HK1158180A

HK1158180A - Substituted aminoindanes and analogs thereof, and the pharmaceutical use thereof

Info

Publication number: HK1158180A
Application number: HK11112352.4A
Authority: HK
Inventors: Nils Rackelmann; Laurent Bialy; Heinrich Englert; Klaus Wirth; Petra Arndt; John Weston; Uwe Heinelt; Markus Follmann
Original assignee: 赛诺菲-安万特
Priority date: 2008-09-02
Filing date: 2009-08-25
Publication date: 2012-07-13

Description

Substituted aminoindanes and analogs thereof and their pharmaceutical uses

The present invention relates to substituted aminoindanes and analogues thereof, and to the medical use thereof. Medicaments comprising such compounds are suitable for the prophylaxis or treatment of various diseases.

Previously disclosed NHE3 inhibitors are derived, for example, from compounds of the acylguanidine type (EP 0825178), norbornylamine type (WO 01/44164), 2-guanidino-quinazoline type (WO 01/79186, WO 03/051866), benzamidine type (WO 01/21582, WO 01/72742), 4-phenyltetrahydroisoquinoline type (WO 06/074813) or benzimidazole type (WO 03/101984). Squalamine, which is also described as an NHE3 inhibitor (m.donowitz et al am.j. physiol.276(Cell physiol.45): C136-C144), does not appear to act directly but through an indirect mechanism, and therefore reaches maximum intensity of action only after 1 hour.

Starting from this, it has surprisingly been found that the compounds of the formula I show excellent inhibitors of sodium hydrogen exchanger (NHE), in particular of the sodium hydrogen exchanger subtype 3(NHE 3). The invention therefore relates to compounds of the formula I

Wherein

A is 6-10 membered aryl or 5-10 membered heteroaryl, wherein the aryl and heteroaryl may be monocyclic or bicyclic, and the heteroaryl may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur;

wherein one or more hydrogen atoms of the monocyclic or bicyclic aryl or heteroaryl group may be replaced by a substituent R1, R1 is independently selected from F, Cl, Br, I, (C)₁-C₁₀) -alkyl-, (C)₂-C₁₀) -alkenyl-, (C)₂-C₁₀) -alkynyl-, (C)₃-C₁₄) -cycloalkyl-, (C)₄-C₂₀) -cycloalkylalkyl-, (C)₄-C₂₀) -cycloalkylalkyloxy-, (C)₁-C₁₀) -alkoxy-, (C)₁-C₁₀) -alkylthio-, (C)₆-C₁₄) -aryl-, (C)₂-C₁₃) -heteroaryl, -CN, -NR13R14, -C (O) R12, -SF₅、-S(O)_nR12、-C(O)OR12、-C(O)NR13R14、-S(O)_nNR13R14；

Wherein two vicinal radicals R1 may also form saturated or partially unsaturated (C)₅-C₁₀) Cycloalkyl or saturated or partially unsaturated (C)₂-C₉) -heterocycloalkyl, wherein the heterocycloalkyl may contain 1, 2 or 3 nitrogens, 1 or 2 oxygens, 1 or 2 sulfurs, 1 or 2 nitrogens and 1 oxygens or 1 sulfur;

wherein the alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, heterocycloalkyl, alkoxy and alkylthio groups may be substituted one or more times, independently of each other, by: F. OH or (C) ₁-C₁₀) -an alkoxy group;

b is a monocyclic or fused bicyclic group selected from:

a 6-to 10-membered aryl group,

a 5-to 10-membered heteroaryl group,

a 3-to 10-membered cycloalkyl group,

a 9-to 14-membered cycloalkylaryl group,

an 8-14 membered cycloalkyl heteroaryl group,

a 3-to 10-membered heterocycloalkyl group,

9-14 membered heterocycloalkylaryl and

an 8-14 membered heterocycloalkyl heteroaryl group,

wherein the cycloalkyl or heterocycloalkyl unit may be saturated or partially unsaturated, and wherein

The heterocyclic group may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur;

wherein one or more hydrogen atoms in the group B may be replaced by a substituent R5, R5 being independently of one another selected from (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkylthio group(s), (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₄-C₂₀) -cycloalkylalkyloxy, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₃-C₁₁) -cycloalkyloxy, (C)₂-C₁₁) -heterocycloalkyloxy, (C)₆-C₁₀) -aryl, (C)₁-C₉) -heteroaryl, (C)₉-C₁₄) -cycloalkylaryl, (C)₅-C₁₃) -cycloalkylheteroaryl, (C)₇-C₁₃) -heterocycloalkylaryl, (C)₄-C₁₂) -heterocycloalkylheteroaryl, wherein

The cycloalkyl and heterocycloalkyl units may be saturated or partially unsaturated,

and wherein one or more hydrogen atoms of the group R5 may be replaced by other groups independently selected from R11,

For R5Can be one or more radicals selected, independently of one another, from the following: 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，

Wherein 16, R17 and R18 are independently selected from H, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₄) -cycloalkyl, (C)₆-C₁₀) -aryl, (C)₁-C₁₀) -alkyl, all groups being substitutable independently of one another by: 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, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl and (C)₁-C₉) -a heteroaryl group,

and wherein R17 and R18 may form together with the nitrogen to which they are bonded a 4-7 membered, saturated, unsaturated or partially unsaturated heterocyclic ring having from 1 to 13 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, -N-and-NR 15-,

wherein the heterocyclic ring formed may be substituted one or more times independently of each other by: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocyclic ringAlkyl, (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C) ₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group;

l is a covalent bond or an alkylene bridge having from 1 to 10 carbon atoms,

which may bear, independently of one another, one or more substituents selected from the group consisting of: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) Cycloalkylalkyl, -COR12, -CO (NR13R14), S (O)_nR12、-S(O)₂NR13R14, (═ O), and F; wherein the alkyl, cycloalkyl and cycloalkyl groups may be substituted one or more times by F;

x is a group-N (R6) -, -O-, -S (O)_nOr alkylene having 1 to 5 carbon atoms, wherein R6 may be hydrogen or may be (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, all of which may be substituted one or more times by groups F independently of each other, or R6 may be-COR 12; -CO (NR13R14), S (O)_nR12、-S(O)₂NR13R14；

R2 is absent or is one or more substituents independently selected from the group consisting of: F. (C)₁-C₁₀) -alkyl and (C)₁-C₁₀) -alkoxy, wherein the alkyl and alkoxy may be substituted one or more times by groups F independently of each other;

r3 and R4 are each independently a hydrogen atom or a group selected from: (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl, (C)₇-C₂₀) Arylalkyl, (C)₁-C₉) -heteroaryl, (C) ₂-C₁₉) -heteroarylalkyl, wherein

The groups R3 and R4 may be substituted one or more times independently of each other by a group selected from: OH, 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, or

R3 and R4, together with the nitrogen to which they are bonded, form a 4-to 10-membered, saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more substituents selected from the group consisting of-O-, -S (O)_nA heteroatom of-N-and-NR 8-, wherein

The heterocyclic group may be substituted one or more times by groups selected from R7 and R9 independently of each other,

and wherein

The heterocyclic group may be bridged by a chemical bond, by a saturated or unsaturated (C)₁-C₁₀) -alkyl or (C)₁-C₉) -a heteroalkyl chain is bridged or bridged by-NR 15-, -O-, -S-, and wherein

The alkyl and heteroalkyl chains may also form spiro ring systems with the ring system formed by R3 and R4, wherein the alkyl and heteroalkyl bridges may be substituted one or more times, independently of each other, by groups selected from R7 and R9,

and wherein

R8 in the group NR8 may form, with the ring formed by R3 and R4, a further saturated, unsaturated or partially unsaturated heterocyclic ring which may be substituted one or more times, independently of one another, by a group selected from R7 and R9 and may additionally comprise one or more substituents selected from-O-, -S (O)_n-N ═ and-NR 19 —;

r7 is (C)₁-C₁₀) -alkyl or (C) ₁-C₁₄) -RingAlkyl, wherein the alkyl may be substituted one or more times by a group R9 independently of each other;

r8 is H, (C)₁-C₁₀) -alkyl or (C)₁-C₁₄) -cycloalkyl, COR12, -CO (NR13R14), -S (O)_nR12、-S(O)₂NR13R14, wherein the alkyl group may be substituted one or more times by groups R10 independently of each other;

r9 is a group selected from: OH, (═ 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, (C)₄-C₂₀) -cycloalkylalkyl, (C)₁-C₁₀) -alkoxy, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl, (C)₁-C₉) -a heteroaryl group;

r10 is a group selected from: F. OH, CN, (C)₁-C₁₀) -alkoxy, (C)₁-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 is a group selected from: (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₁-C₁₀) -alkoxy, (C)₁-C₂₀) Alkylthio group(s), (C)₃-C₁₄) -cycloalkyl, (C)₄-C₁₀) -cycloalkylalkyl, (C)₂-C₁₃) -heterocycloalkyl, (C)₄-C₁₉) -heterocycloalkyl alkyl group, (C)₃-C₁₄) -cycloalkyloxy, (C)₂-C₁₃) -a heterocycloalkyloxy group,

all these groups may be substituted one or more times by the groups R10 independently of one another; (═ O), Cl, Br, I, and R10;

r12, R13 and R14 may be independently of each other H, (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₁₀) -cycloalkylalkyl, (C)₂-C₁₃) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C) ₆-C₁₀) -aryl, each of which may be substituted one or more times independently of each other by: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group;

or wherein R13 and R14 may form together with the nitrogen atom to which they are bonded a 4-7 membered, saturated, unsaturated or partially unsaturated heterocyclic ring having from 1 to 13 carbon atoms, which may additionally contain one or more substituents selected from the group consisting of-O-, -S (O)_nA heteroatom of-N-and-NR 15-, wherein

The heterocyclic ring formed may be substituted one or more times independently of each other by: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group;

r15 is selectedA group selected from: H. (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₃) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl, each of which may be substituted one or more times independently of the other by: F. OH, CN or (C) ₁-C₁₀) -an alkoxy group;

r19 is H, (C)₁-C₁₀) -alkyl or (C)₁-C₁₄) Cycloalkyl, COR12, -CO (NR13R14), S (O)_nR12、-S(O)₂NR13R14, wherein the alkyl group may be substituted one or more times by groups R10 independently of each other;

and wherein

n is 0, 1 or 2;

p is 1 or 2, and

q is 0 or1 and q is a linear or branched,

and the pharmaceutically acceptable salts thereof, and to pharmaceutically acceptable salts thereof,

and wherein

i) In which A is phenyl, B is phenyl or benzodioxolyl, X is-O-or-S-, L is a bond, and R3 and R4 are H, (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₇-C₂₀) In the case of arylalkyl or R3 and R4 together being unsubstituted pyrrolidinyl, morpholinyl, piperidinyl or piperazinyl or 4-methylpiperazinyl, there must be at least one other than (C)₁-C₁₀) Alkyl radicals, (C)₁-C₁₀) Alkoxy, OH, CF₃R5 radical of F, Cl, Br or I,

ii) in which A is phenyl, X is-O-, -S-or-NH-, and R3 and R4 are (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl or (C)₄-C₂₀) In the case of cycloalkylalkyl, at least one must be presentR5 of a group other than: F. cl, Br, I, (C)₁-C₄) Alkyl radicals, (C)₁-C₄) -alkoxy, CF₃、OCF₃、CN、NO₂、NH₂、-NH((C₁-C₁₀) -alkyl), -N ((C)₁-C₁₀) -alkyl groups)₂Unsubstituted or substituted benzoyl or unsubstituted or substituted phenyl- (CH)₂)_r-Y-(CH₂)_s-, where Y is a bond or oxygen and r and s are 0 to 4, where r + s is not more than 4.

In one embodiment, preference is given to compounds of the formula I and pharmaceutically acceptable salts thereof, wherein

L is a covalent bond;

x is a group-O-;

and is

q is 0.

Preferred substances of the invention are compounds having the formula Ia and pharmaceutically acceptable salts thereof

Wherein

A is phenyl or 5-to 6-membered heteroaryl, wherein the heteroaryl may contain 1, 2 or 3 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen and 1 oxygen or 1 sulfur atom as heteroatoms, wherein one or more hydrogen atoms in the phenyl or heteroaryl may be replaced independently of one another by a group R1, and/or

B is 6-to 10-membered monocyclic or fused bicyclic aryl, 5-to 10-membered monocyclic or fused bicyclic heteroaryl, 9-to 14-membered fused bicyclic cycloalkylaryl, 8-to 14-membered fused bicyclic cycloalkylheteroaryl, 9-to 14-membered fused bicyclic heterocycloalkylaryl or 8-to 14-membered fused bicyclic heterocycloalkylheteroaryl, each of which may be substituted one or more times independently of the other by a radical R5,

wherein the cycloalkyl and heterocycloalkyl units may be saturated or partially unsaturated, and

wherein the heterocycloalkylaryl may contain 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 nitrogen atom and 1 oxygen or 1 sulfur atom, or 1 oxygen and 1 sulfur atom as heteroatoms,

And the heteroaryl and cycloalkylheteroaryl groups may contain 1, 2, 3, or 4 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atoms and 1 oxygen or sulfur atom, or 1 oxygen and 1 sulfur atom,

and the heterocycloalkylheteroaryl group may contain 1, 2, 3 or 4 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1, 2 or 3 nitrogen atoms and 1 oxygen or 1 sulfur atom, or 1 oxygen and 1 sulfur atom as heteroatoms, and/or

X is a group-N (R6) -, -O-or-S (O)_n-，

Wherein R6 is H or (C)₁-C₅) -alkyl, and n is 1 or 2, and/or

R2 is absent or is one or more radicals independently selected from F and (C)₁-C₆) -substituents of alkyl groups, wherein the alkyl groups may be substituted one or more times by groups F independently of each other, and/or

L is a covalent bond, -C (O) -bridge or methylene bridge, wherein one or both hydrogen atoms may be replaced by F;

wherein the radicals R1, R3, R4 and R5 have the abovementioned meanings.

L is a covalent bond;

and is

X is a group-O-.

Particularly preferred compounds of the invention are tetrahydronaphthalenes of formula Ib and pharmaceutically acceptable salts thereof

Wherein

B can be phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, indolyl, benzothienyl, chromanyl, benzofuranyl, dihydrofuranyl, isobenzodihydrofuranyl, benzopyrrolidinyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, benzothiazolyl, benzoxathiolyl, dihydroindolyl, benzodioxolyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, wherein one, two, three or four hydrogen atoms of group B can be replaced by group R5, wherein

Each R5 group is independently selected from:

(C₁-C₄) Alkyl, which may be fully or partially fluorinated, or hydrogen may be substituted by CN, NH₂、OH、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂、(C₁-C₄) -an alkoxy substitution,

(C₁-C₄) Alkoxy, which may be fluorinated in whole or in part,

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

(C₂-C₅) -heterocycloalkyl and (C)₂-C₅) -heterocycloalkyl- (C)₁-C₄) -an alkyl group,

wherein the heterocycloalkyl ring may be monocyclic, bicyclic, saturated or partially unsaturated, and may contain 1 or 2 nitrogen atoms, 1 oxygen atom, 1 nitrogen and 1 sulfur atom, or 1 nitrogen and 1 oxygen atom, and

wherein the heterocycloalkyl ring may also bearWith substituents selected from the group consisting of: -F, -Cl, -Br, ═ O, -NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂、(C₁-C₄) -alkoxy, -CN, (C)₁-C₄) Alkyl radicals, (C)₃-C₁₀) -a cycloalkyl group,

a phenyl group, a naphthyl group,

(C₁-C₆) -heteroaryl, wherein the heteroaryl ring may be monocyclic or fused bicyclic, which may contain 1, 2, 3 or 4 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atoms and 1 oxygen or sulfur atom, and

wherein the heteroaryl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -OH, -NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂、(C₁-C₄) -alkoxy, -CN, (C)₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl, -C (O) O- (C) ₁-C₄) -an alkyl group,

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 wherein n is 1 or 2, -S (O)₂NR17R18, wherein

R16, R17 and R18 may be, independently of one another, a hydrogen atom or are selected from unsubstituted or substituted (C)₁-C₄) -a group of alkyl groups,

wherein the alkyl substituents are selected from F, OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂-CN or (C)₁-C₁₀) -an alkoxy group,

r17 and R18 may form, together with the nitrogen atom to which they are bonded, a 5-to 6-membered, saturated, unsaturated or partially unsaturated heterocyclic ring having 1 to 5 carbon atomsWhich may additionally comprise one or more heteroatoms selected from: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and-N ((C)₁-C₄) Alkyl), wherein the heterocyclic rings formed may, independently of one another, be substituted one or more times by: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O) or (C)₁-C₁₀) -an alkoxy group,

r1 is absent or is one, two or three radicals independently of one another selected from the group consisting of: F. cl, Br, I, (C)₁-C₆) Alkyl radicals, (C)₁-C₆) Alkoxy, where the alkyl and alkoxy radicals may be substituted one or more times by F, and/or

L is a bond or-CH ₂-, and/or

R3 and R4 are independently of each other a group selected from: H. (C)₁-C₄) -alkyl-, (C)₃-C₇) -cycloalkyl-, (C)₃-C₆) -heterocycloalkyl, phenyl- (C)₁-C₄) Alkyl radicals, (C)₁-C₅) -heteroaryl, wherein the groups R3 and R4 may be substituted once, twice or three times, independently of each other, by a group selected from: OH, (═ 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，

Wherein R12, R13 and R14 are H or (C)₁-C₄) -an alkyl group,

or

R3 and R4 together with the nitrogen to which they are bonded form a 4-to 8-membered, saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally containOne or more heteroatoms selected from: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-and-NR 8-, where

wherein the heterocyclic group may be bonded through a chemical bond, (C)₁-C₇) Alkyl, saturated or unsaturated (C)₁-C₆) A heteroalkyl chain bridged or bridged by-NH-, -N (C)₁-C₄) -alkyl) -bridges, and wherein the alkyl and heteroalkyl chains may also form spiro ring systems with the ring system formed by R3 and R4,

and wherein R8 may form with the ring which may be formed by the groups R3 and R4 other saturated, unsaturated or partially unsaturated heterocyclic rings which may additionally contain one or two of the following heteroatoms: -O-, -S (O) _n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and-N ((C)₁-C₄) -an alkyl group);

wherein R7, R8 and R9 have the aforementioned meanings.

In one embodiment, preference is given to compounds of the formula Ib, and pharmaceutically acceptable salts thereof, wherein

L is a covalent bond.

Other preferred compounds have the structure of formula Ic and pharmaceutically acceptable salts thereof

Wherein

B is 6-to 10-membered monocyclic or fused bicyclic aryl, 5-to 10-membered monocyclic or fused bicyclic heteroaryl, 9-to 14-membered fused bicyclic cycloalkylaryl, 8-to 14-membered fused bicyclic cycloalkylheteroaryl, fused 9-to 14-membered bicyclic heterocycloalkylaryl or 8-to 14-membered fused bicyclic heterocycloalkylheteroaryl, each of which may be substituted one or more times independently of the other by R5,

and the heteroaryl and cycloalkylheteroaryl groups may contain 1, 2, 3, or 4 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atoms and 1 oxygen or 1 sulfur atom, or 1 oxygen and 1 sulfur atom,

X is a group-N (R6) -, -O-or-S (O)_n-，

Wherein R6 is H or (C)₁-C₅) -alkyl, n is 1 or 2, and/or

R2 is absent or is one or more substituents independently selected from the group consisting of: f and (C)₁-C₆) -alkyl, wherein the alkyl may be substituted one or more times by F independently of each other, and/or

L is a covalent bond, -C (O) -bridge or methylene bridge, which may be substituted one or more times independently of each other by F;

q is 0 or 1;

wherein the radicals A, R1, R3, R4 and R5 have the abovementioned meanings.

Particularly preferred are compounds having the structure of formula Ic and pharmaceutically acceptable salts thereof, wherein

A is phenyl or 5-to 6-membered heteroaryl,

wherein the heteroaryl radical may contain 1, 2 or 3 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen and 1 oxygen or 1 sulfur atom as heteroatoms, wherein one or more hydrogen atoms in the phenyl or heteroaryl radical may be replaced independently of one another by a radical R1, and/or

B is 6-to 10-membered monocyclic or fused bicyclic aryl, 5-to 10-membered monocyclic or fused bicyclic heteroaryl, 9-to 14-membered fused bicyclic cycloalkylaryl, 8-to 14-membered fused bicyclic cycloalkylheteroaryl, fused 9-to 14-membered bicyclic heterocycloalkylaryl or 8-to 14-membered fused bicyclic heterocycloalkylheteroaryl, each of which may be substituted one or more times, independently of one another, by the following radicals R5,

wherein the heterocycloalkylaryl may contain 1 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 nitrogen atom and 1 oxygen or 1 sulfur atom, or 1 oxygen and 1 sulfur atom as heteroatoms,

and the heteroaryl and cycloalkylheteroaryl groups may contain 1, 2 or 3 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 nitrogen and 1 oxygen or sulfur atom, or 1 oxygen and 1 sulfur atom,

and the heterocycloalkyl heteroaryl group may contain 1, 2, 3 or 4 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 or 2 nitrogen atoms and 1 oxygen or 1 sulfur atom, or 1 oxygen and 1 sulfur atom as heteroatoms, and/or

X is a group-N (R6) -, -O-or-S (O)_n-，

Wherein R6 is H or (C)₁-C₅) -alkyl, n is 1 or 2, and/or

L is a covalent bond, -C (O) -bridge or methylene bridge, which may be substituted once or twice by F;

q is 0 or 1;

wherein the R1, R3, R4 and R5 groups have the above-mentioned meanings.

In one embodiment, preference is given to compounds of the formula Ic and pharmaceutically acceptable salts thereof, wherein

L is a covalent bond;

x is a group-O-;

and is

q is 0.

Particularly preferred aminoindanes of formula Id and pharmaceutically acceptable salts thereof

Wherein

B can be phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, indolyl, benzothienyl, chromanyl, benzofuranyl, dihydrofuranyl, isobenzodihydrofuranyl, benzopyrrolidinyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, benzothiazolyl, benzoxathioheterocyclopentenyl, indolinyl, benzodioxolyl, tetrahydroisoquinolinyl, tetrahydroquinolyl, wherein one, two, three or four hydrogen atoms in group B can be replaced by a group R5, wherein

Each R5 group is independently selected from:

(C₁-C₄) Alkyl, which may be fully or partially fluorinated, or one hydrogen may be replaced by CN, NH₂、OH、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂、(C₁-C₄) The substitution of the alkoxy group is carried out,

(C₁-C₄) Alkoxy, which may be fluorinated in whole or in part,

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

(C₂-C₅) -heterocycloalkyl and (C)₂-C₅) -heterocycloalkyl- (C)₁-C₄) -alkyl, wherein the heterocycloalkyl ring may be saturated or partially unsaturated, and may contain 1 or 2 nitrogen atoms, 1 oxygen atom, 1 nitrogen and 1 sulfur atom, or 1 nitrogen and 1 oxygen atom, and

Wherein the heterocycloalkyl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂、-CN、(C₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl, OH, NH (C)₁-C₄) Alkyl, N ((C)₁-C₄) -alkyl groups)₂、(C₁-C₁₀) -alkoxy, phenyl, naphthyl,

(C₁-C₆) Heteroaryl, wherein the heteroaryl ring may be monocyclic or fused bicyclic, which may contain 1, 2, 3 or 4 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atoms and 1 oxygen or sulfur atom, and

wherein the heteroaryl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂、-CN、(C₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl, OH, NH (C)₁-C₄) Alkyl, N ((C)₁-C₄) -alkyl groups)₂、(C₁-C₁₀) Alkoxy, -C (O) O- (C)₁-C₄) -an alkyl group,

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 wherein n is 1 or 2, -S (O)₂NR17R18, wherein

wherein the alkyl substituents are selected from F, OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group,

r17 and R18 may form together with the nitrogen atom to which they are bonded a 5-6 membered, saturated, unsaturated or partially unsaturated heterocyclic ring having 1-5 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and N ((C) ₁-C₄) Alkyl) -, wherein the heterocyclic rings formed are substituted one or more times, independently of each other, by: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group,

R3 and R4 are independently of each other a group selected from: H. (C)₁-C₄) -alkyl, (C)₃-C₇) -cycloalkyl-, (C)₃-C₇) -cycloalkyl- (C)₁-C₄) -alkyl-, (C)₃-C₆) -heterocycloalkyl-, phenyl- (C)₁-C₄) -alkyl-, (C)₁-C₅) -heteroaryl, wherein

The radicals R3 and R4 may be substituted once or twice independently of one another by radicals from the groupSecond or third time: OH, (═ 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，

Wherein R12, R13 and R14 are H or (C)₁-C₄) -an alkyl group,

or

R3 and R4 together with the nitrogen to which they are bonded form a 4-8 membered, saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O) _n-, where N ═ 0, 1 or 2, ═ N-and-NR 8-, where

wherein the heterocyclic group may be bonded through a chemical bond, (C)₁-C₇) Alkyl radicals, (C)₁-C₆) -a saturated or unsaturated heteroalkyl chain bridged or bridged by-NH-, -N (C)₁-C₄) -alkyl-bridges, and wherein the alkyl and heteroalkyl chains may also form spiro ring systems with the ring system formed by R3 and R4,

and wherein R8 in the group NR8 may form with the ring formed by the groups R3 and R4 an additional saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or two heteroatoms selected from: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-and-NR 19-, where R19 is equal to H or (C)₁-C₄) -an alkyl group,

wherein the radicals R7, R8 and R9 have the abovementioned meanings.

Preferred aminoindanes and pharmaceutically acceptable salts thereof are those having the structure of formula Id, wherein

B is phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, indolyl, benzothienyl, chromanyl, benzofuranyl, dihydrofuranyl, isobenzodihydrofuranyl, benzopyrrolidinyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, benzothiazolyl, benzothiophenyl, indolinyl, benzodioxolyl, tetrahydroisoquinolinyl, tetrahydroquinolyl, wherein one, two, three or four hydrogen atoms in group B may be replaced by a group R5, wherein

One R5 group is selected from:

(C₂-C₅) -a heterocycloalkyl group,

wherein the heterocycloalkyl ring may be saturated or partially unsaturated and may contain 1 or 2 nitrogen atoms, 1 oxygen atom, 1 nitrogen and 1 sulfur atom, or 1 nitrogen and 1 oxygen atom, and

wherein the heterocycloalkyl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂-、-CN、(C₁-C₄) -alkyl, (C)₃-C₁₀) -a cycloalkyl group,

wherein the heteroaryl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂、-CN、(C₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl, -C (O) O- (C)₁-C₄) -an alkyl group,

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、-S(O)₂NR17R18，

wherein

R16, R17 and R18 can be, independently of one another, a hydrogen atom or are selected from unsubstituted or substitutedIs (C)₁-C₄) -a group of alkyl groups,

r17 and R18 may form together with the nitrogen atom to which they are bonded a 5-6 membered, saturated, unsaturated or partially unsaturated heterocyclic ring having 1-5 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O) _n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and-N ((C)₁-C₄) -alkyl) -, wherein the heterocyclic rings formed may be substituted one or more times, independently of each other, by: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl groups, which in turn may each, independently of one another, carry one or more groups selected from: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group,

and is

The further radicals R5 are independently of one another selected from:

(C₁-C₄) Alkoxy, which may be fluorinated in whole or in part,

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

a phenyl group,

OH, (═ O), F, Cl, Br, CN, -NR17R18, NR16COR17, -COOR16, -COR 16; -CO (NR17R18), wherein

r17 and R18 may form together with the nitrogen atom to which they are bonded a 4-7 membered, saturated, unsaturated or partially unsaturated heterocyclic ring having 1-5 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O) _n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and N ((C)₁-C₄) Alkyl) -, wherein the heterocyclic rings formed are substituted one or more times, independently of each other, by: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl groups, which in turn may each, independently of one another, carry one or more groups selected from: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group,

and/or

R3 and R4 are independently from each other selected from the group consisting of: H. (C)₁-C₅) -alkyl-, phenyl- (C)₁-C₄) -alkyl-, NH₂-(C₁-C₄) Alkyl-, N ((C)₁-C₄) -alkyl groups)₂-(C₁-C₄) -alkyl-, (C)₁-C₄) -alkoxy- (C)₁-C₄) -alkyl-, (C)₃-C₇) -cycloalkyl- (C)₁-C₄) Alkyl-and (C) containing-NH-, -O-or-S-₄-C₆) -heterocycloalkyl-, or

R3 and R4 together with the nitrogen to which they are bonded form a 4-8 membered, saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-and-NR 8-, where

wherein the heterocyclic group may be bonded through a chemical bond, (C)₁-C₇) Alkyl radicals, (C)₁-C₆) -a saturated or unsaturated heteroalkyl chain bridged or bridged by-NH-, N ((C)₁-C₄) Alkyl) -bridged, and wherein the alkyl and heteroalkyl chains may also form spiro ring systems with the ring system formed by R3 and R4,

and wherein R8 may form with the ring formed by the groups R3 and R4 other saturated, unsaturated or partially unsaturated heterocyclic rings which may additionally contain one or two heteroatoms selected from: -O-, -S (O)_n-, where N ═ 0, 1 or 2, -NH-and-N ((C)₁-C₄) Alkyl) -, and/or

R7 is H, (C)₁-C₅) -alkyl or (C)₃-C₆) Cycloalkyl, wherein the alkyl may be substituted one or more times by radicals R9 independently of one another, and/or

R8 is H, (C)₁-C₅) -alkyl or (C)₁-C₆) -cycloalkyl, wherein the alkyl group may be substituted one or more times independently of each other by: F. OH, NH₂、CN、NO₂、(C₁-C₁₀)-Alkoxy group, (C)₁-C₁₀) Alkylthio, -NR13R14, -NR13COR12, -NR13COOR12, -NR13CONR13R14, -NR13-S (O)₂-R12、-NR12-S(O)₂-NR13R14、-COOR12、-COR12；-CO(NR13R14)、S(O)_nR12、-S(O)₂NR13R14、COR12、-CO(NR13R14)、S(O)_nR12、-S(O)₂NR13R14, and/or

R9 is a group selected from: OH, NH₂、(＝O)、F、Cl、Br、I、CN、-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-C₆) -cycloalkyl, (C)₄-C₇) -cycloalkylalkyl, (C)₁-C₅) -alkoxy, (C)₂-C₆) -heterocycloalkyl, (C)₃-C₁₀) -heterocycloalkyl alkyl, phenyl, (C) ₁-C₅) -a heteroaryl group,

wherein R12, R13 and R14 are each independently of the other a hydrogen atom or are selected from unsubstituted or substituted (C)₁-C₄) -alkyl radicals, wherein the alkyl substituents are chosen from F, OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group,

in one embodiment, compounds of formula I, Ia, Ib, Ic and Id are preferred, wherein

R3 and R4 together with the nitrogen to which they are bonded form a 4-to 10-membered, saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, -N-and-NR 8-, wherein

and wherein

The heterocyclic group formed by R3 and R4 may be represented byChemical bond bridging, through saturated or unsaturated (C)₁-C₁₀) -alkyl or (C)₁-C₉) -a heteroalkyl chain is bridged or bridged by-NR 15-, -O-or-S-, and wherein

and wherein

R8 in the group-NR 8-may form, with the ring formed by R3 and R4, a further saturated, unsaturated or partially unsaturated heterocyclic ring which may be substituted one or more times, independently of one another, by a group selected from R7 and R9 and may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O) _n-, -N ═ and-NR 19-;

and wherein n, R7, R8, R9 and R19 have the above-mentioned meanings.

In one embodiment, more preferred are compounds of formula I, Ia, Ib, Ic and Id, wherein

and wherein R8 may form with the ring formed by the groups R3 and R4 an additional saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally comprise one or twoA heteroatom selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, -NH-and-N ((C)₁-C₄) Alkyl) -;

and wherein R7, R8 and R9 have the above-mentioned meanings.

In another embodiment, particular preference is given to compounds of the formulae I, Ia, Ib, Ic and Id, where

and wherein R8 may form together with the ring formed by the groups R3 and R4 and the adjacent C atom a fused triazole or pyrrolidine ring;

and wherein R7, R8 and R9 have the above-mentioned meanings.

In another embodiment, compounds of formula I, Ia, Ib, Ic and Id are preferred, wherein

R3 and R4 are each independently a hydrogen atom or a group selected from: (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl, (C)₇-C₂₀) Arylalkyl, (C)₁-C₉) -heteroaryl, (C)₂-C₁₉) -heteroarylalkyl, wherein

The groups R3 and R4 may be substituted one or more times independently of each other by a group selected from:

OH、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；

and wherein R12, R13 and R14 have the above-mentioned meanings.

R3 and R4 are independently selected from H, (C) ₁-C₅) -alkyl-, phenyl- (C)₁-C₄) -alkyl-, NH₂-(C₁-C₄) Alkyl-, N ((C)₁-C₄) -alkyl groups)₂-(C₁-C₄) -alkyl-, (C)₁-C₄) -alkoxy- (C)₁-C₄) -alkyl-, (C)₃-C₇) -cycloalkyl- (C)₁-C₄) Alkyl-and (C) containing-NH-, -O-or-S-₄-C₆) -heterocycloalkyl-.

The number of ring members within the scope of the present invention refers to the number of ring atoms forming the respective ring system or fused ring system.

6-to 10-membered aryl groups which may represent cyclic groups A and B are, in particular, phenyl and naphthyl.

Preferred 5-to 10-membered heteroaryl groups which may represent a cyclic group A are selected from furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl,Azolyl radical, isoOxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, and cinnolinyl. Particularly preferred heteroaryl groups a are thienyl groups.

In one embodiment of the invention, A is phenyl or 5-or 6-membered heteroaryl, in another embodiment A is phenyl or thienyl, in another embodiment A is phenyl, in another embodiment A is thienyl, each of which may be substituted as shown.

Preferred 5-to 10-membered heteroaryl groups which may represent a cyclic group B are selected from furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, triazolyl, Azolyl radical, isoOxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl, benzothienyl, isobenzothienyl, benzofuranyl, isobenzofuranyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, benzofuranyl, benzoxazolyl, pyridazinyl, indolyl, quinolyl, quinolAzolyl radical, isobenzoylOxazolyl, benzothiazolyl, isobenzothiazolyl.

Preferred 3-to 10-membered cycloalkyl groups which may represent the cyclic group B are selected from the group consisting of cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl and norbornene.

Preferred 9-14 membered cycloalkylaryl groups which may represent a cyclic group B are selected from fused ring systems having a cycloalkyl ring and an aryl ring. Particularly preferred cycloalkylaryl groups are indenyl, dihydronaphthyl, tetrahydronaphthyl and indanyl.

Preferred 8-14 membered cycloalkylheteroaryl groups which may represent the cyclic group B are selected from fused ring systems having a cycloalkyl ring and a heteroaryl ring.

Preferred 3-to 10-membered heterocycloalkyl groups which may represent the cyclic group B are selected from the group consisting of oxetanyl (oxiranyl), thietanyl (thiiranyl), aziridinyl, oxetanyl (oxiranyl), thietanyl (thietanyl), azetidinyl, pyrrolidinyl, dihydropyrrolyl, dihydroimidazolyl, dihydropyrazolyl, tetrahydropyrazolyl, oxolanyl (oxolanyl), dihydrofuranyl, dioxolanyl (dioxolanyl), thietanyl (thiolanyl), dihydrothienyl, Oxazolidinyl, dihydroAzolyl radical, isoOxazolidinyl, dihydroisosOxazolyl, thiazolidinyl, dihydrothiazolyl, isothiazolyl, dihydroisothiazolyl, oxathiolanyl (oxathiolanyl), 2H-pyranyl, 4H-pyranyl, tetrahydropyranyl, 2H-thiopyranyl, 4H-thiopyranyl, di-, tetrahydrothiopyranyl, piperidinyl, di-, tetrahydropyridinyl, piperazinyl, tetrahydropyrazinyl, di-, tetra-, hexahydropyridazinyl, di-, tetra-, hexahydropyrimidinyl, morpholinyl, thiomorpholinyl, dioxanyl, dithianyl, azepanyl, thiepanyl and oxepinyl, wherein two of these heterocycles may also form a saturated or partially unsaturated fused bicyclic ring system. An example of such a bicyclic ring system is octahydropyrrolo [1, 2-a ]]Pyrazinyl, octahydropyrrolo [3, 4-b ]]Pyrrolyl, hexahydropyrrolo [3, 4-c ] s]Pyrrolyl and octahydropyrrolo [3, 4-c)]A pyrrolyl group.

Preferred 9-14 membered heterocycloalkylaryl groups which may represent a cyclic group B are selected from those having a heterocycloalkyl ring and an aryl ringA fused ring system. Particularly preferred heterocycloalkylaryl radicals are benzodioxolyl, benzodihydropyrazolyl, benzodioxolyl, benzodihydrothiazolyl, benzomorpholinyl, benzodihydropyrrolyl Azolyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, benzoxathiopentenyl, isobenzoxathiopentenyl, and benzodioxolyl.

Preferred 8-14 membered heterocycloalkylheteroaryl groups which may represent the cyclic group B are selected from fused ring systems having a heterocycloalkyl ring and a heteroaryl ring.

Particularly preferred mono-or bicyclic radicals which may represent the cyclic radical B are selected from the group consisting of phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, indolyl, chromapyrrolyl, benzothiophenyl, chromathiophenyl, benzofuranyl, benzisofuranyl, chromafuranyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, thiazolyl, benzothiazolyl, benzothiophenyl, benzodioxolyl, tetrahydroisoquinolinyl or tetrahydroquinolinyl. In this connection, the radical B may be bonded to the radical-LX-as pyridin-2, 3 or 4-yl, quinolin-1, 2, 3, 4, 5, 6, 7 or 8-yl, isoquinolin-1, 2, 3, 4, 5, 6, 7 or 8-yl, indol-1, 2, 3, 4, 5, 6 or 7-yl, isoindol-1, 2, 3, 4, 5, 6 or 7-yl, benzo [ B ] thiophen-2, 3, 4, 5, 6 or 7-yl, benzo [ c ] thiophen-1, 3, 4, 5, 6 or 7-yl, benzo [ B ] dihydrothiophen-2, 3, 4, 5, 6 or 7-yl, benzo [ c ] dihydrothiophen-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, benzimidazole-1, 2, 3, 4, 5, 6 or 7-yl, benzopyrazol-1, 2, 3, 4, 5, 6 or 7-yl, benzotriazole-1, 2, 4, 5, 6 or 7-yl, thiazole-2, 4 or 5-yl, benzothiazole-2, 3, 4, 5, 6 or 7-yl, benzoxathioent-2, 4, 5, 6 or 7-yl, benzodioxol-2, 4, 5, 6 or 7-yl, tetrahydroisoquinoline-1, 2, 3, 4, 5, 6, 7 or 8-yl or tetrahydroquinoline-1, 2, 3, 4, 5, 6, 7 or 8-yl.

One, two, three or four hydrogen atoms in the group B can preferably be replaced by groups selected independently of one another from R5. In one embodiment of the invention, one, two or three hydrogen atoms, and in another embodiment one or two hydrogen atoms, may be replaced by a group selected independently from R5.

Particularly preferred B groups are the following groups:

wherein the substituents R5 in the bicyclic ring system B may be located on both rings.

In one embodiment of the invention, B is selected from phenyl, naphthyl, pyridyl, quinolyl or isoquinolyl, in another embodiment from phenyl and pyridyl, in another embodiment B is phenyl, in another embodiment pyridyl, all of which may be substituted as shown.

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

In one embodiment of the invention, L is a covalent single bond, in another embodiment a-C (O) -bridge, in another embodiment a methylene bridge.

X is preferably a group-N (R6) -, -O-or-S (O)_n-。

In the inventionIn one embodiment, X is a group-N (R6) -, in another embodiment-O-, in another embodiment-S (O) _n-。

In one embodiment of the present invention, one, two or three H atoms, in another embodiment one or two H atoms, in an aryl or heteroaryl group representing a may be replaced by a substituent R1.

Preferred R1 groups are selected from F, Cl, Br, I, (C)₁-C₆) Alkyl radicals, (C)₁-C₆) -alkoxy, wherein the alkyl and alkoxy groups may be substituted one or more times by F. A particularly preferred R1 group is selected from F, Cl, methyl, ethyl, propyl, butyl, methoxy, ethoxy, trifluoromethyl, pentafluoroethyl, trifluoroethyl, especially-CH₂-CF₃Difluoroethyl, especially-CH₂-CHF₂Monofluoroethyl radical, especially-CH₂-CH₂F. Methoxy, ethoxy, trifluoromethoxy, pentafluoroethoxy, trifluoroethoxy, especially-O-CF₂-CF₃Difluoroethoxy, especially-O-CH₂-CHF₂Monofluoroethoxy, especially-O-CH₂-CH₂F。

Preferred R2 groups are selected from F, (C)₁-C₆) Alkyl, where the alkyl radical may be substituted one or more times by F independently of one another, particularly preferred radicals being F, methyl, ethyl, propyl, butyl, trifluoromethyl, trifluoroethyl, for example-CF₂-CF₃、-CH₂-CHF₂、-CH₂-CH₂F。

Preferred R3 and R4 groups are independently from each other selected from halogen, (C)₁-C₄) Alkyl radicals, such as the methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl radicals,

Wherein the alkyl group may be substituted by one or two-N (C)₁-C₄-alkyl groups)₂and-O- (C)₁-C₄-alkyl) (especially by-N (CH)₃)₂and-N (C)₂H₅)₂) Radical (I)By substitution to form (e.g.) -CH₂-N(CH₃)₂、-CH₂-CH₂-N(CH₃)₂、-CH₂-CH₂-CH₂-N(CH₃)₂、-CH₂-OCH₃or-CH₂-CH₂-OCH₃The radical(s) is (are),

(C₃-C₇) Cycloalkyl, for example, cyclopropylalkyl, cyclobutylalkyl, cyclopentylalkyl, cyclohexylalkyl or cycloheptylalkyl,

(C₃-C₇) -cycloalkyl- (C)₁-C₄) Alkyl radicals, such as the cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl or cyclohexylethyl radical,

(C₃-C₆) Heterocycloalkyl, for example piperidinyl, piperazinyl, hexahydropyrimidyl, hexahydropyridazolyl (pyridazolyl), morpholinyl, thiomorpholinyl, pyrrolidinyl, tetrahydrofuranyl or tetrahydrothienyl,

phenyl, phenyl- (C)₁-C₄) Alkyl radicals, such as phenylmethyl, phenylethyl, phenylpropyl or phenylbutyl,

(C₁-C₅) Heteroaryl, e.g. furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, triazolyl,Azolyl radical, isoOxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, or pyridazinyl.

The R3 and R4 groups preferably form, together with the nitrogen atom to which they are bonded, the following groups:

the R3 and R4 groups particularly preferably form a 4-to 8-membered, saturated, unsaturated or partially unsaturated heterocyclic ring. The 4-to 8-membered, saturated, unsaturated or partially unsaturated heterocyclic ring may additionally comprise one or more groups selected from: -O-, -S (O) _n- (wherein N ═ 0, 1, or 2), ═ N-, and-NR 8-. -NR 8-may form, together with the adjacent C atom, a fused triazole or pyrrolidine ring, e.g. octahydropyrrolo [1, 2-a ]]Pyrazinyl and tetrahydro- [1, 2, 4]Triazolo [4, 3-a]A pyrazinyl group.

Preferred heterocycles formed by R3 and R4 are selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, oxothiomorpholinyl, dioxothiomorpholinyl, azepanyl, 1, 4-diazepanyl, pyrrolyl, pyrazolyl and imidazolyl. The heterocyclic ring may be covalently bonded to (C)₁-C₇) An alkylene bridge or (C)₁-C₆) A heteroalkylene bridge or an-NH-bridge or-N (C)₁-C₄) An alkylene bridge, thereby forming a fused or bridged bicyclic ring system. The (C)₁-C₇) An alkylene bridge or (C)₁-C₆) The heteroalkylene bridge can also form a spiro ring system with the ring system formed by R3 and R4. Examples of such fused, bridged or spiro ring systems formed from R3 and R4 are diazabicyclo [3.2.1]Octyl, especially 3, 8-diazabicyclo [3.2.1 ]]Octyl, diazabicyclo [2.2.1 ]]Heptylalkyl radicals, especially 2, 5-diazabicyclo [2.2.1 ]]Heptalkyl octahydropyrrolo [3, 4-b]Pyrrolyl, hexahydropyrrolo [3, 4-c ] s ]Pyrrolyl, octahydropyrrolo [3, 4-c)]Pyrrolyl and diazaspiro-nonanyl radicals, especially 2, 7-diazaspiro [4.4 ]]A nonyl group.

In one embodiment of the invention, R3 and R4 together with the nitrogen atom to which they are bonded form a heterocyclic group selected from: azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, azepanyl, and 1, 4-diazepanyl groups, and in another embodiment, form a group selected from: azetidinyl, pyrrolidinyl, piperidinyl and morpholinyl, and in another embodiment, form a group selected from: azetidinyl, pyrrolidinyl, piperidinyl, in another embodiment azetidinyl, in another embodiment pyrrolidinyl, in another embodiment piperidinyl, in another embodiment morpholinyl, all of which may be substituted as shown.

The heterocyclic ring formed by R3 and R4 may carry further substituents which are selected independently of one another from R7 and R9. Preferred substituents for this group are:

F、Cl、Br、I，

(C₁-C₄) Alkyl, where the alkyl may be substituted one or more times by F, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, -CF ₃、-CH₂-CF₃、-CH₂-CH₂-CF₃、-CH₂-CH₂-CH₂-CF₃、-CH₂F、-CH₂-CH₂F、-CH₂-CH₂-CH₂-CH₂F，

(C₃-C₇) Cycloalkyl radicals, such as cyclopropyl, cyclopentyl,

-OH, hydroxy- (C)₁-C₄) Alkyl radicals, e.g., -CH₂-OH、-CH₂-CH₂-OH、-CH₂-CH₂-CH₂-OH，(C₁-C₄) -alkyl-O-, e.g., -OCH₃，

(C₁-C₄) -alkoxy- (C)₁-C₄) Alkyl radicals, e.g., -CH₂-OCH₃、-CH₂-CH₂-OCH₃、-CH₂-CH₂-CH₂-OCH₃，

-SO₂-(C₁-C₄) Alkyl radicals, e.g. SO₂-CH₃，

-NH₂、N((C₁-C₄) -alkyl groups)₂-, for example: -N (CH)₃)₂、-N(C₂H₅)₂，

NH₂(C₁-C₄) Alkyl-, N ((C)₁-C₄) -alkyl groups)₂-(C₁-C₄) Alkyl radicals, e.g., -CH₂-NH₂、-CH₂-CH₂-NH₂、-CH₂-CH₂-CH₂-NH₂，

-CN、NC-(C₁-C₄) -alkyl-, e.g., -CH₂-CN、-CH₂-CH₂-CN、-CH₂-CH₂-CH₂-CN，

-NH-(C₁-C₄) Alkyl, wherein the alkyl may be substituted one or more times by F, e.g., -NH-CH₂-F、-NH-CH₂-CH₂-F、-NH-CH₂-CF₃、-NH-CH₂-CH₂-CF₃，

-NH-(C₁-C₄) -alkyl-OH, -NH- (C)₁-C₄) -alkyl-O- (C)₁-C₄) Alkyl radicals, e.g., -NH-CH₂-OH、-NH-CH₂-CH₂-OH，

-NH-(C₁-C₄) alkyl-CN, e.g., -NH-CH₂-CN、-NH-CH₂-CH₂-CN，

-NH-(C₁-C₄) -alkyl-O- (C)₁-C₄) alkyl-OH, e.g., -NH-CH₂-CH₂-O-CH₂-CH₂-OH，

-NH-C(O)-(C₁-C₄) Alkyl, wherein the alkyl may be substituted one or more times by F, e.g., -NH-C (O) -CH₃、-NH-C(O)-CF₃，

Pyrrolidinyl, pyrrolidinyl-, (C₁-C₄) Alkyl radicals, e.g. N-pyrrolidinyl-CH₂Pyrimidinyl, for example pyrimidin-2-yl.

In one embodiment of the invention, the heterocyclic ring formed by R3 and R4 together with the nitrogen atom to which they are bonded may bear substituents R7 and R9, R7 and R9 being selected independently of one another from methyl, ethyl, CF₃、F、Cl、CN、NH₂、N(CH₃)₂、OH、OCH₃、SO₂CH₃In another embodiment the substituents R9 are independently of each other selected from F, Cl, CN, NH₂、N(CH₃)₂、OH、OCH₃、SO₂CH₃. In one embodiment of the invention, the heterocyclic ring formed by R3 and R4 together with the nitrogen atom to which they are bonded may bear one, two or three substituents R7 and R9, in another embodiment one or two substituents, in another embodiment one substituent.

The R3 and R4 groups form with the nitrogen to which they are bonded particularly preferably one of the following heterocyclic ring systems:

preferred R5 groups are independently from each other selected from:

F、Cl、Br、I、＝O、-CN、-OH、-NH₂、-NO₂，

(C₁-C₄) Alkyl, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, wherein the alkyl may be substituted one or more times by F, e.g. as-CF₃、-CF₂H；

(C₁-C₄) Alkoxy radicals, e.g., -OCH₃、-OC₂H₅Wherein the alkyl group may be substituted one or more times by F, e.g. -OCF₃、-OCHF₂、-OCH₂F，

-S-(C₁-C₄) Alkyl radicals, e.g. SCH₃Wherein the alkyl group may be substituted one or more times by F, e.g. as-SCF₃，

(C₁-C₄) -alkoxy- (C)₁-C₄) Alkyl, e.g. as-CH₂-OCH₃、-CH₂-CH₂-OCH₃，

NC-(C₁-C₄) -alkyl-, for example, -CH₂-CN，

NH₂-(C₁-C₄) -alkyl-, for example, -CH₂-NH₂，

N((C₁-C₄) -alkyl groups)₂-(C₁-C₄) -alkyl-, for example, -CH₂-N(CH₃)₂，

(C₁-C₄) -alkyl-C (O) -NH- (C)₁-C₄) -alkyl-, e.g., -CH₂-NH-C(O)CH₃，

N((C₁-C₄) -alkyl groups)₂-C(O)-(C₁-C₄) -alkyl-, e.g., -CH₂-C(O)-N(CH₃)₂，

-SO₂-(C₁-C₄) Alkyl radicals, e.g. SO₂CH₃Wherein the alkyl group may be substituted one or more times by F, e.g. -SO₂CF₃，

-SO₂NH₂、-SO₂N((C₁-C₄) -alkyl groups)₂E.g., -SO₂N(CH₃)₂、-SO₂N(C₂H₅)₂，

-SO₂-NH-(C₁-C₄) Alkyl radicals, e.g. SO₂-NH-CH₃、-SO₂-NH-CH₂-CH₃，-SO₂-NH-CH₂-CH₂-CH₃Wherein the alkyl group may be substituted one or more times by F, e.g. -SO₂-NH-CH₂-CF₃，-SO₂-NH-CH₂-CH₂-CF₃，

-NH-C(O)-(C₁-C₄) Alkyl, e.g., -NH-C (O) -CH₃，

-NH-C(O)-NH₂，-NH-C(O)-N((C₁-C₄) -alkyl groups)₂For example, -NH-C (O) -N (CH)₃)₂，

-NH-C(O)-O-(C₁-C₄) Alkylphenyl radicals, e.g., -NH-C (O) -O-CH₂-C₆H₆，

-NH-C(O)-O-(C₁-C₄) alkyl-COOH, e.g., -NH-C (O) -O-CH₂-COOH，

-NH-C(O)-O-(C₁-C₄) -alkyl-COO (C) ₁-C₄) An alkyl group, for example,

-NH-C(O)-O-CH₂-COOCH₃，

-NH-SO₂-(C₁-C₄) Alkyl radicals, e.g. NH-SO₂CH₃，

-N((C₁-C₄) -alkyl) -SO₂-(C₁-C₄) Alkyl radicals, e.g., -N (CH)₃)-SO₂CH₃，

-C(O)-(C₁-C₄) Alkyl), e.g., -C (O) -CH₃、-C(O)-CH₂-CH₃，

-C(O)-NH₂、-C(O)-N((C₁-C₄) -alkyl groups)₂E.g., -C (O) -N (CH)₃)₂、-C(O)-N(C₂H₅)₂，

-C(O)-O(C₁-C₄) Alkyl, e.g., -C (O) -OCH₃，

-C (O) a phenyl group,

-an O-phenyl group, which is,

-COOH、-COO(C₁-C₄) Alkyl radicals, e.g., -COOCH₃、-COOC₂H₅，

(C₁-C₄) -alkyl- (C)₃-C₇) heterocycloalkyl-C (O) -, e.g. (C)₁-C₄) -alkyl-piperazinyl-or-pyrimidinyl-or-piperidinyl-or-tetrahydropyridazinyl-C (O) -, in particular 4-methylpiperazin-1-yl-C (O) -,

(C₃-C₇) -heterocycloalkyl- (C)₁-C₄) Alkyl-, e.g. piperidinyl-or piperazinyl-or pyrimidinyl-or tetrahydropyridazinyl- (C)₁-C₄) -alkyl-, especially piperidin-1-yl-methyl-.

A preferred aryl group R5 is phenyl.

Other preferred R5 groups are heteroaryl groups, especially those selected from: pyrrol-1, 2 or 3-yl, pyrazol-1, 3, 4 or 5-yl, imidazol-1, 2, 4 or 5-yl, 1, 2, 3-triazol-1, 2, 4 or 5-yl, 1, 2, 4-triazol-1, 3 or 4-yl, tetrazol-1, 2 or 5-yl, 1, 3, 4-Oxadiazol-3-or 4-yl, 1, 2-iso-isomersOxazol-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, thiadiazol-2, 3, 4 or 5-yl, pyridin-2, 3 or 4-yl, benzo [ b ] b]Furan-2, 3, 4, 5, 6 or 7-yl, benzo [ b ] ]Thiophen-2, 3, 4, 5, 6 or 7-yl, indol-1, 2, 3, 4, 5, 6 or 7-yl, isoindol-12, 3, 4, 5, 6 or 7-yl, benzothiazol-2, 4, 5, 6 or 7-yl, benzisothiazol-3, 4, 5, 6 or 7-yl, benzoAzole-2, 4, 5, 6 or 7-yl, benzisoxazinesOxazol-3, 4, 5, 6 or 7-yl, benzodiazole-1, 2, 4, 5, 6 or 7-yl and benzisoxazole-1, 2, 3, 4, 5, 6 or 7-yl.

Preferred heterocycloalkyl radicals R5 are selected from the group consisting of piperidin-1, 2, 3 or 4-yl, piperazin-1, 2 or 3-yl, pyrimidin-1, 2, 4 or 5-yl, tetrahydropyridazin-1, 3 or 4-yl, 2H-pyridin-1, 2, 3, 4, 5 or 6-yl, 4H-pyridin-1, 2, 3 or 4-yl, morpholin-2, 3 or 4-yl, thiomorpholin-2, 3 or 4-yl, pyrrolidin-1, 2 or 3-yl, dihydropyrrolidin-1, 2 or 3-yl, imidazolidin-1, 2 or 4-yl, dihydroimidazol-1, 2 or 4-yl, thiazolidin-2, 3, 4 or 5-yl, isothiazol-2, 3, 4 or 5-yl and.Oxazolidin-2, 3, 4 or 5-yl.

Preferred heterocycloalkylaryl radicals R5 are selected from 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 ] dihydropyrrole-1, 2, 3, 4, 5, 6 or 7-yl, benzodioxolyl-2, 4, 5, 6 or 7-yl and benzodioxolyl-2, 4, 5, 6 or 7-yl, tetrahydroquinoline-2, 3, 4, 5, 6, 7 or 8-yl and isoquinoline-1, 3, 4, 5, 6, 7 or 8-yl.

The preferred aryl, heteroaryl, heterocycloalkyl, heterocycloalkylaryl and heterocycloalkylheteroaryl groups may bear one or more, preferably one, two, three or four, further substituents which are selected independently of one another from the group of R11. Particularly preferred R11 groups are selected from:

F、Cl、Br、I、-CN、NH₂、OH、＝O，

(C₁-C₄) Alkyl-, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl and (C)₁-C₄) -alkyloxy-, for example, -OCH₃、-OC₂H₅Wherein the alkyl and alkoxy groups may be substituted one or more times by F,

-SO₂CH₃、-SO₂NH₂、-NH-C(O)-CH₃、-C(O)-NH₂and-NH-C (O) -NH₂、-COOCH₃、-COOC₂H₅。

Particularly preferred aryl, heteroaryl, heterocycloalkyl, heterocycloalkylaryl and heterocycloalkylheteroaryl groups R5 are:

in one embodiment of the invention, the R5 groups may be selected independently of one another from the group consisting of F, Cl, Br, CN, methyl, ethyl, propyl, tert-butyl, NH₂、OCH₃、SO₂CH₃、SO₂NH₂、C(O)NH₂、-NH-C(O)-CH₃Pyrazol-1, 2 or 3-yl, imidazol-1, 2 or 3-yl, 1, 2, 3-triazol-1 or 2-yl, 1, 2, 4-triazol-1, 3 or 4-yl, tetrazol-1, 2 or 5-yl, thiazol-2, 3 or 4-yl, 1, 3, 4-Oxadiazol-3-or 4-yl,Azol-2 or 3-yl, isoOxazol-2 or 3-yl, triazol-1 or 2-yl, piperidin-1-yl, piperazin-1-yl, pyrrolidin-1-yl,Oxazolidin-3-yl, isoOxazolidin-2-yl, tetrahydroimidazol-1-yl, dihydroimidazol-1-yl, isothiazol-1-yl, and morpholin-4-yl, where the cyclic group R5 may carry further substituents R11. In another embodiment, one R5 group is selected from F, Cl, CN, methyl, ethyl, t-butyl, OCH ₃、SO₂CH₃、SO₂NH₂、C(O)NH₂and-NH-C (O) -CH₃. In another embodiment, one R5 group is selected from pyrazol-1, 2 or 3-yl, imidazol-1-yl, 1, 2, 3-triazol-1 or 2-yl, 1, 2, 4-triazol-1, 3 or 4-yl, thiazol-2 or 4-yl, di-or tri-azolyl, di,Azol-2 or 3-yl, isoOxazol-2 or 3-yl, triazol-1 or 2-yl, tetrazol-1-yl, all of which may bear further substituents selected from: methyl, ethyl, cyclopropyl, methoxy, CN, OH, NH₂、N(CH₃)₂Or from piperidin-1-yl, piperazin-1-yl, pyrrolidin-1-yl,oxazolidin-3-yl, isoOxazolidin-2-yl, tetrahydroimidazol-1-yl, all of which may bear further substituents R11 selected from: methyl, ethyl, cyclopropyl, methoxyRadical, CN, (═ O), OH, NH₂And N (CH)₃)₂。

In one embodiment of the invention, one R5 group is selected from F, Cl, Br, CN, methyl, ethyl, propyl, tert-butyl, NH₂、OCH₃、SO₂CH₃、SO₂NH₂、C(O)NH₂、-NH-C(O)-CH₃And one R5 group is selected from pyrazol-1, 2 or 3-yl, imidazol-1, 2 or 3-yl, 1, 2, 3-triazol-1 or 2-yl, 1, 2, 4-triazol-1, 3 or 4-yl, thiazol-2, 3 or 4-yl, 1, 3, 4-An oxadiazol-3-or 4-yl group,azol-2 or 3-yl, isoOxazol-2, or 3-yl, triazol-1 or 2-yl, tetrazol-1-yl, all of which may bear substituents R11 selected from: methyl, ethyl, cyclopropyl, methoxy, CN, OH, NH ₂，N(CH₃)₂Or from piperidin-1-yl, piperazin-1-yl, pyrrolidin-1-yl,oxazolidin-3-yl, isoOxazolidin-2-yl, tetrahydroimidazol-1-yl, dihydroimidazol-1-yl, isothiazol-1-yl, and morpholin-4-yl, all of which may bear substituents R11 selected from: methyl, ethyl, cyclopropyl, methoxy, CN, (═ O), OH, NH₂And N (CH)₃)₂。

In one embodiment of the invention, the substituent R11 is selected from methyl, ethyl, cyclopropyl, methoxy, CN, (═ O), OH, NH₂，N(CH₃)₂，SO₂Me and CO₂Me。

Within the scope of the invention of (C)₁-C₁₀) The alkyl group may be linear or branched. This also applies when they bear substituents or occur as substituents of other groups, for example in fluoroalkyl or alkoxy. Examples of alkyl are methyl, ethyl, n-propyl, isopropyl (═ 1-methylethyl), n-butyl, isobutyl (═ 2-methylpropyl), sec-butyl (═ 1-methylpropyl), tert-butyl (═ 1, 1-dimethylethyl), n-pentyl, tert-pentyl, neopentyl and hexyl. Preferred alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl and tert-butyl.

Within the scope of the invention of (C)₂-C₁₀) Alkenyl groups may similarly be straight-chain or branched. This also applies when they bear substituents or occur as substituents of other groups. Examples of alkenyl are ethenyl, propenyl and butenyl.

Within the scope of the invention of (C)₂-C₁₀) Alkynyl groups may similarly be straight-chain or branched. This also applies when they bear substituents or occur as substituents of other groups. Examples of alkynyl groups are ethynyl, propynyl and butynyl.

Within the scope of the invention of (C)₃-C₁₄) Cycloalkyl groups may be saturated or partially unsaturated. This also applies when they bear substituents or occur as substituents of other groups. Preferred cycloalkyl groups have 3, 4, 5, 6, 7 or 8 carbon atoms. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

Within the scope of the invention of (C)₂-C₁₉) The heterocycloalkyl group may be saturated or partially unsaturated. This also applies when they bear substituents or occur as substituents of other groups. The heterocycloalkyl group preferably has a heteroatom selected from nitrogen, oxygen and sulfur. Preferably, the heterocycloalkyl group has 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms, there may be 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 nitrogen and 1 oxygen atom or 1 sulfur atom, or 1 oxygen and 1 sulfur atomThe atom is taken as a hetero atom. The heterocycloalkyl group is attached through an arbitrary position. Examples of such heterocycles are selected from the group consisting of oxacyclopropane, thietanepropyl, aziridine, oxetane, thietane, azetidine, diazetidine, pyrrolidinyl, dihydropyrrolyl, dihydroimidazolyl, dihydropyrazolyl, tetrahydropyrazolyl, oxacyclopentyl, dihydrofuranyl, dioxolanyl, thietane, dihydrothienyl, and mixtures thereof, Oxazolidinyl, dihydroAzolyl radical, isoOxazolidinyl, dihydroisosOxazolyl, thiazolidinyl, dihydrothiazolyl, isothiazolyl, dihydroisothiazolyl, oxathiolanyl (oxathiolidinyl), 2H-pyranyl, 4H-pyranyl, tetrahydropyranyl, 2H-thiopyranyl, 4H-thiopyranyl, tetrahydrothiopyranyl, piperidinyl, di-, tetrahydropyridinyl, piperazinyl, di-, tetrahydropyrazinyl, di-, tetra-, hexahydropyridazinyl, di-, tetra-, hexahydropyrimidinyl, morpholinyl, thiomorpholinyl, azepanyl, thiepanyl and oxepanyl groups, it also being possible for two of these heterocycles to form a saturated or partially unsaturated fused bicyclic ring system. An example of such a bicyclic ring system is octahydropyrrolo [1, 2a ]]Pyrazinyl octahydropyrrolo [3, 4b ]]Pyrrolyl, hexahydropyrrolo [3, 4-c ] s]Pyrrolyl-and octahydropyrrolo [3, 4-c)]A pyrrolyl group.

Preferably (C)₆-C₁₀) Examples of aryl are phenyl and naphthyl. This also applies when they bear substituents or occur as substituents of other groups.

(C₁-C₉) Heteroaryl is an aromatic ring compound, one of whichThe one or more ring atoms are oxygen, sulfur or nitrogen atoms, for example, 1, 2 or 3 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms or a combination of heteroatoms. This also applies when they bear substituents or occur as substituents of other groups. The heteroaryl group may be attached through any position. Heteroaryl means, for example, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, Azolyl radical, isoOxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, and cinnolinyl.

Particularly preferred heteroaryl groups are 2-or 3-thienyl, 2-or 3-furyl, 1-, 2-or 3-pyrrolyl, 1-, 2-, 4-or 5-imidazolyl, 1-, 3-, 4-or 5-pyrazolyl, 1, 2, 3-triazol-1-, -4-or-5-yl, 1, 2, 4-triazol-1-, -3-or-5-yl, 1-or 5-tetrazolyl, 2-, 4-or 5-propanoylAzolyl, 3-, 4-or 5-isoAzolyl, 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-isothiazolyl, 1, 3, 4-thiadiazol-2-or-5-yl, 1, 2, 4-thiadiazol-3-or-5-A group, a 1, 2, 3-thiadiazol-4-or-5-yl group, a 2-, 3-or 4-pyridyl group, a 2-, 4-, 5-or 6-pyrimidinyl group, a 3-or 4-pyridazinyl group, a pyrazinyl group, a 1-, 2-, 3-, 4-, 5-, 6-or 7-indolyl group, a 1-, 2-, 4-or 5-benzimidazolyl group, a 1-, 3-, 4-, 5-, 6-or 7-indazolyl group, a 2-, 3-, 4-, 5-, 6-, 7-or 8-quinolyl group, a 1-, 3-, 4-, 5-, 6-, 7-or 8-isoquinolyl group, 2-, 4-, 5-, 6-, 7-or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7-or 8-cinnolinyl, 2-, 3-, 5-, 6-, 7-or 8-quinoxalinyl, 1-, 4-, 5-, 6-, 7-or 8-phthalazinyl.

(C₉-C₁₄) The cycloalkylaryl group is preferably selected from fused ring systems having a cycloalkyl ring and an aryl ring, in particular a phenyl ring. Particularly preferred cycloalkylaryl groups are indenyl, dihydronaphthyl, tetrahydronaphthyl and indanyl.

(C₅-C₁₃) The cycloalkylheteroaryl group is preferably selected from fused ring systems having a cycloalkylcycloheteroaryl ring.

(C₇-C₁₃) The heterocycloalkylaryl is preferably selected from fused ring systems having a heterocycloalkyl ring and an aryl ring, in particular a phenyl ring. Particularly preferred heterocycloalkylaryl radicals are the benzodihydrophenyl radicals, the benzothiophenyl radicals, the benzodihydrofuranyl radicals, the benzoxacyclopentenyl radicals, the benzodioxolyl radicals, the benzodihydropyrrolyl radicals, the benzodihydroimidazolyl radicals, the benzodihydropyrazolyl radicals, the benzodihydrotriazolyl radicals, the benzopiperazinyl radicals, the benzodihydropyrazolyl radicals, the benzomorpholinyl radicals, the benzodihydropyrazolyl radicals, the benzopiperazinyl radicals, the benzodihydropyrrolyl radicals, the benzodihydrothiazolyl radicals, the benzomorpholinOxazolyl, dihydroquinolinyl, dihydroisoquinolinyl, tetrahydroisoquinolinyl, and tetrahydroquinolinyl.

(C₄-C₁₂) The heterocycloalkylheteroaryl group is preferably selected from fused ring systems having a heterocycloalkyl ring and a heteroaryl ring.

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

If the compounds of the formula I contain one or more asymmetric centers, these may, independently of one another, have the S or R configuration. The compounds can be formed as optical isomers, diastereoisomers, racemates or mixtures thereof in all ratios. Furthermore, the compounds of formula I may be in the form of rotamers.

Particularly preferred stereoisomers of formula I, wherein the group XLBR5 bonded in position 1 is oriented downwards and the group- (CH) bonded in position 2₂)_qThe NR3R4 is oriented upwards, the orientation being determined by the plane formed by the three carbon atoms in the 1, 2 and 3 positions, and the molecule adopts the following orientation (formula Ie):

preference is given to compounds of the formula I having the trans-1S, 2S configuration in the 1-and 2-positions.

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

Particularly preferred compounds of formula I are selected from:

and pharmaceutically acceptable salts thereof.

Due to their NHE-inhibiting properties, the compounds of formula I are suitable for the prevention and treatment of diseases caused by activated NHE or by activated NHE, as well as diseases secondary to NHE-related injuries. The compounds of formula I may also be suitable for the treatment and prevention of diseases in which NHE is only partially inhibited, for example by using lower doses. When reference is made herein to one or more compounds of formula I of the present invention, pharmaceutically acceptable salts thereof are generally included, even when not explicitly stated.

The invention therefore also relates to the use of the compounds of the formula I for the prophylaxis and treatment of acute or chronic diseases in veterinary and human medicine.

Due to their pharmacological action, the compounds of the formula I are particularly suitable for improving respiratory drive. They are therefore useful in the treatment of impaired respiratory diseases (such as may occur, for example, in the following clinical conditions and diseases): central impaired respiratory drive (e.g., central sleep apnea (central sudden death), post-operative hypoxia (positive hyperoxia)), muscle-related respiratory damage (muscle-related respiratory damage), respiratory damage after prolonged ventilation (respiratory damage following high ventilation), respiratory damage associated with adaptation to high altitude (respiratory damage with acquired accommodation to high activity), obstructive and mixed sleep apnea (acquired and mixed form of sleep apnea), sleep-related respiratory system impairment (sleep-related respiratory syndromes), sleep hypopnea syndrome (sleep hypopnea syndrome), upper airway resistance syndrome (upper airway resistance syndrome), acute and chronic lung diseases with concomitant hypoxia (acute and chronic pulmonary diseases with hypercapnia), and hypercapnia.

In addition, the compound increases the tension of the muscles of the upper respiratory tract, thereby suppressing snoring. The compounds are therefore particularly useful for the prevention and treatment of sleep apnea, upper respiratory resistance syndrome, muscle-related impairment of the respiratory system, and for the prevention and treatment of snoring.

The combination of the NHE inhibitor of formula I with a carbonic anhydrase inhibitor (e.g. acetazolamide) is also advantageous in this respect, the latter causing metabolic acidosis and thus enhancing respiratory movement by itself, whereby an increased effect and a reduced amount of active ingredient can be achieved.

The compounds of the invention preserve (as a result of their NHE 3-inhibiting effect) the cellular energy reserve (which is rapidly depleted in toxic and pathogenic events and thus leads to cell damage or cell death). In this respect, the high energy consumption of ATP sodium uptake in the proximal tubule is temporarily stopped under the influence of NHE3 inhibitors, and thus the cells are able to survive acute pathogenic, ischemic or toxic conditions. The compounds are therefore suitable, for example, as medicaments for the treatment of ischemic conditions, in particular ischemic lesions, such as acute renal failure.

The compounds are also suitable for the treatment of chronic kidney disease and various types of nephritis (which is caused as a result of increased protein excretion), the latter leading to chronic renal failure. The compounds of the formula I are therefore suitable for the preparation of medicaments for the treatment of late-stage damage from diabetes, diabetic nephropathy and chronic kidney disease, in particular all kidney inflammations (nephritis) which are associated with increased protein/albumin excretion.

It has been shown that the compounds of the invention have an inhibitory and delaying effect on glucose absorption and are therefore capable of lowering blood glucose as well as having a beneficial effect on other metabolic parameters such as triglycerides. Due to these effects, the compounds of the present invention can be advantageously used for the prevention and treatment of metabolic syndrome, diabetes and hyperlipidemia.

It has been shown that the compounds of the invention have a mild laxative effect and can therefore also be advantageously used as laxatives or for the prevention and treatment of constipation if there is a risk of constipation.

The compounds of the invention can further be advantageously used for the prophylaxis and treatment of acute and chronic intestinal diseases which are caused, for example, by ischemic states of the intestinal region and/or by subsequent reperfusion or by inflammatory states and events. Such complications may be caused by, for example, a lack of intestinal motility (often observed after, for example, surgery), association with constipation, or a greatly reduced intestinal activity.

The compounds of the invention are useful for preventing the formation of gallstones.

In summary, the NHE inhibitors described herein may be advantageously combined with other compounds that similarly modulate intracellular pH, those compounds that are suitable as inhibitors of enzyme members of carbonic anhydrase, inhibitors of systems that transport bicarbonate ions, such as sodium bicarbonate cotransporter (NBC) or sodium-dependent chloride-bicarbonate exchanger (NCBE), and with other NHE inhibitors that have inhibitory effects on other NHE subtypes, as combination partners, as they may enhance or modulate the pharmacologically relevant pH-modulating effects of the NHE inhibitors described herein.

Since sodium ion/proton exchange is significantly increased in essential hypertension, the compounds of formula I are suitable for the prevention and treatment of hypertension and cardiovascular diseases. In this respect, they can be used alone or together with suitable combination drugs for the treatment of hypertension and for the treatment of cardiovascular diseases. Thus, for example, one or more diuretics having a thiazide-like action, loop diuretics, aldosterone and aldosterone-like (pseudoaldsterone) antagonists, such as hydrochlorothiazide, indapamide, polythiazide, furosemide, piretanide, torasemide, bumetanide, amiloride, triamterene, spironolactone or eplerenone (eplerene) may be combined with a compound of formula I. The NHE inhibitors of the invention may also be used in combination with calcium antagonists such as verapamil, diltiazem, amlodipine or nifedipine, and with ACE inhibitors such as ramipril, enalapril, lisinopril, fosinopril or captopril. Further advantageous combinations are beta blockers such as metoprolol, salbutamol and the like, antagonists of the angiotensin receptor and its subtype receptors such as losartan, irbesartan, valsartan, omatrara, Gernopatrilat, endothelin antagonists, renin inhibitors, adenosine receptor agonists, inhibitors and activators of the potassium channel such as glibenclamide, glimepiride, diazoxide, cromoALim, minoxidil and the like, activators of the mitochondrial ATP-sensitive potassium ATP channel (mitoK () channel), inhibitors of other potassium channels such as Kv1.5 and the like.

NHE inhibitors are also suitable for the treatment of non-insulin dependent diabetes mellitus (NIDDM), for example in cases where insulin resistance is limited. In this respect, in order to enhance the anti-diabetic efficacy and the quality of action of the compounds of the invention, it is advantageous to combine them with biguanides, such as metformin, with anti-diabetic sulfonylureas, such as glibenclamide, glimepiride, tolbutamide, etc., with glucosidase inhibitors, with PPAR agonists, such as rosiglitazone, pioglitazone, etc., with insulin products in different administration forms, with DB4 inhibitors, with insulin sensitizers or with meglitinide.

The compounds are therefore advantageously used alone or in combination with other medicaments or active ingredients for the preparation of medicaments for the treatment or prophylaxis of the following diseases: impaired respiratory drive, respiratory diseases, sleep-related respiratory diseases, sleep apnea, snoring, acute and chronic kidney disease, acute and chronic renal failure, impaired bowel function, hypertension, essential hypertension.

The compounds of the invention are also suitable for the treatment of cystic fibrosis (mucoviscidosis). It has been shown that deficiency of the CFTR protein in cystic fibrosis activates NHE3, leading to excessive salt and water absorption in the intestine (gut, biliary system, pancreas), semen, upper respiratory tract and lungs. This leads to desiccation of stool (obstipation), intestinal secretions, and lung fluid, resulting in viscoelastic mucus in the lungs, which subsequently causes frequent respiratory infections that ultimately impair lung function, a significant cause of death. In addition, this overactivation of NHE3 results in a more acidic environment in the gut and a more acidic pH in the lung fluid (favoring bacterial infections, especially pseudomonas aeruginosa infections) that impairs digestion (dyspepsia). The compounds may be administered systemically (peros, i.m., i.v., s.c.) or as inhalants to treat respiratory and pulmonary symptoms.

The compounds have efficacy in acute and chronic respiratory diseases and infections, as mucolytics, by inhibiting salt and water absorption in the upper respiratory tract and lungs, thereby causing mucus liquefaction. This effect is of therapeutic use in acute and chronic viral, bacterial and fungal infections of the upper respiratory tract and lungs as well as in chronic lung diseases such as asthma and COPD.

The invention also relates to the use of compounds of formula I and their pharmaceutically acceptable salts as medicaments, and to medicaments comprising compounds of formula I or their pharmaceutically acceptable salts.

The invention also relates to the use of these compounds or their pharmaceutically acceptable salts for the treatment or prevention of Na by total or partial inhibition of NHE3⁺/H⁺Use of the exchanged disease.

A further aspect of the present invention is therefore the use of a compound of the formula I according to one or more of claims 1 to 15 and/or of a pharmaceutically acceptable salt thereof, alone or in combination with other medicaments or active ingredients, for the preparation of a medicament for the treatment or prophylaxis of the following diseases: impaired respiratory drive, respiratory diseases, sleep-related respiratory diseases, sleep apnea (sleep apneas), snoring (snoring), cystic fibrosis, upper and lower respiratory diseases associated with mucus viscosity, acute and chronic renal failure (acute and chronic), impaired bowel function (cardiovascular diseases), constipation (constipation), hypertension (high blood pressure), essential hypertension (CNS), CNS hyperreactivity, CNS hyperresponsiveness (chronic and chronic obstructive diseases), and other respiratory diseases, Epilepsy (epilepsy) and centrally induced spasms or anxiety states, depression and psychosis, ischemic states or strokes of the peripheral or central nervous system, degenerative CNS diseases, reduced memory capacity (reduced memory capacity), dementia and alzheimer's disease, acute and chronic damage and diseases of peripheral organs or limbs caused by ischemic or reperfusion events, atherosclerosis, impaired lipid metabolism (ischemic disorders of hyperlipidemia), thrombosis, diabetes, impaired biliary function (impaired vascular function), ectoparasitic infections (injury to ectoparasites), diseases of vascular endothelial function, impaired malaria, malaria or stroke, and diabetic conditions, or primary or secondary cell proliferation, for the preservation and storage of surgical grafts, for surgery and organ transplantation, and for health maintenance and longevity.

The invention also relates to a medicament for human, veterinary or plant protection, which comprises an effective amount of a compound of the formula I and/or a pharmaceutically acceptable salt thereof, alone or in combination with one or more other pharmacologically active ingredients or medicaments.

Medicaments comprising a compound of formula I or a pharmaceutically acceptable salt thereof can be administered, for example, orally, parenterally, intramuscularly, intravenously, rectally, intranasally, intrapharyngeally, by inhalation, subcutaneously or by suitable transdermal dosage forms, the preferred administration depending on the respective manifestation of the condition. Furthermore, the compounds of the formula I can be used alone or together with pharmaceutical excipients, in particular in veterinary and human medicine and in crop protection. The medicament comprises the active ingredient of formula I and/or a pharmaceutically acceptable salt thereof in an amount of typically 0.01mg to 1g per dosage unit.

The person skilled in the art is familiar, on the basis of his expert knowledge, with excipients which are suitable for the desired pharmaceutical preparation. In addition to solvents, gel formers, suppository bases, tablet excipients and other active ingredient carriers, it is possible to use, for example, antioxidants, dispersants, emulsifiers, antifoams, odor masking agents, preservatives, cosolvents or colorants.

For oral administration, the active compounds are mixed with additives suitable for this purpose, such as carriers, stabilizers or inert diluents, and converted by customary methods into suitable dosage forms, such as tablets, coated tablets, hard gelatin capsules, aqueous, alcoholic or oily solutions. Examples of inert carriers which may be used are gum arabic, magnesium oxide, magnesium carbonate, potassium phosphate, lactose, glucose or starch, in particular corn starch. Furthermore, dry and wet granules are also possible for this formulation. Examples of suitable oily carriers or solvents are vegetable or animal oils, such as sunflower oil or cod liver oil.

For subcutaneous, transdermal or intravenous administration, the active compounds used, if desired, are converted with substances used for this purpose, such as cosolvents, emulsifiers or other excipients, into solutions, suspensions or emulsions. Examples of suitable cosolvents are: water, physiological saline or alcohols, e.g. ethanol, propanol, glycerol, and sugar solutions such as glucose or mannitol solutions, or mixtures of the various solvents mentioned.

Pharmaceutical formulations which are suitable for administration in the form of aerosols or sprays are, for example, solutions, suspensions or emulsions of the active ingredient of formula I in a pharmaceutically acceptable solvent such as, inter alia, ethanol or water or a mixture of such solvents. The formulation may also contain, if desired, other pharmaceutical excipients such as surfactants, emulsifiers and stabilizers, and a drive gas. Such formulations typically comprise the active ingredient at a concentration of about 0.1-10, especially about 0.3-3% by weight.

The dose and frequency of administration of the active ingredient of formula I to be administered depend on the potency and duration of action of the compound used; and also on the nature and severity of the disease requiring treatment, as well as on the sex, age, weight and individual response of the mammal requiring treatment.

For a patient weighing about 75kg, the average daily dose of a compound of formula I is at least 0.001mg/kg, preferably 0.1mg/kg, up to 30mg/kg, preferably 1mg/kg body weight. Higher doses may also be necessary in emergency situations, for example, immediately after asphyxiation at high altitudes. Up to 300mg/kg may be necessary per day, especially at i.v. administration, for example for intensive care infarcted patients. The daily dose may be divided into one or more, for example up to 4, individual doses.

If the compounds of the formula I contain one or more acidic or basic groups or one or more basic heterocycles, corresponding physiologically or toxicologically acceptable salts are also included in the invention, in particular pharmaceutically acceptable salts. Thus, the compounds of the formula I can be deprotonated at the acidic group and can be employed, for example, as alkali metal salts, preferably sodium or potassium salts, or ammonium salts, for example with ammonia or organic amines or amino acids. The compounds of the formula I which contain at least one basic group can also be prepared in the form of their physiologically acceptable acid addition salts, for example with the following acids: inorganic acids such as sulfuric acid or phosphoric acid or organic acids such as acetic acid, citric acid, tartaric acid, lactic acid, malonic acid, methanesulfonic acid, fumaric acid. Suitable acid addition salts in this connection are all pharmacologically acceptable salts, for example halides, in particular hydrochloride, lactate, sulfate, citrate, tartrate, acetate, phosphate, methanesulfonate, p-toluenesulfonate, adipate, fumarate, gluconate, glutamate, glycerophosphate, maleate and pamoate (pamoates) (which also correspond to physiologically acceptable anions); but may also be a trifluoroacetate salt.

The invention also encompasses derivatives, e.g. solvates, of the compounds of formula I, such as hydrates and alcohol adducts, esters, precursors and other physiologically acceptable derivatives of the compounds of formula I, active metabolites of the compounds of formula I. The invention likewise comprises all crystalline forms of the compounds of the formula I.

A process for preparing a compound of formula I:

general procedures suitable for preparing compounds of formula I are described below. The compounds of the formula I in this connection can be prepared by different chemical processes. The groups A, B, L, X, R1, R2, R3, R4 and R5 and the index p mentioned in the following methods have the above-mentioned meanings unless they are explicitly stated otherwise.

Abbreviations:

the method A comprises the following steps:

starting from the epoxide of formula II, as shown in reaction scheme a, after initial opening of the epoxide ring using an amine of formula HNR3R4, the corresponding 1-amino-2-ol intermediate of formula III is obtained, which is subsequently subjected to a Mitsunobu reaction with an aryl or heteroaryl compound B-OH, which may be substituted one or more times by R5. Phenol is preferably used in this reaction. Aryl or heteroaryl thiophenols B-SH or aryl-or heteroarylcarboxylic acids B-CO may alternatively be used₂H (which may be substituted one or more times by R5) to obtain the corresponding-S-or-CO₂H-bridged derivatives. The Mitsunobu reaction, which is known, is carried out in the presence of a phosphine (e.g., triphenylphosphine) and an azodicarboxylate (e.g., diisopropyl azodicarboxylate) in an inert solvent (e.g., acetonitrile, CH) ₂Cl₂Or tetrahydrofuran). In the case of 1-amino-2-alcohols of the formula III, this leads to a migration of the amine group NR3R4 to the 2-position of the parent structure (J.org.chem.1991, 56, 670-.

Reaction scheme a: synthesis of Compounds of formula I by Mitsunobu conversion

Wherein L is a covalent bond, -C (═ O) -, and X is O,

or L is a covalent bond and X is S.

In this way, it is possible to prepare a large number of compounds I (preferably those in which the two substituents are in the trans configuration relative to one another). If one of the groups R3 and R4 of the amine substituent is to be replaced by another functional group (e.g. a hydroxyl or amino group), care must be taken (if necessary) to protect such groups during the Mitsunobu reaction. This can be done, for example, by trialkyl or triarylsilyl groups (in the case of OH groups) or by BOC protecting groups (in the case of amino groups). After the Mitsunobu reaction, the protecting group is then removed (e.g., by treatment with hydrochloric acid or trifluoroacetic acid) to provide the compound of formula I. After deprotection, these functional groups may be further modified (if desired), for example by alkylation with alkylating agents, or acylation followed by reduction to give further compounds I.

The starting materials used in reaction scheme a (for example epoxides of formula II, amines NHR3R4 and hydroxyaryl or hydroxyheteroaryl groups or thiol derivatives thereof) are either commercially available, known in the literature or can be readily synthesized (analogous to compounds known in the literature). Some suitable synthetic schemes for such starting materials are reproduced by the examples in the experimental section.

Method B

Other methods for preparing compounds of formula I are described in reaction scheme B.

Reaction scheme B: synthesis of Compound I by nucleophilic aromatic substitution

In this process, 2-bromo 1-keto compounds of the formula IV are reacted with amines of the formula R3-NH-R4 to give the corresponding aminoketones V. The keto group is then reduced to the 1-hydroxy group to give an intermediate of formula VI. It is also possible to prepare the relevant product VI having both cis and trans configuration in the centers 1 and 2. The resulting intermediate of formula VI is then arylated by nucleophilic aromatic substitution on aryl or heteroaryl compound B-Y (where B may be substituted one or more times by R5), using a strong base, e.g., sodium hydride or NaOH powder, in an inert solvent such as DMSO. Y is a related suitable leaving group (e.g., fluoro, chloro or trifluoromethanesulfonyloxy). If the groups R3 and R4 are substituted, for example, with amino or hydroxyl groups, the substituents, if desired, should be protected with base-stable protecting groups, such as alkyl-or aryl-substituted silyl groups.

Using this method, it is also possible to use widely known or commercially available bromoketone IV, or can be conveniently prepared from the appropriate ketone, e.g., by bromination under standard conditions.

Method C

Other processes concern those compounds of formula I in which the amine group NR3R4 is linked to position 2 by a carbon-containing bridge, i.e. q is 1 in formula I.

Reaction scheme C: synthesis of Compounds of formula I through Mannich-like products

In this case, the ketone of the formula VII is reacted with a formamide acetal, preferably N, N-dimethylformamide dimethyl acetal, to give the corresponding dimethylaminomethylene compound of the formula VIII. This dimethylamino group can be replaced in the next stage by another amino group to give the aminomethylene compound of formula IX. This can be done by heating the compound of formula VIII, for example in DMF, in the presence of excess amine HNR3R 4. Subsequent reduction (e.g., by sodium borohydride in methanol) typically yields a mixture of stereoisomeric aminoalcohols of formula X, which can be separated (if desired) into individual components and then arylated in analogy to that shown in reaction scheme B, to yield compound I of the present invention.

Method D

Other methods of preparing compounds of formula I are shown in reaction scheme D. 1-amino-2-indanol III and analogs thereof are reacted under Mitsunobu conditions in an inert solvent such as THF in the presence of a suitable azide source such as diphenylphosphonyl azide (DPPA). In this case, the amine group also migrates from position 1 to position 2 (as shown in reaction scheme a). Preferentially form 1-azido-2-indanes having the trans configuration upon addition of a suitable reducing agent (e.g., LiAlH) ₄) And then directly reacting in situ to obtain the diamine with the trans configuration and the general formula XI. To obtain the compounds of the formula I, the compounds of the formula XI are arylated using palladium catalysts, for example under Buchwald conditions known from the literature (J.Am.chem.Soc.1997, 8451-8458).

Reaction scheme D: synthesis of Compound I by Mitsunobu conversion followed by arylation

Method E

Other methods of preparing compounds of formula I are described in reaction scheme E. Benzoate I, which is synthesized according to reaction scheme A, is hydrolyzed in a known manner to form a compound of formula VI. This can be done, for example, in a solvent such as an acetone/water mixture, and with a suitable base such as sodium hydroxide. The compound of formula VI is then reacted with a suitable alkylating agent (e.g., benzyl bromide) in a solvent (e.g., THF) in the presence of a suitable base (e.g., sodium hydride). The compound I obtained in this way can be used for further processing (when required).

Reaction scheme E: synthesis of Compound I by alkylation

If the compounds I contain further functional groups (for example alcohols or amines), these compounds can be reacted further in a known manner according to reaction scheme F. Suitable examples are sequential operations of acylation, alkylation or acylation/reduction. This procedure is described in the experimental part by way of an exemplary embodiment.

Reaction scheme F: optional further reaction of Compounds I

Method G: other processes involve compounds of formula I in which one or two substituents R3 or R4 at the amine group NR3R4 are equal to hydrogen, i.e. R3 ═ H or R3 ═ R4 ═ H.

Reaction scheme G: synthesis of Compounds of formula I by Pd-catalyzed deprotection of allylamines

In this process, allylamine XI, which can be synthesized, for example, according to Process A, is reacted with a nucleophile, such as thiosalicylic acid or dimethyl barbituric acid, in an inert solvent, such as CH₂Cl₂Or THF). The reaction is catalyzed by Pd. A suitable Pd source is for example Pd (PPh)₃)₄Or Pd (dba)₂And in the presence of a stabilizing ligand such as bis (diphenylphosphino) butane. In the case of bis-allylamine (R3 ═ R4 ═ allyl), both allyl groups can be removed using at least 2 equivalents of the appropriate nucleophile and extended reaction times. The compounds of formula I, which are synthesized according to scheme G, can be used for further operations, such as acylation or alkylation.

Exemplary embodiments:

unless explicitly mentioned, equivalents used in the following steps refer to the amount of material.

The following LC method was used to analyze the exemplary embodiments.

Reaction scheme 1: general synthetic reaction scheme for indane oxides

The general synthetic method comprises the following steps:

step 1/2: cinnamic acid (1 equivalent) and PtO₂(2.2 mol%) suspended in ethanol (EtOH) (8ml/mmol cinnamic acid) in H₂Stirring vigorously under an atmosphere (1bar) until the reaction mixture no longer absorbs H₂Until now. The suspension was filtered and the residue was washed with EtOH. The solvent of the filtrate was removed in vacuo and the resulting crude mixture of propionic acid and propionate was used in the next reaction without further purification.

The mixture of reaction step 1 was dissolved in EtOH (2ml/mmol intermediate of step 1) and aqueous NaOH (2.5 equivalents based on intermediate of step 1) was added. The solution was stirred for 16 hours and the volume of the mixture was reduced by applying vacuum. The resulting solution was diluted with water and acidified with 2N aqueous HCl. The suspension was filtered and the residue was washed with water. The desired propionic acid was obtained as a solid.

Step 3/4: oxalyl chloride (3.40 equiv.) was carefully added to propionic acid (1 equiv.) to CH₂Cl₂(1.4ml/mmol propionic acid) and DMF (0.01ml/mmol propionic acid) to form a solution. The resulting clear solution was stirred for an additional 6 hours, and then the volatile components were removed under vacuum. The appropriate acid chloride is used in the next reaction step without further work-up.

Acid chloride was added to CH at 0 deg.C₂Cl₂(1.2ml/mmol of propionic acid from step 3) solution AlCl was added dropwise₃(1.30 equiv.) to CH₂Cl₂(0.75ml/mmol AlCl₃) In the solution of (1). After the addition was complete, the ice bath was removed and reflux was heated for an additional 3 hours. The mixture was poured into ice water and the aqueous phase was taken up with CH₂Cl₂And (4) extracting. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography. If ring closure does not occur regioselectively, the regioisomers are separated by column chromatography.

And 5: at 10 ℃ adding NaBH₄(1mmol/mmol indanone) is added portionwise carefully to a solution of indanone (1 equiv) in EtOH (4ml/mmol indanone). After the addition was completed, the solution was stirred at room temperature for 3 to 16 hours, and then the volume of the reaction solution was reduced under vacuum. The suspension was added to ice water and the aqueous phase was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Step 6: dowex(MarathonMsc (h) ion exchange resin; 0.02g/mmol of indanol) to a solution of indanol (1 eq) in toluene (3ml/mmol of indanol), the suspension is heated to reflux and separated using a water separator for 1 hour. The cooled suspension was filtered, the residue was washed with toluene and the solvent of the combined organic phases was removed in vacuo. The crude product was purified by column chromatography.

Alternatively, in step 6, a solution of indanol (1 equiv.) and p-toluenesulfonic acid monohydrate (0.1 equiv.) in toluene (4ml/mmol indanol) is heated under reflux and separated using a dehydrator for 1-2 hours. The solution was cooled to room temperature using saturated NaHCO₃And (4) washing with an aqueous solution. The organic phase is Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

And 7: 4- (3-phenylpropyl) pyridine N-oxide (0.04 eq) was added to indene (1 eq) in CH₂Cl₂(1.2ml/mmol of indene) and (S, S) - (+) -N, N' -bis (3, 5-di-tert-butyl-o-hydroxybenzylidene) -1, 2-cyclohexanediaminommanganese (III) chloride (0.01 equiv.). The reaction solution was stirred for 10 minutes and cooled to-2 ℃. Addition of half-saturated K₂CO₃Aqueous solution (0.5ml/mmol of indene) with vigorous stirring, aqueous NaOCl solution (1.25ml/mmol of indene; 13% free chlorine) is slowly added dropwise. Immediately thereafter, the pH was adjusted to pH 11-12 using 0.1M phosphate buffer (pH 7.5). The biphasic system was stirred vigorously for 4 hours, during which time the temperature slowly rose to 5 ℃. Separating the phases, using CH as the aqueous phase₂Cl₂And (4) extracting. The combined organic phases used Na₂S₂O₃Aqueous solution and water washing, using Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography. The product obtained is further recrystallized from heptane.

And 8: NBS (2 equiv.) was added in small portions to a solution of indene (1 equiv.) in DMSO (1ml/mmol indene) and water (0.025ml/mmol indene) at 25 ℃ and the temperature was allowed to rise to no more than 35 ℃. The solution was stirred at room temperature for 2 hours and poured onto ice. The aqueous phase is extracted with ethyl acetate and the combined organic phases areWashed with brine, then Na was used₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

And step 9: NaOH powder (6.6 equiv.) was added to a solution of bromohydrin (1 equiv.) in THF (7ml/mmol of bromohydrin). The suspension was stirred at room temperature until the precursor reaction was complete and the reaction was monitored by Thin Layer Chromatography (TLC). The suspension was filtered and the residue was washed with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered again and the solvent removed under vacuum. The crude product was purified by column chromatography.

Step 10: mCPBA (1.1 equiv) was added in small portions to indene (1 equiv) in CH₂Cl₂(2.5ml/mmol indene). The suspension was stirred vigorously for 2 days and then filtered. The residue was CH₂Cl₂Washing, combining the organic phases and successively using saturated Na₂SO₃Aqueous solution and saturated NaHCO₃Washing with aqueous solution using Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Reaction scheme 2: synthesis of indane oxide analogs

The general synthetic method comprises the following steps:

step 1: 2, 5-Dichlorothiophene (1.0 eq.) in CH at 0 deg.C₂Cl₂(0.75ml/mmol thiophene) solution was slowly added dropwise to AlCl₃(1.25 equiv.) and succinic anhydride (1.0 equiv.) in CH₂Cl₂(1.00ml/mmol AlCl₃) Of (4) is added. After the addition was complete, the ice bath was removed and stirred at room temperature for an additional 4 hours. The mixture was poured into ice water and the aqueous phase was taken up with CH₂Cl₂And (4) extracting. The combined organic phases were extracted with 2N aqueous NaOH and the combined aqueous phases were then acidified with concentrated HCl. Acid water solubleUsing CH as liquid₂Cl₂Extracting, and mixing the organic phase with Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product obtained is purified by column chromatography.

Step 2: precursors (1.0 equiv.) and N (C) were added at 0 deg.C₂H₅)₃(1.10 equiv.) in THF (0.80mL/mmol precursor) was slowly added dropwise ClSi (CH)₃)₃(1.10 equiv.) in THF (1.70ml/mmol ClSi (CH)₃)₃) In the solution of (1). After the addition was complete, stirring was continued at 0 ℃ for 15 minutes and the resulting suspension was filtered. The solvent of the filtrate was removed in vacuo and the residue was dissolved in CH₂Cl₂(2.00ml/mmol precursor). Mixing HSi (C)₂H₅)₃(3.0 equiv.) and TiCl₄(3.0 equiv., 1M CH₂Cl₂Solution) was added to the solution at room temperature. The solution was stirred at room temperature for 20 hours and then poured into ice water. Using CH as the aqueous phase ₂Cl₂And (4) extracting. The combined organic phases were taken up in saturated NaHCO₃Aqueous extraction and the combined aqueous phases were then carefully acidified with concentrated HCl. The acidic aqueous solution was extracted with ethyl acetate and the combined organic phases were extracted with Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

And step 3: the carboxylic acid (1.00 eq.) was dissolved in concentrated H at 0 deg.C₂SO₄(6.30ml/mmol carboxylic acid) and then stirred at room temperature for 4 hours. The solution was poured into ice water and the aqueous phase was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Other reactions to prepare epoxides were carried out analogously to scheme 1/route B.

Reaction scheme 3: synthesis of Tetrahydronaphthalene epoxide (route D)

The general synthetic method comprises the following steps:

step 1: 1, 2-dihydronaphthalene (1.00 eq.) and 1, 1, 1-trifluoroacetone (0.15 eq.) were added to 1.5M aqueous potassium carbonate (4X 10) at 0 deg.C^-4M, 1.55ml/mmol of 1, 2-dihydronaphthalene and acetonitrile (1.55ml/mmol of 1, 2-dihydronaphthalene) in EDTA and stirred for 5 minutes. Then 30% hydrogen peroxide (4.00 eq) was carefully added. The reaction mixture was stirred at 0 ℃ for 4.5 h (reaction monitored by TLC), then ethyl acetate was added. After separation of the phases, the aqueous phase was extracted twice with ethyl acetate and the combined organic phases were washed with aqueous NaCl, MgSO ₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Reaction scheme 4: synthesis of indane oxide intermediates

The general synthetic method comprises the following steps:

step 1: mCPBA (m-chloroperbenzoic acid, 2.2 equivalents) was added in small portions to indanone (1 equivalent) in CH at room temperature₂Cl₂(4.0ml/mmol of indanone). The suspension was stirred vigorously overnight, then Na was added at 0 deg.C₂S₂O₅An aqueous solution. The two-phase mixture was stirred for 10 minutes, filtered, the phases separated and the aqueous phase used CH₂Cl₂And (4) extracting. The combined organic phases were taken up in saturated NaHCO₃Washing with aqueous solution using Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The following indane oxides and analogues are synthesized by the process:

general synthesis of phenol:

reaction scheme 5: deprotection of phenol ethers

The general synthetic method comprises the following steps:

step 1/2: at-10 deg.C, BBr₃(1M CH₂Cl₂A solution; 2.5 equiv.) to methyl ether (1 equiv.) in CH₂Cl₂(7ml/mmol ether), the cooling bath was removed. The suspension was stirred for a total of 4 hours, the progress of the reaction was monitored by TLC, and after completion of the reaction, the suspension was added to ice water. The aqueous suspension obtained was NaHCO₃Neutralization, extraction with ethyl acetate. The combined organic phases used Na ₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

BCl was incubated at-78 deg.C₃(1M Hexane solution; 2.0 equiv.) Add dropwise to isopropyl ether (1 equiv.) in CH₂Cl₂(6ml/mmol ether), the cooling bath was removed. The suspension was stirred for a total of 3 hours (monitored by TLC) and added to ice water. The aqueous suspension obtained was NaHCO₃Neutralization, extraction with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Reaction scheme 6: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: SnCl₂×2H₂O (5 equiv.) is added in small portions to a solution of nitrophenol (1 equiv.) in ethyl acetate (6ml/mmol precursor). The suspension was heated to reflux for 1-6 hours (TLC monitoring). The reaction was quenched with water and basified with 2N aqueous NaOH. The resulting suspension was filtered, and the filtrate was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Step 2/3: the appropriate aniline (1.0 equiv.) and Hunig base (1.1 equiv.) are added to CH at 0 deg.C₂Cl₂(1.3ml/mmol aniline) to 4-nitrophenyl chloroformate (1.5 equiv.) in CH ₂Cl₂(0.4ml/mmol formate) and the temperature is allowed to rise to no more than 5 ℃. The solution was stirred at room temperature for an additional 2 hours, then cooled to 0 ℃. The appropriate aminoacetal (2.3 equivalents) was added and the suspension was stirred at room temperature for another 4 hours. Reaction using CH₂Cl₂Diluting, using water, 2N NaOH aqueous solution and saturated NH in sequence₄And (4) washing with an aqueous Cl solution. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was used in the next reaction step without further purification.

The crude product from the previous step (1 eq) was dissolved in formic acid (1.5ml/mmol precursor) at 0 ℃ and stirred at room temperature for 2-16 h (monitored using TLC). The volume of the reaction solution was reduced to half in vacuo, and the resulting solution was diluted with water. The aqueous phase was extracted with ethyl acetate and the combined organic phases were carefully extracted with saturated NaHCO₃And (4) washing with an aqueous solution. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

And 4, step 4: to PtO₂(5 mol%) was added to the previous stageSolution of body (1 eq) in an EtOH/ethyl acetate mixture (1: 15ml/mmol precursor). Suspension in H₂Stirring vigorously under an atmosphere (1.5bar) for 5 hours (TLC monitoring). The suspension was filtered and the residue was washed with EtOH. The solvent of the organic phase was removed in vacuo and the crude product obtained was used in the next reaction step.

Step 5/6: the appropriate aniline (1.0 equiv.) and Hunnig base (3.5 equiv.) are added to CH at 0 deg.C₂Cl₂(1.3ml/mmol aniline) to 4-nitrophenyl chloroformate (1.5 equiv.) in CH₂Cl₂(0.4ml/mmol formate) and the temperature is allowed to rise to no more than 5 ℃. The solution was stirred at room temperature for an additional 2 hours, then cooled to 0 ℃. The ammonium salt of the appropriate amino acid (1.6 equivalents) was added and the suspension was stirred at room temperature for a further 16 hours. The reaction mixture used CH₂Cl₂Diluting, using water, 2N NaOH aqueous solution and saturated NH in sequence₄And (4) washing with an aqueous Cl solution. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was used in the next reaction step without further purification.

The crude product obtained from the previous step, step (1 eq), was suspended in 10% aqueous HCl (3.0ml/mmol precursor) at 0 ℃ and heated to reflux for 2-16 h (TLC monitoring). The pH of the solution was adjusted to pH 8 using 2N NaOH aqueous solution and extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography. The phenol ether obtained in this way is cleaved as described in reaction scheme 5.

The following phenols were synthesized by the method:

reaction scheme 7: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: the well-blended mixture of the appropriate aniline (1 eq.) and succinic acid (1 eq.) was stirred at 180 ℃ for 2 hours, during which time a melt was formed. The melt was cooled to room temperature (solidification of the melt) and dissolved in EtOH. The resulting solution was mixed with activated carbon, filtered and the solvent removed under vacuum. The residue was dissolved in ethyl acetate and NaHCO was used₃And (4) washing with an aqueous solution. The organic phase is Na₂SO₄Dried, filtered again and the solvent removed under vacuum. The crude product was purified by column chromatography.

Step 2: the well-mixed mixture of the appropriate aniline (1 eq.) and gamma-butyrolactone (1 eq.) was stirred at 180 ℃ for 2 hours, during which time a melt was formed. The melt was cooled to room temperature (solidification of the melt) and dissolved in EtOH. The resulting solution was mixed with activated carbon, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The phenol ether obtained in this way is cleaved as described in reaction scheme 5.

The following phenols were synthesized by the method:

reaction scheme 8: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: boric acid (1 equivalent), aryl iodide (1 equivalent) and Na ₂CO₃(3.0 equiv.) is suspended in a water/DME mixture (1: 1; 3ml/mmol boric acid). Addition of PdCl₂(PPh₃)₂(2 mol%) the suspension was stirred at 80 ℃ for 20 h (TLC monitoring). The suspension was diluted with ethyl acetate and water in succession, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The following phenols were synthesized by the method:

reaction scheme 9: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: the aryl bromide (1 equivalent) was reacted with,oxazolone (1 equivalent), K₂CO₃(2.0 equiv.), trans-diaminocyclohexane (10 mol%) and CuI (5 mol%) were suspended in the di-tert-butyl acetateAlkane (0.5ml/mmol aryl bromide). The suspension was heated to reflux for 16 h (TLC monitoring)) Diluted with ethyl acetate and filtered through a small amount of Celite (Celite). The organic phase is Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The following phenols were synthesized by the method:

reaction scheme 10: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

Step l: aryl bromide (1 equivalent), boric acid (1 equivalent), K₂CO₃(2.0 equiv.) and Pd (PPh)₃)₄(10 mol%) was suspended in DME (1.0ml/mmol aryl bromide). The suspension was heated to reflux for 48 h and the reaction was monitored by TLC. The reaction mixture was diluted with ethyl acetate and water, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The following phenols were synthesized by the method:

reaction scheme 11: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1/2: the appropriate hydroxy ester (2 equiv.) is added to a solution of isocyanate (1 equiv.) in toluene (1.0ml/mmol isocyanate). The solution was heated in a closed vessel at 110 ℃ for 4 hours and the reaction was monitored by TLC. The solvent was removed under vacuum and the crude product was purified by column chromatography. The product of the previous reaction was heated at 180 ℃ for 4 hours (no solvent was used). After the reaction solution was cooled to room temperature, the crude product was purified by column chromatography.

The following phenols were synthesized by the method:

Reaction scheme 12: conversion reaction to sulfonamides

The general synthetic method comprises the following steps:

step 1: the appropriate ammonium hydrochloride salt (3 equiv.) was added to a solution of sulfonyl chloride (1 equiv.) in ethyl acetate (2ml/mmol) and pyridine (6 equiv.) at 0 ℃. The suspension was stirred at room temperature for 16 h and the reaction was monitored by TLC. The reaction mixture was diluted with ethyl acetate and water, the phases were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases use NH₄Washed with aqueous Cl solution and Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The following phenols were synthesized by the method:

reaction scheme 13: oxidation of phenyl sulfides

The general synthetic method comprises the following steps:

step 1: periodic acid (2.1 equivalents) was added to CH₃The suspension in CN (3ml/mmol periodic acid) was stirred at room temperature until a clear solution formed (about 50 minutes). Chromium trioxide (10 mol% relative to the sulfide) was added and stirred for another 10 minutes. The orange solution was slowly added to a solution of the appropriate sulfide (1 eq) in ethyl acetate (10ml/mmol sulfide) at-35 ℃. During which the temperature rises to not more than-35 ℃. The resulting suspension is stirred at this temperature for a further 60 minutes, using 5ml of saturated Na ₂SO₃The aqueous solution is terminated. The suspension was filtered and the residue was washed with ethyl acetate. The filtrate was saturated with Na₂SO₃Washing with aqueous solution using Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The following phenols were synthesized by the method:

reaction scheme 14: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 0 (optional): 4.5 equivalents of SnCl₂To a solution of aniline F (1 eq) in concentrated aqueous hydrochloric acid (0.36ml/mmol precursor) was added and the solution was heated to 60 ℃. After stirring overnight, the mixture was poured onto ice, adjusted to pH > 10 using 10M KOH, extracted four times with dichloromethane, the combined organic phases were washed with NaCl solution, Na₂SO₄And (5) drying. The solvent was removed under vacuum.

Step 1: 1.1 equivalents of dimethylamide dimethylacetal or orthoester C are added to a solution of hydrazide B (1.1 equivalents) in acetonitrile (6ml/mmol precursor) and the solution is stirred for 30 minutes at 50 ℃. After addition of a solution of aniline (A) in acetonitrile (3ml/mmol precursor) and acetic acid (9ml/mmol precursor), the mixture was heated in an open flask at 120 ℃ for 16 h. The solvent was removed under vacuum. The crude product was purified by column chromatography using a dichloromethane/methanol gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 15: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: argon was bubbled through a mixture of boronic acid a (1 eq), heteroaryl iodide/bromine B (1 eq) in water/DME 1/1(3ml/mmol precursor) for 15 minutes. Bis-triphenylphosphine palladium dichloride (0.02 eq.) and Na were added₂CO₃(3.0 equiv.) the mixture was heated at 80 ℃ under argon (20 h). After completion of the reaction (monitored by LC-MS), the mixture was reacted with ethyl acetate and saturated NaHCO₃The aqueous solutions were mixed and extracted twice with ethyl acetate. The combined organic phases were washed with NaCl solution, Na₂SO₄And (5) drying. The solvent was removed under vacuum. The crude product was purified by column chromatography using a heptane/ethyl acetate gradient for elution.

Variation a: after stirring for 1 hour, the resulting mixture was extracted three times with dichloromethane, the combined organic phases were washed with NaCl solution, Na₂SO₄And (5) drying. The solvent was removed under vacuum.

Variation B: after stirring for 1 hour, the mixture obtained is neutralized with NaOH, the product is filtered with suction or extracted three times with dichloromethane, the combined organic phases are washed with NaCl solution, Na ₂SO₄And (5) drying. The solvent was removed under vacuum.

The following phenols were synthesized by the method:

reaction scheme 16: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: mixing three ethylThe amine (2 eq) and 3-chloropropanesulfonyl chloride (1.3 eq) were added dropwise in this order to a solution of aniline A (1 eq) in dichloromethane (1.5ml/mmol precursor) and the mixture was stirred at room temperature for 16 h. After addition of dichloromethane (1ml/mmol precursor), the mixture was successively washed with 1N aqueous HCl and saturated NaHCO₃And (4) washing the solution. The solvent was removed under vacuum. The product was dissolved in DMF (1.3ml/mmol precursor) and 1, 8-diazabicyclo [5.4.0 ] was added]Undec-7-ene (DBU) (1.1 equiv.). After stirring for 3 hours at 25 ℃ and addition of ethyl acetate/heptane 2/1, the organic phase was washed twice with 0.1N HCl, the organic phase was washed with saturated NaCl solution, Na₂SO₄And (5) drying. The solvent was removed under vacuum.

The following phenols were synthesized by the method:

reaction scheme 17: conversion reaction to sulfonamides

The general synthetic method comprises the following steps:

step 1: bromide A (1 equivalent), N-methylmethanesulfonamide (1.2 equivalent), copper (I) iodide (0.2 equivalent), sarcosine (0.2 equivalent), K ₃PO₄A mixture (2.5 equivalents) in DMF (6ml/mmol precursor) was stirred at 150 ℃ for 24 h. The solvent was removed under vacuum. After addition of dichloromethane, the organic phase is taken up in saturated NaHCO₃Washing with solution, Na₂SO₄And (5) drying. The solvent was removed under vacuum. The crude product was purified by flash chromatography on silica gel using a dichloromethane/methanol gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 18: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: a mixture of amine (1 eq), 2, 6-dimethyl-gamma-pyrone (2.5 eq) in 2N aqueous HCl was heated in a microwave at 160 ℃ for 30 minutes. After addition of dichloromethane, the organic phase is taken up in saturated NaHCO₃Washing with solution, Na₂SO₄And (5) drying. The solvent was removed under vacuum. The crude product was purified by flash chromatography on silica gel using a dichloromethane/methanol gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 19: synthesis of heterocyclic phenols

The general synthetic method comprises the following steps:

step 1: the compound of amine (1 equivalent) and diglycolic anhydride (2 equivalents) was heated at 160 ℃ for 48 hours. After addition of dichloromethane, the organic phase is washed with saturated NaCl solution, Na ₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using a dichloromethane/methanol gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 20: use of^tProtection of secondary alcohols by BDPSiCl in the Presence of Secondary amines

The general synthetic method comprises the following steps:

mixing AgNO₃(2.1 equiv.) to a suspension of the appropriate amino alcohol hydrochloride (1 equiv.) and tert-butyldiphenylchlorosilane (1.2 equiv.) in a solution mixture of THF and pyridine (4: 3; 1ml/mmol of amino alcohol) the temperature was increased slightly. The suspension was stirred at room temperature for 16 hours, filtered and the residue was washed with ethyl acetate. The filtrate was diluted with ethyl acetate and saturated NaHCO was used₃And (4) washing with an aqueous solution. The organic phase is Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The following silyl ethers were synthesized by the method:

reaction scheme 21: synthesis of heterocyclic phenols using CuCl

The general synthetic method comprises the following steps:

step 1: the bromide (1 equivalent), imidazole (1.25 equivalents), CuCl (0.06 equivalent) and K were combined₂CO₃A suspension of (1 eq.) in NMP (2ml/mmol of bromide) was heated at 210 ℃ for 10 hours. The mixture was cooled to room temperature and diluted with water. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with NaCl solution, Na ₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using an ethyl acetate/MeOH gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 22: synthesis of heterocyclic phenols by amidines

The general synthetic method comprises the following steps:

step 1: AlCl was added in small portions to a suspension of aniline (1 equivalent) in the corresponding nitrile (1 equivalent) at 0 deg.C₃(1 equivalent). The mixture was heated to 100 ℃ for 1 hour, during which time a solution was formed. The reaction mixture was cooled to 0 ℃ and carefully quenched with water. The aqueous suspension was adjusted to pH 10 using 2N aqueous NaOH solution. The aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with NaCl solution, Na₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using ethyl acetate/heptane/MeOH/NH₃For elution.

Step 2: to amidine (1 eq) and NaHCO₃(3 equivalents) to twoTo the suspension in alkane (2ml/mmol amidine) was added α -chloro-ketone (1.1 equiv) and heated to 100 ℃ for 1 hour. The mixture was cooled to room temperature, diluted with water, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with NaCl solution, Na ₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using ethyl acetate/MeOH for elution.

The following phenols were synthesized by the method:

reaction scheme 23: synthesis of heterocyclic phenols by sulfur compounds

The general synthetic method comprises the following steps:

step 1: to a solution of imidazole (1 eq) in THF (5ml/mmol of imidazole) at-78 deg.C was added nBuLi (1.1 eq, 1M in hexane). The solution was brought to-30 ℃ over 30 minutes. The solution was cooled to-50 ℃ and dialkyl disulfide (1.1 eq) was added. The cooling bath was removed and stirring was continued for 90 minutes during which time the suspension was allowed to warm to room temperature. Adding water, extracting the aqueous layer with ethyl acetate, washing the combined organic layers with NaCl solution, and adding Na₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using an ethyl acetate/heptane gradient for elution.

Step 2: to the alkylsulphide (1 equivalent) in CH at 0 deg.C₂Cl₂Peroxybenzoic acid (3 equivalents) was added in small portions to a solution (12ml/mmol sulfide). The cloudy solution was stirred vigorously for 14 hours. Solution using CH ₂Cl₂Diluting with Na₂CO₃The aqueous solution was washed three times. Na for organic layer₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using an ethyl acetate/MeOH gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 24: synthesis of heterocyclic phenols by carboxylic esters

The general synthetic method comprises the following steps:

step 1: to a solution of imidazole (1 eq) in THF (5ml/mmol of imidazole) was added nBuLi dropwise at-78 ℃. Within 30 minutes, the solution was allowed to rise to-30 ℃. The solution was cooled to-78 ℃ and trimethylchlorosilane (1.1 eq) was added dropwise. The ice bath was removed and the solution was allowed to warm to room temperature over 60 minutes. The solution was cooled to-78 deg.C, chloroformate (1.1 eq) was added and the ice bath removed. After 2 hours, the reaction mixture was poured into water, extracted with ethyl acetate, washed with NaCl solution, Na₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using an ethyl acetate/MeOH gradient for elution.

Step 2: the carboxylate (1 eq) was dissolved in a 2M solution of the corresponding amine (10 eq) in MeOH at 60 deg.C and stirred for 12 hours. The solvent was removed and the crude product was purified by flash chromatography on silica gel using an ethyl acetate/methanol gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 25: synthesis of heterocyclic phenols using sulfonyl chlorides

The general synthetic method comprises the following steps:

step 1: to a sulfonyl chloride (1 equivalent) in CH at 0 deg.C₂Cl₂(2ml/mmol of sulphuryl chloride) amine (4 equivalents) was added. The suspension was stirred at room temperature for 3 hours. Adding water, waterLayer using CH₂Cl₂And (4) extracting. The combined organic layers were washed with NaCl solution, Na₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using an ethyl acetate/methanol gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 26: synthesis of heterocyclic phenols by hydrazides

The general synthetic method comprises the following steps:

step 1: triphosgene (0.33 equiv.) was added portionwise to a solution of hydrazide (1 equiv.) in toluene (3ml/mmol hydrazide) at 0 ℃. The suspension was heated to reflux for 2 hours during which time a solution formed. The solution was cooled to room temperature and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel using an ethyl acetate/heptane gradient for elution.

The following phenols were synthesized by the method:

reaction scheme 27: synthesis of heterocyclic phenols via dihydrazides

The general synthetic method comprises the following steps:

step 1: hydrazide (1 equivalent) to CH at room temperature₂Cl₂To a solution in (1.5ml/mmol hydrazide) was added isocyanate (12 equivalents). The solution was heated to 55 ℃ in a sealed vial. The solution was cooled to room temperature and the solvent was removed under vacuum. The crude product was purified by flash chromatography on silica gel using ethyl acetate/heptane/MeOH for elution.

Step 2: NaOH (1.25 equiv.) was dissolved in MeOH (3ml/mmol NaOH) and diacylhydrazine (1 equiv.) was added. The solution was stirred at room temperature for 16 hours. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with NaCl solution, Na₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel using an ethyl acetate/MeOH gradient for elution.

The following phenols were synthesized by the method:

the specific synthesis method corresponds to: reaction scheme a/method a: synthesis of Compound I by Mitsunobu conversion

The synthesis method comprises the following steps:

step 1: a solution of epoxide (1 eq) and the appropriate secondary amine (1.05 eq) in acetonitrile (1ml/mmol of epoxide) was heated at 80 ℃ for 1-6 hours, monitored by TLC. The solvent was removed under vacuum and the crude product was purified by column chromatography.

Step 2: a solution of DIAD (diisopropyl azodicarboxylate, 1.15 equivalents) in THF was added dropwise to amino alcohol (1 equivalent), PPh₃(1.15 equiv.) and a solution/suspension of the appropriate phenol (1.15 equiv.) in THF (3ml/mmol of amino alcohol). The solution was stirred at room temperature for 1-16 hours, monitored by TLC, and the solvent was removed under vacuum. The crude product was purified by column chromatography.

Step 3 (optional): tert-butyl diphenylsilyl ether is cleaved using TBAF (tetra-n-butylammonium fluoride) or HF/pyridine complex. N-Boc protected group Using 4N HCl bisAlkane solution or use of TFA/CH₂Cl₂1/1 is removed.

The specific synthesis method corresponds to: reaction scheme B/method B: synthesis of Compound I (1) by nucleophilic aromatic substitution

The synthesis method comprises the following steps:

1 equivalent of 2-bromo-1-indanone is dissolved in dimethylformamide, and the amine R-NH-R (as pure form free base or as DMF solution) is added as quickly as possible, preferably at ice bath temperature. After a relatively short reaction time (30 seconds to 1 hour), the reaction is terminated by adding a sufficient amount of dilute hydrochloric acid to give a reaction mixture having a pH of 1-5. The suspension was extracted several times with ethyl acetate and 2-10 equivalents of sodium borohydride were added in portions to the remaining aqueous solution, which now contains the intermediate ketone. After stirring at room temperature for several hours, concentration was carried out, and the reaction mixture was dissolved in water and made weakly alkaline with concentrated sodium bicarbonate solution. The product is obtained by extraction with ethyl acetate, initially as a mixture of cis/trans isomers, which is in most cases subjected to chromatographic purification, it also being possible in some cases to separate the isomers in this way. However, in many cases, the cis/trans mixture is used in the following arylation reaction, and then the isomers are isolated.

The following 1-indanols are synthesized by the process:

the specific synthesis method corresponds to: reaction scheme B/method B: synthesis of Compound I (2) by nucleophilic aromatic substitution

The synthesis method comprises the following steps:

1 equivalent of an indanol of the general formula VI or X (as pure stereoisomer or mixture of cis/trans isomers) is dissolved in 5-10 times the amount of anhydrous dimethylsulfoxide and 1.2 to 2 equivalents of a suitable aryl halide, preferably aryl fluoride or aryl chloride, are added. 1.2 to 5 equivalents of freshly prepared sodium hydroxide powder are added to the solution while stirring at room temperature, and the mixture is stirred at room temperature for about 1 hour or at 60-80 ℃ for several hours, depending on the nature of the aryl halide. For working up, the mixture isDiluting with water, extracting the resulting suspension several times with ethyl acetate, washing the combined extracts with water, MgSO₄Dried, concentrated on a rotary evaporator and purified by chromatography on silica gel.

The specific synthesis method corresponds to: reaction scheme C/method C: synthesis of Mannich like product (1)

The synthesis method comprises the following steps:

step 1: 1 equivalent of indan-2-one is dissolved in an inert solvent such as tetrahydrofuran, dimethylformamide or acetonitrile, 2-3 equivalents of dimethylformamide dimethyl acetal are added, and the mixture is boiled under reflux for several hours, or in the case of DMF, stirred at 80 to 120 ℃ maximum for about 3-5 hours. Alternatively, complete dispersion using a solvent may be used, in which case the precursor is dissolved in a sufficient amount of dimethylformamide dimethyl acetal and then stirred at 120 ℃ until the conversion is complete. After cooling, the crystallized product can usually be filtered off with suction directly and purified further by chromatography or recrystallization.

Step 2: 1 equivalent of 2-dimethylaminomethylene-1-indanone obtained in this way is dissolved in dimethylformamide and at least 2 equivalents of secondary amine NHR3R4 (as free base or as hydrochloride salt) are added. The mixture was stirred at a temperature of 60 ° to 120 ° for several hours. After cooling, the solution is washed with water and the product is isolated by suction filtration or by extraction with ethyl acetate.

And step 3: 1 equivalent of 2-aminomethylene-1-indanone obtained in this way is dissolved in methanol, and 10 to 20 equivalents (divided into 10 to 20 portions, separated by 15 to 30 minutes) are added while stirring at room temperature. After the precursor had completely disappeared, the solvent was removed under vacuum and the residue was dissolved in water. The crude product is obtained by extraction with ethyl acetate, initially as a mixture of cis/trans isomers, which is in most cases subjected to chromatography, it also being possible in some cases to separate the isomers in this way. However, in many cases, cis/trans mixtures are used for the following arylation reactions, and then the isomers are separated.

The following 2-aminomethyl-1-indanols are synthesized by the process:

the specific synthesis method corresponds to: reaction scheme C/method C: synthesis of Mannich like product (2)

The synthesis method comprises the following steps:

1 equivalent of an indanol of the general formula VI or X (as pure stereoisomer or as a mixture of cis/trans isomers) is dissolved in 5-10 times the amount of anhydrous dimethylsulfoxide and 1.2 to 2 equivalents of a suitable aryl halide, preferably an aryl fluoride or aryl chloride, are added. 1.2 to 5 equivalents of freshly prepared sodium hydroxide powder are added to the solution while stirring at room temperature, and the mixture is stirred at room temperature for about 1 hour or at 60-80 ℃ for several hours, depending on the nature of the aryl halide. For work-up, the mixture is diluted with water, the resulting suspension is extracted several times with ethyl acetate, the combined extracts are washed with water, MgSO₄Dried, concentrated on a rotary evaporator and then purified by chromatography on silica gel.

The specific synthesis method corresponds to: reaction scheme D/method D: synthesis of diamines using configuration inversion reaction followed by Buchwald arylation

The synthesis method comprises the following steps:

step 1: a solution of 1M DIAD (1.10 equiv.) in THF was added dropwise to the amino alcohol (1 equiv.), PPh at 0 deg.C₃(1.10 equiv.) and DPPA (1.10 equiv.) in THF (7ml/mmol of amino alcohol), the solution/suspension was stirred at 0 ℃ for 60 minutes (LC/MS monitoring) and cooled to-10 ℃. At this temperature, LiAlH was carefully added all at once ₄(2.00 equivalents, based on the amino alcohol used), the mixture is stirred while cooling in ice for a further 60 minutes. The suspension was poured into ice water and the aqueous phase was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Step 2: aryl bromide (0.95 equiv.) to diamine (1. equiv.), Pd₂(dba)₃(0.04 eq.), rac-BINAP (0.08 eq.), NaO^tBu (1.40 equiv.) in toluene (12ml/mmol diamine) and the mixture was heated at 70 ℃ for 10-18 h (TLC monitoring). The reaction was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with ethyl acetate and the combined organic phases were extracted with Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The specific synthesis method corresponds to: reaction scheme E/method E: synthesis of Compound I by alkylation

The synthesis method comprises the following steps:

step 1: aqueous 2N NaOH (1.10 equiv) was added to a solution of benzoate (1 equiv) in acetone (20ml/mmol benzoate) at room temperature and the mixture was stirred at room temperature for several hours until the precursor was fully reacted (TLC monitoring). The solvent was removed under vacuum and the residue was mixed with water. The aqueous phase is extracted with ethyl acetate and the combined organic phases are With Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

Step 2: NaH (1.30 equiv., 80% in mineral oil) was added to a solution of amino alcohol (1 equiv.) in THF (7ml/mmol of amino alcohol) at 0 deg.C, the ice bath was removed and the mixture was warmed to room temperature over 1 hour. Alkylating reagent (1.10 equivalents) was added and the reaction stirred at room temperature until no further conversion was indicated (TLC monitoring). The mixture was poured into saturated NaHCO₃In the aqueous solution, the aqueous phase was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography.

The specific synthesis method corresponds to: reaction scheme F: optional further reaction of Compounds I

The synthesis method comprises the following steps:

step 1: mixing I-WH (1 equivalent), bromide RBr (1.6-6 equivalents) and K₂CO₃(1-2 equiv.) the mixture was stirred in acetonitrile (5ml/mmol) at 80 deg.C (16-48 h). Dichloromethane and saturated NaHCO were added₃The solution was then extracted 3 times with dichloromethane. The combined organic phases were washed with saturated NaCl solution and dried (Na)₂SO₄). The solvent was removed under vacuum and the crude product was purified by column chromatography.

Step 2: (R ═ CF)₃) A solution of I-WH (1 eq.) and ethyl trifluoroacetate (1.3 eq.) was stirred in methanol overnight. The solvent was removed under vacuum. Dichloromethane and saturated NaHCO were added ₃The solution was then extracted 3 times with dichloromethane. The combined organic phases were washed with saturated NaCl solution and dried (Na)₂SO₄). The solvent was removed under vacuum and the crude product was purified by column chromatography.

Or:

(R＝CH₃) A solution of amine A (1 eq) in 1/2 acetic anhydride/pyridine (9ml/mmol precursor) was stirred. The solvent was removed under vacuum. The crude product was purified by column chromatography.

And step 3: a solution of 1M borane-THF complex in THF (2-9 equivalents) was added dropwise to a solution of the amide (1 equivalent) in THF (5ml/mmol precursor) at 0 ℃. After heating to reflux, concentrated hydrochloric acid was added carefully to the mixture at 0 ℃, the mixture was basified with NaOH and extracted 3 times with dichloromethane. The combined organic phases were washed with saturated NaCl solution and dried (Na)₂SO₄). The solvent was removed under vacuum and the crude product was purified by column chromatography.

The specific synthesis method corresponds to: reaction scheme G/method G: synthesis of Compound I by Pd-catalyzed deprotection of allylamine

The synthesis method comprises the following steps:

step 1: to 1, 3-Dimethylbarbituric acid (2-6 equiv.) and Pd (PPh) at room temperature under argon atmosphere₃)₄(0.05-0.10 equiv.) to CH₂Cl₂To a suspension in (1.0ml/mmol barbituric acid) was added allylamine (1 equivalent) to CH ₂Cl₂(2.0ml/mmol allylamine). The solution was heated to reflux until complete conversion of the starting material (TLC monitoring). The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed with saturated Na₂CO₃Aqueous solution, Na₂SO₄Dried and the solvent removed under vacuum. The crude product was purified by flash chromatography on silica gel.

Specific example (example 226) was synthesized by method a:

step 1: a suspension of 4, 6-dichloroepoxide (500mg, 1 eq.) and the appropriate secondary amine (486mg, 1.05 eq.) in acetonitrile (2.5ml) was heated at 80 ℃ for 6 hours. The solvent is removed in vacuo and the crude product is purified by column Chromatography (CH)₂Cl₂MeOH). 875mg of a colorless foam were obtained.

Step 2: a solution of 1M DIAD (1.87ml, 1.15 equivalents) in THF was added dropwise to an amino alcohol (630mg, 1 equivalent), PPh₃(490mg, 1.15 equiv.) and 4-methylsulfonylphenol (310mg, 1.15 equiv.) in a suspension in THF (3 ml). The solution was stirred at room temperature for 5 hours and the solvent was removed under vacuum. The crude product was purified by column chromatography (ethyl acetate/heptane/methanol). The product was obtained as a colorless foam, which still contained some OPPh₃(930mg)。

Step 3 (optional): at 0 deg.C, add 4M HCl bisAn alkane solution (5ml) was added to Boc-protected precursor (930mg) in bis To a solution in alkane (5ml), the mixture was stirred at room temperature for 3.5 hours. The resulting suspension was diluted with ether, filtered, and washed with ether. The white solid was suspended in saturated NaHCO₃Aqueous, aqueous phase extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The desired product was obtained as a pale yellow solid (600 mg).

Step 4 (optional): 1-bromo-2-fluoroethane (164mg, 3 equivalents) was added to the deprotected 3-aminopyrrolidine (190mg, 1 equivalent) and K at room temperature₂CO₃(60mg, 1 eq) in acetonitrile (4ml) and the mixture heated under reflux for 6 hours. The solvent was removed in vacuo, the residue was suspended in water and the aqueous phase was taken up in ethyl acetateAnd (4) extracting. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column Chromatography (CH)₂Cl₂MeOH). The desired product was obtained as a pale yellow oil (120 mg).

The following examples were synthesized in analogy to example 226:

specific examples (example 623) were synthesized by method B:

step 1: 1.055g of 2-bromoindanone (5mmol) was dissolved in 7.5ml of dimethylformamide while stirring under ice bath cooling, and 0.98ml of cyclopentylamine was added over 60 seconds. After 25 minutes at ice bath temperature, 7.5ml of 2N hydrochloric acid and 15ml of water were added and the mixture was stirred well. The extraction was carried out 3 times with 15ml of ethyl acetate each time. The product, 2-cyclopentylaminoindanone, is obtained as a solution in an aqueous hydrochloric acid phase.

Step 2: 0.5g of sodium borohydride was added in 4 portions under stirring over about 1 hour to an aqueous solution (pH 3, about 20ml) of 2-cyclopentylaminoindanone obtained in step 1. After stirring at room temperature for about 3 to 4 hours, a white precipitate precipitated. After suction filtration and drying in air, stirring with n-heptane. 320mg of trans-2-cyclopentylamino-1-hydroxyindan are obtained.

And step 3: 300mg (1.38mmol) of trans-2-cyclopentylamino-1-hydroxyindan are dissolved in 3.5ml of DMSO, and 481mg (2.76mmol) of 4-fluorophenylmethyl sulfone and 300mg of sodium hydroxide powder are added. The mixture was stirred until the components were completely dissolved and allowed to stand at room temperature overnight. After addition of 5ml of water, extraction is carried out several times with ethyl acetate, the combined ethyl acetate phases are washed briefly with a little water until neutral, dried over magnesium sulfate and the solvent is removed in vacuo. The remaining residue was purified by flash chromatography on a 20g column of packed silica gel. The product was eluted with pure ethyl acetate.

The following examples were synthesized analogously to example 623:

specific example (example 280) was synthesized by method C:

step 1: 202mg (1mmol) of 4, 6-dichloroindan-1-one are dissolved in 2ml of tetrahydrofuran and 263mg of dimethylformamide dimethyl acetal (2.2mmol) are added. The solution was stirred at 83 ℃ for 3 hours and concentrated in vacuo. The residue was triturated with ether and filtered with suction. 216mg of 4, 6-dichloro-2- [ 1-dimethylaminomethylene ] indan-1-one are obtained as yellow crystals.

Step 2: 255mg (1mmol) of 4, 6-dichloro-2- [ 1-dimethylaminomethylene ] indan-1-one was dissolved in 2.5ml of dimethylformamide, and 140mg of pyrrolidine was added thereto, followed by stirring at 70 ℃ for 4.5 hours. The reaction mixture was stirred into hot water and allowed to crystallize by standing at room temperature for 1 day. Suction filtration gave 270mg of yellow crystals.

And step 3: the product obtained in step 2 (4, 6-dichloro-2-pyrrolidin-1-ylmethyl-indan-1-one) is dissolved in 5ml of methanol and after 7 hours a total of 700mg of NaBH is added in portions₄(18.5 equivalents). The mixture is concentrated in vacuo and the residue is dissolved in 50ml of water. The extraction was carried out 4 times with 10ml of ethyl acetate each time, and then dried over magnesium sulfate, and the solvent was removed. The residue was chromatographed on silica gel using methanol and ethyl acetate in a ratio of 3: 10 as eluent. The product is obtained as a mixture of cis/trans isomers.

And 4, step 4: the cis/trans mixture of 4, 6-dichloro-2-pyrrolidinylmethylindanol (84mg) obtained in step 3 was dissolved in 1ml DMSO, and 100mg of 4-fluorophenylmethyl sulfone and 100mg of sodium hydroxide powder were added. The mixture was stirred at room temperature for up to 40 minutes. After addition of 5ml of water, extraction is carried out several times with ethyl acetate, the combined ethyl acetate phases are washed briefly with a little water until neutral, dried over magnesium sulfate and the solvent is removed in vacuo. The remaining residue was subjected to flash chromatography on a 20g packed silica gel column. Elution first with pure ethyl acetate gave 64mg of trans-4, 6-dichloro-1- (4-methylsulfonylphenyloxy) -2-pyrrolidinylmethyl indane, followed by elution with ethyl acetate/methanol 9: 1 to give 9mg of the corresponding cis isomer.

The following examples were synthesized in analogy to example 280:

specific examples (example 26) were synthesized by method D:

step 1: A1M solution of DIAD (0.84ml, 1.10 equiv.) in THF was added dropwise to the Si-protected aminoalcohol (400mg, 1eq.), PPh, at 0 deg.C under Ar atmosphere₃(220mg, 1.10 equiv.) and DPPA (0.23ml, 1.10 equiv.) in dry THF (5 ml). The suspension was stirred at 0 ℃ for 60 minutes (monitored by LC/MS) and cooled to-10 ℃. At this temperature, LiAlH is carefully added all at once₄(57mg, 2mol equivalent), the mixture was stirred while cooling in ice for another 60 minutes. The suspension was poured into ice water and the aqueous phase was extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography (ethyl acetate/methanol). The product was obtained as a colourless oil (90 mg).

Step 2: 4-bromophenyl methyl sulfone (38.2mg, 0.95 equiv.) to diamine (90mg, 1. equiv.), Pd₂(dba)₃(6.3mg, 0.04 eq), rac-BINAP (8.5mg, 0.08 eq), NaOtBu (23.0mg, 1.40 eq) in toluene (2ml) and the mixture was heated at 70 ℃ for 10 h (monitored by TLC). The reaction was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with ethyl acetate and the combined organic phases were extracted with Na ₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography (ethyl acetate/MeOH). The product was obtained as a colorless oil (75 mg).

And step 3: HF/pyridine (100. mu.l, 65-70% pure) was added to a solution of the silyl-protected diamine (75mg, 1 eq.) in THF (2ml) at room temperature, and the mixture was stirred at room temperature for 6 hours. It was poured to saturation NaHCO₃Aqueous, aqueous phase extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography (ethyl acetate/MeOH). The desired product was obtained as a pale yellow oil (20 mg).

The following examples were synthesized in analogy to example 26:

specific examples (example 482) were synthesized by method E:

step 1: aqueous 2N NaOH (3.59ml, 1.10 equivalents) was added to a solution of benzoate (4.41g, 1 equivalent) in acetone (125ml) at room temperature and the mixture was stirred at room temperature for 5 hours until the precursor was completely reacted (TLC monitoring). The acetone was removed under vacuum and the residue was mixed with water. The aqueous phase was extracted with ethyl acetate and the combined organic phases were extracted with Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column chromatography (ethyl acetate/n-heptane). The product was obtained as a pale yellow oil (3.20g).

Step 2: NaH (24mg, 1.30 equiv., 80% in mineral oil) was added to a solution of amino alcohol (300mg, 1 equiv.) in THF (4ml) at 0 deg.C, the ice bath was removed and the mixture was warmed to room temperature over 1 hour. 4-cyano-2-fluorobenzyl bromide (134mg, 1.10 eq) was added and the reaction stirred at room temperature for 3 h (TLC monitoring). The mixture was poured into saturated NaHCO₃Aqueous, aqueous phase extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column Chromatography (CH)₂Cl₂MeOH). The product was obtained as a colorless oil (227 mg).

And step 3: A1M THF solution of TBAF (0.52ml, 1.5 equiv.) was added to a solution of the silyl-protected aminobenzyloxyalcohol (227mg, 1 equiv.) in THF (2ml) at room temperature and the mixture was stirred at room temperature for 2 h. It was poured into saturated NaHCO₃Aqueous, aqueous phase extracted with ethyl acetate. The combined organic phases used Na₂SO₄Dried, filtered and the solvent removed under vacuum. The crude product was purified by column Chromatography (CH)₂Cl₂MeOH). The desired product was obtained as a pale yellow oil (68 mg).

The following examples were synthesized analogously to example 482:

specific examples (example 755) were synthesized by method G:

Step 1: to 1, 3-Dimethylbarbituric acid (364mg, 2 equiv.) and Pd (PPh) at room temperature under argon atmosphere₃)₄(67mg, 0.05 eq) in CH₂Cl₂To a suspension in (2.0ml) was added allylamine (583mg, 1 eq) to CH₂Cl₂(2.0ml/mmol allylamine). The solution was heated to reflux for 1 hour. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic layer was saturated Na₂CO₃Washing with an aqueous solution of Na₂SO₄Dried and the solvent removed under vacuum. The crude product was passed over silica gelPurify by flash chromatography, eluting with ethyl acetate/heptane/MeOH (5: 10: 1). The product was obtained as a colorless oil (211 mg).

The following examples were synthesized analogously to example 755:

test methods for determining pharmacological activity:

in this assay, the intracellular pH (pH) of acidified LAP1 cells, which stably express sodium hydrogen exchanger subtype 3(NHE3), was determined_i) The recovery of (1). This recovery occurs even in bicarbonate free conditions (function NHE 3). For this purpose, the pH_iMeasured using the pH-sensitive fluorescent dye BCECF (Molecular Probes, Eugene, OR, USA, using the precursor BCECF-AM). Cells were first plated using BCECF (5. mu.M BCECF-AM) at NH₄Cl buffer (NH)₄Cl buffer solution: 115mM choline Cl, 20mM NH ₄Cl，5mM KCl，1mM CaCl₂，1mM MgCl₂20mM Hepes, 5mM glucose, pH 7.4, adjusted with 1M KOH). The intracellular acidification is achieved by using a non-NH containing solution₄Cl buffer (133.8mM choline chloride, 4.7mM KCl, 1.25mM CaCl)₂，1.25mM MgCl₂，0.97mM K₂HPO₄，0.23mM KH₂PO₄5mM Hepes, 5mM glucose, pH 7.4, adjusted with 1M KOH) in NH₄Cells cultured in Cl buffer. After the washing step, 90. mu.l of NH-free medium were placed on the cells₄A buffer of Cl. On a measuring instrument (FLIPR, "flash Imaging Plate Reader", Molecular Devices, Sunnyvale, Ca., USA) by adding 90. mu.l of Na-containing⁺Buffer (133.8mM NaCl, 4.7mM KCl, 1.25mM CaCl)₂，1.25mM MgCl₂，0.97mM Na₂HPO₄，0.23mM NaH₂PO₄10mM Hepes, 5mM glucose, pH 7.4, adjusted with 1M NaOH) to initiate pH recovery. The BCECF fluorescence was measured using an excitation wavelength of 498nm and a FLIPR emission filter 1 (bandpass: 510-570 nm). The subsequent change in fluorescence as a measure of pH recovery was recorded for two minutes. To calculate the NHE 3-inhibiting potency of the test substance, the cells were first studied in a buffer in which no or complete pH recovery occurred. For complete pH recovery (100%), the cells were incubated in the presence of Na⁺In the buffer (as above) and for determining the 0% value, it is incubated in the absence of Na ⁺The buffer (as above). Preparing the substance to be tested in Na-containing solution⁺In the buffer of (1). The recovery of intracellular pH at each tested concentration of the substance was expressed as a percentage of the maximum recovery. IC of respective substance for NHE3₅₀The percentage recovery from pH was calculated using the program XLFit (idbs, Surrey, UK).

Inhibition of NHE3 is detailed in the following table and is divided into three activity ranges:

wherein the meaning is

Activity range 1: 20-50% inhibition at 10. mu.M

Activity range 2: IC (integrated circuit)₅₀1-10μM

Activity range 3: IC (integrated circuit)₅₀＜1μM

Claims

1. Compounds of formula (I) and pharmaceutically acceptable salts thereof,

wherein

A is 6-10 membered aryl or 5-10 membered heteroaryl,

wherein

The aryl and heteroaryl groups may be monocyclic or bicyclic,

and the heteroaryl group may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur;

wherein one or more hydrogen atoms of the monocyclic or bicyclic aryl or heteroaryl group may be replaced by a substituent R1, R1 is independently selected from F, Cl, Br, I, (C)₁-C₁₀) -alkyl-, (C)₂-C₁₀) -alkenyl-, (C)₂-C₁₀) -alkynyl-, (C)₃-C₁₄) -cycloalkyl-, (C)₄-C₂₀) -cycloalkylalkyl-, (C)₄-C₂₀) -cycloalkylalkyloxy-, (C)₁-C₁₀) -alkoxy-, (C)₁-C₁₀) -alkylthio-, (C)₆-C₁₄) -aryl-, (C)₂-C₁₃) -heteroaryl, -CN, -NR13R14, -C (O) R12, -SF₅、-S(O)_nR12, -C (O) OR12, -C (O) NR13R14 and-S (O)_nNR13R14；

Wherein two vicinal radicals R1 may also form saturated or partially unsaturated (C)₅-C₁₀) Cycloalkyl or saturated or partially unsaturated (C)₂-C₉) -heterocycloalkyl, wherein the heterocycloalkyl may contain 1, 2 or 3 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 or 2 nitrogen atoms, and 1 oxygen atom or1 sulfur atom;

wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, heterocycloalkyl, alkoxy and alkylthio group may be F, OH or (C) ₁-C₁₀) -alkoxy groups are substituted one or more times independently of each other;

b is a mono-or fused bicyclic group selected from:

a 6-to 10-membered aryl group,

a 5-to 10-membered heteroaryl group,

a 3-to 10-membered cycloalkyl group,

a 9-to 14-membered cycloalkylaryl group,

an 8-14 membered cycloalkyl heteroaryl group,

a 3-to 10-membered heterocycloalkyl group,

9-14 membered heterocycloalkylaryl, and

an 8-14 membered heterocycloalkyl heteroaryl group,

wherein the cycloalkyl or heterocycloalkyl unit may be saturated or partially unsaturated, and

wherein the heterocyclic group may contain one or more heteroatoms selected from nitrogen, oxygen and sulfur;

wherein one or more hydrogen atoms in the group B may be replaced by a substituent R5, R5 being independently of one another selected from (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkylthio group(s), (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₄-C₂₀) -cycloalkylalkyloxy, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₃-C₁₁) -cycloalkyloxy, (C)₂-C₁₁) -heterocycloalkyloxy, (C)₆-C₁₀) -aryl, (C)₁-C₉) -heteroaryl, (C)₉-C₁₄) -cycloalkylaryl, (C)₅-C₁₃) -cycloalkylheteroaryl, (C)₇-C₁₃) -heterocycloalkylaryl and (C)₄-C₁₂) -heterocycloalkylheteroaryl, wherein

and wherein one or more hydrogen atoms of the group R5 may be replaced by a group selected independently of one another from R11,

It is also possible for R5 to be one or more radicals selected, independently of one another, from the following: 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 and-S (O)₂NR17R18, wherein

R16, R17 and R18 are independently selected from H, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₄) -cycloalkyl, (C)₆-C₁₀) -aryl and (C)₁-C₁₀) -an alkyl group,

all radicals may be substituted independently of one another by the following radicals: 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, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl or (C)₁-C₉) -a heteroaryl group,

and wherein R17 and R18 may form together with the nitrogen to which they are bonded a 4-7 membered saturated, unsaturated or partially unsaturated heterocyclic ring having 1-13 carbon atoms, which may additionally contain one or more substituents selected from the group consisting of-O-, -S (O)_nA heteroatom of-N-and-NR 15-,

wherein the heterocyclic ring formed may be substituted one or more times independently of each other by: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical) ₂CN or (C)₁-C₁₀) -an alkoxy group;

l is a covalent bond;

x is a group-O-;

r2 is absent or is one or more substituents independently selected from the group consisting of: F. (C)₁-C₁₀) -alkyl and (C)₁-C₁₀) -alkoxy, wherein the alkyl and alkoxy may be substituted one or more times by F independently from each other;

r3 and R4 are each independently hydrogen atomOr a group selected from: (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl, (C)₇-C₂₀) Arylalkyl, (C)₁-C₉) -heteroaryl and (C)₂-C₁₉) -heteroarylalkyl, wherein

OH、NH₂、(＝O)、F、Cl、Br、I、CN、NO₂、-NR13R14、-NR13COR12、-NR13COOR12、-NR12CONR13R14、-NR13-S(O)₂-R12、-NR13-S(O)₂-NR13R14, -COOR12, -COR 12; -CO (NR13R14) and S (O)_nR12、-S(O)₂R13R14, or

R3 and R4, together with the nitrogen to which they are bonded, form a 4-to 10-membered saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more substituents selected from the group consisting of-O-, -S (O)_nA heteroatom of-N-and-NR 8-,

wherein

The heterocyclic group may be substituted one or more times by a group selected from R7 and R9, independently of each other, and wherein

The heterocyclic group formed by R3 and R4 may be bonded via a chemical bond, via a saturated or unsaturated (C) ₁-C₁₀) -alkyl or (C)₁-C₉) A heteroalkyl chain or is bridged by-NR 15-, -O-or-S-, and wherein

and wherein

R8 in the group-NR 8-may form, with the ring formed by R3 and R4, a further saturated, unsaturated or partially unsaturated heterocyclic ring which may be substituted one or more times, independently of one another, by a group selected from R7 and R9 and may additionally comprise one or moreA plurality selected from-O-, -S (O)_n-N ═ and-NR 19 —;

r7 is (C)₁-C₁₀) -alkyl or (C)₁-C₁₄) -cycloalkyl, wherein the alkyl may be substituted one or more times by R9 independently from each other;

r8 is H, (C)₁-C₁₀) -alkyl or (C)₁-C₁₄) Cycloalkyl, COR12, -CO (NR13R14), S (O)_nR12 or-S (O)₂NR13R14, wherein the alkyl can be substituted one or more times by R10 independently of each other;

r9 is a group selected from: OH, (═ 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, (C)₄-C₂₀) -cycloalkylalkyl, (C)₁-C₁₀) -alkoxy, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl and (C)₁-C₉) -a heteroaryl group;

r10 is a group selected from: F. OH, CN, (C) ₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkylthio, NO₂、-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；

R11 is a group selected from: (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₁-C₁₀) -alkoxy, (C)₁-C₂₀) Alkylthio group(s), (C)₃-C₁₄) -cycloalkyl, (C)₄-C₁₀) -cycloalkylalkyl, (C)₂-C₁₃) -heterocycloalkyl, (C)₄-C₁₉) -heterocycloalkyl alkyl group, (C)₃-C₁₄) -cycloalkyloxy and (C)₂-C₁₃) -a heterocycloalkyloxy group,

all of which may be substituted one or more times by R10 independently of each other;

(═ O), Cl, Br, I, and R10;

r12, R13 and R14 may be independently of each other H, (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₁₀) -cycloalkylalkyl, (C)₂-C₁₃) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl, each of which may be substituted one or more times, independently of each other, by: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group; or

R13 and R14 may form, together with the nitrogen to which they are bonded, a 4-7 membered saturated, unsaturated or partially unsaturated heterocyclic ring having 1 to 13 carbon atoms, which may additionally contain one or more substituents selected from the group consisting of-O-, -S (O)_nA heteroatom of-N-and-NR 15-, wherein

The heterocycles formed may be substituted one or more times independently of one another by: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C) ₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl or (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group;

r15 is a group selected from: H. (C)₁-C₁₀) -alkanesBase, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₃) -heterocycloalkyl and (C)₃-C₁₉) -heterocycloalkylalkyl, which may each be substituted one or more times, independently of each other, by: F. OH, CN or (C)₁-C₁₀) -an alkoxy group;

r19 is H, (C)₁-C₁₀) -alkyl or (C)₁-C₁₄) Cycloalkyl, COR12, -CO (NR13R14), S (O)_nR12 or-S (O)₂NR13R14, wherein the alkyl can be substituted one or more times by R10 independently of each other;

and wherein

n is 0, 1 or 2;

p is 1 or 2, and

q is a number of 0 and q is,

and wherein

i) When A is phenyl, B is phenyl or benzodioxolyl, and R3 and R4 are H, (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl or (C)₇-C₂₀) Arylalkyl, or in the case where R3 and R4 together are unsubstituted pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl or 4-methylpiperazinyl, it is necessary for at least one other than (C) ₁-C₁₀) Alkyl radicals, (C)₁-C₁₀) Alkoxy, OH, CF₃R5 radical of F, Cl, Br or I,

ii) when A is phenyl and R3 and R4 are (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl or (C)₄-C₂₀) In the case of cycloalkylalkyl, it is necessary for at least one other than F, Cl, Br, I, (C)₁-C₄) Alkyl radicals, (C)₁-C₄) -alkoxy, CF₃、OCF₃、CN、NO₂、NH₂、-NH((C₁-C₁₀) -alkyl), -N ((C)₁-C₁₀) -alkyl groups)₂Unsubstituted or substituted benzoyl, or unsubstituted or substituted phenyl- (CH)₂)_r-Y-(CH₂)_sOf (A) toA group R5, wherein Y is a bond or oxygen, and R and s are 0 to 4, wherein R + s is no greater than 4.

2. The compound of claim 1 having formula Ic and pharmaceutically acceptable salts thereof

Wherein

B is 6-to 10-membered monocyclic or fused bicyclic aryl, 5-to 10-membered monocyclic or fused bicyclic heteroaryl, 9-to 14-membered fused bicyclic cycloalkylaryl, 8-to 14-membered fused bicyclic cycloalkylheteroaryl, fused 9-to 14-membered bicyclic heterocycloalkylaryl or 8-to 14-membered fused bicyclic heterocycloalkylheteroaryl, each of which may be substituted one or more times, independently of the other, by R5,

wherein the heterocycloalkylaryl may contain 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 nitrogen atom and 1 oxygen or 1 sulfur atom or 1 oxygen and 1 sulfur atom as heteroatoms,

And the heteroaryl and cycloalkylheteroaryl groups may contain 1, 2, 3, or 4 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atoms and 1 oxygen or 1 sulfur atom or 1 oxygen and 1 sulfur atom,

and the heterocycloalkylheteroaryl group may contain 1, 2, 3 or 4 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1, 2 or 3 nitrogen atoms and 1 oxygen or 1 sulfur atom or 1 oxygen and 1 sulfur atom as heteroatoms,

r2 is absent or is one or more radicals independently selected from F and (C)₁-C₆) -substituents of alkyl, wherein the alkyl may be substituted one or more times by F independently of each other,

wherein the groups A, X, L, q, R1, R3, R4 and R5 have the meanings indicated in claim 1.

3. A compound according to claim 1 or 2, and pharmaceutically acceptable salts thereof, wherein

A is phenyl or 5-to 6-membered heteroaryl,

wherein the heteroaryl group may contain 1, 2 or 3 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen and 1 oxygen or 1 sulfur atom as heteroatoms, wherein one or more hydrogen atoms in the phenyl or heteroaryl group may be replaced independently of one another by a group R1;

wherein the heterocycloalkylaryl may contain 1 nitrogen atom, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 nitrogen atom and 1 oxygen or 1 sulfur atom or 1 oxygen and 1 sulfur atom as heteroatoms,

and the heteroaryl and cycloalkylheteroaryl groups may contain 1, 2 or 3 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 nitrogen and 1 oxygen or sulfur atom or 1 oxygen and 1 sulfur atom,

and the heterocycloalkylheteroaryl group may contain 1, 2, 3 or 4 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1 or 2 nitrogen atoms and 1 oxygen or 1 sulfur atom or 1 oxygen and 1 sulfur atom as heteroatoms;

r2 is absent or is one or more radicals independently selected from F and (C)₁-C₆) -substituents of alkyl, wherein the alkyl may be substituted one or more times independently of each other by F;

wherein the groups X, L, q, R1, R3, R4 and R5 have the meanings indicated in claim 1.

4. A compound according to any one of claims 1, 2 or 3 having the formula Id, and pharmaceutically acceptable salts thereof

Wherein

B is phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, indolyl, benzothienyl, chromanyl, benzofuranyl, dihydrofuranyl, benzopyrrolidinyl, isobenzodihydrofuranyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, benzothiazolyl, benzothiophenyl, indolinyl, benzodioxolyl, tetrahydroisoquinolinyl, or tetrahydroquinolyl, wherein one, two, three, or four hydrogen atoms in group B may be replaced by a group R5, wherein

Each R5 group is independently selected from:

(C₁-C₄) Alkoxy, which may be fluorinated in whole or in part,

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

(C₂-C₅) -heterocycloalkyl, (C)₂-C₅) -heterocycloalkyl- (C)₁-C₄) -an alkyl group,

wherein the heterocycloalkyl ring may be saturated or partially unsaturated and may contain 1 or 2 nitrogen atoms, 1 oxygen atom, 1 nitrogen and 1 sulfur atom or 1 nitrogen and 1 oxygen atom, and

wherein the heterocycloalkyl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂、-CN、(C₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl, OH, NH (C)₁-C₄) Alkyl, N ((C)₁-C₄) -alkyl groups)₂And (C)₁-C₁₀) -alkoxy, phenyl, naphthyl,

wherein the heteroaryl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂、-CN、(C₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl, OH, NH (C)₁-C₄) Alkyl, N ((C)₁-C₄) -alkyl groups)₂、(C₁-C₁₀) Alkoxy and-C (O) O- (C)₁-C₄) -an alkyl group,

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 wherein n is 1 or 2, and-s (o)₂NR17R18, wherein

wherein the alkyl substituents are selected from F, OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN and (C)₁-C₁₀) -an alkoxy group,

r17 and R18 may form together with the nitrogen to which they are bonded a 5-6 membered saturated, unsaturated or partially unsaturated heterocyclic ring having 1-5 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and N ((C)₁-C₄) Alkyl) -, wherein the heterocyclic ring formed is substituted one or more times, independently of each other, by: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl or (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group;

r1 is absent or is one, two or three radicals independently of one another selected from the group consisting of: F. cl, Br, I, (C)₁-C₆) -alkyl and (C)₁-C₆) -alkoxy, wherein the alkyl and alkoxy groups may be substituted one or more times by F;

r3 and R4 are independently of each other a group selected from: H. (C) ₁-C₄) Alkyl radicals, (C)₃-C₇) -cycloalkyl-, (C)₃-C₇) -cycloalkyl- (C)₁-C₄) -alkyl-, (C)₃-C₆) -heterocycloalkyl-, phenyl- (C)₁-C₄) -alkyl-and (C)₁-C₅) -heteroaryl, wherein

The groups R3 and R4 may be substituted once, twice or three times independently of each other by a group selected from: OH, (═ 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 and-S (O)₂NR13R14，

Wherein R12, R13 and R14 are each independently H or (C)₁-C₄) -an alkyl group,

or

R3 and R4 together with the nitrogen to which they are bonded form a 4-8 membered saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-and-NR 8-, where

wherein the heterocyclic group may be bonded through a chemical bond, (C)₁-C₇) Alkyl radicals, (C)₁-C₆) -a saturated or unsaturated heteroalkyl chain bridge or through-NH-or-N (C)₁-C₄) -alkyl-bridging, and wherein the alkyl and heteroalkyl chains may also form a spiro ring system with the ring system formed by R3 and R4，

And wherein R8 in the NR8 group forms with the ring formed by the groups R3 and R4 a further saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or two heteroatoms selected from: -O-, -S (O) _n-, where N ═ 0, 1 or 2, ═ N-and-NR 19-, where R19 is equal to H or (C)₁-C₄) -an alkyl group;

wherein the radicals R7, R8 and R9 have the meanings indicated in claim 1.

5. The compound of any one of claims 1, 2, 3 or 4, and pharmaceutically acceptable salts thereof, wherein

One R5 group is selected from:

(C₂-C₅) -a heterocycloalkyl group,

wherein the heterocycloalkyl ring may be saturated or partially unsaturated and, may contain 1 or 2 nitrogen atoms, 1 oxygen atom, 1 nitrogen and 1 sulfur atom or 1 nitrogen and 1 oxygen atom, and

wherein the heterocycloalkyl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂-、-CN、(C₁-C₄) -alkyl and (C)₃-C₁₀) -a cycloalkyl group,

wherein the heteroaryl ring may also bear substituents selected from: -F,-Cl、-Br、＝O、-NH₂、-CN、(C₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl and-C (O) O- (C)₁-C₄) -an alkyl group,

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，

Wherein

r17 and R18 may form together with the nitrogen to which they are bonded a 5-6 membered saturated, unsaturated or partially unsaturated heterocyclic ring having 1-5 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and-N ((C)₁-C₄) -alkyl) -, wherein the heterocyclic ring formed may be substituted one or more times, independently of each other, by: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl or (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH ₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group,

and

the other radicals R5 are independently of one another selected from:

(C₁-C₄) Alkyl, which may be fully or partially fluorinated, or hydrogen may be substituted by CN, NH₂、OH、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂Or (C)₁-C₄) -an alkoxy substitution,

(C₁-C₄) Alkoxy, which may be fluorinated in whole or in part,

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

a phenyl group,

OH, (═ O), F, Cl, Br, CN, -NR17R18, NR16COR17, -COOR16, -COR16 and-CO (NR17R18), where

wherein the alkyl substituents are selected from F, OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN and (C)₁-C₁₀) -alkoxy-, or

R17 and R18 may form together with the nitrogen to which they are bonded a 4-7 membered saturated, unsaturated or partially unsaturated heterocyclic ring having 1-5 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and N ((C)₁-C₄) Alkyl) -, wherein the heterocyclic ring formed is substituted one or more times independently of each other with the following substituents: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl or (C) ₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN or (C)₁-C₁₀) -an alkoxy group;

r3 and R4 are independently of each other a group selected from: H. (C)₁-C₅) -alkyl-, phenyl- (C)₁-C₄) -alkyl-, NH₂-(C₁-C₄) Alkyl-, N ((C)₁-C₄) -alkyl groups)₂-(C₁-C₄) -alkyl-, (C)₁-C₄) -alkoxy- (C)₁-C₄) -alkyl-, (C)₃-C₇) -cycloalkyl- (C)₁-C₄) Alkyl-and (C) containing-NH-, -O-or-S-₄-C₆) -heterocycloalkyl-, or

And wherein R8 may form with the ring formed by the groups R3 and R4 other saturated, unsaturated or partially unsaturated heterocyclic rings which may additionally contain one or two heteroatoms selected from: -O-, -S (O)_n-, where N ═ 0, 1 or 2, -NH-, and-N ((C)₁-C₄) Alkyl) -;

r7 is H, (C)₁-C₅) -alkyl or (C)₃-C₆) -cycloalkyl, wherein the alkyl may be substituted one or more times by R9 independently from each other;

r8 is H, (C)₁-C₅) -alkyl or (C)₁-C₆) -cycloalkyl, wherein the alkyl group may be substituted one or more times independently of each other by: F. OH, NH₂、CN、NO₂、(C₁-C₁₀) -alkoxy, (C)₁-C₁₀) Alkylthio, -NR13R14, -NR13COR12, -NR13COOR12, -NR13CONR13R14, -NR13-S (O)₂-R12、-NR12-S(O)₂-NR13R14、-COOR12、-COR12；-CO(NR13R14)、S(O)_nR12、-S(O)₂NR13R14、COR12、-CO(NR13R14)、S(O)_nR12 or-S (O)₂NR13R14；

R9 is a group selected from: OH, NH₂、(＝O)、F、Cl、Br、I、CN、-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-C₆) -cycloalkyl, (C)₄-C₇) -cycloalkylalkyl, (C)₁-C₅) -alkoxy, (C)₂-C₆) -heterocycloalkyl, (C)₃-C₁₀) -heterocycloalkyl alkyl, phenyl or (C)₁-C₅) -a heteroaryl group,

wherein R12, R13 and R14 are each independently of the other a hydrogen atom or are selected from unsubstituted or substituted (C)₁-C₄) -alkyl radicals, wherein the alkyl substituents are chosen from F, OH, (═ O), NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂CN and (C)₁-C₁₀) -alkoxy groups.

6. A compound of claim 1 having the formula Ia and pharmaceutically acceptable salts thereof

Wherein

A is phenyl or 5-to 6-membered heteroaryl, wherein the heteroaryl may contain 1, 2 or 3 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen and 1 oxygen atom or1 sulfur atom as heteroatoms, wherein one or more hydrogen atoms in the phenyl or heteroaryl may be replaced independently of one another by a group R1;

and the heteroaryl and cycloalkylheteroaryl groups may contain 1, 2, 3 or 4 nitrogen atoms, 1 oxygen atom, 1 sulfur atom, 1 or 2 nitrogen atoms and 1 oxygen or sulfur atom or 1 oxygen and 1 sulfur atom,

and the heterocycloalkyl heteroaryl group may contain 1, 2, 3 or 4 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 sulfur atoms, 1, 2 or 3 nitrogen atoms and 1 oxygen or 1 sulfur atom or 1 oxygen and 1 sulfur atom as heteroatoms;

r2 is absent or is one or more substituents independently selected from the group consisting of: f and (C) ₁-C₆) -an alkyl group, wherein the alkyl group may be substituted one or more times by groups F independently of each other;

7. Compound 1 according to claim 1 having formula Ib and pharmaceutically acceptable salts thereof

Wherein

B is phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, indolyl, benzothienyl, chromanyl, benzofuranyl, dihydrofuranyl, isobenzodihydrofuranyl, benzopyrrolidinyl, benzimidazolyl, benzopyrazolyl, benzotriazolyl, benzothiazolyl, benzothiophenyl, indolinyl, benzodioxolyl, tetrahydroisoquinolinyl, or tetrahydroquinolyl, wherein one, two, three, or four hydrogen atoms in group B may be replaced by a group R5, wherein

Each R5 group is independently selected from:

(C₁-C₄) Alkoxy, which may be fluorinated in whole or in part,

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

Wherein the heterocycloalkyl ring may be monocyclic, bicyclic, saturated or partially unsaturated, and may contain 1 or 2 nitrogen atoms, 1 oxygen atom, 1 nitrogen and 1 sulfur atom or 1 nitrogen and 1 oxygen atom, and

wherein the heterocycloalkyl ring may additionally bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂、(C₁-C₄) -alkoxy, -CN, (C)₁-C₄) -alkyl and (C)₃-C₁₀) -a cycloalkyl group,

a phenyl group, a naphthyl group,

wherein the heteroaryl ring may also bear substituents selected from: -F, -Cl, -Br, ═ O, -NH₂、OH、NH(C₁-C₄) Alkyl, N ((C)₁-C₄) Alkyl radical)₂、(C₁-C₄) -alkoxy, -CN, (C)₁-C₄) Alkyl radicals, (C)₃-C₁₀) Cycloalkyl and-C (O) O- (C)₁-C₄) -an alkyl group,

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 wherein n is 1 or 2, and-s (o)₂NR17R18, wherein

r17 and R18 may form together with the nitrogen to which they are bonded a 5-6 membered saturated, unsaturated or partially unsaturated heterocyclic ring having 1-5 carbon atoms, which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O) _n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and-N ((C)₁-C₄) Alkyl), wherein the heterocyclic ring formed may be substituted one or more times independently of each other by the following substituents: (C)₁-C₁₀) Alkyl radicals, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₂₀) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkylalkyl, which in turn may each, independently of one another, carry one or more of the following groups: F. OH, (═ O) or (C)₁-C₁₀) -an alkoxy group;

r1 is absent or is one, two or three radicals independently of one another selected from the group consisting of: F. cl, Br, I, (C)₁-C₆) Alkyl radicals, (C)₁-C₆) -alkoxy, wherein the alkyl and alkoxy groups may be substituted one or more times by F;

r3 and R4This is independently a group selected from: H. (C)₁-C₄) -alkyl-, (C)₃-C₇) -cycloalkyl-, (C)₃-C₆) -heterocycloalkyl, phenyl- (C)₁-C₄) -alkyl and (C)₁-C₅) -heteroaryl, wherein the groups R3 and R4 may be substituted once, twice or three times, independently of each other, by a group selected from: OH, (═ 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，

Wherein R12, R13 and R14 are each independently H or (C)₁-C₄) -an alkyl group;

or

R3 and R4 together with the nitrogen to which they are bonded form a 4-8 membered saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more heteroatoms selected from the group consisting of: -O-, -S (O) _n-, where N ═ 0, 1 or 2, ═ N-and-NR 8-, where

wherein the heterocyclic group may be bonded through a chemical bond, (C)₁-C₇) Alkyl, saturated or unsaturated (C)₁-C₆) -heteroalkyl chains bridged or bridged by-NH-or-N (C)₁-C₄) -alkyl-bridging, and wherein the alkyl and heteroalkyl chains may also form a spiro ring system with the ring system formed by R3 and R4, and wherein R8 may form with the ring formed by the groups R3 and R4 other saturated, unsaturated or partially unsaturated heterocyclic rings, which may additionally contain one or two heteroatoms selected from the group consisting of: -O-, -S (O)_n-, where N ═ 0, 1 or 2, ═ N-, -NH-, and-N ((C)₁-C₄) -an alkyl group);

wherein R7, R8 and R9 have the meanings indicated in claim 1.

8. The compound of any one of claims 1, 2, 3, 4, 5 or 6, and pharmaceutically acceptable salts thereof, wherein

R3 and R4, together with the nitrogen to which they are bonded, form a 4-to 10-membered saturated, unsaturated or partially unsaturated heterocyclic ring which may additionally contain one or more substituents selected from the group consisting of-O-, -S (O)_nA heteroatom of-N-and-NR 8-, wherein

The heterocyclic groups may be substituted one or more times, independently of each other, by a group selected from R7 and R9, and wherein

The heterocyclic group formed by R3 and R4 may be bonded via a chemical bond, via a saturated or unsaturated (C)₁-C₁₀) -alkyl or (C)₁-C₉) A heteroalkyl chain or is bridged by-NR 15-, -O-or-S-, and wherein

The alkyl and heteroalkyl chains may also form spiro ring systems with the ring system formed by R3 and R4, wherein the alkyl and heteroalkyl bridges may be substituted one or more times, independently of each other, with a group selected from R7 and R9,

and wherein

R8 in the group-NR 8-may form, together with the ring formed by R3 and R4, a further saturated, unsaturated or partially unsaturated heterocyclic ring which may be substituted one or more times, independently of one another, by a group selected from R7 and R9, and which may additionally comprise one or more substituents selected from-O-, -S (O)_n-N ═ and-NR 19 —;

wherein n, R7, R8, R9 and R19 have the meanings indicated in claim 1.

9. The compound of any one of claims 1, 2, 3, 4, 5, 6, 7 or 8, and pharmaceutically acceptable salts thereof, wherein

The heterocyclic group may be substituted one or more times by groups selected from R7 and R9 independently of each other, and wherein R8 may form together with the ring formed by the groups R3 and R4 and the adjacent C atom a fused triazole or pyrrolidine ring;

Wherein R7, R8 and R9 have the meanings indicated in claim 1.

10. The compound of any one of claims 1, 2, 3, 4, 5, 6 or 7, and pharmaceutically acceptable salts thereof, wherein

R3 and R4 are each independently a hydrogen atom or a group selected from: (C)₁-C₁₀) Alkyl radicals, (C)₂-C₁₀) -alkenyl, (C)₂-C₁₀) -alkynyl, (C)₃-C₁₄) -cycloalkyl, (C)₄-C₂₀) -cycloalkylalkyl, (C)₂-C₁₉) -heterocycloalkyl, (C)₃-C₁₉) -heterocycloalkyl alkyl group, (C)₆-C₁₀) -aryl, (C)₇-C₂₀) Arylalkyl, (C)₁-C₉) -heteroaryl and (C)₂-C₁₉) -heteroarylalkyl, wherein

The groups R3 and R4 may be substituted one or more times independently of each other by a group selected from: OH, 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 and-S (O)₂R13R14；

Wherein R12, R13 and R14 have the meanings indicated in claim 1.

11. A compound of formula I according to claim 1, wherein the compound is selected from:

(R) -1- [ rac-trans- (1, 2) -1- (1H-benzotriazol-4-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2, 4-difluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2, 6-dimethoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-bromo-4-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-bromophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-chloro-4-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-chloro-6-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-chloropyridin-4-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-chloroquinolin-8-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-fluoro-4-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-fluoro-5-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-fluoro-6-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-methanesulfonylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-methoxy-5-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-morpholin-4-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-trifluoromethoxy-phenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3, 4-difluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-chloro-4-fluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-chloro-4-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-chloro-5-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-chlorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-difluoromethoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-fluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-tetrazol-1-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4- [1, 2, 4] triazol-1-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-bromo-3-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-chloro-2-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-chloro-3-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-chlorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-dimethylaminomethylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-fluoro-2-isoOxazol-5-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl]Piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-fluoro-3-trifluoromethylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-fluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-imidazol-1-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-methylthiophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-trifluoromethylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (5, 7-dimethylquinolin-8-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (5-fluoroquinolin-8-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (6-aminonaphthalen-1-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (6-chloropyridin-3-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (isoquinolin-7-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (quinolin-3-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (quinolin-5-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(R) -1- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

(R) -1- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

(R) -1- { rac-trans- (1, 2) -1- [ 4-chloro-2- (1H-pyrazol-3-yl) phenoxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

(R) -1- { rac-trans- (1, 2) -1- [ 4-fluoro-2- (1H-pyrazol-3-yl) phenoxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (1H-benzotriazol-4-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (1H-indol-6-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2, 4-difluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-bromo-4-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-bromophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-chloro-4-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-chloropyridin-4-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-chloroquinolin-8-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-fluoro-5-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-methanesulfonylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-methoxy-5-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-morpholin-4-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (2-trifluoromethoxy-phenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-chloro-2-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-chloro-4-methylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-chloro-5-fluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-chloro-5-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-chlorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-difluoromethoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-fluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4- [1, 2, 4] triazol-1-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-bromo-3-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-chloro-2-methoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-chlorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-difluoromethoxyphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-dimethylaminomethylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-fluoro-)-2-isoOxazol-5-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl]Piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-fluorophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-imidazol-1-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-methylthiophenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-trifluoromethylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (5, 7-dimethylquinolin-8-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (5-fluoroquinolin-8-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (6-aminonaphthalen-1-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (6-chloropyridin-3-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (pyridin-4-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (quinolin-3-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (quinolin-5-yloxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] piperidin-3-ylamine;

(S) -1- { rac-trans- (1, 2) -1- [3- (2-aminoethyl) -1H-indol-5-yloxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

(S) -1- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

(S) -1- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

(S) -1- { rac-trans- (1, 2) -1- [ 4-fluoro-2- (1H-pyrazol-3-yl) phenoxy ] -1, 2, 3, 4-tetrahydronaphthalen-2-yl } piperidin-3-ylamine;

[ 3-methoxy-2- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) phenyl ] acetonitrile;

{2- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-methoxyphenyl } acetonitrile;

{3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } acetonitrile;

{4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } carbamic acid benzyl ester;

{4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } carbamic acid benzyl ester;

1- [1, 3-dichloro-4- (4-methanesulfonylphenoxy) -4, 5, 6, 7-tetrahydrobenzo [ c ] thiophen-5-yl ] pyrrolidine;

1- {4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } pyrrolidine-2, 5-dione;

1- {4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3, 5-difluorophenyl } propan-1-one;

1- {4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } pyrrolidine-2, 5-dione;

2- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -5-chlorobenzamide;

2- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -5-chlorobenzonitrile;

2- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -6-fluorobenzonitrile;

2- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] benzamide;

2- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -5-bromobenzonitrile;

2- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -5-chlorobenzamide;

2- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -5-chlorobenzonitrile;

2- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -6-fluorobenzonitrile;

2- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] benzamide;

2- {4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } -N, N-dimethylacetamide;

2- {4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } -N, N-dimethylacetamide;

2-chloro-8- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) quinoline;

2-fluoro-4- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) benzonitrile;

2-methyl-4- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) -1H-indole;

3- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) quinoline;

3- [ rac-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 ] thiophen-4-yloxy) -3-fluorophenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [4- (1, 3-dichloro-5-pyrrolidin-1-yl-4, 5, 6, 7-tetrahydrobenzo [ c ] thiophen-4-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [ rac-trans- (1, 2) -1- (2-methanesulfonylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] morpholine;

4- [ rac-trans- (1, 2) -1- (4-fluoro-2-iso-isomer Oxazol-5-ylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl]Morpholine;

4- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) -1, 2, 3, 4-tetrahydronaphthalen-2-yl ] morpholine;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -2, 3-difluorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -2-fluorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3, 5-dimethylbenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-chloro-5-methoxy-benzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-chlorobenzoic acid methyl ester;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-fluorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] benzonitrile;

4' - [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] biphenyl-4-carbonitrile;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -2, 3-difluorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -2-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -2-fluorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-chlorobenzoic acid methyl ester;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-fluorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -3-nitrobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] benzonitrile;

5- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) -naphthalen-2-ylamine;

5- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) quinoline;

5, 7-dimethyl-8- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) quinoline;

5- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] benzo [1, 3] oxathiolan-2-one;

5- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] benzo [1, 3] oxathiolan-2-one;

5- {4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy]Phenyl radical }Oxazole-4-carboxylic acid ethyl ester;

5- {4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy]Phenyl radical }Oxazole-4-carboxylic acid ethyl ester;

5-chloro-2- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) benzonitrile;

5-fluoro-8- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) quinoline;

7- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) -isoquinoline;

8- (rac-trans- (1, 2) -2-morpholin-4-yl-1, 2, 3, 4-tetrahydronaphthalen-1-yloxy) quinoline-2-carbonitrile;

8- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] quinoline-2-carbonitrile;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -4-propylphenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] -4-propylphenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) -1, 2, 3, 4-tetrahydronaphthalen-1-yloxy ] phenyl } acetamide.

12. A compound of formula I according to claim 1, wherein the compound is selected from:

(S) -1- [ rac-trans- (1, 2) -1- (3-dimethylaminomethylphenoxy) indan-2-yl ] piperidin-3-ylamine;

{ 3-chloro-4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenylcarbamoyloxy } acetic acid;

benzyl {4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] phenyl } carbamate;

1- [1- (4-methanesulfonylphenoxy) -2-methylindan-2-yl ] pyrrolidine;

2- {5- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] -1H-indol-3-yl } acetamide;

2- {5- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] -1H-indol-3-yl } acetamide;

2- {5- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] -1H-indol-3-yl } acetamide;

4- [4- (rac-trans- (1, 2) -3, 3-dimethyl-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

n, N-dimethyl-2- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzyl ] acetamide;

((R) -1- { trans- (1S, 2S) -1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } piperidin-3-yl) - (3, 3, 3-trifluoropropyl) amine;

2- [ rac-trans- (1, 2) -1- (2, 4-dichloro-3-methylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (2-fluoro-6-methoxyphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (3-chloro-2-methylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (4-imidazol-1-ylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (2, 4-difluorophenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (2-bromo-4-methylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (2-bromophenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (2-tert-butyl-4-ethylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (3-piperidin-1-ylmethylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (3-piperidin-1-ylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (4-fluoro-2-methylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ rac-trans- (1, 2) -1- (6-chloropyridin-3-yloxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] indan-2-yl } -octahydropyrrolo [3, 4-c ] pyrrole;

2- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } -octahydropyrrolo [3, 4-c ] pyrrole;

(4-methylpiperazin-1-yl) - [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] methanone;

(R) -1- (trans- (1R, 2R) -4, 6-dichloro-1-phenoxyindan-2-yl) piperidin-3-ylamine;

(R) -1- [ (1S, 2S) -4, 6-dichloro-1- (2-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ (1S, 2S) -4, 6-dichloro-1- (5-fluoroquinolin-8-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (1H-indol-4-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2, 3-dichloro-4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2, 4-difluorophenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-chloro-4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-methylbenzothiazol-5-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (2-tert-butyl-4-ethylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-piperidin-1-ylmethylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (3-piperidin-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-imidazol-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (6-chloropyridin-3-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (benzo [1, 3] dioxol-5-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (isoquinolin-7-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (pyridin-4-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -1- (quinolin-4-yloxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ trans- (1R, 2R) -4, 6-dichloro-1- (2-fluoro-6-methoxyphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ trans- (1S, 2S) -1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] indan-2-yl } piperidin-3-ylamine;

(R) -1- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } piperidin-3-ylamine;

(R) -1- { trans- (1S, 2S) -1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-chloro-5-methoxyphenoxy) indan-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (3-piperidin-1-ylmethylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-imidazol-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(S) -1- [ rac-trans- (1, 2) -1- (quinolin-5-yloxy) indan-2-yl ] piperidin-3-ylamine;

(S) -1- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } piperidin-3-ylamine;

[3- (rac-trans- (1, 2) -2-diethylaminoindan-1-yloxy) phenyl ] urea;

[ rac-trans- (1, 2) -1- (1H-indol-4-yloxy) indan-2-yl ] methylpiperidin-3-ylamine;

[ rac-trans- (1, 2) -1- (2-fluoro-6-methoxyphenoxy) indan-2-yl ] methylpiperidin-4-ylamine;

[ rac-trans- (1, 2) -4, 6-dichloro-1- (4-imidazol-1-ylphenoxy) indan-2-yl ] -dimethylamine;

[ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - (2-methoxyethyl) methylamine;

{ (R) -1- [ trans- (1S, 2S) -1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-yl } - (2, 2, 2-trifluoroethyl) amine;

{ (R) -1- [ trans- (1S, 2S) -1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-yl } - (3, 3, 3-trifluoropropyl) amine;

{3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] phenyl } urea;

{3- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) indan-1-yloxy ] phenyl } urea;

{3- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] phenyl } urea;

{3- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] phenyl } urea;

{3- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] phenyl } urea;

benzyl {4- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] phenyl } carbamate;

benzyl {4- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] phenyl } carbamate;

{ trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } - (2-methoxyethyl) methylamine;

1- [1- (2-chloro-4-nitrophenoxy) indan-2-yl ] pyrrolidine;

1- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -1, 3-dihydroimidazol-2-one;

1- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] pyrrolidin-2-one;

1- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] pyrrolidine-2, 5-dione;

1- [ rac-cis- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] -1H-imidazole;

1- [ rac-trans- (1, 2) -1- (1H-indol-6-yloxy) indan-2-yl ] pyrrolidin-3-ylamine;

1- [ rac-trans- (1, 2) -1- (2, 3-dichloro-4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine,

1- [ rac-trans- (1, 2) -1- (2, 6-dichloro-4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (2-chloro-4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (2-fluoro-6-methoxyphenoxy) indan-2-yl ] pyrrolidin-3-ylamine;

1- [ rac-trans- (1, 2) -1- (2-tert-butyl-4-ethylphenoxy) indan-2-yl ] pyrrolidin-3-ylamine;

1- [ rac-trans- (1, 2) -1- (3-chloro-4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (3-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] pyrrolidin-3-ylamine;

1- [ rac-trans- (1, 2) -1- (4-methanesulfonyl-3-methylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (quinolin-4-yloxy) indan-2-yl ] pyrrolidin-3-ylamine;

1- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] indan-2-yl } pyrrolidin-3-ylamine;

1- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } piperidin-4-ylamine;

1-methyl-3- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -1, 3-dihydroimidazol-2-one;

2, 2, 2-trifluoro-N- { (R) -1- [ trans- (1S, 2S) -1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-yl } acetamide;

2, 3-dichloro-4- (rac-trans- (1, 2) -2-diethylaminoindan-1-yloxy) benzenesulfonamide;

2, 3-dichloro-4- (rac-trans- (1, 2) -2-dimethylaminoindan-1-yloxy) benzenesulfonamide;

2, 3-dichloro-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

2, 3-dichloro-4- [ rac-trans- (1, 2) -2- ((R) -3-methoxypyrrolidin-1-yl) indan-1-yloxy- ] benzenesulfonamide;

2, 3-dichloro-4- [ rac-trans- (1, 2) -2- (methylpiperidin-3-ylamino) indan-1-yloxy ] benzenesulfonamide;

2, 3-dichloro-4- [ trans- (1S, 2S) -2- (3-hydroxypiperidin-1-yl) indan-1-yloxy ] benzenesulfonamide;

2, 3-dichloro-N, N-dimethyl-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

2- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] isothiazolidine 1, 1-dioxide;

2- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] thiazole;

2- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] -6-fluorobenzonitrile;

2- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] -5-chlorobenzonitrile;

2- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] -5-chlorobenzonitrile;

2- {4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] phenyl } -thiazole-4-carbonitrile;

2-chloro-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzonitrile;

2-chloro-4- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] benzonitrile;

2-fluoro-4- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] benzonitrile;

2-fluoro-6- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] benzonitrile;

3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenylamine;

3, 5-dichloro-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

3, 5-dichloro-N, N-dimethyl-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

3, 5-dimethyl-4- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -4H- [1, 2, 4] triazole;

3, 5-dimethyl-4- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -4H- [1, 2, 4] triazole;

3, 5-dimethyl-4- [4- (trans- (1S, 2S) -2-pyrrolidin-1-ylindan-1-yloxy) -3-trifluoromethylphenyl ] -4H- [1, 2, 4] triazole;

3, 5-dimethyl-4- [4- (trans- (1S, 2S) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl]-isoAzole;

3, 5-dimethyl-4- [ 5-methyl-2- (trans- (1S, 2S) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl]Different from each otherAzole;

3- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl]Oxazolidin-2-one;

3- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] benzamide;

3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] benzamide;

3- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) indan-1-yloxy ] benzamide;

3- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] benzamide;

3- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] benzamide;

3-chloro-4- (2-pyrrolidin-1-ylindan-1-yloxy) pyridine;

3-chloro-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

3-chloro-4- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] benzonitrile;

3-chloro-N, N-dimethyl-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

3-cyclopropyl-5-methyl-4- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -4H- [1, 2, 4] triazole;

3-fluoro-4- (2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

3-methyl-4- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -4H- [1, 2, 4] triazole;

4- ((1S, 2S) -2-azetidin-1-yl-4, 6-dichloroindan-1-yloxy) -3-fluorobenzonitrile;

4- ((1S, 2S) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) -3-fluorobenzonitrile;

4- (2-benzylamino indan-1-yloxy) -3-fluorobenzenesulfonamide;

4- (2-cyclopentylaminoindan-1-yloxy) -3-fluorobenzenesulfonamide;

4- (rac-trans- (1, 2) - (R) -2- [1, 3 '] bipyrrolidinyl-1' -ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-azacycloheptan-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-piperidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzoic acid methyl ester;

4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzonitrile;

4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) -N- (2, 2, 2-trifluoroethyl) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) -N- (3, 3, 3-trifluoropropyl) benzenesulfonamide;

4- (trans- (1S, 2S) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) -3-fluorobenzonitrile;

4- [ (1R, 2S) -1- (2-chloro-4-nitrophenoxy) indan-2-yl ] morpholine;

4- [ (1S, 2S) -2- ((R) -3-aminopiperidin-1-yl) -4, 6-dichloroindan-1-yloxy ] -3-fluorobenzonitrile;

4- [ (1S, 2S) -4, 6-dichloro-2- (4-methylpiperazin-1-yl) indan-1-yloxy ] -3-fluorobenzonitrile;

4- [2, 3-dimethyl-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [ 2-fluoro-5- (trans- (1S, 2S) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl]-3, 5-dimethylisoAzole;

4- [ 3-chloro-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [ 3-chloro-4- (trans- (1S, 2S) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [ 3-fluoro-4- (-2-methyl-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [ 5-fluoro-2- (trans- (1S, 2S) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl]-3, 5-dimethylisoAzole;

4- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] -1H-indole;

4- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] -2, 6-dimethylbenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] -2, 3-dichlorobenzenesulfonamide;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] -2, 3-dichloro-N, N-dimethylbenzenesulfonamide;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] -2-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] -2-fluorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] -3-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] benzamide;

4- [ rac-trans- (1, 2) -2- ((R) -3-hydroxymethylpyrrolidin-1-yl) indan-1-yloxy ] benzenesulfonamide;

4- [ rac-trans- (1, 2) -2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] benzenesulfonamide;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) indan-1-yloxy ] -2, 3-dichlorobenzenesulfonamide;

4- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) indan-1-yloxy ] benzamide;

4- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] -2, 3-dichlorobenzenesulfonamide;

4- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] -2, 6-dimethylbenzonitrile;

4- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] -2-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] -3-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] -2, 3-dichlorobenzenesulfonamide;

4- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] -3-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] benzamide;

4- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] -2, 3-dichlorobenzenesulfonamide;

4- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] -2-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] -3-chlorobenzonitrile;

4- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] benzamide;

4- [ trans- (1S, 2S) -2- ((R) -3-aminopiperidin-1-yl) -4, 6-dichloroindan-1-yloxy ] -3-fluorobenzonitrile;

4- [ trans- (1S, 2S) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] benzenesulfonamide;

4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorobenzonitrile;

4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((S) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorobenzonitrile;

4- [ trans- (1S, 2S) -4, 6-dichloro-2- (4-methyl- [1, 4] diazepan-1-yl) indan-1-yloxy ] -3-fluorobenzonitrile;

4- [ trans- (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorobenzonitrile;

5- (rac-trans- (1, 2) -2-diethylaminoindan-1-yloxy) -1, 3-dimethyl-1, 3-dihydro-indol-2-one;

5- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) -3H-isobenzofuran-1-one;

5- [ 5-fluoro-2- (trans- (1S, 2S) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -1H-pyrazole;

5- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] -2-methylbenzothiazole;

5- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] benzo [1, 3] oxathiolan-2-one;

5- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] benzo [1, 3] oxathiolan-2-one;

6- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] -1H-indole;

7- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] -isoquinoline;

7- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] -5, 6, 7, 8-tetrahydro- [1, 2, 4] triazolo [4, 3-a ] pyrazine;

8- ((1S, 2S) -2-azetidin-1-yl-4, 6-dichloroindan-1-yloxy) -5-fluoroquinoline;

8- ((1S, 2S) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) -5-fluoroquinoline;

8- ((1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) -5-fluoroquinoline;

8- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) quinoline;

benzyl [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

c- (1- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] indan-2-yl } pyrrolidin-3-yl) -methylamine;

c- (1- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } piperidin-4-yl) methylamine;

C- (1- { rac-trans- (1, 2) -1- [ 4-bromo-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } pyrrolidin-3-yl) methylamine;

c- {1- [ rac-trans- (1, 2) -1- (1H-indol-4-yloxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2, 4-difluorophenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2-bromo-4-methylphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2-fluoro-6-methoxyphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2-fluoro-6-methoxyphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2-methoxy-5-methylphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2-methoxy-5-methylphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2-methylbenzothiazol-5-yloxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (2-tert-butyl-4-ethylphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

C- {1- [ rac-trans- (1, 2) -1- (2-tert-butyl-4-ethylphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (3-chloro-2-methylphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (3-chloro-5-methoxyphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (3-chloro-5-methoxyphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (3-ethoxyphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (3-ethoxyphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-4-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (benzo [1, 3] dioxol-5-yloxy) indan-2-yl ] piperidin-4-yl } methylamine;

C- {1- [ rac-trans- (1, 2) -1- (benzo [1, 3] dioxol-5-yloxy) indan-2-yl ] pyrrolidin-3-yl } methylamine;

c- {1- [ rac-trans- (1, 2) -1- (quinolin-4-yloxy) indan-2-yl ] piperidin-4-yl } methylamine

Cyclopentyl- [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

cyclopropylmethyl- [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

diethyl- [ rac-trans- (1, 2) -1- (2-methylbenzothiazol-5-yloxy) indan-2-yl ] amine;

diethyl- [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] amine;

diethyl- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] amine;

diethyl- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] indan-2-yl } amine;

methyl- [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-4-ylamine;

methyl- [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-4-ylamine;

n- (3- { trans- (1S, 2S) -2- [ (R) -3- (2-fluoroethylamino) piperidin-1-yl ] indan-1-yloxy } phenyl) acetamide;

n- (3- { trans- (1S, 2S) -2- [ (R) -3- (3, 3, 3-trifluoropropylamino) piperidin-1-yl ] indan-1-yloxy } phenyl) acetamide;

N, N-diethyl-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzamide;

n- [2- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-azacycloheptan-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-diethylaminoindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-dimethylaminoindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-piperazin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-thiomorpholin-4-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4, 6-dichloro-2-dimethylaminoindan-1-yloxy) phenyl ] acetamide;

n- [3- (trans- (1S, 2S) -2-piperidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) pyridin-2-yl ] acetamide;

N- [6- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) pyridin-2-yl ] acetamide;

n- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] -N, N' -trimethylpropane-1, 3-diamine;

n- [ rac-trans- (1, 2) -3- ((R) -2- [1, 3 '] bipyrrolidinyl-1' -ylindan-1-yloxy) phenyl ] acetamide;

n- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -N, N' -trimethylethane-1, 2-diamine;

n- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -N, N' -trimethylpropane-1, 3-diamine;

n- {3- [ rac-trans- (1, 2) -2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-hydroxymethylpyrrolidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-methoxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

N- {3- [ rac-trans- (1, 2) -2- ((S) -3-aminopiperidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- (3-aminomethylpyrrolidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- (4-aminomethylpiperidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -2- ((R) -3-aminopiperidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -2- ((R) -3-dimethylaminopiperidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n-ethyl-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

tert-butyl- [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

3- [ trans- (1S, 2S) -4, 6-dichloro-1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] -3, 8-diazabicyclo [3.2.1] octane;

2- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -5-methyloctahydropyrrolo [3, 4-c ] pyrrole;

(3R, 5S) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3, 5-dimethylpiperazine;

(R) -1- [ (1S, 2S) -4, 6-difluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ol;

(R) -1- [ rac-trans- (1, 2) -4-chloro-6-fluoro-1- (3-methyl-4-trifluoromethanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -4-chloro-6-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -6-chloro-4-fluoro-1- (3-methyl-4-trifluoromethanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ rac-trans- (1, 2) -6-chloro-4-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (2-methylbenzothiazol-5-yloxy) indan-2-yl ] pyrrolidin-3-ol;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-imidazol-1-ylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1 '- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - [1, 3' ] bipyrrolidinyl;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-fluoropyrrolidine;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-methylpiperazine;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamine;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ol;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ylamine;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine-3-carbonitrile;

(R) -1- [ trans- (1S, 2S) -6-chloro-1- (2-chloro-4-methanesulfonylphenoxy) -4-fluoroindan-2-yl ] pyrrolidin-3-ol;

(R) -1- [ trans- (1S, 2S) -6-chloro-1- (2-chloro-4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ol;

(R) -1- [ trans- (1S, 2S) -6-chloro-4-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ol;

(R) -1- { (1S, 2S) -1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] -4, 6-difluoroindan-2-yl } pyrrolidin-3-ol;

(R) -1- { (1S, 2S) -1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] -4, 6-difluoroindan-2-yl } pyrrolidin-3-ol;

(R) -1- { (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } -3-methylpyrrolidin-3-ol;

(R) -1- { (1S, 2S) -4, 6-dichloro-1- [4- (5-methyltetrazol-1-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { (1S, 2S) -4, 6-dichloro-1- [ 4-fluoro-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } piperidin-3-ylamine;

(R) -1- { (1S, 2S) -4, 6-dichloro-1- [5- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [3- (1, 1-dioxo-1. lamda.)⁶-isothiazol-2-yl) phenoxy]Indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (1, 3, 5-trimethyl-1H-pyrazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (2, 4-dimethylthiazol-5-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2, 3-difluorophenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2, 3-dimethylphenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-methylphenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } piperidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } pyrrolidine-3-carbonitrile;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyliso-iso-cyclo-)Oxazol-4-yl) phenoxy]Indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethylpyrazol-1-yl) -2-fluorophenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [ 4-fluoro-2- (2H-pyrazol-3-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] -4-fluoroindan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (1, 3, 5-trimethyl-1H-pyrazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2, 3-dimethylphenoxy ] -4-fluoroindan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] -4-fluoroindan-2-yl ] pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] -4-fluoroindan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(S) -1- [ (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-methylpyrrolidin-3-ol;

(S) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -2-pyrrolidin-1-ylmethyl pyrrolidine;

(S) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-fluoropyrrolidine;

(S) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-methylpiperazine;

(S) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ol;

(S) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ylamine;

(S) -1- { (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] indan-2-yl } pyrrolidin-3-ol;

(S) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(S) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ylamine;

(S) -2- [ (S) -4- (S) -chloro-6-chloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] octahydropyrrolo [1, 2-a ] pyrazine;

(S) -2- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -2, 5-diazabicyclo [2.2.1] heptane;

(S) -3- {3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]-4-fluorophenyl } 4-isopropyl groupOxazolidin-2-one;

(S) -3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl } -4-isopropyl groupOxazolidin-2-one;

{ (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] piperidin-3-yl } - (3, 3, 3-trifluoropropyl) amine;

{ (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-yl } - (2-fluoroethyl) amine;

{ (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-yl } - (3, 3, 3-trifluoropropyl) amine;

{ (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-yl } dimethylamine;

{ (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamino } acetonitrile;

{ (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-yl } - (2-fluoroethyl) amine;

{ (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-yl } methanol;

{ (S) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-2-yl } methanol;

{4- [ rac-trans- (1, 2) -6-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazin-1-yl } acetonitrile;

1- [ (1S, 2S) -4, 6-dichloro-1- (2-methanesulfonylphenoxy) indan-2-yl ] azetidine;

1- [ (1S, 2S) -4, 6-dichloro-1- (2-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ (1S, 2S) -4, 6-dichloro-1- (2-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ (1S, 2S) -4, 6-dichloro-1- (3-tetrazol-1-ylphenoxy) indan-2-yl ] piperazine;

1- [ (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-methanesulfonylpyrrolidine;

1- [ (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -4, 4-difluoropiperidine;

1- [3- (rac-trans- (1, 2) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) phenyl ] -3-methyl-1, 3-dihydroimidazol-2-one;

1- [3- (rac-trans- (1, 2) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) phenyl ] -3-methylimidazolidin-2-one;

1- [4- ((1S, 2S) -2-azetidin-1-yl-4, 6-dichloroindan-1-yloxy) phenyl ] pyrrolidin-2-one;

1- [4- ((1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] pyrrolidin-2-one;

1- [ rac-trans- (1, 2) -4, 6-dichloro-1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - [1, 4] diazepane;

1- [ rac-trans- (1, 2) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -1H-imidazole;

1- [ rac-trans- (1, 2) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -4-methyl- [1, 4] diazepane;

1- [ rac-trans- (1, 2) -4-chloro-6-fluoro-1- (4-methanesulfonyl-3-methylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -4-chloro-6-fluoro-1- (4-methanesulfonyl-3-methylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -4-chloro-6-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -4-chloro-6-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -4-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -5, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - [1, 4] diazepane;

1- [ rac-trans- (1, 2) -5, 7-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -6, 7-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - [1, 4] diazepane;

1- [ rac-trans- (1, 2) -6-chloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -6-chloro-4-fluoro-1- (3-methyl-4-trifluoromethanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -6-chloro-4-fluoro-1- (4-methanesulfonyl-3-methylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -6-chloro-4-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -6-chloro-4-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -6-fluoro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (2-chloro-4-methanesulfonylphenoxy) indan-2-yl ] - [1, 4] diazepane;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] -4-methylpiperazine;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-imidazol-1-ylphenoxy) indan-2-yl ] -4-methylpiperazine;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - [1, 4] diazepane;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-propylpiperidin-3-ylamine;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-trifluoromethylpiperazine;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -3-trifluoromethylpyrrolidin-3-ylamine;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -4- (2-fluoroethyl) - [1, 4] diazepane;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -4- (2-methoxyethyl) - [1, 4] diazepane;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -4-methyl- [1, 4] diazepane;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -4-methylpiperazine;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -azetidin-3-ol;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- { (1S, 2S) -4, 6-dichloro-1- [ 4-fluoro-2- (1H-pyrazol-3-yl) phenoxy ] indan-2-yl } piperazine;

1- { 2-chloro-5- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- { 2-chloro-5- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methylimidazolidin-2-one;

1- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -2-methylphenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } -3-methylimidazolidin-2-one;

1- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidin-2-one;

1- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidine-2, 5-dione;

1- {3- [ (1S, 2S) -4, 6-difluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- {3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- {3- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methylimidazolidin-2-one;

1- {3- [ trans- (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methylimidazolidin-2-one;

1- { 3-chloro-4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidin-2-one;

1- { 3-chloro-4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidine-2, 5-dione;

1- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorophenyl } -1, 3-dihydroimidazol-2-one;

1- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorophenyl } -2, 6-dimethyl-1H-pyridin-4-one;

1- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -1, 3-dihydroimidazol-2-one;

1- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorophenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorophenyl } -3-methylimidazolidin-2-one;

1- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methylimidazolidin-2-one;

1- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidin-2-one;

1- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidine-2, 5-dione;

1- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidin-2-one;

1- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidine-2, 5-dione;

1- { 4-chloro-3- [ (1S, 2S) -4, 6-difluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methyl-1, 3-dihydroimidazol-2-one;

1- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3-methylimidazolidin-2-one;

1- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } pyrrolidin-2-one;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } - [1, 4] diazepane;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } -4-methyl- [1, 4] diazepane;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] indan-2-yl } -4-methyl- [1, 4] diazepane;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } - [1, 4] diazepane;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } -4- (2-methoxyethyl) - [1, 4] diazepane;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } -4-methyl- [1, 4] diazepane;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyliso-iso-cyclo-)Oxazol-4-yl) phenoxy]Indan-2-yl } -4- (2-methoxyethyl) - [1, 4]Diazacyclo ringHeptane;

1-cyclopropyl-4- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

2- ((1S, 2S) -2-azetidin-1-yl-4, 6-dichloroindan-1-yloxy) -5-chlorobenzamide;

2, 3-dichloro-4- (rac-trans- (1, 2) -4, 6-dichloro-2-morpholin-4-ylindan-1-yloxy) benzenesulfonamide;

2- [ rac-trans- (1, 2) -4, 6-dichloro-1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] octahydropyrrolo [3, 4-c ] pyrrole;

2- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -2, 7-diaza-spiro [4.4] nonane;

2- { (R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperidin-3-ylamino } ethanol;

2- {4- [ rac-trans- (1, 2) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - [1, 4] diazepan-1-yl } ethanol;

2- {4- [ rac-trans- (1, 2) -6-chloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazin-1-yl } ethanol;

2- {4- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] - [1, 4] diazepan-1-yl } ethanol;

3- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } -5, 5-dimethylimidazolidine-2, 4-dione;

3- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } imidazolidine-2, 4-dione;

3- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]-4-fluorophenyl }Oxazolidine-2, 4-dione;

3- {3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl radical }Oxazolidin-2-one;

3- {3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } -5, 5-dimethylimidazolidine-2, 4-dione;

3- {3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } imidazolidine-2, 4-dione;

3- { 3-chloro-4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -1-methylimidazolidine-2, 4-dione;

3- { 3-chloro-4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -5, 5-dimethylimidazolidine-2, 4-dione;

3- { 3-chloro-4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl radical }Oxazolidine-2, 4-dione;

3- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -5, 5-dimethylimidazolidine-2, 4-dione;

3- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } imidazolidine-2, 4-dione;

3- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl radical }Oxazolidine-2, 4-dione;

3- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } thiazolidine-2, 4-dione;

3- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ]Phenyl radical }Oxazolidin-2-one;

3- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -1-methylimidazolidine-2, 4-dione;

3- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -5, 5-dimethylimidazolidine-2, 4-dione;

3- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl } -5, 5-dimethylOxazolidine-2, 4-dione;

3- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } imidazolidine-2, 4-dione;

3- { 4-chloro-3- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl radical }Oxazolidin-2-one;

3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -1-methylimidazolidine-2, 4-dione,

3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -5, 5-dimethylimidazolidine-2, 4-dione;

3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl } -5, 5-dimethylOxazolidine-2, 4-dione;

3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } imidazolidine-2, 4-dione;

3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl radical }Oxazolidin-2-one;

3-chloro-4- [ trans- (1S, 2S) -6-chloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] benzoic acid methyl ester;

4- ((1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -4-chloro-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -4-methyl-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -6-chloro-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -6-fluoro-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -6-methyl-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -7-chloro-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- [ (1S, 2S) -2- ((R) -3-aminopiperidin-1-yl) -4, 6-dichloroindan-1-yloxy ] benzenesulfonamide;

4- [ (1S, 2S) -4, 6-dichloro-2- (1, 1-dioxo-1. lamda.) ⁶-thiomorpholin-4-yl) indan-1-yloxy]A benzenesulfonamide;

4- [ (1S, 2S) -4, 6-dichloro-2- (4, 4-difluoropiperidin-1-yl) indan-1-yloxy ] benzenesulfonamide;

4- [ 3-chloro-4- (trans- (1S, 2S) -6-chloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [4- (rac-trans- (1, 2) -5, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [4- (trans- (1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) -3-fluorophenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [4- (trans- (1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [4- (trans- (1S, 2S) -6-chloro-2-pyrrolidin-1-ylindan-1-yloxy) -3-fluorophenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [4- (trans- (1S, 2S) -6-chloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- [ rac-trans- (1, 2) -4, 6-dichloro-1- (4- [1, 2, 4] triazol-1-ylphenoxy) indan-2-yl ] morpholine;

4- [ trans- (1S, 2S) -2- ((R) -3-aminopiperidin-1-yl) -4, 6-dichloroindan-1-yloxy ] -2, 3-dichlorobenzenesulfonamide;

4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorobenzoic acid methyl ester;

4- { 3-chloro-4- [ trans- (1S, 2S) -6-chloro-2- ((R) -3-fluoropyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- { 3-chloro-4- [ trans- (1S, 2S) -6-chloro-2- ((S) -3-fluoropyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3-fluorophenyl } morpholine-3, 5-dione;

4- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-fluoropyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((S) -2-methoxymethylpyrrolidin-1-yl) indan-1-yloxy ] phenyl } -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- {4- [ trans- (1S, 2S) -6-chloro-2- ((R) -3-fluoropyrrolidin-1-yl) indan-1-yloxy ] -3-fluorophenyl } -3, 5-dimethyl-4H- [1, 2, 4] triazole;

4- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] indan-2-yl } morpholine;

4- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] indan-2-yl } thiomorpholine 1, 1-dioxide;

4- { trans- (1S, 2S) -6-chloro-1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } morpholine;

4- { trans- (1S, 2S) -6-chloro-1- [ 2-chloro-4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) phenoxy ] indan-2-yl } thiomorpholine 1, 1-dioxide;

5- (rac-trans- (1, 2) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) -2-methylbenzothiazole;

5- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -3, 4-dihydro-1H-quinolin-2-one;

5- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] -1-methyloctahydropyrrolo [3, 4-b ] pyrrole;

n- [3- (rac-trans- (1, 2) -4, 6-dichloro-2- [1, 4] diazepan-1-ylindan-1-yloxy) phenyl ] acetamide;

N- [3- (rac-trans- (1, 2) -4, 6-dichloro-2-morpholin-4-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4-chloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4-chloro-6-fluoro-2-piperazin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4-chloro-6-fluoro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4-fluoro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -4-methyl-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -5, 7-dichloro-2-dimethylaminoindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -5-chloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -5-fluoro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

N- [3- (rac-trans- (1, 2) -6-chloro-2-piperazin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -6-chloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -6-chloro-4-fluoro-2-piperazin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -6-chloro-4-fluoro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -6-fluoro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -7-chloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (trans- (1S, 2S) -4, 6-dichloro-2-3, 8-diazabicyclo [3.2.1] oct-3-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (trans- (1S, 2S) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- {3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] -4-fluorophenyl } -N-methylmethanesulfonamide;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -4-chloro-6-fluoroindan-1-yloxy ] phenyl } acetamide;

n- {3- [ rac-trans- (1, 2) -2- ((R) -3-aminopiperidin-1-yl) -6-chloro-4-fluoroindan-1-yloxy ] phenyl } acetamide;

N- {3- [ rac-trans- (1, 2) -4, 6-dichloro-2- (hexahydropyrrolo [3, 4-c ] pyrrol-2-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -2- ((R) -3-aminopiperidin-1-yl) -4, 6-dichloroindan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -2- (3-amino-3-propylpiperidin-1-yl) -4, 6-dichloroindan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-dimethylaminopiperidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxymethylpyrrolidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {3- [ trans- (1S, 2S) -4, 6-dichloro-2- (4-methylpiperazin-1-yl) indan-1-yloxy ] phenyl } acetamide;

n- {4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -N-methylmethanesulfonamide;

2- { [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -methyl-amino } -ethanol;

4- (rac-trans- (1, 2) -2-cyclopropylamino-indan-1-yloxy) -3-fluoro-benzenesulfonamide;

2- ({ trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluoro-phenoxy ] -indan-2-yl } -methyl-amino) -ethanol;

cyclopentylmethyl- [ rac-trans- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -amine;

cyclobutyl- [ rac-cis- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -amine;

cyclobutyl- [ rac-trans- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -amine;

4- (rac-trans- (1, 2) -2-cyclobutylamino-indan-1-yloxy) -3-fluoro-benzenesulfonamide;

cycloheptyl- [ rac-trans- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -amine;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (2-ethyl-4-methyl-imidazol-1-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

4- (rac-trans- (1, 2) -2-cycloheptylamino-indan-1-yloxy) -3-fluoro-benzenesulfonamide;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (2-isopropyl-4-methyl-imidazol-1-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3-isopropyl-5-methyl- [1, 2, 4] triazol-4-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3-ethyl-5-isopropyl- [1, 2, 4] triazol-4-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

cyclobutylmethyl- [ rac-trans- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -amine;

4- [ rac-trans- (1, 2) -2- (cyclobutylmethyl-amino) -indan-1-yloxy ] -3-fluoro-benzenesulfonamide;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (2-ethyl-4-methyl-imidazol-1-yl) -phenoxy ] -4-fluoro-indan-2-yl } -pyrrolidin-3-ol;

(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;

(R) -1- { trans- (1S, 2S) -6-chloro-4-fluoro-1- [4- (3-isopropyl-5-methyl- [1, 2, 4] triazol-4-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (3-ethyl-5-isopropyl- [1, 2, 4] triazol-4-yl) -phenoxy ] -4-fluoro-indan-2-yl } -pyrrolidin-3-ol;

(1-ethyl-propyl) - [ rac-trans- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -amine;

(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;

(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;

n- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluoro-phenoxy ] -indan-2-yl } -N, N' -trimethyl-ethane-1, 2-diamine;

(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;

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-imidazol-1-yl-phenoxy) -indan-2-yl ] -pyrrolidin-3-ol;

(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;

cyclopentyl- [ rac-trans- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -methyl-amine;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (2-methanesulfonyl-imidazol-1-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (2-isopropyl-imidazol-1-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

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-one;

cyclobutyl- [ rac-trans- (1, 2) -1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -methyl-amine;

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-one;

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] triazol-3-one;

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] triazol-3-one;

(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;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [ 2-fluoro-4- (2-methanesulfonyl-imidazol-1-yl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

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;

4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxy-pyrrolidin-1-yl) -indan-1-yloxy ] -3-fluoro-benzenesulfonamide;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (4-methyl-piperazine-1-sulfonyl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxy-pyrrolidin-1-yl) -indan-1-yloxy ] -benzenesulfonamide;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (morpholine-4-sulfonyl) -phenoxy ] -indan-2-yl } -pyrrolidin-3-ol;

1- {5- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxy-pyrrolidin-1-yl) -indan-1-yloxy ] -2-fluoro-phenyl } -3-methyl-1, 3-dihydro-imidazol-2-one;

cyclopentyl- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluoro-phenoxy ] -indan-2-yl } -amine;

cyclopentyl- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -amine;

4- (trans- (1S, 2S) -4, 6-dichloro-2-cyclopentylamino-indan-1-yloxy) -3-fluoro-benzenesulfonamide;

{ trans- (1S, 2S) -6-chloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluoro-phenoxy ] -4-fluoro-indan-2-yl } -cyclopentyl-amine;

4- (trans- (1S, 2S) -6-chloro-2-cyclopentylamino-4-fluoro-indan-1-yloxy) -3-fluoro-benzenesulfonamide;

[ trans- (1S, 2S) -6-chloro-4-fluoro-1- (4-methanesulfonyl-phenoxy) -indan-2-yl ] -cyclopentyl-amine;

1- [4- (trans- (1S, 2S) -6-chloro-2-cyclopentylamino-4-fluoro-indan-1-yloxy) -3-fluoro-phenyl ] -pyrrolidine-2, 5-dione;

3- [4- (trans- (1S, 2S) -6-chloro-2-cyclopentylamino-4-fluoro-indan-1-yloxy) -3-fluoro-phenyl ] -imidazolidine-2, 4-dione;

{ trans- (1S, 2S) -6-chloro-4-fluoro-1- [ 2-fluoro-4- (2-methanesulfonyl-imidazol-1-yl) -phenoxy ] -indan-2-yl } -cyclopentyl-amine;

1- [4- (trans- (1S, 2S) -6-chloro-2-cyclopentylamino-4-fluoro-indan-1-yloxy) -3-fluoro-phenyl ] -3-methyl-1, 3-dihydro-imidazol-2-one;

1- [3- (trans- (1S, 2S) -6-chloro-2-cyclopentylamino-4-fluoro-indan-1-yloxy) -4-fluoro-phenyl ] -3-methyl-1, 3-dihydro-imidazol-2-one.

13. A compound of formula I according to claim 4, wherein the compound is selected from:

[3- (rac-trans- (1, 2) -2-diethylaminoindan-1-yloxy) phenyl ] urea;

[ rac-trans- (1, 2) -1- (2-fluoro-6-methoxyphenoxy) indan-2-yl ] -methylpiperidin-4-ylamine;

1- [1- (2-chloro-4-nitrophenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-cis- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] -1H-imidazole;

1- [ rac-trans- (1, 2) -1- (2, 3-dichloro-4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (3-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

1- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine;

1- [ rac-trans- (1, 2) -1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidine;

2, 3-dichloro-4- [ rac-trans- (1, 2) -2- ((R) -3-methoxypyrrolidin-1-yl) indan-1-yloxy ] benzenesulfonamide;

2- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] thiazole;

2-chloro-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzonitrile;

3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenylamine;

3- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] benzamide;

3-chloro-4- (2-pyrrolidin-1-ylindan-1-yloxy) pyridine;

3-fluoro-4- (2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (2-benzylamino indan-1-yloxy) -3-fluorobenzenesulfonamide;

4- (2-cyclopentylaminoindan-1-yloxy) -3-fluorobenzenesulfonamide;

4- (rac-trans- (1, 2) -2-azacycloheptan-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-piperidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzonitrile;

4- [ (1R, 2S) -1- (2-chloro-4-nitrophenoxy) indan-2-yl ] morpholine;

4- [ rac-trans- (1, 2) -2- (3-aminopyrrolidin-1-yl) indan-1-yloxy ] benzamide;

5- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) -3H-isobenzofuran-1-one;

8- ((1S, 2S) -2-azetidin-1-yl-4, 6-dichloroindan-1-yloxy) -5-fluoroquinoline;

8- ((1S, 2S) -4, 6-dichloro-2-piperazin-1-ylindan-1-yloxy) -5-fluoroquinoline;

8- ((1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) -5-fluoroquinoline;

8- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) quinoline;

benzyl [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

c- (1- { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] indan-2-yl } pyrrolidin-3-yl) methylamine;

c- {1- [ rac-trans- (1, 2) -1- (quinolin-4-yloxy) indan-2-yl ] piperidin-4-yl } methylamine;

cyclopentyl [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

cyclopropylmethyl [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

diethyl [ rac-trans- (1, 2) -1- (2-methylbenzothiazol-5-yloxy) indan-2-yl ] amine;

diethyl [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] amine;

diethyl [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] amine;

diethyl { rac-trans- (1, 2) -1- [4- (2-methoxyethyl) phenoxy ] indan-2-yl } amine;

methyl [ rac-trans- (1, 2) -1- (3-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-4-ylamine;

methyl [ rac-trans- (1, 2) -1- (4-piperazin-1-ylphenoxy) indan-2-yl ] piperidin-4-ylamine;

N, N-diethyl-4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) benzamide;

n- [2- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-diethylaminoindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-dimethylaminoindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-piperazin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [3- (trans- (1S, 2S) -2-piperidin-1-ylindan-1-yloxy) phenyl ] acetamide;

n- [4- (rac-trans- (1, 2) -2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide;

tert-butyl [1- (4-methanesulfonylphenoxy) indan-2-yl ] amine;

(R) -1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (2, 4-dimethyl-thiazol-5-yl) phenoxy ] indan-2-yl } pyrrolidin-3-ol;

(R) -1- { trans- (1S, 2S) -6-chloro-1- [4- (3, 5-dimethyl- [1, 2, 4] triazol-4-yl) -2-fluorophenoxy ] -4-fluoroindan-2-yl } pyrrolidin-3-ol;

(S) -3- {3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]-4-fluorophenyl } -4-isopropyl groupOxazolidin-2-one;

1- [ (1S, 2S) -4, 6-dichloro-1- (2-methanesulfonylphenoxy) indan-2-yl ] -azetidine;

1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyliso-iso-cyclo-)Oxazol-4-yl) phenoxy]Indan-2-yl } -4- (2-methoxyethyl) - [1, 4]Diazepane;

2- ((1S, 2S) -2-azetidin-1-yl-4, 6-dichloroindan-1-yloxy) -5-chlorobenzamide;

3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ] phenyl } -1-methylimidazolidine-2, 4-dione;

4- ((1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

n- [3- (rac-trans- (1, 2) -5-chloro-2-pyrrolidin-1-ylindan-1-yloxy) phenyl ] acetamide,

1- [3- (trans- (1S, 2S) -6-chloro-2-cyclopentylamino-4-fluoro-indan-1-yloxy) -4-fluoro-phenyl ] -3-methyl-1, 3-dihydro-imidazol-2-one;

(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;

1- {5- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxy-pyrrolidin-1-yl) -indan-1-yloxy ] -2-fluoro-phenyl } -3-methyl-1, 3-dihydro-imidazol-2-one.

14. A compound of formula I according to claim 5, wherein the compound is selected from:

(R) -1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] pyrrolidin-3-ol,

(S) -3- { 4-chloro-3- [ (1S, 2S) -6-chloro-4-fluoro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ]Phenyl } -4-isopropyl groupOxazolidin-2-one;

1- [ trans- (1S, 2S) -4, 6-dichloro-1- (4-methanesulfonylphenoxy) indan-2-yl ] piperazine,

1- { trans- (1S, 2S) -4, 6-dichloro-1- [4- (3, 5-dimethyliso-iso-cyclo-) Oxazol-4-yl) phenoxy]Indan-2-yl } -4- (2-methoxyethyl) - [1, 4]Diazepane;

2- ((1S, 2S) -2-azetidin-1-yl-4, 6-dichloroindan-1-yloxy) -5-chlorobenzamide;

3- { 3-chloro-4- [ (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy ]Phenyl radical }Oxazolidine-2, 4-dione;

3- {4- [ trans- (1S, 2S) -4, 6-dichloro-2- ((R) -3-hydroxypyrrolidin-1-yl) indan-1-yloxy]Phenyl radical }Oxazolidin-2-one;

4- ((1S, 2S) -4, 6-dichloro-2-pyrrolidin-1-ylindan-1-yloxy) benzenesulfonamide;

4- [ (1S, 2S) -4, 6-dichloro-2- (1, 1-dioxo-1. lamda.)⁶-thiomorpholin-4-yl) indan-1-yloxy]A benzenesulfonamide;

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-one;

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-one;

15. A compound of formula I according to any one of claims 1 to 14, wherein the group XLBR5 bonded in position 1 is oriented downwards and the group- (CH) bonded in position 2 is a pharmaceutically acceptable salt thereof₂)_qThe direction of NR3R4 is upward, the direction is determined by the plane formed by the carbon atoms at the 1, 2 and 3 positions, and the orientation of the compound is shown as the formula Ie

16. A compound of formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof for use as a medicament.

17. Use of a compound according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment or prophylaxis of Na by total or partial inhibition of NHE3⁺/H⁺Use in the manufacture of a medicament for the treatment of a disease of exchange.

18. The use of a compound of formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment or prevention of: impaired respiratory drive, respiratory diseases, sleep-related respiratory diseases, sleep apnea, snoring, cystic fibrosis, upper and lower respiratory diseases associated with viscous mucus, acute and chronic kidney disease, acute renal failure and chronic renal failure, impaired bowel function, constipation, impaired biliary function, hypertension, essential hypertension, cardiovascular disease, diabetes, metabolic syndrome, and hyperlipidemia.

19. The use of a compound of the formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof in combination with a further medicament or active ingredient for the preparation of a medicament for the treatment or prophylaxis of: impaired respiratory drive, respiratory diseases, sleep-related respiratory diseases, sleep apnea, snoring, cystic fibrosis, upper and lower respiratory diseases associated with viscous mucus, acute and chronic kidney disease, acute renal failure and chronic renal failure, impaired bowel function, constipation, impaired biliary function, hypertension, essential hypertension, cardiovascular disease, diabetes, metabolic syndrome, and hyperlipidemia.

20. A compound of the formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof alone or in combination with other medicaments or active ingredients for the treatment or prevention of impaired respiratory drive and/or impaired sleep-related respiratory system.

21. A compound of formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof alone or in combination with other medicaments or active ingredients for the treatment or prevention of sleep apnea.

22. A compound of the formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof alone or in combination with other medicaments or active ingredients for the treatment or prophylaxis of snoring.

23. A compound of formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof, alone or in combination with other medicaments or active ingredients, for the treatment of cystic fibrosis.

24. A compound of formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof, alone or in combination with other medicaments or active ingredients, for use in mucolysis for the treatment of upper and lower respiratory tract disorders associated with viscous mucus.

25. A pharmaceutical formulation for human, veterinary or plant protection comprising an effective amount of a compound of formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof.

26. A pharmaceutical preparation for human, veterinary or plant protection, which comprises an effective amount of a compound of the formula I according to any one of claims 1 to 15 and/or a pharmaceutically acceptable salt thereof, and a further pharmacologically active ingredient or medicament.

27. A compound of formula I as described in any one of claims 1-15, and pharmaceutically acceptable salts thereof in solvate, prodrug or crystal form.