[3,4-C]pyrrol
4rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(2,4-dichloro-3-methylphenoxy)indan-2-yl]octahedral[3,4-C]pyrrol

5rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]octahedral[3,4-C]pyrrol
6rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(3-chloro-2-methylphenoxy)indan-2-yl]octahedral[3,4-C]pyrrol
7rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)indan-2-yl]octahedral[3,4-C]pyrrol
8TRANS-1S,2S-2-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-5-metalocherepitsya[3,4-C]pyrrol
9rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(2,4-divergence)indan-2-yl]octahedral[3,4-C]pyrrol
rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)indan-2-yl]octahedral[3,4-C]pyrrol
11rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(2-bromophenoxy)indan-2-yl]octahedral[3,4-C]pyrrol
12rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]octahedral[3,4-C]pyrrol
13rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]octahedral[3,4-C]pyrrol
14rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(3-piperidine-1-

ylmethylene)indan-2-yl]octahedral[3,4-C]pyrrol
15rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(3-piperidine-1-elfenix)indan-2-yl]octahedral[3,4-C]pyrrol
16rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(4-fluoro-methylphenoxy)indan-2-yl]octahedral[3,4-C]pyrrol
17rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]octahedral[3,4-C]pyrrol
18rat-TRANS-1,2-2-[rat-TRANS-(1,2)-1-(6-chloropyridin-3-yloxy)indan-2-yl]octahedral[3,4-C]pyrrol
19rat-TRANS-1,2-2-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}octahedral[3,4-C]pyrrol
20rat-TRANS-1,2-2-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}octahedral[3,4-C]pyrrol
21TRANS-1S,2S-CIS-3'-5'-(3R,5S)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl] - for 3,5-dimethylpiperazine
22rat-TRANS-1,2-(4-methylpiperazin-1-yl)-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]metano
23TRANS-1S,2S-3'R-(R)-1-(TRANS-(1R,2R)-4,6-dichloro-1-venexiana-2-yl)piperidine-3-ylamine
24 TRANS-1S,2S-3'R-(R)-1-[(1S,2S)-4,6-dichloro-1-(2-chloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-

/tr>
ol
25TRANS-1S,2S-3'R(R)-1-[(1S,2S)-4,6-dichloro-1-(2-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine
26TRANS-1S,2S-3'R-(R)-1-[(1S,2S)-4,6-dichloro-1-(4-methanesulfonanilide)indan-2-yl]pyrrolidin-3-ol
27TRANS-1S,2S-3'R(R)-1-[(1S,2S)-4.6-dichloro-1-(5-ftorhinolon-8 yloxy)indan-2-yl]piperidine-3-ylamine
28TRANS-1S,2S-3'R(R)-1-[(1S,2S)-4,6-debtor-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-ol
29rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(1H-benzotriazol-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
30rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(1H-indol-4-yloxy)indan-2-yl]piperidine-3-ylamine
31rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2,3-dichloro-4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine
32rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2,4-divergence)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
33rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2,4-divergence)indan-2-yl]piperidine-3-ylamine
34rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2,6-dimethoxyphenoxy)-1,2,3,4-

tetrahydronaphthalen-2-yl]piperidine-3-ylamine
35rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
36rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-bromophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
37rat-Tr is the na-1,2-3'R- (R)-1-[rat-TRANS-(1,2)-1-(2-chloro-4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine
38rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
39rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-chloro-6-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
40rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-chloropyridin-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
41rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-chlorhydrin-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
42rat-TRANS-1,2-3'R-R)-1-[rat-TRANS-(1,2)-1-(2-fluoro-4-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
43rat-TRANS-1,2-3'R-R)-1-[rat-TRANS-(1,2)-1-(2-fluoro-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
44 rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine

45rat-TRANS-1,2-3'R-R)-1-[rat-TRANS-(1,2)-1-(2-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
46rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
47rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-methylbenzothiazol-5-yloxy)indan-2-yl]piperidine-3-ylamine
48rat-TRANS-1,2-3'R-R)-1-[rat-TRANS-(1,2)-1-(2-morpholine-4-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
49rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]piperidine-3-ylamine
50rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(2-triftormetilfosfinov)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-yl) - Rev. Jn
51rat-TRANS-1,2-3'R(R)-1-[rat-TRANS-(1,2)-1-(3,4-divergence)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
52rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-chloro-4-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
53rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
54rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
55rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine

65
56rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-deformationally)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
57rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1(3-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
58rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-piperidine-1-ylmethylene)indan-2-yl]piperidine-3-ylamine
59rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-piperidine-1-elfenix)indan-2-yl]piperidine-3-ylamine
60rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(3-tetrazol-1 elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
61rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
62rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]piperidine-3-ylamine
63rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-bromo-3-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
64rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-chloro-2-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-chloro-3-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
66rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine

67rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-dimethylaminomethylphenol)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
68rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-fluoro-2-isoxazol-5-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
69rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-fluoro-3-triptoreline)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
70rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
71rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-yl is enocsi)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
72rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)indan-2-yl]piperidine-3-ylamine
73rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
74rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-methylsulfinylphenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
75rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
76rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-3-ylamine
77rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(4-triptoreline)-

1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
78 rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(5,7-dimethylindoline-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
79rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(5-ftorhinolon-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
80rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(6-aminonaphthalene-1 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
81rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(6-chloropyridin-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
82rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(6-chloropyridin-3-yloxy)indan-2-yl]piperidine-3-ylamine
83rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(benzo[1,3]dioxol-5-yloxy)indan-2-yl]piperidine-3-ylamine
84rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(isoquinoline-7-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
85 rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(isoquinoline-7-yloxy)indan-2-yl]piperidine-3-ylamine
86rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(pyridine-4-yloxy)indan-2-yl]piperidine-3-ylamine
87rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(quinoline-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine

88rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(quinoline-4-yloxy)indan-2-yl]piperidine-3-ylamine
89rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-1-(quinoline-5-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
90rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-4-chloro-6-fluoro-1-(3-methyl-4-triftormetilfullerenov)indan-2-yl]piperidine-3-ylamine
91rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-4-chloro-6-fluoro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine
92 rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-6-chloro-4-fluoro-1-(3-methyl-4-triftormetilfullerenov)indan-2-yl]piperidine-3-ylamine
93rat-TRANS-1,2-3'R-(R)-1-[rat-TRANS-(1,2)-6-chloro-4-fluoro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine
94TRANS-1S,2S-3'R-(R)-1-[TRANS-(1R,2R)-4,6-dichloro-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]piperidine-3-ylamine
95TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine
96TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(2-methylbenzothiazol-5-yloxy)indan-2-yl]pyrrolidin-3-ol
97TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-[1,2,4]triazole-1-

elfenix)indan-2-yl]piperidine-3-ylamine
98TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-imida the ol-1-elfenix)indan-2-yl]piperidine-3-ylamine
99TRANS-1S,2S-3'R-(R)-1'-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-[1,3']bipirimidiny
100TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-ftorpirimidinu
101TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-methylpiperazin
102TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine
103TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-ol
104TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-ylamine
105TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-carbonitril
106 TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-6-chloro-1-(2-chloro-4-methysulfonylmethane)-4-Florinda-2-

Il]pyrrolidin-3-ol
107TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-6-chloro-1-(2-chloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-ol
108TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-6-chloro-4-fluoro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-ol
109TRANS-1S,2S-3'R-(R)-1-{(1S,2S)-1-[2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]-4,6-defterinden-2-yl}pyrrolidin-3-ol
110TRANS-1S,2S-3'R-(R)-1-{(1S,2S)-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]-4,6-defterinden-2-yl}pyrrolidin-3-ol
111TRANS-1S,2S-rat-3'-(R)-1-{(1S,2SH,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-3-methylpyrrolidine-3-ol
112TRANS-1S,2S-3'R-(R)-1-{(1S,2S)-4,6-dichlo the-1-[4-(5-methyltetrazol-1-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
113TRANS-1S,2S-3'R-(R)-1-{(1S,2S)-4,6-dichloro-1-[4-fluoro-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-3-ylamine
114TRANS-1S,2S-3'R-(R)-1-{(1S,2S)-4,6-dichloro-1-[5-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]indan-2-yl}pyrrolidin-3-ol
115rat-TRANS-1,2-3'R-(R)-1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine
116rat-TRANS-1,2-3'R-(R)-1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}piperidine-3-ylamine

117rat-TRANS-1,2-3'R-(R)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidin-3-ylamine
118rat-TRANS-1,2-3'R-(R)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-3-ylamine
119rat-TRANS-1,2-3'R-(R)-1-{rat-TRANS-(1,2)-1-[4-chloro-2-(1H-piraso the-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine
120rat-TRANS-1,2-3'R-(R)-1-{rat-TRANS-(1,2)-1-[4-fluoro-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine
121TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}piperidine-3-ylamine
122TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
123TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[3-(1,1-dioxo-lambda-isothiazolin-2-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
124TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(1,3,5-trimethyl-1H-pyrazole-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
125TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(2,4-dimethyl-thiazol-5-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol

126TRANS-1S,2S-3'R-(R)-1-{TRANS-(S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2,3-divergence]indan-2-yl}pyrrolidin-3-ol
127TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2,3-dimethylphenoxy]indan-2-yl}pyrrolidin-3-ol
128TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2,3-dimethylphenoxy]indan-2-yl}pyrrolidin-3-ol
130TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]indan-2-yl}pyrrolidin-3-ol
131TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-methylphenoxy]indan-2-yl}pyrrolidin-3-ol
132TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}piperidine-3-ol
133TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
134TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazo the-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-carbonitril
135TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethylisoxazol-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol

136TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)46-dichloro-1-[4-(3,5-dimethylpyrazol-1-yl)-2-fervency]indan-2-yl}pyrrolidin-3-ol
137TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-fluoro-2-(2H-pyrazole-3-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
138TRANS-1S,2S-3'R-(R)-{TRANS-(1S,2S)-6-chloro-1-[2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]-4-Florinda-2-pyrrolidin-3-ol
139TRANS-1S,2S-3'R-(R)-{TRANS-(1S,2S)-6-chloro-1-[2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
140TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-1-[4-(1,3,5-trimethyl-1H-pyrazole-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
141TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-1-[4-(3,5-dimethy the-[1,2,4]triazole-4-yl)-2,3-dimethylphenoxy]-4-Florinda-2-yl}pyrrolidin-3-ol
142TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]-4-Florinda-2-yl}pyrrolidin-3-ol
143TRANS-1S,2S-3'R-(R)-{TRANS-(1S,2S)-6-chloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]indan-2-yl}pyrrolidin-3-ol
144TRANS-1S,2S-3'R-(R)-{TRANS-(1S,2S)-6-chloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]-4-Florinda-2-yl}pyrrolidin-3-ol

145TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-1-[4-(3,5-dimetyl-[1,2,4]triazole-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
146TRANS-1S,2S-rat-3'-(S)-1-[(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-methylpyrrolidine-3-ol
147rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(1H-benzotriazol-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
148rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(1 is-indole-6-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
149rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2,4-divergence)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
150rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
151rat-TRANS-1,2-3'S-S)-1-[rat-TRANS-(1,2)-1-(2-bromophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
152rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
153rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-chloropyridin-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
154rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-chlorhydrin-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
155rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-fluoro-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-and the]piperidine-3-ylamine

156rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
157rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
158rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-morpholine-4-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-8-ylamine
159rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(2-triftormetilfosfinov)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
160rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-2-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
161rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
162rat-TRANS-1,2-3'S- (S)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
163rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
164rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)indan-2-yl]piperidine-3-ylamine
165rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
166rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-deformationally)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-8-ylamine

167rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-dimethylaminomethylene)indan-2-yl]piperidine-3-ylamine
168rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
169(S)-1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]piperidine-3-ylamine
170rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(3-piperidine-1-ylmethylene)indan-2-yl]piperidine-3-ylamine
171rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
172rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]piperidine-3-ylamine
173rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-bromo-3-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
174rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-chloro-2-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
175rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
176rat-TRANS-1,23'S- (S)-1-[rat-TRANS-(1,2)-1-(4-deformationally)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
177rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-

dimethylaminomethylphenol)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
178rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-fluoro-2-isoxazol-5-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidin-3-ylamine
179rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
180rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
181rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)indan-2-yl]piperidine-3-ylamine
182rat-TRANS-1,2-3'S-S)-1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
183rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-methylsulfinylphenyl)-1,A-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
184rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
185rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-3-ylamine
186rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(4-triptoreline)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
187rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(5,7-dimethylindoline-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine

188rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(5-ftorhinolon-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
189rat-TRANS-1,2-3'S-(S)-1-[rat-t is ANS-(1,2)-1-(6-aminonaphthalene-1 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
190rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(6-chloropyridin-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
191rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(pyridine-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
192rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(quinoline-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
193rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(quinoline-5-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine
194rat-TRANS-1,2-3'S-(S)-1-[rat-TRANS-(1,2)-1-(quinoline-5-yloxy)indan-2-yl]piperidine-3-ylamine
195TRANS-1S,2S-2'S-(S)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-2-pyrrolidin-1-iletilenlerin
196TRANS-1S,2S-3'S-(S)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-ftorpirimidinu
197TRANS-1S,2S-3'S-(S)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-methylpiperazin
198TRANS-1S,2S-3'S-(S)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-ol

199TRANS-1S,2S-3'S-(S)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-ylamine
200TRANS-1S,2S-3'S-(S)-1-{(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]indan-2-yl}pyrrolidin-3-ol
201rat-TRANS-1,2-3S-(S)-1-{rat-TRANS-(1,2)-1-[3-(2-amino-ethyl)-1H-indol-5-elohel-]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-S-ylamine
202rat-TRANS-1,2-3S-(S)-1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine
203rat-TRANS-1,2-3S-(S)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahedron the Talin-2-yl}piperidine-3-ylamine
204rat-TRANS-1,2-3S-(S)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-3-ylamine
205rat-TRANS-1,2-3S-(S)-1-{rat-TRANS-(1,2)-1-[4-fluoro-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine
206TRANS-1S,2S-3S-(S)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ol
207TRANS-1S,2S-3S-(S)-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}pyrrolidin-3-ylamine

208TRANS-1S,2S-3S-(S)-2-[(S)-4-(S)-chloro-6-chloro-1-(4-methysulfonylmethane)indan-2-yl]octahedral[1,2-a]pyrazin
209TRANS-1S,2S-2'R-5'S(S)-2-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-2,5-diazabicyclo[2.2.1]heptane
210TRANS-1S,2S-3S-S)-3-{3-[(1S,2S)-6-chloro-4-ftor-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-4-isopropylimidazole-2-he
211TRANS-1S,2S-3S-S)-3-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-4-isopropylimidazole-2-he
212rat-TRANS-1,2-[3-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)phenyl]-urea
213rat-TRANS-1,2-[3-methoxy-2-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)phenyl]acetonitrile
214rat-TRANS-1,2-rat-3'-[rat-TRANS-(1,2)-1-(1H-indol-4-yloxy)indan-2-yl]methylpiperidine-3-ylamine
215rat-TRANS-1,2-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]methylpiperidin-4-ylamine
216rat-TRANS-1,2-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-imidazol-1-elfenix)indan-2-yl]dimethylamine
217rat-TRANS-1,2-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-

methysulfonylmethane)indan-2-ylmethyl]dimethylamine
218TRANS-1S,2S[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-(2-methoxyethyl)-methylamine
219TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}-(2,2,2-triptorelin)Amin
220TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}-(3,3,3-cryptochromes)Amin
221TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]piperidine-3-yl}-(3,3,3-cryptochromes)Amin
222TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}-(2-foradil)Amin
223TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}-(3,3,3-cryptochromes)Amin
224TRANS-1S,2S-3'R- {(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}-dimethylamine
225TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamino}acetonitrile
226TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-

methysulfonylmethane)indan-2-yl]pyrrolidin-3-yl}-(2-foradil)Amin
227TRANS-1S,2S-3'R-{(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-3-yl} methanol
228TRANS-1S,2S-2'S{(S)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin-2-yl} methanol
229rat-TRANS-1,2-3R-{2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-methoxyphenyl}acetonitrile
230rat-TRANS-1,2-3'R- {3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}acetonitrile
231rat-TRANS-1,2-3'R-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}urea
232rat-TRANS-1,2-3'S-{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-3'S-yloxy]phenyl}urea
233rat-TRANS-1,2-rat-3'-{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-3'S-yloxy]phenyl}urea
234rat-TRANS-1,2-rat-3'-{3-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]phenyl}urea
235rat-TRANS-1,2-{3-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]phenyl}urea
236TRANS-1S,2S-3'R-{3-chloro-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-

1-yl)indan-1-yloxy]phenylcarbamoyloxy}acetic acid the acid
237rat-TRANS-1,2-3'R-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}carbamino acid benzyl ester
238rat-TRANS-1,2-3'R-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}carbamino acid benzyl ester
239rat-TRANS-1,2-3'S-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}carbamino acid benzyl ester
240rat-TRANS-1,2-rat-3'-{4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]phenyl}carbamino acid benzyl ester
241rat-TRANS-1,2-rat-3'-{4-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]phenyl}carbamino acid benzyl ester
242rat-TRANS-1,2-{4-[rat-TRANS-(1,2)-6-fluoro-1-(4-methysulfonylmethane)indan-2-yl]piperazine-1-yl}acetonitrile
243TRANS-1S,2S {TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-(2-methoxyethyl)-methylamine
244rat-TRANS-1,2-1-(4-methysulfonylmethane)indan-2-ylmethyl]-dimethylamine
245TRANS-1S,2S1-[(1S,2S)-4,6-dichloro-1-(2-methysulfonylmethane)indan-2-yl]azetidine

246TRANS-1S,2S1-[(1S,2S)-4,6-dichloro-1-(2-methysulfonylmethane)indan-2-yl]piperazine
247TRANS-1S,2S1-[(1S,2S)-4,6-dichloro-1-(2-methysulfonylmethane)indan-2-yl]pyrrolidin
248TRANS-1S,2S1-[(1S,2S)-4,6-dichloro-1-(3-tetrazol-1 elfenix)indan-2-yl]piperazine
249TRANS-1S,2S-rat-3'-1-[(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-methanesulfonanilide
250TRANS-1S,2S1-[(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-4,4-d is foreperiod
251rat-TRANS-1,2-1-[1-(2-chloro-4-nitrophenoxy)indan-2-yl]pyrrolidin
252rat-TRANS-1,2-1-[1-(4-methysulfonylmethane)-2-methylindol-2-yl]pyrrolidin
253rat-TRANS-4,5-1-[1,3-dichloro-4-(4-methysulfonylmethane)-4,5,6,7-tetrahydrobenzo[C]thiophene-5-yl]pyrrolidin
254rat-TRANS-1,2-1-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-1,3-dihydroimidazole-2-he
255rat-TRANS-1,2-1-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]pyrrolidin-2-he
256rat-TRANS-1,2-1-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]pyrrolidin-2,5-dione
257rat-TRANS-1,2-1-[3-(rat-TRANS-(1,2)-4,6-dichloro-2-piperazine-1-Ilinden-1-

ilox is)phenyl]-3-methyl-1,3-dihydroimidazole-2-he
258rat-TRANS-1,2-1-[3-(rat-TRANS-(1,2)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)phenyl]-3-methylimidazolidine-2-he
259TRANS-1S,2S-1-[4-((1S,2S)-2-azetidin-1-yl-4,6-dichloride-1 yloxy)phenyl]pyrrolidin-2-he
260TRANS-1S,2S-1-[4-((1S,2S)-4,6-dichloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]pyrrolidin-2-he
261rat-CIS-1,21-[rat-CIS-(1,2)-1-(4-methysulfonylmethane)indan-2-yl]-1H-imidazol
262rat-TRANS-1,2-rat-3'-1-[rat-TRANS-(1,2)-1-(1H-indol-6-yloxy)indan-2-yl]pyrrolidin-3-ylamine
263rat-TRANS-1,21-[rat-TRANS-(1,2)-1-(2,3-dichloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin
264rat-TRANS-1,21-[rat-TRANS-(1,2)-1-(2,6-dichloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin
265rat-TRANS-1,21-[rat-Tran is-(1,2)-1-(2-chloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin
266rat-TRANS-1,2-rat-3'-1-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]pyrrolidin-3-ylamine
267rat-TRANS-1,2-rat-3'-1-[rat-TRANS-(1,2)-1-(2-tert-butyl-ethylenoxy)indan-2-yl]pyrrolidin-3-ylamine
268rat-TRANS-1,21-[rat-TRANS-(1,2)-1-(3-chloro-4-

methysulfonylmethane)indan-2-yl]pyrrolidin
269rat-TRANS-1,21-[rat-TRANS-(1,2)-1-(3-methysulfonylmethane)indan-2-yl]pyrrolidin
270rat-TRANS-1,2-rat-3'-1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]pyrrolidin-3-ylamine
271rat-TRANS-1,2-1-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-3-methylphenoxy)indan-2-yl]pyrrolidin
272rat-TRANS-1,2-1-[rat-TRANS-(1,2)-1-(4-metasolv is Difenoxin)indan-2-yl]piperazine
273rat-TRANS-1,2-1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin
274rat-TRANS-1,2-1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)indan-2-ylmethyl]pyrrolidin
275rat-TRANS-1,2-rat-3'-1-[rat-TRANS-(1,2)-1-(quinoline-4-yloxy)indan-2-yl]pyrrolidin-3-ylamine
276rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]piperazine
277rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-[1,4]diazepan
278rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-1H-imidazol
279rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-

meanswhen is phenoxy)indan-2-yl]-4-methyl-[1,4]diazepan
280rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-ylmethyl]pyrrolidin
281rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4-chloro-6-fluoro-1-(4-methanesulfonyl-3-methylphenoxy)indan-2-yl]piperazine
282rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4-chloro-6-fluoro-1-(4-methanesulfonyl-3-methylphenoxy)indan-2-yl]pyrrolidin
283rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4-chloro-6-fluoro-1-(4-methysulfonylmethane)indan-2-yl]piperazine
284rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4-chloro-6-fluoro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin
285rat-TRANS-1,2-1-[rat-TRANS-(1,2)-4-fluoro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin
286rat-TRANS-1,2-1-[rat-TRANS-(1,2)-5,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-[1,4]diazepan
287rat-the Rance-1,2- 1-[rat-TRANS-(1,2)-5,7-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperazine
288rat-TRANS-1,2-1-[rat-TRANS-(1,2)-6,7-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-[1,4]diazepan
289rat-TRANS-1,2-1-[rat-TRANS-(1,2)-6-chloro-1-(4-methysulfonylmethane)indan-2-yl]piperazine
290rat-TRANS-1,2-1-[rat-TRANS-(1,2)-6-chlorc-4-fters-1-(3-methyl-4-

triftormetilfullerenov)indan-2-yl]piperazine
291rat-TRANS-1,2-1-[rat-TRANS-(1,2)-6-chloro-4-fluoro-1-(4-methanesulfonyl-3-methylphenoxy)indan-2-yl]pyrrolidin
292rat-TRANS-1,2-1-[rat-TRANS-(1,2)-6-chloro-4-fluoro-1-(4-methysulfonylmethane)indan-2-yl]piperazine
293rat-TRANS-1,2-1-[rat-TRANS-(1,2)-6-chloro-4-fluoro-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin
294rat-TRANS-1,2-1-[rat-TRANS-(1,2)-6-fluoro-1-(4-methysulfonylmethane)indan-2-yl]piperazine
295TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(2-chloro-4-methysulfonylmethane)indan-2-yl]-[1,4]diazepan
296TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]-4-methylpiperazin
297TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-imidazol-1-elfenix)indan-2-yl]-4-methylpiperazin
298TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-[1,4]diazepan
299TRANS-1S,2S-3 epimer-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-propylpiperidine-3-ylamine
300TRANS-1S,2S-3 epimer-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-propylpiperidine-3-ylamine

301TRANS-1S,2S-rat-3'-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-triftorperasin
302TRANS-1S,2S-rat-3'-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-3-triftormetilfullerenov-3-ylamine
303TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-4-(2-foradil)-[1,4]diazepan
304TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-4-(2-methoxyethyl)-[1,4]diazepan
305TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-4-methyl-[1,4]diazepan
306TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-4-methylpiperazin
307TRANS-1S,2S1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]azetidin-3-ol
308TRANS-1S,2S/td> 1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperazine
309TRANS-1S,2S-1-{(1S,2S)-4,6-dichloro-1-[4-fluoro-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperazine
310TRANS-1S,2S-3'R-1-{2-chloro-5-[(1S,2S)-4,6-dichloro-2-((R)-3-

hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methyl-1,3-dihydroimidazole-2-he
311TRANS-1S,2S-3'R-1-{2-chloro-5-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methylimidazolidine-2-he
312TRANS-1S,2S-3'R-1-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-2-were}-3-methyl-1,3-dihydroimidazole-2-he
313TRANS-1S,2S-3'R-1-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-3-methyl-1,3-dihydroimidazole-2-he
314TRANS-1S,2S-3'R- 1-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-3-methylimidazolidine-2-he
315TRANS-1S,2S-3'R-1-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2-he
316TRANS-1S,2S-3'R-1-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2,5-dione
317TRANS-1S,2S-3'R-1-{3-[(1S,2S)-4,6-debtor-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-3-methyl-1,3-dihydroimidazole-2-he
318TRANS-1S,2S-3'R-1-{3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-3-methyl-1,3-dihydroimidazole-2-he
319TRANS-1S,2S-3'R-1-{3-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methylimidazolidine-2-he

320TRANS-1S,2S-3'R-1-{3-[TRANS-(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-IU is eliminatedin-2-he
321TRANS-1S,2S-3'R-1-{3-chloro-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2-he
322TRANS-1S,2S-3'R-1-{3-chloro-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2,5-dione
323TRANS-1S,2S-3'R-1-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-forfinal}-1,3-dihydroimidazole-2-he
324TRANS-1S,2S-3'R-1-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-forfinal}-2,6-dimethyl-1H-pyridin-4-one
325TRANS-1S,2S-3'R-1-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-1,3-dihydroimidazole-2-he
326rat-TRANS-1,2-3'R-1-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}pyrrolidin-2,5-dione
327rat-TRANS-1,2-3'S-1-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopyrene the Jn-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]for 3,5-differenl}propane-1-he
328rat-TRANS-1,2-3'S-1-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}pyrrolidin-2,5-dione
329TRANS-1S,2S-3'R-1-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-

1-yl)indan-1-yloxy]-3-forfinal}-3-methyl-1,3-dihydroimidazole-2-he
330TRANS-1S,2S-3'R-1-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-forfinal}-3-methylimidazolidine-2-he
331TRANS-1S,2S-3'R-1-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methyl-1,3-dihydroimidazole-2-he
332TRANS-1S,2S-3'R-1-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methylimidazolidine-2-he
333TRANS-1S,2S-3'R-1-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine the-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2-he
334TRANS-1S,2S-3'R-1-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2,5-dione
335TRANS-1S,2S-3'R-1-{4-chloro-3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methyl-1,3-dihydroimidazole-2-he
336TRANS-1S,2S-3'R-1-{4-chloro-3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2-he
337TRANS-1S,2S-3'R-1-{4-chloro-3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2,5-dione
338TRANS-1S,2S-3'R-1-{4-chloro-3-[(1S,2S)-4,6-debtor-2-((R)-3-hydroxypyrrolidine-

1-yl)indan-1-yloxy]phenyl}-3-methyl-1,3-dihydroimidazole-2-he
339TRANS-1S,2S-3'R-1-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methyl-1,3-is hydromedusa-2-he
340TRANS-1S,2S-3'R-1-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-3-methylimidazolidine-2-he
341TRANS-1S,2S-3'R-1-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}pyrrolidin-2-he
342rat-TRANS-1,2-rat-3'-1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}pyrrolidin-3-ylamine
343rat-TRANS-1,2-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-4-ylamine
344TRANS-1S,2S-1-{TRANS-(1S,2S)-4,6-dichloro-1-[2-chloro^-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-[1,4]diazepan
345TRANS-1S,2S-1-{TRANS-(1S,2S)-4,6-dichloro-1-[2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-4-methyl-[1,4]diazepan
346TRANS-1S,2S-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]indan-2-yl}-4-methyl-[,4]diazepan
347TRANS-1S,2S-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-[1,4]diazepan

348TRANS-1S,2S-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-4-(2-methoxyethyl)-[1,4]diazepan
349TRANS-1S,2S-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-4-methyl-[1,4]diazepan
350TRANS-1S,2S-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethylisoxazol-4-yl)phenoxy]indan-2-yl}-4-(2-methoxyethyl)-[1,4]diazepan
351TRANS-1S,2S-1-cyclopropyl-4-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperazine
352rat-TRANS-1,2-1-methyl-3-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-1,3-dihydroimidazole-2-he
353TRANS-1S,2S-2-((1S,2S)-2-azetidin-1-yl-4,6-declaring the n-1 yloxy)-5-chlorobenzamide
354TRANS-1S,2S-3'R-1-2,2,2-Cryptor-N-{(R)-1-[TRANS-(1S,2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}ndimethylacetamide
355rat-TRANS-1,2-2,3-dichloro-4-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)benzosulfimide
356rat-TRANS-1,2-2,3-dichloro-4-(rat-TRANS-(1,2)-2-dimethylaminoethyl-1 yloxy)benzosulfimide
357rat-TRANS-1,2-2,3-dichloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
358rat-TRANS-1,2-2,3-dichloro-4-(rat-TRANS-(1,2)-4,6-dichloro-2-morpholine-4-

2,3-dichloro-4-[rat-TRANS-(1,2)-2-(methylpiperidin-3-ylamino)indan-1-yloxy]benzosulfimide
Ilinden-1 yloxy)benzosulfimide
359rat-TRANS-1,2-3'R-2,3-dichloro-4-[rat-TRANS-(1,2)-2-((R)-3-ethoxypyrrolidine-1-yl)indan-1-yloxy]benzosulfimide
360rat-TRANS-1,2-rat-3'-
361TRANS-1S,2S-rat-3'-2,3-dichloro-4-[TRANS-(1S,2S)-2-(3-hydroxy-piperidine-1-yl)indan-1-yloxy]benzosulfimide
362rat-TRANS-1,2-2,3-dichloro-N,N-dimethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
363rat-TRANS-1,2-2-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]isothiazolin 1,1-dioxide
364rat-TRANS-1,2-2-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]thiazole
365rat-TRANS-1,2-3'R-2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzamide
366rat-TRANS-1,2-3'R-2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzonitrile
367rat-TRANS-1,2-3'R-2-[rat-TRANS-(1,2)-2-((R)3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-6-perbenzoate
368rat-TRANS-1,2-3'R-2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzamide
369rat-TRANS-1,2-3'S-2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-

tetrahydronaphthalen-1 yloxy]-5-bromobenzonitrile
370rat-TRANS-1,2-3'S-2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzamide
371rat-TRANS-1,2-3'S-2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzonitrile
372rat-TRANS-1,2-3'S-2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-6-perbenzoate
373rat-TRANS-1,2-3'S-2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzamide
374rat-TRANS-1,2-rat-3'-2-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-6-perbenzoate
375rat-TRANS-1,2-rat-3'-2-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]-5-chlorobenzonitrile
376rat-TRANS-1,2-2-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-5-chlorobenzonitrile
377rat-TRANS-1,2-2-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]octahedral[3,4-C]pyrrol
378TRANS-1S,2S-rat-3'-2-[TRANS-(1S,2SH,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-2,7-diaza-Spiro[4.4]nonan
379TRANS-1S,2S-3'R-2-{(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamino}-ethanol

380rat-TRANS-1,2-3'R-2-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]FeNi is}-N,N-dimethylacetamide
381rat-TRANS-1,2-3'R-2-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}thiazol-4-carbonitril
382rat-TRANS-1,2-3'S-2-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}-N,N-dimethylacetamide
383rat-TRANS-1,2-2-{4-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-[1,4]diazepan-1-yl}-ethanol
384rat-TRANS-1,2-2-{4-[rat-TRANS-(1,2)-6-chloro-1-(4-methysulfonylmethane)indan-2-yl]piperazine-1-yl}-ethanol
385TRANS-1S,2S2-{4-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-[1,4]diazepan-1-yl}-ethanol
386rat-TRANS-1,2-rat-3'-2-{5-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-1H-indol-3-yl}ndimethylacetamide
387rat-TRANS-1,2-rat-3'-2-{5-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]-1H-indol-3-yl}are the amide
388rat-TRANS-1,2-2-{5-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-1H-indol-3-yl}ndimethylacetamide
389rat-TRANS-1,2-2-chloro-4-(2-pyrrolidin-1-ylmethylene-1 yloxy)benzosulfimide

390rat-TRANS-1,2-2-chloro-4-(2-pyrrolidin-1-ylmethylene-1 yloxy)benzoic acid
391rat-TRANS-1,2-2-chloro-4-(2-pyrrolidin-1-ylmethylene-1 yloxy)benzonitrile
392rat-TRANS-1,2-2-chloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzonitrile
393rat-TRANS-1,2-2-chloro-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]benzonitrile
394TRANS-1S,2S-2-chloro-4-methanesulfonylaminoethyl acid (1S.2S)-2-pyrrolidin-1-Ilinden-1 silt ether
395 rat-TRANS-1,2-2-chloro-8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline
396rat-TRANS-1,2-2-fluoro-4-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)benzonitrile
397rat-TRANS-1,2-2-fluoro-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]benzonitrile
398rat-TRANS-1,2-2-fluoro-6-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]benzonitrile
399rat-TRANS-1,2-2-methyl-4-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)-1H-indole
400rat-TRANS-1,2-3-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline

td align="justify"> 3,5-dichloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
401rat-TRANS-1,2-3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenylamine
402rat-TRANS-1,2-
403rat-TRANS-1,2-3,5-dichloro-N,N-dimethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
404rat-TRANS-1,2-3,5-dimethyl-4-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole
405rat-TRANS-1,2-3,5-dimethyl-4-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole
406TRANS-1S,2S-3,5-dimethyl-4-[4-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)-3-triptoreline]-4H-[1,2,4]triazole
407TRANS-1S,2S-3,5-dimethyl-4-[4-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-isoxazol
408TRANS-1S,2S-3,5-dimethyl-4-[5-methyl-2-(TRANS-(1S,2S)-2-pyrrolidin-Ilinden-1 yloxy)phenyl]isoxazol
409rat-TRANS-1,2-3-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)Fe is Il]oxazolidin-2-he
410rat-TRANS-1,2-3-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]benzamide
411rat-TRANS-1,2-3'R-3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide

412rat-TRANS-1,2-3'S-3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzamide
413rat-TRANS-1,2-3'S-3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide
414rat-TRANS-1,2-rat-3'-3-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]benzamide
415rat-TRANS-1,2-rat-3'-3-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]benzamide
416TRANS-1S,2S-3'R-3-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-5,5-dimethylimidazolidine-2,4-dione
417TRANS-1S,2S-3'R-3-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}imidazolidin-2,4-dione
418TRANS-1S,2S-3'R-3-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}oxazolidin-2,4-dione
419TRANS-1S,2S-3'R-3-{3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}oxazolidin-2-he
420TRANS-1S,2S-3'R-3-{3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-5,5-dimethylimidazolidine-2,4-dione
421TRANS-1S,2S-3'R-3-{3-[(1S,2S)-6-chloro^-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}imidazolidin-2,4-dione
422TRANS-1S,2S-3'R-3-{3-chloro-4-[(1S,2S)-4,6-dichloro-2-((R)-3-

hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-1-methylimidazolidine-2,4-dione
423TRANS-1S,2S-3'R-3-{3-chloro-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-5,5-dimethylimidazolidine-2,4-dione
424TRANS-1S,2S-3'R-3-{3-chloro-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}oxazolidin-2,4-dione
425TRANS-1S,2S-3'R-3-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-5,5-dimethylimidazolidine-2,4-dione
426TRANS-1S,2S-3'R-3-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}imidazolidin-2,4-dione
427TRANS-1S,2S-3'R-3-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}oxazolidin-2,4-dione
428TRANS-1S,2S-3'R-3-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}thiazolidine-2,4-dione
429TRANS-1S,2S-3'R-3-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}oxazol the DIN-2-he
430TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)^,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-1-methylimidazolidine-2,4-dione
431TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-4,6-dichloro-2-((R)-3-

hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-5,5-dimethylimidazolidine-2,4-dione
432TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-5,5-dimethyloxazolidine-2,4-dione
433TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}imidazolidin-2,4-dione
434TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}oxazolidin-2-he
435TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]the dryer is l}-1-methylimidazolidine-2,4-dione
436TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-6-chloro^-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-5,5-dimethylimidazolidine-2,4-dione
437TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}-5,5-dimethyloxazolidine-2,4-dione
438TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}imidazolidin-2,4-dione
439TRANS-1S,2S-3'R-3-{4-chloro-3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-

yloxy]phenyl}oxazolidin-2-he
440rat-TRANS-1,2-3-chloro-4-(2-piperidine-1-ylmethylene-1 yloxy)benzosulfimide
441rat-TRANS-1,2-3-chloro-4-(2-pyrrolidin-1-Ilinden-1 yloxy)pyridine
442 rat-TRANS-1,2-3-chloro-4-(2-pyrrolidin-1-ylmethylene-1 yloxy)benzosulfimide
443rat-TRANS-1,2-3-chloro-4-(2-pyrrolidin-1-ylmethylene-1 yloxy)pyridine
444rat-TRANS-1,2-3-chloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
445rat-TRANS-1,2-3-chloro-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]benzonitrile
446TRANS-1S,2S-3'R-3-chloro-4-[TRANS-(1S,2S)-6-chloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]benzoic acid methyl ester
447rat-TRANS-1,23-chloro-N,N-dimethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
448rat-TRANS-1,23-cyclopropyl-5-methyl-4-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole
449rat-TRANS-1,23-fluoro-4-(2-morpholine-ylmethylene-1 yloxy)benzosulfimide
450rat-TRANS-1,23-fluoro-4-(2-piperidine-1-ylmethylene-1 yloxy)benzosulfimide

451rat-TRANS-1,23-fluoro-4-(2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
452rat-TRANS-1,23-fluoro-4-(2-pyrrolidin-1-ylmethylene-1 yloxy)benzosulfimide
453rat-TRANS-1,23-methyl-4-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole
454TRANS-1S,2S-4-((1S,2S)-2-azetidin-1-yl-4,6-dichloride-1 yloxy)-3-perbenzoate
455TRANS-1S,2S-4-((1S,2S)-2-pyrrolidin-1-Ilinden-1-ylsulphonyl)benzonitrile
456TRANS-1S,2S-4-((1S,2S)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)-3-perbenzoate
457TRANS-1S,2S-4-((1S,2S)-4,6-dichloro-2-feast of alidin-1-Ilinden-1 yloxy)benzosulfimide
458TRANS-1S,2S-4-(2,5-dioxopiperidin-1-yl)benzoic acid (1S,2S)-2-pyrrolidin-1-Ilinden-1 silt ether
459rat-TRANS-1,2-4-(2-benzylamino-1 yloxy)-3-forbindelsesfaneblad
460rat-TRANS-1,2-4-(2-cyclopentylamine-1 yloxy)-3-forbindelsesfaneblad
461TRANS-1S,2S-4-(2-oxopyrrolidin-1-yl)benzoic acid (1S,2S)-2-pyrrolidin-1-Ilinden-1 silt ether

td align="justify"> 4-(rat-TRANS-(1,2)-2-piperidine-1-Ilinden-1 yloxy)benzosulfimide
462rat-TRANS-1,2-4-(2-pyrrolidin-1-ylmethylene-1 yloxy)-3-triptorelin
463rat-TRANS-1,2-3'R-4-(rat-TRANS-(1,2)-(R)-2-[1,3]bipirimidiny-1'-Ilinden-1 yloxy)benzosulfimide
464rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-azepan-1-Ilinden-1 yloxy)benzosulfimide
465rat-TRANS-1,2-
466rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
467rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzoic acid methyl ester
468rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzonitrile
469rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-N-(2,2,2-triptorelin)benzosulfimide
470rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-N-(3,3,3,cryptochromes)benzosulfimide
471rat-TRANS-1,2-4-(rat-TRANS-(1,2)-4-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
472rat-TRANS-1,2-4-(rat-TRANS-(1,2)-4-methyl-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide

473rat-TRANS-1,2-4-(rat-TRANS-(1,2)-6-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
474rat-TRANS-1,2-4-(rat-TRANS-(1,2)-6-fluoro-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
475rat-TRANS-1,2-4-(rat-TRANS-(1,2)-6-methyl-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
476rat-TRANS-1,2-4-(rat-TRANS-(1,2)-7-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
477TRANS-1S,2S-4-(TRANS-(1S,2S)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)-3-perbenzoate
478rat-CIS-1,2-4-[(1R,2S)-1-(2-chloro-4-nitrophenoxy)indan-2-yl]morpholine
479TRANS-1S,2S-3'R4-[(1S,2S)-2-((R)-3-aminopiperidin-1-yl-4,6-dichloride-1 yloxy]-3-perbenzoate
480TRANS-1S,2S-3'R4-[(1S,2S)-2-((R)-3-aminopiperidin-1-yl-4,6-ehleringer-1 yloxy]benzosulfimide
481TRANS-1S,2S-3'R-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-ylamino]-N,N-dimethylbenzenesulfonamide
482TRANS-1S,2S-3'R-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-intoximeter]-3-perbenzoate
483TRANS-1S,2S-4-[(1S12S)-4,6-dichloro-2-(1,1-dioxo-lambda-thiomorpholine-4-yl)indan-1-yloxy]benzosulfimide

4-[4-((4S,5S)-1,3-dichloro-5-pyrrolidin-1-yl-4,5,6,7-
484TRANS-1S,2S-4-[(1S,2S)-4,6-dichloro-2-(4,4-deformability-1-yl)indan-1-yloxy]benzosulfimide
485TRANS-1S,2S-4-[(1S,2S)-4,6-dichloro-2-(4-methylpiperazin-1-yl)indan-1-yloxy]-3-perbenzoate
486rat-TRANS-1,2-4-[1-(3-chloropyridin-4-yloxy)indan-2-ylmethyl]morpholine
487rat-TRANS-1,2-4-[1-(4-methysulfonylmethane)indan-2-ylmethyl]morpholine
488 rat-TRANS-1,2-4-[2,3-dimethyl-4-(rat-TRANS-(1I2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
489TRANS-1S,2S-4-[2-fluoro-5-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethylisoxazole
490rat-TRANS-1,2-4-[3-chloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
491TRANS-1S,2S-4-[3-chloro-4-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
492TRANS-1S,2S-4-[3-chloro-4-(TRANS-(1S,2S)-6-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
493TRANS-1S,2S-4-[3-chloro-4-(TRANS-(1S,2S)-6-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
494rat-TRANS-1,2-4-[3-fluoro-4-(-2-methyl-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
495rat-TRANS-1,2-

tetrahydrobenzo[C]thiophene-4-yloxy)-3-forfinal]for 3,5-dimethyl-4H-[1,2,4]triazole
496rat-TRANS-4,5-4-[4-(1,3-dichloro-5-pyrrolidin-1-yl-4,5,6,7-tetrahydrobenzo[C]thiophene-4-yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
497rat-TRANS-1,2-4-[4-(rat-TRANS-(1,2)-3,3-dimethyl-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
498rat-TRANS-1,2-4-[4-(rat-TRANS-(1,2)-5,6-dichloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
499TRANS-1S,2S-4-[4-(TRANS-(1S,2S)-4,6-dichloro-2-pyrrolidin-1-Ilinden-1 yloxy)-3-forfinal]for 3,5-dimethyl-4H-[1,2,4]triazole
500TRANS-1S,2S-4-[4-(TRANS-(1S,2S)-4,6-dichloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
501TRANS-1S,2S-4-[4-(Proc. of the na-(1S,2S)-6-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)-3-forfinal]for 3,5-dimethyl-4H-[1,2,4]triazole
502TRANS-1S,2S-4-[4-(TRANS-(1S,2S)-6-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole
503TRANS-1S,2S-4-[5-fluoro-2-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethylisoxazole
504rat-TRANS-1,2-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]-1H-indole
505rat-TRANS-1,2-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]-2,6-dimethylbenzonitrile

506rat-TRANS-1,2-4-[rat-TRANS-(1,2)-1-(2-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]morpholine
507rat-TRANS-1,2-4-[rat-TRANS-(1,2)-1-(4-fluoro-2-isoxazol-5-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]morpholine
508rat-TRANS-1,2-4-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen--yl]morpholine
509rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2,3-diferential
510rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2-perbenzoate
511rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]for 3,5-dimethylbenzonitrile
512rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chloro-5-methoxy-benzonitrile
513rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorbenzoyl acid methyl ester
514rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorobenzonitrile
515rat-TRANS-1,2-3'R- 4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-perbenzoate

516rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzonitrile
517rat-TRANS-1,2-3'R-4'-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-biphenyl-4-carbonitrile
518rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate
519rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate
520rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2,3-dichloro-N,N-dimethylbenzenesulfonamide
521rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2-chlorobenzonitrile
522rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2-perbenzoate
523rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-3-chlorobenzonitrile
524rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide
525rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide
526rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-hydroxyethylpyrrolidine-1-yl)indan-1-yloxy]benzosulfimide

527rat-TRANS-1,2-3'R-4-[rat-TRANS-(1,2)-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]benzosulfimide
528rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2,3-diferential
52 rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2-chlorobenzonitrile
530rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2-perbenzoate
531rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorbenzoyl acid methyl ester
532rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorobenzonitrile
533rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-perbenzoate
534rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-nitrobenzonitrile
535rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzonitrile
536rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate
537rat-TRANS-1,2-3'S-4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide

538rat-TRANS-1,2-rat-3'-4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate
539rat-TRANS-1,2-rat-3'-4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-2,6-dimethylbenzonitrile
540rat-TRANS-1,2-rat-3'-4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-2-chlorobenzonitrile
541rat-TRANS-1,2-rat-3'-4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-3-chlorobenzonitrile
542rat-TRANS-1,2-rat-3'-4-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-is loxi]-2,3-dichlorobenzenesulfonate
543rat-TRANS-1,2-rat-3'-4-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]-3-chlorobenzonitrile
544rat-TRANS-1,2-rat-3'-4-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]benzamide
545rat-TRANS-1,2-4-[rat-TRANS-(1I2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate
546rat-TRANS-1,2-4-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-2-chlorobenzonitrile
547rat-TRANS-1,2-4-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-3-chlorobenzonitrile
548rat-TRANS-1,2-4-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]benzamide

549rat-TRANS-1,2-4-[rat-TRANS-(1,2)-4,6-dichloro-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]morpholine
550TRANS-1S,2S-3'R-4-[TRANS-(1S,2S)-2-((R)-3-aminopiperidin-1-yl)-4,6-dichloride-1 yloxy]-2,3-dichlorobenzenesulfonate
551TRANS-1S,2S-3'R-4-[TRANS-(1S,2S)-2-((R)-3-aminopiperidin-1-yl)-4,6-dichloride-1 yloxy]-3-perbenzoate
552TRANS-1S,2S-3'R-4-[TRANS-(1S,2S)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzosulfimide
553TRANS-1S,2S-3'R-4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-fermenting acid methyl ester

554TRANS-1S,2S-3'R-4-[TRANS-(1S,2SH,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-perbenzoate
555TRANS-1S,2S-3'S-4-[TRANS-(1S,2S)-4,6-dichloro-2-((S)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-perbenzoate
556TRANS-1S,2S4-[TRANS-(1S,2S)-4,6-dichloro-2-(4-methyl-[1,4]diazepan-1-yl)indan-1-yloxy]-3-torbenson the Rhyl
557TRANS-1S,2S-3'R-4-[TRANS-(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-perbenzoate
558TRANS-1S,2S-3'R-4-{3-chloro-4-[TRANS-(1S,2S)-6-chloro-2-((R)-3-ftorpirimidinu-1-yl)indan-1-yloxy]phenyl} - for 3,5-dimethyl-4H-[1,2,4]triazole
559TRANS-1S,2S-3'S-4-{3-chloro-4-[TRANS-(1S,2S)-6-chloro-2-((S)-3-ftorpirimidinu-1-yl)indan-1-yloxy]phenyl} - for 3,5-dimethyl-4H-[1,2,4]triazole
560TRANS-1S,2S-3'R-4-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-forfinal}morpholine-3,5-dione
561TRANS-1S,2S-3'R-4-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-ftorpirimidinu-1-yl)indan-1-yloxy]phenyl} - for 3,5-dimethyl-4H-[1,2,4]triazole
562TRANS-1S,2S-2'S-4-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((S)-2-methoxypiperidine-1-yl)indan-1-yloxy]phenyl} - for 3,5-dimethyl-4H-[1,2,4]triazole
563TRANS-1S,2S-3'R-4-{4-[TRANS-(1S,2S)-6-chloro-2-((R)-3-forperiod the n-1-yl)indan-1-yloxy]-3-forfinal}for 3,5-dimethyl-4H-

[1,2,4]triazole
564TRANS-1S,2S4-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]indan-2-yl}morpholine
565TRANS-1S,2S4-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fervency]indan-2-yl}thiomorpholine 1,1-dioxide
566TRANS-1S,2S-4-{TRANS-(1S,2S)-6-chloro-1-[2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}morpholine
567TRANS-1S,2S-4-{TRANS-(1S,2S)-6-chloro-1-[2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}thiomorpholine 1,1-dioxide
568rat-TRANS-1,2-5-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)-1,3-dimethyl-1,3-dihydroindol-2-he
569rat-TRANS-1,2-5-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)naphthalene-2-ylamine
570 rat-TRANS-1,2-5-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline
571rat-TRANS-1,2-5-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-3H-isobenzofuran-1-he
572rat-TRANS-1,2-5-(rat-TRANS-(1,2)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)-2-methylbenzothiazol
573rat-TRANS-1,2-5,7-dimethyl-8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline

574TRANS-1S,2S-3'R-5-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3,4-dihydro-1H-quinoline-2-he
575TRANS-1S,2S-5-[5-fluoro-2-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-1H-pyrazole
576rat-TRANS-1,2-5-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]-2-methylbenzothiazol
577rat-TRANS-1,2- 5-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]benzo[1,3]oxalyl-2-one)
578rat-TRANS-1,2-3'R-5-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzo[1,3]oxalyl-2-he
579rat-TRANS-1,2-3'R-5-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzo[1,3]oxalyl-2-he
580rat-TRANS-1,2-3S-5-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzo[1,3]oxalyl-2-he
581TRANS-1S,2S-diastereoisomer 15-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-1-metalocherepitsya[3,4-b]pyrrol
582TRANS-1S,2S-diastereoisomer 25-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-1-metalocherepitsya[3,4-b]pyrrol
583rat-TRANS-1,2-3'R-5-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}oxazol-4-carboxylic acid ethyl ester

584rat-TRANS-1,2-3'S-5-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}oxazol-4-carboxylic acid ethyl ester
585rat-TRANS-1,2-5-chloro-2-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)benzonitrile
586rat-TRANS-1,2-5-fluoro-8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline
587rat-TRANS-1,2-6-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]-1H-indole
588rat-TRANS-1,2-7-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)isoquinoline
589rat-TRANS-1,2-7-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]isoquinoline
590rat-TRANS-1,2-7-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)indan-yl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin
591TRANS-1S,2S-8-((1S,2S)-2-azetidin-1-yl-4,6-dichloride-1 yloxy)-5-ftorhinolon
592TRANS-1S,2S-8-((1S,2S)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)-5-ftorhinolon
593TRANS-1S,2S-8-((1S,2S)-4,6-dichloro-2-pyrrolidin-1-Ilinden-1 yloxy)-5-ftorhinolon
594rat-TRANS-1,2-8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-

tetrahydronaphthalen-1 yloxy)quinoline-2-carbonitrile
595rat-TRANS-1,2-8-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)quinoline
596rat-TRANS-1,2-3'S-8-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]quinoline-2-carbonitrile
597rat-TRANS-1,2-benzyl[1-(4-methysulfonylmethane)indan-2-yl]amine
598rat-TRANS-1,2-rat-3'-C-(1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}pyrrolidin-3-yl)methylamine
599rat-TRANS-1,2-C-(1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-4-yl)methylamine
600rat-TRANS-1,2-rat-3'-C-(1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}pyrrolidin-3-yl)methylamine
601rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(1H-indol-4-yloxy)indan-2-yl]pyrrolidin-3-yl}methylamine
602rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(2,4-divergence)indan-2-yl]pyrrolidin-3-yl}methylamine
603rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)indan-2-yl]piperidine-4-yl}methylamine
604rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]piperidine-4-yl}methylamine
605 rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine

606rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)indan-2-yl]piperidine-4-yl}methylamine
607rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine
608rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(2-methylbenzothiazol-5-yloxy)indan-2-yl]pyrrolidin-3-yl}methylamine
609rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]piperidine-4-yl}methylamine
610rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine
611rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(3-chloro-2-methylphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine
612rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)indan-2-yl]piperidine-4-yl}methylamine
613rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine
614rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(3-ethoxyphenoxy)indan-2-yl]piperidine-4-yl}methylamine
615rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(3-ethoxyphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine
616rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]piperidine-4-yl}methylamine

617rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]pyrrolidin-3-yl}methylamine
618rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]pyrrolidin-3-yl}methylamine
619rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-4-yl}methylamine
620rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(benzo[1,3]dioxol-5-yloxy)indan-2-yl]piperidine-4-yl}methylamine
621rat-TRANS-1,2-rat-3'-C-{1-[rat-TRANS-(1,2)-1-(benzo[1,3]dioxol-5-yloxy)indan-2-yl]pyrrolidin-3-yl}methylamine
622rat-TRANS-1,2-C-{1-[rat-TRANS-(1,2)-1-(quinoline-4-yloxy)indan-2-yl]piperidine-4-yl}methylamine
623rat-TRANS-1,2-cyclopentyl-[1-(4-methysulfonylmethane)indan-2-yl]amine
624rat-TRANS-1,2-cyclopropylmethyl-[1-(4-methysulfonylmethane)indan-2-yl]amine
625rat-TRANS-1,2-diethyl-[rat-TRANS-(1,2)-1-(2-methylbenzothiazol-5-yloxy)indan-2-yl]amine
626rat-TRANS-1,2-diethyl-[rat-TRANS-(1,2)-1-(3-piperazine-1-yl is enocsi)indan-2-yl]amine
627rat-TRANS-1,2-diethyl-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]amine

628rat-TRANS-1,2-diethyl-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}Amin
629rat-TRANS-1,2-methyl-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]piperidine-4-ylamine
630rat-TRANS-1,2-methyl-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-4-ylamine
631TRANS-1S,2S-3'R-N-(3-{TRANS-(1S,2S)-2-[(R)-3-(2-foretelling)piperidine-1-yl]indan-1-yloxy}phenyl)-ndimethylacetamide
632TRANS-1S,2S-3'R-N-(3-{TRANS-(1S,2S)-2-[(R)-3-(3,3,3-triptoreline)piperidine-1-yl]indan-1-yloxy}-phenyl)ndimethylacetamide
633rat-TRANS-1,2-N,N-diethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzamide
634 rat-TRANS-1,2-N,N-dimethyl-2-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
635rat-TRANS-1,2-N-[2-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
636rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-2-azepan-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
637rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)phenyl]ndimethylacetamide
638rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-2-dimethylaminoethyl-1-

yloxy)phenyl]ndimethylacetamide
639rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-2-piperazine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
640rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzyl]ndimethylacetamide
641rat-TRANS-1,2- N-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
642rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-2-thiomorpholine-4-Ilinden-1 yloxy)phenyl]ndimethylacetamide
643rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-2-thiomorpholine-4-Ilinden-1 yloxy)phenyl]ndimethylacetamide
644rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4,6-dichloro-2- [1,4]diazepan-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
645rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4,6-dichloro-2-dimethylaminoethyl-1 yloxy)phenyl]ndimethylacetamide
646rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4,6-dichloro-2-morpholine-4-Ilinden-1 yloxy)phenyl]ndimethylacetamide
647rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
648rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4,6-dichloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
649 rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4-chloro-2-pyrrolidin-1-Ilinden-1-

yloxy)phenyl]ndimethylacetamide
650rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4-chloro-6-fluoro-2-piperazine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
651rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4-chloro-6-fluoro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
652rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4-fluoro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
653rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-4-methyl-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
654rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-5,7-dichloro-2-dimethylaminoethyl-1 yloxy)phenyl]ndimethylacetamide
655rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-5-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
656rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-5-fluoro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
657rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-6-chloro-2-piperazine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
658rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-6-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
659rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-6-chloro-4-fluoro-2-piperazine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
660rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-6-chloro-4-fluoro-2-pyrrolidin-1-

Ilinden-1 yloxy)phenyl]ndimethylacetamide
661rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-6-tluoro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
662rat-TRANS-1,2-N-[3-(rat-TRANS-(1,2)-7-chloro-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
663TRANS-1S,2SN-[3-(TRANS-(1S,2S)-2-piperidine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
664TRANS-1S,2SN-[3-(TRANS-(1S,2S)-4,6-dichloro-2-3,8-diazabicyclo[3.2.1]Oct-3-Ilinden-1 yloxy)phenyl]ndimethylacetamide
665TRANS-1S,2SN-[3-(TRANS-(1S,2S)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
666rat-TRANS-1,2-N-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide
667rat-TRANS-1,2-N-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-pyridine-2-yl]ndimethylacetamide
668rat-TRANS-1,2-N-[6-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-pyridine-2-yl]ndimethylacetamide
669rat-TRANS-1,2-N-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)indan-2-yl]-N,N',N'-trimethylpropane-1,3-diamine
670rat-TRANS-1,2-3'R-N-[rat-TRANS-(1,2)-3-(R)-2-[1,3']bipirimidiny-1'-Ilinden-1 yloxy)phenyl]ndimethylacetamide

671TRANS-1S,2S-N-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-N,N',N'-trimethyl-ethane-1,2-diamine
672TRANS-1S,2S-N-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-N,N',N'-trimethylpropane-1,3-diamine
673TRANS-1S,2S-3'R-N-{3-[(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-4-forfinal}-N-methyl-methanesulfonamide
674rat-TRANS-1,2-N-{3-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]phenyl}ndimethylacetamide
675rat-TRANS-1,2-3'R-N-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-4-propylphenyl}ndimethylacetamide
676rat-TRANS-1,2-3'R-N-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}ndimethylacetamide
677rat-TRANS-1,2-3'R-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-4-chloro-6-Florinda-1 yloxy]phenyl}ndimethylacetamide
678rat-TRANS-1,2-3'RN-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-6-chloro-4-Florinda-1 yloxy]phenyl}ndimethylacetamide
679rat-TRANS-1,2-3'RN-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
680rat-TRANS-1,2-3'RN-{3-[rat-TRANS-(1,2)-2-((R)-3-hydroxyethylpyrrolidine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide

681rat-TRANS-1,2-3'RN-{3-[rat-TRANS-(1,2)-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
682rat-TRANS-1,2-3'R-N-{3-[rat-TRANS-(1,2)-2-((R)-3-ethoxypyrrolidine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
683rat-TRANS-1,2-3 S-N-{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-4-propylphenyl}ndimethylacetamide
684rat-TRANS-1,2-3 S-N-{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tet is Aeronavale-1 yloxy]phenyl}ndimethylacetamide
685rat-TRANS-1,2-3S-N-{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
686rat-TRANS-1,2-rat-3'-N-{3-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
687rat-TRANS-1,2-rat-3'-N-{3-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
688rat-TRANS-1,2-N-{3-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
689rat-TRANS-1,2-N-{3-[rat-TRANS-(1,2)-4,6-dichloro-2-(hexahydrofuro[3,4-C]pyrrol-2-yl)indan-1-yloxy]phenyl}ndimethylacetamide
690TRANS-1S,2S-3'R-N-{3-[TRANS-(1S,2S)-2-((R)-3-aminopiperidin-1-yl)-4,6-dichloride-1 yloxy]phenyl}ndimethylacetamide
691TRANS-1S,2S-3'R-N-{3-[TRANS-(1S,2S)-2-((R)-3-aminopiperidin-1-yl)indan-

1 yloxy]phenyl}ndimethylacetamide
692TRANS-1S,2S-3'R-N-{3-[TRANS-(1S,2S)-2-((R)-3-dimethylpiperidin-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
693TRANS-1S,2S-rat-3'-N-{3-[TRANS-(1S,2S)-2-(3-amino-3-propylpiperidine-1-yl)-4,6-dichloride-1 yloxy]phenyl}ndimethylacetamide
694TRANS-1S,2S-3'R-N-{3-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-dimethylpiperidin-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
695TRANS-1S,2S-3'R-N-{3-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxyethylpyrrolidine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
696TRANS-1S,2S-3'R-N-{3-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
697TRANS-1S,2SN-{3-[TRANS-(1S,2S)-4,6-dichloro-2-(4-methylpiperazin-1-yl)indan-1-yloxy]phenyl}ndimethylacetamide
698TRANS-1S,2S-3'R-N-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroc pirrolidone-1-yl)indan-1-yloxy]phenyl}-N-methylmethanesulfonamide
699TRANS-1S,2S-3'R-N-{4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-ylsulphonyl]phenyl}ndimethylacetamide
700rat-TRANS-1,2-N-ethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide
701rat-TRANS-1,2-tert-butyl[1-(4-methysulfonylmethane)indan-2-yl]amine

702TRANS-1S,2S-2-{[TRANS-(1S,2S)-4,6-dichloro-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-methyl-amino}-ethanol
703rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-cyclopropylamino-indan-1-yloxy)-3-fluoro-benzosulfimide
704TRANS-1S,2S-2-({TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fluoro-phenoxy]-indan-2-yl}-methyl-amino)-ethanol
705rat-TRANS-1,2-cyclopentylmethyl-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-amine
706rat-CIS-1,2-cyclobutyl-[rat-CIS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-amine
707TRANS-1S,2S-(4-methanesulfonyl-phenyl)-((1S,2S)-2-pyrrolidin-1-yl indan-1-yl)-amine
708rat-TRANS-1,2-cyclobutyl-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-amine
709rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-cyclobutylamine-indan-1-yloxy)-3-fluoro-benzosulfimide
710TRANS-1S,2S-3'R-2-chloro-4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-benzoic acid TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-silt ether
711rat-TRANS-1,2-cycloheptyl-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-amine
712TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(2-ethyl-4-methyl-

imidazol-1-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
713rat-TRANS-1,2-4-(rat-TRANS-(1,2)-2-cycloheptylamine-indan-1-yloxy)-3-fluoro-benzosulfimide
714TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(2-isopropyl-4-methyl-imidazol-1-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
715TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3-isopropyl-5-methyl-[1,2,4]triazole-4-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
716TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3-ethyl-5-isopropyl-[1,2,4]triazole-4-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
717rat-TRANS-1,2-cyclobutylmethyl-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-amine 4-[rat-TRANS-(1,2)-2-
718rat-TRANS-1,2-cyclobutylmethyl-amino)-indan-1-yloxy]-3-fluoro-benzosulfimide
719TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-1-[4-(2-ethyl-4-meta the-imidazol-1-yl)-phenoxy]-4-fluoro-indan-2-yl}-pyrrolidin-3-ol
720TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-4-fluoro-1-[4-(2-isopropyl-4-methyl-imidazol-1-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
721TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-4-fluoro-1-[4-(3-isopropyl-5-methyl-[1,2,4]triazole-4-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol

722TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-1-[4-(3-ethyl-5-isopropyl-[1,2,4]triazole-4-yl)-phenoxy]-4-fluoro-indan-2-yl}-pyrrolidin-3-ol
723rat-TRANS-1,2-(1-ethyl-propyl)-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-amine
724TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-1-[4-(4-tert-butyl-2-isopropyl-imidazol-1-yl)-phenoxy]-6-chloro-4-fluoro-indan-2-yl}-pyrrolidin-3-ol
725TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[5-(2-ethyl-4-methyl-imidazol-1-yl)-2-fluoro-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
726TRANS-1S,2S- N-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,3]triazole-4-yl-2-fluoro-phenoxy]-indan-2-yl}-N,N',N'-trimethyl-ethane-1,2-diamine
727TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(2,4-dimethyl-imidazol-1-yl)-2-fluoro-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
728TRANS-1S,2S-3'R-(R)-1-[TRANS-(1S,2S)-4,6-dichloro-1-(4-imidazol-1-yl-phenoxy)-indan-2-yl]-pyrrolidin-3-ol
729TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-1-[4-(4-tert-butyl-2-methyl-imidazol-1-yl)-2-fluoro-phenoxy]-4,6-dichloro-indan-2-yl}-pyrrolidin-3-ol
730rat-TRANS-1,2-cyclopentyl-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-methyl-amine

731TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(2-methanesulfonyl-imidazol-1-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
732TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(2-isopropyl-imidazol-1-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
733TRANS-1S,2S-3'R-3-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-phenyl}-5-methyl-3H-[1,3,4]oxadiazol-2-he
734rat-TRANS-1,2-cyclobutyl-[rat-TRANS-(1,2)-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-methyl-amine
735TRANS-1S,2S-3'R-3-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-phenyl}-3H-[1,3,4]oxadiazol-2-he
736TRANS-1S,2S-3'R-2-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-phenyl}-4-ethyl-2,4-dihydro-[1,2,4]triazole-3-one
737TRANS-1S,2S-3'R-2-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-phenyl}-4-ethyl-5-methyl-2,4-dihydro-[1,2,4]triazole-3-one
738TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-6-chloro-1-[4-(2,4-dimethyl-imidazol-1-yl)-2-fluoro-phenoxy]-4-fluoro-indan-2-yl}-pyrrolidin-3-ol
739TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[2-fluoro-4-(2-metasul who were radioactive-imidazol-1-yl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol

740TRANS-1S,2S-3'R-1-{4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-3-fluoro-phenyl}-1H-imidazole-2-carboxylic acid methyl ester
741TRANS-1S,2S-3'R-4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-3-fluoro-benzosulfimide
742TRANS-1S,2S-3'R-(R)-[TRANS-(1S,2S)-4,6-dichloro-1-[4-(4-methyl-piperazine-1-sulfonyl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
743TRANS-1S,2S-3'R-4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-benzosulfimide
744TRANS-1S,2S-3'R-(R)-1-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(morpholine-4-sulfonyl)-phenoxy]-indan-2-yl}-pyrrolidin-3-ol
745TRANS-1S,2S-3'R-1-{5-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxy-pyrrolidin-1-yl)-indan-1-yloxy]-2-fluoro-phenyl}-3-methyl-3-dihydro-imidazol-2-he
746TRANS-1S,2S- cyclopentyl-{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fluoro-phenoxy]-indan-2-yl}-amine
747TRANS-1S,2S-cyclopentyl-[TRANS-(1S,2S)-4,6-dichloro-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-amine
748TRANS-1S,2S-4-(TRANS-(1S,2S)-4,6-dichloro-2-cyclopentylamine-indan-1-yloxy)-3-fluoro-benzosulfimide
749TRANS-1S,2S-{TRANS-(1S,2S)-6-chloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-fluoro-phenoxy]-4-fluoro-indan-2-yl}-cyclopentyl-Amin

td align="justify"> TRANS-1S,2S-
750TRANS-1S,2S-4-(TRANS-(1S,2S)-6-chloro-2-cyclopentylamine-4-fluoro-indan-1-yloxy)-3-fluoro-benzosulfimide
751TRANS-1S,2S-[TRANS-(1S,2S)-6-chloro-4-fluoro-1-(4-methanesulfonyl-phenoxy)-indan-2-yl]-cyclopentyl-Amin
752TRANS-1S,2S-1-[4-(TRANS-(1S,2S)-6-chloro-2-cyclopentylamine-4-fluoro-indan-1-yloxy)-3-fluoro-phenyl]-pyrrolidin-2,5-dione
7533-[4-(TRANS-(1S,2S)-6-chloro-2-cyclopentylamine-4-fluoro-indan-1-yloxy)-3-fluoro-phenyl]-imidazolidin-2,4-dione
754TRANS-1S,2S-{TRANS-(1S,2S)-6-chloro-4-fluoro-1-[2-fluoro-4-(2-methanesulfonyl-imidazol-1-yl)-phenoxy]-indan-2-yl}-cyclopentyl-Amin
755TRANS-1S,2S-1-[4-(TRANS-(1S,2S)-6-chloro-2-cyclopentylamine-4-Florinda-1 yloxy)-3-fluoro-phenyl]-3-methyl-1,3-dihydro-imidazol-2-he
756TRANS-1S,2S-1-[3-(TRANS-(1S,2S)-6-chloro-2-cyclopentylamine-4-fluoro-indan-1-yloxy)-4-fluoro-phenyl]-3-methyl-1,3-dihydro-imidazol-2-he

and their pharmaceutically acceptable salts.

Due to their properties of inhibiting NHE compounds of formula I can be used for the prevention and treatment of diseases caused by activation or activated NHE NHE, and diseases, a secondary cause of which is associated with NHE defeat. The compounds of formula I can also be used for the treatment and prevention of diseases with only partial inhibition of NHE, for example, through the use of smaller doses. At the mention of further compounds of the formula I or compounds according to the invention in their number is always included their pharmaceutically acceptable salts, even without a direct reference.

Accordingly, the present invention additionally proposed the use of compounds of formula I for the prevention and treatment of acute and chronic diseases in both animals and humans.

Due to its pharmacological actions of the compounds of formula I are particularly applicable in order to achieve improved breathing pulse. Thus, they can be used to treat breathing disorders, for example, which can occur when the following clinical conditions and diseases, including: impaired Central respiratory pulse (e.g., apnea during sleep, sudden death of an infant during sleep, postoperative hypoxia), muscle respiratory disorders, respiratory disorders due to long-term ventilation, respiratory disorders associated with adaptation to high altitude above sea level, obstructive and mixed apnea during sleep-related breathing disorders during sleep, symptoms of hypoventilation during sleep, the syndrome of resistance to upper respiratory ways, acute and chronic lung diseases associated with hypoxia and hypercapnia.

In addition, the proposed connections improve the muscle tone of the upper respiratory tract and, therefore, inhibit snoring. Thus, the above-mentioned compounds applicable in particular for the prevention and treatment of apnea during sleep, syndrome of resistance of the upper respiratory tract, muscular breathing disorders and for the prevention and treatment of snore.

Accordingly, preferred is also a combination of an NHE inhibitor having the formula I, and carbonic anhydrase inhibitor (eg, acetazolamide), which causes metabolic acidosis and, therefore, he improves respiratory activity, due to what can be achieved with enhanced activity and reduced use of active ingredient.

Due to its inhibitory effect against NHE3 compounds according to the invention retain the cellular energy reserves, which are being rapidly depleted during toxic and pathogenic States that leads to the damage or cell death. Accordingly, under the influence of NHE3 inhibitors temporarily stops high energy absorption of sodium with the consumption of adenosine triphosphate (ATP) in the proximal tubule, and therefore, the cell can survive acute pathogenic, ischemic or toxic condition. Thus, the compounds applicable, for example, as pharmaceuticals for the treatment of ischemic conditions, particularly ischemic lesions such as acute renal failure

In addition, connections are also applicable for the treatment of chronic renal diseases and varieties of jade, the actuator is related to chronic renal failure due to increased excretion of protein. Accordingly, the compounds of formula I is applicable for the manufacture of a medicinal product for the treatment of long-term consequences of diabetes, diabetic nephropathy and chronic renal diseases, in particular of all renal inflammation, which is accompanied by increased excretion of protein/albumin.

It was found that the compounds according to the invention have an inhibiting and retarding effect on glucose absorption and thus is able to reduce the glucose content in the blood, and also have a favorable effect on additional factors of metabolism, such as triglycerides. Due to this, the compounds according to the invention can advantageously be used for the prevention and treatment of metabolic syndrome, diabetes and various forms of hyperlipidemia.

It was found that the compounds according to the invention have a mild laxative effect and, accordingly, can also advantageously be used as laxatives or at risk of constipation and for the prevention and treatment of constipation.

Compounds according to the invention can advantageously be used for the prevention and treatment of acute and chronic intestinal diseases caused by, for example, ischemic conditions in the gut and(or) subsequent reperfusion or inflammatory conditions, and I had the thoughts. Such complications can arise, for example, due to insufficient peristalsis of the intestines, is often observed, for example, after surgery, concomitant constipation or caused significantly weakened the activity of the intestine.

Using the compounds according to the invention can prevent the formation of gallstones.

In General, the NHE inhibitors described in the invention can be combined with other compounds that also regulate intracellular pH, which include inhibitors of enzymes from the group of carbonic anhydrase inhibitors systems vectors alkaline ions, such as superelastic sodium bicarbonate (NBC) or metrizability chloro-bicarbonate exchanger (NCBE) and with other NHE inhibitors with inhibitory effect on NHE other subspecies, as constituent parts due to the ability to enhance or modulate pharmacologically significant regulatory pH effects described in the invention of NHE inhibitors.

Because sodium ion-proton exchange is greatly enhanced with primary hypertension, the compounds of formula I is applicable for the prevention and treatment of high blood pressure and cardiovascular disease. Accordingly, they can be used separately or in combination with an appropriate medium spans the PTO to treat high blood pressure and cardiovascular disease. So, for example, compounds having formula I may be combined with one or more diuretics action, such action thiazide, loop diuretics, aldosterone antagonists or pseudoaldosteronism, such as hydrochlorothiazide, indapamide, polythiazide, furosemide, piretanide, torasemide, bumetanide, amiloride, triamterene, spironolactone or aleron. In addition, the NHE inhibitors according to the present invention can be used in combination with calcium antagonists such as verapamil, diltiazem, amlodipine or nifedipine, and ACE inhibitors, such as ramipril, enalapril, lisinopril, fosinopril or captopril. Additional useful combination as component parts can also include beta-blockers, such as metoprolol, albuterol etc. antagonists angiotensin receptor and its variants, such as losartan, irbesartan, valsartan, omapatrilat, gemopatrilat, endothelin antagonists, renin inhibitors, adenosine agonists of the receptor, inhibitors and activators of potassium channels, such as glibenclamide, glimepiride, diazoxide, cromakalim, Minoxidil and derivatives thereof, activators of mitochondrial ATP-sensitive potassium channel (channel mitok(ATP)), additional inhibitors of potassium channels, such as Kv1,5, etc.

The NHE inhibitors additionally primenenija treat non-insulin dependent diabetes (NIDDM), for example, if a limited resistance to insulin. Accordingly, it can be useful to improve antidiabetic efficacy and quality of action of the compounds according to the invention in combination with biguanides, so Metformin, with antidiabetic sulfonylurea, such as gliburid, glimepiride, tolbutamide, etc. with a glucosidase inhibitor, a PPAR agonist such as rosiglitazone, pioglitazone, etc. with insulin, used in various forms, with inhibitor DB4 with insulin sensitizer or meglitinides.

Thus, the above-mentioned compounds are effectively used alone or in combination with other drugs or active ingredients for the manufacture of a medicinal product for treatment or prevention of disorders of the respiratory pulse, respiratory disorders, respiratory disorders during sleep, apnea during sleep, snore, acute and chronic renal disease, acute renal failure and chronic renal failure, disorders of bowel function, high blood pressure, primary arterial hypertension.

Compounds according to the invention is additionally applicable for the treatment of cystic fibrosis (mucoviscidosis). It is proved that a lack of protein CFTR (cystic fibrosis transmembrane regulator PR is Vedemosti, English - Cystic Fibrosis Transmembrane conductance Regulator) in patients with cystic fibrosis activates NHE3, which leads to excessive absorption of salt and water in the intestine (gut, gall bladder, pancreas), seminal fluid, the upper respiratory tract and lungs. As a result, drying of the feces (bowel obstruction, intestinal secretions and lung fluid with the formation of a viscoelastic mucus in the lungs, which causes frequent infections of the respiratory tract and ultimately to the deterioration of lung function, which is an important cause of mortality. In addition, as a result of excessive activation of NHE3 increases the pH in the digestive tract, which leads to poor digestion (impaired digestion) and becomes more acidic pH of the pulmonary fluid, which contributes to bacterial infections (particularly infections Pseudomonas aeruginosa). Connections can be applied systemically (orally, intramuscularly, intravenously, subcutaneously) or in the form of inhalation for the treatment of symptoms of the respiratory tract and lungs.

Compounds have mucolytic capacity in acute and chronic diseases and respiratory tract infections by inhibiting the absorption of salt and water in the upper respiratory tract and lungs, resulting in the liquefaction of mucus. This action has healing what voistom in acute and chronic viral, bacterial and fungal infections of the upper respiratory tract and lungs and chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease.

The invention additionally relates to the use of the compounds and their pharmaceutically acceptable salts of formula I as medicinal products and medicinal product containing the compounds or their pharmaceutically acceptable salts of formula I.

The invention additionally relates to the use of these compounds or their pharmaceutically acceptable salts for the treatment or prevention of disease by complete or partial inhibition of the exchange of Na+/H+by NHE3.

Thus, according to one additional invention proposed the use of the compounds and / or pharmaceutically acceptable salts of formula I according to one or more items 1-15 alone or in combination with other drugs or active ingredients for the manufacture of a medicinal product for treatment or prevention of disorders of the respiratory pulse, respiratory disorders, respiratory disorders during sleep, apnea during sleep, snore, cystic fibrosis, diseases of the upper and lower respiratory tract, which is accompanied by the formation of viscous mucus, acute and chronic the definition of renal diseases, acute renal failure and chronic renal failure, disorders of bowel function, constipation, high blood pressure, essential hypertension, cardiovascular diseases, Central nervous system diseases, diseases due to increased excitability of the CNS, epilepsy, and Central-induced spasms or anxiety, depression and psychosis, ischemic States of the peripheral or Central nervous system or cerebral circulatory disorders, degenerative diseases of the Central nervous system, memory loss, dementia and Alzheimer's disease, and acute and chronic lesions and diseases of peripheral organs or limbs caused by phenomena ischemia or reperfusion, atherosclerosis, lipid metabolism disorders, various forms hyperlipidemia, thrombosis, diabetes, disorders of the biliary functions, invasion, parasites, diseases caused by endothelial dysfunction, protozoal diseases, malaria, States of shock or diabetes and long-term consequences of diabetes or diseases, primary or secondary cause of which is the proliferation of cells, for conservation and preservation of transplants for surgical procedures, for use in surgical operations and organ transplants and to preserve health and prolong what isni.

The invention also relates to medicinal products for human, animal or plant protection, containing the effective amount of the compound or its pharmaceutically acceptable salt of formula I, and also for medicinal products for human, animal or plant protection, containing the effective amount of the compound or its pharmaceutically acceptable salt of formula I, alone or in combination with one or more other active medicinal ingredients or drugs.

Drugs, which contain the compound or its pharmaceutically acceptable salt of formula I may be administered, for example, oral, parenteral, intramuscular, intravenous, rectal, nasal, faringealna, by inhalation, subcutaneously, or in the form of a corresponding percutaneous dosage forms, while the preferred form of application depends on the corresponding manifestations of violations. In addition, the compounds of formula I can be used separately or with the pharmaceutical excipients in particular in the sphere of veterinary medicine and for crop protection. Medicinal preparations containing active ingredients and / or their pharmaceutically acceptable salts of formula I in General in amounts of from 0.01 mg to 1 g per standard dose.

Specialists in the art of famous napolnitel is, applicable for the desired pharmaceutical composition. In addition to solvents, gel-forming substances, suppositories, tablets and other carriers of active ingredients can be used, for example, oxidation inhibitors, dispersants, emulsifiers, antifoams, masking fragrances, conservatives, soljubilizatory or dyes.

In the case of forms for the oral administration of active compound is mixed with applicable for this purpose additives such as carriers, stabilizers or inert diluents, and conventional methods produce the appropriate dosage forms, such as tablets, coated tablets, hard gelatin capsules, aqueous, alcoholic or oily solutions. Examples of inert carriers which can be used are gum Arabic, deadburned magnesia, magnesium carbonate, potassium phosphate, lactose, glucose or starch, in particular corn starch. In addition, the drug can be manufactured in the form of both dry and wet granules. Examples of applicable oily carriers or solvents are vegetable or animal oils, such as sunflower oil or fat from the liver of fish.

In the case of subcutaneous, percutaneous or intravenous application of existing connections transform optionally in combination with commonly used for these purposes, substances and, such as solubilization, emulsifiers or more fillers, in solution, suspension or emulsion. Examples of applicable solubilization are water, saline solution or alcohols, for example ethanol, propanol, glycerol, as well as sugar solutions such as glucose or mannitol, or a mixture of the mentioned solvents.

As a pharmaceutical composition for use in the form of aerosols or liquids for spraying applicable, for example, solutions, suspensions or emulsions of the active ingredient of the formula I in a pharmaceutically acceptable solvent, such as, in particular, ethanol or water or a mixture of such solvents. If necessary, the composition may also contain other pharmaceutical excipients such as surfactants, emulsifiers and stabilizers and gas propellant. This product usually contains the active ingredient in a concentration of from about 0.1 to 10, in particular from about 0.3 to 3% by weight.

The dose of the applied active ingredient of formula I and the frequency of administration depend on the potency and duration of action of the compounds used; additionally also on the nature and severity of the disease and gender, age, weight and individual response of the patient.

The average daily dose of the compounds of formula I for a patient weighing about 75 CT,is at least 0.001 mg/kg, preferably 0.1 mg/kg and a maximum of 30 mg/kg, preferably 1 mg/kg of body weight. In acute conditions, for example immediately after suffering apnea at high altitude above sea level also may need a higher dose. In particular, may require the introduction of up to 300 mg/kg per day intravenously, for example, to a patient after a heart attack in intensive care. The daily dose may be divided into one or more, for example up to 4 single doses.

If the compounds of formula I contain one or more acidic or basic groups or one or more of the basic heterocyclic compounds, the invention also includes the corresponding physiologically or toxicologically acceptable salts, in particular pharmaceutically acceptable salts. Thus, the acid group of compounds of formula I, can be deprotoniruya, and they can be used, for example, in the form of salts of alkali metals, preferably sodium and potassium salts, or ammonium salts, such as salts using ammonia or organic amines or amino acids. The compounds of formula I containing at least one basic group can also be obtained in the form of their physiologically-tolerated salts of joining acids, such as the following: inorganic acids such as hydrochloric acid, sulfuric acid or phospho what Naya acid, or organic acids such as acetic acid, citric acid, tartaric acid, lactic acid, malonic acid, methanesulfonate, fumaric acid. Applicable salts accession acids, respectively, are salts of all pharmaceutically acceptable acids, such as halide, in particular chlorhydrate, lactates, sulfates, citrates, tartratami, acetates, phosphates, methylsulfonate, p-toluensulfonate, adipate, fumarate, gluconate, glutamate, glycerophosphate, maleate and pamoate (this group also corresponds to the physiologically acceptable anions); but also triptoreline.

In the present invention also include derivatives of compounds of formula I, for example, a solvate such as a hydrate and the addition products of alcohols, esters, prodrugs and other physiologically acceptable derivatives of compounds of formula I, and active metabolites of compounds of formula I. the invention also includes all crystal modifications of compounds of formula I.

Methods for obtaining compounds of formula I

The following describes the General methods applicable for producing compounds of General formula I. Accordingly, the compounds of formula I can be obtained by various chemical methods. Group and the radicals a, b, L, X, R1, R2, R3, R4 and R5, and the index of p, referred to in the following ways have the higher the value, unless they are in the nternet form is not given a different definition.

Reduction

GHUR - Liquid chromatography high-resolution

LC - Liquid chromatography

EAP - Time

THF - Tetrahydrofuran

TFA - Triperoxonane acid

FA - Formic acid

DMSO - dimethyl Sulfoxide

abs. Absolute

DMF - Dimethylformamide

AcN - Acetonitrile

CT Room temperature

min - Minutes

h - Hour(s)

HEE - Chemical ionization

ERIE - Electrospray ionization

DBA - Dibenzylideneacetone

Method And

For example, as shown in scheme A, the reaction begins with epoxides of the formula II, which after opening the epoxy ring by means of an amine of formula HNR3R4, initially provide the corresponding intermediate 1-amino 2-ol of formula III, which subsequently reacts Mitsunobu with aryl or heteroaryl compounds IN IT that one or more times can be substituted by R5. In this reaction it is preferable to use phenols. Alternatively, can also be used aryl or heteroaryl thiols B-SH or aryl - or heteroarylboronic acid-CO2N which one or more times can be substituted by R5, with the aim of obtaining relevant-S - or-CO2H - bridge derived. As is known, the reaction of Mitsunobu occur in the presence of a phosphine, such as esters of triphenylphosphite the new and azodicarboxylic acid, such as, for example, diisopropylcarbodiimide in inert solvents, such as acetonitrile, CH2Cl2or tetrahydrofuran. In the case of 1-amino-2 tins of formula III is the migration of amine residue NR3R4 in position 2 of the base structure (J. Org. Chem. 1991, 56, 670-672).

Scheme And

The synthesis of compounds of formula I by the inversion of Mitsunobu

in which L denotes a covalent bond to-C(=O)-, and X denotes O or

L denotes a covalent bond, and X represents S.

This method can be obtained a large number of compounds of the formula I, preferably those with both Deputy have mutual transconfiguration. If one of the radicals R3 and R4 amine substituent must be replaced by an additional functional group, such as, for example, the hydroxy-group or amino group, you must, when appropriate, to ensure the protection of such groups during the reaction of Mitsunobu. This can be done, for example, using trialkyl or triarylsulfonium groups in the case of groups HE or protective groups VOS in the case of amino groups. After completion of the reaction, Mitsunobu the protective group is then removed, for example, by treatment with hydrochloric acid or triperoxonane acid in order to obtain compounds of formula I. After removing the protective groups, these functional groups can be on the further modified, when appropriate, for example by alkylation with an alkylating agent or acylation subsequent recovery with the aim of further compounds I.

The source materials used in the scheme And such as the epoxides of formula II, AMI NHR3R4 and hydroxyaryl or hydroxyatrazine or tirinya derivatives are available on the market, known from the literature or can be easily synthesized by analogy with the compounds known from the literature. In the experimental section as the example shows several relevant schemes of synthesis of such materials.

Method In

In the scheme presented In one of the additional methods of preparing compounds of formula I.

Schema

The synthesis of compounds I by nucleophilic substitution in the aromatic nucleus

In this process, the compound 2-bromo-1-it formula IV, is introduced into reaction with amines having the formula R3-NH-R4, resulting in formation of the corresponding aminoketone V. Then the ketone group is reduced to 1-hydroxy group, resulting in the formation of intermediate compounds of formula VI. Accordingly, there can be obtained products VI as CIS - and transconfiguration with respect to the centers 1 and 2. Then we obtain the intermediate compounds of formula VI arriraw by nucleophilic substitution in the aroma of the strategic core of the aryl or heteroaryl compounds B-Y, in which one or such as, for example, sodium hydride or NaOH powder in an inert solvent, such as DMSO. Y, respectively, means applies a leaving group, such as, for example, fluoride, chromista or cryptometrics group. If the radicals R3 and R4 are substituted, for example amino groups or hydroxy groups, they should be protected, where appropriate, protecting groups with a stable base, such as, for example, alkyl - or aryl-substituted silyl group.

This method can also be used largely known or available on the market brometane IV, or they can be easily obtained from the corresponding ketones, for example, by the synthesized under standard conditions.

Way

One of the additional ways refers to those compounds of the formula I, in which the amino group NR3R4 attached through a carbon bridge in position 2, that is, when q in the General formula I is 1.

Scheme

The synthesis of compounds of formulas I through products such as foundations, manniche

In this case, the ketones of formula VII is introduced into reaction with acetals of preferably formamide dimethyl acetal of N,N-dimethylformamide to obtain relevant dimethylaminomethylene compounds of formula VIII. Dimethylaminopropan can be replaced by the next stage of the other amino groups with the aim of obtaining aminomethylbenzoic compounds of formula IX. This can be done, for example, by heating compounds of formula VIII in DMF in the presence of excess amine HNR3R4. In the subsequent recovery, for example, using sodium borohydride in methanol usually get a stereoisomeric mixture of aminoalcohols of formula X, which, after separation into individual components may, where appropriate, be allerban by analogy with the process illustrated in the diagram In order to obtain compounds of the formula I according to the invention.

Method D

In scheme D presents one of the additional methods of preparing compounds of formula I. 1-amino-2-indanol III and its analogues is introduced into the reaction in an inert solvent, such as THF in the presence of the applicable source of azides, such as, for example, diphenylphosphoryl (DPPA) in the reaction conditions, Mitsunobu. And in this case, the amine residue migrates from position 1 to position 2, as described in scheme A. Preferably, the formation of 1-azido-2-indanamine with TRANS-configuration, which is introduced into the reaction in situ immediately after adding an appropriate reducing agent, such as, for example, LiAlH4with the aim of obtaining diamines of General formula XI having the TRANS configuration. To obtain the compounds of formula I arriraw the compounds of formula XI, by palladium catalysis, for example, under the reaction conditions Buchwald, Izv the STN from the literature (J. Am. Chem. Soc. 1997, 8451-8458).

Scheme D

The synthesis of compounds I by the inversion of Mitsunobu and subsequent arilirovaniya

Method E

In scheme E presents one of the additional methods of preparing compounds of formula I. Esters I benzoic acid synthesized according to the scheme And hydrolyzing in a known manner with the aim of obtaining compounds of General formula VI. This is done, for example, in solvents, such as mixtures of acetone and water and using appropriate bases, such as sodium hydroxide. Then the compounds of formula VI, enter into reaction with the appropriate alkylating agents such as, for example, benzylbromide in solvents, such as THF in the presence of appropriate bases, such as sodium hydride. Compound I obtained in this way, affordable, when appropriate, for further processing.

Scheme E

The synthesis of compounds I by alkylation

in which L denotes alkylenes bridge connection.

If the compounds I contain additional functional groups, such as, for example, alcohols or amines, they can be additionally introduced into the reaction in a known manner, as shown in scheme F. the Relevant examples are the sequence of acylation, alkylation or allyouneedislove. This procedure is described in the experimental section on examples of implementation.

Scheme F

Optional additional compounds I

Method G

One additional method refers to those compounds of formula I in which one or two substituents R3 or R4 in the amino group NR3R4 is hydrogen, that is, R3=H or R3=R4=H in the General formula I.

Scheme G

The synthesis of compounds of formula I via palladium-catalyzed removal of the protective groups allylamino

During this process, with the use of nucleophiles, such as thiosalicylic acid or dimethylbarbituric acid in inert solvents such as CH2Cl2or THF, remove the protective group allylamino XI, which, for example, can be synthesized according to method A. the Catalyst reaction is Pd. Applicable Pd sources are, for example, Pd(PPh3)4or Pd(dba)2in the presence of stabilizing ligands, such as bis(diphenylphosphino)butane. In the case of billiluna (R3 = R4 = allyl) both allyl groups can be split using at least two equivalents of applicable nucleophile and prolonged reaction time. Compounds of General formula I, which are synthesized according to method G, is available for further education is otki, for example acylation or alkylation.

Examples of implementation

Mentioned in the following equivalents apply to the designation of quantity of the substance, unless expressly stated otherwise.

For analysis of examples of implementation of the following methods were used LC.

YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 5:95 (2.5 minutes); 1.3 ml/min, CT
MethodConditions
1 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 2:98 (1 min) to 95:5 (5,0 min) to 95:5 (6,25 min); 1.0 ml/min, CT
2 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 95:5 (0.5 min) to 5:95 (3,5 min) to 5:95 (4 min); 1.3 ml/min, CT
3 LC method:YMC Jsphere H80, 33*2,4 µ, 2O of + 0.1% FA:AcN + 0,08% FA 95:5 (0 min) to 5:95 (2.5 minutes) to 5:95 (3 min); 1.3 ml/min, CT
4 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 5:95 (2.5 minutes) to 5:95 (3 min); 1.3 ml/min, CT
5 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0,05% FA:AcN + 0.05% of FA 95:5 (0 min) to 5:95 (2.5 minutes); 1.0 ml/min, CT
6 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 5:95(0 min) to 95:5 (3.4 min) to 95:5 (4,4 min); 1.0 ml/min, CT
7 LC method:
8 LC method:Waters XBridge C18 4.6*50 mm; 2,5 µ, H2O + 0,1% FA:AcN + 0,08% FA 97:3 (0 min) to 40:60 (3.5 minutes) to 2:98 (4 min) to 2:98 (5 min) 97:3 (5,2 min) 97:3 (6,5 min); 1.3 ml/min, CT
9 LC method:Waters XBridge C18, 4,6*50, 2,5 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 95:5 (0,3 min) to 5:95 (3,5 min) to 5:95 (4 min); 1.7 ml/min, 40°C
10 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 5:95 (2.5 minutes) to 95:5; 1.3 ml/min, CT
11 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 5:95 (2.5 minutes) to 95:5 (3.2 min); 1.3 ml/min, CT

12 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 5:95 (3.7 min); 1.0 ml/min, CT
13 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0,1% FA:AcN + 0,08% FA 95:5 (0 min) to 5:95 (2.5 minutes); 1.3 ml/min, CT
14 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 95:5 (0.5 min) to 5:95 (3,5 min) to 5:95 (4 min); 1.3 ml/min, CT
15 LC method:Waters XBridge C18, 4,6*50, 2,5 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 95:5 (0,2 min) to 5:95 min 2,4) - :5:95 (3.2 min)to 95:5 (3,3 min) to 95:5 (4,0 min); 1.7 ml/min, 40°C
16 LC method:Waters XBridge C18, 4,6*50, 2,5 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 5:95 (3.3 min) to 5:95 (3.85 min) to 95:5 (4 min); 1.7 ml/min, 40°C
17 LC method:YMC Jsphere H80 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 98:2 (1 min) to 5:95 (5.0 min) to 5:95 (6.25 min); 1.0 ml/min, CT
18 LC method:YMC Jsphere H80, 33*2,4 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 5:95 (0 min) to 95:5 (2.5 minutes) to 95:5 (3 min); 1.3 ml/min, CT
19 LC method:Waters XBridge C18, 4,6*50, 2,5 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 95:5 (0,2 min) to 5:95 (2,4 min) to 5:95 (3.2 min), -95:5 (3,3 min)to 95:5 (3,8 min)to 95:5 (4.0 min) 1.7 ml/min, 40°C
20 LC method:Merck Chromolith FastGrad. RP-18e, 50×2 mm, 0,05% TFA:AcN + 0.05% of TFA 98:2 (0.2 min) to 2:98 (2.4 min) to 2:98 (3.2 min) to 98:2 (3.3 min) to 98:2 (4 min); 2.0 ml/min, 50°C
21 LC method:Merck Chromolith FastGrad. RP-18e, 50×2 mm, 0,05% TFA:AcN + 0.05% of TFA 98:2 (0.2 min) to 2:98 (2.4 min) to 2:98 (3.2 min) to 98:2 (3.3 min) to 98:2 (4 min); 2.4 ml/min, 50°C
22 LC method:Waters UPLC VEINS C18XBridge C18 to 2.1*50 mm, 1.7 μ, H2O + 0,1% FA:AcN + 0,08% FA 95:5 (0 min) to 5:95 (1,1 min) to 5:95 (1,7 min) to 95:5 (1,8 min) to 95:5 (2 min); 0.9 ml/min, 55°C
23 LC method:Watrs XBridge C18 4.6*50 mm; 2,5 µ, +0,1% FA:AcN + 0.1% of FA 97:3 (0 min) to 40:60 (3.5 minutes) to 2:98 (4 min) to 2:98 (5 min) 97:3 (5,2 min) 97:3 (6,5 min); 1.3 ml/min, 45°C

24 method LCWaters XBridge C18, 4,6*50, 2,5 µ, H2O + 0.05% of TFA:AcN + 0.05% of TFA 95:5 (0 min) to 95:5 (0,2 min) to 5:95 (2,4 min) to 5:95 (3.5 minutes), -95:5 (3,6 min) to 95:5 (4.5 min); 1.7 ml/min, 50°C
25 LC method:YMC-Pack Jsphere H80 33*2.1, 4 µ, H2O + 0.05% of TFA:CH3OH + 0,05% TFA 98:2 (1 min) to 5:95 (5.0 min) to 5:95 (6,25 min); 1 ml/min, CT

Scheme 1

The General scheme of synthesis of oxide of Indiana

General synthesis methods

Stage 1/2: cinnamic acid (1 equivalent) and PtO2(2,2 mol.%) was suspiciously in ethanol (EtOH) (8 ml/mmol cinnamic acid) and vigorously stirred in the environment of H2(1 bar)until the reaction mixture has not ceased to absorb H2. The suspension was filtered and washed the residue with EtOH. The solvent of the filtrate was removed under vacuum and without additional purification used the resulting crude mixture of propionic acid and ester of propionic acid in the following reaction.

The mixture obtained in stage 1 of reaction, was dissolved in EtOH (2 ml/mmol of intermediate compounds obtained in stage 1) and added aqueous NaOH solution (2.5 equivalent in terms of the intermediate compound obtained in stage 1). The solution is eremetical for 16 h and reduced the volume of the mixture by vacuum. The resulting solution was diluted with water and acidified with an aqueous solution of 2 N HCl. The suspension was filtered and washed the residue with water. The desired propionic acid were obtained in the form of solids.

Stage 3/4: to a solution of propionic acid (1 equivalent) in CH2Cl2(1,4 ml/mmol propionic acid) and DMF (0.01 ml/mmol propionic acid) was carefully added oxalicacid (3.40 equivalent)to emulsify the solution. The obtained transparent solution was additionally stirred for 6 h and then removed under vacuum volatile components. In the next stage of the reaction without additional processing used the appropriate acid chloride.

In the solution of AlCl3(1.30 equivalents) in CH2Cl2(0.75 ml/mmol AlCl3) at 0°C dropwise added a solution of acid chloride in CH2Cl2(1.2 ml/mmol propionic acid, obtained in stage 3). After the addition was completed, the ice bath was removed and another for 3 h were delegirovali. The mixture is poured into melt water, and extracted the aqueous phase with the help of CH2Cl2. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography. If was not regioselective ring closure, the regioisomers were separated by the method column x is omatography.

Stage 5: to a solution of the indanone (1 equivalent) in EtOH (4 ml/mmol indanone) at 10°With portions carefully added NaBH4(1 mmol/mmol indanone). After complete addition the solution was stirred at room temperature (RT) for 3-16 h and then reduced the volume of the reaction solution under vacuum. The suspension is added in the melt water, and extracted the aqueous phase with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Step 6: to a solution of indanone (1 equivalent) in toluene (3 ml/mmol of Indianola) was added ion-exchange resin Dowex® (Marathon® MSC (H); 0.02 g/mmol of Indianola) and within 1 h were delegirovali suspension with water bolt. The cooled suspension was filtered, washed the residue with toluene under vacuum, removed the solvent of the combined organic phases. The crude product was purified by the method of column chromatography.

Alternatively, in stage 6 solution indanol (1 equivalent) and the monohydrate p-toluensulfonate acid (0.1 equivalent) in toluene (4 ml/mmol of Indianola) for 1-2 h were delegirovali with water bolt. The solution was cooled to room temperature (CT) and washed with saturated aqueous solution of NaHCO3. The organic phase is dried with the help of Na 2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Step 7: to a solution of indene (1 equivalent) in CH2Cl2(1.2 ml/mmol of indene) chloride and (S,S)-(+)-N,N'-bis(3,5-titlebarcolor)-1,2-cyclohexanediamine-manganese (III) (0.01 equivalent) was added 4-(3-phenylpropyl)pyridine N-oxide (0.04 equivalent). The reaction solution was stirred for 10 min and cooled to -2°C. was Added Polynesians aqueous solution To a2CO3(0.5 ml/mmol of indene) while vigorously stirring this suspension is slowly dropwise added an aqueous solution of NaOCl (1.25 ml/mmol of indene; 13% free chlorine). Immediately after that, using 0.1 M phosphate buffer (pH=7,5) bringing the pH to 11-12. A two-phase system was vigorously stirred for 4 h, during which the temperature slowly rose to 5°C. the Phases were separated and the aqueous phase is extracted with CH2Cl2. The combined organic phases are washed with a saturated aqueous solution of Na2S2O3and water, dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography. The resulting product has additionally recrystallize from heptane.

Step 8: to a solution of indene (1 equivalent) in DMSO (1 m is/mmol of indene) and water (0,025 ml/mmol of indene) at 25°C in small portions was added NBS (2 equivalent) thus, to ensure that the temperature did not exceed 35°C. the Solution was stirred at room temperature (RT) for 2 h and poured into ice. The aqueous phase was extracted with ethyl acetate, washed the combined organic phase with brine and then dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Step 9: to a solution of bromohydrin (1 equivalent) in THF (7 ml/mmol of bromohydrin) was added powdered NaOH (6.6 equivalent). The suspension was stirred at room temperature (RT), is not yet fully entered the reaction product of the preceding reaction stage, the reaction is controlled by thin layer chromatography (TLC). The suspension was filtered and washed the residue with ethyl acetate. The combined organic phases are dried with Na2SO4again was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Step 10: to a solution of indene (1 equivalent) in CH2Cl2(2.5 ml/mmol of indene) in small portions was added mCPBA (1.1 equivalent). The suspension was vigorously stirred for 2 hours and then was filtered. The residue is washed CH2Cl2a combined organic phases are successively washed with a saturated aqueous solution of Na2SO3the saturated aqueous NaHCO 3, dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Scheme 2

The synthesis of analogues of oxides of Indiana

General synthesis methods

Stage 1: a suspension of AlCl3(1.25 equivalents) and succinic anhydride (1.0 equivalent) in CH2Cl2(1,00 ml/mmol AlCl3) at 0°C was slowly added dropwise a solution of 2,5-dichlorothiophene (1.0 equivalent) in CH2Cl2(0.75 ml/mmol of thiophene). After the addition was complete, the ice bath was removed and stirred at room temperature (RT) for 4 h the Mixture was poured into melt water and the aqueous phase is extracted with CH2Cl2. Using 2N aqueous solution of NaOH was extracted with the combined organic phase was then acidified combined aqueous phase with concentrated HCl. The acidic aqueous solution was extracted with CH2Cl2,dried combined organic phases with the help of Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography.

Stage 2: in the solution ClSi(CH3)3(1.10 equivalents) in THF (1.70 ml/mmol ClSi(CH3)3) at 0°C was slowly added dropwise a solution of the product of the previous stavileci (1.0 equivalent) and N(C 2H5)3(1.10 equivalents) in THF (0,80 ml/mmol of the product of the preceding reaction stage). After the addition was completed, stirring at 0°C for 15 min continued, and the resulting suspension was filtered. The solvent of the filtrate was removed under vacuum and the residue was dissolved in CH2Cl2(2.00 ml/mmol of the product of the preceding reaction stage). In solution at room temperature (RT) was added HSi(C2H5)3(3.0 equivalent) and TiCl4(3.0 equivalent, 1M in CH2Cl2). The solution was stirred at room temperature (RT) for 20 h and then poured into water from melted snow. With the help of CH2Cl2were extracted aqueous phase. Was extracted with the combined organic phases with saturated aqueous NaHCO3and then carefully acidified combined aqueous phase with concentrated HCl. Was extracted with an acidic aqueous solution with ethyl acetate, dried the combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography.

Stage 3: carboxylic acid (1.00 equivalent) was dissolved at 0°C in concentrated H2SO4(6.30 ml/mmol of carboxylic acid) and then for 4 h and stirred at room temperature (RT). The solution is poured into tal is th water and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography. The subsequent reactions in order to obtain epoxide proceeded by analogy with scheme 1/route Century.

Scheme 3

Synthesis of oxides of tetrahydronaphthalene (route D)

General synthesis methods

Stage 1: 1.5 M aqueous solution of potassium carbonate (4×10-4M EDTA, 1,55 ml/mmol of 1,2-dihydronaphthalene) and acetonitrile (1,55 ml/mmol of 1,2-dihydronaphthalene) at 0°C was added 1,2-dihydronaphthalene (1.00 equivalent), and 1,1,1-triptorelin (0.15 equivalent) and stirred for 5 minutes then carefully added hydrogen peroxide fortress 30% (4.00 equivalent). The reaction mixture was stirred at 0°C for 4.5 h (the reaction was monitored by TLC), and then added ethyl acetate. After separation of the phases was twice extracted the aqueous phase with ethyl acetate, washed the combined organic phases are saturated aqueous NaCl, dried with MgSO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography.

Scheme 4

Synthesis of intermediate compounds oxides of Indiana

General synthesis methods

Stage 1: in RA is creative indanone (1 equivalent) in CH 2Cl2(4,0 ml/mmol indanone) at room temperature (RT) in small portions was added mCPBA (meta-chloroperbenzoic acid, 2,2 equivalent). The suspension is vigorously stirred overnight and then added an aqueous solution of Na2S2O5at 0°C. the Biphasic mixture was stirred for 10 min, was filtered, divided phase and the aqueous phase is extracted with CH2Cl2. The combined organic phases are washed with a saturated aqueous solution of NaHCO3, dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography.

The described methods were synthesized following the oxides of Indiana and their analogues:

Epoxide
Epoxiderat-CIS-6-chlorinda oxide1S,2R-4,6-differendy oxide1S,2R-4,6-dichloride oxiderat-CIS-4,6-dichloride oxide
Route AndAndAnd
Epoxide
Epoxiderat-CIS-5,6-dichloride oxiderat-CIS-6,7-dichloride oxiderat-CIS-4-chlorinda oxiderat-CIS-4-floridana oxide
RouteInInInIn
Epoxide
Epoxiderat-CIS-7-chlorinda oxiderat-CIS-6-floridana oxiderat-CIS-4-methylindene oxiderat-CIS-7-methylindene oxide
RouteInInInIn
Epoxide
Epoxiderat-CIS-5-floridana oxiderat-CIS-6-chlorinda oxide1S,2R-6-chloro-4-floridana oxiderat-CIS-6-Cryptor-methoxyindole oxide
RouteInInAndIn
Epoxide
Epoxiderat-CIS-6-chloro-4-4,6-dichloro-1A,2,3,6b-tetrahydro-rat-CIS-6-rat-CIS-3,3-

floridana oxide1-oxa-5-titsicle-disappear[e]indenmethoxyindole oxidedimethylindole oxide
RouteInInIn
Epoxide
Epoxiderat-CIS-6-methylindene oxiderat-CIS-4-chloro-6-floridana oxiderat-CIS-6-methylsulfonylamino oxiderat-CIS-1,2-tetralin oxide
RouteInD

Total synthesis of phenols

Scheme 5

Removing the protective groups of ethers of phenol

General synthesis methods

Stage 1/2: a simple solution methyl ester (1 equivalent) in CH2Cl2(7 ml/mmol is simple ether) dropwise added BBr 3at -10°C (1 M solution in CH2Cl2; 2.5 equivalents) and removed the cooling bath. The suspension was stirred in total for 4 hours, checking the reaction by TLC and after completion of the reaction was added to the suspension in the melt water. The resulting aqueous suspension was neutralized with NaHCO3and was extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

The simple solution isopropyl ether (1 equivalent) in CH2Cl2(6 ml/mmol simple ether) dropwise added BCl3at -78°C (1M solution in hexane; 2.0 equivalents) and removed the cooling bath. The suspension was stirred in total for 3 h (monitoring by TLC) and added in the melt water. The resulting aqueous suspension was neutralized with NaHCO3and was extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Scheme 6

Synthesis of heterocyclic phenols

General synthesis methods

Stage 1: in the solution NITROPHENOL (1 equivalent) in utilize the ATA (6 ml/mmol of the product of the preceding reaction stage) in small portions was added SnCl 22H2O (5 equivalents). The suspension was delegirovali within 1-6 h (monitoring by TLC). The reaction was stopped with water and turned into a substrate using an aqueous solution of 2N NaOH. The resulting suspension was filtered and the filtrate was extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Stage 2/3: a solution of 4-nitrophenylphosphate (1.5 equivalent) in CH2Cl2(0.4 ml/mmol of formate) is dropwise added a solution of the appropriate aniline (1.0 equivalent) and base Hunya (1.1 equivalent) in CH2Cl2(1.3 ml/mmol of aniline) at 0°C so that the temperature did not rise above 5°C. the Solution was stirred at room temperature (RT) for 2 h and then cooled to 0°C. was Added the appropriate aminoacetyl (2.3 equivalents) and stirred suspension at room temperature (RT) for 4 h, the Reaction mixture was diluted with CH2Cl2and successively washed with water, 2N aqueous NaOH solution and saturated aqueous NH4Cl. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product is used without additionally the th purification in the next stage of the reaction.

The crude product of the preceding reaction stage (1 equivalent) was dissolved at 0°C in formic acid (1.5 ml/mmol of the product of the preceding reaction stage) and stirred at room temperature (RT) for 2-16 h (monitoring by TLC). The volume of the reaction solution is reduced in 2 times under vacuum and the resulting solution was diluted with water. The aqueous phase was extracted with ethyl acetate and the combined organic phases are carefully washed with a saturated aqueous solution of NaHCO3. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Stage 4: to a solution of the product of the preceding reaction stage (1 equivalent) in a mixture of EtOH/ethyl acetate (1:1.5 ml/mmol of the product of the preceding reaction stage) added PtO2(5 mol.%). The suspension is vigorously stirred in the environment of H2(1.5 bar) for 5 h (monitoring by TLC). The suspension was filtered and washed the residue with EtOH. The organic solvent phase was removed under vacuum and used the obtained crude product in the next stage of the reaction.

Stage 5/6: a solution of 4-nitrophenylphosphate (1.5 equivalent) in CH2Cl2(0.4 ml/mmol of formate) is dropwise added a solution of the appropriate aniline (1.0 in equivale the t) and the base Hunya (3.5 equivalents) in CH 2Cl2(1 to 3 ml/mmol of aniline) at 0°C, so that the temperature did not rise above 5°C. the Solution was stirred at room temperature (RT) for 2 h and then cooled to 0°C. was Added the corresponding ammonium salt of the amino acid (1.6 equivalents) and stirred suspension at room temperature (RT) for 16 h, the Reaction mixture was diluted with CH2Cl2sequentially washed with water, 2N aqueous NaOH solution saturated aqueous NH4Cl. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was used without further purification in the next reaction stage.

The crude product of the previous step (1 equivalent) is added at 0°C in an aqueous solution of HCl with fortress 10% (3.0 ml/mmol of the product of the preceding reaction stage) and delegirovali for 2-16 h (monitoring by TLC). the pH of the solution was brought to 8 with 2 N aqueous NaOH solution and was extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

The resulting ethers of phenols was digested according to the scheme 5.

As described biosynthetically the following phenols:

3-(3-fluoro-4-hydroxyphenyl)-1-methyl-imidazolidin-2,4-dione1-(3-fluoro-4-hydroxyphenyl)-1,3-dihydroimidazole-2-he1-4-hydroxyphenyl)-1,3-dihydro-imidazol-2-he3-(4-hydroxyphenyl)-5,5-dimethyl-imidazolidine-2,4-dione1-(2-chloro-5-hydroxyphenyl)-3-methyl-imidazolidin-2,4-dione
1-(4-hydroxyphenyl)-3-methyl-1,3-dihydroimidazole-2-he1-(2-chloro-5-hydroxyphenyl)-3-methyl-1,3-dihydroimidazole-2-he1-(4-fluoro-3 hydroxyphenyl)-3-methyl-1,3-dihydroimidazole-2-he1-(3-fluoro-4 hydroxyphenyl)-3-methyl-1,3-dihydroimidazole-2-he 1-(3-hydroxyphenyl)-3-methyl-imidazolidin-2-he

1-(4-fluoro-3-hydroxyphenyl)-3-methyl-imidazolidin-2-he1-(4-hydroxyphenyl)-3-methyl-imidazolidin-2-he3-(4-chloro-3-hydroxyphenyl)-1-methyl-imidazolidin-2,4 dione1-(3-fluoro-4-hydroxyphenyl)-3-methyl-imidazolidin-2-he1-(4-chloro-3-hydroxyphenyl)-3-methyl-imidazolidin-2-he
1-(4-chloro-3-hydroxyphenyl)-3-methyl-1,3-dihydroimidazole-2-he1-(4-fluoro-3-hydroxyphenyl)-3-methyl-1,3-dihydroimidazole-2-he1-(2-chloro-5-hydroxyphenyl)-3-methyl-imidazolidin-2-he1-(2-fluoro-hydroxyphenyl)-3-methyl-1,3-dihydroimidazole-2-he 3-(3-fluoro-4-hydroxyphenyl)-imidazolidin-2,4-dione

Scheme 7

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1: a carefully prepared mixture of the appropriate aniline (1 equivalent) and succinic acid (1 equivalent) was stirred at 180°C for 2 h, during which the formed melt. The melt was cooled to room temperature (CT) (hardening of the melt) and dissolved in EtOH. The resulting solution was mixed with activated carbon was filtered under vacuum, removed the solvent. The residue was dissolved in ethyl acetate and washed with saturated aqueous solution of NaHCO3. The organic phase was dried with Na2SO4again was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Stage 2: a carefully prepared mixture of the appropriate aniline (1 equivalent) and gamma-butyrolactone (1 equivalent) was stirred at 180°C for 2 h, during which the formed melt. The melt was cooled to room temperature (CT) (hardening of the melt) and dissolved in EtOH. The resulting solution was mixed with activated carbon was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography.

Recip is installed this way, ethers, phenols split according to the scheme 5.

In the described manner were synthesized following phenols:

1-(4-hydroxyphenyl)-pyrrolidin-2,5-dione1-(3-chloro-4-hydroxyphenyl)-pyrrolidin-2,5-dione1-(4-hydroxyphenyl)-pyrrolidin-2-he1-(3-chloro-4-hydroxyphenyl)-pyrrolidin-2-he1-(4-chloro-3-hydroxyphenyl)-pyrrolidin-2,5-dione
1-(4-chloro-3-hydroxyphenyl)-pyrrolidin-2-he1-(3-hydroxyphenyl)-pyrrolidin-2,5-dione1-(3-hydroxyphenyl)-pyrrolidin-2-he/td> 1-(3-fluoro-4-hydroxyphenyl)-pyrrolidin-2,5-dione

Scheme 8

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1: Bronevoy acid (1 equivalent), allided (1 equivalent) and Na2CO3(3.0 equivalents) was suspiciously in a mixture of water/DME ((1:1; 3 ml/mmol Bronevoy acid). Added PdCl2(PPh3)2(2 mol.%) and was stirred suspension at 80°C for 20 h (monitoring by TLC). Then the suspension was diluted with ethyl acetate and water, separated phase and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

2-(3,5-dimethyl-isoxazol-4-yl)-5-terfenol3-(3,5-dimethyl-isoxazol-4-yl)-4-terfenol

Scheme 9

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1: aryl bromide (1 equivalent), oxazolidin (1 equivalent), K2CO3(2.0 equivalent), TRANS-diaminocyclohexane (10 mol.%) and CuI (5 mol.%) was suspiciously in dioxane (0.5 ml/mmol aryl bromide). The suspension was delegirovali for 16 h (monitoring by TLC), diluted with ethyl acetate and was filtered through a small amount of celite. The organic phase was dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

3-(4-chloro-3-hydroxyphenyl)-oxazolidin-2-he3-(3-hydroxyphenyl)-oxazolidin-2-he3-(4-hydroxyphenyl)-oxazolidin-2-he3-(3-chloro-4-hydroxyphenyl)-oxazolidin-2-he(R)-3-(4-fluoro-3-g is PROXIFIER)-4-isopropyl-oxazolidin-2-he

Scheme 10

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1: aryl bromide (1 equivalent), baronova acid (1 equivalent), K2CO3(2.0 equivalents) and Pd(PPh3)4(10 mol.%) was suspiciously in DME (1.0 ml/mmol aryl bromide). The suspension was delegirovali within 48 h, the reaction was controlled by TLC. The reaction mixture was diluted with ethyl acetate and water, separated phases, the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

The resulting ethers of phenols was digested according to the scheme 5.

The described method was synthesized following phenol:

4-thiazol-2-infenal

Scheme 11

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1/2: a solution of isocyanate (1 equivalent) in toluene (1.0 ml/mmol of isocyanate) was added the corresponding ester of the hydroxy acid (2 equivalents). Rastvorov for 4 h was heated in a closed vessel at a temperature of 110°C, when this reaction was controlled by TLC. The solvent was removed under vacuum and purified the crude products by the method of column chromatography. The product of the preceding reaction stage in a period of 4 h was heated without solvent at a temperature of 180°C. After cooling the reaction solution to room temperature (CT) was purified crude product by the method of column chromatography.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

3-(4-fluoro-3-hydroxyphenyl)-oxazolidin-2,4-dione3-(4-hydroxyphenyl)-oxazolidin-2,4-dione3-(4-fluoro-3-hydroxyphenyl)-5,5-dimethyl-oxazolidin-2,4-dione3-(4-chloro-3-hydroxyphenyl)-5,5-dimethyl-oxazolidin-2,4-dione3-(3-chloro-4-hydroxyphenyl)-oxazolidin-2,4-dione

Scheme 12

Conversion to the sulfonamide

(stage 1; pyridine, ethyl acetate)

General method of synthesis

Stage 1: in the solution of chloride of sulfonyl (1 equivalent) in ethyl acetate (2 ml/mmol) and pyridine (6 equivalents) was added the corresponding hydrochloride ammonium (3 equivalents) at 0°C. the Suspension was stirred at room temperature (RT) for 16 h, the reaction was controlled by TLC. The reaction mixture was diluted with ethyl acetate and water, separated phase and the aqueous phase was extracted with ethyl acetate. The combined organic phases are washed with a saturated aqueous solution of NH4Cl, dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

In the described manner were synthesized following phenols:

4-hydroxy-N-(2,2,2-triptorelin)benzosulfimide4-HYDR the XI-N-(3,3,3-cryptochromes)benzosulfimide N-ethyl-4-hydroxy-benzosulfimide

Scheme 13

Oxidation of persulfide

General method of synthesis

Stage 1: the suspension periodni acid (2.1 equivalents) in CH3CN (3 ml/mmol periodni acid) was stirred at room temperature (RT) until a clear solution is formed (for about 50 min). Added chromium trioxide (10 mol.% relatively sulfide) and stirred for 10 minutes This solution orange color at -35°C was slowly added into the solution of the corresponding sulfide (1 equivalent) in ethyl acetate (10 ml/mmol sulfide). The temperature did not rise above -35°C. the Resulting suspension was stirred at this temperature for 60 min and finished mixing by adding 5 ml of a saturated aqueous solution of Na2SO3. The suspension was filtered and washed the residue with ethyl acetate. The filtrate was washed with a saturated aqueous solution of Na2SO3the solution was dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography.

The described method was synthesized following phenol:

4-methanesulfonyl-3-METHYLPHENOL

Scheme 14

Synthesis of heterocyclic phenols

General method of synthesis

Stage 0 (optional): to a solution of aniline F (1 equivalent) in a concentrated aqueous solution of hydrochloric acid (0,36 ml/mmol of the product of the preceding reaction stage) added 4.5 equivalent SnCl2and heat the solution to 60°C. After stirring overnight the mixture was poured into ice, using 10 M KOH brought the pH to >10, 4 times was extracted with dichloromethane, washed the collected organic phases with saturated solution of NaCl, dried with Na2SO4. Removed under vacuum of the solvent.

Stage 1: in the solution of the hydrazide (1.1 equivalents) in acetonitrile (6 ml/mmol of the product of the preceding reaction stage) added 1.1 equivalent of dimethylaminomethylene or orthoevra With and within 30 minutes was stirred solution at 50°C. After adding a solution of aniline (A) in acetonitrile (3 ml/mmol of the product of the preceding reaction stage) and acetic acid (9 ml/mmol of the product of the preceding stage of the reaction mixture for 16 h was heated in an open flask at a temperature of 120°C. was Removed under vacuum of the solvent. The crude products were purified by the method of column chromatography using gradient is dichloromethane/methanol for elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

4-(3-cyclopropyl-5-methyl-[1,2,4]triazole-4-yl(phenol)4-(3-methyl-[1,2,4]triazole-4-yl)phenol4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-cryptomaterial4-(3-isopropyl-5-methyl-[1,2,4]triazole-4-yl)-phenol4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2,3-dimethylphenol
4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-terfenol3-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenol4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenol4-3-ethyl-5-isopropyl-[1,2,4]triazole-4-yl)-phenol 4-(3,5-dimethyl-[1,2,4]triazole-4-yl)-2-chlorophenol

Scheme 15

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1: a mixture of boric acid (1 equivalent), heteroaromatic/bromide (1 equivalent) in water/DME 1/1 (3 ml/mmol of the product of the preceding reaction stage) for 15 min missed argon. After addition of dichloro-bis-triphenylphosphine palladium (0.02 equivalent) and Na2CO3(3.0 equivalents) and the mixture was heated to a temperature of 80°C in the presence of argon (within 20 hours). After completion of the reaction (controlled by LC-MS, the mixture was mixed with ethyl acetate and saturated aqueous NaHCO3and was extracted twice using ethyl acetate. The collected organic phases are washed with saturated NaCl solution and dried on Na2SO4. Removed solvent under vacuum. The crude products were purified by the method of column chromatography using a gradient of dichloromethane/methanol for elution.

Option a: after stirring for 1 hour the mixture was extracted three times with dichloromethane, washed the collected organic phases with saturated solution of NaCl and dried on Na2SO4. Removed solvent under vacuum.

Option: after stirring for 1 hour the mixture neutral is savali using NaOH, filtered the product by suction or were extracted three times with dichloromethane, washed the collected organic phases with saturated solution of NaCl and dried on Na2SO4. Removed solvent under vacuum.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

4-(2,4-dimethyl-thiazol-5-yl)phenol4-(1,3,5-trimethyl-1H-pyrazole-4-yl)phenol4-(3,5-dimethyl isoxazol-4-yl)phenol

Scheme 16

Synthesis of heterocyclic phenols

General method of synthesis

Step 1: to a solution of aniline (1 equivalent) in dichloromethane (1.5 ml/mmol of the product of the preceding reaction stage) were sequentially added triethylamine (2 equivalents) and dropwise 3-chloropropanesulfonyl (1.3 equivalent)was stirred mixture at room temperature for 16 hours After adding dichloromethane (1 ml/mmol of the product of the preceding reaction stage), the mixture was successively washed 1 N aqueous HCI and saturated dissolve the om NaHCO 3. Removed solvent under vacuum. The product was dissolved in DMF (1.3 ml/mmol of the product of the preceding reaction stage and added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (1.1 equivalent). After stirring at 25°C for 3 h and after adding ethyl acetate/heptane 2/1 organic phase is twice washed with 0.1 N HCI, a the organic phase is washed with saturated NaCl solution and dried on Na2SO4. Removed solvent under vacuum. The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

1,1-dioxide, 2-(3-hydroxyphenyl)-isothiazolinone

Scheme 17

Conversion to the sulfonamide

General method of synthesis

Stage 1: a mixture of the bromide (1 equivalent), N-methylmethanesulfonamide (1.2 equivalents), copper iodide (1) (0.2 equivalent), sarcosine (0.2 equivalent), K3PO4 (2.5 equivalents) in DMF (6 ml/mmol of the product of the preceding reaction stage) for 24 h was stirred 150°C. the solvent was Removed under vacuum. After adding dichloromethane the organic phase is washed with saturated solution of NaHCO3and drank Na2SO4Udalili the solvent under vacuum. The crude product was purified by pulsed chromatography on silica gel using a gradient of dichloromethane/methanol for elution.

The resulting ethers of phenols was digested according to the scheme 5.

The described method was synthesized following phenol:

N-(4-fluoro-3-hydroxyphenyl)-N-methylmethanesulfonamide

Scheme 18

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1: a mixture of amine (1 equivalent), 2,6-dimethyl-gamma-pyrone (2.5 equivalents) in 2 N aqueous solution of HCl for 30 min was heated to 160°C. in microwave ovens. After adding dichloromethane the organic phase is washed with a saturated solution of NaHCO3and drank Na2SO4. Removed solvent under vacuum. The crude product was purified by pulsed chromatography on silica gel, using a gradient of dichloromethane/methanol for elution.

The resulting ethers of phenols was digested according to the scheme 5.

The described method was synthesized following phenol:

1-(3-fluoro-4-hydroxyphenyl)-2,6-dimethyl-1H-pyridin-4-one

Scheme 19

Synthesis of heterocyclic phenols

General method of synthesis

Stage 1: a mixture of amine (1 equivalent) and diglycolic anhydride (2 equivalents) within 48 hours was heated to 160°C. After addition of dichloromethane the organic phase is washed with saturated NaCl solution and dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of dichloromethane/methanol for elution.

The resulting ethers of phenols was digested according to the scheme 5.

The described method was synthesized following phenol:

4-(3-fluoro-4-hydroxyphenyl)-morpholine-3,5-dione

Scheme 20

Protection of secondary alcohols using TBDPSiCl in the presence of secondary amines

General method of synthesis

In a suspension of the corresponding hydrochloride amerosport (1 equivalent) and tert-butyldiphenylsilyl (1.2 EQ is Valens) in a solution mixture of THF and pyridine (4:3; 1 ml/mmol of amerosport) added AgNO3(2.1 equivalent), while there was a slight increase in temperature. Suspension for 16 h and was stirred at room temperature (RT), was filtered and washed the residue with ethyl acetate. The filtrate was diluted with ethyl acetate and washed with saturated aqueous solution of NaHCO3. The organic phase was dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

In the described manner were synthesized following simple Silovye esters:

3-(tert-butylbiphenyl-silyloxy)-piperidine3-(tert-butyldiphenylsilyl)-azetidin(R)-3-(tert-butyldiphenylsilyl)-pyrrolidin

Scheme 21

Synthesis of heterocyclic phenols using CuCl

General method of synthesis

Stage 1: a suspension of the bromide (1 equivalent), imidazole (1.25 equivalent), CuCl (0.06 equivalent) and K2CO3(1 equivalent) in NMP (2 ml/mmol bromide) for 10 h was heated to 210 the S. The mixture was cooled to CT and diluted with water. The aqueous layer was extracted with ethyl acetate, washed the combined organic layers with saturated NaCl solution, dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/Meon for elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

4-(2-methyl-imidazol-1-yl)-phenol2-fluoro-4-imidazol-1-yl-phenol4-(2-isopropyl-imidazol-1-yl)-phenol

Scheme 22

Synthesis of heterocyclic phenols by amidino

General method of synthesis

Step 1: to a suspension of aniline (1 equivalent) in an appropriate nitrile (1 equivalent) at 0°C in small portions was added AlCl3(1 equivalent). The mixture for 1 h was heated to 100°C until the formed solution. The reaction mixture was cooled to 0°C and carefully cooled water. Trust and pH of the aqueous suspension to 10 with 2N aqueous NaOH. Were extracted aqueous layer with ethyl acetate, the combined organic layers were washed with saturated NaCl solution, dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/heptane/Meon/NH3 for elution.

Stage 2: a suspension of amidine (1 equivalent) and NaHCO3(3 equivalent) in dioxane (2 ml/mmol of amidine) was added α-chloro-ketone (1.1 equivalent) and for 1 h was heated to 100°C. the Mixture was cooled to CT, diluted with water and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with saturated NaCl solution, dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/Meon for elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

4-(2-ethyl-4-methyl-imidazol-1-yl)-phenol 5-(2-ethyl-4-methyl-imidazol-1-yl)-2-fluoro-phenol4-(4-tert-butyl-2-isopropyl-imidazol-1-yl)-phenol

4-(4-tert-butyl-2-methyl-imidazol-1-yl)-2-fluoro-phenol4-(2-isopropyl-4-methyl-imidazol-1-yl)-phenol4-(2,4-dimethyl-imidazol-1-yl)-2-fluoro-phenol

Scheme 23: Synthesis of heterocyclic phenols by sulphides

General method of synthesis

Step 1: to a solution of imidazole (1 equivalent) in THF (5 ml/mmol of imidazole) at -78°C. dropwise added nBuLi (1.1 equivalent, 1 M in hexano). The temperature of the solution within 30 min brought to -30°C. the Solution was cooled to -50°C and added diallyldisulfide (1.1 equivalent). Removed the cooling bath and continued stirring for 90 min, while the temperature of the suspension is not reached CT. Added ice water, extracted the aqueous layer with ethyl acetate, washed the combined organic layers with saturated NaCl solution, dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by the method of pulse chromatogra the AI on silica gel using a gradient of ethyl acetate/heptane to elution.

Stage 2: in the solution alkylsulfate (1 equivalent) at 0°C in CH2Cl2(12 ml/mmol sulfide) in small portions was added peroxybenzoyl acid (3 equivalents). A cloudy solution was vigorously stirred for 14 h, the Solution was diluted with CH2Cl2and thrice washed aqueous solution of Na2CO3. The organic layer was dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/Meon for elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

4-(2-methanesulfonyl-imidazol-1-yl)-phenol2-fluoro-4-(2-methane-sulfonyl-imidazol-1-yl)-phenol

Scheme 24

Synthesis of heterocyclic phenols by esters of carboxylic acids

General method of synthesis

Step 1: to a solution of imidazole (1 equivalent) in THF (5 ml/mmol of imidazole) at -78°C. dropwise added nBuLi. The temperature of the solution within 30 min brought to -30°C. the Solution ohla the or to -78°C. and dropwise added trimethylchlorosilane (1.1 equivalent). Removed ice bath and for 60 min increased the temperature of the solution to CT. Once cooled the solution to -78°C, was added chloroformate (1.1 equivalent) and removed the ice bath. After 2 h the reaction mixture was poured into ice water, extracted with ethyl acetate, washed with saturated NaCl solution, dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/Meon for elution.

Stage 2: an ester of carboxylic acid (1 equivalent) was dissolved in 2 M solution Meon the appropriate amine (10 equivalents) for 12 h was stirred at 60°C. the Solvent was removed and purified the crude product by pulsed chromatography on silica gel using a gradient of ethyl acetate/methanol for elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

1-(3-fluoro-4-hydroxy-phenyl)-1H-imidazole-2-carboxylic acid methyl ester1-(3-fluoro-4-hydroxy-phenyl)-1H-imidazole-2-carboxylic acid Dima is ilamed

Scheme 25

Synthesis of heterocyclic phenols using sulfochlorides

General method of synthesis

Stage 1: in the solution sulfochloride (1 equivalent) in CH2Cl2(2 ml/mmol of sulfochloride) at 0°C dropwise added amine (4 equivalent). Suspension for 3 h and stirred at RT. Added water and the aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with saturated NaCl solution, dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/methanol for elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

4-(4-methyl-piperazine-1-sulfonyl)-phenol4-(morpholine-4-sulfonyl)-phenol

Scheme 26

Synthesis of heterocyclic phenols by acylhydrazines

General method of synthesis

Stage 1: in the solution acylhydrazone (1 equivalent) is toluene (3 ml/mmol of acylhydrazone) at 0°With portions added triphosgene (0.33 equivalent). Suspension for 2 h were delegirovali until the formed solution. The solution was cooled to CT and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/heptane to elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

3-(4-hydroxy-phenyl)-3H-[1,3,4]oxadiazol-2-he3-(4-hydroxy-phenyl)-5-methyl-3H-[1,3,4]oxadiazol-2-he

Scheme 27

Synthesis of heterocyclic phenols by diacylhydrazines have

General method of synthesis

Stage 1: in the solution acylhydrazone (1 equivalent) in CH2Cl2(1.5 ml/mmol of acylhydrazone) at RT was added the isocyanate (12 equivalents). The solution was heated to 55°C. in a sealed vessel. The solution was cooled to CT and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/heptane/Meon for elution.

Stage 2: NaOH (1.25 equivalents) was dissolved in MeO is (3 ml/mmol NaOH) and added diacylhydrazine (1 equivalent). The solution for 16 h and was stirred at RT. The mixture was diluted with water and was extracted with ethyl acetate. The combined organic layers were washed with saturated NaCl solution, dried on Na2SO4and under vacuum, removed the solvent. The crude product was purified by pulsed chromatography on silica gel using a gradient of ethyl acetate/Meon for elution.

The resulting ethers of phenols was digested according to the scheme 5.

In the described manner were synthesized following phenols:

4-ethyl-2-(4-hydroxy-phenyl)-5-methyl-2,4-dihydro-[1,2,4]triazole-3-one-ethyl-2-(4-hydroxy-phenyl)-2,4-dihydro-[1,2,4]triazole-3-one

Private methods of synthesis, the relevant scheme/method And

The synthesis of compounds I by the inversion of Mitsunobu

The method of synthesis

Stage 1: a solution of epoxide (1 equivalent) and the appropriate secondary amine (1.05 equivalents) in acetonitrile (1 ml/mmol epoxide) for 1-6 h was heated at 80°C with monitoring by TLC. The solvent was removed under vacuum and purified the crude products by the method column is cromatografia.

Stage 2: 1 M solution of DIAD (diisopropylcarbodiimide, 1.15 equivalents) in THF dropwise added to a solution/suspension of amerosport (1 equivalent), PPh3(1.15 equivalents) and the appropriate phenol (1.15 equivalents) in THF (3 ml/mmol of amerosport). The solution for 1-16 h was stirred at room temperature (RT), the reaction was controlled by TLC, and under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Stage 3 (optional): split simple tert-butyldiphenylsilyl esters using TBAF (Tetra-n-butylphthalide ammonium) or HF/pyridine complex. Using 4N HCl solution in dioxane or TFA/CH2Cl21/1 removed the protective N-Boc group.

Private methods of synthesis, the relevant scheme/method In

The synthesis of compounds I by nucleophilic substitution in the aromatic nucleus (1)

The method of synthesis

Dissolving 1 equivalent of 2-bromo-1-indanone in dimethylformamide and preferably at a temperature of the ice bath quickly added amine R-NH-R in its pure form as a free base or in the form of a solution of DMF. After a relatively short reaction time (from 30 seconds to 1 hour) the reaction was stopped by diluting the reaction mixture with hydrochloric acid in a quantity sufficient to Costigan what I pH from 1 to 5. The suspension was extracted several times using ethyl acetate acetic acid and the remaining aqueous solution portions added 2-10 equivalents of sodium borohydride, resulting in an intermediate ketone. After stirring at room temperature for several hours made concentration, saturated reaction mixture with water and made her slightly alkaline with concentrated sodium bicarbonate solution. By extraction with ethyl acetate acetic acid received the original product as a mixture of CIS/TRANS-isomers, which in most cases was subjected to chromatography, but in some cases this method can also separate the isomers. However, mixture of CIS/TRANS-isomers in many cases used for subsequent arilirovaniya and only then carry out the separation of the isomers.

In the described manner were synthesized following 1-indanol:

2 cyclopentylamine-indan-1-ol2-benzylamino-1-ol2-morpholine-4-Ilinden-1-ol
2-pyrrolidin-1-Ilinden-1-ol5-chloro-2-imidazol-1-Ilinden-1-ol4,6-dichloro-2-imidazol-1-Ilinden-1-ol
2-imidazol-1-Ilinden-1-ol2-tert-butylamino-indan-1-ol2-(cyclopropylmethyl-amino)indan-1-ol
2-cyclobutylmethyl-amino-indan-1-ol2-(cycloheptylmethyl-amino)-indan-1-ol2 cyclobutylamine-indan-1-ol
2 cyclopropylamino-indan-1-ol

Private methods of synthesis, the relevant scheme/method In

Synthesis of connecting the I by nucleophilic substitution in the aromatic nucleus (2)

The method of synthesis

1 equivalent of Indianola General formula VI or X (in the form of a pure stereoisomer or a mixture of CIS/TRANS isomers) was dissolved in 5-10 times the number of absolute dimethyl sulfoxide and added from 1.2 to 2 equivalents applicable glodariu, preferably fluorinated aryl or aryl chloride. To the solution was added 1.2 to 5 equivalents fresh svejesmolotogo sodium hydroxide with stirring at room temperature and the mixture was stirred at room temperature for about 1 h or another for several hours at 60-80°C, depending on the nature of halodrol. For processing the mixture was diluted with water, the resulting suspension was extracted several times using ethyl acetate acetic acid, washed the combined extracts with water, dried with MgSO4and concentrated in a rotary evaporator, and then chromatography on silica gel.

Private methods of synthesis, the relevant scheme/method

The synthesis of products such as foundations, manniche (1)

The method of synthesis

Step 1: dissolving 1 equivalent of indan-2-it in an inert solvent, such as tetrahydrofuran, dimethylformamide or acetonitrile, added 2-3 equivalent dimethylformamidine and delegirovali the mixture for several hours or in the case of DMF was stirred at ambient temperature the re from 80°C to a maximum of 120°C for about 3-5 hours. Alternatively, it is also possible to dispense with a solvent, and in this case, the product of the preceding reaction stage can be dissolved in sufficient quantity of dimethylformamidine followed and stirring at 120°C. until the conversion is complete. After cooling by absorption usually can be directly filtered crystallized product, which is optionally purified by chromatography or recrystallization.

Stage 2: the resulting 1 equivalent of 2-dimethylaminomethylene-1-indanone was dissolved in dimethylformamide and added at least 2 equivalents of a secondary amine NHR3R4 in the form of free base or hydrochloride. The mixture for several hours was stirred at temperatures from 60° to 120°. After cooling, the solution was diluted with water and filtration method by suction or by means of extraction using ethyl acetate was isolated product.

Stage 3: the resulting 1 equivalent of 2-aminomethyl-1-indanone was dissolved in methanol and added 10-20 equivalents divided by 10 to 20 portions, at intervals of 15-30 minutes with stirring at room temperature. After the product of the preceding reaction stage almost completely disappeared under vacuum, removed the solvent and filled the rest with water. By extraction with the aid of the using ethyl acetate acetic acid obtained crude product is initially in the form of a mixture of CIS/TRANS-isomers, which in most cases was subjected to chromatography, in some cases, this method can also separate the isomers. However, mixture of CIS/TRANS-isomers in many cases it can be used for subsequent arilirovaniya and only then carry out the separation of the isomers.

In the described manner were synthesized following 2-aminomethyl-1-indanol:

4,6-dichloro-2-pyrrolidin-1-elitelendo-1-ol4,6-dichloro-2-di-methylaminomethyl-1-ol2-morpholine-4-yl-methylinden-1-ol
2-dimethylamino-methylinden-1-ol2-pyrrolidin-1-ylmethylene-1-ol2-piperidine-1-ylmethylene-1-ol

Private methods of synthesis, the relevant scheme/method

The synthesis of products such as foundations, manniche (2)

The method of synthesis

Dissolved 1 equivalent shall alent of Indianola General formula VI or X (in the form of a pure stereoisomer or a mixture of CIS/TRANS-isomers) at 5-10 times the number of absolute dimethyl sulfoxide and added from 1.2 to 2 equivalents applicable glodariu, preferably fluorinated aryl or aryl chloride. To the solution was added 1.2 to 5 equivalents svejesmolotogo sodium hydroxide with stirring at room temperature and the mixture was stirred at room temperature for 1 h or another for several hours at 60-80°C, depending on the nature of halodrol. For processing the mixture was diluted with water, the resulting suspension was extracted several times using ethyl acetate acetic acid, washed the combined extracts with water, dried with MgSO4and concentrated in a rotary evaporator, and then subjected to chromatography on silica gel.

Private methods of synthesis, the corresponding diagram D/mode D

Synthesis of diamines with TRANS-configuration and subsequent atilirovanie Buchwald

The method of synthesis

Stage 1: in the solution amerosport (1 equivalent), PPh3(1.10 equivalents) and DPPA (1.10 equivalents) in THF (7 ml/mmol of amerosport) at 0°C dropwise added a 1 M solution of DIAD (1.10 equivalents) in THF. The solution/suspension for 60 min was stirred at 0°C (controlled by LC/MS) and cooled to -10°C. At this temperature, carefully added LiAlH4(2.00 equivalent in terms of used amerosport) in one portion and another for 60 min mixture was stirred with cooling in ice. The suspension is poured into melt the ode and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Stage 2: to the solution of diamine (1 equivalent), Pd2(dba)3(0.04 equivalent), RAC-BINAP (0.08 equivalent), NaOTBu (1.40 equivalent) in toluene (12 ml/mmol of diamine) was added aryl bromide (0.95 equivalent) and for 10-18 h mixture was heated at 70°C (control by TLC). The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with ethyl acetate, the combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography.

Private methods of synthesis, the corresponding diagram E/way E

The synthesis of compounds I by alkylation

The method of synthesis

Stage 1: a solution of ester benzoic acid (1 equivalent) in acetone (20 ml/mmol of ester benzoic acid) was added 2N aqueous NaOH solution (1.10 equivalents) at RT and the mixture was stirred at RT for several hours, until fully reacted product of the previous step of the reaction (monitoring by TLC). The solvent was removed under vacuum and mixed the rest with water. In the dnow phase was extracted with ethyl acetate, the combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Stage 2: in the solution amerosport (1 equivalent) in THF (7 ml/mmol of amerosport) at 0°C was added NaH (1.30 equivalent of 80% mineral oil), removed ice bath and within one hour gave the mixture to warm to CT. Added alkylating agent (1.10 equivalents) and stirred the reaction mixture at RT to prevent further conversion (control by TLC). The mixture was poured into a saturated aqueous solution of NaHCO3and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography.

Private methods of synthesis, the corresponding scheme F

Optional reaction of compounds I

The method of synthesis

Stage 1: a Mixture of I-WH (1 equivalent), bromide (RBr 1.6 to 6 equivalents) and K2CO3(1-2 equivalents) was stirred in acetonitrile (5 ml/mmol) at 80°C (16-48 h). After adding dichloromethane and a saturated solution of NaHCO3thrice made the extraction with dichloromethane. The collected organic f the PS washed with saturated solution of NaCl and dried (Na 2SO4). The solvent was removed under vacuum and purified the crude products by the method of column chromatography.

Stage 2: (R=CF3) during the night was stirred in methanol solution I-WH (1 equivalent) and ethyltryptamine (1.3 equivalent). Removed solvent under vacuum. After adding dichloromethane and a saturated solution of NaHCO3thrice made the extraction with dichloromethane. The collected organic phases are washed with saturated NaCl solution and dried (Na2SO4). The solvent was removed under vacuum and purified the crude products by the method of column chromatography.

Or (R=CH3) was stirred in acetic anhydride/pyridine 1/2 (9 ml/mmol of the product of the preceding reaction stage) solution of amine (1 equivalent). Removed solvent under vacuum. The crude products were purified by the method of column chromatography.

Stage 3: to the solution of amide (1 equivalent) in THF (5 ml/mmol of the product of the preceding reaction stage) at 0°C dropwise added a 1M solution of a complex of borane-THF in THF (2-9 equivalent). After deregulirovania in the mixture at 0°C. was carefully added concentrated hydrochloric acid and using NaOH turned the mixture into the base and carried out three times extraction with dichloromethane. The collected organic phases are washed with saturated NaCl solution and dried (Na2SO4 ). The solvent was removed under vacuum and purified the crude products by the method of column chromatography.

Private methods of synthesis, corresponding to the diagram G/method G

The synthesis of compounds of formula I via palladium-catalyzed removal of the protective groups allylamino

The method of synthesis

Step 1: to a suspension of 1,3-dimethylbarbituric acid (2-6 equivalents) and Pd(PPh3)4(0.05-0.10 equivalent) in CH2Cl2(1.0 ml/mmol barbituric acid) in argon was added a solution of allylamine (1 equivalent) in CH2Cl2(2.0 ml/mmol of allylamine) at room temperature. The solution was delegirovali until complete conversion of the product extract (control by TLC). The reaction mixture was cooled to room temperature and diluted with ethyl acetate. Washed the organic layer with a saturated aqueous solution of Na2CO3, dried on Na2SO4, removed the solvent under vacuum. The crude product was purified by pulsed chromatography on silica gel.

Example of synthesis (Example 226) And

Stage 1: a suspension of 4,6-dichloroarsine (500 mg, 1 equivalent) and the appropriate secondary amine (486 mg, 1.05 equivalents) in acetonitrile (2.5 ml) for 6 h was heated at 80°C. the Solvent was removed under vacuum and the eyes of the tili the crude products by the method of column chromatography (CH 2Cl2/MeOH). Received 875 mg of a colorless foam.

Stage 2: a suspension of amerosport (630 mg, 1 equivalent), PPh3(490 mg, 1.15 equivalents) and 4-methylsulfonylbenzoyl (310 mg, 1.15 equivalents) in THF (3 ml) was dropwise added a 1 M solution of DIAD (of 1.87 ml, 1.15 equivalents) in THF. The solution for 5 h and stirred at room temperature (RT) and under vacuum, removed the solvent. The crude products were purified by the method of column chromatography (ethyl acetate/heptane/methanol). The quality of the product received a colorless foam, still containing traces of OPPh3(930 mg).

Stage 3 (optional): to a solution of protected BOC-groups of the product of the preceding reaction stage (930 mg) in dioxane (5 ml) at 0°C was added 4 M HCl solution in dioxane (5 ml) and for 3.5 h mixture was stirred at RT. The resulting suspension was filtered and washed with diethyl ether. Solid white color suspended in a saturated aqueous solution of NaHCO3and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. As the target product obtained solid pale yellow color (600 mg).

Stage 4 (optional): to a suspension of 3-aminopyrrolidine (190 mg, 1 equivalent) and K2CO3(60 mg, 1 equivalent) in acetonitrile (4 ml) were removed and the protective groups at RT was added 1-bromo-2-foraten (164 mg, 3 equivalent) and delegirovali the mixture for 6 hours, the Solvent was removed under vacuum, the residue suspended in water and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography (CH2Cl2/MeOH). As the target product was obtained oil is a pale yellow color (120 mg).

By analogy with Example 226 were synthesized examples the following connections:

ExampleStructureThe method of synthesisMethod LCVP (min)MS [M+H+] ERIE+
1And141.56500.30
2And12.90456.15

3 And41.20467.13
4And121.48403.20
5And121.16369.24
6And121.40369.23
7And120.83387.27
8And141.81481.13

9/td> And121.22357.23
10And121.38413.18
11And121.23399.16
12And121.25405.23
13And120.87405.32
14And120.92418.34

15A 121.28404.32
16A121.32353.25
17A120.83405.33
18A121.08356.20
19A121.20379.29
20A121.33465.19

21A14 2.06469.12
22A141.36406.27
23A41.27377.21
25A12.50455.13
27A12.54446.15
28A92.36410.10

td align="center"> 364.19
29A12.67
30A121.12695.42 2M+H
31A61.20455.14
32A12.43359.14
33A121.16345.15
34A12.27383.19

35A12.60415.09
36A92.41401.09
37A61.10421.18
38A12.57371.14
39A12.32371.16
40A12.30358.14

41And12.45408.14
42 And12.40371.16
43And12.47355.18
44And12.37371.16
45And12.22401.1
46And12.65367.2

47A121.16380.18
48A/td> 92.23408.25
49A121.18393.17
50A12.64407.13
51A12.45359.15
52A12.52375.1

53A12.60371.14
54A1 2.40387.15
55A11.92357.17
56A12.50389.1
57A12.40341.15
58A120.88406.27

59A121.38392.30
60A12.2991.17
61A12.20390.17
62A121.00376.20
63A12.55431.09
64A12.54387.13

65And12.64371.15
66And12.48357.13
67And12.05380.25
68And12.57408.13
69And12.64409.11
70And12.37341.12

71A91.88389.22
72A120.82375.21
73 A12.22401.13
74A12.47369.15
75A11.97407.25
76A120.80393.27

77A92.52391.14
78A12.47402.17
79A 12.40392.14
80A12.34388.21
81A12.57358.14
82A121.05344.16

0.85
83A121.08353.20
84A12.02374.18
85A12360.23
86A120.66619.42 2M+N
87A92.16374.21
88A121.00360.23

89A91.93374.22
90A12.99507.1
91A141.76 439.1
92A142.19507.07
93A12.45439.14
94A41.27425.19

95And40.95387.2
96And12.84434.99
97And41.20444.16
98And41.04443.17
99And141.93495.14
100And12.74485.15 M+H+CH3CN

101A92.70455.06
102A41.22455.09
103A41.24442.21
104 A141.78441.21
105A12.89492.14 M+H+CH3CN
106A92.62459.98

107A92.49442.14
108A12.54426.05
109A92.20461.13
110 A92.16445.17
111A92.40473.13
112A92.68446.16

113A12.65461.16
114A92.42477.07
115A12.39381.19
116A 121.15367.23
117A12.54469.11 M+H{Hal}
118A121.32453.10

119A12.82423.12
120A12.42407.17
121A141.42404.26
122A 92.28493.01
123A12.75483.17
124A92.50472.08

125A92.62475.02
126A92.42495.04
127A12.48487.19
128A9 487.14
130A92.27477.25
131A92.41473.12

132A12.40473.09
133A92.22459.25
134A12.59468.18
135A92.83459.
136A12.90476.09
137A12.77448.16

138A82.91477.16
139A12.39459.08
140A12.55438.21
141A12.40471.28
142A12.32461.15
143A92.11443.13

144And12.34443.13
145And92.11425.13
146And92.87456.03
147And12.39364.16
148 And12.34362.18
149And12.43359.13

150A13.00417.09 M+H{Hal}
151A12.48401.07
152A12.57371.14
153A12.27358.13
154 A12.42408.12
155A12.50355.17

156A92.12401.13
157A31.32367.47
158A12.35408.22
159A12.60407.11
160A 12.52371.14
161A12.62371.14

162A12.57375.1
163A12.95387.12
164A121.30373.18
165A12.47357.12
166A1 2.52389.13
167A120.80366.27

168A12.39341.15
169A120.87393.29
170A120.90406.30
171A12.20390.17
172A12102 376.23
173A12.57431.08

174And12.50387.12
175And12.54357.13
176And12.50389.13
177And12.05380.24
178And12.57408.13
179And92.29341.16

180A11.97389.19
181A120.80375.23
182A12.23401.12
183A12.52369.16
184A11.92407.23
185A120.82393.29

186A12.64391.13
187A92.36402.22
188A92.30392.19
189A12.37388.2
190A12.57358.12
191 A12.09647.33 2M+H

192A12.27374.19
193A12.04374.18
194A120.83360.23
195A41.28509.18
196A12.68444.13
197 A92.69455.06

198And12.65442
199And12.54440.98
200And172.40477.21
201And12.14405.22
202And12.40381.2
20312.68467.08

204A121.30453.16
205A92.63407.17
206A12.40459.09
207A82.77458.2
208A142.06481.14
209A 141.88453.14

210A92.86493.15
211A93.17509.10
212A121.16340.18
213A12.57379.15
214A121.15723.48 2M+H
215A12 1.10371.13

216A131.06388.05
218A12.77443.99
219A141.86469.16
220A41.09483.22
221A41.39540.19
222A41.28 501.14

223And41.40551.14
224And41.28483.15
225And41.30494.13
226And92.22487.09
227And12.64456.06
228And12.67456.03

229A92.22392.19
230A12.32362.17
231A120.97367.21
232A120.95367.23
233A120.97367.24
234A120.95353.16

235And110.97381.21
236And92.76515.07
237And12.67472.21
238And121.40458.21
239And12.70472.22
240And121.41458.25

241 A121.41444.16
242A41.12430.18
243A12.45461.11
245A12.65412.09
246A12.72441.16
247A12.67426.11

248 And12.80431.18
249And172.82504.13
250And13.15476.13
252And92.51372.06
253And92.73446.06
254And41.14362.17

25592.44363.15
256And41.10377.16
257And12.79459.21
258And142.03461.17
259And12.72417.15
260And12.77431.17

262A 121.22667.31 2M+H
263A41.27426.19
264A61.30426.06
265A61.34392.15
266A121.12343.11
267A121.22379.09

268A14 1.77392.13
269A41.09358.14
270A110.87379.22
271A41.13372.15
272A41.05373.26
273A41.09358.18

275And120.97 346.16
276And41.32430.17
277And41.30455.26
279And41.35469.17
281And41.31439.15
282And41.27424.13

283A41.24425.14
284A41.21410.11
285A41.18376.22
286A141.84455.16
287A41.33441.08
288A141.90455.15

289A41.19407.24
290 A142.32493.09
291A141.94424.1
292A141.90425.11
293A141.85410.09
294A11.10391.25

295A92.50489.06
296 A41.35444.19
297A41.14443.2
298A141.92455.1
299A41.51497.31
300A41.54497.32

301A142.11509.18
302A 142.07509.07
303A142.02501.13
304A12.84513.05
305A141.98469.11
306A41.37455.15

307And12.60428.04
308And1 2.77441.07
309And12.87447.19
310And92.75494.04
311And92.97496.07
312And172.67474.19

313A172.72478.13
314A17480.15
315A92.85447.07
316A92.68461.08
317A92.70446.30
318A172.60462.17

319And12.77462.05
320And92.74 446.08
321And92.87481.03
322And92.72495.04
323And92.54464.10
324And172.43503.16

325A92.59446.04
326A12.17420.17
327A12.70415.18
328A12.15420.17
329A12.67478.09
330A92.79480.05

331A12.62460.1
332A92.75462.06
333A92.71447.05
334A92.59461.04
335A92.86494.03
336A92.90481.01

337A92.82495.05
338A92.58462.29
339 A92.78478.04
340A92.97480.10
341A92.74465.11
342A121.16353.16

343A111.16453.12
344A92.17506.12
345A 12.65520.24
346A12.59504.26
347A141.73472.23
348A92.40530.34

349A92.32486.18
350A93.03530.25
351A4 1.39481.14
352A41.30376.13
353A21.85411.07
354A141.83483.08

355A121.37429.06
356A121.24401.15
357A41.9 427.15
358A41.42511.11
359A41.20457.07
360A121.18470.13

361A41.14457.1
362A41.39455.16
363A92.43399.3
364A31.41363.32
365A12.34400.12
366A12.55382.09

367A92.40366.16
368A12.12366.18
369A12.59426.04
370A12.29400.11
371A12.57382.12
372A12.48366.13

373A12.12366.18
374A121.18352.20
375A121.27354.11
376 A121.22382.16
377A41.17456.2
378A141.74481.17

379A41.36499.02
380A12.27408.19
381A121.28417.17
382 A12.25408.19
383A41.28499.18
384A41.20451.3

385A141.91499.22
386A120.97405.27
387A110.94391.19
388120.97419.27
392A41.31339.14
393A121.25380.20

394A151.85435.07
395A12.72395.11
396A12.64353.13
397A 121.20364.23
398A121.16364.22
399A12.65363.17

400A12.37361.14
401A120.84295.31
402A141.69427.13
403A14 2.01455.1
404A141.44375.24
405A141.50375.24

406A92.22443.13
407A12.85375.12
408A92.82389.21
409A92.40 365.15
410A110.88364.19
411A120.92352.22

412A12.10366.18
413A120.90352.22
414A120.93352.24
415A120.92338.15
416A92.76508.03
417A92.58480.05

418A172.74481.12
419A92.69449.08
420A92.64492.08
421A92.48464.05
422 A172.65510.13
423A172.79524.15

424A172.75497.13
425A172.59490.16
426A172.43462.14
427A92.65463.08
428 A172.68479.11
429A12.65449.09

430A172.75510.16
431A92.88524.03
432A93.16524.99
433A172.67496.11
434 A92.82483.04
435A92.60494.10

436A92.77508.06
437A92.88508.99
438A172.55480.14
439A92.87467.09
444A1.26434.23 H+H+CH3CN
445A121.25380.21

446A92.74422.14
447A41.33421.16
448A92.08401.21
453A141.56361.21
454A2377.08
455A151.94320.13

456A22.12406.12
457A12.59427.11
458A151.77405.15
461A151.85391.17
463A131.04 428.2
464A41.12387.23

465A41.04373.19
466A121.05359.25
467A141.88338.25
468A41.30305.13
469A41.30441.22
470A41.35455.16

471And41.13393.14
472And41.10373.14
473And41.15393.11
474And41.12377.16
475And41.08373.13
476 And61.14393.1

477And142.12406.12
479And22.02420.14
480And12.47456.15
483And13.39491.11
484And12.99477.12
485 And22.14420.14

488And92.14403.23
489And12.80393.23
490And141.57409.2
491And92.13409.13
492And92.31443.16
493 And12.42443.07

494A92.37407.21
495A92.46481.02
496A82.83463.14
497A92.16403.18
498A92.28443.13
499A2.46461.19

500A141.70443.17
501A12.43427.09
502A12.30409.12
503A92.74393.2
504A121.10360.26
505A12 1.28374.26

506And12.39388.08
507And12.77395.12
508And12.35388.11
509And12.59384.12
510And12.42366.14
511And12.55 376.2

512A12.55412.12
513A12.60415.12
514A12.57382.14
515A12.42366.15
516A12.32348.15
517A12.68424.18

518A121.12456.13
519A121.12456.07
520A61.35484.17
521A121.27368.16
522A121.22352.18
523A121.20368.13

524A120.88352.23
525A120.88352.23
526A41.05389.23
527A131.00375.21
528A12.59384.13
529A12.54382.12

530 A12.43366.15
531A12.60415.12
532A12.59382.12
533A92.35366.15
534A12.60393.16
535A12.32348.15

536 And121.12456.12
537And120.88352.22
538And121.10456.12
539And121.32362.25
540And121.25368.18
541And121.22368.17

542 A121.08442.01
543A121.20354.08
544A110.91338.16
545A111.09470.10
546A121.22382.14
547A111.15382.15

548And 120.85366.23
549And41.28431.1
550And41.37525.98 M+H{Hal}
551And142.02420.14
552And120.87388.27
553And92.79440.13

554A9 2.71407.03
555A12.85407.04
556A13.02434.03
557A12.75391.06
558A92.41461.1
559A12.37461.25

560And92.71 495.09
561And92.35461.13
562And92.36487.09
563And92.22445.17
564And12.47477.25
565And13.04525.2

566A92.90459.14
567A92.76507.09
568A121.33365.23
569A12.57375.17
570A12.07361.16
571A141.71336.13

572A12.92434.02
573 A12.70389.17
574A92.51433.09
575A92.52364.23
576A121.20392.23
577A121.23395.20

578A12.43397.09
579 A121.22383.13
580A12.43397.09
581A141.95481.15
582A142.02481.14
583A92.32462.18

584And12.47462.18
585 And12.77369.09
586And12.62379.13
587And120.98360.28
588And12.04361.16
589And120.83372.26

590A41.27411.16
591A 12.74403.11
592A12.68432.16
593A12.77417.12
594A12.65386.14
595A141.38331.24

596And12.37399.15
598And12 1.18367.26
599And111.20467.14
600And121.30453.16
601And121.13348.24
602And121.16345.19

603A111.22415.12
604A111.08605A121.13357.21
606A111.15367.22
607A121.20353.24
608A121.20380.20

609And111.11407.16
610And121.23393.20
611And121.38357.20
612And121.32387.19
613And121.33373.20
614And121.25367.22

615A121.30353.26
616A120.87407.30
617 A120.87393.31
618A121.03376.24
619A110.78407.27
620A121.13367.21

621And121.15353.21
622And120.78374.22
625 And121.43353.15
626And121.02366.28
627And120.97366.25
628And121.48340.21

629A120.83407.34
630A110.95407.27
631 A41.05412.22
632A121.15462.19
633A92.51379.21
634A31.31365.42

635And131.16337.2
636And41.19365.29
637And 121.22339.18
638And121.08311.24
639And12.25352.18
640And92.27351.14

641And41.10337.25
642And41.11369.16
643And18 1.11368.16
644And31.44434.3
645And41.27379.09
646And41.29421.09

647A41.28420.21
648A41.30405.08
649A41.20 371.18
650A141.83404.13
651A41.21389.14
652A131.29355.31

653A121.27351.19
654A41.28379.1
655A41.21371.14
656A41.11355.17
657A41.16386.2
658A41.23371.14

659A141.83404.15
660A141.87389.12
661A121.24355.16
662 A41.14371.11
663A131.26351.23
664A41.42446.19

665A131.45420.21
666A131.15337.2
667A40.77338.19
668 A41.14338.15
669A12.14403.16
670A131.14406.21

671And12.75457.05
672And12.39471.05
673And172.68473.12
674 And121.05378.28
675And12.54422.2
676And12.20380.2

677And12.37418.18
678And12.40418.18
679And120.98366.20
680And 41.07367.17
681And131.21353.23
682And41.11367.16

683A12.52422.21
684A12.20380.19
685A121.02366.24
686A12 1.02366.24
687A121.00352.15
688A110.96380.19

689A41.16446.2
690A41.22434.16
691A120.99366.39
692A41.06 394.25
693A41.54476.2
694A41.24462.32

695A12.60435.11
696A41.24421.24
697A41.34434.19
698A83.33471.11
699A92.71437.02
700A41.18773.47 2M+H

702And151.90430.00
704And151.74465.07
710And151.88521.06
712And241.70472.14
714 And241.75486.13
715And241.76487.14

716And241.79501.12
719And241.68456.27
720And241.72470.26
721And241.70471.29
722 And241.75485.30
724And241.87512.30

725A241.76490.20
726A233.19491.96
727A241.73476.14
728A241.64430.14
729 A241.85518.24
731A211.30508.14

732And211.18472.18
733And211.38462.09
735And252.74448.02
736And252.67475.05
737And 211.33489.19
738And252.27460.15

739A201.42526.03
740A201.39506.05
741A201.36461.03
742A201.30526.17
743A20 1.31443.09
744A201.43513.13

745A201.43478.14

Example of synthesis (Example 623) method

Stage 1: in 7.5 ml of dimethylformamide was dissolved 1,055 g 2-bromoindene (5 mmol) and under stirring while cooling in an ice bath was added to 0.98 ml of cyclopentylamine for 60 seconds. After another 25 minutes at a temperature of an ice bath was added 7.5 ml of 2N hydrochloric acid and 15 ml of water and thoroughly mixed mixture. Thrice made the extraction each time with 15 ml of ethyl acetate. The quality of the product received 2-cyclopentylamine in the form of a solution in the aqueous phase of hydrochloric acid.

Stage 2: obtained in stage 1 2-cyclopentylamine in aqueous solution with a pH of 3 (about 20 ml) for about 1 hour added divided by 4 servings 0.5 g of sodium borohydride while stirring. After additional PE is emiliania at room temperature for about 3-4 hours in the sediment had a white product. After filtration by suction and drying in the air it was mixed with n-heptane. Received 320 mg of TRANS-2-cyclopentylamine-1-hydroxyindole.

Stage 3: in 3.5 ml of DMSO was dissolved 300 mg (1.38 mmol) of TRANS-2-cyclopentylamine-1-hydroxyindole and added 481 mg (was 2.76 mmol) 4-performativity and 300 mg of powdered sodium hydroxide. The mixture was stirred until complete dissolution of the components and during the night kept at room temperature. After adding 5 ml of water several times carried out the extraction with ethyl acetate acetic acid and quickly washed the combined ethyl acetate phase a small amount of water until neutralization and dried with magnesium sulfate and solvent removed under vacuum. The residue was subjected to pulse chromatography filled with 20 g silica gel column. The product was suirable using pure ethyl acetate.

By analogy with Example 623 were synthesized examples the following connections:

ExampleStructureThe method of synthesisMethod LCVP (min)MS [M+H+] ERIE+

251 In93.06359.08
261In12.40355.08
278In92.62423.08
441In82.56315.15
451In92.34377.22

459In92.63413.06
460 In92.52391.06
478In92.92375.06
597In92.62394.01
623In82.94372.36
624In151.76358.10

701In92.47360.10
703In 252.32363.08
705In151.96386.13
706In151.76358.16
708In151.82358.17
709In151.83377.15

711In152.24400.15
713In24419.07
717In241.85372.10
718In232.83391.08
723In241.87374.18

730In241.85386.20
734In232.73372.17

Example of synthesis (Example 280) method

Example 280

Stage 1: in 2 ml of tetrahydrofuran was dissolved 202 mg (1 mmol) of 4,6-dichloride-1-she and EXT the wheelie 263 mg dimethylformamidine (2.2 mmol). The solution for 3 h and stirred at 83°C and concentrically under vacuum. The residue was ground into powder with diethyl ether and filtered by suction. Received 216 mg of yellow crystals of 4,6-dichloro-2-[1-dimethylamino methylidene]indan-1-it.

Stage 2: in 2.5 ml of dimethylformamide was dissolved 255 mg (1 mmol) of 4,6-dichloro-2-[1-dimethylaminomethylene]indan-1-it, and after addition of 140 mg pyrrolidine within 4.5 hours was stirred at 70°C. the Reaction mixture was Vesali in hot water and kept for 1 day at room temperature to crystallization. By filtering by suction obtained 270 mg of yellow crystals.

Stage 3: in 5 ml of methanol was dissolved 4,6-dichloro-2-pyrrolidin-1-ylmethylene-1-he obtained in stage 2, and within 7 hours portions added a total of 700 mg NaBH4(18.5 equivalent). The mixture was concentrated under vacuum and saturated the residue 50 ml of water. After 4-fold extraction each time with 10 ml of ethyl acetate the mixture was dried with magnesium sulfate and solvent removed. The residue was subjected to chromatography on silica gel using as eluent methanol and ethyl acetate in a ratio of 3:10. The quality of the product received a mixture of CIS/TRANS-isomers.

Stage 4: in 1 ml of DMSO was dissolved a mixture of CIS/TRANS-4,6-dichloro-2-pyrrolidineethanol (84 mg)obtained in stage 3, was added 100 mg of 4-performativity and 100 mg of powdered sodium hydroxide. The mixture for 40 minutes was stirred at room temperature. After adding 5 ml of water several times carried out the extraction with ethyl acetate acetic acid, the combined ethyl acetate phase was quickly washed with a small amount to neutralize, dried with magnesium sulfate and solvent removed under vacuum. The residue was subjected to pulse chromatography filled with 20 g silica gel column. After Burovaya using pure ethyl acetate obtained 64 mg of TRANS-4,6-dichloro-1-(4-methylsulphonyl-phenyloxy)-2-pyrrolidineethanol, and after elution with ethyl acetate/methanol in the ratio 9:1 received 9 mg of the corresponding cisisomer.

In analogy to Example 280 were synthesized examples the following connections:

ExampleStructureThe method of synthesisMethod LCVP (min)MS [M+H+] ERIE+
21712.70414.15
24492.42346.12
27412.42372.2
28092.74440
38992.52407.08

39092.51372.12
39192.91353.13
440 83.09421.20
44292.55407.08
44392.04329.17
44992.62407.13

450172.43405.18
45282.96391.18
4629 2.33363.20
48692.02345.17
48792.37388.17

Example of synthesis (Example 26) D

Step 1: to a solution of protected sellowii groups amerosport (400 mg, 1 equivalent), PPh3(220 mg, 1.10 equivalents) and DPPA (0.23 ml, 1.10 equivalents) in anhydrous THF (5 ml) at 0°C dropwise added a 1 M solution of DIAD (from 0.84 ml, 1.10 equivalents) in THF in the Ar environment. Suspension for 60 min was stirred at 0°C (controlled by LC/MS) and cooled to -10°C. At this temperature in one portion cautiously added LiAlH4(57 mg, 2 molar equivalent) and for 60 min mixture was stirred while cooling in ice. The suspension is poured into the melt water and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of speakers chromatog is the her (ethyl acetate/methanol). The quality of the product obtained colorless oil (90 mg).

Stage 2: to the solution of diamine (90 mg, 1 equivalent), RA2(dba)3(6.3 mg, 0.04 equivalent), RAC-BINAP (8.5 mg, 0.08 equivalent), NaOtBu (23,0 mg, 1.40 equivalent) in toluene (2 ml) was added 4-bromophenylacetate (38,2 mg, 0.95 equivalent) and within 10 h mixture was heated at 70°C (control by TLC). The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with ethyl acetate, the combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography (ethyl acetate/Meon). The quality of the product obtained colorless oil (75 mg).

Stage 3: to a solution of protected sellowii groups of the diamine (75 mg, 1 equivalent) in THF (2 ml) at RT was added HF/pyridine (100 l, purity 65-70%) and for 6 h and stirred the mixture at RT. The mixture was poured into a saturated aqueous solution of NaHCO3and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography (ethyl acetate/Meon). As the target product was obtained oil is pale yellow (20 mg).

By analogy with Example 26 were si is testirovany examples of the following compounds:

ExampleStructureThe method of synthesisMethod LCVP (min)MS [M+H+] ERIE+
26D162.03441.10
481D191.94469.10
707D151.73357.16

Example of synthesis (Example 482) method E

Stage 1: a solution of ester benzoic acid (to 4.41 g, 1 equivalent) in acetone (125 ml) at RT was added 2N aqueous NaOH solution (3,59 ml, 1.10 equivalents) and for 5 h mixture was stirred at RT until fully reacted product of the previous step of the reaction (monitoring by TLC). Removed the acetone under vacuum and mixed OST is OK with water. The aqueous phase was extracted with ethyl acetate, the combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography (ethyl acetate/n-heptane). The quality of the product received the oil is pale yellow (3,20 g).

Stage 2: in the solution amerosport (300 mg, 1 equivalent) in THF (4 ml) at 0°C was added NaH (24 mg, 1.30 equivalent of 80% mineral oil), removed ice bath and for 1 hour gave the mixture to warm to CT. Added 4-cyano-2-terbisil bromide (134 mg, 1.10 equivalents) and for 3 h and stirred the reaction mixture at RT (control by TLC). The mixture was poured into a saturated aqueous solution of NaHCO3and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude products were purified by the method of column chromatography (CH2Cl2/MeOH). The quality of the product obtained colorless oil (227 mg).

Stage 3: to a solution of protected sellowii groups aminoacetanilide alcohol (227 mg, 1 equivalent) in THF (2 ml) at RT was added 1 M solution of TBAF in THF (0,52 ml, 1.5 equivalents) and for 2 h and stirred the mixture at RT. The mixture was poured into a saturated aqueous solution of NaHCO3and were extracted aqueous phase is by using ethyl acetate. The combined organic phases are dried with Na2SO4that was filtered under vacuum, removed the solvent. The crude product was purified by the method of column chromatography (CH2Cl2/Meon). As the target product was obtained oil is pale yellow (68 mg).

By analogy with Example 482 were synthesized examples the following connections:

ExampleStructureThe method of synthesisMethod LCVP (min)MS [M+H+] ERIE+
24E152.00489.03
482E152.06420.08

Example of synthesis (Example 755) method G

Step 1: to a suspension of 1,3-dimethylbarbituric acid (364 mg, 2 equivalents) and Pd(PPh3)4(67 mg, 0.05 equivalent) in CH2Cl2(2.0 ml) in argon was added Rast is the Ohr allylamine (583 mg, 1 equivalent) in CH2Cl2(2.0 ml/mmol of allylamine) at room temperature. The solution was delegirovali for 1 h, the Reaction mixture was cooled to room temperature and diluted with ethyl acetate. Washed the organic layer with a saturated aqueous solution of Na2CO3the solution was dried on Na2SO4and solvent removed under vacuum. The crude product was purified by pulsed chromatography on silica gel using ethyl acetate/heptane/Meon (5:10:1) for elution. The quality of the product obtained colorless oil (211 mg).

By analogy with Example 755 were synthesized examples the following connections:

ExampleStructureThe method of synthesisMethod LCVP (min)MS [M+H+] ERIE+

746G233.28475.16
747G22 1.02440.15
748G252.79459.22
749G201.31459.16
750G201.38443.10
751G201.41424.10

752G201.41461.19
753G201.37 462.19
754G201.42508.16
755G201.43460.20
756G201.46460.19

Method of analysis in order to determine the pharmacological activity

During this analysis determined the recovery of intracellular pH (pHi) cells LAP1, which, after acidification stably Express the sodium-hydrogen exchanger of subtype 3 (NHE3). Recovery occurs even in the absence of bicarbonate functional NHE3. To determine the pH of the used probe-based sensitive to pH fluorescent dye (produced by the company Molecular Probes, Eugene, Oregon, USA using predecessors BCECF-AM). Cells initially incubated with BCECF (5 µm BCECF-AM) in the buffer of NH4Cl (buffer of NH4Cl: 115 mm holdingarea, 20 mm NH4Cl, 5 mm Kl, 1 mm CaCl2, 1 mm MgCl2, 20 mm Hepes, 5 mm glucose, using 1 M KOH brought the pH to 7.4). Induced intracellular acidification by washing cells incubated in the buffer of NH4Cl, not containing NH4Cl buffer (133,8 mm holdingarea, of 4.7 mm KCl, 1.25 mm CaCl2, 1.25 mm MgCl2, 0,97 mm K2HPO4, 0.23 mm KH2PO4, 5 mm Hepes, 5 mm glucose, using 1 M KOH brought the pH to 7.4). Stage after washing the cells remained 90 l not containing NH4Cl buffer. Restoring the pH was started by adding 90 l containing Na+buffer (133,8 mm NaCl, of 4.7 mm KCl, 1.25 mm CaCl2, 1.25 mm MgCl2, 0,97 mm Na2HPO4, 0.23 mm NaH2PO4, 10 mm Hepes, 5 mm glucose, using 1 M NaOH brought the pH to 7.4) in the measuring device (FLIPR, "Fluorometric Imaging Plate Reader", the production company Molecular Devices, Sunnyvale, California, USA). The BCECF fluorescence was determined using wave excitation length of 498 nm and emission filter 1 FLIPR (with bandwidth 510-570 nm). Within two minutes recorded subsequent changes of fluorescence as an indicator of recovery of LV. To calculate the strength of inhibition of NHE3 in the test substance, the cells initially investigated in the buffers, the use of which was completely restore pH. For full recovery of pH (100%), cells were incubated in containing Na+ buffer (see above), and to determine the rate of 0% of the cells incubated in not containing Na+buffer (see above). The test substance was placed in the containing Na+buffer. Recovery of intracellular pH at each test concentration of the substances was determined in percent of the maximum recovery. Based on the percentages of recovery of pH for the respective substances were calculated value IC50using XLFit (production company idbs, Surrey, UK).

Inhibitory effect on NHE3 shown forth in the following table, broken down into three levels of activity:

the degree of activity 1: 20-50% inhibition at a concentration of 10 µM

activity 2: IC50at concentrations of 1-10 µm

activity 3: IC50<1 μm

ExampleThe degree of activityExampleThe degree of activityExampleThe degree of activity
12241473
2 2253481
33262492
42273501
52282511
62292521
72302531
83313541
9232155 1
102332561
112341571
123351582
132361592

142373602
152381612
162391623
17 2401631
182412641
192421651
202431661
213441671
222451681
232461691
701933 1162
7129411172
7239531182
7339611193
7419731203
7519831212
7629931223
77110031232
7810131242
79310231251
80210331263
81110431273

82210521283
8321063
84310721303
85210 21313
86210931323
87111031333
88211131343
89211221351
90211331361
91311421371
9211151138139316211852
140216321861
141316421871
142316511882
143316611892
144316721901
145316811911
146231921
147317021932
148117121942
149117221953

150117311963
151117411973
152117511983
1531176 11993
154217712003
155117812012
156117912021
157118012031
158118122042
159118222051
160118312063
118412073
208123132543
209323222552
210223322562
211123422573
212223522583
213123632591
2142237 12602
215223822611
216123912622
217124022633

218124122642
219124212653
220324332662
22132441 2672
222324512681
223324622691
224324712702
225324832712
226324912722
227225012733
228225112742
229 125212752
230125312763
277330023233
278230113243
279330213253
280230333262
281330433271
28213053 3281
283330623293
284230723303
285230833313

286230933322
287331013333
288331113343
28933121335 3
290131333363
291231433372
292331523382
293231623393
294231723403
295331833413
296131923422
297123432
298332133443
299332233453
346336913922
347337033932
348337113942
349337213951
35023733396 1
351137423972
352337523982
353137623991

354137734001
355237834012
356337934022
357338014032
358238124041
359238214053
360238334063
361238414073
362338534081
363238624093
364238724102
3652388 24113
366138924121
367139014132
368239114142
415243824611
416243934621
417244014632
418244124643
244224653
420244314663
421244434672

422344534682
423244614692
424344734702
425344834711
426 344914722
427245014733
428345134742
429245224752
430345334762
431245414773
432245514781
43324563 4793
434345734803
435245814812
436245914821
437246034833
484150715301
485150815311
486150925322
487 151035333
488351115341
489151215352

490351315362
491351425372
492351525382
493351635392
4942 51715402
495251835412
496251935423
497152035432
498152125442
499352225452
500352325462
50135243547 2
502352525482
503152625491
504252725503
505252825513
506152915523
553257625992
554257726002
555216012
556357926022
557258016032

558358136043
559358226052
560358326062
561358426072
5622585 16082
563358616092
564358726102
565358816112
566358926122
567259016132
568259116142
569159216152
159316162
571259416172
572259526182
573159626192
574259716202
575159826212
622264526683
6232646 16692
624264726701
625264826713

626264916723
627265036732
628265126742
629265226752
63026532 6762
631365416773
632365526783
633265626793
634265726802
635165836812
636365936822
637266026832
638 266136841
639166226852
640366336862
641366436872
642266536882
643166626893
644366726903
69137142 7372
692371537383
693371637393

694371727403
695271837413
696371927422
697272027433
69837212744 2
699272227451
700372317463
701272417472
702372527482
703272637492
704372737502
705272827512
706127522
707273027532
708273137543
709373227552
710273327562
71117342
71227352
71327362

1. The compound of formula I:

in which:
A denotes a six-membered aryl radical or a five-membered heteroaryl radical, where the heteroaryl radical may contain one heteroatom selected from the group comprising oxygen and sulfur,
one or more hydrogen atoms in the above-mentioned aryl or heteroaryl radicals can be substituted for the placeholder groups R1 are independently from each other selected from the group comprising: F, Cl, Br, I, (C1-C10)-alkyl, (C1-C10)-alkoxy, -NR13R14,
mentioned alkyl and alkoxy radicals can be once or several times substituted by F
In denotes the radical with mono - or condensed bicyclic ring selected from the group including:
six-desyatiletnie aryl radicals,
five-desyatiletnie heteroaryl radicals and
nine-chetyrnadcatiletnie cyclohexanemethylamine radicals, where cyclogeranyl groups can be saturated or partially unsaturated,
and heterocyclic groups can contain one or more heteroatoms selected from the group comprising nitrogen, oxygen and sulfur,
one or more hydrogen atoms in the radical groups may be replaced by replacing the groups R5, which are independently from each other selected from the group comprising: (C1 4)-alkyl radicals, (C1-C4-alkoxyalkyl, (C1-C4-alkylthiomethyl, (C2-C5)-cyclogeranyl radicals, (C2-C5-cyclogeranyl (C1-C4)alkyl radicals, where cycloheptatriene ring in both residues may contain 1 or 2 nitrogen atom, 1 nitrogen atom and 1 oxygen atom or sulfur or 1 oxygen atom or 1 sulfur atom, family, (C1-C9)-heteroaryl radicals, cyclogeranyl groups can be saturated or partially unsaturated,
and one or more hydrogen atoms in the above-mentioned radical groups R5 may be substituted by further radicals, which are independently from each other selected from the group including: radical groups R11,
R5 may also represent one or more radicals independently from each other selected from the group comprising: OH, (=O)NH2, F, Cl, Br, I, CN, NO2, -NR17R18, -NR16COR17, -NR16COOR17, -NR16CONR17R18, -NR16-S(O)2-R17, -NR16-S(O)2-NR17R18, -COOR16, -COR16, -CO(NR17R18), S(O)nR16, -S(O)2NR17R18,
R16, R17 and R18 independently of one another may represent a radical selected from the group comprising: H, and (C1-C4) -alkyl radicals,
where the alkyl radicals may be independently from each other substituted by one or more F, or OH, (=O), CN, -NR13R14, -COOR12, or (C6-C10)-aryl and
R17 and R18 together with the nitrogen which, with which they are linked, may form a four-semiline saturated, unsaturated or partially unsaturated heterocyclic compound containing 1-5 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-, =N -, and-NR15-,
formed heterocyclic compound may be one or more times independently from each other substituted with F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C4)-alkoxy, (C1-C4) -alkyl, (C3-C7-cycloalkyl, each of which is independently from each other, in turn, may contain one or more radicals F, OH, (=O)NH2, NH (C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy,
L denotes a covalent bond,
X denotes the group-O-,
R2 is absent or represents one or more substituents, which independently of one another may be selected from the group comprising F, and (C1-C4)-alkyl radical,
this alkyl radical may be substituted by one or more F atoms,
R3 and R4 independently of one another denote a radical selected from the group comprising (C1-C10)-alkyl radicals, (C3-C14)-cycloalkyl radicals, (C4-C20)-cycloalkylation Radik the crystals, (C2-C19)-cyclogeranyl radicals, (C3-C19)-cyclohexanediamine radicals, (C6-C10)-aryl radicals, (C7-C20)-arylalkyl radicals, (C1-C9)-heteroaryl radicals, (C2-C19)-heteroarylboronic radicals, the radicals R3 and R4 independently of one another one or more times may be substituted by a radical from the group comprising: OH, NH2, F, Cl, CN, or-NR13R14, or
R3 and R4 together with the nitrogen to which they are bound, may form a four-desatino saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-, =N -, and-NR8-,
where heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group of R7 and R9, and
heterocyclic radicals formed by R3 and R4 may be connected in bridge connection or saturated (C1-C10)-alkyl chain, where
R8 in the group NR8 may form with the ring formed by R3 and R4, additional saturated, unsaturated or partially unsaturated heterocyclic compound, which may
optionally contain one or more heteroatoms is N=,
R7 denotes (C1-C4)-alkyl radical, with skinny radical may be independently of one another once or several times substituted by R9,
R8 denotes H, (C1-C4)-alkyl radical or cyclopropyl, this alkyl radical can be, independently of one another once or several times substituted by R10,
R9 denotes a radical selected from the group comprising: OH, F, Cl, CN, -NR13R14, -NR13COR12, S(O)nR12, -S(O)2NR13R14, (C1-C4)-alkoxy, pyrrolidinyl, pyrimidinyl, N-pyrrolidinyl-CH2,
R10 represents a radical selected from the group comprising: F, OH, CN, (C1-C4)-alkoxy and-NR13R14,
R11 represents a radical selected from the group comprising: (C1-C4)-alkyl, (C1-C4)-alkoxy, (C3-C7-cycloalkyl, (C2-C13-cyclogeranyl,
they are all independent from one another one or more times can be replaced by F, or where (C1-C4- can be substituted by one CN, (C1-C4)-alkoxy, NR13R14, -NR13COR12, -NR13COOR12, -NR13CONR13R14, -NR13-S(O)2-R12, -NR12-S(O)2-NR13R14, -COOR12, -COR12, -CO(NR13R14), S(O)nR12, and-S(O)2NR13R14;
(=O)OH, F, Cl, Br, I, CN, (C1-C4)-alkoxy, NR13R14, -NR13COR12, -NR13COOR12, -NR13CONR13R14, -NR13-S(O)2-R12, -NR12-S(O)2-NR13R14, -COOR12, -COR12, -CO(NR13R14), S(O)nR12, and-S(O)2NR13R14;
R12, R13 and R14 are independently from each other denote H, (C1-C10)-alkyl, each of which may be independently of one another once or several times substituted by F or one OH, NH2, NH(C1-C4)-alkyl, N((C1-C4)-Ala is l) 2, CN or (C1-C10)-alkoxy, or
R15 denotes a radical selected from the group comprising: H, (C1-C4)-alkyl, (C3-C14-cycloalkyl, (C4-C20-cycloalkenyl, (C2-C13-cyclogeranyl, (C3-C19-cyclohexanoltramadol, each of which may be independently of one another once or several times substituted by F, OH, CN or (C1-C10)-alkoxy,
n denotes 0, 1 or 2,
p denotes 1 or 2 and
q denotes 0,
and its pharmaceutically acceptable salts,
and in which:
i) where A denotes a phenyl, A represents phenyl or benzodioxolyl, X denotes-O - or-S-, L denotes a bond, and R3 and R4 represent H, (C1-C10)-alkyl, (C3-C14-cycloalkyl, (C7-C20-arylalkyl or R3 and R4 together represent unsubstituted pyrrolidinyl, morpholinyl, piperidinyl or piperazinilnom radical or 4-methylpiperazine radical must be present at least one radical R5 that is not (C1-C10)-alkyl, (C1-C10)-alkoxy, OH, CF3, F, Cl, Br or I, radical,
ii) when A represents phenyl, X is-O-, -S - or-NH-, and R3 and R4 represent (C1-C10)-alkyl, (C3-C14)-cycloalkenyl or (C4-C20)-cycloalkylcarbonyl radical must be present at least one radical R5, the which is not F, Cl, Br, I, (C1-C4)-alkyl, (C1-C4)-alkoxy, CF3, OCF3, CN, NO2, NH2, -NH((C1-C10)-alkyl), -N((C1-C10)-alkyl)2, unsubstituted or substituted benzoline or unsubstituted or substituted phenyl-(CH2)r-Y-(CH2)s-radical, in which Y represents a bond or oxygen, and r and s is equal to from 0 to 4, wherein r+s is not larger than 4.

2. The compound according to claim 1 of formula Ic:
,
in which
In denotes the six-decatizing monocyclic or condensed bicyclic aryl group, five-decatizing monocyclic or condensed bicyclic heteroaryl group, or condensed nine-chetyrnadtsatiletnyuyu bicyclic cyclogeranyl-aryl group, each of which may be independently of one another once or several times substituted by R5,
cycloalkyl and cyclogeranyl groups can be saturated or partially unsaturated,
cyclohexanemethylamine group as heteroatoms may contain 1 or 2 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom,
heteroaryl groups can contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 atoms of nitrogen and 1 atom of oxygen is a or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom, and
R2 is absent or represents one or more substituents, which independently of one another may be selected from the group comprising: F (C1-C6)-alkyl radicals which, independently of one another one or more times can be replaced by F,
the radicals A, X, L, q, R1, R3, R4 and R5 have the meanings indicated in claim 1, and
its pharmaceutically acceptable salt.

3. The compound according to claim 1, in which:
A represents phenyl or a five-heteroaryl radical, which as heteroatoms may contain 1 oxygen atom or 1 sulfur atom, one or more hydrogen atoms in the above-mentioned phenyl or heteroaryl radical may be independently from each other substituted radicals R1,
In denotes the six-decatizing monocyclic or condensed bicyclic aryl group, five-decatizing monocyclic or condensed bicyclic heteroaryl group, nine chetyrnadtsatiletnyuyu monocyclic or condensed bicyclic cyclohexanoltramadol group, each of which may be independently of one another once or several times substituted by R5,
cycloalkyl and cyclogeranyl groups can be saturated or partially unsaturated,
cyclohexanemethylamine group as heteroatoms may contain 1 or 2 nitrogen atom, 1 or 2 at the mA oxygen, 1 or 2 sulfur atom, 1 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom,
heteroaryl groups can contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or sulfur or 1 oxygen atom and 1 sulfur atom, and
R2 is absent or represents one or more substituents, which may be independently from each other selected from the group comprising: F (C1-C6)-alkyl radicals, with the alkyl radicals independently of one another one or more times can be replaced by F,
mentioned radicals X, L, q, R1, R3, R4 and R5 have the meanings indicated in claim 1, and
its pharmaceutically acceptable salt.

4. The compound according to claim 1 of the formula Id:
,
in which:
In may denote a phenyl group, naftalina group, pyridinyl group, hyalinella group, athinodorou group, indolenine group, benzothiophene group, benzodithiophene group, benzofuranyl group, benzodithiophene group, salesdipyridamole group, benzopyranyl group, benzoimidazolyl group, benzimidazolyl group, benzothiazolyl group, benzothiazolyl group, pentoxifylline group, indolinyl group, benzodioxolyl group, tetrahydroisoquinoline group, then it is carbonated is rhinolining group, in which one, two, three or four of the hydrogen atom in the group may be substituted by radicals from the group R5,
each radical R5 independently from each other selected from the group including:
(C1-C4)-alkyl, which may be fully or partially fluorinated, or in which one hydrogen atom may be replaced by CN, NH2, OH, NH (C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-alkoxy,
(C1-C4)-alkoxy, which may be partially or fully fluorinated,
(C1-C4)-alkylthio, which may be partially or fully fluorinated,
(C2-C5-cyclogeranyl and
(C2-C5-cyclogeranyl-(C1-C4)-alkyl, which
cycloheptatriene ring may be saturated or partially unsaturated and may contain 1 or 2 nitrogen atom and 1 oxygen atom, 1 nitrogen atom and 1 sulfur atom or 1 nitrogen atom and 1 oxygen atom, and
cycloheptatriene ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -NH2, -CN, (C1-C4)-alkyl, (C3-C7-cycloalkyl, OH, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-alkoxy,
phenyl, naphthyl,
(C1-C6-heteroaryl, which heteroaryl ring may be monocyclic or articulated bizi the symbolic ring, which may contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or sulfur, and
heteroaryl ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -NH2, -CN, (C1-C4)-alkyl, (C3-C10-cycloalkyl, OH, NH (C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C10)-alkoxy, -C(O)O-(C1-C4)-alkyl,
H, OH, (=O), F, Cl, Br, CN, NO2, -NR17R18, -NR16COR17, -NR16COOR17, -NR16CONR17R18, -NR16-S(O)2-R17, -NR16-S(O)2-NR17R18, -COOR16, -COR16, -CO(NR17R18), S(O)nR16, where n=1 or 2, -S(O)2NR17R18,
R16, R17 and R18 independently of one another may denote a hydrogen radical or a radical selected from the group comprising: unsubstituted or substituted (C1-C4)-alkyl radicals in which the substituents are alkyl radicals selected from F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2and CN,
R17 and R18 together with the nitrogen to which they are bound, may form a five or six-membered saturated, unsaturated or partially unsaturated heterocyclic compound containing 1-5 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N-, -NH - and-N((C1-C4)-alkyl)-, while the formed heterocyclic compound independently from each other and one is several times substituted (C 1-C4)-alkyl, (C3-C7-cycloalkyl, each of which can in turn independently from each other to contain one or more radicals F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C4)-alkoxy,
R1 is absent or represents one, two or three radicals, which are independently from each other selected from the group comprising: F, Cl, (C1-C4)-alkyl, (C1-C4)-alkoxy, where alkyl and alkoxyalkyl substituted one or more times can be F, and(or)
R3 and R4 independently of one another denote a radical selected from the group comprising (C1-C4)-alkyl, (C3-C7-cycloalkyl-, (C3-C7-cycloalkyl-(C1-C4)-alkyl, (C3-C6-cyclogeranyl-, phenyl-, phenyl-(C1-C4)-alkyl, (C1-C5-heteroaryl,
the radicals R3 and R4 independently of one another once, twice or three times may be substituted by a radical from the group comprising: OH, F, Cl, -NR13R14, where R13 and R14 represent H or (C1-C4)-alkyl,
R3 and R4 together with the nitrogen to which they are bound, may form a four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-,
GE is eroticlingerie radicals independently of one another one or more times can be substituted radical, selected from the group of radicals R7 and R9,
heterocyclic radicals can be connected in bridge connection, or (C1-C7)-alkyl chains, or-NH-, N((C1-C4)-alkyl), and
R8 in the group NR8 may form with the ring formed by R3 and R4, additional saturated, unsaturated or partially unsaturated heterocyclic compound
the radicals R7, R8 and R9 have the meanings specified in claim 1, and its pharmaceutically acceptable salts.

5. The compound according to claim 1, in which:
In denotes a phenyl group, naftalina group, pyridinyl group, hyalinella group, athinodorou group, indolenine group, benzothiophene group, benzodithiophene group, benzofuranyl group, benzodithiophene group, salesdipyridamole group, benzopyranyl group, benzoimidazolyl group, benzimidazolyl group, benzothiazolyl group, benzothiazolyl group, pentoxifylline group, indolinyl group, benzodioxolyl group, tetrahydroisoquinoline group, tetrahydropyranyloxy group in which one, two, three or four of the hydrogen atom in the group may be substituted by radicals from the group R5,
one of the radicals R5 are selected from the group including
(C2-C5-cyclogeranyl, which
cycloheptatriene ring can is t be saturated or partially unsaturated and may contain 1 or 2 nitrogen atom, 1 oxygen atom, 1 nitrogen atom and 1 sulfur atom or 1 nitrogen atom and 1 oxygen atom, and
cycloheptatriene ring may contain further substituents from the group comprising: -F, -Cl, -Br, =O, -NH2-, -CN, (C1-C4)-alkyl and (C3-C7-cycloalkyl,
(C1-C6-heteroaryl, which heteroaryl ring may be monocyclic or articulated bicyclic ring which may contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or sulfur, and
heteroaryl ring may contain further substituents from the group comprising: -F, -Cl, -Br, =O, -NH2, -CN, (C1-C4)-alkyl, (C3-C7-cycloalkyl and C(O)O-(C1-C4)-alkyl, OH, (=O)NH2, NO2, -NR17R18, -NR16COR17, -NR16COOR17, -NR16CONR17R18, -NR16-S(O)2-R17, -NR16-S(O)2-NR17R18, -COOR16, -COR16, -CO(NR17R18), S(O)2R16 and -- S(O)2NR17R18,
R16, R17 and R18 independently of one another may denote a hydrogen radical or a radical selected from the group comprising: unsubstituted or substituted (C1-C4)-alkyl radicals,
in which the substituents are alkyl radicals selected from F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2and CN,
R17 and R18 together with the nitrogen to which they are bound, may form a five or six-membered saturated, unsaturated or partially nenas is placed heterocyclic compound, containing 1-5 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N-, -NH - and-N((C1-C4)-alkyl)-, heterocyclic this connection independently of one another one or more times can be replaced by (C1-C4)-alkyl, (C3-C7-cycloalkyl, each of which, in turn, independently of one another can contain one or more radicals F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C4)-alkoxy, and
more radicals R5 independently from each other selected from the group including:
(C1-C4)-alkyl, which may be fully or partially fluorinated, or in which hydrogen may be replaced by CN, NH2, OH, NH(C1-C4)-alkyl, N ((C1-C4)-alkyl)2or (C1-C4)-alkoxy,
(C1-C4)-alkoxy, which may be partially or fully fluorinated,
(C1-C4)-alkylthio, which may be partially or fully fluorinated,
phenyl,
OH, (=O), F, Cl, Br, CN, -NR17R18, NR16COR17, -COOR16, -COR16, and-CO(NR17R18),
R16, R17 and R18 independently of one another may denote a hydrogen radical or a radical selected from the group comprising unsubstituted or substituted (C1-C4)-alkyl radicals in which the substituents and killnig radicals selected from F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2and CN, or
R17 and R18 together with the nitrogen to which they are bound, may form a four-semiline saturated, unsaturated or partially unsaturated heterocyclic compound containing 1-5 carbon atoms, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N-, -NH - and-N((C1-C4)-alkyl)-, while the formed heterocyclic compound independently of one another one or more times can be replaced by (C1-C10)-alkyl, (C3-C14-cycloalkyl, (C4-C20-cycloalkenyl, (C2-C20-cyclogeranyl or (C3-C19-cyclohexanoltramadol, each of which, in turn, independently of one another can contain one or more radicals F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN or (C1-C10)-alkoxy,
R1 is absent or represents one, two or three radicals, which are independently from each other selected from the group comprising F, Cl, (C1-C4)-alkyl and (C1-C4)-alkoxy, where alkyl and alkoxy radicals of one or more times can be replaced by F,
R3 and R4 independently of one another denote a radical selected from the group comprising (C1-C )-alkyl-, phenyl-(C1-C4)-alkyl, NH2-(C1-C4)-alkyl, N((C1-C4)-alkyl)2-(C1-C4)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl-), (C3-C7-cycloalkyl-(C1-C4)-alkyl (C4-C6-cyclogeranyl, which contains a group-NH-, -O - and-S-, or
R3 and R4 together with the nitrogen to which they are bound, may form a four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-, while the heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group of radicals R7 and R9,
heterocyclic radicals can be connected in bridge connection, or (C1-C7)-alkyl chains, or-NH-, N((C1-C4)-alkyl)-, and
R8 may form with the ring formed by R3 and R4, additional saturated, unsaturated or partially unsaturated heterocyclic compound
R7 denotes H, (C1-C5)-alkyl radical, this alkyl radical can be, independently of one another once or several times substituted by R9,
R8 denotes H, (C1-C4)-alkyl radical cyclopropyl, with alkylpyridine may be independently of one another once or several times substituted by F, OH, CN, (C1-C4)-alkoxy, and-NR13R14,
R9 denotes a radical selected from the group comprising OH, F, Cl, CN, -NR13R14, -NR13COR12, S(O)nR12, -S(O)2NR13R14, (C1-C4)-alkoxy, pyrrolidinyl, pyrimidinyl, pyrrolidinyl-CH2,
R12, R13 and R14 independently from each other represent a hydrogen radical or a radical selected from the group comprising unsubstituted or substituted (C1-C4)-alkyl radicals in which the substituents are alkyl radicals selected from F, OH, NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, CN and (C1-C4)-alkoxy,
and its pharmaceutically acceptable salts.

6. The compound according to claim 1 of formula Ia:
,
in which:
A represents phenyl or a five or six-membered heteroaryl radical, which as heteroatoms may contain 1 oxygen atom or 1 sulfur atom, one or more hydrogen atoms in the above-mentioned phenyl or heteroaryl radical is independently from each other may be substituted by a radical R1,
In denotes the six-decatizing monocyclic or condensed bicyclic aryl group, pyatidesyatidnevnuyu monocyclic or condensed bicyclic heteroaryl group, or nine-chetyrnadtsatiletnyuyu monocyclic or condensed bicyclic cyclohexanoltramadol group, each is of which independently of one another one or more times may be substituted with R5,
this cycloalkyl and cyclogeranyl groups can be saturated or partially unsaturated,
cyclohexanemethylamine group as heteroatoms may contain 1 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atom, 1 nitrogen atom and 1 oxygen atom or 1 sulfur atom or 1 oxygen atom and 1 sulfur atom,
heteroaryl groups can contain 1, 2 or 3 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 nitrogen atom and 1 oxygen atom or sulfur or 1 oxygen atom and one sulfur atom, and
R2 is absent or represents one or more substituents, which independently of one another may be selected from the group comprising F, and (C1-C4)-alkyl radicals which, independently of one another one or more times can be substituted for F.
the radicals X, L, q, R1, R3, R4 and R5 have the meanings indicated in claim 1, and
its pharmaceutically acceptable salt.

7. The compound of formula Ib according to claim 1
,
in which:
In denotes a phenyl group, naftalina group, pyridinyl group, hyalinella group, athinodorou group, indolenine group, benzothiophene group, benzodithiophene group, benzofuranyl group, benzodithiophene group, salesdipyridamole group, benzopyranyl group, benzoimidazolyl group, benzimidazolyl group benzotriazolyl group, benzothiazolyl group, pentoxifylline group, indolinyl group, benzodioxolyl group, tetrahydroisoquinoline group or tetrahydropyranyloxy group in which one, two, three or four of the hydrogen atom in the group may be substituted by radicals from the group R5,
each radical R5 independently from each other selected from the group including:
(C1-C4)-alkyl, which may be fully or partially fluorinated, or in which hydrogen may be replaced by CN, NH2, OH, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-alkoxy,
(C1-C4)-alkoxy, which may be partially or fully fluorinated,
(C1-C4)-alkylthio, which may be partially or fully fluorinated,
(C2-C5-cyclogeranyl, (C2-C5-cyclogeranyl-(C1-C4)-alkyl, which
cycloheptatriene ring may be a monocyclic, bicyclic, saturated or partially unsaturated ring, and may contain 1 or 2 nitrogen atom and 1 oxygen atom, 1 nitrogen atom and 1 sulfur atom or 1 nitrogen atom and 1 oxygen atom, and
cycloheptatriene ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-Ala is XI, -CN, (C1-C4)-alkyl and (C3-C7-cycloalkyl,
phenyl,
(C1-C6-heteroaryl, which heteroaryl ring may be a monocyclic or condensed bicyclic ring which may contain 1, 2, 3 or 4 nitrogen atom and 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atom and 1 oxygen atom or sulfur, and
heteroaryl ring may contain further substituents from the group comprising-F, -Cl, -Br, =O, -NH2, OH, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2, (C1-C4)-alkoxy, -CN, (C1-C4)-alkyl, (C3-C7-cycloalkyl and-C(O)O-(C1-C4)-alkyl,
H, OH, (=O), F, Cl, Br, CN, NO2, -NR17R18, -NR16COR17, -NR16COOR17, -NR16CONR17R18, -NR16-S(O)2-R17, -NR16-S(O)2-NR17R18, -COOR16, -COR16; -CO(NR17R18), -S(O)nR16, where n=1 or 2, and-S(O)2NR17R18,
R16, R17 and R18 independently of one another may denote a hydrogen radical or a radical selected from the group comprising unsubstituted or substituted (C1-C4)-alkyl radicals in which the substituents are alkyl radicals selected from F, OH, (=O)NH2, NH(C1-C4)-alkyl, N((C1-C4)-alkyl)2and CN,
R17 and R18 together with the nitrogen to which they are bound, may form a five or six-membered saturated, unsaturated or partially unsaturated heterocyclic compound containing 1-5 carbon atoms, which can is optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N-, -NH - and-N((C1-C4)-alkyl)-, while the formed heterocyclic compound independently of one another one or more times substituted (C1-C4)-alkyl, (C3-C7-cycloalkyl, each of which can in turn independently from each other to contain one or more radicals F, OH, (=O) or (C1-C4)-alkoxy,
R1 is absent or represents one, two or three radicals, which are independently from each other selected from the group comprising F, Cl, (C1-C4)-alkyl, (C1-C4)-alkoxy,
which alkyl and alkoxyalkyl one or more times can be replaced by F,
R3 and R4 independently of one another denote a radical selected from the group comprising (C1-C4)-alkyl, (C3-C7-cycloalkyl-, (C3-C6-cyclogeranyl, phenyl, phenyl-(C1-C4)-alkyl and (C1-C5-heteroaryl,
the radicals R3 and R4 may be independently of one another once, twice or three times substituted radical from the group comprising OH, F, Cl, -NR13R14, where R13 and R14 independently of one another denote H, and (C1-C4)-alkyl, or
R3 and R4 together with the nitrogen to which they are bound, may form a four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain the Dean or several heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-,
where heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group of R7 and R9,
heterocyclic radicals can be connected in bridge connection, or (C1-C7)-alkyl chains, or-NH-, N((C1-C4)-alkyl)- and
R8 may form with the ring formed by R3 and R4, additional saturated, unsaturated or partially unsaturated heterocyclic compound
R7, R8 and R9 have the meanings specified in claim 1, and
its pharmaceutically acceptable salt.

8. The compound according to claim 1, in which:
R3 and R4 together with the nitrogen to which they are bound, may form a four-desatino saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-, =N -, and-NR8-,
this heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group of R7 and R9,
heterocyclic radicals formed by R3 and R4 may be connected in bridge connection or a saturated or unsaturated (C1-C4)-alkyl chain, or-NR15-,
R8 in the group-NR8 -, may form with the ring formed by R3 and R4, additional saturated, unsaturated or cha is partially unsaturated heterocyclic compound
n, R7, R8, R9 and R19 have the meanings specified in claim 1, and
its pharmaceutically acceptable salt.

9. The compound according to claim 1, in which:
R3 and R4 together with the nitrogen to which they are bound, may form a four to eight-membered saturated, unsaturated or partially unsaturated heterocyclic compound, which may optionally contain one or more heteroatoms from among-O-, -S(O)n-where n=0, 1, or 2, =N -, and-NR8-,
this heterocyclic radicals independently of one another one or more times can be replaced by radicals selected from the group of radicals R7 and R9,
and R8 ring formed by R3 and R4, together with the neighboring atom, may form an articulated triazole or pyrolidine ring,
R7, R8 and R9 have the meanings specified in claim 1, and
its pharmaceutically acceptable salt.

10. The compound according to claim 1, in which:
R3 and R4 independently of one another denote a radical selected from the group comprising (C1-C4)-alkyl radicals, (C3-C14)-cycloalkyl radicals, (C4-C20)-cycloalkenyl radicals, (C2-C19)-cyclogeranyl radicals, (C3-C19)-cyclohexanediamine radicals, (C6-C10)-aryl radicals, (C7-C20)-arylalkyl radicals, (C1-C9)-heteroaryl radicals, and (C2-C19)-heteroarylboronic the radicals
the radicals R3 and R4 independently of one another one or more times may be substituted by a radical from the group comprising OH, NH2, F, Cl, CN, or-NR13R14,
R12, R13 and R14 have the meanings specified in claim 1, and
its pharmaceutically acceptable salt.

11. The compound of formula I according to claim 1, which is selected from a group including:
(R)-1-[rat-TRANS-(1,2)-1-(1H-benzotriazol-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2,4-divergence)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2,6-dimethoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-bromophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-chloro-6-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-chloropyridin-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-chlorhydrin-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-fluoro-4-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-fluoro-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-f the PR-6-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-morpholine-4-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-triftormetilfosfinov)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1)2)-1-(3,4-divergence)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-chloro-4-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-deformationally)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-tetrazol-1 elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-bromo-3-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-chloro-2-methoxyphenoxy-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-chloro-3-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-dimethylaminomethylphenol)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-fluoro-2-isoxazol-5-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-fluoro-3-triptoreline)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-methylsulfinylphenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-triptoreline)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(5,7-dimethylindoline-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(5-ftorhinolon-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(6-aminonaphthalene-1 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(12)-1-(6-chloropyridin-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(isoquinoline-7-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(quinoline-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(quinoline-5-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(R)-1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
(R)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
(R)-1-{rat-TRANS-(1,2)-1-[4-chloro-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
(R)-1-{rat-TRANS-(1,2)-1-[4-fluoro-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(1H-benzotriazol-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(1H-indol-6-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2,4-divergence)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-bromophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-chloropyridin-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-chlorhydrin-8-ylox is)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-fluoro-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-morpholine-4-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(2-triftormetilfosfinov)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-2-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-4-methylphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-deformationally)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-alamin;
(S)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-bromo-3-methoxyphenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-chloro-2-methoxyphenol the si)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-chlorophenoxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-deformationally)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-dimethylaminomethylphenol)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-fluoro-2-isoxazol-5-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-pertenece)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-methylsulfinylphenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-triptoreline)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(5,7-dimethylindoline-8 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(5-ftorhinolon-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(6-aminonaphthalene-1 yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(6-chloropyridin-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(is iridin-4-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(quinoline-3-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(quinoline-5-yloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]piperidine-3-ylamine;
(S)-1-{rat-TRANS-(1,2)-1-[3-(2-amino-ethyl)-1H-indol-5-yloxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
(S)-1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
(S)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
(S)-1-{rat-TRANS-(1,2)-1-[4-fluoro-2-(1H-pyrazole-3-yl)phenoxy]-1,2,3,4-tetrahydronaphthalen-2-yl}piperidine-3-ylamine;
[3-methoxy-2-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)phenyl]acetonitrile;
{2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-methoxyphenyl}acetonitrile;
{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}acetonitrile;
{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}carbamino acid benzyl ester;
{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}carbamino acid benzyl ester;
1-[1,3-dichloro-4-(4-methysulfonylmethane)-4,5,6,7-tetrahydrobenzo[c]thiophene-5-yl]pyrrolidin;
1-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}pyrrolidin-2,5-dione;
1-{4-[rat-TRANS-(1,2)-2-((S)-3-am is epipedon-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]for 3,5-differenl}propane-1-he;
1-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}pyrrolidin-2,5-dione;
2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzamide;
2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzonitrile;
2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-6-perbenzoate;
2-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzamide;
2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-bromobenzonitrile;
2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzamide;
2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-5-chlorobenzonitrile;
2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-6-perbenzoate;
2-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzamide;
2-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}-N,N-dimethylacetamide;
2-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}-N,N-dimethylacetamide;
2-chloro-8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline;
2-fluoro-4-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)benzonitrile;
2-methyl-4-(RA is-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)-1H-indole;
3-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline;
3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzamide;
4-[4-((4S,5S)-1,3-dichloro-5-pyrrolidin-1-yl-4,5,6,7-tetrahydrobenzo[c]thiophene-4-yloxy)-3-forfinal]for 3,5-dimethyl-4H-[1,2,4]triazole;
4-[4-(1,3-dichloro-5-pyrrolidin-1-yl-4,5,6,7-tetrahydrobenzo[c]thiophene-4-yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole;
4-[rat-TRANS-(1,2)-1-(2-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]morpholine;
4-[rat-TRANS-(1,2)-1-(4-fluoro-2-isoxazol-5-elfenix)-1,2,3,4-tetrahydronaphthalen-2-yl]morpholine;
4-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)-1,2,3,4-tetrahydronaphthalen-2-yl]morpholine;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2,3-diferential;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2-perbenzoate;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]for 3,5-dimethylbenzonitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chloro-5-methoxy-benzonitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorbenzoyl acid methyl ester;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-Forbes the nitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzonitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]biphenyl-4-carbonitrile;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2,3-diferential;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-2-perbenzoate;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorbenzoyl acid methyl ester;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-perbenzoate;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-3-nitrobenzonitrile;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzonitrile;
5-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)-naphthalene-2-ylamine;
5-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline;
5,7-dimethyl-8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline;
5-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzo[1,3]oxalyl-2-he;
5-[rat-Tran is-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]benzo[1,3]oxalyl-2-he;
5-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}oxazol-4-carboxylic acid ethyl ester;
5-{4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}oxazol-4-carboxylic acid ethyl ester;
5-chloro-2-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)benzonitrile;
5-fluoro-8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline;
7-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)-isoquinoline;
8-(rat-TRANS-(1,2)-2-morpholine-4-yl-1,2,3,4-tetrahydronaphthalen-1 yloxy)quinoline-2-carbonitrile;
8-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]quinoline-2-carbonitrile;
N-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-4-propylphenyl}ndimethylacetamide;
N-{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}ndimethylacetamide;
N-{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]-4-propylphenyl}ndimethylacetamide;
N-{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)-1,2,3,4-tetrahydronaphthalen-1 yloxy]phenyl}ndimethylacetamide;
and its pharmaceutically acceptable salts.

12. The compound of formula I according to claim 1, which is selected from a group including:
(S)-1-[rat-TRANS-(1,2)-1-(3-dimethylaminomethylene)indan-2-yl]piperidine-3-ylamine;
{3-chloro-4-[(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-the l)indan-1-yloxy]phenylcarbamoyloxy}acetic acid;
{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}carbamino acid benzyl ester;
1-[1-(4-methysulfonylmethane)-2-methylindol-2-yl]pyrrolidin;
2-{5-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-1H-indol-3-yl}ndimethylacetamide;
2-{5-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]-1H-indol-3-yl}ndimethylacetamide;
2-{5-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-1H-indol-3-yl}ndimethylacetamide;
4-[4-(rat-TRANS-(1,2)-3,3-dimethyl-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole;
N,N-dimethyl-2-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzyl]ndimethylacetamide;
((R)-1-{TRANS-(1S,2S)-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}piperidine-3-yl)-(3,3,3-cryptochromes)amine;
2-[rat-TRANS-(1,2)-1-(2,4-dichloro-3-methylphenoxy)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(3-chloro-2-methylphenoxy)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(2,4-divergence)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)indan-2-yl]octahedral[3,4-C]pyrrole;
2-[rat-TRANS-(1,2)-1-(2-bromophenoxy)indan-2-yl]octahedral[3,4-C]pyrrole;
2-[rat-TRANS-(1,2)-1-(2-what pet-butyl-4-ethylenoxy)indan-2-yl]octahedral[3,4-C]pyrrole;
2-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]octahedral[3,4-C]pyrrole;
2-[rat-TRANS-(1,2)-1-(3-piperidine-1-ylmethylene)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(3-piperidine-1-elfenix)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(4-fluoro-2-methylphenoxy)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]octahedral[3,4-c]pyrrole;
2-[rat-TRANS-(1,2)-1-(6-chloropyridin-3-yloxy)indan-2-yl]octahedral[3,4-c]pyrrole;
2-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}-octahedral[3,4-c]pyrrole;
2-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}-octahedral[3,4-c]pyrrole;
(4-methylpiperazin-1-yl)-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]metano;
(R)-1-(TRANS-(1R,2R)-4,6-dichloro-1-venexiana-2-yl)piperidine-3-ylamine;
(R)-1-[(1S,2S)-4,6-dichloro-1-(2-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine;
(R)-1-[(1S,2S)-4,6-dichloro-1-(5-ftorhinolon-8 yloxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(1H-indol-4-yloxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2,3-dichloro-4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2,4-divergence)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-chloro-4-methysulfonylmethane)indan-2-yl]piperidine-S-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-methylbenzothiazol-5-yloxy)indan-2-reparacin-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-piperidine-1-ylmethylene)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(3-piperidine-1-elfenix)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(6-chloropyridin-3-yloxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(benzo[1,3]dioxol-5-yloxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(isoquinoline-7-yloxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(pyridine-4-yloxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[rat-TRANS-(1,2)-1-(quinoline-4-yloxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[TRANS-(1R,2R)-4,6-dichloro-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]piperidine-3-ylamine;
(R)-1-[TRANS-(1S,2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-ylamine;
(R)-1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}piperidine-3-ylamine;
(R)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-3-ylamine;
(R)-1-{TRANS-(1S,2S)-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)indan-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(3-piperidine-1-ylmethylene)indan-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-[1,2,4]triazole-1-elfenix)indan-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-imidazol-1-elfenix)indan-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-3-ylamine;
(S)-1-[rat-TRANS-(1,2)-1-(quinoline-5-yloxy)indan-2-yl]piperidine-3-ylamine;
(S)-1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-3-ylamine;
[3-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)phenyl]urea;
[rat-TRANS-(1,2)-1-(1H-indol-4-yloxy)indan-2-yl]methylpiperidine-3-ylamine;
[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]methylpiperidin-4-ylamine;
[rat-TRANS-(1,2)-4,6-dichloro-1-(4-imidazol-1-elfenix)indan-2-yl]-dimethylamine;
[TRANS-(1S,2S)-4,6-dichloro-1-(4-methysulfonylmethane)indan-2-yl]-(2-methoxyethyl)methylamine;
{(R)-1-[TRANS-(1S,2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}-(2,2,2-triptorelin)amine;
{(R)-1-[TRANS-(1S)2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}-(3,3,3-cryptochromes)amine;
{3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}urea;
{3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}urea;
{3-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]phenyl}urea;
{3-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]phenyl}urea;
{3-[rat-TRANS-(1,2)-2-(4-amino shall ethylpiperazin-1-yl)indan-1-yloxy]phenyl}urea;
{4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]phenyl}carbamino acid benzyl ester;
{4-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]phenyl}carbamino acid benzyl ester;
{TRANS-(1S,2S)-4,6-dichloro-1-[4-(3,5-dimethyl-[1,2,4]triazole-4-yl)phenoxy]indan-2-yl}-(2-methoxyethyl)methylamine;
1-[1-(2-chloro-4-nitrophenoxy)indan-2-yl]pyrrolidin;
1-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-1,3-dihydroimidazole-2-he;
1-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]pyrrolidin-2-he;
1-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]pyrrolidin-2,5-dione;
1-[rat-CIS-(1,2)-1-(4-methysulfonylmethane)indan-2-yl]-1H-imidazole;
1-[rat-TRANS-(1,2)-1-(1H-indol-6-yloxy)indan-2-yl]pyrrolidin-3-ylamine;
1-[rat-TRANS-(1,2)-1-(2,3-dichloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin;
1-[rat-TRANS-(1,2)-1-(2,6-dichloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin;
1-[rat-TRANS-(1,2)-1-(2-chloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin;
1-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]pyrrolidin-3-ylamine;
1-[rat-TRANS-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]pyrrolidin-3-ylamine;
1-[rat-TRANS-(1,2)-1-(3-chloro-4-methysulfonylmethane)indan-2-yl]pyrrolidin;
1-[rat-TRANS-(1,2)-1-(3-methysulfonylmethane)indan-2-yl]pyrrolidin;
1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]pyrrolidin-3-ylamine;
1-[rat-TRANS-(1,2)-1-(4-metasul who were radioactive-3-methylphenoxy)indan-2-yl]pyrrolidin;
1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)indan-2-yl]piperazine;
1-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)indan-2-yl]pyrrolidin;
1-[rat-TRANS-(1,2)-1-(quinoline-4-yloxy)indan-2-yl]pyrrolidin-3-ylamine;
1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}pyrrolidin-3-ylamine;
1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-4-ylamine;
1-methyl-3-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-1,3-dihydroimidazole-2-he;
2,2,2-Cryptor-N-{(R)-1-[TRANS-(1S,2S)-1-(4-methysulfonylmethane)indan-2-yl]piperidine-3-yl}ndimethylacetamide;
2,3-dichloro-4-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)benzosulfimide;
2,3-dichloro-4-(rat-TRANS-(1,2)-2-dimethylaminoethyl-1 yloxy)benzosulfimide;
2,3-dichloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
2,3-dichloro-4-[rat-TRANS-(1,2)-2-((R)-3-ethoxypyrrolidine-1-yl)indan-1-yloxy]benzosulfimide;
2,3-dichloro-4-[rat-TRANS-(1,2)-2-(methylpiperidin-3-ylamino)indan-1-yloxy]benzosulfimide;
2,3-dichloro-4-[TRANS-(1S,2S)-2-(3-hydroxypiperidine-1-yl)indan-1-yloxy]benzosulfimide;
2,3-dichloro-N,N-dimethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
2-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]isothiazolin 1,1-dioxide;
2-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]thiazole;
2-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-6-torbenson is home to the thrill;
2-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]-5-chlorobenzonitrile;
2-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-5-chlorobenzonitrile;
2-{4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]phenyl}-thiazole-4-carbonitrile;
2-chloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzonitrile;
2-chloro-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy)benzonitrile;
2-fluoro-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]benzonitrile;
2-fluoro-6-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]benzonitrile;
3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenylamine;
3,5-dichloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
3,5-dichloro-N,N-dimethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
3,5-dimethyl-4-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole;
3,5-dimethyl-4-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole;
3,5-dimethyl-4-[4-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)-3-triptoreline]-4H-[1,2,4]triazole;
3,5-dimethyl-4-[4-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-isoxazol;
3,5-dimethyl-4-[5-methyl-2-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]isoxazol;
3-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]oxazolidin-2-he;
3-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]Pyrrhus is l-2-yl)indan-1-yloxy]benzamide;
3-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide;
3-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide;
3-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]benzamide;
3-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]benzamide;
3-chloro-4-(2-pyrrolidin-1-Ilinden-1 yloxy)pyridine;
3-chloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
3-chloro-4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]benzonitrile;
3-chloro-N,N-dimethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
3-cyclopropyl-5-methyl-4-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole;
3-fluoro-4-(2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
3-methyl-4-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-4H-[1,2,4]triazole;
4-((1S,2S)-2-azetidin-1-yl-4,6-dichloride-1 yloxy)-3-perbenzoate; 4-((1S,2S)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)-3-perbenzoate;
4-(rat-TRANS-(1,2)-(R)-2-[1,3']bipirimidiny-1'-Ilinden-1 yloxy)benzosulfimide;
4-(rat-TRANS-(1,2)-2-azepin-1-Ilinden-1 yloxy)benzosulfimide;
4-(rat-TRANS-(1,2)-2-piperidine-1-Ilinden-1 yloxy)benzosulfimide; 4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzosulfimide;
4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzoic acid methyl ester;
4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 and the hydroxy)benzonitrile;
4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-N-(2,2,2-triptorelin)benzosulfimide;
4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-N-(3,3,3-cryptochromes)benzosulfimide;
4-(TRANS-(1S,2S)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)-3-perbenzoate;
4-[(1R,2S)-1-(2-chloro-4-nitrophenoxy)indan-2-yl]morpholine;
4-[(1S,2S)-2-((R)-3-aminopiperidin-1-yl)-4,6-dichloride-1 yloxy]-3-perbenzoate;
4-[(1S,2S)-4,6-dichloro-2-(4-methylpiperazin-1-yl)indan-1-yloxy]-3-perbenzoate;
4-[2,3-dimethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole;
4-[2-fluoro-5-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethylisoxazol;
4-[3-chloro-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole;
4-[3-chloro-4-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole;
4-[3-fluoro-4-(-2-methyl-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethyl-4H-[1,2,4]triazole;
4-[5-fluoro-2-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl] - for 3,5-dimethylisoxazol;
4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]-1H-indole;
4-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]-2,6-dimethylbenzonitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate;
4-[rat-TRANS-(1,2)-2-((R)-3-amino shall piperidin-1-yl)indan-1-yloxy]-2,3-dichloro-N,N-dimethylbenzenesulfonamide;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-2-perbenzoate;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]-3-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide;
4-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide;
4-[rat-TRANS-(1,2)-2-((R)-3-hydroxyethylpyrrolidine-1-yl)indan-1-yloxy]benzosulfimide;
4-[rat-TRANS-(1,2)-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]benzosulfimide;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate;
4-[rat-TRANS-(1,2)-2-((S)-3-aminopiperidin-1-yl)indan-1-yloxy]benzamide;
4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate;
4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-2,6-dimethylbenzonitrile;
4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-2-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-(3-aminomethylpyrrolidine-1-yl)indan-1-yloxy]-3-chlorobenzonitrile;
4-[rat-TRANS-(1,2}-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]-2,3-dichlorobenzenesulfonate;
4-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]-3-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-(3-aminopyrrolidine-1-yl)indan-1-yloxy]benzamide;
4-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-2,3-dichlorobenzoic honami;
4-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-2-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]-3-chlorobenzonitrile;
4-[rat-TRANS-(1,2)-2-(4-aminomethylpyridine-1-yl)indan-1-yloxy]benzamide;
4-[TRANS-(1S,2S)-2-((R)-3-aminopiperidin-1-yl)-4,6-dichloride-1 yloxy]-3-perbenzoate;
4-[TRANS-(1S,2S)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzosulfimide;
4-[TRANS-(1S,2S)-4,6-dichloro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-perbenzoate;
4-[TRANS-(1S,2S)-4,6-dichloro-2-((S)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-perbenzoate;
4-[TRANS-(1S,2S)-4,6-dichloro-2-(4-methyl-[1,4]diazepan-1-yl)indan-1-yloxy]-3-perbenzoate;
4-[TRANS-(1S,2S)-6-chloro-4-fluoro-2-((R)-3-hydroxypyrrolidine-1-yl)indan-1-yloxy]-3-perbenzoate;
5-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)-1,3-dimethyl-1,3-dihydro-indol-2-he;
5-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)-3H-isobenzofuran-1-he;
5-[5-fluoro-2-(TRANS-(1S,2S)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]-1H-pyrazole;
5-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]-2-methylbenzothiazol;
5-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]benzo[1,3]oxalyl-2-he;
5-[rat-TRANS-(1,2)-2-((R)-3-aminopiperidin-1-yl)indan-1-yloxy]benzo[1,3]oxalyl-2-he;
6-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]pyrrol-2-yl)indan-1-yloxy]-1H-indole;
7-[rat-TRANS-(1,2)-2-(hexahydrofuro[3,4-c]is yrrol-2-yl)indan-1-yloxy]-isoquinoline;
7-[rat-TRANS-(1,2)-1-(4-methysulfonylmethane)indan-2-yl]-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin;
8-((1S,2S)-2-azetidin-1-yl-4,6-dichloride-1 yloxy)-5-ftorhinolon;
8-((1S,2S)-4,6-dichloro-2-piperazine-1-Ilinden-1 yloxy)-5-ftorhinolon;
8-((1S,2S)-4,6-dichloro-2-pyrrolidin-1-Ilinden-1 yloxy)-5-ftorhinolon;
8-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)quinoline;
C-(1-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}pyrrolidin-3-yl)-methylamine;
C-(1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}piperidine-4-yl)methylamine;
C-(1-{rat-TRANS-(1,2)-1-[4-bromo-2-(1H-pyrazole-3-yl)phenoxy]indan-2-yl}pyrrolidin-3-yl)methylamine;
C-{1-[rat-TRANS-(1,2)-1-(1H-indol-4-yloxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2,4-divergence)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2-bromo-4-methylphenoxy)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2-fluoro-6-methoxyphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2-methoxy-5-methylphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2-methylbenzothiazol-5-yloxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-Tran is-(1,2)-1-(2-tert-butyl-4-ethylenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(3-chloro-2-methylphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(3-chloro-5-methoxyphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(3-ethoxyphenoxy)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(3-ethoxyphenoxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(4[1,2,4]triazole-1-elfenix)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(benzo[1,3]dioxol-5-yloxy)indan-2-yl]piperidine-4-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(benzo[1,3]dioxol-5-yloxy)indan-2-yl]pyrrolidin-3-yl}methylamine;
C-{1-[rat-TRANS-(1,2)-1-(quinoline-4-yloxy)indan-2-yl]piperidine-4-yl}methylamine
diethyl-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]amine;
diethyl-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]amine;
diethyl-{rat-TRANS-(1,2)-1-[4-(2-methoxyethyl)phenoxy]indan-2-yl}amine;
methyl-[rat-TRANS-(1,2)-1-(3-piperazine-1-elfenix)indan-2-yl]piperidine-4-ylamine;
methyl-[rat-TRANS-(1,2)-1-(4-piperazine-1-elfenix)indan-2-yl]piperidine-4-ylamine;
N-(3-{TRANS-(1S,2S)-2-[(R)-3-(2-foreteller is)piperidine-1-yl]indan-1-yloxy}phenyl)ndimethylacetamide;
N-(3-{TRANS-(1S,2S)-2-[(R)-3-(3,3,3-triptoreline)piperidine-1-yl]indan-1-yloxy}phenyl)ndimethylacetamide;
N,N-diethyl-4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)benzamide;
N-[2-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-2-azepin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-2-diethylaminoethyl-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-2-dimethylaminoethyl-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-2-piperazine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-2-thiomorpholine-4-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(rat-TRANS-(1,2)-4,6-dichloro-2-dimethylaminoethyl-1 yloxy)phenyl]ndimethylacetamide;
N-[3-(TRANS-(1S,2S)-2-piperidine-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)phenyl]ndimethylacetamide;
N-[4-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)pyridine-2-yl]ndimethylacetamide;
N-[6-(rat-TRANS-(1,2)-2-pyrrolidin-1-Ilinden-1 yloxy)pyridine-2-yl]ndimethylacetamide;
N-[rat-TRANS-(1,2)-1-(4-methysu